Abstract Rationale Hermansky-Pudlak Syndrome Type 1 (HPS-1) is an autosomal recessive lysosome-related organelle disorder characterized by oculocutaneous albinism, bleeding diathesis, and progressive pulmonary fibrosis (PF). In Puerto Rico, the founder variant c. 1472₁487dup (p. His497Glnfs*90) is associated with a high prevalence of HPS-1-related PF, which remains a leading cause of mortality among affected adults. Although HRCT is the diagnostic standard for structural assessment, subclinical parenchymal changes preceding radiologic fibrosis are often undetectable by routine imaging interpretation. Quantitative 3D image analysis offers a sensitive approach for identifying early parenchymal alterations in asymptomatic carriers before clinical progression. This study aimed to longitudinally evaluate HRCT scans from an asymptomatic HPS-1 carrier to detect early subclinical parenchymal abnormalities using quantitative 3D imaging reconstruction and segmentation. Methods HRCT scans obtained in 2024 and 2025 were analyzed in 3D Slicer v5. 8. 1. Automated segmentation algorithms identified aerated parenchyma (blue), vascular structures (pink), and regions of suspected parenchymal abnormality or collapse (yellow). Diffusing capacity for carbon monoxide (DLCO) and other pulmonary function parameters were measured at both time points. 3D reconstructions were generated in axial, anterior, and posterior views for visual comparison. Radiologic interpretation by thoracic radiologists classified both HRCTs as “normal, ” with no visible interstitial thickening or ground-glass opacities. Results Although the 2024 HRCT appeared normal by conventional review, 3D segmentation revealed subtle focal areas of decreased aeration in the posterior basal segments bilaterally, comprising 3% of total lung volume. By 2025, these abnormalities became more pronounced and spatially extensive, particularly in the lower lobes, corresponding to a mild decline in DLCO (80%) while spirometry remained within normal limits. The quantitative 3D imaging model demonstrated early regional loss of aerated volume, consistent with subclinical parenchymal remodeling preceding overt fibrosis. Conclusion This case illustrates that quantitative 3D imaging analysis can detect early subclinical structural alterations in HPS-associated PF before radiologic or symptomatic manifestation. Incorporating 3D reconstruction and segmentation into longitudinal follow-up of genetically confirmed HPS-1 patients may improve early detection of disease onset, guide timely therapeutic interventions, and refine clinical monitoring protocols. These findings support the integration of quantitative imaging biomarkers into HPS-1 clinical trials and natural-history studies to identify early disease trajectories in at-risk populations. This abstract is funded by: Ponce Research Institute
Mena-Ventura et al. (Fri,) studied this question.