Systemic amyloidosis is a rare multisystem disease caused by the deposition of misfolded protein in various organs [1]. Cardiac involvement represents the most important prognostic factor and thus early diagnosis is of utmost importance, influencing further management of the patients [2].
There are several types of systemic amyloidosis but the commonest types affecting the heart are light-chain (AL) amyloidosis and transthyretin (ATTR) amyloidosis, the latter being further subdivided into senile amyloidosis and variant ATTR amyloidosis, caused by mutations in the TTR gene. Even though cardiac involvement is the principal driver of outcome, endomyocardial biopsy is seldom performed, mainly due to its invasive risks. Consequently, cardiac amyloidosis can be highly suspected when peripheral tissue histology confirms the diagnosis and qualifying echocardiography parameters are also evident [3].
Clinical and radiological manifestations of amyloidosis are often non-specific, making amyloidosis a diagnostic challenge.
Cardiovascular magnetic resonance imaging (CMR) including conventional sequences, late gadolinium enhancement (LGE), T1-mapping and determination of extracellular volume (ECV) fraction is a multiparametric modality for the diagnosis of amyloidosis and is an excellent tool for risk stratification and disease tracking.
T1-mapping is the quantitative measurement of myocardial signal and can be performed before (native T1) and after i.v. Gadolinium administration [4]. It allows diagnosing diffuse deposition of amyloid in cardiac muscle by measurement of T1 values, which directly correspond to variation in intrinsic myocardial tissue properties. T1-mapping measurements also allow for an estimation of extracellular space by calculation of ECV [5].
The most accepted technique used to obtain T1-mapping is the Modified Look-Locker Inversion-Recovery (MOLLI) sequence with common acquisition scheme denoted as 3(3)3(3)5 [6].
Each sequence chosen to perform T1-mapping requires determination of sequence-specific normal ranges. These are prerequisites for determining the dispersion of values per given sequences, which influence the diagnostic cut-offs between healthy and non-healthy hearts. Every change of parameters and sequence optimization requires a similar process of validation [5].
Myocardial T1-mapping has a high diagnostic accuracy in identifying cardiac amyloid burden and is more sensitive for detecting early disease in gene mutation carriers than LGE imaging [7].
ECV is calculated by multiplying the non-cellular component of blood (haematocrit) by the ratio of rate of change of myocardial T1 [3]. Native T1-mapping has the advantage of not requiring Gadolinium administration, but in a comparison study with ECV, the latter emerged as an independent predictor of mortality in multivariate analyses [8]. This is most likely explained by the fact that native T1 is a composite signal derived from cellular and extracellular relaxation times whereas ECV represents extracellular expansion, which is the closest non-invasive quantifier of amyloid burden within the heart.
Extensive infiltration of the interstitium by amyloid matrix increases native myocardial T1. Karamitsos et al [9] demonstrated in 53 AL amyloidosis patients that mean native myocardial T1 times measured by ShMOLLI on a 1.5T scanner were significantly raised (1140 ms) compared with healthy volunteers (958 ms). Higher values are observed on 3T scanner: Lin et al [10] found that native T1 values measured on 3T scanner in subjects affected by AL amyloidosis were 1438±120 ms (local reference values in healthy subjects = 1283±46 ms), whereas ECV values were 43.9±11% (values in healthy subjects = 27±1.7%).
Therefore the objective of this study was to establish the feasibility of the MOLLI sequence on 3T MR scanner and subsequently to identify local reference values of native T1 and ECV compared to patients affected by cardiac amyloidosis.
