Helen Nadel, MD

  • Helen Ruth Nadel


Nuclear Medicine

Work and Education

Professional Education

University of Manitoba Office of the Registrar, Winnipeg, Canada, 5/25/1977


Toronto General Hospital, Toronto Ontario, Canada, 6/12/1978


University of Toronto, Toronto, Ontario, M5S 1A8, 6/30/1983


Hospital For Sick Children, Toronto, Ontario, Canada, 6/30/1983

University of British Columbia, Vancouver, BC, Canada, 12/31/1989

Board Certifications

Diagnostic Radiology, American Board of Radiology

Diagnostic Radiology, Royal College of Physicians and Surgeons of Canada

Nuclear Medicine, American Board of Nuclear Medicine

Nuclear Medicine, Royal College of Physicians and Surgeons of Canada

Pediatric Radiology, American Board of Radiology

All Publications

Use of Neoadjuvant Vandetanib in Aggressive Pediatric Medullary Thyroid Carcinoma. JCO precision oncology Kothari, R., Kreimer, S., Nadel, H., Seeley, H., Hartman, G., Meister, K. D. 2024; 8: e2300257


Novel use of vandetanib in a child with aggressive MTC with prolonged response to treatment.

View details for DOI 10.1200/PO.23.00257

View details for PubMedID 38207224

The evidence-based role of catecholaminergic PET tracers in Neuroblastoma. A systematic review and a head-to-head comparison with mIBG scintigraphy. European journal of nuclear medicine and molecular imaging Piccardo, A., Treglia, G., Fiz, F., Bar-Sever, Z., Bottoni, G., Biassoni, L., Borgwardt, L., de Keizer, B., Jehanno, N., Lopci, E., Kurch, L., Massollo, M., Nadel, H., Roca Bielsa, I., Shulkin, B., Vali, R., De Palma, D., Cecchin, D., Santos, A. I., Zucchetta, P. 2023


BACKGROUND: Molecular imaging is pivotal in staging and response assessment of children with neuroblastoma (NB). [123I]-metaiodobenzylguanidine (mIBG) is the standard imaging method; however, it is characterised by low spatial resolution, time-consuming acquisition procedures and difficult interpretation. Many PET catecholaminergic radiotracers have been proposed as a replacement for [123I]-mIBG, however they have not yet made it into clinical practice. We aimed to review the available literature comparing head-to-head [123I]-mIBG with the most common PET catecholaminergic radiopharmaceuticals.METHODS: We searched the PubMed database for studies performing a head-to-head comparison between [123I]-mIBG and PET radiopharmaceuticals including meta-hydroxyephedrine ([11C]C-HED), 18F-18F-3,4-dihydroxyphenylalanine ([18F]DOPA) [124I]mIBG and Meta-[18F]fluorobenzylguanidine ([18F]mFBG). Review articles, preclinical studies, small case series (<5 subjects), case reports, and articles not in English were excluded. From each study, the following characteristics were extracted: bibliographic information, technical parameters, and the sensitivity of the procedure according to a patient-based analysis (PBA) and a lesion-based analysis (LBA).RESULTS: Ten studies were selected: two regarding [11C]C-HED, four [18F]DOPA, one [124I]mIBG, and three [18F]mFBG. These studies included 181 patients (range 5-46). For the PBA, the superiority of the PET method was reported in two out of ten studies (both using [18F]DOPA). For LBA, PET detected significantly more lesions than scintigraphy in seven out of ten studies.CONCLUSIONS: PET/CT using catecholaminergic tracers shows superior diagnostic performance than mIBG scintigraphy. However, it is still unknown if such superiority can influence clinical decision-making. Nonetheless, the PET examination appears promising for clinical practice as it offers faster image acquisition, less need for sedation, and a single-day examination.

View details for DOI 10.1007/s00259-023-06486-9

View details for PubMedID 37962616

The Global Reading Room: An Anxious Child Awaiting Renal Scintigraphy. AJR. American journal of roentgenology Bar-Sever, Z., Biassoni, L., Chen, S., Nadel, H. R. 2023

View details for DOI 10.2214/AJR.23.30014

View details for PubMedID 37530399

Evaluation of local control strategies on patterns of treatment failure in patients with localized ewing sarcoma treated on AEWS1031: A report from the children's oncology group Ahmed, S. K., Binitie, O., Krailo, M. D., Buxton, A., Indelicato, D. J., Callan, A., Christ, A., Chuba, P. J., Nadel, H., Pawel, B., Gorlick, R., Reed, D. R., DuBois, S. G., Janeway, K. A., Leavey, P., Mascarenhas, L., Laack, N. N. LIPPINCOTT WILLIAMS & WILKINS. 2023
Flip-flop: Two tracers are better than one in pediatric PET/MRI for neuroendocrine neoplasms Guja, K., Nadel, H. SOC NUCLEAR MEDICINE INC. 2023
Theranostic Radiopharmaceuticals: A Universal Challenging Educational Paradigm in Nuclear Medicine. Journal of nuclear medicine : official publication, Society of Nuclear Medicine Urbain, J. L., Scott, A. M., Lee, S. T., Buscombe, J., Weston, C., Hatazawa, J., Kinuya, S., Singh, B., Haidar, M., Ross, A., Lamoureux, F., Kunikowska, J., Wadsak, W., Dierckx, R., Paez, D., Giammarile, F., Lee, K. H., O, J. H., Moshe, M., Louw, L., More, S., Nadel, H., Lee, D., Wahl, R. 2023; 64 (6): 986-991

View details for DOI 10.2967/jnumed.123.265603

View details for PubMedID 37142302

Comparison of the different imaging modalities used to image pediatric oncology patients: A COG diagnostic imaging committee/SPR oncology committee white paper. Pediatric blood & cancer Frush, D. P., Callahan, M. J., Coley, B. D., Nadel, H. R., Paul Guillerman, R. 2023: e30298


Diagnostic imaging is essential in the diagnosis and management, including surveillance, of known or suspected cancer in children. The independent and combined roles of the various modalities, consisting of radiography, fluoroscopy, ultrasonography (US), computed tomography (CT), magnetic resonance imaging (MRI), and nuclear medicine (NM), are both prescribed through protocols but also function in caring for complications that may occur during or subsequent to treatment such as infection, bleeding, or organ compromise. Use of a specific imaging modality may be based on situational circumstances such as a brain CT or MR for a new onset seizure, chest CT for respiratory signs or symptoms, or US for gross hematuria. However, in many situations, there are competing choices that do not easily lend themselves to a formulaic approach as options; these situations depend on the contributions of a variety of factors based on a combination of the clinical scenario and the strengths and limitations of the imaging modalities. Therefore, an improved understanding of the potential influence of the imaging decision pathways in pediatric cancer care can come from comparison among the individual diagnostic imaging modalities. The purpose of the following material to is to provide such a comparison. To do this, pediatric imaging content experts for the individual modalities of radiography and fluoroscopy, US, CT, MRI, and NM will discuss the individual modality strengths and limitations.

View details for DOI 10.1002/pbc.30298

View details for PubMedID 37025033

Serial Lung Perfusion Scintigraphy After Unifocalization and Repair of Tetralogy of Fallot With Major Aortopulmonary Collaterals. World journal for pediatric & congenital heart surgery Wise-Faberowski, L., Long, J., Ma, M., Nadel, H. R., Shek, J., Feinstein, J. A., Martin, E., Hanley, F. L., McElhinney, D. B. 2023: 21501351231162959


BACKGROUND: In patients with tetralogy of Fallot and major aortopulmonary collaterals (MAPCAs), pulmonary blood supply is highly variable. Our approach to this condition emphasizes complete unifocalization of the pulmonary circulation, incorporating all lung segments and addressing stenoses out to the segmental level. Post-repair, we recommend serial lung perfusion scintigraphy (LPS) to assess short-term changes in pulmonary blood flow distribution.METHODS: We reviewed post-discharge and follow-up LPS performed through three years post-repair and analyzed serial changes in perfusion, risk factors for change, and the relationship between LPS parameters and pulmonary artery reintervention.RESULTS: Of 543 patients who had postoperative LPS results in our system, 317 (58%) had only a predischarge LPS available for review, while 226 had 1 (20%) or more (22%) follow-up scans within three years. Overall, pulmonary flow distribution prior to discharge was balanced, and there was minimal change over time; however, there was considerable patient-to-patient variation in both metrics. On multivariable mixed modeling, time after repair (P=.025), initial anatomy consisting of a ductus arteriosus to one lung (P<.001), and age at repair (P=.014) were associated with changes on serial LPS. Patients who had follow-up LPS were more likely to undergo pulmonary artery reintervention, but within that cohort, LPS parameters were not associated with reintervention risk.CONCLUSION: Serial LPS during the first year after MAPCAs repair is a noninvasive method of screening for significant post-repair pulmonary artery stenosis that occurs in a small but important minority of patients. In patients who received follow-up LPS beyond the perioperative period, there was minimal change over time in the population overall, but large changes in some patients and considerable variability. There was no statistical association between LPS findings and pulmonary artery reintervention.

View details for DOI 10.1177/21501351231162959

View details for PubMedID 36972512

Case Series of Precision Delivery of Methylprednisolone in Pediatric Inflammatory Bowel Disease: Feasibility, Clinical Outcomes, and Identification of a Vasculitic Transcriptional Program. Journal of clinical medicine Levitte, S., Yarani, R., Ganguly, A., Martin, L., Gubatan, J., Nadel, H. R., Franc, B., Gugig, R., Syed, A., Goyal, A., Park, K. T., Thakor, A. S. 2023; 12 (6)


Systemic steroid exposure, while useful for the treatment of acute flares in inflammatory bowel disease (IBD), is associated with an array of side effects that are particularly significant in children. Technical advancements have enabled locoregional intraarterial steroid delivery directly into specific segments of the gastrointestinal tract, thereby maximizing tissue concentration while limiting systemic exposure. We investigated the feasibility of intraarterial steroid administration into the bowel in a cohort of nine pediatric patients who had IBD. This treatment approach provided symptom relief in all patients, with sustained relief (>2 weeks) in seven out of nine; no serious adverse effects occurred in any patient. In addition, we identified patterns of vascular morphologic changes indicative of a vasculopathy within the mesenteric circulation of inflamed segments of the bowel in pediatric patients with Crohn's disease, which correlated with disease activity. An analysis of publicly available transcriptomic studies identified vasculitis-associated molecular pathways activated in the endothelial cells of patients with active Crohn's disease, suggesting a possible shared transcriptional program between vasculitis and IBD. Intraarterial corticosteroid treatment is safe and has the potential to be widely accepted as a locoregional approach for therapy delivery directly into the bowel; however, this approach still warrants further consideration as a short-term "bridge" between therapy transitions for symptomatic IBD patients with refractory disease, as part of a broader steroid-minimizing treatment strategy.

View details for DOI 10.3390/jcm12062386

View details for PubMedID 36983386

Role of peripheral blood MRD and 18F-FDG PET in the post-CAR relapse setting: a case study of discordant peripheral blood and bone marrow MRD. Journal for immunotherapy of cancer Schultz, L., Davis, K. L., Walkush, A., Baggott, C., Erickson, C., Ramakrishna, S., Aftandilian, C., Lacayo, N., Nadel, H. R., Oak, J., Mackall, C. L. 2023; 11 (2)


Chimeric antigen receptor (CAR) T cell therapy is an effective salvage therapy for pediatric relapsed B-cell acute lymphoblastic leukemia (B-ALL), yet is challenged by high rates of post-CAR relapse. Literature describing specific relapse patterns and extramedullary (EM) sites of involvement in the post-CAR setting remains limited, and a clinical standard for post-CAR disease surveillance has yet to be established. We highlight the importance of integrating peripheral blood minimal residual disease (MRD) testing and radiologic imaging into surveillance strategies, to effectively characterize and capture post-CAR relapse.Here, we describe the case of a child with multiply relapsed B-ALL who relapsed in the post-CAR setting with gross non-contiguous medullary and EM disease. Interestingly, her relapse was identified first from peripheral blood flow cytometry MRD surveillance, in context of a negative bone marrow aspirate (MRD <0.01%). Positron emission tomography with 18F-fluorodeoxyglucose revealed diffuse leukemia with innumerable bone and lymph node lesions, interestingly sparing her sacrum, the site of her bone marrow aspirate sampling.We highlight this case as both peripheral blood MRD and 18F-fluorodeoxyglucose positron emission tomography imaging were more sensitive than standard bone marrow aspirate testing in detecting this patient's post-CAR relapse. Clinical/Biologic Insight: In the multiply relapsed B-ALL setting, where relapse patterns may include patchy medullary and/or EM disease, peripheral blood MRD and/or whole body imaging, may carry increased sensitivity at detecting relapse in patient subsets, as compared with standard bone marrow sampling.

View details for DOI 10.1136/jitc-2022-004851

View details for PubMedID 36849202

View details for PubMedCentralID PMC9972424

Overview and Recent Advances in 18F-FDG PET/CT for Evaluation of Pediatric Lymphoma Seminars in Nuclear Medicine Guja, K. E., Nadel, H., Iagaru, A. 2023; 53 (3): 400-412
ACR Appropriateness Criteria Ataxia-Child. Journal of the American College of Radiology : JACR Expert Panel on Pediatric Imaging, Radhakrishnan, R., Shea, L. A., Pruthi, S., Silvera, V. M., Bosemani, T., Desai, N. K., Gilbert, D. L., Glenn, O. A., Guimaraes, C. V., Ho, M., Lam, H. F., Maheshwari, M., Mirsky, D. M., Nadel, H. R., Partap, S., Schooler, G. R., Udayasankar, U. K., Whitehead, M. T., Wright, J. N., Rigsby, C. K. 2022; 19 (11S): S240-S255


Childhood ataxia may be due to multifactorial causes of impairment in the coordination of movement and balance. Acutely presenting ataxia in children may be due to infectious, inflammatory, toxic, ischemic, or traumatic etiology. Intermittent or episodic ataxia in children may be manifestations of migraine, benign positional vertigo, or intermittent metabolic disorders. Nonprogressive childhood ataxia suggests a congenital brain malformation or early prenatal or perinatal brain injury, and progressive childhood ataxia indicates inherited causes or acquired posterior fossa lesions that result in gradual cerebellar dysfunction. CT and MRI of the central nervous system are the usual modalities used in imaging children presenting with ataxia, based on the clinical presentation. This document provides initial imaging guidelines for a child presenting with acute ataxia with or without a history of recent trauma, recurrent ataxia with interval normal neurological examination, chronic progressive ataxia, and chronic nonprogressive ataxia. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances in which peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.

View details for DOI 10.1016/j.jacr.2022.09.010

View details for PubMedID 36436955

Local Failure in Non-Metastatic Ewing Sarcoma Patients Treated with Definitive Radiation Therapy on AEWS1031: A Report from the Children's Oncology Group Ahmed, S. K., Indelicato, D. J., Chuba, P. J., Krailo, M., Buxton, A., Randall, R. L., Binitie, O., Nadel, H., Pawel, B., Dubois, S. G., Janeway, K. A., Reed, D., Leavey, P., Mascarenhas, L., Laack, N. N. ELSEVIER SCIENCE INC. 2022: S69-S70
Time to resolution of iodine-123 metaiodobenzylguanidine (123 I-MIBG) avidity and local control outcomes for high-risk neuroblastoma following radiation therapy. Journal of medical imaging and radiation oncology Oh, J., Gutkin, P., Wang, Y. P., Sandhu, N., Majzner, R. G., Nadel, H., Shimada, H., Lansinger, O., von Eyben, R., Donaldson, S., Bruzoni, M., Sodji, Q. H., Hiniker, S. M. 2022


INTRODUCTION: 123 I-MIBG scan is used in neuroblastoma (NB) to monitor treatment response. Time to resolution of 123 I-MIBG avidity after radiation therapy (RT) is unknown. We sought to determine time to resolution of 123 I-MIBG avidity after RT and local failure (LF) rate.METHODS: We performed a retrospective review of children with high-risk NB who underwent 123 I-MIBG scans pre- and post-RT from 2003 to 2019. Time from RT to resolution of 123 I-MIBG activity was analysed. LF and cumulative incidence of local progression (CILP) after RT stratified by site, presence of residual disease and use of boost RT were determined.RESULTS: Forty-two patients with median age 3.9years (1.9-4.7years) were included, with median follow-up time 3.9years (1.4-6.9). Eighty-six lesions were treated with RT to median dose of 21.6Gy. Eighteen of 86 lesions were evaluable for time to resolution of MIBG avidity after RT, with median resolution time of 78days (36-208). No LF occurred among 26 patients who received RT to primary sites after GTR, versus 4/12 (25%) patients treated with residual primary disease. 2-year CILP was 19% (12% primary disease 25% metastatic disease (P=0.18)). 2-year CILP for non-residual primary, residual primary, non-residual metastatic and residual metastatic lesions was 0%, 42%, 11% and 30% respectively (P=0.01) and for boosted and non-boosted residual lesions was 29% and 35% (P=0.44).CONCLUSION: Median time to MIBG resolution after RT was 78days. Primary lesions without residual disease had excellent local control. LF rate was higher after RT for residual disease, with no benefit for boost RT.

View details for DOI 10.1111/1754-9485.13487

View details for PubMedID 36300562

Imaging of pediatric bone tumors: A COG Diagnostic Imaging Committee/SPR Oncology Committee White Paper. Pediatric blood & cancer Cederberg, K. B., Iyer, R. S., Chaturvedi, A., McCarville, M. B., McDaniel, J. D., Sandberg, J. K., Shammas, A., Sharp, S. E., Nadel, H. R. 2022: e30000


Malignant primary bone tumors are uncommon in the pediatric population, accounting for 3%-5% of all pediatric malignancies. Osteosarcoma and Ewing sarcoma comprise 90% of malignant primary bone tumors in children and adolescents. This paper provides consensus-based recommendations for imaging in children with osteosarcoma and Ewing sarcoma at diagnosis, during therapy, and after therapy.

View details for DOI 10.1002/pbc.30000

View details for PubMedID 36250990

Imaging recommendations in pediatric lymphoma: A COG Diagnostic Imaging Committee/SPR Oncology Committee White Paper PEDIATRIC BLOOD & CANCER Mhlanga, J., Alazraki, A., Cho, S., Lai, H., Nadel, H., Pandit-Taskar, N., Qi, J., Rajderkar, D., Voss, S., Watal, P., McCarten, K. 2022: e29968


Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) are both malignancies originating in the lymphatic system and both affect children, but many features differ considerably, impacting workup and management. This paper provides consensus-based imaging recommendations for evaluation of patients with HL and NHL at diagnosis and response assessment for both interim and end of therapy (follow-up).

View details for DOI 10.1002/pbc.29968

View details for Web of Science ID 000854364200001

View details for PubMedID 36114654

Poverty, race, ethnicity, and survival among US children with non-metastatic osteosarcoma treated on EURAMOS-1: A report from the Children's Oncology Group. Ilcisin, L., Han, R., Krailo, M. D., Gorlick, R., Nadel, H., Binitie, O., Janeway, K. A., Bona, K. LIPPINCOTT WILLIAMS & WILKINS. 2022
Predictive Patterns of Pediatric PTLD on PET/MRI Jayapal, P., Sandberg, J., Seekins, J., Nadel, H. SOC NUCLEAR MEDICINE INC. 2022
ACR Appropriateness Criteria Osteomyelitis or Septic Arthritis-Child (Excluding Axial Skeleton). Journal of the American College of Radiology : JACR Expert Panel on Pediatric Imaging, Shet, N. S., Iyer, R. S., Chan, S. S., Baldwin, K., Chandra, T., Chen, J., Cooper, M. L., Creech, C. B., Gill, A. E., Levin, T. L., Moore, M. M., Nadel, H. R., Saidinejad, M., Schooler, G. R., Squires, J. H., Swenson, D. W., Rigsby, C. K. 2022; 19 (5S): S121-S136


Imaging plays an integral role in the evaluation of suspected musculoskeletal infections in children, not only in the accurate identification of infection such as osteomyelitis or septic arthritis, but also in guiding management. Various diagnostic modalities serve different purposes in the assessment of suspected pediatric musculoskeletal infections. The purpose of this document is to provide imaging guidance in the most frequently encountered clinical scenarios in which osteomyelitis and/or septic arthritis are suspected, outside of the axial skeleton. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion.

View details for DOI 10.1016/j.jacr.2022.02.017

View details for PubMedID 35550797

ACR Appropriateness Criteria Crohn Disease-Child. Journal of the American College of Radiology : JACR Expert Panel on Pediatric Imaging, Moore, M. M., Gee, M. S., Iyer, R. S., Chan, S. S., Ayers, T. D., Bardo, D. M., Chandra, T., Cooper, M. L., Dotson, J. L., Gadepalli, S. K., Gill, A. E., Levin, T. L., Nadel, H. R., Schooler, G. R., Shet, N. S., Squires, J. H., Trout, A. T., Wall, J. J., Rigsby, C. K. 2022; 19 (5S): S19-S36


Crohn disease is an inflammatory condition of the gastrointestinal tract with episodes of exacerbation and remission occurring in children, adolescents, and adults. Crohn disease diagnosis and treatment depend upon a combination of clinical, laboratory, endoscopic, histological, and imaging findings. Appropriate use of imaging provides critical information in the settings of diagnosis, assessment of acute symptoms, disease surveillance, and therapy monitoring. Four variants are discussed. The first variant discusses the initial imaging for suspected Crohn disease before established diagnosis. The second variant pertains to appropriateness of imaging modalities during suspected acute exacerbation. The third variant is a substantial discussion of recommendations related to disease surveillance and monitoring of Crohn disease. Finally, panel recommendations and discussion of perianal fistulizing disease imaging completes the document. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

View details for DOI 10.1016/j.jacr.2022.02.020

View details for PubMedID 35550801

VALIDATION OF CONVOLUTIONAL NEURAL NETWORK FOR FAST DETERMINATION OF WHOLE-BODY METABOLIC TUMOR BURDEN IN PEDIATRIC LYMPHOMA. Journal of nuclear medicine technology Etchebehere, E., Andrade, R., Camacho, M., Lima, M., Brink, A., Cerci, J. J., Nadel, H., Bal, C., Rangarajan, V., Pfluger, T., Kagna, O., Alonso, O., Begum, F. K., Mir, K. B., Magboo, V. P., Menezes, L. J., Paez, D. D., Pascual, T. D. 2022


INTRODUCTION: 18F-FDG PET/CT whole-body tumor burden in lymphoma is not routinely performed due to the lack of fast quantification methods. Although the semi-automatic method is fast, it still lacks the necessary speed required to quantify tumor burden in daily clinical practice. PURPOSE: To evaluate the performance of the convolutional neural networks (CNN) software to localize neoplastic lesions in whole-body 18F-FDG PET/CT images of pediatric lymphoma patients. METHODS: This retrospective image data set, derived from the data pool under the IAEA (CRP# E12017), included 102 baseline staging 18F-FDG PET/CTs of pediatric lymphoma patients (mean age 11 yrs). Images were quantified to determine the whole-body (wb) tumor burden (wbMTV and wbTLG) using a semi-automatic (SEMI) software and an CNN-based software. Both were displayed as wbMTVSEMI & wbTLGSEMI and wbMTVCNN & TLGCNN. The intraclass correlation coefficient (ICC) was applied to evaluate concordance between the CNN-based software and the SEMI software. RESULTS: Twenty-six patients were excluded from the analyses because the software was unable to perform calculation. In the remaining 76 patients, wbMTVCNN and wbMTVSEMI whole-body tumor burden metrics were highly correlated (ICC=0.993; 95%CI: 0.989 -0.996; p-value<0.0001) as were wbTLGCNN and wbTLGSEMI (ICC=0.999; 95%CI: 0.998-0.999; p-value<0.0001). However, the time spent calculating these metrics was significantly (<0.0001) faster by CNN (mean = 19 seconds; 11 - 50 seconds) compared to the semi-automatic method (mean = 21.6 minutes; 3.2 - 62.1 minutes), especially in patients with advanced disease. CONCLUSION: Determining whole-body tumor burden in pediatric lymphoma patients using CNN is fast and feasible in clinical practice.

View details for DOI 10.2967/jnmt.121.262900

View details for PubMedID 35440476

SNMMI procedure standard/EANM practice guideline on pediatric [Tc-99m]Tc-DMSA renal cortical scintigraphy: an update CLINICAL AND TRANSLATIONAL IMAGING Vali, R., Armstrong, I. S., Bar-Sever, Z., Biassoni, L., Borgwardt, L., Brown, J., Grant, F. D., Mandell, G. A., Majd, M., Nadel, H. R., Ng, T. C., Roca-Bielsa, I., Rohringer, T. J., Santos, A., Seghers, V., Shaikh, N., Ted Treves, S., Zaffino-Nevrotski, T., Zucchetta, P., Lim, R. 2022
Simultaneously Acquired MRI Arterial Spin-Labeling and Interictal FDG-PET Improves Diagnosis of Pediatric Temporal Lobe Epilepsy. AJNR. American journal of neuroradiology Khalaf, A. M., Nadel, H. R., Dahmoush, H. M. 2022


BACKGROUND AND PURPOSE: Interictal FDG-PET scans are a routine diagnostic technique for the identification of epileptogenic foci in the presurgical work-up of medically refractory pediatric epilepsy. With the advent of PET/MR imaging, it has become possible to simultaneously acquire FDG-PET and arterial spin-labeling perfusion data. The objective of this study was to evaluate whether the incorporation of arterial spin-labeling data with interictal FDG-PET could improve the diagnostic performance metrics of FDG-PET for identification of epileptogenic foci.MATERIALS AND METHODS: Forty-five pediatric patients with a mean age of 10.8years were retrospectively included in this study. These patients all underwent PET/MR imaging to diagnose suspected focal epilepsy.RESULTS: When compared to interpretations of interictal FDG findings alone, FDG combined with arterial spin-labeling findings resulted in significantly decreased sensitivity (0.64 versus 0.52, P=.02), significantly increased specificity (0.50 versus 0.75, P=.04), and an increased positive predictive value (0.59 versus 0.75). The decreased sensitivity was found to be primarily driven by patients with extratemporal lobe epilepsy, as a subgroup analysis showed decreased sensitivity for patients with extratemporal epilepsy (0.52 versus 0.38, P=.04), but not for temporal epilepsy (0.83 versus 0.75, P=.16). Additionally, substantial agreement between focal FDG hypometabolism and arterial spin-labeling hypoperfusion was demonstrated with the Cohen kappa (0.70, P<.01).CONCLUSIONS: These findings suggest that simultaneously acquired interictal FDG-PET and arterial spin-labeling data can improve the diagnosis of epileptogenic foci, especially in the setting of temporal lobe epilepsy where they improve specificity and positive predictive value, with preservation of sensitivity.

View details for DOI 10.3174/ajnr.A7421

View details for PubMedID 35210273

Phase III Trial Adding Vincristine-Topotecan-Cyclophosphamide to the Initial Treatment of Patients With Nonmetastatic Ewing Sarcoma: A Children's Oncology Group Report. Journal of clinical oncology : official journal of the American Society of Clinical Oncology Leavey, P. J., Laack, N. N., Krailo, M. D., Buxton, A., Randall, R. L., DuBois, S. G., Reed, D. R., Grier, H. E., Hawkins, D. S., Pawel, B., Nadel, H., Womer, R. B., Letson, G. D., Bernstein, M., Brown, K., Maciej, A., Chuba, P., Ahmed, A. A., Indelicato, D. J., Wang, D., Marina, N., Gorlick, R., Janeway, K. A., Mascarenhas, L. 2021: JCO2100358


PURPOSE: The primary aim of this phase III randomized trial was to test whether the addition of vincristine, topotecan, and cyclophosphamide (VTC) to interval compressed chemotherapy improved survival outcomes for patients with previously untreated nonmetastatic Ewing sarcoma.METHODS: Patients were randomly assigned to receive standard five-drug interval compressed chemotherapy (regimen A) for 17 cycles or experimental therapy with five cycles of VTC within the 17 cycles (regimen B). Patients were stratified by age at diagnosis (< 18 years and 18 years) and tumor site (pelvic bone, nonpelvic bone, and extraosseous). Tumor volume at diagnosis was categorized as < 200 mL or 200 mL. Local control occurred following six cycles. Histologic response was categorized as no viable or any viable tumor. Event-free survival (EFS) and overall survival (OS) were compared between randomized groups with stratified log-rank tests.RESULTS: Of 642 enrolled patients, 309 eligible patients received standard and 320 received experimental therapy. The 5-year EFS and OS were 78% and 87%, respectively. There was no difference in survival outcomes between randomized groups (5-year EFS regimen A v regimen B, 78% v 79%; P = .192; 5-year OS 86% v 88%; P = .159). Age and primary site did not affect the risk of an EFS event. However, age 18 years was associated with an increased risk of death at 5 years (hazard ratio 1.84; 95% CI, 1.15 to 2.96; P = .009). The 5-year EFS rates for patients with pelvic, nonpelvic bone, and extraosseous primary tumors were 75%, 78%, and 85%, respectively. Tumor volume 200 mL was significantly associated with lower EFS.CONCLUSION: While VTC added to five-drug interval compressed chemotherapy did not improve survival, these outcomes represent the best survival estimates to date for patients with previously untreated nonmetastatic Ewing sarcoma.

View details for DOI 10.1200/JCO.21.00358

View details for PubMedID 34652968

MANAGEMENT OF DIFFERENTIATED THYROID CANCER: THE STANDARD OF CARE. Journal of nuclear medicine : official publication, Society of Nuclear Medicine Avram, A. M., Zukotynski, K., Nadel, H. R., Giovanella, L. M. 2021


In the past decade the management of differentiated thyroid cancer (DTC) underwent a paradigm shift towards the use of risk-stratification with the goal of maximizing benefit and minimizing morbidity of radioiodine (131I) therapy. 131I therapy is guided by information derived from surgical histopathology, molecular markers, postoperative diagnostic radioiodine scintigraphy and thyroglobulin (Tg) levels. 131I is used for diagnostic imaging and therapy of DTC based on physiologic sodium-iodine symporter expression in normal and neoplastic thyroid tissue. We summarize the essential information at the core of multidisciplinary DTC management, which emphasizes individualization of 131I therapy according to the patient's risk for tumor recurrence.

View details for DOI 10.2967/jnumed.121.262402

View details for PubMedID 34413146

The Accuracy of Incident Vertebral Fracture Detection in Children Using Targeted Case-Finding Approaches. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research Ma, J., Siminoski, K., Wang, P., Jaremko, J. L., Koujok, K., Matzinger, M. A., Shenouda, N., Lentle, B., Alos, N., Cummings, E. A., Ho, J., Houghton, K., Miettunen, P. M., Scuccimarri, R., Rauch, F., Ward, L. M., Canadian STOPP Consortium, Ward, L. M., Konji, V., Scharke, M., Sykes, E., Ho, J., Kloiber, R., Lewis, V., Midgley, J., Miettunen, P., Stephure, D., Lentle, B. C., Blydt-Hansen, T., Cabral, D., Dix, D. B., Houghton, K., Nadel, H. R., Hay, J., Feber, J., Halton, J., Jurencak, R., Koujok, K., Matzinger, M., Roth, J., Shenouda, N., Watanabe-Duffy, K., Cairney, E., Clarson, C., Filler, G., Grimmer, J., McKillop, S., Sparrow, K., Stein, R., Cummings, E., Fernandez, C., Huber, A. M., Lang, B., O'Brien, K., Arora, S., Atkinson, S., Barr, R., Coblentz, C., Dent, P. B., Larche, M., Ma, J., Abish, S., Bell, L., LeBlanc, C., Sbrocchi, A. M., Scuccimarri, R., Moher, D., Taljaard, M., Rauch, F., Alos, N., Dubois, J., Laverdiere, C., Phan, V., Saint-Cyr, C., Barsalou, J., Couch, R., Ellsworth, J., Jaremko, J., Siminoski, K., Wilson, B., Grant, R., Charron, M., Hebert, D., Gaboury, I., Taback, S., Israels, S., Oen, K., Pinsk, M., Reed, M., Rodd, C. 2021


Vertebral fractures are clinically important sequelae of a wide array of pediatric diseases. In this study we examined the accuracy of case-finding strategies for detecting incident vertebral fractures (IVF) over two years in glucocorticoid-treated children (n=343) with leukemia, rheumatic disorders, or nephrotic syndrome. Two clinical situations were addressed: the prevalent vertebral fracture (PVF) scenario (when baseline PVF status was known), which assessed the utility of PVF and low lumbar spine bone mineral density (LS BMD; Z-score<-1.4), and the Non-PVF scenario (when PVF status was unknown), which evaluated low LS BMD and back pain. LS BMD was measured by dual-energy x-ray absorptiometry, vertebral fractures were quantified on spine radiographs using the modified Genant semi-quantitative method, and back pain was assessed by patient report. Forty-four patients (12.8%) had IVF. In the PVF scenario, both low LS BMD and PVF were significant predictors of IVF. Using PVF to determine which patients should have radiographs, 11% would undergo radiography (95% CI, 8, 15) with 46% of IVF (95% CI, 30, 61) detected. Sensitivity would be higher with a strategy of PVF or low LS BMD at baseline (73%; 95% CI, 57, 85), but would require radiographs in 37% of children (95% CI, 32, 42). In the Non-PVF scenario, the strategy of low LS BMD and back pain produced the highest specificity of any non-PVF model at 87% (95% CI, 83, 91), the greatest overall accuracy at 82% (95% CI, 78, 86), and the lowest radiography rate at 17% (95% CI, 14, 22). Low LS BMD or back pain in the non-PVF scenario produced the highest sensitivity at 82% (95% CI, 67, 92), but required radiographs in 65% (95% CI, 60, 70). These results provide guidance for targeting spine radiography in children at risk for IVF.

View details for DOI 10.1002/jbmr.4294

View details for PubMedID 33784410

The paediatric thymus: recognising normal and ectopic thymic tissue. Clinical radiology Wee, T., Lee, A. F., Nadel, H., Bray, H. 2021


The appearance of the paediatric thymus changes as the normal process of thymic involution occurs. Thymic tissue may be orthotopic within the anterior mediastinum or ectopically located along the course of its embryological development. The variable appearance of orthotopic and ectopic thymic tissue in children on imaging studies may lead to misinterpretation of the normal thymus as pathology. Recognition of normal thymic tissue can mitigate unnecessary further diagnostic testing and patient anxiety. In this review, we discuss the embryological development and anatomical variants of normal thymus, and demonstrate the multimodality imaging features of the normal thymus in children, including positron-emission tomography, and diffusion-weighted imaging and in- and opposed-phase imaging on magnetic resonance imaging. We demonstrate the normal thymus mimicking pathological processes and discuss features that distinguish normal thymus, including thymic rebound hyperplasia, from pathology.

View details for DOI 10.1016/j.crad.2021.02.017

View details for PubMedID 33762135

Questions and comments about 'Pediatric applications of Dotatate: early diagnostic and therapeutic experience'. Pediatric radiology Shulkin, B. L., Nadel, H. R., Parisi, M. T. 2020

View details for DOI 10.1007/s00247-020-04872-1

View details for PubMedID 33175200

Time to Resolution of Iodine 123 Metaiodobenzylguanidine (I-123-MIBG) Avidity in Neuroblastoma Following Radiation Therapy Sodji, Q., Sandhu, N., Majzner, R., Nadel, H., Callejas, M., Donaldson, S. S., Hiniker, S. M. ELSEVIER SCIENCE INC. 2020: E238E239
Maximum tumor dimension and tumor volume as prognostic factors in patients with newly diagnosed localized Ewing sarcoma (ES)- a report from the Children's Oncology Group (COG). Mascarenhas, L., Buxton, A., DuBois, S. G., Wang, D., Laack, N. N., Brown, K. B., Pawel, B., Nadel, H., Davis, J., Hawkins, D. S., Grier, H. E., Womer, R. B., Stringham, D., Reed, D. R., Janeway, K. A., Gorlick, R., Marina, N., Bernstein, M. L., Krailo, M. D., Leavey, P., Bone Sarcoma Comm, Children's Oncology Grp AMER SOC CLINICAL ONCOLOGY. 2020
PET/MR findings in large vessel vasculitis in children Young, V., Khalsa, U., Balboni, I., Nadel, H. SOC NUCLEAR MEDICINE INC. 2020
The Utility of PET/CT in Guiding Radiotherapy Reduction for Children With Hodgkin Lymphoma Treated With ABVD JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY Ingley, K. M., Nadel, H. R., Potts, J. E., Wilson, D. C., Eftekhari, A., Deyell, R. J. 2020; 42 (2): E87E93


ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) is standard upfront chemotherapy for adults diagnosed with Hodgkin lymphoma (HL), but positron emission tomography (PET)-based response data following ABVD is lacking for pediatrics. Among children who received ABVD for HL, we document interim and end of therapy PET-computed tomography (CT) response by Deauville criteria, and survival outcomes following a response-based reduction in involved field radiotherapy (IFRT). Children 18 years of age or below with HL treated with ABVD between 2006 and 2015 who had interim PET/CT scans after 2 cycles of chemotherapy were included. Interim and end of therapy PET/CT scans were retrospectively re-evaluated using Deauville criteria by 3 radiologists. Among 45 children, 32 (71%) met criteria for intermediate risk, 86% achieved rapid early response (RER) and only 4 (9%) received upfront IFRT. Patients achieving RER had superior 5-year event-free survival (EFS) 95%4% versus 50%18% (P0.001) and overall survival (OS) 100% versus 83%15% (P=0.025). Patients with bulk who achieved RER and received no IFRT achieved 5-year EFS of 92%6% and OS 100%. Low, intermediate, and high risk patients had 5-year EFS of 100%, 94%4%, and 50%18% (P=0.002) and 5-year OS of 100%, 100%, and 75%15% (P=0.03). RER following 2 cycles of ABVD is predictive of survival outcomes in children and adolescents with HL and may identify a group who may omit IFRT.

View details for DOI 10.1097/MPH.0000000000001534

View details for Web of Science ID 000517240500004

View details for PubMedID 31259825

Ifosfamide, gemcitabine, and vinorelbine is an effective salvage regimen with excellent stem cell mobilization in relapsed or refractory pediatric Hodgkin lymphoma. Pediatric blood & cancer Marr, K. n., Ronsley, R. n., Nadel, H. n., Douglas, K. n., Gershony, S. n., Strahlendorf, C. n., Davis, J. H., Deyell, R. J. 2020: e28167


We describe 12 pediatric patients (8-16 years) with primary refractory (N=6) or first relapse (N=6) Hodgkin lymphoma (HL) treated with ifosfamide, gemcitabine, and vinorelbine (IGEV). The overall response rate to IGEV was 100%, with seven (58%) complete responses (CR) and five (42%) partial responses. Successful CD34+ stem cell mobilization was achieved in all patients. Following subsequent autologous stem cell transplantation, 10 patients (83%) achieved CR. At a median follow-up of 71 months, 11 patients had no evidence of disease. Five-year second event-free survival and overall survival were 83% 11.0% and 90.0% 9.5%, respectively. IGEV is an effective salvage regimen for children with relapsed/refractory HL.

View details for DOI 10.1002/pbc.28167

View details for PubMedID 31925920

Effects of Bisphosphonate Therapy on Bone Mineral Density in Boys with Duchenne Muscular Dystrophy. Clinical medicine insights. Endocrinology and diabetes Ronsley, R. n., Islam, N. n., Kang, M. n., Nadel, H. n., Reilly, C. n., Metzger, D. n., Selby, K. n., Panagiotopoulos, C. n. 2020; 13: 1179551420972400


The objective of this study was to estimate the comparative effectiveness of bisphosphonate therapy on bone mineral density (BMD) in patients with corticosteroid-treated Duchenne muscular dystrophy (DMD). A retrospective, comparative effectiveness study evaluating changes in BMD and fragility fractures in patients with DMD presenting to British Columbia Children's Hospital from 1989 to 2017 was conducted. Marginal structural generalized estimating equation models weighted by stabilized inverse-probability of treatment weights were used to estimate the comparative effectiveness of therapy on BMD. Of those treated with bisphosphonates (N = 38), 7 (18.4%), 17 (44.7%), and 14 (36.8%) cases were treated with pamidronate, zoledronic acid, or a combination of both, respectively, while 36 cases of DMD were untreated. Mean age of bisphosphonate initiation was 9.2 (SD 2.7) years. Mean fragility fractures declined from 3.5 to 1.0 following bisphosphonate therapy. Compared to the treated group, the untreated group had an additional 0.63-SD decrease (95% confidence interval [CI]: -1.18, -0.08, P = .026) in total BMD and an additional 1.04-SD decrease (95% CI: -1.74, -0.34; P = .004) in the left hip BMD, but the change in lumbar spine BMD (0.15, 95% CI: -0.36, 0.66; P = .57) was not significant. Bisphosphonate therapy may slow the decline in BMD in boys with corticosteroid-treated DMD compared to untreated counterparts. Total number of fragility fractures decreased following bisphosphonate therapy.

View details for DOI 10.1177/1179551420972400

View details for PubMedID 33335437

View details for PubMedCentralID PMC7724415

The Accuracy of Prevalent Vertebral Fracture Detection in Children Using Targeted Case-Finding Approaches JOURNAL OF BONE AND MINERAL RESEARCH Ma, J., Siminoski, K., Wang, P., Alos, N., Cummings, E. A., Feber, J., Halton, J., Ho, J., Houghton, K., Lang, B., Miettunen, P. M., Scuccimarri, R., Jaremko, J. L., Koujok, K., Lentle, B., Matzinger, M., Shenouda, N., Rauch, F., Ward, L. M., Ward, L. M., Ho, J., Kloiber, R., Lewis, V., Midgley, J., Miettunen, P., Stephure, D., Lentle, B. C., Blydt-Hansen, T., Cabral, D., Dix, D. B., Houghton, K., Nadel, H. R., Hay, J., Feber, J., Halton, J., Jurencak, R., Ma, J., Matzinger, M., Roth, J., Shenouda, N., Watanabe-Duffy, K., Cairney, E., Clarson, C., Filler, G., Grimmer, J., McKillop, S., Sparrow, K., Stein, R., Cummings, E., Fernandez, C., Huber, A. M., Lang, B., O'Brien, K., Arora, S., Atkinson, S., Barr, R., Coblentz, C., Dent, P. B., Larche, M., Abish, S., Bell, L., LeBlanc, C., Sbrocchi, A., Scuccimarri, R., Moher, D., Taljaard, M., Rauch, F., Alos, N., Dubois, J., Laverdiere, C., Phan, V., Saint-Cyr, C., Barsalou, J., Couch, R., Ellsworth, J., Jaremko, J., Siminoski, K., Wilson, B., Grant, R., Charron, M., Hebert, D., Gaboury, I., Taback, S., Israels, S., Oen, K., Pinsk, M., Reed, M., Rodd, C., Canadian Steroid-Induced 2020; 35 (3): 46068


Due to concerns about cumulative radiation exposure in the pediatric population, it is not standard practice to perform spine radiographs in most conditions that predispose to vertebral fracture (VF). In this study we examined the accuracy of two clinical predictors, back pain and lumbar spine bone mineral density (LS BMD), to derive four case-finding paradigms for detection of prevalent VF (PVF). Subjects were 400 children at risk for PVF (leukemia 186, rheumatic disorders 135, nephrotic syndrome 79). Back pain was assessed by patient report, LS BMD was measured by dual-energy X-ray absorptiometry, and PVF were quantified on spine radiographs using the modified Genant semiquantitative method. Forty-four patients (11.0%) had PVF. Logistic regression analysis between LS BMD and PVF produced an odds ratio (OR) of 1.9 (95% confidence interval [CI], 1.5 to 2.5) per reduction in Z-score unit, an area under the receiver operating characteristic curve of 0.70 (95% CI, 0.60 to 0.79), and an optimal BMD Z-score cutoff of -1.6. Case identification using either low BMD alone (Z-score<-1.6) or back pain alone gave similar results for sensitivity (55%, 52%, respectively), specificity (78%, 81%, respectively), positive predictive value (PPV; 24%, 25%, respectively), and negative predictive value (NPV; 93%, 93%, respectively). The paradigm using low BMD plus back pain produced lower sensitivity (32%), higher specificity (96%), higher PPV (47%), and similar NPV (92%). The approach using low BMD or back pain had the highest sensitivity (75%), lowest specificity (64%), lowest PPV (20%), and highest NPV (95%). All paradigms had increased sensitivities for higher fracture grades. Our results show that BMD and back pain history can be used to identify children with the highest risk of PVF so that radiography can be used judiciously. The specific paradigm to be applied will depend on the expected PVF rate and the clinical approach to the use of radiography. 2019 American Society for Bone and Mineral Research.

View details for DOI 10.1002/jbmr.3922

View details for Web of Science ID 000502939900001

View details for PubMedID 31742768

Imaging for diagnosis, staging and response assessment of Hodgkin lymphoma and non-Hodgkin lymphoma. Pediatric radiology McCarten, K. M., Nadel, H. R., Shulkin, B. L., Cho, S. Y. 2019; 49 (11): 154564


Hodgkin lymphoma and non-Hodgkin lymphoma are common malignancies in children and are now highly treatable. Imaging plays a major role in diagnosis, staging and response using conventional CT and MRI and metabolic imaging with positron emission tomography (PET)/CT and PET/MRI. Cross-sectional imaging has replaced staging laparotomy and splenectomy by demonstrating abdominal nodal groups and organ involvement. [F-18]2-fluoro-2-deoxyglucose (FDG) PET provides information on bone marrow involvement, and MRI elucidates details of cortical bone and confirmation of bone marrow involvement. The staging system for Hodgkin lymphoma is the Ann Arbor system with Cotswald modifications and is based on imaging, whereas the non-Hodgkin staging system is the St. Jude Classification by Murphy or the more recent revised International Pediatric Non-Hodgkin Lymphoma Staging System (IPNHLSS). Because all pediatric lymphomas are metabolically FDG-avid and identify all nodal, solid organ, cortical bone and bone marrow disease, staging evaluations require FDG PET as PET/CT or PET/MRI in both Hodgkin and non-Hodgkin lymphoma. Both diseases have in common issues of airway compromise at presentation demonstrated by imaging. Differences exist in that Hodgkin lymphoma has several independent poor prognostic factors seen by imaging such as large mediastinal adenopathy, Stage IV disease, systemic symptoms, pleural effusion and pericardial effusion. Non-Hodgkin lymphoma includes more organ involvement such as renal, ovary, central nervous system and skin. Early or interim PET-negative scans are a reliable indicator of improved clinical outcome and optimize risk-adapted therapy and patient management; imaging may not, however, predict who will relapse. A recent multicenter trial has concluded that it is usually sufficient for pediatric lymphoma at staging and interim assessment to evaluate children with PET imaging from skull base to mid-thigh. Various systems of assessment of presence of disease or response are used, including the Deauville visual scale, where avidity is compared to liver; Lugano, which includes size change as part of response; or quantitative PET, which uses standardized uptake values to define more accurate response. Newer methods of immunotherapy can produce challenges in FDG PET evaluation because of inflammatory changes that may not represent disease.

View details for DOI 10.1007/s00247-019-04529-8

View details for PubMedID 31620854

ALK-Positive Lung Adenocarcinoma Arising in an Adolescent Treated for Relapsed Neuroblastoma. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer Alwelaie, Y., Deyell, R. J., Nadel, H. R., Tucker, T., Laskin, J., Rassekh, S. R., Zhou, C., English, J. C., Lee, A. F. 2019; 14 (6): e132e135

View details for DOI 10.1016/j.jtho.2019.02.010

View details for PubMedID 31122568

Use of optimized post-contrast enhanced PET/CT to improve diagnostic accuracy, staging, and follow-up of children with cancer Nadel, H., Kong, M., Potts, J., Strahlendorf, C. SOC NUCLEAR MEDICINE INC. 2019
Assessment of the Reconstructed Pulmonary Circulation With Lung Perfusion Scintigraphy After Unifocalization and Repair of Tetralogy of Fallot With Major Aortopulmonary Collaterals. World journal for pediatric & congenital heart surgery Wise-Faberowski, L., Irvin, M., Lennig, M., Long, J., Nadel, H. R., Bauser-Heaton, H., Asija, R., Hanley, F. L., McElhinney, D. B. 2019; 10 (3): 31320


BACKGROUND: Pulmonary vascular supply in tetralogy of Fallot (TOF) with major aortopulmonary collaterals (MAPCAs) is highly variable. Our approach to surgical management of this condition emphasizes early repair including unifocalization and reconstruction of the pulmonary circulation, incorporating all lung segments and addressing stenoses both proximal to and within the lung, in addition to ventricular septal defect closure. At our institution, we have over 15 years of experience using lung perfusion scintigraphy (LPS) to assess the distribution of pulmonary blood flow after complete unifocalization and repair.METHODS: We reviewed clinical and quantitative LPS data in 310 patients who underwent complete unifocalization and repair of TOF/MAPCAs from 2003 to 2018 at our institution. Postrepair relative lung perfusion distributions were determined from LPS initially obtained at our institution within 60 days after repair and thereafter.RESULTS: Total lung perfusion to the right and left lungs was 58.0% 14.2% and 42.0% 14.2%, respectively. Perfusion was balanced in 75% of patients and unbalanced in 25%, including 11% in whom it was extremely unbalanced. On multivariable analysis, older age at repair, surgery other than a single-stage complete unifocalization, and native anatomy consisting of unilateral pulmonary blood supply through a ductus arteriosus were associated with unbalanced perfusion.CONCLUSION: We present our experience using LPS as an outcome measure after surgical repair of TOF/MAPCAs. Balanced lung perfusion was present in the majority of patients who had complete repair of TOF/MAPCAs performed at our center.

View details for PubMedID 31084304

Impact of Vertebral Fractures and Glucocorticoid Exposure on Height Deficits in Children During Treatment of Leukemia JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM Ma, J., Siminoski, K., Alos, N., Halton, J., Ho, J., Cummings, E. A., Shenouda, N., Matzinger, M., Lentle, B., Jaremko, J. L., Wilson, B., Stephure, D., Stein, R., Sbrocchi, A., Rodd, C., Lewis, V. A., Laverdiere, C., Israels, S., Grant, R. M., Fernandez, C., Dix, D. B., Couch, R., Cairney, E., Barr, R., Atkinson, S., Abish, S., Moher, D., Rauch, F., Ward, L. M., Kloiber, R., Lewis, V., Midgley, J., Miettunen, P., Lentle, B. C., Blydt-Hansen, T., Cabral, D., Houghton, K., Nadel, H. R., Hay, J., Feber, J., Jurencak, R., Ma, J., Matzinger, M., Roth, J., Watanabe-Duffy, K., Clarson, C., Filler, G., Grimmer, J., McKillop, S., Sparrow, K., Huber, A. M., Lang, B., O'Brien, K., Arora, S., Dent, P. B., Coblentz, C., Larche, M., Bell, L., LeBlanc, C., Scuccimarri, R., Dubois, J., Phan, V., Saint-Cyr, C., Ellsworth, J., Jaremko, J., Grant, R., Charron, M., Hebert, D., Gaboury, I., Oen, K., Pinsk, M., Reed, M., Taback, S., Canadian STOPP Consortium 2019; 104 (2): 21322


To assess the effect of vertebral fractures (VF) and glucocorticoid (GC) exposure on height deficits in children during treatment of acute lymphoblastic leukemia (ALL).Children with ALL treated without cranial radiation therapy (n = 160; median age, 5.1 years; 58.1% male) were followed prospectively for 6 years. Spinal deformity index (SDI) was used to quantify VF status.Baseline height z score SD was 0.3 1.2. It fell by 0.5 0.4 in the first 6 months for boys and by 0.4 0.4 in the first 12 months for girls (P < 0.01 for both) and then subsequently recovered. The prevalence of VF peaked at 1 year (17.6%). Among those with VF, median SDI rose from 2 [interquartile range (IQR): 1, 7] at baseline to 8 (IQR: 1, 8) at 1 year. A mixed model for repeated measures showed that height z score declined by 0.13 (95% CI: 0.02 to 0.24; P = 0.02) for each 5-unit increase in SDI during the previous 12 months. Every 10 mg/m2 increase in average daily GC dose (prednisone equivalent) in the previous 12 months was associated with a height z score decrement of 0.26 (95% CI: 0.20 to 0.32; P < 0.01).GC likely plays a major role in the observed height decline during therapy for ALL. Because only a minority of children had VF, fractures could not have contributed significantly to the height deficit in the entire cohort but may have been important among the subset with VF.

View details for DOI 10.1210/jc.2018-01083

View details for Web of Science ID 000462864100001

View details for PubMedID 30247635

View details for PubMedCentralID PMC6291659

Is True Whole-body FDG-PET/CT required in paediatric lymphoma? An IAEA Multicentre Prospective Study. Journal of nuclear medicine : official publication, Society of Nuclear Medicine Cerci, J. J., Etchebehere, E. C., Nadel, H., Brink, A., Bal, C. S., Rangarajan, V., Pfluger, T., Kagna, O., Alonso, O., Begum, F. K., Bashir Mir, K., Magboo, V. P., Menezes, L. J., Paez, D., Pascual, T. N. 2019


INTRODUCTION: Guidelines recommend true whole body (TWB) FDG-PET/CT scans from vertex to toes in paediatric lymphoma patients, although this suggestion has not been validated in large clinical trials. The objective of the study is to evaluate the incidence and clinical impact of lesions outside the "eyes to thighs" regular field of view (R-FOV) in FDG-PET/CT staging (sPET) and interim (iPET) scans in paediatric lymphoma patients. MATERIALS AND METHODS: TWB sPET and iPET scans were prospectively performed in paediatric lymphoma patients (11 worldwide centres). Expert panel central review of sPET and iPET scans were evaluated for lymphoma lesions outside the R-FOV, and clinical relevance of this findings. RESULTS: A total of 610 scans were performed in 305 patients. The sPET scans did not show lesions outside the R-FOV in 91.8% of the patients, while in 8.2% patients the sPET scans demonstrated lesions also outside the R-FOV (soft tissue, bone, bone marrow and skin); however, the presence of these lesions did not change the clinical stage of any patient and did not impact on treatment decision. Among the 305 iPET scans, there were no new positive FDG-avid lesions outside the R-FOV, when compared to their paired sPET scans. A single lesion outside the R-FOV on iPET occurred in one patient (0.3%) with the primary lesion diagnosed in the femur on sPET that persisted on iPET. CONCLUSION: The identification of additional lesions outside RFOV (eyes to thighs) FDG-PET/CT has no impact in the definition of the clinical stage of disease and minimal impact in the treatment definition of patients with pediatric lymphoma. As so, reduced field of view for both staging and interim FDG-PET/CT scans could be performed.

View details for PubMedID 30683766

Update 2018: 18F-FDG PET/CT and PET/MRI in Head and Neck Cancer. Clinical nuclear medicine Sanli, Y., Zukotynski, K., Mittra, E., Chen, D. L., Nadel, H., Niederkohr, R. D., Subramaniam, R. M. 2018; 43 (12): e439e452


There are recent advances, namely, a standardized method for reporting therapy response (Hopkins criteria), a multicenter prospective cohort study with excellent negative predictive value of F-FDG PET/CT for N0 clinical neck, a phase III multicenter randomized controlled study establishing the value of a negative posttherapy F-FDG PET/CT for patient management, a phase II randomized controlled study demonstrating radiation dose reduction strategies for human papilloma virus-related disease, and Food and Drug Administration approval of nivolumab for treatment of recurrent head and neck squamous cell carcinoma.

View details for PubMedID 30394934

Computer-assisted Curie scoring for metaiodobenzylguanidine (MIBG) scans in patients with neuroblastoma PEDIATRIC BLOOD & CANCER Sokol, E. A., Engelmann, R., Kang, W., Pinto, N., Starkey, A., Lai, H., Nadel, H., Shulkin, B. L., Pu, Y., Appelbaum, D., Yanik, G. A., Cohn, S. L., Armato, S. G., Volchenboum, S. 2018; 65 (12): e27417


Radiolabeled metaiodobenzylguanidine (MIBG) is sensitive and specific for detecting neuroblastoma. The extent of MIBG-avid disease is assessed using Curie scores. Although Curie scoring is prognostic in patients with high-risk neuroblastoma, there is no standardized method to assess the response of specific sites of disease over time. The goal of this study was to develop approaches for Curie scoring to facilitate the calculation of scores and comparison of specific sites on serial scans.We designed three semiautomated methods for determining Curie scores, each with increasing degrees of computer assistance. Method A was based on visual assessment and tallying of MIBG-avid lesions. For method B, scores were tabulated from a schematic that associated anatomic regions to MIBG-positive lesions. For method C, an anatomic mesh was used to mark MIBG-positive lesions with automatic assignment and tallying of scores. Five imaging physicians experienced in MIBG interpretation scored 38 scans using each method, and the feasibility and utility of the methods were assessed using surveys.There was good reliability between methods and observers. The user-interface methods required 57 to 110 seconds longer than the visual method. Imaging physicians indicated that it was useful that methods B and C enabled tracking of lesions. Imaging physicians preferred method B to method C because of its efficiency.We demonstrate the feasibility of semiautomated approaches for Curie score calculation. Although more time was needed for strategies B and C, the ability to track and document individual MIBG-positive lesions over time is a strength of these methods.

View details for DOI 10.1002/pbc.27417

View details for Web of Science ID 000447556600055

View details for PubMedID 30198643

View details for PubMedCentralID PMC6317352

Pediatric Esophageal Squamous Cell Carcinoma Staged With 18F-FDG PET/CT CLINICAL NUCLEAR MEDICINE Kong, M., Nadel, H. 2018; 43 (12): 94648


A 15-year-old boy with autism and swallowing dysfunction presented with a 6-month history of fatigue, intermittent abdominal pain, and weight loss. He later became febrile and had multiple episodes of coffee ground emesis and melena stools. An upper endoscopy showed an esophageal mass, and a subsequent F-FDG PET/CT scan confirmed this finding. PET/CT also revealed metastatic disease in local lymph nodes, thus upstaging the patient and indicating poor prognosis. Consideration of these severe results and the patient's quality of life helped guide decision making in patient management, with the ultimate decision to pursue palliative care.

View details for DOI 10.1097/RLU.0000000000002319

View details for Web of Science ID 000450431900036

View details for PubMedID 30325821

Update 2018: 18F-FDG PET/CT and PET/MRI in Head and Neck Cancer CLINICAL NUCLEAR MEDICINE Sanli, Y., Zukotynski, K., Mittra, E., Chen, D. L., Nadel, H., Niederkohr, R. D., Subramaniam, R. M. 2018; 43 (12): E439E452
True Whole-Body Versus Standard F-18-FDG PET/CT Acquisition For Staging Pediatric Lymphoma Cerci, J., Etchebehere, E., Nadel, H., Brink, A., Bal, C., Rangarajan, V., Pfluger, T., Kagna, O., Alonso, O., Begum, F., Mir, K., Magboo, V., Menezes, L., Paez, D., Pascual, T. SPRINGER. 2018: S187S188
Guidelines on nuclear medicine imaging in neuroblastoma EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING Bar-Sever, Z., Biassoni, L., Shulkin, B., Kong, G., Hofman, M. S., Lopci, E., Manea, I., Koziorowski, J., Castellani, R., Boubaker, A., Lambert, B., Pfluger, T., Nadel, H., Sharp, S., Giammarile, F. 2018; 45 (11): 200924


Nuclear medicine has a central role in the diagnosis, staging, response assessment and long-term follow-up of neuroblastoma, the most common solid extracranial tumour in children. These EANM guidelines include updated information on 123I-mIBG, the most common study in nuclear medicine for the evaluation of neuroblastoma, and on PET/CT imaging with 18F-FDG, 18F-DOPA and 68Ga-DOTA peptides. These PET/CT studies are increasingly employed in clinical practice. Indications, advantages and limitations are presented along with recommendations on study protocols, interpretation of findings and reporting results.

View details for DOI 10.1007/s00259-018-4070-8

View details for Web of Science ID 000443332200017

View details for PubMedID 29938300

18F-FDG PET/CT With Diffusely High FDG Uptake Throughout Subcutaneous Adipose Tissues CLINICAL NUCLEAR MEDICINE Kong, M., Nadel, H. 2018; 43 (10): 76263


A 9-year-old girl presented with facial rash, angioedema, fevers, and night sweats. She was diagnosed with chronic active Epstein-Barr virus infection and placed on chronic steroid treatment. F-FDG PET/CT performed 3 weeks following presentation revealed diffuse subcutaneous soft tissue FDG activation throughout the entire body, with likely localization to white subcutaneous adipose tissue. This highly unusual appearance may have been due to the patient being treated with corticosteroids at the time of the scan.

View details for DOI 10.1097/RLU.0000000000002216

View details for Web of Science ID 000444969500030

View details for PubMedID 30036247

Validation of Standardized Interpretation Criteria for Early Response Evaluation with (18)FDG-PET/CT in Pediatric Lymphoma-A Report on an IAEA Multicenter Prospective Study Nadel, H., Etchebehere, E., Cerci, J., Brink, A., Bal, C., Rangarajan, V., Pfluger, T., Kagna, O., Alonso, O., Begum, F., Bashir Ali, K., Magboo, V., Menezes, L., Paez, D., Pascual, T. SPRINGER. 2018: S187
Initial Experience in Children Using Solid State SPECT/CT Gamma Camera for I-123 mIBG Imaging Nadel, H. R., Kong, M. C., Anderton, W. SPRINGER. 2018: S710
Case - Bladder paraganglioma in a pediatric patient CUAJ-CANADIAN UROLOGICAL ASSOCIATION JOURNAL Malhotra, A. K., Yan, R., Tabeshi, R., Nadel, H., Tran, H., Masterson, J. 2018; 12 (5): E260E264

View details for DOI 10.5489/cuaj.4937

View details for Web of Science ID 000435124700011

View details for PubMedID 29405904

View details for PubMedCentralID PMC5966941

Application of genomics to identify therapeutic targets in recurrent pediatric papillary thyroid carcinoma COLD SPRING HARBOR MOLECULAR CASE STUDIES Ronsley, R., Rassekh, S., Shen, Y., Lee, A. F., Jantzen, C., Halparin, J., Albert, C., Hawkins, D. S., Amed, S., Rothstein, R., Mungall, A. J., Dix, D., Blair, G., Nadel, H., Jones, S. M., Laskin, J., Marra, M. A., Deyell, R. J. 2018; 4 (2)


Children with papillary thyroid carcinoma (PTC) may relapse despite response to radioactive iodine (RAI). Two children with multiply relapsed PTC underwent whole-genome and transcriptome sequencing. A TPM3-NTRK1 fusion was identified in one tumor, with outlier NTRK1 expression compared to the TCGA thyroid cancer compendium and to Illumina BodyMap normal thyroid. This patient demonstrated resolution of multiple pulmonary nodules without toxicity on oral TRK inhibitor therapy. A RET fusion was identified in the second tumor, another potentially actionable finding. Identification of oncogenic drivers in recurrent pediatric PTC may facilitate targeted therapy while avoiding repeated RAI.

View details for DOI 10.1101/mcs.a002568

View details for Web of Science ID 000450956000013

View details for PubMedID 29610391

View details for PubMedCentralID PMC5880264

Validation of Postinduction Curie Scores in High-Risk Neuroblastoma: A Children's Oncology Group and SIOPEN Group Report on SIOPEN/HR-NBL1 JOURNAL OF NUCLEAR MEDICINE Yanik, G. A., Parisi, M. T., Naranjo, A., Nadel, H., Gelfand, M. J., Park, J. R., Ladenstein, R. L., Poetschger, U., Boubaker, A., Valteau-Couanet, D., Lambert, B., Castellani, M., Bar-Sever, Z., Oudoux, A., Kaminska, A., Kreissman, S. G., Shulkin, B. L., Matthay, K. K. 2018; 59 (3): 5028


A semiquantitative 123I-metaiodobenzylguanidine (123I-MIBG) scoring method (the Curie score, or CS) was previously examined in the Children's Oncology Group (COG) high-risk neuroblastoma trial, COG A3973, with a postinduction CS of more than 2 being associated with poor event-free survival (EFS). The validation of the CS in an independent dataset, International Society of Paediatric Oncology European Neuroblastoma/High-Risk Neuroblastoma 1 (SIOPEN/HR-NBL1), is now reported. Methods: A retrospective analysis of 123I-MIBG scans obtained from patients who had been prospectively enrolled in SIOPEN/HR-NBL1 was performed. All patients exhibited 123I-MIBG-avid, International Neuroblastoma Staging System stage 4 neuroblastoma. 123I-MIBG scans were evaluated at 2 time points, diagnosis (n = 345) and postinduction (n = 330), before consolidation myeloablative therapy. Scans of 10 anatomic regions were evaluated, with each region being scored 0-3 on the basis of disease extent and a cumulative CS generated. Cut points for outcome analysis were identified by Youden methodology. CSs from patients enrolled in COG A3973 were used for comparison. Results: The optimal cut point for CS at diagnosis was 12 in SIOPEN/HR-NBL1, with a significant outcome difference by CS noted (5-y EFS, 43.0% 5.7% [CS 12] vs. 21.4% 3.6% [CS > 12], P < 0.0001). The optimal CS cut point after induction was 2 in SIOPEN/HR-NBL1, with a postinduction CS of more than 2 being associated with an inferior outcome (5-y EFS, 39.2% 4.7% [CS 2] vs. 16.4% 4.2% [CS > 2], P < 0.0001). The postinduction CS maintained independent statistical significance in Cox models when adjusted for the covariates of age and MYCN gene copy number. Conclusion: The prognostic significance of postinduction CSs has now been validated in an independent cohort of patients (SIOPEN/HR-NBL1), with a postinduction CS of more than 2 being associated with an inferior outcome in 2 independent large, cooperative group trials.

View details for DOI 10.2967/jnumed.117.195883

View details for Web of Science ID 000426474300048

View details for PubMedID 28887399

View details for PubMedCentralID PMC5868501

COMPUTER-ASSISTED CURIE SCORING OF METAIODOBEN-ZYLGUANIDINE SCANS FOR PATIENTS WITH NEUROBLASTOMA. Sokol, E., Engelmann, R., Pinto, N., Starkey, A., Nall, M., Lai, H., Nadel, H., Shulkin, B., Pu, Y., Appelbaum, D., Yanik, G., Cohn, S., Armato, S., Volchenboum, S. WILEY. 2018: S51
Nivolumab in the Treatment of Refractory Pediatric Hodgkin Lymphoma JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY Foran, A. E., Nadel, H. R., Lee, A. F., Savage, K. J., Deyell, R. J. 2017; 39 (5): E263E266


The programmed death-1 (PD-1) pathway of immune evasion is exploited by many malignancies to limit host T-cell-mediated immune responses. Nivolumab is a PD-1-blocking monoclonal antibody that disrupts this pathway and is FDA approved for the treatment of metastatic melanoma, renal cell carcinoma, and squamous non-small cell lung cancer. In this case report, we describe the first published pediatric experience of nivolumab in refractory classic Hodgkin lymphoma. In this patient with primary refractory disease and high disease burden, cytokine release syndrome requiring inotropic support developed following the first infusion of nivolumab. The patient subsequently demonstrated a dramatic clinical response with resolution of fevers, transfusion independence, improvement in functional status, and very good partial response on PET/CT following a single dose. Nivolumab was continued with corticosteroid and antihistamine premedication without further adverse events and clinical benefit was sustained at 11 months after therapy initiation, despite evidence of slow radiographic disease progression.

View details for DOI 10.1097/MPH.0000000000000703

View details for Web of Science ID 000404121900006

View details for PubMedID 27841828

American College of Radiology and Society of Nuclear Medicine and Molecular Imaging Joint Credentialing Statement for PET/MR Imaging: Body. Journal of nuclear medicine Subramaniam, R. M., Jadvar, H., Colletti, P. M., Guimaraes, A., Gullapali, R., Iagaru, A. H., McConathy, J., Meltzer, C. C., Nadel, H., Noto, R. B., Packard, A. B., Rohren, E., Oates, M. E. 2017


This joint statement is intended to guide credentialing bodies that privilege physicians to oversee the performance of and participation in the interpretation of PET/MR imaging in adult and pediatric patients in the United States.

View details for DOI 10.2967/jnumed.117.193524

View details for PubMedID 28473601

Response Assessment Criteria and Their Applications in Lymphoma: Part 2 JOURNAL OF NUCLEAR MEDICINE Moghbel, M. C., Mittra, E., Gallamini, A., Niederkohr, R., Chen, D. L., Zukotynski, K., Nadel, H., Kostakoglu, L. 2017; 58 (1): 13-22


Interim and end-of-treatment PET/CT have become central to the evaluation of Hodgkin and non-Hodgkin lymphoma. This review article seeks to aid clinical decision making by providing an overview of available data on the diagnostic and prognostic value of PET/CT imaging for response assessment and pretransplant evaluation in lymphoma. The relative strengths and limitations of these techniques in various disease subtypes and clinical scenarios are explored, along with their current standards for reporting and latest developments. Particular attention is given to response-adapted therapy, which is emerging as a cornerstone of clinical management.

View details for DOI 10.2967/jnumed.116.184242

View details for Web of Science ID 000391343400012

View details for PubMedID 27879369

The Way Towards an International MIBG Skeletal Score for High Risk Neuroblastoma: The Statistical Perspective Poetschger, U., Naranjo, A., Yanik, G., Castellani, M. R., Lambert, B., Lewington, V., Bar-Server, Z., Oudoux, A., Kaminska, A., Taborska, K., Biassoni, L., Parisi, M. T., Shulkin, B. L., Nadel, H. R., Gelfand, M., Park, J., Kreissman, S. G., Valteau-Couanet, D., Matthay, K. K., Ladenstein, R. WILEY-BLACKWELL. 2016: S39S40
Response Assessment Criteria and Their Applications in Lymphoma: Part 1 JOURNAL OF NUCLEAR MEDICINE Moghbel, M. C., Kostakoglu, L., Zukotynski, K., Chen, D. L., Nadel, H., Niederkohr, R., Mittra, E. 2016; 57 (6): 928-935


The effectiveness of cancer therapy, both in individual patients and across populations, requires a systematic and reproducible method for evaluating response to treatment. Early efforts to meet this need resulted in the creation of numerous guidelines for quantifying posttherapy changes in disease extent, both anatomically and metabolically. Over the past few years, criteria for disease response classification have been developed for specific cancer histologies. To date, the spectrum of disease broadly referred to as lymphoma is perhaps the most common for which disease response classification is used. This review article provides an overview of the existing response assessment criteria for lymphoma and highlights their respective methodologies and validities. Concerns over the technical complexity and arbitrary thresholds of many of these criteria, which have impeded the long-standing endeavor of standardizing response assessment, are also discussed.

View details for DOI 10.2967/jnumed.115.166280

View details for Web of Science ID 000377052400045

View details for PubMedID 27127227

Skeletal scintigraphy with SPECT/CT in benign pediatric bone conditions CLINICAL AND TRANSLATIONAL IMAGING De Palma, D., Nadel, H. R., Bar-Sever, Z. 2016; 4 (3): 191201
Computer-assisted Curie scoring for metaiodobenzylguanidine mIBG) scans in patients with neuroblastoma. Sokol, E., Engelmann, R., Pinto, N. R., Starkey, A., Nall, M., Lai, H., Nadel, H. R., Shulkin, B. L., Pu, Y., Applebaum, D., Yanik, G. A., Cohn, S., Armato, S., Volchenboum, S. AMER SOC CLINICAL ONCOLOGY. 2016
Peritoneal-pericardial communication in an adolescent on peritoneal dialysis PEDIATRIC NEPHROLOGY Teoh, C., Nadel, H., Armstrong, K., Harris, K. C., White, C. T. 2016; 31 (1): 15356


Dialysate leakage into the pericardium is a rare but potentially life-threatening complication of peritoneal dialysis (PD). There has been one reported pediatric case of spontaneous peritoneo-pericardial fistula in a 2-year-old boy with tissue fragility due to malnutrition and two reported adult cases in PD patients with a history of previous cardiac surgery and/or pericardiocentesis.We describe a 15-year-old girl with end-stage renal disease secondary to granulomatosis with polyangiitis, with recurrent pericardial effusions secondary to a peritoneo-pericardial fistula while on continuous cycling peritoneal dialysis (CCPD). She had previously presented with chylous pericardial effusion that required pericardiocentesis and subsequently developed recurrent pericardial effusions when she was commenced on CCPD 9 months later. Pericardial fluid chemistry revealed a sterile, serous fluid containing 15.1 mmol/L of glucose and <0.11 mmol/L of triglycerides. Peritoneal scintigraphy with Tc-99m labeled sulfur colloid injected intra-peritoneally confirmed the presence of a peritoneo-pericardial fistula. The pericardial effusions resolved upon switching the patient to hemodialysis (HD).Our case of recurrent pericardial effusions in a child on PD secondary to a peritoneo-pericardial fistula highlights the need for close follow-up in patients with a history of previous pericardiocentesis who are commenced on PD.

View details for DOI 10.1007/s00467-015-3206-3

View details for Web of Science ID 000365100500019

View details for PubMedID 26386589

Incident Vertebral Fractures and Risk Factors in the First Three Years Following Glucocorticoid Initiation Among Pediatric Patients With Rheumatic Disorders JOURNAL OF BONE AND MINERAL RESEARCH LeBlanc, C. A., Ma, J., Taljaard, M., Roth, J., Scuccimarri, R., Miettunen, P., Lang, B., Huber, A. M., Houghton, K., Jaremko, J. L., Ho, J., Shenouda, N., Matzinger, M., Lentle, B., Stein, R., Sbrocchi, A., Oen, K., Rodd, C., Jurencak, R., Cummings, E. A., Couch, R., Cabral, D. A., Atkinson, S., Alos, N., Rauch, F., Siminoski, K., Ward, L. M., Canadian STeroid Associated Osteop 2015; 30 (9): 166775


Vertebral fractures are an important yet underrecognized manifestation of osteoporosis in children with chronic, glucocorticoid-treated illnesses. Our goal was to determine the incidence and clinical predictors of vertebral fractures in the 3 years following glucocorticoid initiation among pediatric patients with rheumatic disorders. Incident vertebral fractures were evaluated according to the Genant semiquantitative method on lateral radiographs at baseline and then annually in the 3 years following glucocorticoid initiation. Extended Cox models were used to assess the association between vertebral fractures and clinical risk predictors. A total of 134 children with rheumatic disorders were enrolled in the study (mean standard deviation (SD) age 9.9 4.4 years; 65% girls). The unadjusted vertebral fracture incidence rate was 4.4 per 100 person-years, with a 3-year incidence proportion of 12.4%. The highest annual incidence occurred in the first year (6.0%; 95% confidence interval (CI) 2.9% to 11.7%). Almost one-half of the patients with fractures were asymptomatic. Every 0.5 mg/kg increase in average daily glucocorticoid (prednisone equivalents) dose was associated with a twofold increased fracture risk (hazard ratio (HR) 2.0; 95% CI 1.1 to 3.5). Other predictors of increased vertebral fracture risk included: (1) increases in disease severity scores between baseline and 12 months; (2) increases in body mass index Z-scores in the first 6 months of each 12-month period preceding the annual fracture assessment; and (3) decreases in lumbar spine bone mineral density Z-scores in the first 6 months of glucocorticoid therapy. As such, we observed that a clinically significant number of children with rheumatic disorders developed incident vertebral fractures in the 3 years following glucocorticoid initiation. Almost one-half of the children were asymptomatic and thereby would have been undiagnosed in the absence of radiographic monitoring. In addition, discrete clinical predictors of incident vertebral fractures were evident early in the course of glucocorticoid therapy.

View details for DOI 10.1002/jbmr.2511

View details for Web of Science ID 000359866800014

View details for PubMedID 25801315

View details for PubMedCentralID PMC4556451

Methotrexate, Doxorubicin, and Cisplatin (MAP) Plus Maintenance Pegylated Interferon Alfa-2b Versus MAP Alone in Patients With Resectable High-Grade Osteosarcoma and Good Histologic Response to Preoperative MAP: First Results of the EURAMOS-1 Good Response Randomized Controlled Trial. Journal of clinical oncology Bielack, S. S., Smeland, S., Whelan, J. S., Marina, N., Jovic, G., Hook, J. M., Krailo, M. D., Gebhardt, M., Ppai, Z., Meyer, J., Nadel, H., Randall, R. L., Deffenbaugh, C., Nagarajan, R., Brennan, B., Letson, G. D., Teot, L. A., Goorin, A., Baumhoer, D., Kager, L., Werner, M., Lau, C. C., Sundby Hall, K., Gelderblom, H., Meyers, P., Gorlick, R., Windhager, R., Helmke, K., Eriksson, M., Hoogerbrugge, P. M., Schomberg, P., Tunn, P., Khne, T., Jrgens, H., van den Berg, H., Bhling, T., Picton, S., Renard, M., Reichardt, P., Gerss, J., Butterfass-Bahloul, T., Morris, C., Hogendoorn, P. C., Seddon, B., Calaminus, G., Michelagnoli, M., Dhooge, C., Sydes, M. R., Bernstein, M. 2015; 33 (20): 2279-2287


EURAMOS-1, an international randomized controlled trial, investigated maintenance therapy with pegylated interferon alfa-2b (IFN--2b) in patients whose osteosarcoma showed good histologic response (good response) to induction chemotherapy.At diagnosis, patients age 40 years with resectable high-grade osteosarcoma were registered. Eligibility after surgery for good response random assignment included two cycles of preoperative MAP (methotrexate, doxorubicin, and cisplatin), macroscopically complete surgery of primary tumor, < 10% viable tumor, and no disease progression. These patients were randomly assigned to four additional cycles MAP with or without IFN--2b (0.5 to 1.0 g/kg per week subcutaneously, after chemotherapy until 2 years postregistration). Outcome measures were event-free survival (EFS; primary) and overall survival and toxicity (secondary).Good response was reported in 1,041 of 2,260 registered patients; 716 consented to random assignment (MAP, n = 359; MAP plus IFN--2b, n = 357), with baseline characteristics balanced by arm. A total of 271 of 357 started IFN--2b; 105 stopped early, and 38 continued to receive treatment at data freeze. Refusal and toxicity were the main reasons for never starting IFN--2b and for stopping prematurely, respectively. Median IFN--2b duration, if started, was 67 weeks. A total of 133 of 268 patients who started IFN--2b and provided toxicity information reported grade 3 toxicity during IFN--2b treatment. With median follow-up of 44 months, 3-year EFS for all 716 randomly assigned patients was 76% (95% CI, 72% to 79%); 174 EFS events were reported (MAP, n = 93; MAP plus IFN--2b, n = 81). Hazard ratio was 0.83 (95% CI, 0.61 to 1.12; P = .214) from an adjusted Cox model.At the preplanned analysis time, MAP plus IFN--2b was not statistically different from MAP alone. A considerable proportion of patients never started IFN--2b or stopped prematurely. Long-term follow-up for events and survival continues.

View details for DOI 10.1200/JCO.2014.60.0734

View details for PubMedID 26033801

Characterizing standardized uptake values on diagnostic PET/CT scans according to pediatric lymphoma subtypes Halparin, J., Rassekh, S., Nadel, H. SOC NUCLEAR MEDICINE INC. 2015
Common normal variants of pediatric vertebral development that mimic fractures: a pictorial review from a national longitudinal bone health study PEDIATRIC RADIOLOGY Jaremko, J. L., Siminoski, K., Firth, G. B., Matzinger, M., Shenouda, N., Konji, V. N., Roth, J., Sbrocchi, A., Reed, M. H., O'Brien, M., Nadel, H., McKillop, S., Kloiber, R., Dubois, J., Coblentz, C., Charron, M., Ward, L. M., Canadian STOPP Consortium Natl 2015; 45 (4): 593605


Children with glucocorticoid-treated illnesses are at risk for osteoporotic vertebral fractures, and growing awareness of this has led to increased monitoring for these fractures. However scant literature describes developmental changes in vertebral morphology that can mimic fractures. The goal of this paper is to aid in distinguishing between normal variants and fractures. We illustrate differences using lateral spine radiographs obtained annually from children recruited to the Canada-wide STeroid-Associated Osteoporosis in the Pediatric Population (STOPP) observational study, in which 400 children with glucocorticoid-treated leukemia, rheumatic disorders, and nephrotic syndrome were enrolled near glucocorticoid initiation and followed prospectively for 6years. Normal variants mimicking fractures exist in all regions of the spine and fall into two groups. The first group comprises variants mimicking pathological vertebral height loss, including not-yet-ossified vertebral apophyses superiorly and inferiorly, which can lead to a vertebral shape easily over-interpreted as anterior wedge fracture, physiological beaking, or spondylolisthesis associated with shortened posterior vertebral height. The second group includes variants mimicking other radiologic signs of fractures: anterior vertebral artery groove resembling an anterior buckle fracture, Cupid's bow balloon disk morphology, Schmorl nodes mimicking concave endplate fractures, and parallax artifact resembling endplate interruption or biconcavity. If an unexpected vertebral body contour is detected, careful attention to its location, detailed morphology, and (if available) serial changes over time may clarify whether it is a fracture requiring change in management or simply a normal variant. Awareness of the variants described in this paper can improve accuracy in the diagnosis of pediatric vertebral fractures.

View details for DOI 10.1007/s00247-014-3210-y

View details for Web of Science ID 000352213900022

View details for PubMedID 25828359

View details for PubMedCentralID PMC4519278

The Choice of Normative Pediatric Reference Database Changes Spine Bone Mineral Density Z-Scores But Not the Relationship Between Bone Mineral Density and Prevalent Vertebral Fractures JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM Ma, J., Siminoski, K., Alos, N., Halton, J., Ho, J., Lentle, B., Matzinger, M., Shenouda, N., Atkinson, S., Barr, R., Cabral, D. A., Couch, R., Cummings, E. A., Fernandez, C. V., Grant, R. M., Rodd, C., Sbrocchi, A., Scharke, M., Rauch, F., Ward, L. M., Canadian STOPP Consortium 2015; 100 (3): 101827


Our objectives were to assess the magnitude of the disparity in lumbar spine bone mineral density (LSBMD) Z-scores generated by different reference databases and to evaluate whether the relationship between LSBMD Z-scores and vertebral fractures (VF) varies by choice of database.Children with leukemia underwent LSBMD by cross-calibrated dual-energy x-ray absorptiometry, with Z-scores generated according to Hologic and Lunar databases. VF were assessed by the Genant method on spine radiographs. Logistic regression was used to assess the association between fractures and LSBMD Z-scores. Net reclassification improvement and area under the receiver operating characteristic curve were calculated to assess the predictive accuracy of LSBMD Z-scores for VF.For the 186 children from 0 to 18 years of age, 6 different age ranges were studied. The Z-scores generated for the 0 to 18 group were highly correlated (r 0.90), but the proportion of children with LSBMD Z-scores -2.0 among those with VF varied substantially (from 38-66%). Odds ratios (OR) for the association between LSBMD Z-score and VF were similar regardless of database (OR = 1.92, 95% confidence interval 1.44, 2.56 to OR = 2.70, 95% confidence interval 1.70, 4.28). Area under the receiver operating characteristic curve and net reclassification improvement ranged from 0.71 to 0.75 and -0.15 to 0.07, respectively.Although the use of a LSBMD Z-score threshold as part of the definition of osteoporosis in a child with VF does not appear valid, the study of relationships between BMD and VF is valid regardless of the BMD database that is used.

View details for DOI 10.1210/jc.2014-3096

View details for Web of Science ID 000353358900051

View details for PubMedID 25494661

View details for PubMedCentralID PMC4519277

EURAMOS-1, an international randomised study for osteosarcoma: results from pre-randomisation treatment. Annals of oncology Whelan, J. S., Bielack, S. S., Marina, N., Smeland, S., Jovic, G., Hook, J. M., Krailo, M., Anninga, J., Butterfass-Bahloul, T., Bhling, T., Calaminus, G., Capra, M., Deffenbaugh, C., Dhooge, C., Eriksson, M., Flanagan, A. M., Gelderblom, H., Goorin, A., Gorlick, R., Gosheger, G., Grimer, R. J., Hall, K. S., Helmke, K., Hogendoorn, P. C., Jundt, G., Kager, L., Kuehne, T., Lau, C. C., Letson, G. D., Meyer, J., Meyers, P. A., Morris, C., Mottl, H., Nadel, H., Nagarajan, R., Randall, R. L., Schomberg, P., Schwarz, R., Teot, L. A., Sydes, M. R., Bernstein, M. 2015; 26 (2): 407-414


Four international study groups undertook a large study in resectable osteosarcoma, which included two randomised controlled trials, to determine the effect on survival of changing post-operative chemotherapy based on histological response.Patients with resectable osteosarcoma aged 40 years were treated with the MAP regimen, comprising pre-operatively of two 5-week cycles of cisplatin 120 mg/m(2), doxorubicin 75 mg/m(2), methotrexate 12 g/m(2) 2 (MAP) and post-operatively two further cycles of MAP and two cycles of just MA. Patients were randomised after surgery. Those with 10% viable tumour in the resected specimen received MAP or MAP with ifosfamide and etoposide. Those with <10% viable tumour were allocated to MAP or MAP followed by pegylated interferon. Longitudinal evaluation of quality of life was undertaken.Recruitment was completed to the largest osteosarcoma study to date in 75 months. Commencing March 2005, 2260 patients were registered from 326 centres across 17 countries. About 1334 of 2260 registered patients (59%) were randomised. Pre-operative chemotherapy was completed according to protocol in 94%. Grade 3-4 neutropenia affected 83% of cycles and 59% were complicated by infection. There were three (0.13%) deaths related to pre-operative chemotherapy. At definitive surgery, 50% of patients had at least 90% necrosis in the resected specimen.New models of collaboration are required to successfully conduct trials to improve outcomes of patients with rare cancers; EURAMOS-1 demonstrates achievability. Considerable regulatory, financial and operational challenges must be overcome to develop similar studies in the future. The trial is registered as NCT00134030 and ISRCTN 67613327.

View details for DOI 10.1093/annonc/mdu526

View details for PubMedID 25421877

Impact of Post-Induction Curie Scores in High-Risk Neuroblastoma Yanik, G., Naranjo, A., Parisi, M. T., Shulkin, B. L., Nadel, H., Gelfand, M. J., Ladenstein, R., Boubaker, A., Poetschger, U., Valteau-Couanet, D., Kreissman, S. G., Park, J. R., Matthay, K. K. ELSEVIER SCIENCE INC. 2015: S107
Combined PET/MR: Where Are We Now? Summary Report of the Second International Workshop on PET/MR Imaging April 8-12, 2013, Tubingen, Germany MOLECULAR IMAGING AND BIOLOGY Bailey, D. L., Barthel, H., Beuthin-Baumann, B., Beyer, T., Bisdas, S., Boellaard, R., Czernin, J., Drzezga, A., Ernemann, U., Franzius, C., Gueckel, B., Handgretinger, R., Hartenbach, M., Hellwig, D., Nadel, H., Nekolla, S. G., Pfluger, T., Pichler, B. J., Quick, H. H., Sabri, O., Sattler, B., Schaefer, J., Schick, F., Siegel, B. A., Schlemmer, H. P., Schwenzer, N. F., van den Hoff, J., Veit-Haibach, P., Wehrl, H. F. 2014; 16 (3): 295310


This workshop was held a year after the initial positron emission tomography/magnetic resonance (PET/MR) workshop in Tbingen, which was recently reported in this journal. The discussions at the 2013 workshop, however, differed substantially from those of the initial workshop, attesting to the progress of combined PET/MR as an innovative imaging modality. Discussions were focused on the search for truly novel, unique clinical and research applications as well as technical issues such as reliable and accurate approaches for attenuation and scatter correction of PET emission data. The workshop provided hands-on experience with PET and MR imaging. In addition, structured and moderated open discussion sessions, including six dialogue boards and two roundtable discussions, provided input from current and future PET/MR imaging users. This summary provides a snapshot of the current achievements and challenges for PET/MR.

View details for DOI 10.1007/s11307-014-0725-4

View details for Web of Science ID 000335734900001

View details for PubMedID 24668195

Validation of postinduction Curie scores in high-risk neuroblastoma. Yanik, G. A., Naranjo, A., Parisi, M. T., Shulkin, B. L., Nadel, H. R., Gelfand, M. J., Ladenstein, R. L., Boubaker, A., Poetschger, U., Lambert, B., Castellani, M., Valteau-Couanet, D., Kreissman, S. G., Park, J. R., Matthay, K. K. AMER SOC CLINICAL ONCOLOGY. 2014
The added value of optimized co-registered diagnostic CT scan for I-123 mIBG SPECT-CT in children with neuroblastoma Nadel, H. SOC NUCLEAR MEDICINE INC. 2014
SPECT/CT in pediatric patient management EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING Nadel, H. R. 2014; 41: S104S114


Hybrid SPECT/CT imaging is becoming the standard of care in pediatric imaging. Indications are mainly for oncologic imaging including mIBG scintigraphy for neuroblastoma and I-123 post surgical imaging of children with thyroid carcinoma, bone scintigraphy for back pain, children referred from sports medicine and neurodevelopmentally delayed children presenting with pain symptoms. The studies provide improved diagnostic accuracy, and oncologic imaging that includes optimized CT as part of the SPECT/CT study may decrease the number of studies and sedation procedures an individual child may need. The studies, however, must be tailored on an individual basis as the addition of the CT study can increase exposure to the child and should only be performed after appropriate justification and with adherence to optimized low dose pediatric protocols.

View details for DOI 10.1007/s00259-014-2697-7

View details for Web of Science ID 000348400900011

View details for PubMedID 24554052

Observer agreement in pediatric semiquantitative vertebral fracture diagnosis PEDIATRIC RADIOLOGY Siminoski, K., Lentle, B., Matzinger, M., Shenouda, N., Ward, L. M., Canadian STOPP Consortium 2014; 44 (4): 45766


The Genant semiquantitative (GSQ) method has been a standard procedure for diagnosis of vertebral fractures in adults but has only recently been shown to be of clinical utility in children. Observer agreement using the GSQ method in this age group has not been described.To evaluate observer agreement on vertebral readability and vertebral fracture diagnosis using the GSQ method in pediatric vertebral morphometry.Spine radiographs of 186 children with acute lymphoblastic leukemia were evaluated independently by three radiologists using the same GSQ methodology as in adults. A subset of 100 radiographs was evaluated on two occasions.An average of 4.7% of vertebrae were unreadable for the three radiologists. Intraobserver Cohen's kappa () on readability ranged from 0.434 to 0.648 at the vertebral level and from 0.416 to 0.611 at the patient level, while interobserver for readability had a range of 0.330 to 0.504 at the vertebral level and 0.295 to 0.467 at the patient level. Intraobserver for the presence of vertebral fracture had a range of 0.529 to 0.726 at the vertebral level and was 0.528 to 0.767 at the patient level. Interobserver for fracture at the vertebral level ranged from 0.455 to 0.548 and from 0.433 to 0.486 at the patient level.Most values for both intra- and interobserver agreement in applying the GSQ method to pediatric spine radiographs were in the moderate to substantial range, comparable to the performance of the technique in adult studies. The GSQ method should be considered for use in pediatric research and clinical practice.

View details for DOI 10.1007/s00247-013-2837-4

View details for Web of Science ID 000333529100010

View details for PubMedID 24323185

View details for PubMedCentralID PMC3900460

Skeletal findings in the first 12 months following initiation of glucocorticoid therapy for pediatric nephrotic syndrome OSTEOPOROSIS INTERNATIONAL Phan, V., Blydt-Hansen, T., Feber, J., Alos, N., Arora, S., Atkinson, S., Bell, L., Clarson, C., Couch, R., Cummings, E. A., Filler, G., Grant, R. M., Grimmer, J., Hebert, D., Lentle, B., Ma, J., Matzinger, M., Midgley, J., Pinsk, M., Rodd, C., Shenouda, N., Stein, R., Stephure, D., Taback, S., Williams, K., Rauch, F., Siminoski, K., Ward, L. M., Canadian STOPP Consortium 2014; 25 (2): 62737


Incident vertebral fractures and lumbar spine bone mineral density (BMD) were assessed in the 12 months following glucocorticoid initiation in 65 children with nephrotic syndrome. The incidence of vertebral fractures was low at 12 months (6 %) and most patients demonstrated recovery in BMD Z-scores by this time point.Vertebral fracture (VF) incidence following glucocorticoid (GC) initiation has not been previously reported in pediatric nephrotic syndrome.VF was assessed on radiographs (Genant method); lumbar spine bone mineral density (LS BMD) was evaluated by dual-energy X-ray absorptiometry.Sixty-five children were followed to 12 months post-GC initiation (median age, 5.4 years; range, 2.3-17.9). Three of 54 children with radiographs (6 %; 95 % confidence interval (CI), 2-15 %) had incident VF at 1 year. The mean LS BMD Z-score was below the healthy average at baseline (mean standard deviation (SD), -0.5 1.1; p = 0.001) and at 3 months (-0.6 1.1; p < 0.001), but not at 6 months (-0.3 1.3; p = 0.066) or 12 months (-0.3 1.2; p = 0.066). Mixed effect modeling showed a significant increase in LS BMD Z-scores between 3 and 12 months (0.22 SD; 95 % CI, 0.08 to 0.36; p = 0.003). A subgroup (N = 16; 25 %) had LS BMD Z-scores that were -1.0 at 12 months. In these children, each additional 1,000 mg/m(2) of GC received in the first 3 months was associated with a decrease in LS BMD Z-score by 0.39 at 12 months (95 % CI, -0.71 to -0.07; p = 0.017).The incidence of VF at 1 year was low and LS BMD Z-scores improved by 12 months in the majority. Twenty-five percent of children had LS BMD Z-scores -1.0 at 12 months. In these children, LS BMD Z-scores were inversely associated with early GC exposure, despite similar GC exposure compared to the rest of the cohort.

View details for DOI 10.1007/s00198-013-2466-7

View details for Web of Science ID 000330981100026

View details for PubMedID 23948876

View details for PubMedCentralID PMC4100956

The Role of PET/CT in Assessing Pulmonary Nodules in Children With Solid Malignancies AMERICAN JOURNAL OF ROENTGENOLOGY McCarville, M., Billups, C., Wu, J., Kaufman, R., Kaste, S., Coleman, J., Sharp, S., Nadel, H., Charron, M., Lederman, H., Don, S., Shochat, S., Daw, N. C., Shulkin, B. 2013; 201 (6): W900W905


OBJECTIVE. The purpose of this article is to assess the feasibility and utility of PET/CT in distinguishing benign from malignant pulmonary nodules in patients with solid childhood malignancies. SUBJECTS AND METHODS. This prospective study was conducted between March 2008 and August 2010. We enrolled 25 subjects 21 years old or younger with solid childhood malignancies and at least one pulmonary nodule measuring 0.5-3.0 cm. PET/CT was performed within 3 weeks of diagnostic chest CT. Three panels of three reviewers each reviewed diagnostic CT only (panel 1), PET/CT only (panel 2), or diagnostic CT and PET/CT concurrently (panel 3) and predicted each nodule's histologic diagnosis as benign, malignant, or indeterminate. Interreviewer agreement was assessed with the kappa statistic. Using nodule biopsy or clinical follow-up as reference standards, the sensitivity, specificity, and accuracy for each panel was assessed. Logistic regression was used to assess the nodule's maximum standardized uptake value (SUVmax) association with its histologic diagnosis. RESULTS. There were 75 nodules with a median size of 0.74 cm (range, 0.18-2.38 cm); 48 nodules were malignant. Sensitivity was 85% (41/48) for panel 1, 60% (29/48) for panel 2, and 67% (32/48) for panel 3. All panels had poor specificities. Interreviewer agreement was moderate for panel 1 (0.43) and poor for panels 2 (0.22) and 3 (0.33). SUVmax was a significant predictor of histologic diagnosis (p = 0.004). CONCLUSION. PET/CT assessment of pulmonary nodules is feasible in children with solid malignancies but may not reliably improve our ability to predict a nodule's histologic diagnosis. The SUVmax may improve the performance of PET/CT in this setting.

View details for DOI 10.2214/AJR.12.10205

View details for Web of Science ID 000327501500013

View details for PubMedID 24261397

View details for PubMedCentralID PMC4276039

Anatomical distribution of vertebral fractures: comparison of pediatric and adult spines OSTEOPOROSIS INTERNATIONAL Siminoski, K., Lee, K., Jen, H., Warshawski, R., Matzinger, M. A., Shenouda, N., Charron, M., Coblentz, C., Dubois, J., Kloiber, R., Nadel, H., O'Brien, K., Reed, M., Sparrow, K., Webber, C., Lentle, B., Ward, L. M., STOPP Consortium 2012; 23 (7): 19992008


We compared the distribution of vertebral fractures in adults and children and found that fractures occurred in different locations in the two age groups. This likely relates to the different shape of the immature spine.We hypothesized that the anatomical distribution of vertebral fractures (VF) would be different in children compared to adults.We compared the distribution of VF defined using the Genant semi-quantitative method (GSQ method) in adults (N=221; 545 fractures) and in children early in the course of glucocorticoid therapy (N=44; 94 fractures).The average age in the adult cohort was 62.9 years (standard deviation (SD), 13.4 years), 26% was male, the mean lumbar spine Z-score was -1.0 (SD, 1.5), and the corresponding T-score was -2.4 (SD, 1.4). The pediatric cohort median age was 7.7 years (range, 2.1-16.6 years), the mean lumbar spine Z-score was -1.7 (SD, 1.5), 52% was male, and disease categories were acute lymphoblastic leukemia (66%), rheumatological conditions (21%), and nephrotic syndrome (14%). The VF distribution was biphasic in both populations, but the peaks differed in location. In adults, the peaks were at T7/T8 and at T12/L1. In children, the focus was higher in the thoracic spine, at T6/T7, and lower in the lumbar spine, at L1/L2. When children were assessed in two age-defined sub-groups, a biphasic VF distribution was seen in both, but the upward shift of the thoracic focus to T6 was observed only in the older group, with the highest rates of fracture present between ages 7 and 10 years.These results suggest that the anatomical distribution of VF differs between children and adults, perhaps relating to the different shape of the immature spine, notably the changing ratio of kyphosis to lordosis.

View details for DOI 10.1007/s00198-011-1837-1

View details for Web of Science ID 000304878900018

View details for PubMedID 22109742

View details for PubMedCentralID PMC4067402

Long-term Risk of CKD in Children Surviving Episodes of Acute Kidney Injury in the Intensive Care Unit: A Prospective Cohort Study AMERICAN JOURNAL OF KIDNEY DISEASES Mammen, C., Al Abbas, A., Skippen, P., Nadel, H., Levine, D., Collet, J. P., Matsell, D. G. 2012; 59 (4): 52330


The development of standardized acute kidney injury (AKI) definitions has allowed for a better understanding of AKI epidemiology, but the long-term renal outcomes of AKI in the pediatric critical care setting have not been well established. This study was designed to: (1) determine the incidence of chronic kidney disease (CKD) in children 1-3 years after an episode of AKI at a tertiary-care pediatric intensive care unit (ICU), (2) identify the proportion of patients at risk of CKD, and (3) compare ICU admission characteristics in those with and without CKD.Prospective cohort study.Patients admitted to the British Columbia Children's Hospital pediatric ICU from 2006-2008 with AKI, as defined by AKI Network (AKIN) criteria. Surviving patients, most with short-term recovery from their AKI, were assessed at 1, 2, or 3 years after AKI.Severity of AKI as defined by AKIN and several ICU admission characteristics, including demographics, diagnosis, severity of illness, and ventilation data.CKD was defined as the presence of albuminuria and/or glomerular filtration rate (GFR) < 60 mL/min/1.73 m2. Being at risk of CKD was defined as having a mildly decreased GFR (60-90 mL/min/1.73 m2), hypertension, and/or hyperfiltration (GFR 150 mL/min/1.73 m2).The proportion of patients with AKI stages 1, 2, and 3 were 44 of 126 (35%), 47 of 126 (37%), and 35 of 126 (28%), respectively. The number of patients with CKD 1-3 years after AKI was 13 of 126 (10.3% overall; 2 of 44 [4.5%] with stage 1, 5 of 47 [10.6%] with stage 2, and 6 of 35 [17.1%] with stage 3; P = 0.2). In addition, 59 of 126 (46.8%) patients were identified as being at risk of CKD.Several patients identified with AKI were lost to follow-up, with the potential of underestimating the incidence of CKD.In tertiary-care pediatric ICU patients, 10% develop CKD 1-3 years after AKI. The burden of CKD in this population may be higher with further follow-up because several patients were identified as being at risk of CKD. Regardless of the severity of AKI, all pediatric ICU patients should be monitored regularly for long-term kidney damage.

View details for DOI 10.1053/j.ajkd.2011.10.048

View details for Web of Science ID 000302117500322

View details for PubMedID 22206744

Skeletal findings in children recently initiating glucocorticoids for the treatment of nephrotic syndrome OSTEOPOROSIS INTERNATIONAL Feber, J., Gaboury, I., Ni, A., Alos, N., Arora, S., Bell, L., Blydt-Hansen, T., Clarson, C., Filler, G., Hay, J., Hebert, D., Lentle, B., Matzinger, M., Midgley, J., Moher, D., Pinsk, M., Rauch, F., Rodd, C., Shenouda, N., Siminoski, K., Ward, L. M., Canadian STOPP Consortium 2012; 23 (2): 75160


Eighty children with nephrotic syndrome underwent lumbar spine densitometry and vertebral morphometry soon after glucocorticoid initiation. We found an inverse relationship between glucocorticoid exposure and spine areal bone mineral density (BMD) Z-score and a low rate of vertebral deformities (8%).Vertebral fractures are an under-recognized complication of childhood glucocorticoid-treated illnesses. Our goal was to study the relationships among glucocorticoid exposure, lumbar spine areal BMD (LS BMD), and vertebral shape in glucocorticoid-treated children with new-onset nephrotic syndrome.Lateral thoracolumbar spine radiography and LS BMD were performed in 80 children with nephrotic syndrome (median age 4.4 years; 46 boys) within the first 37 days of glucocorticoid therapy. Genant semiquantitative grading was used as the primary method for vertebral morphometry; the algorithm-based qualitative (ABQ) method was used for secondary vertebral deformity analysis.Six of the 78 children with usable radiographs (8%; 95% confidence interval 4 to 16%) manifested a single Genant grade 1 deformity each. All deformities were mild anterior wedging (two at each of T6, T7, and T8). Four of the 78 children (5%; 95% confidence interval 2 to 13%) showed one ABQ sign of fracture each (loss of endplate parallelism; two children at T6 and two at T8). Two of the children with ABQ signs also had a Genant grade 1 deformity in the same vertebral body. None of the children with a Genant or ABQ deformity reported back pain. An inverse relationship was identified between LS BMD Z-score and glucocorticoid exposure.Although we identified an inverse relationship between steroid exposure and LS BMD soon after glucocorticoid initiation for childhood nephrotic syndrome, there was only a low rate of vertebral deformities. The clinical significance of these findings requires further study.

View details for DOI 10.1007/s00198-011-1621-2

View details for Web of Science ID 000299306300036

View details for PubMedID 21494860

View details for PubMedCentralID PMC4000256

Incident vertebral fractures among children with rheumatic disorders 12 months after glucocorticoid initiation: A national observational study ARTHRITIS CARE & RESEARCH Rodd, C., Lang, B., Ramsay, T., Alos, N., Huber, A. M., Cabral, D. A., Scuccimarri, R., Miettunen, P. M., Roth, J., Atkinson, S. A., Couch, R., Cummings, E. A., Dent, P. B., Ellsworth, J., Hay, J., Houghton, K., Jurencak, R., Larche, M., LeBlanc, C., Oen, K., Saint-Cyr, C., Stein, R., Stephure, D., Taback, S., Lentle, B., Matzinger, M., Shenouda, N., Moher, D., Rauch, F., Siminoski, K., Ward, L. M., Canadian Steroid-Associated 2012; 64 (1): 12231


To determine the frequency of incident vertebral fractures (IVF) 12 months after glucocorticoid (GC) initiation in children with rheumatic diseases and to identify children at higher risk.Children with rheumatic diseases initiating GC were enrolled in a prospective observational study. Annual spine radiographs were evaluated using the Genant semiquantitative method. Spine areal bone mineral density (aBMD) was measured every 6 months. Clinical features, including cumulative GC dose, back pain, disease and physical activity, calcium and vitamin D intake, and spine aBMD Z scores, were analyzed for association with IVF.Seven (6%) of 118 children (95% confidence interval 2.9-11.7%) had IVF. Their diagnoses were: juvenile dermatomyositis (n = 2), systemic lupus erythematosus (n = 3), systemic vasculitis (n = 1), and mixed connective tissue disease (n = 1). One child was omitted from the analyses after 4 months because of osteoporosis treatment for symptomatic IVF. Children with IVF received on average 50% more GC than those without (P = 0.030), had a greater increase in body mass index (BMI) at 6 months (P = 0.010), and had greater decrements in spine aBMD Z scores in the first 6 months (P = 0.048). Four (67%) of 6 children with IVF and data to 12 months had spine aBMD Z scores less than -2.0 at 12 months compared to 16% of children without IVF (P = 0.011).The incidence of VF 12 months following GC initiation was 6%; most children were asymptomatic. Children with IVF received more GC, had greater increases in BMI, and had greater declines in spine aBMD Z scores in the first 6 months.

View details for DOI 10.1002/acr.20589

View details for Web of Science ID 000298536700019

View details for PubMedID 22213727

View details for PubMedCentralID PMC4459856

Novel use of F-DOPA PET/CT imaging in a child with paraganglioma/pheochromocytoma syndrome PEDIATRIC RADIOLOGY Levine, D. S., Metzger, D. L., Nadel, H. R., Oviedo, A., Adam, M. J., Skarsgard, E. 2011; 41 (10): 132125


We report the use of F-DOPA PET/CT imaging in the evaluation of a teenager with marked hypertension and right pararenal, left adrenal and left para-aortic mass lesions. The use of the modality for this clinical application has not been described previously within the pediatric imaging literature. The value of this technique relative to conventional imaging modalities is discussed and warrants consideration of its use, if available, for evaluating children with suspected paragangliomas/pheochromocytomas.

View details for DOI 10.1007/s00247-011-2109-0

View details for Web of Science ID 000294690500013

View details for PubMedID 21567141

FDG positron emission tomography/computed tomography studies of Wilms' tumor EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING Hossain, A., Shulkin, B. L., Gelfand, M. J., Bashir, H., Daw, N. C., Sharp, S. E., Nadel, H. R., Dome, J. S. 2010; 37 (7): 13001308


The purpose of this analysis was to evaluate the utility of FDG PET/CT scanning in patients with Wilms' tumors.A total of 58 scans were performed in 27 patients (14 male, 13 female; ages: 1.9-23 years, median: 7 years) with proven Wilms' tumor. Twenty-six patients (56 scans) were studied at the time of suspected relapse, progressive disease, persistent disease, or for monitoring of therapy.In the 27 patients with Wilms' tumor, 34 scans showed areas of abnormal uptake consistent with metabolically active tumors. Of the patients, 8 (24 scans) had pulmonary metastases larger than 10 mm in diameter, 10 (12 scans) had hepatic metastases, 11 (11 scans) had regional nodal involvement, 3 (3 scans) had bone metastases, 1 (1 scan) had chest wall involvement, 2 (2 scans) had pancreatic metastasis, and 5 (5 scans) had abdominal and pelvic soft tissue involvement. Two of eight patients with lung metastases had variable uptakes. Lung lesions 10 mm or smaller were not consistently visualized on PET scans. One patient with a liver metastasis showed no uptake on PET scan after treatment (size decreased from 45 to 15 mm).Most Wilms' tumors concentrate FDG. However, small pulmonary metastases may be better visualized with CT. FDG PET/CT appears useful for defining the extent of involvement and assessing the response to treatment.

View details for DOI 10.1007/s00259-010-1396-2

View details for Web of Science ID 000278833100007

View details for PubMedID 20204356

View details for PubMedCentralID PMC4720968

Prevalent Vertebral Fractures Among Children Initiating Glucocorticoid Therapy for the Treatment of Rheumatic Disorders ARTHRITIS CARE & RESEARCH Huber, A. M., Gaboury, I., Cabral, D. A., Lang, B., Ni, A., Stephure, D., Taback, S., Dent, P., Ellsworth, J., Leblanc, C., Saint-Cyr, C., Scuccimarri, R., Hay, J., Lentle, B., Matzinger, M., Shenouda, N., Moher, D., Rauch, F., Siminoski, K., Ward, L. M., Canadian Steroid-Associated 2010; 62 (4): 51626


Vertebral fractures are an under-recognized problem in children with inflammatory disorders. We studied spine health among 134 children (87 girls) with rheumatic conditions (median age 10 years) within 30 days of initiating glucocorticoid therapy.Children were categorized as follows: juvenile dermatomyositis (n = 30), juvenile idiopathic arthritis (n = 28), systemic lupus erythematosus and related conditions (n = 26), systemic arthritis (n = 22), systemic vasculitis (n = 16), and other conditions (n = 12). Thoracolumbar spine radiograph and dual x-ray absorptiometry for lumbar spine (L-spine) areal bone mineral density (BMD) were performed within 30 days of glucocorticoid initiation. Genant semiquantitative grading was used for vertebral morphometry. Second metacarpal morphometry was carried out on a hand radiograph. Clinical factors including disease and physical activity, calcium and vitamin D intake, cumulative glucocorticoid dose, underlying diagnosis, L-spine BMD Z score, and back pain were analyzed for association with vertebral fracture.Thirteen vertebral fractures were noted in 9 children (7%). Of these, 6 patients had a single vertebral fracture and 3 had 2-3 fractures. Fractures were clustered in the mid-thoracic region (69%). Three vertebral fractures (23%) were moderate (grade 2); the others were mild (grade 1). For the entire cohort, mean +/- SD L-spine BMD Z score was significantly different from zero (-0.55 +/- 1.2, P < 0.001) despite a mean height Z score that was similar to the healthy average (0.02 +/- 1.0, P = 0.825). Back pain was highly associated with increased odds for fracture (odds ratio 10.6 [95% confidence interval 2.1-53.8], P = 0.004).In pediatric rheumatic conditions, vertebral fractures can be present prior to prolonged glucocorticoid exposure.

View details for DOI 10.1002/acr.20171

View details for Web of Science ID 000280979400013

View details for PubMedID 20391507

View details for PubMedCentralID PMC3958950

Pediatric Applications for PET/CT and SPECT/CT HYBRID PET/CT AND SPECT CT IMAGING Nadel, H. R., Byrne, A. T., Delbeke, D., Israel, O. 2010: 62156
Pediatric Bone Scintigraphy Update SEMINARS IN NUCLEAR MEDICINE Nadel, H. R. 2010; 40 (1): 3140


Bone scintigraphy is a sensitive tool to evaluate the musculoskeletal system in children. Hybrid imaging using computed tomography (CT) in combination with conventional bone scan and single photon emission computed tomography improves specificity and diagnostic accuracy. It also improves laboratory efficiency and may save the patient an additional visit to the hospital for a separate cross-sectional imaging study. We have found this technique to be particularly helpful in localizing a cause for pain in children who are nonverbal and to better delineate small bone and soft-tissue lesions that can occur with diagnoses of trauma, infection, and tumor. Special attention to technique of positioning the patient for potential CT examination is an adaptation that must be made by the technologist. Because of radiation concerns of the additional CT, obviously these examinations should be tailored to the individual child and be performed for limited sites directed to the abnormality observed on the associated single photon emission computed tomography examination or directed by the appropriate history.

View details for DOI 10.1053/j.semnuclmed.2009.10.001

View details for Web of Science ID 000277440600005

View details for PubMedID 19958848

Prevalent vertebral compression in children with newly diagnosed rheumatic conditions: Results of a national chronic illness osteoporosis surveillance program Miettunen, P. M., Roth, J., Huber, A., Ni, A., Matzinger, M., Alos, N., Atkinson, S., Couch, B., Cummings, E., Glorieux, F. H., Hay, J., Lentle, B., Nadel, H., Rauch, F., Rodd, C., Stein, R., Stephure, D., Taback, S., Shenouda, N., Siminoski, K., Ward, L. M., Canadian STOPP Consortium ELSEVIER SCIENCE INC. 2009: S73
Advanced Vertebral Fracture Among Newly Diagnosed Children With Acute Lymphoblastic Leukemia: Results of the Canadian Steroid-Associated Osteoporosis in the Pediatric Population (STOPP) Research Program JOURNAL OF BONE AND MINERAL RESEARCH Halton, J., Gaboury, I., Grant, R., Alos, N., Cummings, E. A., Matzinger, M., Shenouda, N., Lentle, B., Abish, S., Atkinson, S., Cairney, E., Dix, D., Israels, S., Stephure, D., Wilson, B., Hay, J., Moher, D., Rauch, F., Siminoski, K., Ward, L. M., Canadian STOPP Consortium 2009; 24 (7): 132634


Vertebral compression is a serious complication of childhood acute lymphoblastic leukemia (ALL). The prevalence and pattern of vertebral fractures, as well as their relationship to BMD and other clinical indices, have not been systematically studied. We evaluated spine health in 186 newly diagnosed children (median age, 5.3 yr; 108 boys) with ALL (precursor B cell: N = 167; T cell: N = 19) who were enrolled in a national bone health research program. Patients were assessed within 30 days of diagnosis by lateral thoraco-lumbar spine radiograph, bone age (also used for metacarpal morphometry), and BMD. Vertebral morphometry was carried out by the Genant semiquantitative method. Twenty-nine patients (16%) had a total of 75 grade 1 or higher prevalent vertebral compression fractures (53 thoracic, 71%; 22 lumbar). Grade 1 fractures as the worst grade were present in 14 children (48%), 9 patients (31%) had grade 2 fractures, and 6 children (21%) had grade 3 fractures. The distribution of spine fracture was bimodal, with most occurring in the midthoracic and thoraco-lumbar regions. Children with grade 1 or higher vertebral compression had reduced lumbar spine (LS) areal BMD Z-scores compared with those without (mean +/- SD, -2.1 +/- 1.5 versus -1.1 +/- 1.2; p < 0.001). LS BMD Z-score, second metacarpal percent cortical area Z-score, and back pain were associated with increased odds for fracture. For every 1 SD reduction in LS BMD Z-score, the odds for fracture increased by 80% (95% CI: 10-193%); the presence of back pain had an OR of 4.7 (95% CI: 1.5-14.5). These results show that vertebral compression is an under-recognized complication of newly diagnosed ALL. Whether the fractures will resolve through bone growth during or after leukemia chemotherapy remains to be determined.

View details for DOI 10.1359/JBMR.090202

View details for Web of Science ID 000267234400022

View details for PubMedID 19210218

View details for PubMedCentralID PMC3890351

Incident vertebral compression 1 year following glucocorticoid initiation among children with rheumatic conditions: Results of a National Chronic Illness Osteoporosis Surveillance Program Ward, L. M., Roth, J., Miettunen, P. M., Ni, A., Matzinger, M., Alos, N., Atkinson, S., Stein, R., Couch, R., Cummings, E., Glorieux, F. H., Hay, J., Lentle, B., Nadel, H., Rauch, F., Rodd, C., Stephure, D., Taback, S., Shenouda, N., Siminoski, K., Canadian STOPP Consortium ELSEVIER SCIENCE INC. 2009: S55
Short-term skeletal changes in children with newly diagnosed glucocorticoid-treated nephrotic syndrome Feber, J., Roth, J., Miettunen, P. M., Ni, A., Alos, N., Atkinson, S., Stein, R., Couch, R., Cummings, E., Glorieux, F. H., Hay, J., Lentle, B., Matzinger, M., Nadel, H., Rauch, F., Rodd, C., Stephure, D., Taback, S., Shenouda, N., Siminoski, K., Ward, L. M., Canadian STOPP Consortium ELSEVIER SCIENCE INC. 2009: S73
Occurrence of Basal Ganglia Germ Cell Tumors Without a Mass ARCHIVES OF NEUROLOGY Almubarak, S., Gan, Y., Steinbok, P., Hendson, G., Poskitt, K., Nadel, H., Goddard, K., Hukin, J. 2009; 66 (6): 78992


To report a case series in which basal ganglia calcifications without mass effect proved to be germ cell tumors.Case series.Tertiary care hospital.Four patients.Computed tomography, magnetic resonance imaging, positron emission tomography, biopsy, chemotherapy, and radiation therapy.Recognition of clinical syndrome and radiological features.All patients had progressive hemiparesis, and 1 patient also had frontal lobe dementia. Imaging demonstrated progressive asymmetric signal abnormality with basal ganglia calcification and associated brainstem atrophy. Fludeoxyglucose F 18-positron emission tomography showed hypometabolism in contrast to malignant glioma.Germ cell tumor should be considered in patients with an indolently progressive neurological course, particularly if basal ganglia calcification is present with or without enhancement, asymmetric brain atrophy, or a mass.

View details for DOI 10.1001/archneurol.2009.74

View details for Web of Science ID 000266772200018

View details for PubMedID 19506143

Early experience with PET/CT scan in the evaluation of pediatric abdominal neoplasms Murphy, J. J., Tawfeeq, M., Chang, B., Nadel, H. W B SAUNDERS CO-ELSEVIER INC. 2008: 218692


Positron emission tomography/computerized tomography (PET/CT) scan provides both functional and anatomical information in a single diagnostic test. It has the potential to be a valuable tool in the evaluation of pediatric abdominal tumors. The goal of this study is to report our early experience with this technology.Children who underwent PET/CT scan in the workup for abdominal neoplasms between July 2005 and January 2008 were identified. Retrospective review of all radiologic studies, operative notes, and pathologic reports was undertaken.A total of 36 patients were collected. These included Burkitt's lymphoma (8), neuroblastoma (7), rhabdomyosarcoma (6), ovarian tumor (3), Wilms' tumor (2), hepatocellular carcinoma (2), paraganglioma (1), germ cell tumor (1), undifferentiated sarcoma (1), renal primitive neuroectodermal tumor (1), gastrointestinal stromal tumor (1), adrenocortical carcinoma (1), inflammatory pseudotumor (1), and adrenal adenoma (1). All neoplasms were fluorodeoxyglucose (FDG) were avid. Our experience identified several potential uses for PET/CT scan in this group of patients. These include (1) preoperative staging, (2) selection of appropriate site for biopsy, (3) identification of occult metastatic disease, (4) follow-up for residual or recurrent disease, and (5) assessment of response to chemotherapy. It can also be valuable when the standard diagnostic studies are equivocal or conflicting.Preliminary data indicate that PET/CT is a promising tool in the evaluation of pediatric abdominal malignancies. The delineation of the exact role of this diagnostic modality will require additional experience.

View details for DOI 10.1016/j.jpedsurg.2008.08.064

View details for Web of Science ID 000261853700011

View details for PubMedID 19040932

Advanced Vertebral Compression at Diagnosis among Children with Acute Lymphoblastic Leukemia. Ward, L. M., Matinger, M., Alos, N., Atkinson, S., Clarson, C., Couch, R., Cummings, E., Glorieux, F. H., Grant, R., Halton, J., Lentle, B., Nadel, H., Rodd, C., Siminoski, K., Stephure, D., Taback, S., Shenouda, N., Rauch, F., Canadian STOPP Consortium AMER SOC BONE & MINERAL RES. 2008: S367
Embryonal rhabdomyosarcoma as a second malignancy following multimodal therapy for advanced-stage neuroblastoma PEDIATRIC RADIOLOGY Mann, G. S., Byrne, A. T., Nadel, H. R., Bray, H. 2008; 38 (9): 101720


Second malignancy as a long-term complication in survivors of advanced-stage neuroblastoma is rare, but it is becoming recognized more frequently. We report an unusual case of a soft-tissue sarcoma developing within a retroperitoneal primary following previous extensive treatment for metastatic neuroblastoma using multimodality imaging including PET/CT.

View details for DOI 10.1007/s00247-008-0905-y

View details for Web of Science ID 000258118700014

View details for PubMedID 18594803

Imaging guidelines for children with Ewing sarcoma and osteosarcoma: A report from the Children's Oncology Group Bone Tumor Committee PEDIATRIC BLOOD & CANCER Meyer, J. S., Nadel, H. R., Marina, N., Womer, R. B., Brown, K. L., Eary, J. F., Gorlick, R., Grier, H. E., Randall, R. L., Lawlor, E. R., Lessnick, S. L., Schomberg, P. J., Kailo, M. D. 2008; 51 (2): 163-170


The Children's Oncology Group (COG) is a multi-institutional cooperative group dedicated to childhood cancer research that has helped to increase the survival of children with cancer through clinical trials. These clinical trials include a standardized regimen of imaging examinations performed prior to, during, and following therapy. This article presents imaging guidelines developed by a multidisciplinary group from the COG Bone Tumor Committee. These guidelines provide both required and recommended studies. Recommended examinations may become required in the future. These guidelines should be considered a work in progress that will evolve with advances in imaging and childhood cancer research.

View details for DOI 10.1002/pbc.21596

View details for Web of Science ID 000256871800004

View details for PubMedID 18454470

Pediatric positron emission tomography-computed tomography protocol considerations SEMINARS IN ULTRASOUND CT AND MRI Nadel, H. R., Shulkin, B. 2008; 29 (4): 27176


Pediatric body oncology positron emission tomography-computed tomography studies require special considerations for optimal diagnostic performance while limiting radiation exposure to young patients. Differences from routine adult procedures include the patient preparation phase, radiopharmaceutical dose, computed tomography acquisition parameters, and approach to computed tomography contrast materials and imaging sequence. Attention to these differences define the best practice for positron emission tomography-computed tomography examinations of children with cancer contributing to optimal care of these patients.

View details for DOI 10.1053/j.sult.2008.05.004

View details for Web of Science ID 000258968200007

View details for PubMedID 18795494

Addition of muramyl tripeptide to chemotherapy for patients with newly diagnosed metastatic osteosarcoma: A report from the Children's Oncology Group Chou, A. J., Kleinerman, E., Krailo, M. D., Betcher, D., Healey, J., Nadel, H., Nieder, M., Weiner, M., Wells, R. J., Meyers, P. A. AMER SOC CLINICAL ONCOLOGY. 2008
Bone scan update SEMINARS IN NUCLEAR MEDICINE Nadel, H. R. 2007; 37 (5): 33239


The radionuclide bone scan is one of the most commonly performed pediatric nuclear medicine procedures. Bone scintigraphy is used as the diagnostic procedure of choice for diagnosis of bone and soft-tissue infection and can aid in the diagnosis of occult trauma without radiographic findings. There is a complimentary role for bone scintigraphy in the assessment of a child with suspected nonaccidental injury. The use of bone scan in a child with unexplained bone pain or limp may provide a diagnosis that could be related to trauma, tumor, or inflammation. A negative bone scan can help relieve concern for significant pathology. Bone scans in children require careful attention to technique to obtain high-quality diagnostic images. Routine whole-body imaging, magnification, additional views, and the use of single-photon emission computed tomography also are a routine part of this examination in children. Correlation with conventional radiographs is mandatory, and the judicious use of hybrid imaging with the addition of computed tomography may further improve diagnostic acumen, confidence and accuracy. New radiopharmaceuticals such as fluorine-18 may also play a role in changing techniques for pediatric bone scintigraphy.

View details for DOI 10.1053/j.semnuclmed.2007.06.001

View details for Web of Science ID 000249042300003

View details for PubMedID 17707240

Upfront window trial of topotecan in previously untreated children and adolescents with poor prognosis metastatic osteosarcoma CANCER Seibel, N. L., Krailo, M., Chen, Z., Healey, J., Breiffeld, P. R., Drachtman, R., Greffe, B., Nachman, J., Nadel, H., Sato, J. K., Meyers, P. A., Reaman, G. H. 2007; 109 (8): 164653


Patients with metastatic osteosarcoma have a poor prognosis. The objectives of the study were to determine the antitumor activity and toxicity of topotecan (daily x5) in newly diagnosed patients with metastatic osteosarcoma followed by chemotherapy (ifosfamide, carboplatin, etoposide [ICE], alternating with cisplatin and doxorubicin [CD]).Newly diagnosed patients (< or =30 years of age) with extensive metastatic disease (primary and > or =5 pulmonary nodules and/or bone metastases) with normal hepatic, renal, and cardiac function were eligible. Patients were eligible to receive further topotecan after standard chemotherapy if they exhibited a response. Twenty-eight patients were enrolled. Seventeen had metastases to the lung only and 11 had metastases to the bone or multiple sites. Of 28 patients enrolled, 27 could be evaluated for response. A limited dose escalation was incorporated.No responses were seen in the 11 patients treated at 3 mg/m(2)/day. One partial response (PR) and 1 clinical response (CLR) were reported among 15 patients who received topotecan at 3.5 mg/m(2)/day. No dose-limiting toxicity was observed. Principal nondose-limiting toxicities were hematologic and gastrointestinal. The 2- and 5-year event-free survival rates were low, 7% and 4%, respectively, but the 2- and 5-year overall survival rates were 44% and 22%, respectively.Topotecan at dose of 3.5 mg/m(2)/day can be safely administered upfront to newly diagnosed patients without excessive toxicity. Insufficient activity was seen with topotecan in this schedule to warrant further studies in osteosarcoma. The combination of ICE and CD was tolerable when delivered after initial topotecan therapy.

View details for DOI 10.1002/cncr.22553

View details for Web of Science ID 000245570900026

View details for PubMedID 17334983

Bone mineral density in children and adolescents with systemic lupus erythematosus, juvenile dermatomyositis, and systemic vasculitis: Relationship to disease duration, cumulative corticosteroid dose, calcium intake, and exercise JOURNAL OF RHEUMATOLOGY Alsufyani, K. A., Ortiz-Alvarez, O., Cabral, D. A., Tucker, L. B., Petty, R. E., Nadel, H., Malleson, P. N. 2005; 32 (4): 72933


To describe the frequency of abnormal bone mineralization in a population of children with juvenile systemic lupus erythematosus (JSLE), juvenile dermatomyositis (JDM), and systemic vasculitis; and to investigate the relationship of bone mineral density (BMD) to cumulative corticosteroid dose, disease duration, Tanner stage, calcium intake, and exercise in these patients.A retrospective chart review of children attending the pediatric rheumatology clinic at British Columbia's Children's Hospital was conducted to obtain demographic data (sex, ethnicity, disease duration, cumulative corticosteroid dose, and mean daily corticosteroid dose). All patients had at least one BMD measurement by dual energy x-ray absorptiometry (DEXA) at lumbar spine, hip, and total body. BMD was expressed as g/cm2 and Z scores; an abnormal Z score was defined as

View details for Web of Science ID 000228370500026

View details for PubMedID 15801032

Nuclear medicine topics in pediatric musculoskeletal disease - Techniques and applications RADIOLOGIC CLINICS OF NORTH AMERICA Nadel, H. R., Stilwell, M. E. 2001; 39 (4): 619-+


Musculoskeletal scintigraphy has excellent sensitivity for the evaluation of benign disease in children. Using illustrative cases, a spectrum of techniques and applications of nuclear medicine studies for benign bone diseases are presented. An approach to the use and evaluation of bone density evaluation in children also is discussed.

View details for DOI 10.1016/S0033-8389(05)70303-1

View details for Web of Science ID 000171760400003

View details for PubMedID 11549163

Hereditary heterotopic ossification: Are there overlaps between the different types? Chanoine, J. P., Cheng, P. S., Ostry, A., de Sa, D., Nadel, H., Prendiville, J. NATURE PUBLISHING GROUP. 2001: 6P
Laparoscopy as a cause of a false-positive Meckel's scan CLINICAL NUCLEAR MEDICINE McKevitt, E. C., Baerg, J. E., Nadel, H. R., Webber, E. M. 1999; 24 (2): 1024


A new cause of a false-positive result of a Meckel's scan is reported. An 11-year-old girl had a 3-week history of constant right lower quadrant pain that was initially managed by laparoscopic appendectomy. A repeated laparoscopy for persistent pain was nondiagnostic. A missed Meckel's diverticulum was considered as the cause of this pain, which prompted a Meckel scan. This scan revealed a periumbilical focus of activity that was interpreted as a Meckel's diverticulum attached to the anterior abdominal wall by a band. The laparotomy showed no Meckel's diverticulum. The false-positive result of the Meckel scan may be the result of inflammation from the periumbilical laparoscopic port site.

View details for DOI 10.1097/00003072-199902000-00005

View details for Web of Science ID 000078322600005

View details for PubMedID 9988066

The DMSA scan in paediatric urinary tract infection. Australasian radiology Ditchfield, M. R., Nadel, H. R. 1998; 42 (4): 31820


The objective of the present paper was to review the use of the dimercaptosuccinic acid (DMSA) scan in urinary tract infection at British Columbia's Children's Hospital to determine the frequency of cortical defects and the association between vesico-ureteric reflux and the presence of cortical defects in children with urinary tract infection. A total of 129 consecutive children with a urinary tract infection referred for a DMSA scan in a 2-year period (January 1992-January 1994) were retrospectively studied. The results were analysed in terms of kidneys, and the incidence of cortical defects was determined. Eighty-eight patients (68%) had a radiographic micturating cysto-urethrogram within 6 months of the DMSA scan, and in this group the relationship of defects with vesico-ureteric reflux was determined. Overall, 81/258 (31%) of kidneys had a cortical defect on a DMSA scan. Of those who had a micturating cysto-urethrogram, 53/176 (30%) kidneys had vesico-ureteric reflux, and of those that had reflux, 21/53 (40%) had a cortical defect on a DMSA scan. In the group of children without reflux, 38/123 (31%) had a cortical defect. Renal cortical scan defects are common findings in paediatric urinary infection, and frequently occur in the absence of vesico-ureteric reflux. These defects represent either established scars or acute pyelonephritis that can proceed to scarring. The micturating cysto-urethrogram alone is insufficient as a screening modality to identify those kidneys at risk of renal scarring.

View details for DOI 10.1111/j.1440-1673.1998.tb00530.x

View details for PubMedID 9833368

B mode ultrasonography - spectrum of paediatric ocular disease Long, G., Stringer, D. A., Nadel, H. R., Fink, A. M., Lewis, P., Carruthers, J. D., Lyons, C. ELSEVIER IRELAND LTD. 1998: 13247


Despite having appropriate sonographic equipment available many radiologists remain unfamiliar with B mode sonography of the eye.This article reviews the advantages and disadvantages of B mode sonography of the paediatric eye. We illustrate the spectrum of eye abnormalities occurring in paediatric practice and the sonographic appearance of clinical entities for which sonography is appropriate.We reviewed our experience of eye sonography within a paediatric radiology department over 8 years. A total of 212 sonographic examinations were performed on 206 eyes in 103 children, aged from 3 days to 16 years (mean 4.6 years).Sonography was well tolerated by the children, was a very useful imaging modality and was the only diagnostic imaging modality required in 94%. Supplementary computed tomography (CT) was performed in ten of 206 eyes (5%) and magnetic resonance imaging (MR) was performed in two of 206 eyes (1%).B mode sonography is a very useful imaging modality for suspected ocular or orbital pathology in children and is often the appropriate first line investigation following clinical evaluation. Radiologists familiar with sonography of the eye can provide valuable support to their ophthalmology colleagues.

View details for DOI 10.1016/S0720-048X(97)00089-2

View details for Web of Science ID 000071764300005

View details for PubMedID 9518222

Procedure guideline for radionuclide cystography in children JOURNAL OF NUCLEAR MEDICINE Mandell, G. A., Eggli, D. F., Gilday, D. L., Heyman, S., Leonard, J. C., Miller, J. H., Nadel, H. R., Treves, S. T. 1997; 38 (10): 165054

View details for Web of Science ID A1997XZ76600036

View details for PubMedID 9379209

Procedure guideline for renal cortical scintigraphy in children JOURNAL OF NUCLEAR MEDICINE Mandell, G. A., Eggli, D. F., Gilday, D. L., Heyman, S., Leonard, J. C., Miller, J. H., Nadel, H. R., Treves, S. T. 1997; 38 (10): 164446

View details for Web of Science ID A1997XZ76600034

View details for PubMedID 9379207

Hepatobiliary scintigraphy in children SEMINARS IN NUCLEAR MEDICINE Nadel, H. R. 1996; 26 (1): 2542


Hepatobiliary scintigraphy using iminodiacetic (IDA) radiopharmaceuticals provides clinically useful information on the function of the biliary tract in a variety of pathological processes in children, including neonatal jaundice, gallbladder dysfunction, trauma, and liver transplantation. Phenobarbital premedication (5 mg/kg per day for a minimum of 5 days in divided doses) is used in infants who are being examined for neonatal jaundice to increase the accuracy of 99mTc-IDA scintigraphy in differentiating extrahepatic biliary atresia from neonatal hepatitis. Biliary atresia can be ruled out in an infant if a patent biliary tree is shown with passage of activity into the bowel. If no radiopharmaceutical is noted in the bowel on imaging up to 24 hours, distinction between severe hepatocellular disease and biliary atresia cannot be made. The literature reports 91% accuracy, 97% sensitivity, and 82% specificity for hepatobiliary imaging in the diagnosis of biliary atresia. The impairment of both intrahepatic and extrahepatic biliary drainage is an important cause of liver disease in cystic fibrosis. Hepatobiliary scintigraphy in cystic fibrosis has shown characteristic patterns of dilatation of mainly the left hepatic duct, narrowing of the distal common bile duct, gallbladder dysfunction, and delayed bowel transit. Cholecystitis in children may be acalculous. Sensitivity and specificity for the scintigraphic diagnosis of acute acalculous cholecystitis is reported to range from 68% to 93% and 38% to 93%, respectively. Cholescintigraphy in a suspected bile leak provides information generally not available with other techniques, except for direct cholangiography. If the amount of intraperitoneal accumulation of the tracer is greater than that entering the gastrointestinal tract, surgery is usually indicated. Hepatobiliary imaging in children who have undergone liver transplantation will assess graft vascularity, parenchymal function, biliary drainage, presence of a leak, and obstruction.

View details for DOI 10.1016/S0001-2998(96)80014-6

View details for Web of Science ID A1996TR43600005

View details for PubMedID 8623049

Where are we with nuclear medicine in pediatrics? EUROPEAN JOURNAL OF NUCLEAR MEDICINE Nadel, H. R. 1995; 22 (12): 143351


The practice of nuclear medicine in children is different from that in adults. Technical considerations including immobilization, dosing of radiopharmaceuticals, and instrumentation are of major importance. Image magnification and the capability to perform single-photon emission tomography are essential to performing state of the art pediatric nuclear medicine. New advances in instrumentation with multiple detector imaging, the possibility of clinical positron emission tomography imaging in children, and new radiopharmaceuticals will further enhance pediatric scintigraphic imaging. This review highlights advances in pediatric nuclear medicine and discusses selected clinical problems.

View details for DOI 10.1007/BF01791153

View details for Web of Science ID A1995TL31200012

View details for PubMedID 8586090



Obstructive lung disease is a major complication of bone marrow transplantation related to graft-versus-host disease. The purpose of this study was to determine the usefulness of high-resolution CT to evaluate obstructive lung disease occurring in children after bone marrow transplantation.Ten high-resolution CT scans of the lungs were obtained in seven children who developed chronic obstructive lung disease after bone marrow transplantation. All seven patients had chronic graft-versus-host disease. Spirometry, the gold standard test, confirmed airflow obstruction in each case, five prior to high-resolution CT. Two patients were too young to have spirometry until 10 and 15 months respectively after successful high-resolution CT. Selected images from these studies were randomized with similar images from five control subjects and reviewed blindly. All images from scans in patients with obstructive lung disease were analyzed retrospectively for parenchymal hypoattenuation, bronchial dilatation, bronchial wall thickening, and abnormal parenchymal opacity. Expiratory air-trapping was assessed on cine high-resolution CT done in four cases.Three blinded observers each correctly identified all five controls among 15 high-resolution CT examinations. No scan from a patient with obstructive lung disease was considered normal. Areas of parenchymal hypoattenuation affected 35 of 35 lobes of the lung. Expiratory air-trapping was shown by cine high-resolution CT. Subsegmental or segmental bronchial dilatation was seen in 23 of 25 lobes in five patients. Bronchial wall thickening was not a prominent feature. Increasing abnormality was demonstrated in three patients on follow-up high-resolution CT. The high-resolution CT abnormalities were similar to those reported in patients with bronchiolitis obliterans.High-resolution CT of the lungs can show extensive abnormality in children who develop chronic obstructive lung disease after bone marrow transplantation. High-resolution CT is a useful noninvasive technique in the evaluation of this disease.

View details for DOI 10.2214/ajr.164.3.7863896

View details for Web of Science ID A1995QH86000029

View details for PubMedID 7863896



We report two children who developed hypersensitivity reactions of varying severity following barium meal examination, the more severe of which was associated with documented severe food allergy. For children with this risk factor, contrast studies should be performed only where facilities and personnel are available for immediate resuscitation of all sizes of child. For children such as these, consideration should be given to the use of pure barium sulphate.

View details for DOI 10.1007/BF02014970

View details for Web of Science ID A1993MU29900004

View details for PubMedID 8152869



Many pediatric centers are beginning to accumulate a large experience in the use of thallium-201 (201Tl) imaging with 201Tl requires a state-of-the-art high-resolution gamma camera computer system with single photon emission computed tomography (SPECT) capability and a physician-directed tailored examination. Tumor imaging with 201Tl, with its multifactorial localization mechanisms that are different from those for gallium-67, offers a distinct advantage over gallium tumor imaging with a short total imaging time. Tumors are variable in avidity and intensity of thallium uptake. Primary and metastatic disease can be detected with 201Tl scintigraphy. Baseline pretreatment determination of thallium avidity is crucial to its efficacy in therapeutic response assessment. Adjunctive SPECT imaging provides greater sensitivity for lesion detection and direct comparison of physiology (thallium uptake) with anatomy (computed tomography and magnetic resonance imaging). The sensitivity and specificity for detection of pediatric brain tumors has been reported as 77% and 93%, respectively. Thallium-201 brain SPECT also provides a less expensive and more readily available alternative to positron emission tomography for assessing the functional state of pediatric brain tumors. Extremity osteogenic sarcoma and Ewing's sarcoma have 100% sensitivity for 201Tl uptake pretreatment. Early results confirm an association between 201Tl uptake and histological tumor response. The determination of residual/recurrent disease versus thymic rebound and other nonneoplastic change in thallium-avid lymphoma, rhabdomyosarcoma, and germ cell tumors that involve the thorax can be confirmed with a 201Tl SPECT examination. Soft-tissue tumors elsewhere in the body may be detected with 201Tl scintigraphy. Thallium-201 does not exhibit 100% specificity for tumors. False-positive 201Tl uptake has been seen in histiocytosis X, benign bone tumors, stress fractures, and inflammation.

View details for DOI 10.1016/S0001-2998(05)80105-9

View details for Web of Science ID A1993LQ56300005

View details for PubMedID 8378797



Partial pulmonary resection in early childhood is well tolerated. Although long-term outcome has been described in several follow-up studies, almost no information is available on postoperative lung perfusion. We studied 14 patients 3 to 20 years (mean, 11.6 years) after they underwent partial pulmonary resection at 1 week to 30 months of age (mean, 6.8 months). We examined development, pulmonary function, endurance, radiographs and ventilation-perfusion scans. We used predicted pulmonary function test values, which were corrected for the relative amount of lung removed and called predicted-corrected values. We hypothesized that the remaining lung would have altered ventilation-perfusion characteristics. We found no abnormalities in the patients' physical development. Most children had abnormal regional ventilation, but normal equilibration occurred; five patients had gas retention; all had decreased perfusion to the area of resection; nine patients showed ventilation-perfusion mismatch characterized by dead-space ventilation. Lung volumes were within the predicted range in 12 patients. Residual volume and functional residual capacity were larger than predicted-corrected values in most patients but residual volume in relation to total lung capacity was at or below normal in 6 of 11 and did not correlate with the amount of lung removed. Most patients had prolonged expiratory flows. We conclude that lung resection in early childhood leads to good functional recovery. However, decreased expiratory flows, regional ventilation abnormalities, and decreased perfusion suggest dysplastic parenchyma and vascular bed in the area of resection.

View details for Web of Science ID A1993KW48300020

View details for PubMedID 8469008



Duplex ultrasound was used to assess the vascular status and predict the angiographic findings in 3 patients with Takayasu's arteritis. The most striking sonographic feature was the presence of concentric arterial wall thickening. Using pulsed Doppler, stenotic lesions were quantified, occlusive lesions were identified and collateral circulation was demonstrated. A high resistive flow pattern was demonstrated in diseased vessels compared with carotid wave-forms of control subjects. Subtle mural irregularity, minor stenotic lesions and areas of stenosis in branch vessels were missed by duplex evaluation. The thoracic aorta and occasionally major arterial branches in the abdomen were impossible to evaluate with ultrasound. Vascular magnetic resonance imaging was successful in delineating major aortic branches but was inferior to real-time ultrasound in resolving mural thickening. While angiography plays a major role as a baseline assessment of the entire vascular tree, duplex ultrasound can monitor disease progression and the effects of therapy. Serial duplex studies should greatly reduce the need for interval angiographic followup.

View details for Web of Science ID A1991FY15900026

View details for PubMedID 1681101



Fatal pneumococcal sepsis due to functional asplenia in a child with systemic lupus erythematosus (SLE) and transient hyposplenism in a 2nd child during an acute flare of SLE are described. Splenic ultrasound examinations and radionuclide spleen scans in 11 other children with SLE were normal. Splenic atrophy and dysfunction is an uncommon but potentially fatal complication of SLE in childhood.

View details for Web of Science ID A1988R308600010

View details for PubMedID 3070028


View details for DOI 10.2214/ajr.150.5.1129

View details for Web of Science ID A1988N010100032

View details for PubMedID 3258716



A retrospective clinical review was done to study the value of ultrasound and renography in the investigation of 100 neonates with renomegaly. Abnormalities in 73 patients were detected antenatally with ultrasonography. Of the neonates 47 had lower urinary tract pathological conditions and ultrasound was more than 90 per cent accurate in identifying the accompanying ureteral dilatation. A total of 53 neonates had upper tract anomalies (ureteropelvic junction obstruction or cystic dysplasia). With ultrasonography the degree of pyelocaliectasis in patients with ureteropelvic junction obstruction was classified as mild (22 units), moderate (13) or severe (7). Initial treatment and followup were reviewed to study the clinical course of neonates with mild to moderate degrees of pyelocaliectasis followed nonoperatively, and to determine whether the diuretic renogram had a predictive role in identifying which kidneys were most likely to deteriorate.

View details for DOI 10.1016/S0022-5347(17)43488-4

View details for Web of Science ID A1987K313500018

View details for PubMedID 3309371



Medical imaging in the pediatric age group presents special problems. The modern pediatric radiology department is a specialized area, and ensuring an adequate examination requires meticulous care from technician, radiologist and referring clinician. Radiation dose must be kept to a minimum, and constant modifications are being made to the "routine" methods of investigating common problems. These modifications include the introduction and rational integration of all the newer modalities. This presentation offers a modern diagnostic approach to a variety of common pediatric clinical problems.

View details for Web of Science ID A1986C626000034

View details for PubMedID 21267200

View details for PubMedCentralID PMC2327949



The immotile cilia syndrome (ICS) is an uncommon disorder characterized by specific and genetically determined defects of cilia that cause upper and lower respiratory disease. We reviewed the radiographic patterns in 30 patients who had ICS (15 females, 15 males) and ranged in age from newborn to 26 years. Except for two neonates, sinusitis and otitis were present in all patients. Chest radiographic abnormalities, universally present, included bronchial wall thickening, hyper-inflation, segmental atelectasis or consolidation, and segmental bronchiectasis. Situs inversus, present in 50% (7 females, 8 males), was not an essential part of this disorder. Radiologically, the disease progresses from bronchial wall thickening with or without hyperinflation, to increasing hyperinflation plus parenchymal changes including segmental atelectasis, consolidation, and bronchiectasis. There is also a predilection for anatomic middle lobe abnormalities. The radiological appearance and clinical state have similarities to cystic fibrosis, although they are less severe and less progressive. ICS should be considered in the differential diagnosis of slowly progressive chronic lung disease, sinusitis, and otitis.

View details for DOI 10.1148/radiology.154.3.3969467

View details for Web of Science ID A1985ABW2900018

View details for PubMedID 3969467