Improved Detection of Bone Metastases in Children and Young Adults with Ferumoxytol-enhanced MRI.

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.

Detection of bone marrow metastases in children and young adults with solid cancers with diffusion-weighted MRI.

OBJECTIVE: To compare the diagnostic accuracy of diffusion-weighted (DW)-MRI with b-values of 50 s/mm2 and 800 s/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: 1-25 years) 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 = 50 s/mm2 and 800 s/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 = 50 s/mm2 (mean ± SD: 978.436 ± 1239.436 vs. 108.881 ± 109.813, p < 0.001) and b = 800 s/mm2 DW-MRI (499.638 ± 612.721 vs. 86.280 ± 89.120; p < 0.001). On 30 out of 32 post-treatment DW-MRI scans, reconverted marrow demonstrated low signal with low ADC values (0.385 × 10-3 ± 0.168 × 10-3mm2/s). The same number of metastases (556/588; 94.6%; p > 0.99) was detected on b = 50 s/mm2 and 800 s/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 = 50 s/mm2 and 800 s/mm2 images, but ADC values can be misleading.

Diagnostic Accuracy of 2-[18F]FDG-PET and whole-body DW-MRI for the detection of bone marrow metastases in children and young adults.

OBJECTIVES: To compare the diagnostic accuracy of 2-[18F]fluoro-2-deoxy-D-glucose-enhanced positron emission tomography (2-[18F]FDG-PET) and diffusion-weighted magnetic resonance imaging (DW-MRI) for the detection of bone marrow metastases in children and young adults with solid malignancies. METHODS: In this cross-sectional single-center institutional review board-approved study, we investigated twenty-three children and young adults (mean age, 16.8 years ± 5.1 [standard deviation]; age range, 7-25 years; 16 males, 7 females) with 925 bone marrow metastases who underwent 66 simultaneous 2-[18F]FDG-PET and DW-MRI scans including 23 baseline scans and 43 follow-up scans after chemotherapy between May 2015 and July 2020. Four reviewers evaluated all foci of bone marrow metastasis on 2-[18F]FDG-PET and DW-MRI to assess concordance and measured the tumor-to-bone marrow contrast. Results were assessed with a one-sample Wilcoxon test and generalized estimation equation. Bone marrow biopsies and follow-up imaging served as the standard of reference. RESULTS: The reviewers detected 884 (884/925, 95.5%) bone marrow metastases on 2-[18F]FDG-PET and 893 (893/925, 96.5%) bone marrow metastases on DW-MRI. We found different "blind spots" for 2-[18F]FDG-PET and MRI: 2-[18F]FDG-PET missed subcentimeter lesions while DW-MRI missed lesions in small bones. Sensitivity and specificity were 91.0% and 100% for 18F-FDG-PET, 89.1% and 100.0% for DW-MRI, and 100.0% and 100.0% for combined modalities, respectively. The diagnostic accuracy of combined 2-[18F]FDG-PET/MRI (100.0%) was significantly higher compared to either 2-[18F]FDG-PET (96.9%, p < 0.001) or DW-MRI (96.3%, p < 0.001). CONCLUSIONS: Both 2-[18F]FDG-PET and DW-MRI can miss bone marrow metastases. The combination of both imaging techniques detected significantly more lesions than either technique alone. KEY POINTS: • DW-MRI and 2-[18F]FDG-PET have different strengths and limitations for the detection of bone marrow metastases in children and young adults with solid tumors. • Both modalities can miss bone marrow metastases, although the "blind spot" of each modality is different. • A combined PET/MR imaging approach will achieve maximum sensitivity and specificity for the detection of bone marrow metastases in children with solid tumors.