Multimodal Quantitative Imaging of the Microvascular Component in Cellulite: Candidate Imaging Biomarkers of Treatment Response

Background/Objectives: Cellulite is a complex alteration of the dermal–subcutaneous interface involving structural and microvascular components. This study evaluated changes in quantitative imaging parameters following ALIDYA mesotherapy using a multimodal protocol and explored candidate imaging biomarkers potentially reflecting the microvascular component of cellulite. Methods: In this prospective, single-arm, exploratory before–after study, thirty women aged 20–45 years with Nürnberger–Müller grade I–IV cellulite of the posterior thighs underwent six weekly ALIDYA mesotherapy sessions. Assessments were performed at baseline (T1), at an intermediate assessment after the third treatment (T2), and at final follow-up (T3). Cross-polarized photography with Gray-Level Co-occurrence Matrix (GLCM) analysis, infrared thermography with GLCM analysis, hyperspectral imaging, and Antera 3D erythema assessment were performed. Longitudinal changes were analyzed using non-parametric methods. Results: Photographic GLCM Contrast decreased and Homogeneity increased significantly over time (p ≤ 0.002). Thermographic Contrast decreased (p ≤ 0.003), while thermographic Homogeneity increased (p ≤ 0.012). Hyperspectral HbDepth560 decreased (p = 0.002), whereas R560/R650 and R577/R650 increased (both p < 0.001). VIS slope increased (p = 0.016), while Water970_800 (p = 0.967) and NIR slope (p = 0.792) remained unchanged. Antera 3D Redness Score and its minimum and maximum values decreased significantly (all p < 0.001), whereas Uniformity remained unchanged. Effect sizes (Kendall’s W) were largest for the Antera 3D erythema parameters (0.32–0.55) and the hemoglobin-related hyperspectral indices (0.20–0.31) and smallest for the VIS slope (0.14). Treatment was well tolerated; transient bruising with local tenderness at the injection sites was the only adverse event, and no participant discontinued treatment. Conclusions: Several optical, thermal and multispectral imaging parameters changed concordantly during the ALIDYA treatment period. These parameters can be regarded as candidate imaging biomarkers of the microvascular component of cellulite that require further validation; without a control group, reproducibility data or direct perfusion measurements, the changes cannot be attributed to a specific mechanism of the product or interpreted as evidence of improved microcirculation. The main contribution of the study is methodological: it shows that complementary quantitative imaging techniques can be combined in a single protocol to monitor cellulite-associated tissue changes.