Advanced MRI unravels the nature of tissue alterations in early multiple sclerosis

Abstract

IntroductionIn patients with multiple sclerosis (MS), conventional magnetic resonance imaging (MRI) provides only limited insights into the nature of brain damage with modest clinic-radiological correlation. In this study, we applied recent advances in MRI techniques to study brain microstructural alterations in early relapsing-remitting MS (RRMS) patients with minor deficits. Further, we investigated the potential use of advanced MRI to predict functional performances in these patients.MethodsBrain relaxometry (T1, T2, T2*) and magnetization transfer MRI were performed at 3T in 36 RRMS patients and 18 healthy controls (HC). Multicontrast analysis was used to assess for microstructural alterations in normal-appearing (NA) tissue and lesions. A generalized linear model was computed to predict clinical performance in patients using multicontrast MRI data, conventional MRI measures as well as demographic and behavioral data as covariates.ResultsQuantitative T2 and T2* relaxometry were significantly increased in temporal normal-appearing white matter (NAWM) of patients compared to HC, indicating subtle microedema (P = 0.03 and 0.004). Furthermore, significant T1 and magnetization transfer ratio (MTR) variations in lesions (mean T1 z-score: 4.42 and mean MTR z-score: −4.09) suggested substantial tissue loss. Combinations of multicontrast and conventional MRI data significantly predicted cognitive fatigue (P = 0.01, Adj-R2 = 0.4), attention (P = 0.0005, Adj-R2 = 0.6), and disability (P = 0.03, Adj-R2 = 0.4).ConclusionAdvanced MRI techniques at 3T, unraveled the nature of brain tissue damage in early MS and substantially improved clinical–radiological correlations in patients with minor deficits, as compared to conventional measures of disease.

How to choose the right MR sequence for your research question at 7 T and above?

“…Despite all these improvements, it is not yet clear if the better visualization of intracortical lesions, central vein sign and susceptibility signal within the lesion does have a clinical value and should therefore be part of the diagnostic work-up (Rovira et al, 2015). T1 weighted images nevertheless seem to be amongst the most robust methods for the detection of cortical lesions (Bonnier et al, 2014), and it has been shown that carefully choosing the inversion times of phase sensitive inversion recovery sequences can enhance the detectability of intracortical lesions (Mougin et al, 2015). Alternatively, to the gradient echo readouts mentioned earlier, FSE readouts following a T1 preparation such as provided by double inversion recovery are also valid alternatives (de Graaf et al, 2012).…”

Automated detection of white matter and cortical lesions in early stages of multiple sclerosis

“…Thus, these previously proposed, automated methods seem to be infrequently used in clinical practice, where detecting new lesions, particularly of small size, is very important in diagnosis and follow‐up of MS patients. Moreover, most of this prior work has not been applied systematically to high‐resolution 3D MS acquisition protocols, which are increasingly utilized in clinical practice, nor to some other sequences that optimize the contrast of cortical lesions such as double‐inversion recovery (DIR), phase‐sensitive inversion recovery, and magnetization‐prepared 2 rapid acquisition gradient‐echo (MP2RAGE) …”

Statistical estimation of T1 relaxation times using conventional magnetic resonance imaging

“…Therefore, we do not recommend the use of CSF as a reference region in intensity normalization. Furthermore, in addition to NAWM, several other regions have been shown to be diffusely affected by MS, including cerebellar white matter (CBWM) (Bonnier et al, 2014; Casanova et al, 2003; Deppe et al, 2015), cortical gray matter (Kutzelnigg et al, 2005; Pirko et al, 2007; Vrenken et al, 2006) and deep gray matter (Griffin et al, 2002; Parry et al, 2002; Pirko et al, 2007; Vrenken et al, 2006). …”

“…Cerebellar gray matter (CBGM), on the other hand, has not been found to be diffusely affected by MS, and a recent investigation of T 1 , T 2 , $T_2^{\ast }$, and magnetization transfer ratio (MTR) in early-stage RRMS looked for but found no changes to CBGM (Bonnier et al, 2014). Furthermore, the cerebellum has been utilized previously as a reference region for intensity normalization of positron emission tomography (PET) in the contexts of MS (Ratchford et al, 2012) and Alzheimer’s disease (Kropholler et al, 2007), though to the best of our knowledge it has not been used for intensity normalization of MRI.…”

“…In MS, elevated T 1 relaxation times have been consistently observed in normal-appearing white matter (NAWM), relative to that of healthy control subjects (Bonnier et al, 2014; Castriota-Scanderbeg et al, 2004; Griffin et al, 2002; Parry et al, 2002; Vaithianathar et al, 2002; Vrenken et al, 2006). There is also evidence for elevated T 1 in MS patients in deep gray matter, particularly in the thalamus (Griffin et al, 2002; Parry et al, 2002; Vrenken et al, 2006), and in cortical gray matter (CGM) (Vrenken et al, 2006).…”