Magnetization Transfer Ratio Changes Research Articles

Tract-specific magnetization transfer ratio provides insights into the severity of degenerative cervical myelopathy.

Cross-sectional study. This study's goal is to report whether Magnetization Transfer Ratio (MTR) can evaluate the severity of white matter (WM) injury in degenerative cervical myelopathy (DCM). Laureate Institute of Brain Research, USA; Department of Neurosurgery, University of Oklahoma Health Sciences Center, USA. 27 DCM patients were aged-matched with 20 healthy controls (HC) and categorized into treatment groups based on modified Japanese Orthopedic Association (mJOA) severity (11 mild and 16 moderate/severe). Regional and tract MTRs were extracted from the two vertebral levels containing maximum compression within magnetization transfer images. MTR differences between groups were assessed using a one-way ANOVA or Kruskal-Wallis test. The association between MTR and mJOA measures was evaluated using Spearman's correlation. Significant decreases in MTR were found between HC and moderate/severe groups in the overall (p = 0.0065) and ventral (p = 0.0009) WM regions; and ventral corticospinal (p = 0.0101), ventral reticulospinal (p = 0.0084), spinal lemniscus (p = 0.0079), and fasciculus cuneatus (p = 0.0219) tracts. The spinal lemniscus MTR also significantly decreased between HC and mild groups (p = 0.038). Ventral reticulospinal tract MTR correlated with upper (r = 0.439; p = 0.022) and lower (r = 0.386; p = 0.047) limb motor mJOA scores. Significant tract-based MTR changes and correlations align with known DCM symptoms, are demonstrated to be lost at the regional level, and display the inhomogeneous compressive damage occurring within DCM spinal cords.

QOL-23. POTENTIAL MYELIN REPAIR AFTER IRRADIATED PEDIATRIC BRAIN TUMOR: A MAGNETIZATION TRANSFER IMAGING ANALYSIS

Abstract BACKGROUND Exercise training and metformin treatment may improve cognition after cranial irradiation in pediatric brain tumors (PBT), but the neuronal mechanisms underlying the effect of these interventions remains unknown. Magnetization transfer imaging (MTI) is an imaging technique that may be sensitive to white matter microstructure – including myelin. METHODS In this work, we analyzed changes in magnetization transfer ratio (MTR) over a 12-week period in irradiated PBT survivors who participated in pilot clinical trials entailing 12 weeks of exercise training (exercise group, n=17), or metformin treatment (n=12). Pre- and post-intervention assessment included MRI scanning and neurocognitive tests. A no intervention control group, (n=7) was also included and seen before and after a 12 week period of time. We used a longitudinal Tract-Based Spatial Statistics (TBSS) approach to analyze differences in MTR across the 12 weeks in the three groups, using as covariates: age at baseline, sex, handedness, age at diagnosis and delay from diagnosis. Then we performed correlations between mean MTR changes and behavioral outcomes. RESULTS Clusters of significant increase in MTR were observed in the right temporal lobe in the exercise group after intervention and in the right minor forceps in the metformin group after treatment. These changes respectively correlated with higher performance in free recall score in exercise group and with higher performances in inhibitory control and attention in metformin group. There was no difference in MTR changes between groups nor within the control group. DISCUSSION This exploratory work suggests either a 12-week period of exercise training or metformin may promote myelination in PBT survivors in brain regions. These changes appear to be associated with improved memory and executive function, two core domains of neurocognitive deficit in this population.

Quantitative Analysis of Early White Matter Damage in Cuprizone Mouse Model of Demyelination Using 7.0 T MRI Multiparametric Approach.

Magnetic Resonance Imaging (MRI) is commonly used to follow the progression of neurodegenerative conditions, including multiple sclerosis (MS). MRI is limited by a lack of correlation between imaging results and clinical presentations, referred to as the clinico-radiological paradox. Animal models are commonly used to mimic the progression of human neurodegeneration and as a tool to help resolve the paradox. Most studies focus on later stages of white matter (WM) damage whereas few focus on early stages when oligodendrocyte apoptosis has just begun. The current project focused on these time points, namely weeks 2 and 3 of cuprizone (CPZ) administration, a toxin which induces pathophysiology similar to MS. In vivo T2-weighted (T2W) and Magnetization Transfer Ratio (MTR) maps and ex vivo Diffusion Tensor Imaging (DTI), Magnetization Transfer Imaging (MTI), and relaxometry (T1 and T2) values were obtained at 7 T. Significant changes in T2W signal intensity and non-significant changes in MTR were observed to correspond to early WM damage, whereas significant changes in both corresponded with full demyelination. Some DTI metrics decrease with simultaneous increase in others, indicating acute demyelination. MTI metrics T2A, T2B, f and R were observed to have contradictory changes across CPZ administration. T1 relaxation times were observed to have stronger correlations to disease states during later stages of CPZ treatment, whereas T2 had weak correlations to early WM damage. These results all suggest the need for multiple metrics and further studies at early and late time points of demyelination. Further research is required to continue investigating the interplay between various MR metrics during all weeks of CPZ administration.

Longitudinal analysis of new multiple sclerosis lesions with magnetization transfer and diffusion tensor imaging

ObjectiveThe potential of magnetization transfer imaging (MTI) and diffusion tensor imaging (DTI) for the detection and evolution of new multiple sclerosis (MS) lesions was analyzed.MethodsNineteen patients with MS obtained conventional MRI, MTI, and DTI examinations bimonthly for 12 months and again after 24 months at 1.5 T MRI. MTI was acquired with balanced steady-state free precession (bSSFP) in 10 min (1.3 mm3 isotropic resolution) yielding both magnetization transfer ratio (MTR) and quantitative magnetization transfer (qMT) parameters (pool size ratio (F), exchange rate (kf), and relaxation times (T1/T2)). DTI provided fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD).ResultsAt the time of their appearance on MRI, the 21 newly detected MS lesions showed significantly reduced MTR/F/kf and prolonged T1/T2 parameters, as well as significantly reduced FA and increased AD/MD/RD. Significant differences were already observed for MTR 4 months and for qMT parameters 2 months prior to lesions’ detection on MRI. DTI did not show any significant pre-lesional differences. Slightly reversed trends were observed for most lesions up to 8 months after their detection for qMT and less pronounced for MTR and three diffusion parameters, while appearing unchanged on MRI.ConclusionsMTI provides more information than DTI in MS lesions and detects tissue changes 2 to 4 months prior to their appearance on MRI. After lesions’ detection, qMT parameter changes promise to be more sensitive than MTR for the lesions’ evolutional assessment. Overall, bSSFP-based MTI adumbrates to be more sensitive than MRI and DTI for the early detection and follow-up assessment of MS lesions.Clinical relevance statementWhen additionally acquired in routine MRI, fast bSSFP-based MTI can complement the MRI/DTI longitudinal lesion assessment by detecting MS lesions 2–4 months earlier than with MRI, which could implicate earlier clinical decisions and better follow-up/treatment assessment in MS patients.Key Points• Magnetization transfer imaging provides more information than DTI in multiple sclerosis lesions and can detect tissue changes 2 to 4 months prior to their appearance on MRI.• After lesions’ detection, quantitative magnetization transfer changes are more pronounced than magnetization transfer ratio changes and therefore promise to be more sensitive for the lesions’ evolutional assessment.• Balanced steady-state free precession–based magnetization transfer imaging is more sensitive than MRI and DTI for the early detection and follow-up assessment of multiple sclerosis lesions.

Quantitative MRI Identifies Heterogeneous Bone Marrow Treatment Responses in a Mouse Model of Myelofibrosis

Myeloproliferative neoplasms (MPNs), a class of blood cancers, typically arise from mutations in the thrombopoietin receptor (MPL), JAK2, or calreticulin that constitutively activate JAK/STAT signaling in hematopoietic stem and progenitor cells. Myelofibrosis (MF), the most aggressive of the MPNs, can arise as a primary neoplasm or secondary to other MPNs. MF is characterized by progressive fibrosis of bone marrow (BM), destruction of the hematopoietic niche, and eventual BM failure. Recently, the focus of treatment in MF has shifted toward restoration of healthy BM architecture and a functional hematopoietic niche rather than focusing solely on alleviating symptoms. Accomplishing this paradigm shift in drug development and therapy requires new approaches to monitor spatial and temporal changes in BM in patients during treatment. We present a quantitative magnetic resonance imaging (MRI) approach to analyze key pathologic changes in BM in a mouse model of MPN driven by MPLW515L. To evaluate disease extent, progression, and response to therapy in mice, we use anatomical MRI for spleen volume and three quantitative MRI metrics for BM: 1) apparent diffusion coefficient (ADC), 2) proton density fat fraction (PDFF), and 3) magnetization transfer ratio (MTR). PDFF and ADC assess the fat content and water movement of the BM and are useful in identifying cellularity changes such as hypercellularity in MPNs and MF. MTR probes changes in macromolecular structure, such as those observed with increasing fibrosis in MF. We used quantitative MRI to measure response to treatment in BM and change in spleen volume in response to three drugs: ruxolitinib (JAK1/2 inhibitor), fedratinib (JAK2 inhibitor), and navitoclax (BCL-2/BCL-xL inhibitor). Within 10 days after starting treatment, diseased spleen volumes in the ruxolitinib group (~3.5x healthy volume) had the greatest average reduction in spleen volume measured by MRI (-73.5% ± 11.4%) followed by the fedratinib group (-52.7% ± 16.7%). Interestingly, the spleens of every ruxolitinib-treated mouse displayed consistent and prolonged spleen volume reductions, while only a subset of mice in the other treatment groups (~70% fedratinib mice; ~33% navitoclax mice) demonstrated reductions in spleen volume. Despite the robust spleen response in ruxolitinib-treated mice, only some of the mice (~60%) exhibited sustained changes in BM ADC, MTR, and PDFF signals expected with reversion to healthy BM (decreased ADC, decreased MTR, and increased PDFF). In mice treated with fedratinib or navitoclax, even fewer mice (~40% and ~33% respectively) showed reversion toward healthy BM. Importantly, we observed spatial heterogeneity of BM response within the tibia of single mice, where proximal and distal tibia regions often responded disparately (~49% of cases). Because improving BM cellularity and fibrosis is increasingly the target of therapy in MPNs and in MF specifically, there is a distinct need for better techniques for longitudinally evaluating variations in treatment efficacy in living subjects. In this study, we demonstrate that the combination of three quantitative MRI metrics (ADC, PDFF, and MTR) can detect the impact of therapy on the BM in a preclinical mouse model of MPN/MF. Interestingly, we identified pronounced heterogeneity at multiple levels during treatment: 1) differences in changes in spleen volume versus BM; 2) disparate treatment responses of mice within a treatment group; and 3) contrasting regional treatment responses of the BM within a single mouse. Because these quantitative MRI metrics are directly translatable to clinical medicine and can identify variations in treatment efficacy in BM, both between and within subjects, this study sets the stage for future drug development and analysis of therapeutic interventions on the BM of patients with MF.

Magnetization transfer imaging of ovarian cancer: initial experiences of correlation with tissue cellularity and changes following neoadjuvant chemotherapy.

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.

Deep gray matter changes in relapsing-remitting multiple sclerosis detected by multi-parametric, high-resolution magnetic resonance imaging (MRI).

To investigate a variety of magnetic resonance imaging (MRI) quantitative metrics, which reflect different aspects of microstructural damage in deep gray matter (dGM) regions and white matter T2 lesions in patients with relapsing-remitting multiple sclerosis (RRMS), and to determine the level of pathological interconnection between these two entities as well as their association with clinical disability. We recruited thirty RRMS patients along with thirty age-matched healthy controls (HCs). Both groups were scanned at 3 T MRI using 3D high-resolution T1-, T2-, and T2*-weighted, magnetization transfer (MT)-prepared gradient echo for MT ratio (MTR) mapping, and eight repeats of T1-weighted images acquired at different inversion times to create T1 maps. dGM structures were segmented from T1-weighted images using FreeSurfer, WM-T2 lesions were extracted from T2-weighted images, and iron maps were calculated from the phase part of the T2*-weighted sequence. Extracted dGM MRI indices were compared between both groups. In the RRMS group, dGM MRI indices were correlated with those of WM-T2 lesions, expanded disability status scale, and disease duration. dGM volumetric metrics of RRMS patients were significantly (p < 0.01) smaller than those of HCs and showed a significant moderate association with lesions' load (p < 0.05) and lesions' iron concentration (p < 0.01). dGM MTRs of RRMS patients were significantly (p < 0.01) smaller than those of HCs and showed a significant (p < 0.01) moderate correlation with lesion T1 times. While T1 changes in some dGM regions of RRMS patients associated weakly with those of T2 lesions, dGM iron concentration did not show any association with any of lesions' metrics. Furthermore, lesions' MTR changes did not show any association with any dGM metrics. Most dGM metrics did not show any correlation with disease severity. Contrarily, most lesions' metrics showed weak association with disease severity. dGM changes occur in a non-uniform pattern and, almost, do not link directly to MS disease severity. Contrarily, most WM-T2 lesions' metrics tend to correlate with MS disease severity better than those of dGM. • Deep gray matter (dGM) structures are very much involved in the MS disease process and quite substantial neurodegeneration is undergone during the relapsing-remitting phase of the MS disease. • Deep gray matter (dGM) quantitative changes occur in a non-uniform and non-linked pattern and, except for CN's iron deposition, do not directly associate with the MS disease severity. • Most white matter T2 lesions' metrics tend to correlate with MS disease severity better than those of dGM structures.

White Matter Alterations in Fmr1 Knockout Mice during Early Postnatal Brain Development

Fragile X syndrome (FXS) is the most commonly inherited form of intellectual disability ascribed to the autism spectrum disorder. Studies with FXS patients have reported altered white matter volume compared to controls. The Fmr1 knockout (KO) mouse, a model for FXS, showed evidence of delayed myelination during postnatal brain development. In this study, we examined several white matter regions in the male Fmr1 KO mouse brain compared to male wild-type (WT) mice at postnatal days (PND) 18, 21, 30, and 60, which coincide with critical stages of myelination and postnatal brain development. White matter volume, T₂ relaxation time, and magnetization transfer ratio (MTR) were measured using magnetic resonance imaging and myelin content was determined with histological staining of myelin. Differences in the developmental accumulation of white matter and myelin between Fmr1 KO and WT mice were observed in the corpus callosum, external and internal capsules, cerebral peduncle, and fimbria. Alterations were more predominant in the external and internal capsules and fimbria of Fmr1 KO mice, where the MTR was lower at PND 18, then elevated at PND 30, and again lower at PND 60 compared to the corresponding regions in WT mice. The pattern of changes in MTR were similar to those observed in myelin staining and could be related to the altered protein synthesis that is a hallmark of FXS. While no significant changes in white matter volumes and T₂ relaxation time between the Fmr1 KO and WT mice were observed, the altered pattern of myelin staining and MTR, particularly in the external capsule, reflecting the abnormalities associated with myelin content is suggestive of a developmental delay in the white matter of Fmr1 KO mouse brain. These early differences in white matter during critical developmental stages may contribute to altered brain networks in the Fmr1 KO mice.

Increasing body mass index in an elderly cohort: Effects on the quantitative MR parameters of the brain.

Body mass index (BMI) is increasing in a large number of elderly persons. This increase in BMI is known to put one at risk for many "diseases of aging," although less is known about how a change in BMI may affect the brains of the elderly. To investigate the relationship between BMI and quantitative water content, T1 , T2 *, and the semi-quantitative magnetization transfer ratio (MTR) of various structures in elderly brains. Cross-sectional. Forty-two adults (BMI range: 19.1-33.5 kg/m2 , age range: 58-80 years). 3T MRI (two multi-echo gradient echoes, actual flip angle imaging, magnetization prepared rapid gradient echo, fluid attenuated inversion recovery). The 3D two-point method was used to derive (semi-)quantitative parameters in global white (WM) and gray matter (GM) and their regions as defined by the Johns Hopkins University and the Montreal Neurological Institute atlases. Multivariate linear regression with BMI as principal regressor, corrected for the additional regressors age, gender, and glycated hemoglobin. Spearman correlation between quantitative parameters of the regions showing significant changes and the lipid spectra / C-reactive protein (CRP). Voxel-based morphometry and analysis of covariance (ANCOVA) to explore changes in the GM volume. T1 increased significantly (P < 0.05) in the frontal, temporal, and parietal cortices, while the bilateral corona radiata, right superior longitudinal fasciculus, as well as the corpus callosum showed significant changes in the WM regions. T2 * increased significantly in the global WM and left corona radiata. Changes in MTR and the free water content did not reach significance. No significant correlation between any quantitative parameter and the lipid spectra or CRP could be identified. These results suggest that an elevated BMI predominantly affects T1 in WM as well as GM structures in the elderly human brain. 3 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2020;51:514-523.

Higher EBV response is associated with more severe gray matter and lesion pathology in relapsing multiple sclerosis patients: A case-controlled magnetization transfer ratio study

Background: Epstein–Barr virus (EBV) infection has been associated with higher clinical activity and risk of multiple sclerosis (MS). Objective: To evaluate associations between EBV-specific humoral response and magnetization transfer ratio (MTR)-derived measure in MS patients and healthy controls (HCs). Methods: The study included 101 MS patients (69 relapsing-remitting multiple sclerosis (RRMS) and 32 secondary-progressive multiple sclerosis (SPMS)) and 41 HCs who underwent clinical, serological, and magnetic resonance imaging (MRI) investigations. MTR values of T1 or T2 lesion volume (LV), normal-appearing (NA) brain tissue (NABT), gray matter (NAGM), and white matter (NAWM) were obtained. Enzyme-linked immunosorbent assay was used to quantify EBV antibody levels. Partial correlations corrected for MRI strength were used, and Benjamini–Hochberg–adjusted p-values < 0.05 were considered significant. Results: MS patients had significantly higher anti-EBV nuclear antigen-1 (EBNA-1) titer when compared to HCs (107.9 U/mL vs 27.8 U/mL, p < 0.001). Within the MS group, higher serum anti-EBNA-1 titer was significantly correlated with lower T1-LV MTR (r = –0.287, p = 0.035). Within the RRMS group, higher serum anti-EBNA-1 titer was associated with T1-LV MTR (r = –0.524, p = 0.001) and NAGM MTR (r = –0.308, p = 0.043). These associations were not present in HCs or SPMS patients. Conclusion: Greater EBV humoral response is associated with lower GM MTR changes and focal destructive lesion pathology in RRMS patients.

Stabilization of T2 relaxation and magnetization transfer in cartilage explants by immersion in perfluorocarbon liquid.

Magnetic resonance imaging of ex vivo cartilage measures parameters such as T2 and magnetization transfer ratio (MTR), which reflect structural changes associated with osteoarthritis. Samples are often immersed in aqueous solutions to prevent dehydration and to to improve susceptibility matching. This study sought to determine the extent to which T2 and MTR changes are attributable to immersion alone and to identify immersion conditions to minimize this confounding factor. T2 and MTR were measured before and after immersion for up to 24 hours at 4°C. Bovine nasal and articular cartilage and human articular cartilage were studied. Experimental groups included undisturbed immersion in Fluorinert FC-770, a susceptibility-matched, hydrophobic liquid with minimal tissue penetration, and immersion in Fluorinert, Dulbecco's phosphate-buffered saline (DPBS), or saline, with removal from the magnet between scans. 19 F and 1 H-MRI were used to detect cartilage penetration by Fluorinert and swelling, respectively. Saline and DPBS immersion rapidly increased T2 , wet weight and cartilage volume and decreased MTR, suggesting increased water content for all cartilage types. Fluorinert-immersed samples exhibited minimal changes in T2 or MTR. No ingress of Fluorinert was detected after 2 weeks of continuous immersion at 4°C. Ex vivo quantitative MR studies of cartilage may be confounded by the effects of immersion in aqueous solution, which may be comparable to or larger than effects attributed to pathology. These effects may be mitigated by immersion in perfluorocarbon liquids such as Fluorinert FC-770.

T167. ABERRANT MYELINATION OF THE CINGULUM BUNDLE IN PATIENTS WITH SCHIZOPHRENIA: A 7T MTI/DTI STUDY

BackgroundThe structural integrity of the anterior cingulum has been repeatedly observed to be abnormal in patients with schizophrenia. Reduced glutathione levels, indicating oxidative stress, is associated with reduced structural integrity of cingulum bundle in patients with schizophrenia. Variations in neuregulin-1, a well-established candidate marker for schizophrenia, results in oligodendrocyte dysfunction and defective myelination, and is shown to affect the structural integrity of the anterior cingulum in patients with schizophrenia. While the evidence to date has been obtained using diffusion tensor imaging, abnormal tract-specific changes in myelin content can be more directly inferred by combining multiple modalities of WM imaging such as diffusion tensor (DTI) and magnetization transfer imaging (MTI) in parallel.MethodsWe used ultra-high resolution (7 Tesla) MTI in 17 patients with schizophrenia and 20 controls, to evaluate the macromolecular (predominantly myelin) content of the brain. Immediately after the 7T scanning, we also obtained a 3T diffusion tensor image (DTI) and undertook probabilistic tractography using FSL software (AutoPtx, ProbTrackX) to delineate anterior cingulum bilaterally. Unpaired t tests were used for group comparisons along with estimates of Cohen’s d or Hedge’s g for effect sizes.ResultsPatients had a significant reduction in magnetization transfer ratio (MTR) in right (Cohen’s d=0.91, p=0.007) but not left (d=0.03, p=0.92) cingulum bundle. There was also a trend level reduction in fractional anisotropy of right (d=0.60, p=0.07) but not left (d=0.47, p=0.17) cingulum bundle. We did not find any significant relationship between the 3 major symptom dimensions of schizophrenia (Reality Distortion, Disorganization, Psychomotor Poverty) and Cingulum MTR. Patients with Schneiderian delusions (n=5) showed a significantly reduced MTR of left cingulum compared to patients (n=12) with no Schneiderian delusions (Hedges’ g=1.36, p=0.02).DiscussionOur findings suggest that MTR changes in anterior cingulum, resulting from either dysmyelination or neuroinflammation, is present in clinically stable patients with schizophrenia despite their medicated status. We lacked sufficient power to detect association between MTR changes of cingulum and symptom dimensions. Nevertheless, our results suggest that MTR changes are of higher magnitude than changes in fractional anisotropy, indicating the sensitivity of measuring myelination as a biological marker of white matter aberrations in schizophrenia.

Long-Term Magnetization Transfer Ratio Evolution in Multiple Sclerosis White Matter Lesions.

Magnetization transfer ratio (MTR), a magnetic resonance imaging technique used to assess tissue integrity, correlates with demyelination and axonal loss in multiple sclerosis (MS) lesions. In acute white matter lesions, short-term MTR changes mainly reflect demyelination and remyelination, in addition to edema and axonal and glial changes. Long-term MTR changes in MS lesions have not been studied extensively. A new quantitative image analysis method was developed to measure long-term MTR changes in MS lesions. The method was applied to a group of 59 patients and 14 healthy control subjects followed for 4 years. MTR changes in white matter lesions were analyzed, where lesion voxels were classified into six categories based on starting MTR and change over time. For each patient, the proportion of lesion voxels in each MTR-change category was calculated. Correlations between long-term MTR evolution, disability progression, and brain atrophy were investigated. The proportion of lesion voxels in the high stable category correlated with less atrophy progression, while the proportion with low and increasing MTR correlated with increased atrophy. The proportion of lesion voxels in the high and stable MTR lesion category was significantly different between MS disease subgroups. The group with disability progression had a higher proportion of lesion voxels with low and increasing MTR. These results suggest that long-term changes in MTR in white matter lesions can be used to distinguish lesion subtypes associated with MS disease progression and improve understanding of the temporal evolution of MS pathology.

Peginterferon beta-1a improves MRI measures and increases the proportion of patients with no evidence of disease activity in relapsing-remitting multiple sclerosis: 2-year results from the ADVANCE randomized controlled trial

BackgroundSubcutaneous peginterferon beta-1a has previously been shown to reduce the number of T2-hyperintense and gadolinium-enhancing (Gd+) lesions over 2 years in patients with relapsing-remitting multiple sclerosis (RRMS), and to reduce T1-hypointense lesion formation and the proportion of patients showing evidence of disease activity, based on both clinical and radiological measures, compared with placebo over 1 year of treatment. The objectives of the current analyses were to evaluate T1 lesions and other magnetic resonance imaging (MRI) measures, including whole brain volume and magnetization transfer ratio (MTR) of normal appearing brain tissue (NABT), and the proportions of patients with no evidence of disease activity (NEDA), over 2 years.MethodsPatients enrolled in the ADVANCE study received continuous peginterferon beta-1a every 2 or 4 weeks for 2 years, or delayed treatment (placebo in Year 1; peginterferon beta-1a every 2 or 4 weeks in Year 2). MRI scans were performed at baseline and Weeks 24, 48, and 96. Proportions of patients with NEDA were calculated based on radiological criteria (absence of Gd + and new/newly-enlarging T2 lesions) and clinical criteria (no relapse or confirmed disability progression) separately and overall.ResultsPeginterferon beta-1a every 2 weeks significantly reduced the number and volume of T1-hypointense lesions compared with delayed treatment over 2 years. Changes in whole brain volume and MTR of NABT were suggestive of pseudoatrophy during the first 6 months of peginterferon beta-1a treatment, which subsequently began to resolve. Significantly more patients in the peginterferon beta-1a every 2 weeks group compared with the delayed treatment group met MRI-NEDA criteria (41% vs 21%; odds ratio [OR] 2.56; p < 0.0001), clinical-NEDA criteria (71% vs 57%; OR 1.90; p < 0.0001) and achieved overall-NEDA (37% vs 16%; OR 3.09; p < 0.0001).ConclusionPeginterferon beta-1a provides significant improvements in MRI measures and offers patients a good chance of remaining free from evidence of MRI, clinical and overall disease activity over a sustained 2-year period.Trial registrationClinicalTrials.gov: NCT00906399; Registered on: May 20, 2009.

Lower Magnetization Transfer Ratio in the Forceps Minor Is Associated with Poorer Gait Velocity in Older Adults.

Gait disturbances in the elderly are disabling and a major public health issue but are poorly understood. In this multimodal MR imaging study, we used 2 voxel-based analysis methods to assess the voxelwise relationship of magnetization transfer ratio and white matter hyperintensity location with gait velocity in older adults. We assessed 230 community-dwelling participants of the Austrian Stroke Prevention Family Study. Every participant underwent 3T MR imaging, including magnetization transfer imaging. Voxel-based magnetization transfer ratio-symptom mapping correlated the white matter magnetization transfer ratio of each voxel with gait velocity. To assess a possible relationship between white matter hyperintensity location and gait velocity, we applied voxel-based lesion-symptom mapping. We found a significant association between the magnetization transfer ratio within the forceps minor and gait velocity (β = 0.134; 95% CI, 0.011-0.258; P = .033), independent of demographics, general physical performance, vascular risk factors, and brain volume. White matter hyperintensities did not significantly change this association. Our study provides new evidence for the importance of magnetization transfer ratio changes in gait disturbances at an older age, particularly in the forceps minor. The histopathologic basis of these findings is yet to be determined.

High-field magnetic resonance imaging of structural alterations in first-episode, drug-naive patients with major depressive disorder

Previous structural imaging studies have found evidence of brain morphometric changes in patients with major depressive disorder (MDD), but these studies rarely excluded compounding effects of certain important factors, such as medications and long duration of illnesses. Furthermore, the neurobiological mechanism of the macroscopic findings of structural alterations in MDD patients remains unclear. In this study, we utilized magnetization transfer imaging, a quantitative measure of the macromolecular structural integrity of brain tissue, to identify biophysical alterations, which are represented by a magnetization transfer ratio (MTR), in MDD patients. To ascertain whether MTR changes occur independent of volume loss, we also conduct voxel-based morphometry (VBM) analysis. The participants included 27 first-episode, drug-naive MDD patients and 28 healthy controls matched for age and gender. Whole-brain voxel-based analysis was used to compare MTR and gray matter volume across groups and to analyse correlations between MTR and age, symptom severity, and illness duration. The patients exhibited significantly lower MTR in the left superior parietal lobule and left middle occipital gyrus compared with healthy controls, which may be related to the attentional and cognitive dysfunction in MDD patients. The VBM analysis revealed significantly increased gray matter volume in right postcentral gyrus in MDD patients. These findings in first-episode, drug-naive MDD patients may reflect microstructural gray matter changes in the parietal and occipital cortices close to illness onset that existed before volume loss, and thus potentially provide important new insight into the early neurobiology of depression.

Development and aging of superficial white matter myelin from young adulthood to old age: Mapping by vertex-based surface statistics (VBSS).

Superficial white matter (SWM) lies immediately beneath cortical gray matter and consists primarily of short association fibers. The characteristics of SWM and its development and aging were seldom examined in the literature and warrant further investigation. Magnetization transfer imaging is sensitive to myelin changes in the white matter. Using an innovative multimodal imaging analysis approach, vertex-based surface statistics (VBSS), the current study vertexwise mapped age-related changes of magnetization transfer ratio (MTR) in SWM from young adulthood to old age (30-85 years, N = 66). Results demonstrated regionally selective and temporally heterochronologic changes of SWM MTR with age, including (1) inverted U-shaped trajectories of SWM MTR in the rostral middle frontal, medial temporal, and temporoparietal regions, suggesting continuing myelination and protracted maturation till age 40-50 years and accelerating demyelination at age 60 and beyond, (2) linear decline of SWM MTR in the middle and superior temporal, and pericalcarine areas, indicating early maturation and less acceleration in age-related degeneration, and (3) no significant changes of SWM MTR in the primary motor, somatosensory and auditory regions, suggesting resistance to age-related deterioration. We did not observe similar patterns of changes in cortical thickness in our sample, suggesting the observed SWM MTR changes are not due to cortical atrophy. Hum Brain Mapp 37:1759-1769, 2016. © 2016 Wiley Periodicals, Inc.

Amide Proton Transfer (APT) MR imaging and Magnetization Transfer (MT) MR imaging of pediatric brain development.

To quantify the brain maturation process during childhood using combined amide proton transfer (APT) and conventional magnetization transfer (MT) imaging at 3 Tesla. Eighty-two neurodevelopmentally normal children (44 males and 38 females; age range, 2-190months) were imaged using an APT/MT imaging protocol with multiple saturation frequency offsets. The APT-weighted (APTW) and MT ratio (MTR) signals were quantitatively analyzed in multiple brain areas. Age-related changes in MTR and APTW were evaluated with a non-linear regression analysis. The APTW signals followed a decreasing exponential curve with age in all brain regions measured (R(2) = 0.7-0.8 for the corpus callosum, frontal and occipital white matter, and centrum semiovale). The most significant changes appeared within the first year. At maturation, larger decreases in APTW and lower APTW values were found in the white matter. On the contrary, the MTR signals followed an increasing exponential curve with age in the same brain regions measured, with the most significant changes appearing within the initial 2years. There was an inverse correlation between the MTR and APTW signal intensities during brain maturation. Together with MT imaging, protein-based APT imaging can provide additional information in assessing brain myelination in the paediatric population. • APTW signals followed a decreasing exponential curve with age. • The most significant APTW changes appeared within the first year • At maturation, larger APTW decreases and lower APTW appeared in white matter • MTR signals followed an increasing exponential curve with age.

Cerebral maturation in the early preterm period—A magnetization transfer and diffusion tensor imaging study using voxel-based analysis

The magnetization transfer ratio (MTR) and diffusion tensor imaging (DTI) correlates of early brain development were examined in cohort of 18 very preterm neonates (27–31 gestational weeks) presenting with normal radiological findings scanned within 2weeks after birth (28–32 gestational weeks). A combination of non-linear image registration, tissue segmentation, and voxel-wise regression was used to map the age dependent changes in MTR and DTI-derived parameters in 3D across the brain based on the cross-sectional in vivo preterm data. The regression coefficient maps obtained differed between brain regions and between the different quantitative MRI indices. Significant linear increases as well as decreases in MTR and DTI-derived parameters were observed throughout the preterm brain. In particular, the lamination pattern in the cerebral wall was evident on parametric and regression coefficient maps. The frontal white matter area (subplate and intermediate zone) demonstrated a linear decrease in MTR. While the intermediate zone showed an unexpected decrease in fractional anisotropy (FA) with age, with this decrease (and the increase in mean diffusivity (MD)) driven primarily by an increase in radial diffusivity (RD) values, the subplate showed no change in FA (and an increase in MD). The latter was the result of a concomitant similar increase in axial diffusivity (AD) and RD values. Interpreting the in vivo results in terms of available histological data, we present a biophysical model that describes the relation between various microstructural changes measured by complementary quantitative methods available on clinical scanners and a range of maturational processes in brain tissue.

Magnetization transfer imaging for in vivo detection of microstructural tissue changes in aging and dementia: a short literature review.

Magnetization-transfer imaging (MTI), a magnetic resonance imaging acquisition protocol, can detect microstructural brain tissue changes by assessing the magnetization exchange between tissue water and protons bound to macromolecules. This short literature review summarizes results of previous MTI studies in normal aging, cerebral small vessel disease, and Alzheimer's disease (AD). During normal aging, the magnetization transfer ratio (MTR), a measure for the magnitude of magnetization transfer between macromolecular and water protons, declines in normal appearing brain tissue and associations between lower MTR and executive dysfunction have been described. In AD, MTR changes follow a disease-specific temporo-parietal pattern, independent of cortical atrophy. The differential diagnostic contribution beyond atrophy seems to be modest and the independent effect of MTR alterations as predictors of conversion from mild cognitive impairment to AD needs to be explored. MTR correlates well with global cognitive measures like the Mini-Mental State Examination, and MTR decreases rapidly over time in AD. Longitudinal studies are needed to determine the clinical relevance of global and regional MTI measures in normal aging and neurodegenerative disease. Moreover, correlative MTI-histopathologic postmortem studies are warranted to determine the full spectrum of tissue destruction underlying MTR lowering apart from demyelination.