Differences In Magnetization Transfer Ratio 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.

Candidate imaging biomarkers for PMP22-related inherited neuropathies.

ObjectiveCharcot–Marie–Tooth type 1A (CMT1A) and hereditary neuropathy with liability to pressure palsy (HNPP) are caused by mutations to the peripheral myelin protein 22 (PMP22) gene. A need exists for sensitive and reliable biomarkers of progression and treatment response. Magnetic resonance imaging (MRI) metrics of nerve pathology and morphology were investigated for this purpose.MethodsMRI was performed at 3.0 T in the thigh of CMT1A (N = 11) and HNPP patients (N = 12) and controls (N = 23). Three potential imaging biomarkers of the sciatic nerve were investigated: 1) magnetization transfer ratio (MTR), which assays myelin content, and 2) cross‐sectional area (CSA) and 3) circularity, which assay morphological changes. Potential imaging biomarkers were compared across cohorts and assessed for relationships with disability in the legs (CMTESL), compound motor action potentials (CMAP), and motor conduction velocities (MCV). Inter‐rater reliability and test–retest repeatability were established for each imaging metric.ResultsSignificant differences in MTR, CSA, and circularity were observed in CMT1A relative to controls (p = 0.02, p < 0.001, and p = 0.003, respectively, via Wilcoxon rank‐sum tests). Differences were not observed in the HNPP cohort. Significant relationships were observed between MTR and clinical metrics (CMTESL: p = 0.003, CMAP: p = 0.03, MCV: p = 0.01); and between CSA and electrophysiology (CMAP: p = 0.002, MCV: p < 0.001). All metrics were reliable and repeatable with MTR the most reliable (intraclass correlation coefficient [ICC] >0.999, CV = 0.30%) and repeatable (ICC = 0.84, CV = 3.16%).InterpretationMTR, CSA, and circularity showed promise as reliable and sensitive biomarkers of CMT1A, but not HNPP. These warrant longitudinal investigation as response biomarkers in upcoming clinical trials of CMT1A, while other methods should be considered for HNPP.

Magnetization transfer imaging alterations and its diagnostic value in antipsychotic-naïve first-episode schizophrenia.

Magnetization transfer imaging (MTI) may provide more sensitivity and mechanistic understanding of neuropathological changes associated with schizophrenia than volumetric MRI. This study aims to identify brain magnetization transfer ratio (MTR) changes in antipsychotic-naïve first-episode schizophrenia (FES), and to correlate MTR findings with clinical symptom severity. A total of 143 individuals with antipsychotic-naïve FES and 147 healthy controls (HCs) were included and underwent 3.0 T brain MTI between August 2005 and July 2014. Voxelwise analysis was performed to test for MTR differences with family-wise error corrections. Relationships of these differences to symptom severity were assessed using partial correlations. Exploratory analyses using a support vector machine (SVM) classifier were conducted to discriminate FES from HCs using MTR maps. Model performance was examined using a 10-fold stratified cross-validation. Compared with HCs, individuals with FES exhibited higher MTR values in left thalamus, precuneus, cuneus, and paracentral lobule, that were positively correlated with schizophrenia symptom severity [precuneus (r = 0.34, P = 0.0004), cuneus (r = 0.33, P = 0.0006) and paracentral lobule (r = 0.37, P = 0.001)]. Whole-brain MTR maps identified individuals with FES with overall accuracy 75.5% (219 of 290 individuals) based on SVM approach. In antipsychotic-naïve FES, clinically relevant biophysical abnormalities detected by MTI mainly in the left parieto-occipital regions are informative about local brain pathology, and have potential as diagnostic markers.

One-minute whole-brain magnetization transfer ratio imaging with intrinsic B1 -correction.

Magnetization transfer ratio (MTR) histograms are used widely for the assessment of diffuse pathological changes in the brain. For broad clinical application, MTR scans should not only be fast, but confounding factors should also be minimized for high reproducibility. To this end, a 1-minute whole-brain spiral MTR method with intrinsic B1 -field correction is introduced. A spiral multislice spoiled gradient-echo sequence with adaptable magnetization-transfer saturation pulses (angle β) is proposed. After a low-resolution single-shot spiral readout and a dummy preparation period, high-resolution images are acquired using an interleaved spiral readout. For whole-brain MTR imaging, 50 interleaved slices with three different magnetization-transfer contrasts (β = 0°, 350°, and 550°) together with an intrinsic B1 -field map are recorded in 58.5 seconds on a clinical 3T system. From the three contrasts, two sets of MTR images are derived and used for subsequent B1 correction, assuming a linear dependency on β. For validation, a binary spin bath model is used. For the proposed B1 -correction scheme, numerical simulations indicate for brain tissue a decrease of about a factor of 10 for the B1 -related bias on MTR. As a result, following B1 correction, MTR differences in gray and white matter become markedly accentuated, and the reproducibility of MTR histograms from scan-rescan experiments is improved. Furthermore, B1 -corrected MTR histograms show a lower variability for age-matched normal-appearing brain tissue. From its speed and offering intrinsic B1 correction, the proposed method shows excellent prospects for clinical studies that explore magnetization-transfer effects based on MTR histogram analysis.

Automated separation of diffusely abnormal white matter from focal white matter lesions on MRI in multiple sclerosis

BackgroundPrevious histopathology and MRI studies have addressed the differences between focal white matter lesions (FWML) and diffusely abnormal white matter (DAWM) in multiple sclerosis (MS). These two categories of white matter T2-weighted (T2w) hyperintensity show different degrees of demyelination, axonal loss and immune cell density on histopathology, potentially offering distinct correlations with symptoms. Objectives1) To automate the separation of FWML and DAWM using T2w MRI intensity thresholds and to investigate their differences in magnetization transfer ratios (MTR), which are sensitive to myelin content; 2) to correlate MTR values in FWML and DAWM with normalized signal intensity values on fluid attenuated inversion recovery (FLAIR), T2w, and T1-weighted (T1w) contrasts, as well as with the ratio of T2w/T1w normalized values, in order to determine whether these normalized intensities can be used when MTR is not available. MethodsWe used three MRI datasets: datasets 1 and 2 had 20 MS participants each, scanned with similar 3T MRI protocols in 2 centers, including: 3D T1w (MP2RAGE), 3D FLAIR, 2D T2w, and 3D magnetization-transfer (MT) contrasts. Dataset 3 consisted of 67 scans of participants enrolled in a multisite study and had T1w and T2w contrasts. We used the first dataset to develop an automated technique to separate FWML from DAWM and the second and third to validate the automation of the technique. We applied the automatic thresholds to all datasets to assess the overlap of the manual and the automated masks using Dice kappa. We also assessed differences in mean MTR values between NAWM, DAWM and FWML, using manually and automatically derived masks in datasets 1 and 2. Finally, we used the mean intensity of manually-traced areas of NAWM on T2w images as the normalization factor for each MRI contrast, and compared these with the normalized-intensity values obtained using automated NAWM (A-NAWM) masks as the normalization factor. ANOVA assessed the MTR differences across tissue types. Paired t-test or Wilcoxon signed-ranked test assessed FWML and DAWM differences between manual and automatically derived volumes. Pearson correlations assessed the relationship between MTR and normalized intensity values in the manual and automatically derived masks. ResultsThe mean Dice-kappa values for dataset 1 were: 0.79 for DAWM masks and 0.90 for FWML masks. In dataset 2, mean Dice-kappa values were: 0.78 for DAWM and 0.87 for FWML. In dataset 3, mean Dice-kappa values were 0.72 for DAWM, and 0.87 for FWML. Manual and automated DAWM and FWML volumes were not significantly different in all datasets. MTR values were significantly lower in manually and automatically derived FWML compared with DAWM in both datasets (dataset 1 manual: F ​= ​111,08, p ​< ​0.0001; automated: F ​= ​153.90, p ​< ​0.0001; dataset 2 manual: F ​= ​31.25, p ​< ​0.0001; automated: F ​= ​74.04, p ​< ​0.0001). In both datasets, manually derived FWML and DAWM MTR values showed significant correlations with normalized T1w (r ​= ​0.77 to 0.94) intensities. ConclusionsThe separation of FWML and DAWM on MRI scans of MS patients using automated intensity thresholds on T2w images is feasible. MTR values are significantly lower in FWML than DAWM, and DAWM values are significantly lower than NAWM, reflecting potentially greater demyelination within focal lesions. T1w normalized intensity values exhibit a significant correlation with MTR values in both tissues of interest and could be used as a proxy to assess demyelination when MTR or other myelin-sensitive images are not available.

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

Recent neuroimaging studies in OCD have reported structural alterations in the brain, not limited to frontostriatal regions. While Diffusion Tensor Imaging (DTI) is typically used to interrogate WM microstructure in OCD, additional imaging metric, such as Magnetization Transfer Imaging (MTI), allows for further identification of subtle but important structural changes across both GM and WM. In this study, both MTI and DTI were utilised to investigate the structural integrity of the brain, in OCD in relation to healthy controls. 38 adult OCD patients were recruited, along with 41 age- and gender-matched controls. Structural T1, MTI and DTI data were collected. Case-control differences in Magnetization Transfer Ratio (MTR) and DTI metrics (FA, MD) were examined, along with MTR/DTI-related associations with symptom severity in patients. No significant group differences were found across MTR, FA, and MD. However, OCD symptom severity was positively correlated with MTR in a distributed network of brain regions, including the striatum, cingulate, orbitofrontal area and insula. Within the same regions, OCD symptoms were also positively correlated with FA in WM, and negatively correlated with MD in GM. These results indicate a greater degree of myelination in certain cortical and subcortical regions in the more severe cases of OCD.

Comparison of Three Magnetization Transfer Ratio Parameters for Assessment of Intestinal Fibrosis in Patients with Crohn's Disease.

ObjectiveTo establish a novel standardized magnetization transfer ratio (MTR) parameter which considers the element of the normal bowel wall and to compare the efficacy of the MTR, normalized MTR, and standardized MTR in evaluating intestinal fibrosis in Crohn's disease (CD).Materials and MethodsAbdominal magnetization transfer imaging from 20 consecutive CD patients were analyzed before performing elective operations. MTR parameters were calculated by delineating regions of interest in specified segments on MTR maps. Specimens with pathologically confirmed bowel fibrosis were classified into one of four severity grades. The correlation between MTR parameters and fibrosis score was tested by Spearman's rank correlation. Differences in MTR, normalized MTR, and standardized MTR across diverse histologic fibrosis scores were analyzed using the independent sample t test or the Mann-Whitney U test. The area under the receiver operating characteristic curve (AUC) was computed to test the efficacies of the MTR parameters in differentiating severe intestinal fibrosis from mild-to-moderate fibrosis.ResultsNormalized (r = 0.700; p < 0.001) and standardized MTR (r = 0.695; p < 0.001) showed a strong correlation with bowel fibrosis scores, followed by MTR (r = 0.590; p < 0.001). Significant differences in MTR (t = −4.470; p < 0.001), normalized MTR (Z = −5.003; p < 0.001), and standardized MTR (Z = −5.133; p < 0.001) were found between mild-to-moderate and severe bowel fibrosis. Standardized MTR (AUC = 0.895; p < 0.001) had the highest accuracy in differentiating severe bowel fibrosis from mild-to-moderate bowel wall fibrosis, followed by normalized MTR (AUC = 0.885; p < 0.001) and MTR (AUC = 0.798; p < 0.001).ConclusionStandardized MTR is slightly superior to MTR and normalized MTR and therefore may be an optimal parameter for evaluating the severity of intestinal fibrosis in CD.

Quantitative MRI outcomes in child and adolescent leukemia survivors: Evidence for global alterations in gray and white matter

IntroductionCure rates for pediatric acute lymphoblastic leukemia (ALL) have reached an all-time high (>90%); however, neurocognitive difficulties continue to affect quality of life in at least a subset of survivors. There are relatively few quantitative neuroimaging studies in child and adolescent ALL survivors treated with chemotherapy only. Use of different outcome measures or limited sample sizes restrict our ability to make inferences about patterns of brain development following chemotherapy treatment. In this study, we used magnetic resonance imaging (MRI) to evaluate brain outcomes in ALL survivors, comparing against a group of typically developing, cancer free peers. Materials and methodsParticipants included 71 ALL survivors, on average 8 years after diagnosis and 8–18 years of age, and 83 typically developing controls. Anatomical MRI was performed to evaluate brain structure; diffusion and magnetization transfer MRI were used to examine brain tissue microstructure. ResultsSuccessful MRI scans were acquired in 67 survivors (94%) and 82 controls (99%). Structurally, ALL survivors exhibited widespread reductions in brain volume, with 6% less white matter and 5% less gray matter than controls (p = 0.003 and 0.0006 respectively). Much of the brain appeared affected – 71 of 90 evaluated structures showed smaller volume – with the most notable exception being the occipital lobe, where no significant differences were observed. Average full-scale IQ in the survivor and control groups were 95 (CI 92–99) and 110 (CI 107–113), respectively. Using data from the NIH Pediatric MRI Data Repository, we evaluated the extent to which elevated IQ in the control group might affect the structural differences observed. We estimated that two thirds of the observed brain differences were attributable to ALL and its treatment. In addition to the structural changes, survivors showed, on average, globally lower white matter fractional anisotropy (-3%) and higher radial diffusivity (+5%) (p < 10−6), but no differences in magnetization transfer ratio. ConclusionsNeuroanatomical alterations in late childhood and adolescent ALL survivors treated with chemotherapy-only protocols are widespread, with white matter being somewhat more affected than gray matter. These MRI results indicate brain development is altered in ALL survivors and highlight the need to examine how these alterations emerge.

Role of glia in prefrontal white matter abnormalities in first episode psychosis or mania detected by diffusion tensor spectroscopy

BackgroundWhite matter (WM) abnormalities are amongst the most commonly described neuroimaging findings in patients with psychotic disorders including schizophrenia (SZ) and bipolar disorder (BD), and may be central to pathophysiology. Few studies have directly compared WM abnormalities in patients with SZ and BD in the first episode of illness, and no studies to date have attempted to separate abnormalities of axon and myelin using complementary MRI techniques. MethodsWe examined WM abnormalities in young adults with SZ (n = 19) or BD (n = 16) within the first year of illness onset, and healthy controls (n = 22) using a combination of diffusion tensor spectroscopy to measure NAA, creatine (Cr), and choline (Cho), and magnetization transfer ratio (MTR). MTR reflects myelin content, NAA diffusion is neuron specific, and Cr and Cho diffusion reflect both neuron and glial signal. ResultsWe found no differences in MTR or NAA ADC in either patient group compared to controls, but significant elevations of both Cr and Cho diffusion in patients with SZ, and elevations of Cho diffusion in patients with BD. Elevations in Cr and Cho diffusion in the absence of NAA diffusion abnormalities indicate that the aberrant signal arises in glia. ConclusionsGlial abnormalities were present and detectable by the first episode of psychosis, whereas major abnormalities in axon and myelin were not. Examination of these neurobiological markers early in the course of illness may clarify the neuroprogressive nature of these distinct aspects of WM, and their associations with early clinical phenotypes.

The diagnostic value of magnetization transfer MRI for bowel inflammation and fibrosis in Crohn disease

Objective To assess the diagnostic value of magnetization transfer MRI (MTI) for bowel inflammation and fibrosis in humans with Crohn disease (CD). Methods From July 2014 through April 2017, 31 patients with a confirmed diagnosis of CD were prospectively recruited from the First Affiliated Hospital of Sun Yat-Sen University. They were scheduled for elective surgery due to bowel obstruction and other complications, and underwent preoperative MR enterography (MRE) and MTI within 15 days of surgery. All cases had available intestinal specimens identified on MRE and resected bowel segments for region-by-region matching. All patients underwent breath-hold conventional MRE and MTI examinations, and then the magnetization transfer ratios (MTRs) of pathological bowel segments were measured. Using region-by-region correlation between MTI and surgical specimen, the bowel segments were resected to stain with HE for evaluating bowel inflammation, Masson for bowel fibrosis, and type Ⅰ collagen staining for the deposition of type Ⅰ collagen within the bowel walls. The histologic sections from the most severe areas were scored as 0 (normal), 1 (mild), 2 (moderate) and 3 (severe). The correlations between MTR and histologic scores were analyzed by using Spearman rank correlation or partial correlation. The differences in MTR among different grades of bowel fibrosis were analyzed by one-way ANOVA. The efficacy of MTR for predicting bowel fibrosis was evaluated by receiver operating characteristic curves analysis. The difference in MTRs between purely inflammatory bowel walls and mixed fibrotic and inflammatory bowel walls was analyzed by Student's t test. Results Sixty-two resected bowel specimens from 31 patients including 9 purely inflammatory bowel walls and 53 mixed fibrotic and inflammatory bowel walls were obtained in this study. There were significant differences in MTR among non-fibrotic [ (21.45±2.65) %], mildly [ (30.88±6.14) %], moderately [ (35.14±4.31) %] and severely [ (35.14±4.31) %] fibrotic walls (F=38.397, P<0.01). MTRs strongly correlated with fibrosis scores (r=0.681, P<0.01). High accuracy of MTRs was shown (curve under area=0.905, P<0.01) for differentiating moderately-severely fibrotic from non-fibrotic and mildly fibrotic bowel walls. Using MTR of 31.50% as a cutoff value, the sensitivity and specificity were 93.6% and 80.0%, respectively. The MTRs of purely inflammatory bowel walls [ (21.45±2.65) %] were significantly higher than that of mixed fibrotic and inflammatory [ (36.28±5.21) %] bowel walls (t=-13.052,P<0.01). MTRs correlated with the scores of type Ⅰ collagen (r=0.325, P=0.044) but did not correlate with inflammation scores (r=-0.024, P=0.857). Conclusions MTI enables quantitative evaluation of bowel fibrosis in patients with CD and can be used to differentiate purely inflammatory CD from mixed fibrotic and inflammatory CD. Key words: Crohn disease; Magnetization transfer imaging; Fibrosis; Inflammation

Magnetization Transfer Imaging of Treatment-resistant Depression.

Purpose To detect biophysical abnormalities in patients with postmedication treatment-resistant depression (TRD) with magnetization transfer imaging. Materials and Methods This study was approved by the local ethics committee, and written informed consent was obtained from all participants. Participants included 69 patients with major depressive disorder (MDD) (30 with TRD; 39 with non-TRD) and 41 healthy control subjects. Age and sex were examined with one-way analysis of variance and χ2 tests and were well matched among the three groups. Whole-brain voxel-based analysis was used to compare the magnetization transfer ratio (MTR) between the three groups. Regional MTR values were used to analyze the correlations with symptom severity and illness duration. Results MTR differences were identified in the bilateral precentral gyrus, left cerebellum posterior lobe, left middle occipital lobe, left precuneus, and left temporal lobe among the three groups. Relative to patients with non-TRD, those with TRD had significantly lower MTR in the task-positive network regions, including the bilateral precentral gyrus and left middle occipital lobe, and had lower MTR in the default mode network regions, including the left precuneus and left temporal lobe. Regional MTRs were not associated with symptom severity or illness duration. Conclusion These results suggest that treatment resistance in patients with MDD may be mediated by macromolecular abnormalities in the task-positive and default mode functional networks. © RSNA, 2017 Online supplemental material is available for this article. An earlier incorrect version of this article appeared online. This article was corrected on March 29, 2017.

Ultra-high field MTR and qR2* differentiates subpial cortical lesions from normal-appearing gray matter in multiple sclerosis

Background: Cortical gray matter (GM) demyelination is frequent and clinically relevant in multiple sclerosis (MS). Quantitative magnetic resonance imaging (qMRI) sequences such as magnetization transfer ratio (MTR) and quantitative R2* (qR2*) can capture pathological subtleties missed by conventional magnetic resonance imaging (MRI) sequences. Although differences in MTR and qR2* have been reported between lesional and non-lesional tissue, differences between lesion types or lesion types and myelin density matched normal-appearing gray matter (NAGM) have not been found or investigated. Objective: Identify quantitative differences in histopathologically verified GM lesion types and matched NAGM at ultra-high field strength. Methods: Using 7T post-mortem MRI, MRI lesions were marked on T2 images and co-registered to the calculated MTR and qR2* maps for further evaluation. In all, 15 brain slices were collected, containing a total of 74 cortical GM lesions and 45 areas of NAGM. Results: Intracortical lesions had lower MTR and qR2* values compared to NAGM. Type I lesions showed lower MTR than type III lesions. Type III lesions showed lower MTR than matched NAGM, and type I and IV lesions showed lower qR2* than matched NAGM. Conclusion: qMRI at 7T can provide additional information on extent of cortical pathology, especially concerning subpial lesions. This may be relevant for monitoring disease progression and potential treatment effects.

Imaging of Primary Brain Tumors and Metastases with Fast Quantitative 3-Dimensional Magnetization Transfer.

This study assesses whether magnetization transfer (MT) imaging provides additive information to conventional MRI in brain tumors. MT data of 26 patients with neoplastic and metastatic brain tumors were analyzed at 1.5 T. For the 3 largest tumor groups investigated in this study--glioblastoma multiforme (GBM), meningiomas, and metastases-statistical comparisons were performed. Analyzed MT parameters included the magnetization transfer ratio (MTR) and 4 quantitative MT parameters (qMT): Relaxation times (T1, T2), exchange rate (kf), and macromolecular content (F). Total imaging time of high-resolution whole brain MTR and qMT imaging with balanced steady-state free precession required 9 minutes. Five ROIs were chosen: Contrast-enhancing (T1W-CE), noncontrast-enhancing (T1W-non-CE), proximal hyperintensity (T2W-pSI), distal hyperintensity (T2W-dSI), and a reference (ref). Pathologies showed significant (P < .05) MT changes (MTR and qMT) compared to the reference. The T1W-CE, T1W-non-CE, and T2W-pSI ROIs of GBMs, meningiomas, and metastases showed significant differences in MTR and qMT estimates. Similar MTR with significant different qMT values were observed in several ROIs among different lesions. MT maps (MTR and qMT) indicated changes in tissue appearing unaffected on MRI in most glial tumors. MTR and qMT imaging enables a better differentiation between brain tumors and provides additive information to MRI.

Comparing free water imaging and magnetization transfer measurements in schizophrenia

Diffusion weighted imaging (DWI) has been extensively used to study the microarchitecture of white matter in schizophrenia. However, popular DWI-derived measures such as fractional anisotropy (FA) may be sensitive to many types of pathologies, and thus the interpretation of reported differences in these measures remains difficult. Combining DWI with magnetization transfer ratio (MTR) – a putative measure of white matter myelination – can help us reveal the underlying mechanisms. Previous findings hypothesized that MTR differences in schizophrenia are associated with free water concentrations, which also affect the DWIs. In this study we use a recently proposed DWI-derived method called free-water imaging to assess this hypothesis. We have reanalyzed data from a previous study by using a fiber-based analysis of free-water imaging, providing a free-water fraction, as well as mean diffusivity and FA corrected for free-water, in addition to MTR along twelve major white matter fiber bundles in 40 schizophrenia patients and 40 healthy controls. We tested for group differences in each fiber bundle and for each measure separately and computed correlations between the MTR and the DWI-derived measures separately for both groups. Significant higher average MTR values in patients were found for the right uncinate fasciculus, the right arcuate fasciculus and the right inferior-frontal occipital fasciculus. No significant results were found for the other measures. No significant differences in correlations were found between MTR and the DWI-derived measures. The results suggest that MTR and free-water imaging measures can be considered complementary, promoting the acquisition of MTR in addition to DWI to identify group differences, as well as to better understand the underlying mechanisms in schizophrenia.

Magnetization Transfer Ratio

Magnetization transfer-magnetic resonance imaging (MT-MRI) uses differences in the magnetization interaction of the free "unbound" water protons and the macromolecular-bound protons. The aim of this study was to evaluate whether the magnetization transfer ratio (MTR) may be used to identify fibrosis in patients with rectal cancer treated with chemoradiotherapy. This study was part of a rectal cancer imaging study, which was approved by the local institutional review board. Twenty-six patients, treated with neoadjuvant chemoradiotherapy, underwent a standard MRI including T2-weighted sequences and a diffusion-weighted sequence. An axially oriented MT sequence was performed at the center of the (former) tumor location. Regions of interest were manually drawn on the MT-MRI (with reference to the T2-weighted and diffusion-weighted images), covering areas of residual tumor, fibrosis, or the normal or edematous rectal wall. The results were compared with that of the histopathological examination. Differences in MTR between the 4 tissue types were analyzed, and a receiver operating characteristic (ROC) curve was generated to assess the diagnostic potential. Thirty-eight regions of interest were analyzed on the MT-MRI. The mean (SD) MTR of the fibrosis was 37.7% (2.7%), which was significantly higher than that of the residual tumor (29.6% [4.2%]; P < 0.001), the normal rectal wall (30.3% [4.7%]; P = 0.003), and the edematous rectal wall (18.2% [4.0%]; P < 0.001). The use of MTR resulted in an area under the ROC-curve of 0.96, a sensitivity of 88%, and a specificity of 90% for the diagnosis of fibrosis. Magnetization transfer ratio can be used to discriminate postradiation fibrosis from residual tumor and the normal rectal wall after chemoradiotherapy. Magnetization transfer imaging can thus be a promising tool for the unsolved dilemma of interpreting postradiation fibrosis in rectal cancer.

Deep Brain Stimulation for Treatment-Resistant Depression

Brian did reasonably well for about 3 years, with occasional worsening of depressive symptoms but generally with good functioning, when he developed his current major depressive episode. This was his most severe episode to date, with active suicidal ideation with a plan (but no immediate intent) to shoot himself. Over the next year, he had a number of treatments, among them multiple antidepressant medications, including selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, mirtazapine, tricyclic antidepressants, and tranylcypromine, as well as augmentation with lithium, thyroid hormone, buspirone, atypical antipsychotics, anticonvulsants, stimulants, light therapy, and ongoing psychotherapy. No treatment was able to achieve remission or a persistent clinically signifi cant reduction in symptoms. Given his degree of treatment resistance and continued overall deterioration, including increased suicidal ideation, he was referred for ECT. He achieved a good response (50%‐60% symptom reduction) with eight highdose right unilateral ECT treatments. ECT was delivered concurrently with ongoing medications, and attempts were made to optimize medications during and after ECT. However, Brian relapsed in about 6 weeks, and repeat ECT (including four right unilateral and eight bitemporal treatments delivered concurrently with ongoing medications) was unsuccessful in achieving signifi cant symptom reduction but was associated with notable cognitive impairment.

Brain pathology in first-episode psychosis: Magnetization transfer imaging provides additional information to MRI measurements of volume loss

BackgroundLoss of brain volume in first-episode psychosis can be detected using conventional magnetic resonance imaging (MRI), but subtle changes – not leading to reduction in volume – that may contribute to clinical and cognitive abnormalities, may go undetected. Magnetization transfer imaging (MTI), a technique more sensitive to subtle neuropathological changes than conventional MRI, could yield important information on the extent and nature of structural abnormalities. MethodsForty-eight patients (33 males) from a population-based sample with first-episode psychosis (41 with schizophrenia and 7 with schizoaffective psychosis) and 47 healthy volunteers (27 males) were studied. Differences in magnetization transfer ratio (MTR) and white and grey matter volumes between groups were investigated. ResultsIn patients, MTR was reduced in right entorhinal cortex, fusiform, dentate and superior frontal gyri and in left superior frontal and inferior/rostral cingulate gyri. Grey matter volume was reduced in right insula, frontal operculum and middle and superior temporal gyri and in left middle temporal gyrus. Grey matter volume increases were seen in patients in the superior frontal gyrus. White matter volume loss was found adjacent to grey matter loss. In patients MTR was lower in all areas of volumetric differences between groups suggesting that both changes may be related. Similar findings were observed when patients with schizoaffective psychosis were removed from the analysis. The correlations between clinical and MRI parameters did not survive correction for multiple comparisons. ConclusionsMTI frontal and temporal abnormalities suggesting neuroaxonal and myelin changes were more extensive in our patients than those detected with conventional MRI. Our findings also suggest that there is regional variation in the severity of structural brain abnormalities.

Focal Subcortical Biophysical Abnormalities in Patients Diagnosed With Type 2 Diabetes and Depression

Major depressive disorder has been consistently identified in patients with type 2 diabetes. Despite its high prevalence and clinical effect, the neurobiological substrates underlying depression in patients with diabetes remain largely unknown. To examine the biophysical integrity of proteins in critical white and gray matter regions in patients with type 2 diabetes and major depression to understand the pathophysiology of depression in diabetes. A cross-sectional magnetization transfer study using magnetic resonance imaging. Regions examined included the anterior cingulate, corpus callosum, frontal and occipital white matter, and the caudate and lenticular nuclei. A tertiary care university hospital. We studied 16 patients diagnosed with type 2 diabetes and major depression, 22 patients diagnosed with diabetes without depression (diabetic controls), and 30 controls without diabetes or major depression (healthy controls). Magnetization transfer ratios, a measure of the biophysical structure of proteins in the gray and white matter. Magnetization transfer ratios were significantly lower bilaterally in the head of the caudate nucleus in the group with diabetes and depression compared with the other 2 groups (P < .001). Diabetic controls had values between the depressed diabetic and healthy control groups. There were no significant differences in magnetization transfer ratios between groups in the other regions examined. These data indicate that there is an important subcortical biophysical component to depression in patients with type 2 diabetes. This finding has broad implications for the neuronal circuitry underlying mood disorders.

A Magnetization Transfer MRI Study of Deep Gray Matter Involvement in Multiple Sclerosis

Gray matter involvement in multiple sclerosis (MS) is of growing interest with respect to disease pathogenesis. Magnetization transfer imaging (MTI), an advanced MRI technique, is sensitive to disease in normal appearing white matter (NAWM) in patients with MS. We tested if MTI detected subcortical (deep) gray matter abnormalities in patients with MS (n= 60) vs. age-matched normal controls (NL, n= 20). Magnetization transfer ratio (MTR) maps were produced from axial proton density, conventional spin-echo, 5 mm gapless slices covering the whole brain. Region-of-interest-derived MTR histograms for the caudate, putamen, globus pallidus, thalamus, and NAWM were obtained. Whole brain MTR was also measured. Mean whole brain MTR and the peak position of the NAWM MTR histogram were lower in patients with MS than NL (P < .001) and mean whole brain MTR was lower in secondary progressive (SP, n= 10) than relapsing-remitting (RR, n= 50, P < .001) patients. However, none of the subcortical gray matter nuclei showed MTR differences in MS vs. NL, RR vs. SP, or SP vs. NL. The MTI technique used in this cohort was relatively insensitive to disease in the deep gray matter nuclei despite showing sensitivity for whole brain disease in MS. It remains to be determined if other MRI techniques are more sensitive than MTI for detecting pathology in these areas.