Chronic T2 Lesions in Multiple Sclerosis are Heterogeneous Regarding Phase MR Imaging.

MTR and T1 relaxation times are abnormal in MS lesions and NAWM, and may reflect tissue damage such as demyelination and axonal loss. Their relationship and potential to provide complementary information in tissue characterisation is explored. The aim of this study was to document the relationship between magnetisation transfer ratio (MTR) and T1 relaxation time in Multiple Sclerosis (MS) lesions and normal appearing white matter (NAWM) in order to determine whether the combination provides a more comprehensive tissue characterisation than either parameter in isolation. Ten patients with relapsing remitting MS and 10 age matched healthy controls underwent imaging using a protocol which included the measurement of both MTR and T1 relaxation times. The MTR and T1 values were compared statistically using a commonly adopted correlation approach and a mixed-model regression approach. There was a strong correlation between MTR and T1 in MS lesions (r=0.74). The correlation was seen equally in T1 hypointense and isointense lesions. The relationship was much weaker in MS NAWM (r=0.24) and no correlation was found in control white matter (r=0.06). Mixed-model regression analysis confirmed that the relationship between T1 and MTR is strongly dependent upon tissue type (MS lesion, MS NAWM, or control white matter). The relationship between MTR and T1 relaxation time measurements varies markedly between pathological and normal tissue types. In MS, the complementary information obtained from MTR and T1 is most apparent in NAWM. The results emphasise the potential for combinations of MR parameters to improve tissue characterisation, which in turn should improve understanding of disease pathology and treatment monitoring. Multiple Sclerosis (2000) 6 327 - 331

In vivo evaluation of remyelination in rat brain by magnetization transfer imaging

We combined tract-based spatial statistics (TBSS) and magnetization transfer (MT) imaging to assess white matter (WM) tract-specific short-term changes in early primary-progressive multiple sclerosis (PPMS) and their relationships with clinical progression. Twenty-one PPMS patients within 5 years from onset underwent MT and diffusion tensor imaging (DTI) at baseline and after 12 months. Patients' disability was assessed. DTI data were processed to compute fractional anisotropy (FA) and to generate a common WM "skeleton," which represents the tracts that are "common" to all subjects using TBSS. The MT ratio (MTR) was computed from MT data and co-registered with the DTI. The skeletonization procedure derived for FA was applied to each subject's MTR image to obtain a "skeletonised" MTR map for every subject. Permutation tests were used to assess (i) changes in FA, principal diffusivities, and MTR over the follow-up, and (ii) associations between changes in imaging parameters and changes in disability. Patients showed significant decreases in MTR over one year in the corpus callosum (CC), bilateral corticospinal tract (CST), thalamic radiations, and superior and inferior longitudinal fasciculi. These changes were located both within lesions and the normal-appearing WM. No significant longitudinal change in skeletonised FA was found, but radial diffusivity (RD) significantly increased in several regions, including the CST bilaterally and the right inferior longitudinal fasciculus. MTR decreases, RD increases, and axial diffusivity decreases in the CC and CST correlated with a deterioration in the upper limb function. We detected tract-specific multimodal imaging changes that reflect the accrual of microstructural damage and possibly contribute to clinical impairment in PPMS. We propose a novel methodology that can be extended to other diseases to map cross-subject and tract-specific changes in MTR.

The aim of this study was to use quantitative magnetisation transfer (MT) imaging to assess the different pathological substrates of tissue damage in multiple sclerosis (MS) and examine whether the MT parameters may be used to explain the disability in relapsing remitting (RR) MS. Thirteen patients with RRMS and 14 healthy controls were prescribed conventional MRI and quantitative MT imaging at 3.0 T. A two-pool model of MT (where A refers to the free pool and B to the macromolecular pool) was fitted to the data yielding a longitudinal relaxation rate R(A), a relative size F of macromolecular pool, transverse relaxation times T(2) (A) and T(2) (B) for the two pools and a forward exchange rate RM(0) (B). The MT ratio (MTR) was also computed. The mean MT parameters of the normal appearing white matter (NAWM) and of lesions in patients, and of white matter in controls were estimated. MT parameters were significantly different between lesions and NAWM in patients, and between the NAWM and the white matter of controls (with the exception of T(2) (B) and the MTR). Two models were investigated using ordered logistic regression, with the expanded disability status scale (EDSS) as the dependent variable. In the first one, mean NAWM MT parameters and lesion load were entered as explanatory variables; in the second one, mean MT variables within lesions and lesion load were entered as explanatory variables. Unexpectedly, T(2) (B) was the parameter most significantly associated with EDSS in NAWM. This parameter might represent a weighted average of the relaxation times of spins with different molecular environments, and therefore its variation could indicate a change in the balance between subpopulations of macromolecular spins. Conversely, in lesions, RM(0) (B), T(2) (B), F, R(A), and lesion load significantly predicted disability only when combined together. This might reflect the complex interaction between demyelination, remyelination, gliosis, inflammation and axonal loss taking place within lesions.

Multiple sclerosis: Classification revisited reveals homogeneity and recapitulation

Oligodendrocyte Progenitor Cell Susceptibility to Injury in Multiple Sclerosis

Magnetisation transfer (MT) imaging provides indirect information on tissue structure abnormalities in areas that otherwise may appear normal on conventional MRI. We determined the evolution of MT changes in normal appearing white matter (NAWM) and lesion on serial examination of 9 multiple sclerosis (MS) patients and age matched controls. The mean NAWM MT ratio (MTR) was found to correlate strongly (R = 0.93) with the length of time since the patient's first clinical presentation and was well characterized by a linear decrease of -0.16%/year (p < 0.0001). The time zero intercept of the NAWM MTR regression was 30.7 +/- 0.2%, not different from the average MTR of white matter from controls (30.4 +/- 0.2 %). An additional gradual decrease in NAWM MTR was observed 6 to 12 months before the appearance of a new lesion on conventional MRI, while a more precipitous decrease in MTR was seen 2 to 6 months before the lesion appeared. Those lesions that exhibited pre-lesion MTR decreases showed less MTR recovery than lesions which had no pre-lesion MTR decrease. The data suggest that the MTR of NAWM in MS undergoes a slow progressive decrease that starts at disease onset and accelerates rapidly in focal areas just prior to lesion appearance on conventional MRI.

In established multiple sclerosis, magnetization transfer ratio (MTR) histograms reveal abnormalities of normal-appearing white matter (NAWM) and grey matter (NAGM). The aim of this study was to investigate for such abnormalities in a large cohort of patients presenting with clinically isolated syndromes suggestive of multiple sclerosis. Magnetization transfer imaging was performed on 100 patients (67 women, 33 men, median age 32 years) a mean of 19 weeks (SD 3.8, range 12-33 weeks) after symptom onset with a clinically isolated syndrome and in 50 healthy controls (34 women, 16 men, median age 32.5 years). SPM99 software was used to generate segmented NAWM and NAGM MTR maps. The volumes of T2 lesions, white matter and grey matter were calculated. Eighty-one patients were followed up clinically and with conventional MRI after 3 years (n = 61) or until they developed multiple sclerosis if this occurred sooner (n = 20). Multiple regression analysis was used to investigate differences between patients and controls with age, gender and volume measures as covariates to control for potential confounding effects. The MTR histograms for both NAWM and NAGM showed a reduction in the mean (NAWM, 38.14 versus 38.33, P = 0.001; NAGM 32.29 versus 32.50, P = 0.009; units in pu) and peak location, with a left shift in the histogram. Mean NAWM and NAGM MTR were also reduced in the patients who developed clinically definite multiple sclerosis and multiple sclerosis according to the McDonald criteria but not in the 24 patients with normal T2-weighted brain magnetic resonance imaging (MRI). MTR abnormalities occur in the NAWM and NAGM at the earliest clinical stages of multiple sclerosis.

Disability in progressive MS is associated with T2 lesion changes

Neural correlates of symptom severity in obsessive-compulsive disorder using magnetization transfer and diffusion tensor imaging

OBJECTIVESTo assess (a) whether the changes in the normal appearing brain tissue (NABT), as revealed by magnetisation transfer (MT) histogram analysis, correlates with cognitive dysfunction in patients with multiple sclerosis...

We obtained magnetization transfer imaging (MTI) scans from individuals with cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) (1) to investigate the presence, extent, and nature of pathology in white and gray matter outside proton density (PD)-visible lesions; (2) to quantify the degree of tissue damage occurring in lesions seen on PD-weighted scans; and (3) to correlate MTI-derived measures of disease burden with age, physical disability, and cognitive performance. Dual-echo, T1-weighted, and MTI scans of the brain were obtained from 33 individuals with CADASIL and 12 control subjects. Magnetization transfer ratio (MTR) values from PD-visible lesions, normal-appearing white matter (NAWM), and normal-appearing gray matter (NAGM) were measured. Histograms of MTR from the whole brain and normal-appearing brain tissue were also produced. All MTR values from NAWM and NAGM regions studied were significantly lower for individuals with CADASIL than for control subjects, with the exception of those obtained from the NAWM of the infratentorial structures and the NAGM of the occipital cortex. The average MTR from PD lesions in individuals with CADASIL was significantly lower than that from all the NAWM regions. Average MTR and peak location from whole-brain and normal-appearing brain tissue histograms were significantly lower for individuals with CADASIL than for control subjects. MTR values from NAWM were strongly correlated with the extent of macroscopic lesions and their average MTR. Apart from NAGM, average MTR from all other tissues studied significantly decreased with increasing age, physical disability, and cognitive impairment. PD lesions of individuals with CADASIL have variable degrees of tissue damage. Brain tissue outside PD abnormalities is also damaged. This study suggests that the extent and the severity of the brain tissue damage are critical factors in determining clinical status in CADASIL.

ObjectiveTo develop a three-dimensional (3D) high-resolution free-breathing magnetization transfer ratio (MTR) sequence for contrast-free assessment of myocardial infarct and coronary vein anatomy.Materials and methodsTwo datasets with and without off-resonance magnetization transfer preparation were sequentially acquired to compute MTR. 2D image navigators enabled beat-to-beat translational and bin-to-bin non-rigid motion correction. Two different imaging sequences were explored. MTR scar localization was compared against 3D late gadolinium enhancement (LGE) in a porcine model of myocardial infarction. MTR variability across the left ventricle and vessel sharpness in the coronary veins were evaluated in healthy human subjects.ResultsA decrease in MTR was observed in areas with LGE in all pigs (non-infarct: 25.1 ± 1.7% vs infarct: 16.8 ± 1.9%). The average infarct volume overlap on MTR and LGE was 62.5 ± 19.2%. In humans, mean MTR in myocardium was between 37 and 40%. Spatial variability was between 15 and 20% of the mean value. 3D whole heart MT-prepared datasets enabled coronary vein visualization with up to 8% improved vessel sharpness for non-rigid compared to translational motion correction.DiscussionMTR and LGE showed agreement in infarct detection and localization in a swine model. Free-breathing 3D MTR maps are feasible in humans but high spatial variability was observed. Further clinical studies are warranted.

Objectives:To investigate the relationship between magnetization transfer (MT) imaging and tissue macromolecules in high-grade serous ovarian cancer (HGSOC) and whether MT ratio (MTR) changes following neoadjuvant chemotherapy (NACT).Methods:This was a prospective observational study. 12 HGSOC patients were imaged before treatment. MTR was compared to quantified tissue histology and immunohistochemistry. For a subset of patients (n = 5), MT imaging was repeated after NACT. The Shapiro–Wilk test was used to assess for normality of data and Spearman’s rank-order or Pearson’s correlation tests were then used to compare MTR with tissue quantifications. The Wilcoxon signed-rank test was used to assess for changes in MTR after treatment.Results:Treatment-naïve tumour MTR was 21.9 ± 3.1% (mean ± S.D.). MTR had a positive correlation with cellularity, rho = 0.56 (p < 0.05) and a negative correlation with tumour volume, ρ = −0.72 (p = 0.01). MTR did not correlate with the extracellular proteins, collagen IV or laminin (p = 0.40 and p = 0.90). For those patients imaged before and after NACT, an increase in MTR was observed in each case with mean MTR 20.6 ± 3.1% (median 21.1) pre-treatment and 25.6 ± 3.4% (median 26.5) post-treatment (p = 0.06).Conclusion:In treatment-naïve HGSOC, MTR is associated with cellularity, possibly reflecting intracellular macromolecular concentration. MT may also detect the HGSOC response to NACT, however larger studies are required to validate this finding.Advances in knowledge:MTR in HGSOC is influenced by cellularity. This may be applied to assess for cell changes following treatment.

The study was undertaken to determine the pathologic basis of subtle abnormalities in magnetization transfer ratio (MTR) and diffusion tensor imaging (DTI) parameters observed in normal-appearing white matter (NAWM) in multiple sclerosis brains. Brain tissues were obtained through a rapid postmortem protocol that included in situ magnetic resonance imaging (MRI). Four types of MRI-defined regions of interest (ROIs) were analyzed: (1) regions that were abnormal on all images (T2T1MTR lesions); (2) NAWM regions with slightly abnormal MTR located close to white matter lesions (sa-WM Close); (3) NAWM regions with slightly abnormal MTR located far from lesions (sa-WM Far); and (4) NAWM regions with normal MTR (NAWM). Immunohistochemical analysis for each ROI comprised immunostaining for myelin, axonal markers, activated microglia/macrophages, astrocytes, plasma proteins, and blood vessels. Forty-eight ROIs from 4 secondary progressive MS brains were analyzed. sa-WM Close ROIs were associated with significantly more axonal swellings. There were more enlarged major histocompatibility complex II(+) microglia and macrophages detected in sa-WM Far, sa-WM Close, and T2T1MTR lesions than in NAWM. Across all ROIs, MTR and DTI measures were moderately correlated with myelin density, axonal area, and axonal counts. Excluding T2T1MTR lesions from analysis revealed that MTR and DTI measures in nonlesional white matter (WM) were correlated with activated microglia, but not with axonal or myelin integrity. The pathologic substrates for MRI abnormalities in NAWM vary based on distance from focal WM lesions. Close to WM lesions, axonal pathology and microglial activation may explain subtle MRI changes. Distant from lesions, microglial activation associated with proximity to cortical lesions might underlie MRI abnormalities.