Comparing 18F-FDG PET/MRI and Diffusion-Weighted MRI for staging and restaging of Langerhans Cell Histiocytosis in children

Introduction: Langerhans Cell Histiocytosis (LCH) is a clonal neoplastic proliferation of myeloid dendritic cells affecting children, that can involve several organs and organ systems in the body. Whole-body staging is important in order to refer patients to appropriate local or systemic therapies. The goal of our study was to compare the diagnostic accuracy of ¹⁸F-FDG PET/MRI and whole-body diffusion-weighted magnetic resonance imaging (DWI-MRI) for staging and treatment monitoring of LCH.

Methods: We enrolled 23 children and young adults with biopsy-proven LCH (n=22) or Rosai Dorfman Disease (n=1) as part of a prospective, non-randomized, health insurance portability and accountability act compliant clinical trial (NCT03458520). Patients underwent simultaneous ¹⁸F-FDG PET/MRI with DWI-MRI (n=20) or sequential ¹⁸F-FDG PET/CT plus DWI-MRI (n=3), including 23 baseline scans and 16 follow-up scans after chemotherapy. We determined the presence or absence of tumor lesions in 8 anatomical areas per patient and calculated sensitivity, specificity, and diagnostic accuracy for the two imaging modalities. In addition, we determined the tumor standardized uptake value ratio, (SUV_ratio = tumor SUV_max/liver SUV_mean) and the mean apparent diffusion coefficient (ADC_mean). Quantitative data before and after chemotherapy were compared with a Mann-Whitney U test. All imaging studies performed within 2 weeks from the¹⁸F-FDG PET/MRI or ¹⁸F-FDG and MRI (including x-rays, bone scans, MRI, and whole-body ¹⁸F-FDG PET/CT scans) were used to determine the standard of reference for the evaluation of sensitivity, specificity, and diagnostic accuracy at baseline, and response to treatment at follow up.

Results: According to the standard of reference, our 23 patients had a total of 65 LCH lesions at baseline. ¹⁸F-FDG PET detected 65 of 65 LCH lesions and DW-MRI detected 63 of 65 lesions. ¹⁸F-FDG PET staged 23 out of 23 patients correctly, while DW-MRI staged 22 out of 23 patients correctly. DW-MRI missed 2 lesions in one patient due to artifacts in the thorax or lower neck.

Sensitivity and specificity were 100% for ¹⁸F-FDG PET for all anatomical regions. Sensitivity was 100% for DW-MRI for all regions but the spine and chest, while specificity was 100% for all anatomical regions.

According to the standard of reference 11 patients out of 16 were classified as responders, while 5 out of 16 were classified as non-responders to chemotherapy. For all lesions, responders had a SUV_ratio of [mean±SD: 3.82±1.85; range: 6.27] at baseline and SUV_ratio of [1.99±1.41; range=5.60] after chemotherapy. Non-responders had a SUV_ratio of [2.99±2.41; range=9.20] at baseline and SUV_ratio of [3.60±3.60; range=14.35] after chemotherapy. For all lesions, responders had an ADC_mean of [1.14±0.43; range=2.25] mm²/s at baseline and ADC_mean of [1.62±0.45; range=1.76] mm²/s after chemotherapy. Non-responders showed an ADC_mean of [0.94±0.42; range=1.33] mm²/s at baseline and ADC_mean of [1.06±0.43; range=1.62] mm²/s after chemotherapy. The difference in the change of both SUV_ratio and ADC_mean from baseline to first follow-up examination between responders and non-responders was significant (p=0.0006, and p=0.003, respectively).

Conclusions: ¹⁸F-FDG PET/MRI and WB DWI-MRI demonstrated significant agreement for the staging of LCH. Both techniques could accurately determine response to chemotherapy. This opens opportunities for personalized imaging protocols. Since patients with multifocal LCH are usually very young and need multiple follow-up scans throughout their lifetime, DW-MRI could be considered as an alternate approach without radiation exposure. Our continued investigations will assess if ¹⁸F-FDG PET/MRI can detect chemotherapy response earlier than DW-MRI.