Quantitative magnetization transfer imaging of pre-lesional white-matter                 changes in multiple sclerosis

Objective: Previous magnetization transfer (MT) studies in multiple sclerosis (MS) suggest a reduction of the MT ratio (MTR) precedes new lesion development. To gain further insight into pre-lesional tissue abnormalities, we investigated the time course of additional quantitative MT parameters. Methods: Serial magnetic resonance imaging (MRI), including a gadolinium-enhanced T1 scan and MT imaging by means of a FastPACE sequence, was performed on 12 patients (4 males, 8 females) with relapsing-remitting MS. Quantitative MT values including the magnetization exchange rate (kfor) and the native relaxation time (T1free) were analysed in the six months prior to the appearance of 44 enhancing lesions and in 88 control regions of persistently normal-appearing white matter (NAWM). Results: Appearance of new active lesions was preceded by a significant decrease of the MTR (F7,166=91.5; p <0.0001) and of kfor (F7,166=105.2; p <0.0001), and by an increase of T1free (F7,166=57.3; p <0.0001). The drop of kfor was the most pronounced pre-lesional change and together with the MTR was statistically significant already four months before the appearance of new lesion. The observed increase of T1free was relatively small. MT variables of reactivated lesions were always different from NAWM but showed no characteristic time course. Conclusions: Multiparametric MT measurements suggest both a reduction of macromolecular material and a focal increase of free water to occur several months before the appearance of an active lesion. Reduction of the magnetization exchange rate, which may result from primary damage to myelin, appears to be the leading event.

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Selective inversion recovery quantitative magnetization transfer imaging: Toward a 3 T clinical application in multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458519833018 ◽

2019 ◽

Vol 26 (4) ◽

pp. 457-467 ◽

Cited By ~ 1

Author(s):

Francesca Bagnato ◽

Giulia Franco ◽

Fei Ye ◽

Run Fan ◽

Patricia Commiskey ◽

...

Keyword(s):

Multiple Sclerosis ◽

White Matter ◽

Magnetization Transfer ◽

Brain Mri ◽

Inversion Recovery ◽

Clinical Disease ◽

Normal Appearing White Matter ◽

Selective Inversion ◽

Pool Model ◽

Magnetic Resonance Imaging Mri

Background:Assessing the degree of myelin injury in patients with multiple sclerosis (MS) is challenging due to the lack of magnetic resonance imaging (MRI) methods specific to myelin quantity. By measuring distinct tissue parameters from a two-pool model of the magnetization transfer (MT) effect, quantitative magnetization transfer (qMT) may yield these indices. However, due to long scan times, qMT has not been translated clinically.Objectives:We aim to assess the clinical feasibility of a recently optimized selective inversion recovery (SIR) qMT and to test the hypothesis that SIR-qMT-derived metrics are informative of radiological and clinical disease-related changes in MS.Methods:A total of 18 MS patients and 9 age- and sex-matched healthy controls (HCs) underwent a 3.0 Tesla (3 T) brain MRI, including clinical scans and an optimized SIR-qMT protocol. Four subjects were re-scanned at a 2-week interval to determine inter-scan variability.Results:SIR-qMT measures differed between lesional and non-lesional tissue ( p < 0.0001) and between normal-appearing white matter (NAWM) of patients with more advanced disability and normal white matter (WM) of HCs ( p < 0.05). SIR-qMT measures were associated with lesion volumes, disease duration, and disability scores ( p ⩽ 0.002).Conclusion:SIR-qMT at 3 T is clinically feasible and predicts both radiological and clinical disease severity in MS.

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Magnetization transfer and adiabatic T1ρ MRI reveal abnormalities in normal-appearing white matter of subjects with multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458513515084 ◽

2013 ◽

Vol 20 (8) ◽

pp. 1066-1073 ◽

Cited By ~ 19

Author(s):

Silvia Mangia ◽

Adam F Carpenter ◽

Andy E Tyan ◽

Lynn E Eberly ◽

Michael Garwood ◽

...

Keyword(s):

Multiple Sclerosis ◽

White Matter ◽

Magnetization Transfer ◽

Magnetic Resonance Images ◽

Relaxation Methods ◽

Normal Appearing White Matter ◽

Relaxation Parameters ◽

Relapsing Remitting ◽

Cortical Gray Matter ◽

The Brain

Background: Diffuse abnormalities are known to occur within the brain tissue of multiple sclerosis (MS) patients that is “normal appearing” on T1-weighted and T2-weighted magnetic resonance images. Objectives: With the goal of exploring the sensitivity of novel MRI parameters to detect such abnormalities, we implemented an inversion-prepared magnetization transfer (MT) protocol and adiabatic T1ρ and T2ρ rotating frame relaxation methods. Methods: Nine relapsing–remitting MS patients and seven healthy controls were recruited. Relaxation parameters were measured in a single slice just above the lateral ventricles and approximately parallel to the AC-PC line. Results: The MT ratio of regions encompassing the normal-appearing white matter (NAWM) was different in MS patients as compared with controls ( p = 0.043); however, the T1 measured during off-resonance irradiation (T1sat) was substantially more sensitive than the MT ratio for detecting differences between groups ( p = 0.0006). Adiabatic T1ρ was significantly prolonged in the NAWM of MS patents as compared to controls (by 6%, p = 0.026), while no differences were found among groups for T2ρ. No differences among groups were observed in the cortical gray matter for any relaxation parameter. Conclusions: The results suggest degenerative processes occurring in the NAWM of MS, likely not accompanied by significant abnormalities in iron content.

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Normal-Appearing White Matter Changes in Multiple Sclerosis: Magnetization Transfer

Normal-appearing White and Grey Matter Damage in Multiple Sclerosis ◽

10.1007/978-88-470-2127-3_4 ◽

2004 ◽

pp. 37-45

Author(s):

F. Fazekas ◽

C. Enzinger ◽

S. Ropele

Keyword(s):

Multiple Sclerosis ◽

White Matter ◽

Magnetization Transfer ◽

White Matter Changes ◽

Normal Appearing White Matter

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Fatigue in multiple sclerosis: The contribution of occult white matter damage

Multiple Sclerosis Journal ◽

10.1177/1352458516628331 ◽

2016 ◽

Vol 22 (13) ◽

pp. 1676-1684 ◽

Cited By ~ 24

Author(s):

Alvino Bisecco ◽

Giuseppina Caiazzo ◽

Alessandro d’Ambrosio ◽

Rosaria Sacco ◽

Simona Bonavita ◽

...

Keyword(s):

Multiple Sclerosis ◽

White Matter ◽

Diffusion Tensor ◽

Cerebral Peduncle ◽

Superior Longitudinal Fasciculus ◽

Normal Appearing White Matter ◽

External Capsule ◽

Mri Protocol ◽

Fatigue Severity ◽

Magnetic Resonance Imaging Mri

Background: A functional cortico-subcortical disconnection has been recognized in fatigued multiple sclerosis (MS) patients. Normal appearing white matter (NAWM) damage might contribute to the abovementioned disconnectivity. Objectives: To assess the relationship between fatigue and microstructural NAWM damage in relapsing-remitting (RR) MS. Methods: Sixty RRMS patients and 29 healthy controls (HC) underwent a magnetic resonance imaging (MRI) protocol including diffusion tensor imaging (DTI). Patients with a mean Fatigue Severity Scale (FSS) score ⩾ 4 were considered fatigued (fatigued MS (F-MS)). Tract-based spatial statistics were applied for voxel-wise analysis of DTI indices. A correlation analysis was performed between FSS score and DTI indices in the entire MS group. Results: Thirty MS patients were F-MS. Compared to HC, F-MS patients showed a more extensive NAWM damage than not fatigued MS (NF-MS) patients, with additional damage in the following tracts: frontal and occipital juxtacortical fibers, external capsule, uncinate fasciculus, forceps minor, superior longitudinal fasciculus, cingulum, and pons. No differences were found between F-MS and NF-MS patients. Fatigue severity correlated to DTI abnormalities of corona radiata, cingulum, corpus callosum, forceps minor, superior longitudinal fasciculus, inferior fronto-occipital fasciculus, thalamus and anterior thalamic radiation, cerebral peduncle, and midbrain. Conclusions: Fatigue is associated to a widespread microstructural NAWM damage, particularly in associative tracts connected to frontal lobes.

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