Magnetization Transfer Ratio Values Research Articles

Quantifying Tendon Degeneration Using Magic Angle Insensitive Ultra-Short Echo Time Magnetization Transfer: A Phantom Study in Bovine Tendons.

The aim of this study was to qualitatively and quantitatively assess changes in bovine flexor tendons before and after collagen degradation and at different angles in relation to the static B0 field using 3-dimensional ultra-short echo time (UTE) magnetization transfer (MT) imaging within a clinically feasible acquisition time. Eight bovine flexor tendons were examined at 3 T magnetic resonance imaging including 3-dimensional UTE MT and UTE T2* research application sequences (acquired within 4:04 and 6:38 minutes, respectively) before and after enzyme-induced degradation. The tendons were divided into 2 groups: group 1 (controls) treated with phosphate-buffered saline and group 2 treated with collagenase I to induce collagen degeneration. Magnetic resonance imaging was repeated at 0, 27, 55, and 90 degrees to the B0 field. To calculate quantitative tissue properties, all tendons were semiautomatically segmented, and changes in quantitative UTE T2* and UTE MT ratios (MTRs) were compared at different angles and between groups. In addition to descriptive statistics, the coefficient of variation was calculated to compare UTE MT and UTE T2* imaging. Ultra-short echo time MTR showed a significantly lower coefficient of variation compared with UTE T2* values, indicating a more robust imaging method (UTE MTR 9.64%-11.25%, UTE T2* 18.81%-24.06%, P < 0.001). Both methods showed good performance in detecting degenerated tendons using histopathology as reference standard, with UTE MT imaging having a better area under the curve than UTE T2* mapping (0.918 vs 0.865). Falsely high UTE T2* values were detected at the 55 degrees acquisition angle, whereas UTE MTR values were robust, that is, insensitive to the MAE. Ultra-short echo time MT imaging is a reliable method for quantifying tendon degeneration that is robust to the MAE and can be acquired in a clinically reasonable time.

Evaluation of the structural integrity of different spinal cord tracts with magnetization transfer ratio in degenerative cervical myelopathy.

Degenerative cervical myelopathy (DCM) is a common cause of spinal cord dysfunction. In this study, we explored the potential of magnetization transfer ratio (MTR) for evaluating the structural integrity of spinal cord tracts in patients with clinically significant DCM. Fifty-three patients with DCM and 41 patients with cervical radiculopathy were evaluated using high-resolution cervical spinal cord magnetic resonance imaging (MRI), which included the magnetization transfer technique. MRI data were analyzed with the Spinal Cord Toolbox (v5.5); MTR values in each spinal tract were calculated and compared between groups after correction for patient age and sex. Correlations between MTR values and patients' clinical disability rate were also evaluated. A statistically significant reduction in the average MTR of the spinal cord white matter, as well as the MTR of the ventral columns and lateral funiculi, was revealed in the DCM group (adjusted p < 0.01 for all comparisons). Furthermore, reductions in MTR values in the fasciculus cuneatus, spinocerebellar, rubrospinal, and reticulospinal tracts were found in patients with DCM (adjusted p < 0.01 for all comparisons). Positive correlations between the JOA score and the MTR within the ventral columns of the spinal cord (R = 0.38, adjusted p < 0.05) and the ventral spinocerebellar tract (R = 0.41, adjusted p < 0.05) were revealed. The findings of our study indicate that demyelination in patients with DCM primarily affects the spinal tracts of the extrapyramidal system, and the extent of these changes is related to the severity of the condition.

The magnetization transfer ratio of the post-mortem canine intervertebral disk is positively correlated to Pfirrmann grading on high field 3.0T MRI: a pilot study.

Intervertebral disk (IVD) degeneration usually occurs earlier in chondrodystrophic dog breeds than in other breeds. Spinal cord compression secondary to IVD degeneration is the most common cause of myelopathy in these dogs. Standard magnetic resonance imaging (MRI) sequences permit the identification of IVD degeneration and its consequences on adjacent neurological structures. In human medicine, quantitative MRI sequences, such as magnetization transfer ratio (MTR) sequences, are developed and used to detect early IVD degeneration. This prospective randomized post-mortem comparative study aimed to evaluate the correlation between a qualitative Pfirrmann MRI grading and the MTR values of the IVD in chondrodystrophic dogs. Vertebral columns of eight canine cadavers were frozen and thawed prior to imaging with T2-weighted and MTR sequences using a 3.0 T high-field MRI. These sequences were reviewed by two observers. A Spearman correlation coefficient was calculated in order to compare the MTR values with the Pfirrmann grade. Pearson correlation coefficients were calculated to evaluate the inter-observer agreement of the delineation of the region of interest (ROI) around the NP and the MTR values. A Wilcoxon-Mann-Whitney test was used to conclude on the significance of the correlation between the MTR values and the Pfirrmann grades. There were 138 intervertebral disks analyzed: 29/138 (21.0%) IVD were grade I, 74/138 (53.6%) grade II, and 35/138 (25.4%) grade III. No grades IV and V were present in this study. Inter-observer agreement for delineation of IVD ROI was fair (r = 0.54) but inter-observer agreement of mean MTR value within the ROI was very good (r = 0.89). Mean MTR values were 16.459% (10.0305-21.0950%) for grade I, 18.888% (10.0750-27.2400%) for grade II, and 22.813% (12.5700-31.7600%) for grade III. The mean MTR value was significantly different between each Pfirrmann grade: between grades I and II (p < 0.005), grades II and III (p < 0.05), and grades I and III (p < 0.005). There was a significant moderate positive correlation between Pfirrmann grading and mean MTR values (r = 0.516). The magnetization transfer ratio seems to be an objective method to detect early intervertebral disk degeneration via quantitative analysis.

Magnetization transfer ratio of the sciatic nerve differs between patients in type 1 and type 2 diabetes

BackgroundPrevious studies on magnetic resonance neurography (MRN) found different patterns of structural nerve damage in type 1 diabetes (T1D) and type 2 diabetes (T2D). Magnetization transfer ratio (MTR) is a quantitative technique to analyze the macromolecular tissue composition. We compared MTR values of the sciatic nerve in patients with T1D, T2D, and healthy controls (HC).Methods3-T MRN of the right sciatic nerve at thigh level was performed in 14 HC, 10 patients with T1D (3 with diabetic neuropathy), and 28 patients with T2D (10 with diabetic neuropathy). Results were subsequently correlated with clinical and electrophysiological data.ResultsThe sciatic nerve’s MTR was lower in patients with T2D (0.211 ± 0.07, mean ± standard deviation) compared to patients with T1D (T1D 0.285 ± 0.03; p = 0.015) and HC (0.269 ± 0.05; p = 0.039). In patients with T1D, sciatic MTR correlated positively with tibial nerve conduction velocity (NCV; r = 0.71; p = 0.021) and negatively with hemoglobin A1c (r = − 0.63; p < 0.050). In patients with T2D, we found negative correlations of sciatic nerve’s MTR peroneal NCV (r = − 0.44; p = 0.031) which remained significant after partial correlation analysis controlled for age and body mass index (r = 0.51; p = 0.016).ConclusionsLower MTR values of the sciatic nerve in T2D compared to T1D and HC and diametrical correlations of MTR values with NCV in T1D and T2D indicate that there are different macromolecular changes and pathophysiological pathways underlying the development of neuropathic nerve damage in T1D and T2D.Trial registrationhttps://classic.clinicaltrials.gov/ct2/show/NCT03022721. 16 January 2017.Relevance statementMagnetization transfer ratio imaging may serve as a non-invasive imaging method to monitor the diseases progress and to encode the pathophysiology of nerve damage in patients with type 1 and type 2 diabetes.Key points• Magnetization transfer imaging detects distinct macromolecular nerve lesion patterns in diabetes patients.• Magnetization transfer ratio was lower in type 2 diabetes compared to type 1 diabetes.• Different pathophysiological mechanisms drive nerve damage in type 1 and 2 diabetes.Graphical

Amide proton transfer (APT) and magnetization transfer (MT) in predicting short-term therapeutic outcome in nasopharyngeal carcinoma after chemoradiotherapy: a feasibility study of three-dimensional chemical exchange saturation transfer (CEST) MRI

BackgroundThe three-dimensional chemical exchange saturation transfer (3D CEST) technique is a novel and promising magnetic resonance sequence; however, its application in nasopharyngeal carcinoma (NPC) lacks sufficient evaluation. This study aimed to assess the feasibility of the 3D CEST technique in predicting the short-term treatment outcomes for chemoradiotherapy (CRT) in NPC patients.MethodsForty NPC patients and fourteen healthy volunteers were enrolled and underwent the pre-treatment 3D CEST magnetic resonance imaging and diffusion-weighted imaging (DWI). The reliability of 3D CEST was assessed in healthy volunteers by calculating the intra- and inter-observer correlation coefficient (ICC) for amide proton transfer weighted-signal intensity (APTw-SI) and magnetization transfer ratio (MTR) values. NPC patients were divided into residual and non-residual groups based on short-term treatment outcomes after CRT. Whole-tumor regions of interest (ROIs) were manually drawn to measure APTw-SI, MTR and apparent diffusion coefficient (ADC) values. Multivariate analysis and the receiver operating characteristic curve (ROC) were used to evaluate the prediction performance of clinical characteristics, APTw-SI, MTR, ADC values, and combined models in predicting short-term treatment outcomes in NPC patients.ResultsFor the healthy volunteer group, all APTw-SI and MTR values exhibited good to excellent intra- and inter-observer agreements (0.736–0.910, 0.895–0.981, all P > 0.05). For NPC patients, MTR values showed a significant difference between the non-residual and residual groups (31.24 ± 5.21% vs. 34.74 ± 1.54%, P = 0.003) while no significant differences were observed for APTw-SI and ADC values (P > 0.05). Moreover, the diagnostic power of MTR value was superior to APTw-SI (AUC: 0.818 vs. 0.521, P = 0.017) and comparable to ADC values (AUC: 0.818 vs. 0.649, P > 0.05) in predicting short-term treatment outcomes for NPC patients. The prediction performance did not improve even when combining MTR values with APTw-SI and/or ADC values (P > 0.05).ConclusionsThe pre-treatment MTR value acquired through 3D CEST demonstrated superior predictive performance for short-term treatment outcomes compared to APTw-SI and ADC values in NPC patients after CRT.

Adiabatic null passage for on-resonance magnetization transfer preparation.

We propose a novel RF pulse providing an adiabatic null passage (ANP) for magnetization transfer preparation with improved insensitivity to and B0 inhomogeneities and mitigated direct saturation and T2 effects. The phase modulation function of a 6-ms time-resampled frequency offset-corrected pulse was modified to achieve zero flip angle at the end of the pulse. The spectral response was simulated, and its insensitivity to B0 and was investigated and compared with a phase-inverted (1 1- 2 ) binomial pulse. The proposed pulse was implemented in a 2D-EPI pulse sequence to generate magnetization transfer (MT) contrast and MT ratio (MTR) maps. In vivo experiments were performed on 3 healthy participants with power-matched settings for ANP and the binomial pulse with the following parameters: 6-ms binomial pulse with a flip angle of 107° (shortest element) and pulse repetition period (PRP) of TRslice = 59 ms, three experiments with 6-ms ANP and constant MT used overdrive factor (OF)/PRP values of 1/TRslice , /2TRslice , and /3TRslice . At gray matter (white matter) in vivo, the MTR decreased from 61% (64%) at OF = 1 to 38% (42%) applying ANP with an OF = and PRP = 3 TRslice , demonstrating the mitigation of T2 /direct effect by 22% (22%). Bloch-McConnell simulations gave similar values. In vivo experiments showed significant improvement in the MTR values for areas with high B0 inhomogeneity. ANP pulse was shown to be advantageous over its binomial counterpart in providing MT contrast by mitigating the T2 effect and direct saturation of the liquid pool as well as reduced sensitivity to and B0 inhomogeneity.

Chemical Exchange Saturation Transfer MRI for Differentiating Radiation Necrosis From Tumor Progression in Brain Metastasis—Application in a Clinical Setting

(a) MTRrNOE,0.52μT map for low power chemical exchange saturation transfer (CEST) for a patient along with (b) the histogram of this metric value in the lesion. The lesion includes a large number of voxels with high magnetization transfer ratio (MTR) values (in the tumor range) as well as a large number of voxels with low chemical exchange saturation transfer (CEST) values (in the radiation necrosis range). The clinical outcome of this lesion is progressive tumor. However, the presence of a large number of voxels with low MTR values lead to the incorrect diagnosis of radiation necrosis when using MTRrNOE,0.52μT. (c) Using MTR of Amide at high power (MTRAmide,2.0μT) on the other hand, suggests that the lesion is tumor, which highlights the need for considering multiple metrics. There are also two distinct metric value clusters in MTRAmide,2.0μT histogram suggesting presence of large areas of both tumor and radiation necrosis. A detailed analysis of the histogram also suggests the presence of a large region with viable tumor even at the low power CEST. By Mehrabian H. et al. (1713–1725).

Magnetization Transfer Contrast - Is it Sensitive Enough to Differentiate Demyelination from Axonal Loss?

Magnetization transfer contrast imaging (MTC) exploits the principle of exchange of energy between the bound and free protons and was shown to be pathologically informative. There is, however, controversy as to whether it correlates with axonal loss (AL), demyelination (DM), or both. This study addresses the pathophysiological process that underlies the white matter injury using the metric derivative of MTC, magnetization transfer ratio (MTR), and defines the role of MTR in identifying the different stages of inflammation, that is, edema, DM, and AL, using optic nerve as the model. One hundred and forty-two patients with a single, unilateral episode of optic neuritis (ON) were included in the study. Patients were divided into three groups - those with AL, those with DM, and those who were clinically optic neurites but without any electrophysiological changes suggestive of either AL or DM. MTR and electrophysiological studies were performed in the post-acute stage of ON and the results were compared to those obtained from the unaffected optic nerve. MTR was significantly reduced in the optic nerves of both DM and AL groups when compared to that in normal optic nerves (P < 0.001). The difference in MTR between the AL and DM groups did not reach statistical significance. Patient group with acute ON did not show any change in the MTR values compared to the normal controls. MTR is a sensitive technique to identify neuronal injury, whether it is DM or AL. It, however, cannot differentiate these two pathological processes. MTR is not sensitive to identify acute ON.

Short-term high-fat diet alters the mouse brain magnetic resonance imaging parameters consistently with neuroinflammation on males and metabolic rearrangements on females. A pre-clinical study with an optimized selection of linear mixed-effects models.

High-fat diet (HFD) consumption is known to trigger an inflammatory response in the brain that prompts the dysregulation of energy balance, leads to insulin and leptin resistance, and ultimately obesity. Obesity, at the same, has been related to cerebral magnetic resonance imaging (MRI) alterations, but the onset of HFD-induced neuroinflammation, however, has been principally reported on male rodents and by ex vivo methods, with the effects on females and the origin of MRI changes remaining unassessed. We characterized the onset and evolution of obesity on male and female mice during standard or HFD administration by physiological markers and multiparametric MRI on four cerebral regions involved in appetite regulation and energy homeostasis. We investigated the effects of diet, time under diet, brain region and sex by identifying their significant contributions to sequential linear mixed-effects models, and obtained their regional neurochemical profiles by high-resolution magic angle spinning spectroscopy. Male mice developed an obese phenotype paralleled by fast increases in magnetization transfer ratio values, while females delayed the obesity progress and showed no MRI-signs of cerebral inflammation, but larger metabolic rearrangements on the neurochemical profile. Our study reveals early MRI-detectable changes compatible with the development of HFD-induced cerebral cytotoxic inflammation on males but suggest the existence of compensatory metabolic adaptations on females that preclude the corresponding detection of MRI alterations.

Preliminary Application of Magnetization Transfer Imaging in the Study of Normal Uterus and Uterine Lesions.

PurposeThe aim of this study is to evaluate the utility of magnetization transfer (MT) imaging in the study of normal uterus and common uterine lesions.MethodsThis prospective study enrolled 160 consecutive patients with suspected uterine lesions. MT ratio (MTR) map was obtained by pelvic MT imaging on a 3.0T MRI scanner. Patients confirmed by pathology were divided into microscopic lesion group and lesion group, according to whether the maximum diameter of the lesion was less than 5 mm. After evaluating and eliminating patients with poor image quality by a three-point Likert scale, MTR values of lesions and normal endometrium, myometrium, and cervix were independently measured on the MTR map by two radiologists. Inter-reader agreement was evaluated. MTR values were compared among different uterine lesions and normal uterine structures using the Mann–Whitney U test with Bonferroni correction. Receiver operating characteristic curve was performed. The correlations between age and MTR values were explored by Pearson correlation analyses.ResultsA total of 96 patients with 121 uterine lesions in the lesion group and 41 patients in the microscopic lesion group were measured. The MTR values among normal endometrium, myometrium, and cervix were statistical significant differences (P < 0.05). There were significant differences between endometrial cancer and normal endometrium and between cervical cancer and normal cervix (both P ≤ 0.001). Area under the curve (AUC) for diagnosing endometrial and cervical cancer were 0.73 and 0.86. Myometrial lesions had significantly higher MTR values than endometrial lesions and cervical cancer (both P < 0.001), and the AUC for differentiating myometrial lesions from them were 0.89 and 0.94. MTR values of endometrial cancer were significantly higher than those of cervical cancer (P = 0.02). There was a critical correlation between age and MTR values in endometrial cancer (r = 0.81, P = 0.04).ConclusionsMTR values showed significant differences among normal uterine structures. It was valuable for diagnosing and differentiating uterine cancer. MTR values could differentiate myometrial lesions from endometrial or cervical lesions.

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.

Magnetization transfer ratio for assessing remyelination after transcranial ultrasound stimulation in the lysolecithin rat model of multiple sclerosis.

It has been shown that transcranial ultrasound stimulation (TUS) is capable of attenuating myelin loss and providing neuroprotection in animal models of brain disorders. In this study, we investigated the ability of TUS to promote remyelination in the lysolecithin (LPC)-induced local demyelination in the hippocampus. Demyelination was induced by the micro-injection of 1.5μL LPC (1%) into the rat hippocampus and the treated group received daily TUS for 5 or 12days. Magnetic resonance imaging techniques, including magnetization transfer ratio (MTR) and T2-weighted imaging, were used to longitudinally characterize the demyelination model. Furthermore, the therapeutic effects of TUS on LPC-induced demyelination were assessed by Luxol fast blue (LFB) staining. Our data revealed that reductions in MTR values observed during demyelination recover almost completely upon remyelination. The MTR values in demyelinated lesions were significantly higher in TUS-treated rats than in the LPC-only group after undergoing TUS. Form histological observation, TUS significantly reduced the size of demyelinated lesion 7days after LPC administration. This study demonstrated that MTR was a sensitive and reproducible quantitative marker to assess remyelination process in vivo during TUS treatment. These findings might open new promising treatment strategies for demyelinating diseases such as multiple sclerosis.

Slowly Expanding Lesions Predict 9-Year Multiple Sclerosis Disease Progression.

Background and ObjectivesChronic active lesions contribute to multiple sclerosis (MS) severity, but their association with long-term disease progression has not been evaluated yet. White matter (WM) lesions showing linear expansion over time on serial T1- and T2-weighted scans (i.e., slowly expanding lesions [SELs]) have been proposed as a marker of chronic inflammation. In this study, we assessed whether SEL burden and microstructural abnormalities were associated with Expanded Disability Status Scale (EDSS) score worsening and secondary progressive (SP) conversion at 9.1-year follow-up in patients with relapsing-remitting (RR) MS.MethodsIn 52 patients with RRMS, SELs were identified among WM lesions by linearly fitting the Jacobian of the nonlinear deformation field between time points obtained combining 3T brain T1- and T2-weighted scans acquired at baseline and months 6, 12, and 24. Logistic regression analysis was applied to investigate the associations of SEL number, volume, magnetization transfer ratio (MTR), and T1-weighted signal intensity with disability worsening (i.e., EDSS score increase) and SP conversion after a median follow-up of 9.1 years.ResultsAt follow-up, 20/52 (38%) patients with MS showed EDSS score worsening; 13/52 (25%) showed SP conversion. A higher baseline EDSS score (for each point higher: OR = 3.15 [95% CI = 1.61; 8.38], p = 0.003), a higher proportion of SELs among baseline lesions (for each % increase: OR = 1.22 [1.04; 1.58], p = 0.04), and lower baseline MTR values of SELs (for each % higher: OR = 0.66 [0.41; 0.92], p = 0.033) were significant independent predictors of EDSS score worsening at follow-up (C-index = 0.892). A higher baseline EDSS score (for each point higher: OR = 6.37 [1.98; 20.53], p = 0.002) and lower baseline MTR values of SELs (for each % higher: OR = 0.48 [0.25; 0.89], p = 0.02) independently predicted SPMS conversion (C-index = 0.947).DiscussionThe proportion of SELs is associated with MS progression after 9 years. More severe SEL microstructural abnormalities independently predict EDSS score worsening and SPMS conversion. The quantification of SEL burden and damage using T1-, T2-weighted, and MTR sequences may identify patients with RRMS at a higher risk of long-term disability progression and SPMS conversion.Classification of EvidenceThis study provides Class III evidence that in patients with RRMS starting treatment with natalizumab or fingolimod, the proportion of SELs on brain MRI was associated with EDSS score worsening and SPMS conversion at 9-year follow-up.

Amide proton transfer and chemical exchange saturation transfer MRI differentiates between growing and non-growing intracranial meningiomas: a pilot study

To differentiate between growing and non-growing intracranial meningiomas using magnetisation transfer ratio (MTR) values with amide proton transfer (APT) and chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI). Seventeen patients with suspected intracranial meningiomas who underwent APT-CEST MRI from November 2020 to April 2021 were evaluated retrospectively. MTR values on APT-CEST imaging as well as conventional MRI features were evaluated. These parameters were compared in growing meningiomas versus non-growing meningiomas and the findings compared with previous MRI examinations. ROC curve analysis was also performed to determine the diagnostic cut-offs for MTR. The cohort comprised 10 patients with growing meningiomas (two men [20%], eight women [80%]; mean age [standard deviation (SD)]: 59.9 years [16]) and seven patients with non-growing meningiomas (seven women [100%]; mean age [SD]: 63.9 years [18.6]). Significant differences were found in MTR values (0.0198±0.0003 versus 0.0131±0.0002; p<0.0001) between the growing meningiomas and non-growing meningiomas groups, respectively. The receiver operating characteristic (ROC) curve analysis showed that MTR values clearly differentiated between growing and non-growing meningiomas. At an area under the ROC curve (AUC) threshold of 0.0151, diagnostic sensitivity, specificity, positive predictive value, and negative predictive values for MTR were 100%, 85.7%, 90.9%, and 100%, respectively. Patients with growing meningiomas could be discriminated from patients with non-growing meningiomas, using the MTR values on post-growth tumour APT-CEST imaging.

Periventricular magnetisation transfer abnormalities in early multiple sclerosis

ObjectiveRecent studies suggested that CSF-mediated factors contribute to periventricular (PV) T2-hyperintense lesion formation in multiple sclerosis (MS) and this in turn correlates with cortical damage. We thus investigated if such PV-changes are observable microstructurally in early-MS and if they correlate with cortical damage. MethodsWe assessed the magnetisation transfer ratio (MTR) in PV normal-appearing white matter (NAWM) and in MS lesions in 44 patients with a clinically isolated syndrome (CIS) suggestive of MS and 73 relapsing-remitting MS (RRMS) patients. Band-wise MTR values were related to cortical mean thickness (CMT) and compared with 49 healthy controls (HCs). For each band, MTR changes were assessed relative to the average MTR values of all HCs. ResultsRelative to HCs, PV-MTR was significantly reduced up to 2.63% in CIS and 5.37% in RRMS (p < 0.0001). The MTR decreased towards the lateral ventricles with 0.18%/mm in CIS and 0.31%/mm in RRMS patients, relative to HCs. In RRMS, MTR-values adjacent to the ventricle and in PV-lesions correlated positively with CMT and negatively with EDSS. ConclusionPV-MTR gradients are present from the earliest stage of MS, consistent with more pronounced microstructural WM-damage closer to the ventricles. The positive association between reduced CMT and lower MTR in PV-NAWM suggests a common pathophysiologic mechanism. Together, these findings indicate the potential use of multimodal MRI as refined marker for MS-related tissue changes.

Assessing Lumbar Plexus and Sciatic Nerve Damage in Relapsing-Remitting Multiple Sclerosis Using Magnetisation Transfer Ratio.

Background: Multiple sclerosis (MS) has traditionally been regarded as a disease confined to the central nervous system (CNS). However, neuropathological, electrophysiological, and imaging studies have demonstrated that the peripheral nervous system (PNS) is also involved, with demyelination and, to a lesser extent, axonal degeneration representing the main pathophysiological mechanisms.Aim: The purpose of this study was to assess PNS damage at the lumbar plexus and sciatic nerve anatomical locations in people with relapsing-remitting MS (RRMS) and healthy controls (HCs) in vivo using magnetisation transfer ratio (MTR), which is a known imaging biomarker sensitive to alterations in myelin content in neural tissue, and not previously explored in the context of PNS damage in MS.Method: Eleven HCs (7 female, mean age 33.6 years, range 24-50) and 15 people with RRMS (12 female, mean age 38.5 years, range 30-56) were recruited for this study and underwent magnetic resonance imaging (MRI) investigations together with clinical assessments using the expanded disability status scale (EDSS). Magnetic resonance neurography (MRN) was first used for visualisation and identification of the lumbar plexus and the sciatic nerve and MTR imaging was subsequently performed using identical scan geometry to MRN, enabling straightforward co-registration of all data to obtain global and regional mean MTR measurements. Linear regression models were used to identify differences in MTR values between HCs and people with RRMS and to identify an association between MTR measures and EDSS.Results: MTR values in the sciatic nerve of people with RRMS were found to be significantly lower compared to HCs, but no significant MTR changes were identified in the lumbar plexus of people with RRMS. The median EDSS in people with RRMS was 2.0 (range, 0-3). No relationship between the MTR measures in the PNS and EDSS were identified at any of the anatomical locations studied in this cohort of people with RRMS.Conclusion: The results from this study demonstrate the presence of PNS damage in people with RRMS and support the notion that these changes, suggestive of demyelination, maybe occurring independently at different anatomical locations within the PNS. Further investigations to confirm these findings and to clarify the pathophysiological basis of these alterations are warranted.

Magnetization Transfer Ratio in Lower Limbs of Late Onset Pompe Patients Correlates With Intramuscular Fat Fraction and Muscle Function Tests.

Objectives: Magnetization transfer (MT) imaging exploits the interaction between bulk water protons and protons contained in macromolecules to induce signal changes through a special radiofrequency pulse. MT detects muscle damage in patients with neuromuscular conditions, such as limb-girdle muscular dystrophies or Charcot-Marie-Tooth disease, which are characterized by progressive fiber loss and replacement by fatty tissue. In Pompe disease, in which there is, in addition, an accumulation of glycogen inside the muscle fibers, MT has not been tested yet. Our aim is to estimate MT ratio (MTR) in the skeletal muscle of these patients and correlate it with intramuscular fat fraction (FF) and results of muscle function tests.Methods: We obtained two-point axial Dixon and Dixon-MT sequences of the right thigh on a 1.5 Teslas MRI scanner in 60 individuals, including 29 late onset Pompe disease patients, 2 patients with McArdle disease, and 29 age and sex matched healthy controls. FF and MTR were estimated. Muscle function using several muscle function tests, including quantification of muscle strength, timed test quality of life scales, conventional spirometry obtaining forced vital capacity while sitting and in the supine position, were assessed in all patients.Results: MTR was significantly lower in Pompe patients compared with controls (45.5 ± 8.5 vs. 51.7 ± 2.3, Student T-test, p < 0.05). There was a negative correlation between the MTR and FF muscles studied (correlation coefficient: −0.65, Spearman test: p < 0.05). MTR correlated with most of the muscle function test results. We analyzed if there was any difference in MTR values between Pompe patients and healthy controls in those muscles that did not have an increase in fat, a measure that could be related to the presence of glycogen in skeletal muscles, but we did not identify significant differences except in the adductor magnus muscle (48.4 ± 3.6 in Pompe vs. 51 ± 1.3 in healthy controls, Student T-test = 0.023).Conclusions: MTR is a sensitive tool to identify muscle loss in patients with Pompe disease and shows a good correlation with muscle function tests. Therefore, the MT technique can be useful in monitoring muscle degeneration in Pompe disease in clinical trials or natural history studies.

Microstructural Tissue Changes in Alzheimer Disease Brains: Insights from Magnetization Transfer Imaging.

Reductions in magnetization transfer ratio have been associated with brain microstructural damage. We aim to compare magnetization transfer ratio in global and regional GM and WM between individuals with Alzheimer disease and healthy control participants to analyze the relationship between magnetization transfer ratio and cognitive functioning in Alzheimer disease. In this prospective study, participants with Alzheimer disease and a group of age-matched healthy control participants underwent clinical examinations and 3T MR imaging. Magnetization transfer ratios were determined in the cortex, AD-signature regions, normal-appearing WM, and WM hyperintensities. Seventy-seven study participants (mean age ± SD, 72 ± 8 years; 47 female) and 77 age-matched healthy control participants (mean age ± SD, 72 ± 8 years; 44 female) were evaluated. Magnetization transfer ratio values were lower in patients with Alzheimer disease than in healthy control participants in all investigated regions. When adjusting for atrophy and extent of WM hyperintensities, significant differences were seen in the global cortex (OR = 0.47; 95% CI: 0.22, 0.97; P = .04), in Alzheimer disease-signature regions (OR = 0.31; 95% CI: 0.14, 0.67; P = .003), in normal-appearing WM (OR = 0.59; 95% CI: 0.39, 0.88; P = .01), and in WM hyperintensities (OR = 0.18; 95% CI: 0.09, 0.33; P ≤ .001). The magnetization transfer ratio in these regions was an independent determinant of AD. When correcting for atrophy and WM hyperintensity extent, lower GM magnetization transfer ratios were associated with poorer global cognition, language function, and constructional praxis. Alzheimer disease is associated with magnetization transfer ratio reductions in GM and WM regions of the brain. Lower magnetization transfer ratios in the entire cortex and AD-signature regions contribute to cognitive impairment independent of brain atrophy and WM damage.

Brain development in children with developmental delay using amide proton transfer-weighted imaging and magnetization transfer imaging.

ABSTRACTImportanceThe process of brain development in children with developmental delay is not well known. Amide proton transfer‐weighted (APTw) imaging is a novel molecular magnetic resonance imaging (MRI) technique that can noninvasively detect cytosolic endogenous mobile proteins and peptides involved in the myelination process, and may be useful for providing insights into brain development.ObjectiveTo assess the contribution of amide proton transfer‐weighted (APTw) imaging and magnetization transfer (MT) imaging to the evaluation of children with developmental delay (DD).MethodsFifty‐one patients with DD were recruited to this study. The patients were divided into two groups according to the state of myelination assessed on conventional magnetic resonance imaging (MRI). Thirty patients (10 girls, 20 boys; age range: 1–8 months; median age: 4 months) in group A showed delayed myelination on MRI, while 21 patients (3 girls, 18 boys; age range: 12–36months; median age: 25months) in group B showed normal myelination on MRI. Fifty‐one age‐ and sex‐matched children with normal developmental quotient (DQ) and normal MRI appearance were recruited as normal controls. Three‐slice APTw/MT axial imaging was performed at the level of the centrum semiovale, the basal ganglia and the pons. Quantitative data of the MT ratio (MTR) and APTw were analyzed for multiple brain regions. Independent‐sample t‐tests were used to compare differences in APTw and MTR signals between the two DD groups and normal controls. Analysis of Covariance was conducted to correct the statistical results. The level of statistical significance was set to P < 0.05.ResultsFor group A, the MTR values were lower in all regions (P = 0.004–0.033) compared with the normal controls, while the APTw values were higher in the pons, middle cerebellar peduncle, corpus callosum, frontal white matter, occipital white matter and centrum semiovale (P = 0.004–0.040 ). For Group B, the MTR values were slightly reduced, and the APTw values were slightly increased compared with the normal controls, but the differences were not statistically significant (P > 0.05).InterpretationFor DD patients showing signs of delayed myelination on MRI, MTR and APTw imaging can help to diagnose myelination delay by quantifying semi‐solid macromolecules and cytosolic endogenous mobile proteins and peptides at a molecular level, providing a new method for comprehensive evaluation of DD. For DD patients with normal myelination on MRI, the clinical values of MTR and APTw imaging remain to be explored.

MRI and pathology correlations in the medulla in sudden unexpected death in epilepsy (SUDEP): a postmortem study.

Sudden unexpected death in epilepsy (SUDEP) likely arises as a result of autonomic dysfunction around the time of a seizure. In vivo MRI studies report volume reduction in the medulla and other brainstem autonomic regions. Our aim, in a pathology series, is to correlate regional quantitative features on 9.4T MRI with pathology measures in medullary regions. Forty-seven medullae from 18 SUDEP, 18 nonepilepsy controls and 11 epilepsy controls were studied. In 16 cases, representing all three groups, ex vivo 9.4T MRI of the brainstem was carried out. Five regions of interest (ROI) were delineated, including the reticular formation zone (RtZ), and actual and relative volumes (RV), as well as T1, T2, T2* and magnetization transfer ratio (MTR) measurements were evaluated on MRI. On serial sections, actual and RV estimates using Cavalieri stereological method and immunolabelling indices for myelin basic protein, synaptophysin and Microtubule associated protein 2 (MAP2) were carried out in similar ROI. Lower relative RtZ volumes in the rostral medulla but higher actual volumes in the caudal medulla were observed in SUDEP (P<0.05). No differences between groups for T1, T2, T2* and MTR values in any region was seen but a positive correlation between T1 values and MAP2 labelling index in RtZ (P<0.05). Significantly lower MAP2 LI were noted in the rostral medulla RtZ in epilepsy cases (P<0.05). Rostro-caudal alterations of medullary volume in SUDEP localize with regions containing respiratory regulatory nuclei. They may represent seizure-related alterations, relevant to the pathophysiology of SUDEP.