Praveen Jayapal, MBBS

Abstract

Purpose To evaluate if ferumoxytol can improve the detection of bone marrow metastases at diffusion-weighted (DW) MRI in pediatric and young adult patients with cancer. Materials and Methods In this secondary analysis of a prospective institutional review board-approved study (ClinicalTrials.gov identifier NCT01542879), 26 children and young adults (age range: 2-25 years; 18 males) underwent unenhanced or ferumoxytol-enhanced whole-body DW MRI between 2015 and 2020. Two reviewers determined the presence of bone marrow metastases using a Likert scale. One additional reviewer measured signal-to-noise ratios (SNRs) and tumor-to-bone marrow contrast. Fluorine 18 (18F) fluorodeoxyglucose (FDG) PET and follow-up chest CT, abdominal and pelvic CT, and standard (non-ferumoxytol enhanced) MRI served as the reference standard. Results of different experimental groups were compared using generalized estimation equations, Wilcoxon rank sum test, and Wilcoxon signed rank test. Results The SNR of normal bone marrow was significantly lower at ferumoxytol-enhanced MRI compared with unenhanced MRI at baseline (21.380 19.878 vs 102.621 94.346, respectively; P = .03) and after chemotherapy (20.026 7.664 vs 54.110 48.022, respectively; P = .006). This led to an increased tumor-to-marrow contrast on ferumoxytol-enhanced MRI scans compared with unenhanced MRI scans at baseline (1397.474 938.576 vs 665.364 440.576, respectively; P = .07) and after chemotherapy (1099.205 864.604 vs 500.758 439.975, respectively; P = .007). Accordingly, the sensitivity and diagnostic accuracy for detecting bone marrow metastases were 96% (94 of 98) and 99% (293 of 297), respectively, with the use of ferumoxytol-enhanced MRI compared with 83% (106 of 127) and 95% (369 of 390) with the use of unenhanced MRI. Conclusion Use of ferumoxytol helped improve the detection of bone marrow metastases in children and young adults with cancer. Keywords: Pediatrics, Molecular Imaging-Cancer, Molecular Imaging-Nanoparticles, MR-Diffusion Weighted Imaging, MR Imaging, Skeletal-Appendicular, Skeletal-Axial, Bone Marrow, Comparative Studies, Cancer Imaging, Ferumoxytol, USPIO RSNA, 2023 ClinicalTrials.gov registration no. NCT01542879 See also the commentary by Holter-Chakrabarty and Glover in this issue.

View details for DOI 10.1148/rycan.220080

View details for PubMedID 36999999

View details for Web of Science ID 000909337401449

Abstract

OBJECTIVE: To compare the diagnostic accuracy of diffusion-weighted (DW)-MRI with b-values of 50s/mm2 and 800s/mm2 for the detection of bone marrow metastases in children and young adults with solid malignancies.METHODS: In an institutional review board-approved prospective study, we performed 51 whole-body DW-MRI scans in 19 children and young adults (14 males, 5 females; age range: 1-25years) with metastasized cancers before (n=19 scans) and after (n=32 scans) chemotherapy. Two readers determined the presence of focal bone marrow lesions in 10 anatomical areas. A third reader measured ADC and SNR of focal lesions and normal marrow. Simultaneously acquired 18F-FDG-PET scans served as the standard of reference. Data of b=50s/mm2 and 800s/mm2 images were compared with the Wilcoxon signed-rank test. Inter-reader agreement was evaluated with weighted kappa statistics.RESULTS: The SNR of bone marrow metastases was significantly higher compared to normal bone marrow on b=50s/mm2 (meanSD: 978.4361239.436 vs. 108.881109.813, p<0.001) and b=800s/mm2 DW-MRI (499.638612.721 vs. 86.28089.120; p<0.001). On 30 out of 32 post-treatment DW-MRI scans, reconverted marrow demonstrated low signal with low ADC values (0.385*10-30.168*10-3mm2/s). The same number of metastases (556/588; 94.6%; p>0.99) was detected on b=50s/mm2 and 800s/mm2 images. However, both normal marrow and metastases exhibited low signals on ADC maps, limiting the ability to delineate metastases. The inter-reader agreement was substantial, with a weighted kappa of 0.783 and 0.778, respectively.CONCLUSION: Bone marrow metastases in children and young adults can be equally well detected on b=50s/mm2 and 800s/mm2 images, but ADC values can be misleading.

View details for DOI 10.1007/s00256-022-04240-0

View details for PubMedID 36441237

Abstract

Ferumoxytol is an ultrasmall iron oxide nanoparticle, originally approved in 2009 by the FDA for IV treatment of iron deficiency in adults with chronic kidney disease. Subsequently, its off-label use as an MRI contrast agent has increased in clinical practice, particularly in pediatric patients in North America. Unlike conventional MRI contrast agents that are based on the rare earth metal gadolinium [gadolinium-based contrast agents (GBCAs)], ferumoxytol is biodegradable and carries no potential risk of nephrogenic systemic fibrosis. At FDA-approved doses, ferumoxytol demonstrates no long-term tissue retention in patients with intact iron metabolism. Ferumoxytol provides unique MRI properties including long-lasting vascular retention (facilitating high-quality vascular imaging) and retention in reticuloendothelial system tissues, thereby supporting a variety of applications beyond those possible with GBCAs. This Clinical Perspective describes clinical and early translational applications of ferumoxytol-enhanced MRI in children and young adults through off-label use for a variety of settings, including vascular, cardiac, and cancer imaging, drawing on the authors' institutional experience. In addition, we describe current preclinical and clinical research advances using ferumoxytol with regard to cellular and molecular imaging, and also as a novel potential cancer therapeutic agent.

View details for DOI 10.2214/AJR.22.28453

View details for PubMedID 36197052

View details for Web of Science ID 000893739700122