Mancini Massimiliano, Bargiacchi Lavinia, De Vitis Claudia, D'Ascanio Michela, De Dominicis Chiara, Ibrahim Mohsen, Rendina Erino Angelo, Ricci Alberto, Di Napoli Arianna, Mancini Rita, Vecchione Andrea
Morphologic and Molecular Pathology Unit, Sant'Andrea University Hospital, 00189 Rome, Italy.
Department of Clinical and Molecular Medicine Sant'Andrea University Hospital, "Sapienza" University of Rome", 00189 Rome, Italy.
Biomedicines. 2023 May 19;11(5):1483. doi: 10.3390/biomedicines11051483.
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrotic lung disorder, ultimately leading to respiratory failure and death. Despite great research advances in understanding the mechanisms underlying the disease, its diagnosis, and its treatment, IPF still remains idiopathic without known biological or histological markers able to predict disease progression or response to treatment. The histologic hallmark of IPF is usual interstitial pneumonia (UIP), with its intricate architectural distortion and temporal inhomogeneity. We hypothesize that normal lung alveolar architecture can be compared to fractals, such as the Pythagoras tree with its fractal dimension (), and every pathological insult, distorting the normal lung structure, could result in variations. In this study, we aimed to assess the UIP histologic fractal dimension in relationship to other morphometric parameters in newly diagnosed IPF patients and its possible role in the prognostic stratification of the disease. Clinical data and lung tissue specimens were obtained from twelve patients with IPF, twelve patients with non-specific interstitial pneumonia (NSIP), and age-matched "healthy" control lung tissue from patients undergoing lung surgery for other causes. Histology and histomorphometry were performed to evaluate and lacunarity measures, using the box counting method on the FracLac ImageJ plugin. The results showed that was significantly higher in IPF patients compared to controls and fibrotic NSIP patients, indicating greater architectural distortion in IPF. Additionally, high values were associated with higher fibroblastic foci density and worse prognostic outcomes in IPF, suggesting that may serve as a potential novel prognostic marker for IPF. The scalability of measurements was demonstrated through repeated measurements on smaller portions from the same surgical biopsies, which were selected to mimic a cryobiopsy. Our study provides further evidence to support the use of fractal morphometry as a tool for quantifying and determining lung tissue remodeling in IPF, and we demonstrated a significant correlation between histological and radiological in UIP pattern, as well as a significant association between and FF density. Furthermore, our study demonstrates the scalability and self-similarity of measurements across different biopsy types, including surgical and smaller specimens.
特发性肺纤维化（IPF）是一种慢性、进行性纤维化肺部疾病，最终会导致呼吸衰竭和死亡。尽管在理解该疾病的潜在机制、诊断及治疗方面取得了重大研究进展，但IPF仍然病因不明，尚无已知的生物学或组织学标志物能够预测疾病进展或对治疗的反应。IPF的组织学特征是普通型间质性肺炎（UIP），伴有复杂的结构扭曲和时间上的不均匀性。我们假设正常肺肺泡结构可与分形相比较，比如具有分形维数（）的毕达哥拉斯树，并且每一次扭曲正常肺结构的病理损伤都可能导致变化。在本研究中，我们旨在评估新诊断的IPF患者中UIP组织学分形维数与其他形态学参数的关系及其在该疾病预后分层中的可能作用。从12例IPF患者、12例非特异性间质性肺炎（NSIP）患者以及因其他原因接受肺手术患者的年龄匹配的“健康”对照肺组织中获取临床数据和肺组织标本。进行组织学和组织形态计量学分析以评估和孔隙率测量，使用FracLac ImageJ插件上的盒计数法。结果显示，与对照组和纤维化NSIP患者相比，IPF患者的显著更高，表明IPF中存在更大的结构扭曲。此外，在IPF中高值与更高的成纤维细胞灶密度及更差的预后结果相关，提示可能作为IPF潜在的新型预后标志物。通过对同一手术活检较小部分进行重复测量来证明测量的可扩展性，这些较小部分被选择用于模拟冷冻活检。我们的研究提供了进一步的证据支持使用分形形态计量学作为量化和确定IPF中肺组织重塑的工具，并且我们证明了UIP模式下组织学和放射学之间的显著相关性以及与FF密度之间的显著关联。此外，我们的研究证明了测量在不同活检类型（包括手术和较小标本）中的可扩展性和自相似性。
