Micro-computed tomography (micro-CT) for the assessment of myocardial disarray, fibrosis and ventricular mass in a feline model of hypertrophic cardiomyopathy

Jose Novo Matos,Owen J Arthurs,J Ciaran Hutchinson,Anna Guy,Andrew C Cook,Virginia Luis Fuentes,Patricia Garcia-Canadilla,Ian C Simcock,Melanie Dobromylskyj

doi:10.1038/s41598-020-76809-5

Abstract

Micro-computed tomography (micro-CT) is a high-resolution imaging modality that provides accurate tissue characterization. Hypertrophic cardiomyopathy (HCM) occurs as a spontaneous disease in cats, and is characterized by myocardial hypertrophy, disarray and fibrosis, as in humans. While hypertrophy/mass (LVM) can be objectively measured, fibrosis and myocyte disarray are difficult to assess. We evaluated the accuracy of micro-CT for detection and quantification of myocardial disarray and fibrosis by direct comparison with histopathology. 29 cat hearts (12 normal and 17 HCM hearts) underwent micro-CT and pathologic examination. Myocyte orientation was assessed using structure tensor analysis by determination of helical angle (HA), fractional anisotropy (FA) and myocardial disarray index (MDI). Fibrosis was segmented and quantified based on comparison of gray-scale values in normal and fibrotic myocardium. LVM was obtained by determining myocardial volume. Myocardial segments with low FA, low MDI and disruption of normal HA transmural profile on micro-CT were associated with myocardial disarray on histopathology. FA was consistently lower in HCM than normal hearts. Assessment of fibrosis on micro-CT closely matched the histopathologic evaluation. LVM determined by micro-CT was higher in HCM than normal hearts. Micro-CT can be used to detect and quantify myocardial disarray and fibrosis and determine myocardial mass in HCM.

Highlights

Hypertrophic cardiomyopathy (HCM) is a myocardial disease characterized by a hypertrophied left ventricle (LV) in the absence of abnormal loading conditions[1,2]
Isolated left ventricular hypertrophy (LVH) can be caused by HCM phenocopies, so accurate quantification of disarray and fibrosis is important for postmortem diagnostic accuracy
Quantification of LV fibrosis was performed in 13/17 HCM hearts, as poor myocardial detail in 4/17 scans hindered accurate fibrosis segmentation

Summary

Introduction

Hypertrophic cardiomyopathy (HCM) is a myocardial disease characterized by a hypertrophied left ventricle (LV) in the absence of abnormal loading conditions[1,2]. Micro-CT has been shown to be highly accurate in cardiac phenotyping in both humans and m ice[8,9,10], with superior assessment of myocardial morphology and coronary artery anatomy compared with dissecting m icroscopy[9]. Iodine-enhanced micro-CT differentiates cardiac tissue types based on differential attenuation of X-rays[6,7,11], and allows assessment of the orientation of aggregated myocytes in canine and human h earts[6,7,12]. HCM has traditionally been diagnosed with histopathology based on the presence of 3 main features: left ventricular hypertrophy (LVH); myocardial disarray; and fibrosis[13,14,15]. Isolated LVH can be caused by HCM phenocopies, so accurate quantification of disarray and fibrosis is important for postmortem diagnostic accuracy

Objectives

Methods

Results

Conclusion