Beyond the root: Geometric characterization for the diagnosis of syndromic heritable thoracic aortic diseases

Abstract

Aorta; Aortic dilatation; Genetic aortopathies

Aorta; Dilatación aórtica; Aortopatías genéticas

Aorta; Dilatació aòrtica; Aortopaties genètiques

Syndromic heritable thoracic aortic diseases (sHTAD), such as Marfan (MFS) or Loeys–Dietz (LDS) syndromes, involve high risk of life threatening aortic events. Diagnosis of syndromic features alone is difficult, and negative genetic tests do not necessarily exclude a genetic or hereditary condition. Periodic 3D imaging of the aorta is recommended in patients with aortic disease. Thus, an imaging-based approach aimed at identifying unique features of aortic geometry can be highly effective for diagnosing sHTAD and assessing risk. In this study, we present a method that can help identify the manifestations of sHTAD by focusing on the entire geometry of the thoracic aorta, rather than only using measurements of dilation of the aortic root. We analyze the geometric phenotype of 97 patients with genetically confirmed sHTAD (79 MF and 18 LDS) and of 45 healthy volunteers, using 3D aorta meshes obtained from phase contrast-enhanced magnetic resonance angiograms computed from 4D flow cardiac magnetic resonance. We build a geometric encoding of the aorta, based on a vessel coordinate system, and use several mathematical models to discriminate between controls and patients with sHTAD: a baseline scenario, based on aortic root dimensions only, a descriptor typically used in sHTAD patients; a low dimensional scenario, with a reduce encoding using principal component analysis; and a high-dimensional scenario, which included the full coefficient representation for geometry encoding, aiming to capture finer geometric details. The results indicate that considering the anatomy of the whole thoracic aorta can improve predictive ability. We achieve precision and sensitivity values over 0.8, with a specificity of over 70% in all the models used, while a single value classifiers (based only on aortic root diameter) demonstrated a trade-off between sensitivity and specificity. Using the mathematical properties of the vessel coordinate system representation, feature importance is mapped onto a set of anatomical traits that are used by the models to do the classification, thus providing interpretability of the results. This analysis indicates that in addition to the diameter of the aortic root, aortic elongation and a narrowing of the descending thoracic aorta may be markers of positive sHTAD.

This work was funded by Generalitat Valenciana Grant AICO/2021/318 (Consolidables 2021). This research is part of Project PID2020-114291RB-I00 funded by MCIN/10.13039/501100011033/FEDER, UE. A. Guala received funding from the La Caixa Foundation (LCF/BQ/PR22/11920008).