# Multi-Modality Cardiovascular Imaging Assessment in Fabry Disease
## 3 Diagnosis: Tissue Characterization in Early Disease
### Cardiac MRI  
CMR is also able to accurately assess for early impairment of GLS similar to echocardiography (see Figure 6). However, a major advantage in performing CMR in FD patients over echocardiography has been the development of T1 mapping as an imaging biomarker of sphingolipid storage (see Figure 7). T1 mapping allows both visualization and quantification of the intracellular storage of sphingolipid, which substantially lowers T1 values below those found in other causes of LVH [28]. T1 lowering can be patchy but, unlike late enhancement imaging, is easily measured and does not require reference to 'normal' myocardium [29]. Low T1 is found in about half of FD patients before onset of LVH and appears to track both reduction in TDI and deterioration in strain values on echocardiography [30]. This may explain why a reduction in exercise capacity has been found on cardiopulmonary exercise testing in FD patients with low T1 but no other features of disease, compared to age and sex-matched controls [31]. In later stages of FD cardiomyopathyopathy when fibrosis develops within the myocardium, typically in the basal inferolateral wall, T1 relaxation times may increase or \"pseudonormalise\" (see Figure 7) [32]. T1 lowering is progressive up until this 'pseudonormalisation'. Native non-contrast T1 may lengthen with interstitial expansion due to a number of processes including the development of myocardial fibrosis and inflammation, likely due to increased free fluid associated with this state [33]. T1 lowering is greater in males than females and, as with LVH-progression, the decline in values continues despite ERT [19]. Furthermore, as perhaps might be expected in an X-linked disease, T1 mapping has confirmed that there is sex-dimorphism in the development of FD cardiomyopathy, with men following a path from T1 lowering to LVH before  
Figure 5: Strain TTE in a patient with Fabry Cardiomyopathy. **Left:** GLS assessment of the LV from the apical 4-chamber view demonstrating reduced GLS (\(-11.1\%\)); **Middle:** GLS assessment of the LV from the apical 2-chamber view demonstrating reduced GLS (\(-12.3\%\)); **Right:** GLS assessment of the RV from the Apical 4-chamber view demonstrating reduced GLS (free wall strain \(-16.1\%\) and longitudinal strain \(-12.2\%\)). the development late gadolinium enhancement (LGE), whereas in women, T1 lowering can be associated with (LGE) before the development of LVH. Low T1, however, is not always the earliest evidence of FD cardiomyopathy. In some patients, other changes can precede T1 lowering, including 12-lead electrocardiographic abnormalities, fall in global longitudinal strain (on echocardiography and CMR), diastolic dysfunction, and, less commonly, elevated biomarkers such as high-sensitive troponin [34]. T1 is an early imaging marker of cardiac involvement and, while useful as a diagnostic marker, it is not yet widely accepted as a trigger for introduction of therapy [35]. The presence of LGE, on the other hand, is an accepted trigger for therapy, despite the fact that this likely reflects a more advanced stage of disease beyond LVH [36]. The presence of LGE  
Figure 6: Long axis CMR assessment of 2D-strain using feature tracking by manually contouring endocardial and epicardial borders in end-diastole. (**A**): apical 4-chamber view, (**B**): apical 2-chamber view, (**C**): apical 3-chamber view, (**D**): myocardial strain curve with normal peak GLS measured (\(-26\%\)). Figure 7: CMR T1 mapping at 2 disease stages in patients with FD. (**Left**) T1 map with reduced relaxation times representing early sphingolipid accumulation in a patient with Fabry and early cardiomyopathy; (**Right**) T1 map with “pseudonormalisation” of T1 representing fibrosis within the myocardium in a patient with advanced Fabry cardiomyopathy. in the inferolateral mid-wall is an important indicator for the diagnosis of FD, with close correlation to macroscopic fibrosis and microscopic evidence of collagen deposition in the absence of sphingolipid [37].