Quantitative susceptibility mapping in myotonic dystrophy: clinical relevance of subcortical iron accumulation

Abstract Myotonic dystrophy type 1 is a dominantly inherited disorder, affecting musculoskeletal and central nervous systems and mainly characterized by progressive muscular atrophy and multisystemic damages including cardiac, respiratory and sleep dysfunctions. Neuroimaging studies conducted in myotonic dystrophy type 1 patients have documented widespread cerebral alterations encompassing structural, microstructural, functional and metabolic aspects of the brain, while comparatively few studies have investigated the role of iron concentration in the pathophysiology of central nervous system impairment. We report here the use of quantitative susceptibility (χ) mapping to explore iron content of both cortical and subcortical structures in myotonic dystrophy type 1 patients and to assess its possible clinical relevance, combining imaging and clinical data. Thirty-four myotonic dystrophy type 1 participants (20 females, 46.8 ± 12.0 years old) and 35 age- and sex- matched healthy controls (20 females, 50.5 ± 17.3 years old) were included in the study. All participants underwent MRI examinations in the same 3-Tesla scanner. The MRI protocol included 3D morphological T1-weighted magnetization prepared rapid gradient echo and T2*weighted multi-echo gradient echo for quantitative susceptibility mapping reconstruction. Cortical and subcortical structures were automatically segmented, and a volume of interest–based analysis was performed; χ distributions were compared between the two groups and myotonic dystrophy type 1 χ values were correlated with clinical and laboratory data. In the myotonic dystrophy type 1 group, a significant increase of χ was found in almost all cortical gyri, as a non-specific sign of neurodegeneration. Among subcortical structures, χ was significantly higher in myotonic dystrophy type 1 group in both thalamus (ventral and pulvinar nuclei) and brainstem (pons and medulla), compared to healthy controls. Additionally, correlation analysis showed some links between χ in subcortical structures and clinical signs, suggesting greater iron concentration with deterioration of clinical conditions. Thalamic χ values were associated with cardiological parameters and disability scores and, as with brainstem χ, they were also positively correlated with the number of central apnoeas; finally, thalamic and brainstem χ were negatively correlated with the age of onset. This study showed a correlation between autonomic dysfunction related to certain subcortical structures and their χ; higher values of χ correlated with greater functional impairment, suggesting iron accumulation detected by the quantitative susceptibility mapping technique is a possible biomarker of disease progression.