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

Abstract

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.

Keywords: Apparent diffusion coefficient; Bone marrow metastases; Children; DW-MRI; b value.

Fig. 1

The flow diagram of the participants. Among 95 potentially eligible patients who were referred to PET/MR for cancer staging or restaging, and based on the inclusion and exclusion criteria, 19 children and young adult patients were included in the study and underwent simultaneous ¹⁸F-FDG-PET, DW-MRI, and contrast-enhanced MRI scans at baseline and after receiving treatment. Our 19 patients received 51 scans: 19 scans at baseline and 32 scans after chemotherapy, which included, 19 scans at the end of their chemotherapy, and 13 scans at 2–6 months after the end of the chemotherapy.

Fig. 2

Normal bone marrow reconversion in a 16-year-old boy with large cell neuroendocrine carcinoma of the lung. ¹⁸F-FDG-PET-MRI demonstrates a low metabolic activity of the normal bone marrow at baseline (a). Immediately (24 hours) after therapy, hypermetabolic marrow is appreciated (b), while after 6 months of therapy, the bone marrow metabolic activity returns to normal (c). The simultaneous DW-MRI demonstrates a similar pattern with restricted diffusion immediately after treatment and relatively less diffusion restriction at baseline and after 6 months of therapy on both b=800s/mm² (d, e, f) and b=50s/mm² (g, h, i). DW-MRI with b=800s/mm² shows higher signal intensity of reconverted marrow compared with b=50s/mm² images immediately after therapy (e and h, respectively), suggesting that the observed effects are due to increased bone marrow cellularity rather than edema. In contrast to ¹⁸F-FDG-PET-MRI and DW-MRI, the ADC map demonstrates a similar pattern of bone marrow on baseline (j), immediately (k), and 6 months after therapy (l) scans. The corresponding fat-only images from the Dixon sequence demonstrate normal intermediate signal intensity of the bone marrow at baseline (m), decreased signal intensity immediately after therapy, apparently indicating decreased fat content and increased cellularity of the reconverted marrow (n), and increasing signal at 6 months after therapy, apparently indicating increasing fact content and decreasing cellularity of normal marrow (o).

Fig. 3

Inverse signal intensity of reconverted bone marrow on ¹⁸F-FDG-PET and DW-MRI scans on the post-treatment scan of a 14-year-old boy with Ewing sarcoma. After chemotherapy, normal bone marrow demonstrates hypermetabolic activity with high FDG uptake on ¹⁸F-FDG-PET (a, blue arrows) and combined ¹⁸F-FDG-PET-MRI (c, blue arrows), while a bone marrow metastasis in the right iliac wing demonstrates low FDG uptake (a and c, yellow arrows). On post-contrast T1-weighted MRI, bone marrow metastasis and normal bone marrow demonstrate no significant contrast enhancement (b, blue and yellow arrows). Note the irregular enhancement of the posterior iliac spine bilaterally after bone marrow aspirations. However, on DW-MRI, reconverted bone marrow shows hypointense signal on both b=50s/mm² (d, blue arrows), b=800s/mm² (e, blue arrows), and the corresponding ADC map (f, blue arrows), while the bone marrow metastasis demonstrates hyperintense signal (d, e, and f, yellow arrows). Also, the bone marrow lesion could be better detected on DW-MRI with a b=50s/mm² (d, yellow arrow), compared to b=800s/mm² (e, yellow arrow) due to the increased water content or necrosis of the lesion after chemotherapy.

Fig. 4

Better detection of a vertebral bone marrow metastasis in a 17-year-old girl with Hodgkin lymphoma on baseline DW-MRI with a b=800s/mm² compared to b=50s/mm². ¹⁸F-FDG-PET scan demonstrates high FDG uptake of a focal bone marrow metastasis in a lumbar vertebral body (a, yellow arrow) and mild FDG uptake of the normal bone marrow. Note also FDG uptake of retroperitoneal lymph nodes (a, blue arrow). While the bone marrow lesion does not enhance on the post-contrast T1-weighted gradient echo MRI (b, yellow arrow), the combined PET-MRI shows the focal bone marrow lesion (c, yellow arrow) and the retroperitoneal lymph nodes next to the inferior vena cava (c, blue arrow). The simultaneously acquired DW-MRI demonstrates the focal bone marrow lesion on both b=50s/mm² (d, yellow arrow) and b=800s/mm² scans (e, yellow arrow). The retroperitoneal lymph nodes are depicted as well on both b=50s/mm² (d, blue arrow) and b=800s/mm² scans (e, blue arrow). The focal bone marrow metastasis in the vertebral body could be better detected on DW-MRI with a b=800s/mm² compared to b=50s/mm², in part due to an increased lesion-to-marrow contrast and in part due to suppression of the cerebrospinal fluid on the long b-value images. On the corresponding ADC map, however, the normal bone marrow and the focal bone marrow metastasis have a similar hypointense signal (f, yellow arrow). This could be due to the high iron content of the bone marrow.

Fig. 5

Signal-to-noise ratios (SNR) of bone marrow and tumors on b=50s/mm² and b=800s/mm² DW-MRI scans and apparent diffusion coefficients (ADC) on the corresponding ADC maps using box plots. DW-MRI: SNR of bone marrow metastases (tumor) are significantly higher compared to the SNR of normal bone marrow on the baseline and post-treatment scans (p < .001, respectively) at both b=50s/mm² and b=800s/mm² DW-MRI scans. On post-treatment scans, the SNR of normal bone marrow (p = .045) and of bone marrow metastases (p < .001) is significantly higher on b=50s/mm² compared to b=800s/mm² scans. ADC map: The corresponding ADC values of bone marrow metastases (tumor) are significantly higher compared to the ADC value of normal bone marrow on baseline and post-treatment scans (p < .001, respectively). The fences indicate the standard deviation and “x” indicate the median.

Fig. 6

Quantitative evaluation of the tumor-to-marrow contrast on b=50s/mm² and b=800s/mm² DW-MRI scans and ADC values on the corresponding ADC map using box plots. DW-MRI: The tumor-to-marrow contrast, measured as the difference between the tumor SNR and normal bone marrow SNR, was not statistically significant between baseline and post-treatment scans at b=50s/mm² (p = .076) and b=800s/mm² (p = .653). ADC map: The lesion-to-marrow contrast on the corresponding ADC map is significantly larger on post-treatment scans compared to the baseline scans (p = .015). The fences indicate the standard deviation and “x” indicate the median.

Fig. 7

Comparison of the tumor-to-marrow contrast on b=50s/mm² and b=800s/mm² at baseline and post-treatment DW-MRI scans map using box plots. The tumor-to-marrow contrast was larger on b=50s/mm² than b=800s/mm² DW-MRI scans on the baseline (p = .009) and post-treatment (p < .001) scans. The fences indicate the standard deviation and “x” indicate the median.