Mean Magnetization Transfer Ratio Research Articles

Migraineurs Without Aura Show Microstructural Abnormalities in the Cerebellum and Frontal Lobe

The involvement of the cerebellum in migraine pathophysiology is not well understood. We used a biparametric approach at high-field MRI (3T) to assess the structural integrity of the cerebellum in 15 migraineurs with aura (MWA), 23 migraineurs without aura (MWoA), and 20 healthy controls (HC). High-resolution T1 relaxation maps were acquired together with magnetization transfer images in order to probe microstructural and myelin integrity. Clusterwise analysis was performed on T1 and magnetization transfer ratio (MTR) maps of the cerebellum of MWA, MWoA, and HC using an ANOVA and a non-parametric clusterwise permutation F test, with age and gender as covariates and correction for familywise error rate. In addition, mean MTR and T1 in frontal regions known to be highly connected to the cerebellum were computed. Clusterwise comparison among groups showed a cluster of lower MTR in the right Crus I of MWoA patients vs. HC and MWA subjects (p = 0.04). Univariate and bivariate analysis on T1 and MTR contrasts showed that MWoA patients had longer T1 and lower MTR in the right and left pars orbitalis compared to MWA (p < 0.01 and 0.05, respectively), but no differences were found with HC. Lower MTR and longer T1 point at a loss of macromolecules and/or micro-edema in Crus I and pars orbitalis in MWoA patients vs. HC and vs. MWA. The pathophysiological implications of these findings are discussed in light of recent literature.

Magnetisation transfer MR imaging of the kidney: evaluation at 3.0 T in association with renal function

To evaluate the feasibility of using magnetisation transfer (MT) MRI of the kidney at 3.0T to assess renal function. Forty-four patients who underwent abdominal MRI on a 3.0-T system including gradient-echo (GRE) sequences with and without MT pulse were included. In each patient, MT ratio (MTR) of the renal cortex and medulla was measured by using regions of interest (ROIs) placed on the MTR map image. Regression analysis showed good correlation between estimated glomerular filtration rate (eGFR) and MTR of the renal cortex (r = -0.645, P < 0.0001). Among 44 patients, 22 were categorised as the normal renal function group and 22 were classified as the decreased eGFR group. The mean MTR of the renal cortex in patients with decreased eGFR (mean MTR, 30.7 ± 3.2%) was significantly higher (P < 0.0001) than that in patients with normal renal function (mean MTR, 25.3 ± 2.2%), although the mean MTRs of the renal medulla in the two groups were not significantly different. There was good correlation between eGFR and MTR of the renal cortex derived from MT MRI at 3.0T. This technique may have the potential to evaluate the degree of renal function non-invasively in patients with renal impairment. • Magnetisation transfer techniques can provide new information about renal disease. • MTR values of the renal cortex correlate well with estimated glomerular filtration. • Higher MTR of the renal cortex exists in patients with renal dysfunction. • MT MRI at 3.0T may be useful for evaluating renal function.

Clinically feasible MTR is sensitive to cortical demyelination in MS

Presently there is no clinically feasible imaging modality that can effectively detect cortical demyelination in patients with multiple sclerosis (MS). The objective of this study is to determine if clinically feasible magnetization transfer ratio (MTR) imaging is sensitive to cortical demyelination in MS. MRI were acquired in situ on 7 recently deceased patients with MS using clinically feasible sequences at 3 T, including relatively high-resolution T1-weighted and proton density-weighted images with/without a magnetization transfer pulse for calculation of MTR. The brains were rapidly removed and placed in fixative. Multiple cortical regions from each brain were immunostained for myelin proteolipid protein and classified as mostly myelinated (MM(ctx)), mostly demyelinated (MD(ctx)), or intermediately demyelinated (ID(ctx)). MRIs were registered with the cortical sections so that the cortex corresponding to each cortical section could be identified, along with adjacent subcortical white matter (WM). Mean cortical MTR normalized to mean WM MTR was calculated for each cortical region. Linear mixed-effects models were used to test if mean normalized cortical MTR was significantly lower in demyelinated cortex. We found that mean normalized cortical MTR was significantly lower in cortical tissue with any demyelination (ID(ctx) or MD(ctx)) compared to MM(ctx) (demyelinated cortex: least-squares mean [LSM] = 0.797, SE = 0.007; MM(ctx): LSM = 0.837, SE = 0.006; p = 0.01, n = 89). This result demonstrates that clinically feasible MTR imaging is sensitive to cortical demyelination and suggests that MTR will be a useful tool to help detect MS cortical lesions in living patients with MS.

Magnetization transfer for the assessment of bowel fibrosis in patients with Crohn’s disease: initial experience

To assess the feasibility of magnetization transfer (MT) imaging of the bowel wall in patients with Crohn's disease (CD), and to evaluate its utility for the detection of intestinal fibrosis. In this prospective study, 31 patients (age 39.0±13.2years) with CD were examined in a 1.5T MR scanner. To establish a standard of reference, two independent readers classified the patients in different disease states using standard MR enterography, available clinical data and histological findings. In addition to the standard protocol, a 2D gradient-echo sequence (TR/TE 32ms/2.17ms; flip angle 25°) with/without 1,100Hz off-resonance prepulse was applied. MT ratios (MTR) of the small bowel wall were computed off-line on a pixel-by-pixel basis. The MT sequences acquired images of sufficient quality and spatial resolution for the evaluation of the small bowel wall without detrimental motion artefacts. In normal bowel wall segments, an intermediate MTR of 25.4±3.4% was measured. The MTR was significantly increased in bowel wall segments with fibrotic scarring (35.3±4.0%, p<0.0001). In segments with acute inflammation, the mean MTR was slightly smaller (22.9±2.2%). MT imaging of the small bowel wall is feasible in humans with sufficient image quality and may help with the identification of fibrotic scarring in patients with CD.

Differentiation of malignant and benign breast lesions using magnetization transfer imaging and dynamic contrast‐enhanced MRI

To evaluate feasibility of using magnetization transfer ratio (MTR) in conjunction with dynamic contrast-enhanced MRI (DCE-MRI) for differentiation of benign and malignant breast lesions at 3 Tesla. This prospective study was IRB and HIPAA compliant. DCE-MRI scans followed by MT imaging were performed on 41 patients. Regions of interest (ROIs) were drawn on co-registered MTR and DCE postcontrast images for breast structures, including benign lesions (BL) and malignant lesions (ML). Initial enhancement ratio (IER) and delayed enhancement ratio (DER) were calculated, as were normalized MTR, DER, and IER (NMTR, NDER, NIER) values. Diagnostic accuracy analysis was performed. Mean MTR in ML was lower than in BL (P < 0.05); mean DER and mean IER in ML were significantly higher than in BL (P < 0.01, P < 0.001). NMTR, NDER, and NIER were significantly lower in ML versus BL (P < 0.007, P < 0.001, P < 0.001). IER had highest diagnostic accuracy (77.6%), sensitivity (86.2%), and area under the ROC curve (.879). MTR specificity was 100%. Logistic regression modeling with NMTR and NIER yielded best results for BL versus ML (sensitivity 93.1%, specificity 80%, AUC 0.884, accuracy 83.7%). Isolated quantitative DCE analysis may increase specificity of breast MR for differentiating BL and ML. DCE-MRI with NMTR may produce a robust means of evaluating breast lesions.

Hippocampal Magnetization Transfer Ratio at 3T: Validation of Automated Postprocessing and Comparison of Quantification Metrics

To investigate the reliability of a novel magnetization transfer ratio (MTR) postprocessing technique for the hippocampus using histogram analysis, and compare results to more established volumetric measurements. This study is conducted in healthy volunteers as a precursor to future applications regarding progressive neurologic diseases, such as Alzheimer's disease. Eight healthy subjects were scanned twice with interval of 1 week using quantitative magnetic resonance imaging (MRI). Automated pixel-wise analysis was performed for the hippocampal regions of each patient. Reliability was assessed using intraclass correlation coefficients (ICCs), coefficients of variation (COVs), and instrumental standard deviation (ISD). Reliable metrics were 25th percentile, median, 75th percentile, peak location, and mean approach (ranges: ICC = .93-.96, COV = 2.71-3.88%, ISD .78-1.01). Histogram peak height had ICC below .7, and a COV above 10%. Volumetric measurements had (ICC = .95-.97, COV = 1.43-3.39%). Excellent scan-rescan reproducibility (ICC > .9, COV < 10%) was observed for specific MTR histogram metrics and the mean MTR approach. These results are comparable to the volumetric approach. Future studies can examine the possibility that MTR changes precede morphological changes as this study suggests that both MTR and volumetric measurements of the hippocampus can be used as reliable imaging tools.

Magnetization transfer imaging in multiple sclerosis treated with alemtuzumab

The magnetization transfer ratio reflects the integrity of tissue structure, including myelination and axonal density. Mean magnetization transfer ratio fell in 18 untreated patients with multiple sclerosis both in normal appearing grey (–0.25 pu/year, p < 0.001) and white matter (–0.12 pu/year, p = 0.004). Conversely, mean magnetization transfer ratio was stable in 20 alemtuzumab-treated patients (grey matter: −0.01 pu/year, p = 0.87; white matter: -0.02 pu/year, p = 0.51). The gradient difference in grey matter was 0.25 pu/year (p < 0.001) after age-adjustment. These data suggest that in multiple sclerosis alemtuzumab protects against tissue damage in normal-appearing grey matter, perhaps by preventing new lesion formation.

A Magnetization Transfer Imaging Study of Corpus Callosum Myelination in Young Children with Autism

Several lines of evidence suggest that autism may be associated with abnormalities in white matter development. However, inconsistencies remain in the literature regarding the nature and extent of these abnormalities, partly because of the limited types of measurements that have been used. Here, we used magnetization transfer imaging to provide insight into the myelination of the corpus callosum in children with autism. Magnetization transfer imaging scans were obtained in 101 children with autism and 35 typically developing children who did not significantly differ with regard to gender or age. The midsagittal area of the corpus callosum was manually traced and the magnetization transfer ratio (MTR) was calculated for each voxel within the corpus callosum. Mean MTR and height and location of the MTR histogram peak were analyzed. Mean MTR and MTR histogram peak height and location were significantly higher in children with autism than in typically developing children, suggesting abnormal myelination of the corpus callosum in autism. The differences in callosal myelination suggested by these results may reflect an alteration in the normally well-regulated process of myelination of the brain, with broad implications for neuropathology, diagnosis, and treatment of autism.

Grey matter damage and overall cognitive impairment in primary progressive multiple sclerosis

Objectives: To identify associations between cognitive impairment and imaging measures in a cross-sectional study of patients with primary progressive multiple sclerosis (PPMS). Methods: Neuropsychological tests were administered to 27 patients with PPMS and 31 controls. Patients underwent brain conventional magnetic resonance imaging (MRI) sequences, volumetric scans and magnetization transfer (MT) imaging; MT ratio (MTR) parameters, grey matter (GM) and normal-appearing white matter (NAWM) volumes, and WM T2 lesion load (T2LL) were obtained. In patients, multiple linear regression models identified the imaging measure associated with the abnormal cognitive tests independently from the other imaging variables. Partial correlation coefficients (PCC) were reported. Results: Patients performed worse on tests of attention/speed of visual information processing, delayed verbal memory, and executive function, and had a worse overall cognitive performance index, when compared with controls. In patients, a lower GM peak location MTR was associated with worse overall cognitive performance (p < 0.001, PCC = 0.77). GM mean and peak height MTR showed the strongest association with the estimated verbal intelligence quotient (IQ) decline (p < 0.001, PCC = -0.62), and executive function (p < 0.001, PCC = 0.79). NAWM volume was associated with attention/speed of visual information processing (p < 0.001, PCC = 0.74), while T2LL was associated with delayed verbal memory (p = 0.007, PCC = -0.55). Conclusions: The finding of strong associations between GM MTR, NAWM volume and T2LL and specific cognitive impairments suggests that models that predict cognitive impairment in PPMS should include comprehensive MRI assessments of both GM and WM. However, GM MTR appears to be the main correlate of overall cognitive dysfunction, underlining the role of abnormal GM integrity in determining cognitive impairment in PPMS.

MRI predictors of cognitive outcome in early multiple sclerosis

To determine MRI predictors for cognitive outcome in patients with early relapsing-remitting multiple sclerosis (MS). Forty-four patients recently diagnosed with clinically definite MS were followed up with clinical and cognitive evaluations at 1, 2, 5, and 7 years and underwent brain MRI including magnetization transfer (MT) imaging at baseline and 2 years. Cognitive evaluation was also performed in 56 matched healthy subjects at baseline. Cognitive testing included the Brief Repeatable Battery. Imaging parameters included lesion load, brain parenchymal fraction (BPF), ventricular fraction (VF), and mean MT ratio (MTR) of lesion and normal-appearing brain tissue (NABT) masks. At baseline, patients presented deficits of memory, attention, and information processing speed (IPS). Over 2 years, all magnetic resonance parameters deteriorated significantly. Over 7 years, Expanded Disability Status Scale score deteriorated significantly. Fifty percent of patients deteriorated on memory cognitive domain and 22.7%of patients on IPS domain. Seven-year change of memory scores was significantly associated with baseline diffuse brain damage (NABT MTR). IPS z score change over 7 years was correlated with baseline global atrophy (BPF), baseline diffuse brain damage, and central brain atrophy (VF) change over 2 years. The main predictors of cognitive changes over 7 years are baseline diffuse brain damage and progressive central brain atrophy over the 2 years after MS diagnosis.

Magnetization transfer helps detect intestinal fibrosis in an animal model of Crohn disease.

To determine the utility of magnetization transfer (MT) in the identification and quantification of intestinal fibrosis in a rat model of Crohn disease. The university committee on the use and care of animals approved this study (UCUCA 08592). Lewis rats injected subserosally with peptidoglycan-polysaccharide (PG-PS) develop bowel inflammation 1 day after laparotomy (early phase) and fibrosis starting 14 days after laparotomy (late phase). The authors performed 2.0-T magnetic resonance (MR) imaging in 25 rats injected with PG-PS and 13 injected with human serum albumin (HSA) (control animals). Imaging was performed before laparotomy and on a weekly basis thereafter for up to 28 days. The MT ratio in the bowel wall was calculated. Resected cecal tissue was scored for inflammation and fibrosis. Tissue fibrosis was determined with colorimetric analysis of trichrome-stained specimens. Collagen content was measured with Western blot analysis. Statistical analyses were performed with the Student t test for continuous bivariate comparisons, the Pearson correlation for continuous variables, and the Spearman correlation for ordinal variables. All rats developed early inflammation, which subsided over time. Rats injected with PG-PS developed increased fibrosis in the late phase, whereas control rats did not. The mean MT ratio of rats injected with PG-PS with late-phase fibrosis was higher than that in rats with early phase inflammation (P = .017). In addition, the MT ratio of rats injected with PG-PS with late-phase fibrosis was higher than that of control animals that did not develop fibrosis in the late phase (P = .0001). The MT ratio of control animals remained unchanged over time as inflammation subsided. The MT ratio in rats injected with PG-PS showed correlation with tissue fibrosis (ρ = 0.63). The MT ratio showed correlation with tissue collagen (R = 0.74). The positive and negative predictive values of the MT ratio in the prediction of fibrosis were 92% (12 of 13 rats) and 83% (five of six rats), respectively. These results indicate that MT is sensitive to bowel wall fibrosis as occurs in Crohn strictures.

Magnetization transfer ratio may be a surrogate of spongiform change in human prion diseases

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 ratio abnormalities reflect clinically relevant grey matter damage in multiple sclerosis

Background In multiple sclerosis, grey matter (GM) damage appears more clinically relevant than either white matter damage or lesion load. Objective We investigated if normal-appearing white matter (NAWM) and grey matter tissue changes assessed by magnetization transfer ratio were associated with long-term disability. Methods Sixty-nine people were assessed 20 years after presentation with a clinically isolated syndrome (CIS) [28 still CIS, 31 relapsing-remitting multiple sclerosis, 10 secondary progressive multiple sclerosis], along with 19 healthy subjects. Mean magnetization transfer ratio, peak height (PH) and peak location of the normalized magnetization transfer ratio histograms were determined in NAWM and grey matter, as well as, white matter and GM Fraction (GMF) and T2-weighted lesion load. Results Median expanded disability status scale for multiple sclerosis patients was 2.5 (range 1–8). GM-PH, and less so, NAWM mean and peak location, were lower in multiple sclerosis patients (P = 0.009) versus controls, relapsing-remitting multiple sclerosis versus CIS (P = 0.008) and secondary progressive multiple sclerosis versus relapsing-remitting multiple sclerosis (P = 0.002). GM-PH (as well as GMF) correlated with expanded disability status scale (r s = −0.49; P = 0.001) and multiple sclerosis functional score (r s = 0.51; P = 0.001). GM-PH independently predicted disability with similar strength to the associations of GMF with clinical measures. Conclusion Grey matter damage was related to long-term disability in multiple sclerosis cohort with a relatively low median expanded disability status scale. Markers of intrinsic grey matter damage (magnetization transfer ratio) and tissue loss offer clinically relevant information in multiple sclerosis.

Tissue-Specific Imaging Is a Robust Methodology to Differentiate In Vivo T1 Black Holes with Advanced Multiple Sclerosis–Induced Damage

Brains of patients with multiple sclerosis (MS) characteristically have "black holes" (BHs), hypointense lesions on T1-weighted (T1W) spin-echo (SE) images. Although conventional MR imaging can disclose chronic BHs (CBHs), it cannot stage the degree of their pathologic condition. Tissue-specific imaging (TSI), a recently introduced MR imaging technique, allows selective visualization of white matter (WM), gray matter (GM), and CSF on the basis of T1 values of classes of tissue. We investigated the ability of TSI-CSF to separate CBHs with longer T1 values, which likely represent lesions containing higher levels of destruction and unbound water. Eighteen patients with MS, who had already undergone MR imaging twice (24 months apart) on a 1.5T scanner, underwent a 3T MR imaging examination. Images acquired at 1.5T included sequences of precontrast and postcontrast T1W SE, T2-weighted (T2W) SE, and magnetization transfer (MT). Sequences obtained at 3T included precontrast and postcontrast T1W SE, T2W SE, T1 inversion recovery prepared fast spoiled gradient recalled-echo (IR-FSPGR) and TSI. A BH on the 3T-IR-FSPGR was defined as a CBH if seen as a hypointense, nonenhancing lesion with a corresponding T2 abnormality for at least 24 months. CBHs were separated into 2 groups: those visible as hyperintensities on TSI-CSF (group A), and those not appearing on the TSI-CSF (group B). Mean MT ratios of group-A lesions (0.22 +/- 0.06, 0.13-0.35) were lower (F(1,13) = 60.39; P < .0001) than those of group-B lesions (0.32 +/- 0.03, 0.27-0.36). Group-A lesions had more advanced tissue damage; thus, TSI is a potentially valuable method for qualitative and objective identification.

Grey matter magnetization transfer ratio independently correlates with neurological deficit in secondary progressive multiple sclerosis

Although there is substantial brain grey matter pathology in secondary progressive multiple sclerosis (MS), there has been limited investigation of its contribution to disability.This study investigated the correlation of magnetization transfer ratio (MTR) measures taken from brain grey matter, normal appearing white matter (NAWM) and lesions with neurological deficit and disability in 113 people with secondary progressive MS. In order to adjust for the potential effects of focal white matter lesions and global brain atrophy, T2 lesion volume and normalized brain volume (NBV) were also calculated for each subject. Clinical measures included the expanded disability status scale (EDSS) and the multiple sclerosis functional composite (MSFC) scores. Linear regression analysis was used to assess the age- and gender-adjusted correlation of MTR histogram mean, peak height and peak location with the MSFC and individual component measures. Logistic regression analysis was used to determine whether imaging measures could be used to predict if subjects were in the higher disability group (EDSS > or = 6.5).Significant correlations were detected between MSFC composite and mean MTR in (i) normal appearing white matter (NAWM; r = 0.327, p < 0.0001), (ii) grey matter (r = 0.460, p < 0.0001) and (iii) lesions (r = 0.394, p < 0.0001). Although NBV and T2 lesion volume correlated significantly with MSFC, grey matter histogram mean emerged as the best predictor of MSFC score. None of the MRI measures significantly predicted higher EDSS.These results suggest that brain grey matter pathology plays an important role in determining neurological impairment. The apparent paucity of correlation between MRI measures and EDSS is likely to represent the relative insensitivity of the latter measure in this study group.

Tract-based Analysis of Magnetization Transfer Ratio and Diffusion Tensor Imaging of the Frontal and Frontotemporal Connections in Schizophrenia

In the pathophysiology of schizophrenia, aberrant connectivity between brain regions may be a central feature. Diffusion tensor imaging (DTI) studies have shown altered fractional anisotropy (FA) in white brain matter in schizophrenia. Focal reductions in myelin have been suggested in patients using magnetization transfer ratio (MTR) imaging but to what extent schizophrenia may be related to changes in MTR measured along entire fiber bundles is still unknown. DTI and MTR images were acquired with a 1.5-T scanner in 40 schizophrenia patients and compared with those of 40 healthy participants. The mean FA and mean MTR were measured along the genu of the corpus callosum and the left and right uncinate fasciculus. A higher mean MTR of 1% was found in the right uncinate fasciculus in patients compared with healthy participants. A significant negative correlation between age and mean FA in the left uncinate fasciculus was found in schizophrenia patients but not in healthy participants. Decreased FA in the left uncinate fasciculus may be more prominent in patients with longer illness duration. The increased mean MTR in the right uncinate fasciculus could reflect a compensatory role for myelin in these fibers or possibly represent aberrant frontotemporal connectivity.

Should SDMT substitute for PASAT in MSFC? A 5-year longitudinal study

Background The multiple sclerosis functional composite (MSFC) includes the Paced Auditory Serial Addition test (PASAT) as a measure of cognition. Objectives and methods We compared the MSFC incorporating the Symbol Digit Modalities test (SDMT) (MSFC [sdmt]) to the usually applied MSFC (MSFC [pasat]) in a sample of 46 ptients with relapsing–remitting MS who were followed over a five-year period. Magnetic resonance imaging was performed at baseline. Results The Expanded Disability Status scale (EDSS) deteriorated significantly over 5 years (P < 0.01), but MSFC scores remained stable. MSFC [sdmt] correlated with EDSS at all time points of evaluation, but MSFC [pasat] correlated with EDSS only at baseline, 1, and 5 years. The 5-year EDSS correlated significantly with baseline MSFC [sdmt] and MSFC [pasat] but did not correlate after adjustment for baseline EDSS. No significant correlation was found at baseline between MSFC and imaging parameters (lesion load, brain parenchymal fraction [BPF], ventricular fraction, mean magnetization transfer ratio of lesions and normal-appearing brain tissue), but baseline BPF correlated significantly with changes of SDMT z score (P = 0.0003), MSFC [pasat] (P = 0.006), and MSFC [sdmt] (P = 0.0002) over 5 years. Conclusion We propose not to substitute PASAT by SDMT in the MSFC but to consider SDMT as a complementary useful approach to evaluate overall MS disease.

Regional Specificity of Magnetization Transfer Imaging in Multiple Sclerosis

The goal of this study was to develop and validate a method for generation of regional magnetization transfer ratio (MTR). We also studied the topography of MTR changes in multiple sclerosis (MS) and in normal controls (NC), and preliminarily examined the clinical usefulness of this method. We examined 45 patients with MS (relapsing remitting [RR] = 28 and secondary progressive[SP] = 17] and 19 NC. Mean disease duration was 14.3 years and median Expanded Disability Status Scale was 3.0. Regions of the brain were determined using semiautomated brain region extraction (SABRE). Twenty-six regional masks were automatically applied to MTR maps that were further split into gray matter (GM) and white matter (WM)compartments. Mean MTR from 12 SABRE regions differed significantly between MS patients and NC. For WM, all regional mean MTRs differed significantly between RR, SP, and NC participants(P < .001). In regression analysis, only 3 regions remained significantly different when corrected for total T2-LV. The regression model predicting disability selected GM mean MTR of the right medial inferior frontal region (P = .031). The study results showed that this regional MTR approach is reproducible, reliable and clinically relevant. MTI changes occur selectively in specific sub-regions.

Localized grey matter damage in early primary progressive multiple sclerosis contributes to disability

Disability in primary progressive multiple sclerosis (PPMS) has been correlated with damage to the normal appearing brain tissues. Magnetization transfer ratio (MTR) and volume changes indicate that much of this damage occurs in the normal appearing grey matter, but the clinical significance of this remains uncertain. We aimed to localize these changes to distinct grey matter regions, and investigate the clinical impact of the MTR changes. 46 patients with early PPMS and 23 controls underwent MT and high-resolution T1-weighted imaging. Patients were scored on the Expanded Disability Status Scale (EDSS), Multiple Sclerosis Functional Composite and subtests (Nine-Hole Peg Test, Timed Walk Test, Paced Auditory Serial Addition Test [PASAT]). Grey matter volume and MTR were compared between patients and controls, adjusting for age. Mean MTR for significant regions within the motor network and in areas relevant to PASAT performance were correlated with appropriate clinical scores, adjusting for grey matter volume. Patients showed reduced MTR and atrophy in the right pre- and left post-central gyri, right middle frontal gyrus, left insula, and thalamus bilaterally. Reduced MTR without significant atrophy occurred in the left pre-central gyrus, left superior frontal gyri, bilateral superior temporal gyri, right insula and visual cortex. Higher EDSS correlated with lower MTR in the right primary motor cortex (BA 4). In conclusion, localized grey matter damage occurs in early PPMS, and MTR change is more widespread than atrophy. Damage demonstrated by reduced MTR is clinically eloquent.

Magnetization transfer MRI for quantitative assessment of intestinal fibrosis in Crohnʼs disease

To develop a non-invasive method for detecting and quantifying intestinal fibrosis in patients with Crohn's disease using magnetization transfer (MT) magnetic resonance imaging (MRI). MT-MRI is more specific than traditional MRI for detecting tissue fibrosis by differentiating between free tissue water and water closely associated with macromolecules such as collagen. We hypothesize that changes in the MT signal profile can be used to differentiate and quantitatively characterize intestinal fibrosis, and will be more sensitive and specific for fibrosis than traditional MRIT1 and T2 relaxation times. Intestinal fibrosis was experimentally induced in Lewis strain rats. During laparotomy peptidoglycan-polysaccharide (PG-PS) was injected subserosally into the intestinal wall of the cecum, ileum, and distal Peyer's patches of four rats. Five control animals were similarly injected with human serum albumin (HSA). The PG-PS injected animals developed chronic intestinal inflammation, granulomas, and intense fibrosis 21 days after injection. Ex vivo intestinal tissue samples were scanned in a Varian Inova 2.0 T, 31 cm clear bore system equipped with Acustar S-180 actively shielded gradients and an MR probe. For magnetization transfer, a series of RF pulses were applied from -100 Hz to + 100 kHz off-resonance at three different RF power levels. In vivo MT-MRI images of a whole rat abdomen were also obtained. After undergoing MT-MRI scanning, intestinal histopathology determined the extent of tissue fibrosis. The standard MR imaging parameters, T1 and T2 relaxation times, as well as the MT data were recorded for both PG-PS and HSA samples. There was no difference between the T1 and T2 relaxation times. The MT data were analyzed and reduced into factors indicating the percent solid matter and overall tissue rigidity. The MT ratio (MTR) = 100*(1 -Msat/Mo) where Msat represents MT signal at 10 kHz off-resonance, and Mo represents MT signal at 100 kHz off-resonance. The mean MTR from PG-PS rats was 46.27 (SD 4.14), and control rats was 38.07 (SD 4.76). This demonstrated a statistically significant difference (p = 0.03) between fibrotic and non-fibrotic tissue. Histopathology confirmed the presence of fibrosis in the PG-PS rats, and lack of fibrosis in the control rats. (1) As expected, the data demonstrate that standard T1 and T2 relaxation times were not appreciably different. This confirms that traditional MRI is not sufficiently sensitive to detect intestinal fibrosis. (2) The MT data collected from rats with experimental Crohn's were statistically significantly different than control rats without fibrosis. This supports our hypothesis that MT-MRI can be used to distinguish intestinal fibrosis from non-fibrotic tissue. Furthermore, the MT profile provides a quantification of tissue fibrosis which will allow the clinician to follow disease progression. This technique has the significant advantage over currently available imaging modalities without exposing the subject to ionizing radiation.