# Multi-Modality Cardiovascular Imaging Assessment in Fabry Disease
## 2 Diagnosis: Maximal Wall Thickness and LV Hypertrophy
### Cardiac MRI  
Cardiac MRI is considered the gold standard non-invasive tool for measuring MWT and LV mass based on multiple studies, relying on the acquisition of serial short-axis balanced steady-state free precession (SSFP) images along perpendicular long axis images of the ventricle. In FD, the clinical impact of the use of CMR in preference to 2D echocardiography has been emphasised in a retrospective study of 78 patients in whom eligibility for disease-specific therapy changed in more than one out of four patients (26%) [12]. TTE consistently over-estimated both MWT and LV mass, suggesting that FD patients frequently are liable to over-estimated MWT and LV mass. These results were replicated in another study of 32 patients with FD (47% male), in whom the highest variability in MWT was the LV inferolateral wall and with consistent over-estimation of LV mass using 2D echocardiography [13].  
Most data for wall thickness and mass on CMR have been produced using semi-automatic software that analyse short axis images on a per slice basis, deriving LV mass and volume by applying the Simpsons' stack of discs' method (see Figure 2). Two issues that continue to affect inter-study repeatability are the selection of the basal slice and consistency in the method used for contouring selected, in terms of detailed contouring [14] as opposed to smooth contouring [15]. Both of these factors can make a big difference to serial assessment in a given individual, with re-classification of 20% of patients with hypertrophy to normal LV mass if using smoothed contours, the latter technique tending to under-estimate measurements particularly in those patients with papillary muscle hypertrophy as is typical of FD [16]. As in echocardiography, the limitations of measurements made by expert readers of MWT have been highlighted in comparison to those made using AI. Figure 3 demonstrates this by indicating the high degree of variability between manual contouring by experts and semi-automated AI quantification of MWT. In a large multicentre study of 60 HCM patients scanned twice, MWT measured by a machine learning algorithm was more precise and reproducible on test-retest than those of 11 human experts. Adoption of machine learning tools may have significant implications for the selection of FD patients to start therapy or to refer for device therapy, with expert test-retest differences ranging from 1.1 to 3.7 mm difference, compared to only 0.7 mm for AI [17].  
Figure 1: **(Left)** Parastermal long axis 2D TTE demonstrating linear measurements of IVS, LVID and LVPW demonstrating severe LVH; **(Right)** Parastermal short axis 2D TTE demonstrating severe LVH with MWT of 21 mm. Both images are taken from an adult male with advanced cardiomyopathy related to FD.  
Figure 2: CMR cine imaging in a patient with Fabry cardiomyopathy; **(Left)** Apical 3-chamber view demonstrating concentric LVH with basal inferolateral wall-thinning; **(Right)** CMR short axis image demonstrating severe concentric LVH.  
Summary points:
* LV maximal wall thickness and LVH are important triggers to treatment in FD;
* Measurement of MWT is highly variable in expert hands-on 2D echocardiography and CMR;
* Further work should be addressed at validating AI-based analysis of 3D echocardiography-raphy and CMR stacks in this population with the aim for this to eventually become the gold standard.