There are three stages of cardiac involvement in FD with different characteristics shown on cardiac MRI:
- Accumulation phase: normal or low native T1 mapping without LVH.
- Inflammation and myocyte hypertrophy phase: low native T1 mapping, presence of late gadolinium enhancement (LGE) with or without LVH.
- Fibrosis and impairment phase: pseudonormalization of native T1 mapping and extensive LGE.
Main Imaging Features on Cardiac MRI:
Left Ventricular Hypertrophy (LVH)
LVH is the most common structural change reported in FD. Cardiac MRI is the gold standard for the assessment of myocardial wall thickness and mass. Patients with FD predominantly start with concentric LVH, which later becomes asymmetrical with a grossly thickened septum compared to the inferolateral left ventricular wall (Fig. 1a). The inferolateral wall appears less thick because of underlying replacement fibrosis. Inadvanced stage, left ventricular outflow tract obstruction may be present both at rest (Fig. 2d) and provoked by exercise.
Late Gadolinium Enhancement (LGE)
LGE reflects replacement fibrosis due to chronic inflammation and it is present in almost half of FD patients. Majority of the cases would start with involving mid-myocardial layer of the basal and mid inferolateral wall of the left ventricle, sparing the subendocardium (Fig. 2a and b). This pattern is typical of FD and can help to distinguish it from other causes of symmetric LVH. In advanced disease, LGE can be extensive with a less specific appearance (Fig. 3a, b and c). In such cases, T1 mapping can be helpful to differentiate with other causes of LVH.
T1 Mapping
Accumulation of glycosphingolipids in lysosomes significantly shortens the native T1 values (Fig. 1b). Native T1 values are reduced in the early stage of FD but they begin to normalize with progressive accumulation of glycosphingolipids (pseudonormalization) (Fig. 3d). T1 values can be increased in the advanced stage due to replacement fibrosis and ongoing inflammation (Fig. 3d). Reduced native myocardial T1 value is the most sensitive and specific Cardiac MRI parameter in FD patients. It can be used to differentiate patients with FD from other pathogenesis with LVH. Reduced native T1 values can also be seen in the absence of LVH and basal inferolateral wall LGE in early stage of the disease (Fig. 4). Therefore, it may help to identify patients with early cardiac involvement and provide appropriate treatments for those patients.
Other Imaging Features:
Cardiac Function and Regional Wall Motion Abnormalities
Left ventricular ejection fraction and diastolic function are usually preserved in the early stage of disease. When posterolateral basal mid-myocardial fibrosis develops, wall thinning and hypokinesia / akinesia could be observed in the region. Mild to moderate diastolic dysfunction and restrictive filling are only seen in very advanced stage. Right ventricular hypertrophy is sometimes present but the ejection function is usually preserved.
Valvular Involvement
Structural valve abnormalities are frequently associated with LVH. The aortic and mitral valves are most commonly involved with mild to moderate regurgitations (Fig. 2d and 5). Aortic remodelling secondary to aortic valve disease could result in mild aortic ectasia or dilatation.
T2 Mapping
Elevated native T2 values in the early stage of myocardial involvement due myocardial oedema or inflammation. In the later stage, native T2 values would elevate corresponding to areas of LGE in the basal inferolateral wall, indicating chronic inflammation (Fig. 6). Chronic T2 elevation in LGE areas and elevation of global T2 values are both associated with poor outcomes.