MON-721 Exploring MRI quantification techniques for phenotypes of adiposity: data from a clinical trial of metreleptin to treat Madelung’s disease

Abstract Disclosure: A. Dill Gomes: None. M.C. Foss de Freitas: None. N. Shah: None. R. Meral: None. T. Chenevert: None. E.A. Oral: Regeneron Pharmaceuticals, Amryt Pharmaceuticals, Chiesi Rare Disease Group, Marea Therapeutics, Rejuvenate Bio, Fractyl Laboratories, Novo Nordisk, Morphic Medical. Background: Precise body fat measurements are essential for assessment of novel phenotypes and follow-up in lipodystrophy syndromes. However, there is a lack of adequate tools for evaluating regional fat distribution in the body. Our radiology team developed software in-house to quantify subcutaneous and visceral compartments in the abdomen. Here, we adapt this method to quantify adipose tissue in the neck and thighs to better assist in diagnosis of abnormal fat distribution disorders. Methods: In a previously reported clinical trial, data from 4 subjects diagnosed with Madelung’s symmetric lipomatosis (a severe phenotype of abnormal fat distribution) were collected before and after leptin replacement therapy. We took MRI image scans from baseline and week 24 of therapy and applied region of interest (ROI) masks over three slices in the neck and mid-thigh regions. We quantified the percentage of fat in these areas and compared them to the same regions in DEXA scans taken at the same timepoints. To analyze the measurement differences between the MRI and DEXA ROI’s, we performed t-tests and Pearson correlation. To determine the agreement of the two methods, we evaluated Bland-Altman Plots. Results: All subjects displayed altered percentages of regional fat between baseline and week 24. MRI showed an average reduction of 17% fat in the neck (baseline = 45%±0.1, week 24 = 37%±0.2) and 36% in the thigh (baseline = 26%±0.2, week 24 = 16.6%±0.2). Meanwhile, DEXA showed a 23% reduction in the neck (baseline = 37.8%±0.05, week 24 = 29%±0.1), and a 26.5% reduction in the thigh (baseline = 11.2%±0.06, week 24 =8.3%±0.03). The change in fat percentages detected by MRI was similar compared to changes detected by DEXA in neck and thigh. Both methods showed good correlation in neck (r = 0.79, 95% CI = 0.18, 0.95, p=0.02) and thigh (r = 0.92, 95% CI = 0.60, 0.98, p=0.001). However, a high correlation does not imply agreement between the methods, therefore we performed Bland-Altman analyses to assess the agreement between the two methods. We found that the two methods were similar for the neck quantification (bias = 1.25, 95% CI = 0.81, 1.69), but not for the thigh quantification (bias = 1.85) with a wide limit of agreement (95% CI = -0.41, 4.11). Conclusions: Despite a difference between the average fat quantification from neck and thigh using MRI and DEXA, both methods show a strong correlation. Our data show a strong agreement between MRI and DEXA for neck fat quantification, but the same agreement was not seen in the thigh. Though preliminary, whole body MRI scans combined with ROI mapping can be utilized to determine precise fat quantification regionally and these methods can be useful during clinical trials testing impact of therapeutic agents on fat distribution. Further work is needed to provide more robust validation in a larger number of patients and across different trials. Presentation: Monday, July 14, 2025