Magnetization Transfer Ratio in the Typically Developing Pediatric Spinal Cord: Normative Data and Age Correlation.

Background: This study aimed to establish normal regional Magnetization Transfer Ratio (MTR) values in white and grey matter using 3-Tesla MRI in healthy adult subjects, with a particular focus on cortical and deep brain structures. It also aims to assess the variability of these values and provide a baseline for further pathological studies. Materials and Methods: Seventy healthy volunteers (28 females, 42 males, mean age 28 years) were included. MRI scans were performed using a 3.0 Tesla MRI scanner. Conventional cranial MRI sequences were acquired, followed by Magnetization Transfer Imaging (MTI) with off-resonance pulses. MTR maps were generated from proton density-weighted images obtained with and without magnetization transfer pre-pulses. Measurements were performed in 31 white matter and 9 grey matter regions, with additional assessments of CSF for noise control. Statistical analysis was carried out to compare MTR values across different brain regions. Results: The mean MTR value was significantly higher in white matter (23.9 ± 0.21) compared to grey matter (17.3 ± 0.77). The corpus callosum had the highest MTR values within the white matter, particularly in the splenium, while the thalamus exhibited the highest MTR values in the grey matter. Regional variations were observed, with higher MTR values in the occipital and temporal lobes and lower values in the frontal and parietal lobes. MTR measurements showed excellent intra-observer (ICC > 0.9) and good inter-observer reliability (ICC 0.80–0.90). Conclusions: This study provides detailed MTR mapping of normal brain tissue, highlighting significant regional dif-ferences between white and grey matter. The findings offer valuable baseline data for assessing structural changes in CNS diseases and for evaluating the efficacy of therapeutic interventions. MTR measurements demonstrate high reproducibility, making this technique a reliable tool in clinical and research applications for monitoring pathological alterations in the central nervous system.

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.

Magnetization transfer and T2 quantitation in normal appearing cortical gray matter and white matter adjacent to focal abnormality in patients with traumatic brain injury.

Magnetization transfer and diffusion tensor MR imaging of the optic radiations and calcarine cortex from patients with Leber's hereditary optic neuropathy

PurposeTo evaluate quantitative T1 and T2 relaxation times and magnetization transfer ratios (MTRs) in the early diagnosis of patellar cartilage osteoarthritis (OA) and to quantify and possibly refine the current Kellgren-Lawrence score criteria.Materials and methodsA total of 92 cases of knee joints with 40 normal volunteers and 30 patients with OA were prospectively evaluated. The knee joints with OA were divided into mild and moderate groups according to the Kellgren-Lawrence score criteria. The discriminative analysis method was used to analyze the accuracy of the original grouped cases correctly classified by age, sex, T1 relaxation times, T2 relaxation times, and MTR values. Linear regression analysis was used between T1 relaxation time, T2 relaxation time, and MTR values.ResultsThe mean T1 relaxation times decreased with the severity of OA, and a significant difference was only found between the normal and moderate OA groups (P<0.05). The mean T2 relaxation times increased, and significant differences were found between the normal and mild OA groups and the normal and moderate OA groups (P<0.001). The MTR values were 35.8%±4.2%, 36.1%±3.2%, and 35.4%±3.8%, respectively. There were no significant differences between the normal and OA groups. In addition, T1 relaxation times were positively correlated with MTR values (P<0.01). A discriminative analysis using a synthesis of all the influential factors indicated a high accuracy rate (93.9%) for the correct classification of the original grouped cases.ConclusionQuantitative T1 and T2 relaxation times were useful in the diagnosis of early OA; T2 relaxation times were more relatively sensitive. The functional usefulness of MTR values may be limited. T1 relaxation times positively correlated with MTR values. Multiple quantitative parameters, combined with some relative nonquantitative clinical parameters and Kellgren-Lawrence scores, may be useful in the early stage of OA and provide better information for clinical treatment and follow-up.

Background: Multiple sclerosis (MS) has traditionally been regarded as a disease confined to the central nervous system (CNS). However, neuropathological, electrophysiological and imaging studies have demonstrated that the peripheral nervous system (PNS) is also involved, with demyelination and, to a lesser extent, axonal degeneration representing the main pathophysiological mechanisms. Aim: The purpose of this study was to assess PNS damage at proximal (lumbar plexus) and distal (sciatic nerve) anatomical locations in people with relapsing-remitting MS (RRMS) and healthy controls (HCs) in vivo using magnetisation transfer ratio (MTR), which is a known imaging biomarker sensitive to alterations in myelin content in neural tissue, and not previously explored in the context of PNS damage in MS. Method: Eleven HCs and 15 people with RRMS were recruited for this study and underwent magnetic resonance imaging (MRI) investigations together with clinical assessments using the expanded disability status scale (EDSS). Magnetic resonance neurography (MRN) was first used for visualisation and identification of the lumbar plexus and the sciatic nerve and MTR imaging was subsequently performed using identical scan geometry to MRN, enabling straightforward co-registration of all data to obtain global and regional mean MTR measurements. Linear regression models were used to identify differences in MTR values between HCs and people with RRMS and to identify an association between MTR measures and EDSS. Results: Significant changes in MTR values in the sciatic nerve of people with RRMS as compared to HCs were demonstrated, but no MTR changes were identified in the lumbar plexus of people with RRMS. Additionally, no relationship between the MTR measures in the PNS and EDSS were identified at any of the anatomical locations studied in this cohort of people with RRMS. Conclusion: The results from this study confirm the presence of PNS damage in people with RRMS and support the notion that these changes, suggestive of demyelination, maybe occurring independently at different anatomical locations within the PNS, thus providing new insight into the pathophysiology of the disease.

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

The purpose of this work was to determine the extent of disease and disease severity in the conventional MR normal-appearing gray matter (NAGM) and white matter (NAWM) in patients with relapsing-remitting (RR) and secondary progressive (SP) multiple sclerosis (MS) utilizing quantitative magnetization transfer ratio (MTR) histogram analysis. Twenty-seven patients with MS (16 RR, 11 SP) and 16 healthy control subjects were studied. MTR was calculated in the totally segmented GM and WM without T2 lesions in each group. Each of the RR and SP MS patient groups had significantly smaller MTR histogram mean values in NAGM and NAWM than the healthy subjects (p </= 0.0015). SP MS patients had a significantly lower first quartile and MTR histogram peak height for NAGM only (p </= 0.004) when compared with both RR MS patients and healthy subjects. The T2 lesion load had a modest negative correlation with MTR values in both RR and SP MS, but only in NAGM. Separate analysis of GM and WM MTR histograms may allow better detection of subtle damage and better understanding of the natural history of MS disease and ultimately the response to therapeutics.

ABSTRACTPurposeTo determine whether magnetization transfer imaging (MTI) is able to detect microstructure alterations in the cervical spinal cord (CSC) in relapsing‐remitting multiple sclerosis (RRMS) patients and whether they correlate with clinical disability.Methods and MaterialsFifteen RRMS patients (5 males, 10 females, mean ± standard deviation (SD) age: 47.0 ± 12.9 years, age range: 18–70 years; median Expanded Disability Status Scale (EDSS) score = 2; (range: 0.5–6.5) and 20 healthy controls (10 male, 10 females, mean ± sd age: 40.7 ± 12.4 years) underwent 3T MRI scans using standard MTI sequences. Spinal Cord Toolbox (SCT) was used for image post‐processing. Data were first segmented and then registered to a template and then the magnetization transfer ratio (MTR) was computed over the volume between the 2nd and 5th cervical vertebrae for the total white matter (WM) and for specific WM regions: dorsal column (DC), ventral column (VC), and lateral column (LC). Independent sample t‐tests were used to conduct a comparative analysis of means between the healthy and RRMS groups. The association between MTR measures over different ROIs and EDSS was investigated by the univariate association using Pearson correlation coefficient (r) and a simple linear regression analysis.ResultsMTR values were significantly decreased in all ROIs (p &lt; 0.01) in RRMS versus Healthy participants. There was no significant correlation between MTR and EDSS in all ROIs.ConclusionThis study demonstrates that clinical trials using MTI techniques are feasible and show that quantitative MTI can monitor tissue changes in degenerative WM patients.

Objective: To determine the effects of intravenous natalizumab and intramuscular interferon beta-1a (IFNβ-1a) on the volume of white-matter (WM) lesions and normal appearing brain tissue (NABT) undergoing voxel-wise (VW) increases in magnetization transfer ratio (MTR) suggestive of remyelination in patients with relapsing multiple sclerosis. Methods: This prospective, open-label, single-blinded study enrolled patients with relapsing–remitting multiple sclerosis (RRMS) and relapsing secondary progressive multiple sclerosis (RSPMS) as well as a group of age/sex-matched healthy controls (n=22). Patients with multiple sclerosis were assigned to receive natalizumab monotherapy (n=77; RRMS/RSPMS) or intramuscular IFNβ-1a (n=26) as either monotherapy (RRMS) or combined with pulsed i.v. methylprednisolone, as needed (RSPMS). The primary endpoint was the two-year change in volume of NABT VWMTR, by quantifying the number of voxels that increased (suggesting remyelination) or decreased (suggesting demyelination) in their MTR value. Results: The volume of tissue undergoing increases in VWMTR was significantly larger in natalizumab compared with IFNβ-1a-treated patients (year 1: p=0.001 in NABT and p<0.006 in WM lesions; year 2: p=0.008 in NABT) and compared with healthy control subjects (year 1: p=0.05 and year 2: p=0.007 in NABT). The larger volume within NABT undergoing decreases in VWMTR was detected in multiple sclerosis patients compared with healthy controls (p<0.001), and in the IFNβ-1a group compared with the natalizumab group (year 1: p=0.05; year 2: p=0.002). One patient on natalizumab died from progressive multifocal leukoencephalopathy eight months after completing the study. Conclusion: Natalizumab may promote remyelination and stabilize demyelination in lesions and NABT in relapsing multiple sclerosis, compared with intramuscular IFNβ-1a.

This study was performed to assess how established diagnostic criteria for brain magnetic resonance imaging (MRI) interpretation in cases of suspected multiple sclerosis (MS) (Barkhofs criteria) would perform in the distinction of MS from other diseases and whether other MR techniques (cervical cord imaging and brain magnetization transfer imaging [MTI]), might help in the diagnostic work-up of these patients. We retrospectively identified 64 MS and 59 non-MS patients. The latter group included patients with systemic immune-mediated disorders (SID; n=44) and migraine (n=15). All patients had undergone MRI scans of the brain (dual echo and MTI) and of the cervical cord (fast short-tau inversion recovery). The number and location of brain T2-hyperintense lesions and the number and size of cervical cord lesions were assessed. Brain images were also postprocessed to quantify the total lesion volumes (TLV) and to create histograms of magnetization transfer ratio (MTR) values from the whole of the brain tissue. Barkhofs criteria correctly classified 108/123 patients, thus showing an accuracy of 87.8%. "False negative" MS patients were 13, while 2 patients with systemic lupus erythematosus (SLE) were considered as "false positives". Using brain T2 TLV, nine of the"false negative" patients were correctly classified. Correct classification of 10 MS patients and both the SLE patients was possible based upon the presence or absence of one cervical cord lesion. Two MS patients with negative Barkhofs criteria and no cervical cord lesions were correctly classified based on their brain MTR values. Overall, only one MS patient could not be correctly classified by any of the assessed MR quantities. These preliminary data support a more extensive use of cervical cord MRI and brain MTI to differentiate between MS and other disorders in case of inconclusive findings on T2-weighted MRI scans of the brain. Multiple Sclerosis (2002) 8, 52-58

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.

Human prion diseases are fatal neurodegenerative disorders caused by misfolding of the prion protein. There are no useful biomarkers of disease progression. Cerebral cortex spongiform change, one of the classical pathological features of prion disease, resolves in prion-infected transgenic mice following prion protein gene knockout. We investigated the cross-sectional, longitudinal and post-mortem cerebral magnetization transfer ratios as a surrogate for prion disease pathology. Twenty-three prion disease patients with various prion protein gene mutations and 16 controls underwent magnetization transfer ratio and conventional magnetic resonance imaging at 1.5 T. For each subject, whole-brain, white and grey matter magnetization transfer ratio histogram mean, peak height, peak location, and magnetization transfer ratio at 25th, 50th and 75th percentile were computed and correlated with several cognitive, functional and neuropsychological scales. Highly significant associations were found between whole brain magnetization transfer ratio and prion disease (P < 0.01). Additionally, highly significant correlations were found between magnetization transfer ratio histogram parameters and clinical, functional and neuropsychological scores (P < 0.01). Longitudinally, decline in the Clinician's Dementia Rating scale was correlated with decline in magnetization transfer ratio. To investigate the histological correlates of magnetization transfer ratio, formalin-fixed cerebral and cerebellar hemispheres from 19 patients and six controls underwent magnetization transfer ratio imaging at 1.5 T, with mean magnetization transfer ratio calculated from six regions of interest, and findings were followed-up in six variant Creutzfeldt-Jakob disease cases with 9.4 T high-resolution magnetization transfer imaging on frontal cortex blocks, with semi-quantitative histopathological scoring of spongiosis, astrocytosis and prion protein deposition. Post-mortem magnetization transfer ratios was significantly lower in patients than controls in multiple cortical and subcortical regions, but not frontal white matter. Measurements (9.4 T) revealed a significant and specific negative correlation between cortical magnetization transfer ratios and spongiosis (P = 0.02), but not prion protein deposition or gliosis. The magnetic resonance imaging measurement of magnetization transfer ratios may be an in vivo surrogate for spongiform change and has potential utility as a therapeutic biomarker in human prion disease.

Magnetization transfer imaging of bone marrow with and without fat suppression.

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.