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To assess the within-participant reliability and measurement error in the determination of MTR in the healthy human cervical spinal cord. A total of twenty healthy controls (10 male, mean ± sd age: 33.9 ± 3.5 years, 10 females, mean ± sd age: 47.5 ± 14.4 years), with no family history of any neurological disorders or a contraindication to MRI scanning were recruited over a period of two months. Each participant was scanned twice with a 3T MRI scanner using standard MTI sequences. Spinal Cord Toolbox (v5.4) was used for image post-processing. Data were first segmented and then registered to a template and then MTR was computed. The within-participant coefficients of variation (CV%), single and average within-participants intraclass correlation coefficients (ICC) and Bland–Altman plots were determined for MT values over the volume between the 2nd and 5th cervical vertebrae for the total WM and for specific WM regions: dorsal column (DC), ventral column (VC) and lateral column (LC). MTR showed poor to excellent within-participant reliability for the total WM, DC, VC and LC with single/average ICC values of 0.03/0.06, 0.10/0.18, 0.39/0.75, and 0.001/0.002, respectively, and the CV% reported an acceptable variation with values less than 10%. The Bland–Altman plots showed good within-participant agreement between the scan-rescan values. This study demonstrates that clinical trials using MTI technique are feasible and shows that quantitative MTI can monitor tissue changes in degenerative WM patients. MTI with its MTR index provide broad assessment of the integrity of white matter tissue and are being studied widely in brain as a diagnostic tool for the assessment of different neurological diseases. [ABSTRACT FROM AUTHOR]

Background The microstructural damage underlying compromise of white matter following treatment for pediatric brain tumors is unclear. We use multimodal imaging employing advanced diffusion tensor imaging (DTI) and magnetization transfer imaging (MTI) MRI methods to examine chronic microstructural damage to white matter in children and adolescents treated for pediatric brain tumor. Notably, MTI may be more sensitive to macromolecular content, including myelin, than DTI. Methods Fifty patients treated for brain tumors (18 treated with surgery ± chemotherapy and 32 treated with surgery followed by cranial–spinal radiation; time from diagnosis to scan ~6 years) and 45 matched healthy children completed both MTI and DTI scans. Voxelwise and region-of-interest approaches were employed to compare white matter microstructure metrics (magnetization transfer ratio (MTR); DTI— fractional anisotropy [FA], radial diffusivity [RD], axial diffusivity [AD], mean diffusivity [MD]) between patients and healthy controls. Results MTR was decreased across multiple white matter tracts in patients when compared to healthy children, P  < .001. These differences were observed for both patients treated with radiation and those treated with only surgery, P  < .001. We also found that children and adolescents treated for brain tumors exhibit decreased FA and increased RD/AD/MD compared to their healthy counterparts in several white matter regions, P s < .02. Finally, we observed that MTR and DTI metrics were related to multiple white matter tracts in patients, P s < .01, but not healthy control children. Conclusions Our findings provide evidence that the white matter damage observed in patients years after treatment of pediatric posterior fossa tumors, likely reflects myelin disruption. [ABSTRACT FROM AUTHOR]

Renal fibrosis is an important marker in the progression of chronic kidney disease, and renal biopsy is the current reference standard for detecting its presence. Currently, non-invasive methods have only been partially successful in detecting renal fibrosis. Magnetization transfer imaging (MTI) allows estimates of renal fibrosis but may vary with scanning conditions. We hypothesized that MTI-derived renal fibrosis would be reproducible at 1.5T and 3T MRI and over time in fibrotic kidneys. Fifteen pigs with unilateral renal artery stenosis (RAS, n = 9) or age-matched sham controls (n = 6) underwent MTI-MRI at both 1.5T and 3T 6 weeks post-surgery and again 4 weeks later. Magnetization transfer ratio (MTR) measurements of fibrosis in both kidneys were compared between 1.5T and 3T, and the reproducibility of MTI at the two timepoints was evaluated at 1.5T and 3T. MTR at 3T with 600 Hz offset frequency successfully distinguished between normal, stenotic, and contralateral kidneys. There was excellent reproducibility of MTI at 1.5T and 3T over the two timepoints and no significant differences between MTR measurements at 1.5T and 3T. Therefore, MTI is a highly reproducible technique which is sensitive to detect changes in fibrotic compared to normal kidneys in the RAS porcine model at 3T. [ABSTRACT FROM AUTHOR]

Preclinical imaging studies of posttraumatic epileptogenesis (PTE) have largely been proof-of-concept studies with limited animal numbers, and thus lack the statistical power for biomarker discovery. Epilepsy Bioinformatics Study for Antiepileptogenic Therapy (EpiBioS4Rx) is a pioneering multicenter trial investigating preclinical imaging biomarkers of PTE. EpiBios4Rx faced the issue of harmonizing the magnetic resonance imaging (MRI) procedures and imaging data metrics prior to its execution. We present here the harmonization process between three preclinical MRI facilities at the University of Eastern Finland (UEF), the University of Melbourne (Melbourne), and the University of California, Los Angeles (UCLA), and evaluate the uniformity of the obtained MRI data. Adult, male rats underwent a lateral fluid percussion injury (FPI) and were followed by MRI 2 days, 9 days, 1 month, and 5 months post-injury. Ex vivo scans of fixed brains were conducted 7 months post-injury as an end point follow-up. Four MRI modalities were used: T2-weighted imaging, multi-gradient-echo imaging, diffusion-weighted imaging, and magnetization transfer imaging, and acquisition parameters for each modality were tailored to account for the different field strengths (4.7 T and 7 T) and different MR hardwares used at the three participating centers. Pilot data collection resulted in comparable image quality across sites. In interim analysis (of data obtained by April 30, 2018), the within-site variation of the quantified signal properties was low, while some differences between sites remained. In T2-weighted images the signal-to-noise ratios were high at each site, being 35 at UEF, 48 at Melbourne, and 32 at UCLA (p

Background Myasthenia gravis (MG) is an autoimmune neuromuscular disorder that most frequently affects the extraocular muscles (EOMs), which causes symptoms such as ptosis and restricted eye movement. The EOMs in MG patients are representative of autoimmune inflammatory changes in muscle tissue. Currently, there is no reliable, and sensitive imaging technique for monitoring EOM changes to assist in the evaluation of underlying pathological changes. Methods This study included MG patients treated between March and November 2022 at the First Affiliated Hospital of Sun Yat-sen University. Healthy controls (matched by age and sex) were included. Participants underwent 3.0 T MRI with magnetization transfer imaging (MTI) and T2-mapping to measure the magnetization transfer ratio (MTR) and T2-mapping values in the superior, inferior, medial, and lateral rectus muscles. Comparisons were made between MG patients and healthy controls, and between MG subgroups with and without ophthalmoparesis. Results The MTR and T2-mapping values successfully reflected EOM fibrosis and inflammatory edema in MG patients. MG patients showed significantly higher MTR and T2-mapping values in the EOMs compared with healthy controls. MG patients with ophthalmoparesis exhibited a lower MTR but higher T2-mapping value compared with those without ophthalmoparesis. Combined MTR and T2-mapping values effectively distinguished between MG patients and healthy controls, and between different severities of EOM involvement, with a superior diagnostic accuracy compared with each parameter alone. Conclusion The combination of MTI and T2-mapping MRI techniques can provide key insight into the pathological changes in EOMs in MG patients. This approach enhances early diagnosis and treatment planning, and therefore may improve clinical outcomes., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: Biomarkers for Alzheimer's disease (AD) are crucial for early diagnosis and treatment monitoring once disease modifying therapies become available.Objective: This study aims to quantify the forward magnetization transfer rate (kfor) map from brain tissue water to macromolecular protons and use it to identify the brain regions with abnormal kfor in AD and AD progression.Methods: From the Cardiovascular Health Study (CHS) cognition study, magnetization transfer imaging (MTI) was acquired at baseline from 63 participants, including 20 normal controls (NC), 18 with mild cognitive impairment (MCI), and 25 AD subjects. Of those, 53 participants completed a follow-up MRI scan and were divided into four groups: 15 stable NC, 12 NC-to-MCI, 12 stable MCI, and 14 MCI/AD-to-AD subjects. kfor maps were compared across NC, MCI, and AD groups at baseline for the cross-sectional study and across four longitudinal groups for the longitudinal study.Results: We found a lower kfor in the frontal gray matter (GM), parietal GM, frontal corona radiata (CR) white matter (WM) tracts, frontal and parietal superior longitudinal fasciculus (SLF) WM tracts in AD relative to both NC and MCI. Further, we observed progressive decreases of kfor in the frontal GM, parietal GM, frontal and parietal CR WM tracts, and parietal SLF WM tracts in stable MCI. In the parietal GM, parietal CR WM tracts, and parietal SLF WM tracts, we found trend differences between MCI/AD-to-AD and stable NC.Conclusion: Forward magnetization transfer rate is a promising biomarker for AD diagnosis and progression. [ABSTRACT FROM AUTHOR]

Obstructive sleep apnea (OSA) is characterized by recurrent upper airway blockage, with continued diaphragmatic efforts to breathe during sleep. Brain structural changes in OSA appear in various regions, including white matter sites that mediate autonomic, mood, cognitive, and respiratory control. However, the relationships between brain white matter changes and disease severity in OSA are unclear. This study examines associations between an index of tissue integrity, magnetization transfer (MT) ratio values (which show MT between free and proton pools associated with tissue membranes and macromolecules), and disease severity (apnea-hypopnea index [AHI]) in OSA subjects. We collected whole-brain MT imaging data from 19 newly diagnosed, treatment-naïve OSA subjects (50.4 ± 8.6 years of age, 13 males, AHI 39.7 ± 24.3 events/hr], using a 3.0-Tesla MRI scanner. With these data, whole-brain MT ratio maps were calculated, normalized to common space, smoothed, and correlated with AHI scores by using partial correlation analyses (covariates, age and gender; P < 0.005). Multiple brain sites in OSA subjects, including superior and inferior frontal regions, ventral medial prefrontal cortex and nearby white matter, midfrontal white matter, insula, cingulate and cingulum bundle, internal and external capsules, caudate nuclei and putamen, basal forebrain, hypothalamus, corpus callosum, and temporal regions, showed principally lateralized negative correlations (P < 0.005). These regions showed significant correlations even with correction for multiple comparisons (cluster-level, family-wise error, P < 0.05), except for a few superior frontal areas. Predominantly negative correlations emerged between local MT values and OSA disease severity, indicating potential usefulness of MT imaging for examining the OSA condition. These findings indicate that OSA severity plays a significant role in white matter injury. © 2016 Wiley Periodicals, Inc.

Background: Diffuse axonal injury (DAI) is a frequent mechanism of traumatic brain injury (TBI) that triggers a sequence of parenchymal changes that progresses from focal axonal shear injuries up to inflammatory response and delayed axonal disconnection. Objective: The main purpose of this study is to evaluate changes in the axonal/myelinic content and the brain volume up to 12 months after TBI and to correlate these changes with neuropsychological results. Methods: Patients with DAI (n = 25) were scanned at three time points after trauma (2, 6, and 12 months), and the total brain volume (TBV), gray matter volume, and white matter volume (WMV) were calculated in each time point. The magnetization transfer ratio (MTR) for the total brain (TB MTR), gray matter (GM MTR), and white matter (WM MTR) was also quantified. In addition, Hopkins verbal learning test (HVLT), Trail Making Test (TMT), and Rey–Osterrieth Complex Figure test were performed at 6 and 12 months after the trauma. Results: There was a significant reduction in the mean TBV, WMV, TB MTR, GM MTR, and WM MTR between time points 1 and 3 (p <.05). There was also a significant difference in HVLT‐immediate, TMT‐A, and TMT‐B scores between time points 2 and 3. The MTR decline correlated more with the cognitive dysfunction than the volume reduction. Conclusion: A progressive axonal/myelinic rarefaction and volume loss were characterized, especially in the white matter (WM) up to 1 year after the trauma. Despite that, specific neuropsychological tests revealed that patients' episodic verbal memory, attention, and executive function improved during the study. The current findings may be valuable in developing long‐term TBI rehabilitation management programs. [ABSTRACT FROM AUTHOR]

Introduction: Quantitative microstructural MRI, such as myelin-sensitive magnetisation transfer ratio (MTR) or saturation (MTsat), axon-sensitive water diffusion Neurite Orientation Dispersion and Density Imaging (NODDI), and the aggregate g-ratio, may provide more specific markers of white matter integrity than conventional MRI for early patient stratification in relapsing-remitting multiple sclerosis (RRMS). The aim of this study was to determine the sensitivity of such markers to longitudinal pathological change within cerebral white matter lesions (WML) and normal-appearing white matter (NAWM) in recently diagnosed RRMS. Methods: Seventy-nine people with recently diagnosed RRMS, from the FutureMS longitudinal cohort, were recruited to an extended MRI protocol at baseline and one year later. Twelve healthy volunteers received the same MRI protocol, repeated within two weeks. Ethics approval and written informed consent were obtained.3T MRI included magnetisation transfer, and multi-shell diffusion-weighted imaging. NAWM and whole brain were segmented from 3D T1-weighted MPRAGE, and WML from T2-weighted FLAIR. MTR, MTsat, NODDI isotropic (ISOVF) and intracellular (ICVF) volume fractions, and g-ratio (calculated from MTsat and NODDI data) were measured within WML and NAWM. Brain parenchymal fraction (BPF) was also calculated.Longitudinal change in BPF and microstructural metrics was assessed with paired t-tests (α = 0.05) and linear mixed models, adjusted for confounding factors with False Discovery Rate (FDR) correction for multiple comparisons. Longitudinal changes were compared with test-retest Bland-Altman limits of agreement from healthy control white matter. The influence of longitudinal change on g-ratio was explored through post-hoc analysis in silico by computing g-ratio with realistic simulated MTsat and NODDI values. Results: In NAWM, g-ratio and ICVF increased, and MTsat decreased over one year (adjusted mean difference = 0.007, 0.005, and −0.057 respectively, all FDR-corrected p

Background The neurological condition known as multiple sclerosis (MS) is crippling and has a complicated pathogenesis as well as a wide range of clinical symptoms, including fatigue, difficulty walking, numbness or tingling, muscle spasms and spasticity, weakness, vision problems, dizziness and vertigo, bladder and bowel dysfunction, cognitive impairment, and emotional changes. The complete scope of MS pathology cannot be fully captured by conventional magnetic resonance imaging (MRI) sequences, which has led to the investigation of sophisticated MRI methods for better diagnosis and treatment. Objective This study aims to evaluate the clinical relevance of advanced MRI sequences in multiple sclerosis. Methodology A retrospective cohort study was conducted across multiple specialized medical centers renowned for treating neurological disorders, particularly multiple sclerosis, and involved 310 patients with diverse geography seeking treatment throughout 2022. Records were searched to obtain patient information, demographics, and treatment history. Descriptive statistics and t-tests were among the statistical studies that investigated relationships between MRI biomarkers and clinical factors to help with the diagnosis and treatment of MS. A p-value of <0.05 was significant. Results The research group consisted of 310 MS patients, the majority of whom were female (67.42%) and had a mean age of 34.7 years. With hypertension (14.52%) and hyperlipidemia (19.35%) as prevalent comorbidities, the majority of patients (72.26%) were on disease-modifying treatments. The results of advanced MRI showed that lesions with white matter had higher mean diffusivity (1.25 ± 0.15 mm²/s) on DWI, lesions with reduced magnetization transfer ratio (MTR) (0.15 ± 0.03) on MTI, and lesions with reduced fractional anisotropy (FA) (0.40 ± 0.08) on diffusion tensor imaging (DTI). Additionally, the blood oxygen level-dependent (BOLD) signals in cognitive processing regions (0.75 ± 0.10) on functional MRI were different from those with normal-appearing white matter (0.40 ± 0.08). Conclusion Advanced MRI sequences are essential for bettering MS diagnosis, prognosis, and treatment because they link imaging biomarkers to important clinical parameters, which improves patient care and quality of life., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Ethical Committee of District Head Quarter Teaching Hospital KDA Kohat issued approval 195/K-21. The study was approved by the Ethical Committee of DHQ, Teaching Hospital KDA Kohat, guaranteeing that ethical standards would be followed and that patient rights and privacy would be protected. Informed permission was not required due to the retrospective nature and use of de-identified patient data, minimizing biases and safeguarding patient privacy. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Siddiqui et al.)

Magnetic resonance imaging (MRI) is the gold standard for the detection of cerebral lesions in X-linked adrenoleukodystrophy (ALD). ALD is one of the most common peroxisomal disorders and is characterized by a defect in degradation of very long chain fatty acids (VLCFA), resulting in accumulation of VLCFA in plasma and tissues. The clinical spectrum of ALD is wide and includes adrenocortical insufficiency, a slowly progressive myelopathy in adulthood, and cerebral demyelination in a subset of male patients. Cerebral demyelination (cerebral ALD) can be treated with hematopoietic cell transplantation (HCT) but only in an early (pre- or early symptomatic) stage and therefore active MRI surveillance is recommended for male patients, both pediatric and adult. Although structural MRI of the brain can detect the presence and extent of cerebral lesions, it does not predict if and when cerebral demyelination will occur. There is a great need for imaging techniques that predict onset of cerebral ALD before lesions appear. Also, imaging markers for severity of myelopathy as surrogate outcome measure in clinical trials would facilitate drug development. New quantitative MRI techniques are promising in that respect. This review focuses on structural and quantitative imaging techniques—including magnetic resonance spectroscopy, diffusion tensor imaging, MR perfusion imaging, magnetization transfer (MT) imaging, neurite orientation dispersion and density imaging (NODDI), and myelin water fraction imaging—used in ALD and their role in clinical practice and research opportunities for the future. [ABSTRACT FROM AUTHOR]

Purpose: Comprehensive understanding glioma metabolic characters is of great help for patient management. We aimed to compare amide proton transfer imaging (APTw) and magnetization transfer imaging (MT) in predicting glioma malignancy and reflecting tumor proliferation. Methods: Thirty low-grade gliomas (LGGs) and 39 high-grade gliomas (HGGs) were prospectively included, of which 58 samples Ki-67 levels were quantified. Anatomical MRI, APTw, and MT were scanned, and magnetization transfer ratio (MTR) and asymmetric magnetic transfer ratio at 3.5 ppm (MTRasym(3.5ppm)) were calculated. ROIs were semi-automatically drawn with ImageJ, from which histogram features, including 5th, 25th, 50th, mean, 70th, 90th, and 95th percentiles were extracted. The independent t test was used to test differences in LGGs and HGGs, and correlations between histogram features and tumor grades, Ki-67 were revealed by Spearman's rank or Pearson's correlation analysis. Results: The maximum correlation coefficient (R) values of APTw were 0.526 (p < 0.001) with tumor grades and 0.397 (p < 0.001) with Ki-67 at 90th percentiles, while only 5th and 25th percentiles of MT significantly correlated with tumor grades. Moreover, APTw features were significantly different in LGGs and HGGs, except 5th percentile. The most significantly different feature was 95th percentile, providing the excellent AUC of 0.808. However, the best feature in MTR was 5th percentiles with AUC of 0.703. Combing 5th and 95th of APTw achieved highest AUC Of 0.837. Conclusions: Both APTw and MT provide quantitative information for tumor metabolite imaging. However, APTw supplys more specific information in reflecting glioma biological behaviors than MT, and well differentiates glioma malignancy. [ABSTRACT FROM AUTHOR]

Multiple advanced imaging methods for multiple sclerosis (MS) have been in investigation to identify new imaging biomarkers for early disease detection, predicting disease prognosis, and clinical trial endpoints. Multiple techniques probing different aspects of tissue microstructure (ie, advanced diffusion imaging, magnetization transfer, myelin water imaging, magnetic resonance spectroscopy, glymphatic imaging, and perfusion) support the notion that MS is a global disease with microstructural changes evident in normal-appearing white and gray matter. These global changes are likely better predictors of disability compared with lesion load alone. Emerging techniques in glymphatic and molecular imaging may improve understanding of pathophysiology and emerging treatments., Competing Interests: Disclosure The authors have no relevant financial disclosures., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Quantitative MRI modalities, such as diffusion tensor imaging (DTI) or magnetization transfer imaging (MTI) are sensitive to the neuronal effects of aging of the cerebral white matter (WM), but lack the specificity for myelin content. Myelin water imaging (MWI) is highly specific for myelin and may be more sensitive for the detection of changes in myelin content inside the cerebral WM microstructure. In this multiparametric imaging study, we evaluated the performance of myelin water fraction (MWF) estimates as a marker for myelin alterations during normal-aging. Multiparametric MRI data derived from DTI, MTI and a novel, recently-proposed MWF-map processing and reconstruction algorithm were acquired from 54 healthy subjects (aged 18–79 years) and region-based multivariate regression analysis was performed. MWFs significantly decreased with age in most WM regions (except corticospinal tract) and changes of MWFs were associated with changes of radial diffusivity, indicating either substantial alterations or preservation of myelin content in these regions. Decreases of fractional anisotropy and magnetization transfer ratio were associated with lower MWFs in commissural fiber tracts only. Mean diffusivity had no regional effects on MWF. We conclude that MWF estimates are sensitive for the assessment of age-related myelin alterations in the cerebral WM of normal-aging brains.

Friedreich ataxia is a progressive neurodegenerative disorder with reported abnormalities in cerebellar, brainstem, and cerebral white matter. White matter structure can be measured using in vivo neuroimaging indices sensitive to different white matter features. For the first time, we examined the relative sensitivity and relationship between multiple white matter indices in Friedreich ataxia to more richly characterize disease expression and infer possible mechanisms underlying the observed white matter abnormalities. Diffusion‐tensor, magnetization transfer, and T1‐weighted structural images were acquired from 31 individuals with Friedreich ataxia and 36 controls. Six white matter indices were extracted: fractional anisotropy, diffusivity (mean, axial, radial), magnetization transfer ratio (microstructure), and volume (macrostructure). For each index, whole‐brain voxel‐wise between‐group comparisons and correlations with disease severity, onset age, and gene triplet‐repeat length were undertaken. Correlations between pairs of indices were assessed in the Friedreich ataxia cohort. Spatial similarities in the voxel‐level pattern of between‐group differences across the indices were also assessed. Microstructural abnormalities were maximal in cerebellar and brainstem regions, but evident throughout the brain, while macroscopic abnormalities were restricted to the brainstem. Poorer microstructure and reduced macrostructural volume correlated with greater disease severity and earlier onset, particularly in peri‐dentate nuclei and brainstem regions. Microstructural and macrostructural abnormalities were largely independent. Reduced fractional anisotropy was most strongly associated with axial diffusivity in cerebral tracts, and magnetization transfer in cerebellar tracts. Multiple mechanisms likely underpin white matter abnormalities in Friedreich ataxia, with differential impacts in cerebellar and cerebral pathways. [ABSTRACT FROM AUTHOR]

Quantitative MRI modalities, such as diffusion tensor imaging (DTI) or magnetization transfer imaging (MTI) are sensitive to the neuronal effects of aging of the cerebral white matter (WM), but lack the specificity for myelin content. Myelin water imaging (MWI) is highly specific for myelin and may be more sensitive for the detection of changes in myelin content inside the cerebral WM microstructure. In this multiparametric imaging study, we evaluated the performance of myelin water fraction (MWF) estimates as a marker for myelin alterations during normal-aging. Multiparametric MRI data derived from DTI, MTI and a novel, recently-proposed MWF-map processing and reconstruction algorithm were acquired from 54 healthy subjects (aged 18–79 years) and region-based multivariate regression analysis was performed. MWFs significantly decreased with age in most WM regions (except corticospinal tract) and changes of MWFs were associated with changes of radial diffusivity, indicating either substantial alterations or preservation of myelin content in these regions. Decreases of fractional anisotropy and magnetization transfer ratio were associated with lower MWFs in commissural fiber tracts only. Mean diffusivity had no regional effects on MWF. We conclude that MWF estimates are sensitive for the assessment of age-related myelin alterations in the cerebral WM of normal-aging brains. [ABSTRACT FROM AUTHOR]

In this study, we investigated the utility of native T1 mapping in differentiating between various grades of fibrosis and compared its diagnostic accuracy to magnetization transfer imaging (MTI) in a rat model of CD. Bowel specimens (64) from 46 CD model rats undergoing native T1 mapping and MTI were enrolled. The longitudinal relaxation time (T1 value) and normalized magnetization transfer ratio (MTR) were compared between none-to-mild and moderate-to-severe fibrotic bowel walls confirmed by pathological assessments. The results showed that the correlation between the T1 value and fibrosis (r = 0.438, p < 0.001) was lower than that between the normalized MTR and fibrosis (r = 0.623, p < 0.001). Overall, the T1 values (t = −3.066, p = 0.004) and normalized MTRs (z = 0.081, p < 0.001) in none-to-mild fibrotic bowel walls were lower than those in moderate-to-severe fibrotic bowel walls. The area under the curve (AUC) of the T1 value (AUC = 0.716, p = 0.004) was significantly lower than that of the normalized MTR (AUC = 0.881, p < 0.001) in differentiating moderate-to-severe fibrosis from none-to-mild fibrosis (z = −2.037, p = 0.042). Our results support the view that the T1 value could be a promising imaging biomarker in grading the fibrosis severity of CD. However, the diagnostic performance of native T1 mapping was not superior to MTI.

At least 85% of individuals with multiple sclerosis report walking dysfunction as their primary complaint. Walking and strength measures are common clinical measures to mark increasing disability or improvement with rehabilitation. Previous studies have shown an association between strength or walking ability and spinal cord MRI measures, and strength measures with brainstem corticospinal tract magnetization transfer ratio. However, the relationship between walking performance and brain corticospinal tract magnetization transfer imaging measures and the contribution of clinical measurements of walking and strength to the underlying integrity of the corticospinal tract has not been explored in multiple sclerosis. The objectives of this study were explore the relationship of quantitative measures of walking and strength to whole-brain corticospinal tract-specific MRI measures and to determine the contribution of quantitative measures of function in addition to basic clinical measures (age, gender, symptom duration and Expanded Disability Status Scale) to structural imaging measures of the corticospinal tract. We hypothesized that quantitative walking and strength measures would be related to brain corticospinal tract-specific measures, and would provide insight into the heterogeneity of brain pathology. Twenty-nine individuals with relapsing-remitting multiple sclerosis (mean(SD) age 48.7 (11.5) years; symptom duration 11.9(8.7); 17 females; median[range] Expanded Disability Status Scale 4.0 [1.0–6.5]) and 29 age and gender-matched healthy controls (age 50.8(11.6) years; 20 females) participated in clinical tests of strength and walking (Timed Up and Go, Timed 25 Foot Walk, Two Minute Walk Test ) as well as 3 T imaging including diffusion tensor imaging and magnetization transfer imaging. Individuals with multiple sclerosis were weaker (p = 0.0024) and walked slower (p = 0.0013) compared to controls. Quantitative measures of walking and strength were significantly related to corticospinal tract fractional anisotropy (r > 0.26; p 0.29; p 0.05). Walk velocity was a significant contributor to magnetization transfer ratio (p = 0.006) and fractional anisotropy (p = 0.011) in regression modeling that included both quantitative measures of function and basic clinical information. Quantitative measures of strength and walking are associated with brain corticospinal tract pathology. The addition of these quantitative measures to basic clinical information explains more of the variance in corticospinal tract fractional anisotropy and magnetization transfer ratio than the basic clinical information alone. Outcome measurement for multiple sclerosis clinical trials has been notoriously challenging; the use of quantitative measures of strength and walking along with tract-specific imaging methods may improve our ability to monitor disease change over time, with intervention, and provide needed guidelines for developing more effective targeted rehabilitation strategies.

As age and Parkinson's disease (PD) both play a role in the degeneration of brain white matter, we aimed to investigate a possible interaction effect of age and disease presence on white matter integrity in patients with PD. We studied white matter hyperintensity volume, global fractional anisotropy, mean diffusivity and mean magnetization transfer ratio of normal appearing white matter in 163 patients with PD and 218 age- and gender-matched healthy control subjects. We investigated the relationship between age and these parameters in both groups, and interaction between age and disease presence. Patients with PD had a higher load of white matter hyperintensities with a preferential periventricular and anterior distribution as compared with healthy control subjects. Visuospatial functioning was related to total and postural instability and gait difficulty was related to periventricular white matter hyperintensity volume in patients with PD. The age-related decline of white matter integrity was similar for both groups. Global microstructural integrity of the normal appearing white matter did not differ between patients and healthy control subjects, suggesting that PD-specific changes do not exceed normal age-associated change in white matter without lesions. • Patients with PD had more white matter hyperintensities as compared with control subjects. • White matter hyperintensities had a preferential periventricular and anterior distribution in patients with PD. • The age-related decline of white matter integrity was similar for both groups. • Global microstructural integrity was relatively normal in patients with PD. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to investigate pathological mechanisms underlying brain tissue alterations in mild cognitive impairment (MCI) using multi-contrast 3 T magnetic resonance imaging (MRI). Methods: Forty-two MCI patients and 77 healthy controls (HC) underwent T1/T2* relaxometry as well as Magnetization Transfer (MT) MRI. Between-groups comparisons in MRI metrics were performed using permutation-based tests. Using MRI data, a generalized linear model (GLM) was computed to predict clinical performance and a support-vector machine (SVM) classification was used to classify MCI and HC subjects. Results: Multi-parametric MRI data showed microstructural brain alterations in MCI patients vs HC that might be interpreted as: (i) a broad loss of myelin/cellular proteins and tissue microstructure in the hippocampus (p ≤ 0.01) and global white matter (p

Systemic lupus erythematosus (SLE) is an autoimmune disease with multi-organ involvement and results in neurological and psychiatric (NP) symptoms in up to 40% of the patients. To date, the diagnosis of neuropsychiatric systemic lupus erythematosus (NPSLE) poses a challenge due to the lack of neuroradiological gold standards. In this study, we aimed to better localize and characterize normal appearing white matter (NAWM) changes in NPSLE by combining data from two quantitative MRI techniques, diffusion tensor imaging (DTI) and magnetization transfer imaging (MTI). 9 active NPSLE patients (37 ± 13 years, all females), 9 SLE patients without NP symptoms (44 ± 11 years, all females), and 14 healthy controls (HC) (40 ± 9 years, all females) were included in the study. MTI, DTI and fluid attenuated inversion recovery (FLAIR) images were collected from all subjects on a 3 T MRI scanner. Magnetization transfer ratio (MTR), mean diffusivity (MD), fractional anisotropy (FA), radial diffusivity (RD), axial diffusivity (AD) maps and white matter lesion maps based on the FLAIR images were created for each subject. MTR and DTI data were then co-analyzed using tract-based spatial statistics and a cumulative lesion map to exclude lesions. Significantly lower MTR and FA and significantly higher AD, RD and MD were found in NPSLE compared to HC in NAWM regions. The differences in DTI measures and in MTR, however, were only moderately co-localized. Additionally, significant differences in DTI measures, but not in MTR, were found between NPSLE and SLE patients, suggesting that the underlying microstructural changes detected by MD are linked to the onset of NPSLE. The co-analysis of the anatomical distribution of MTI and DTI measures can potentially improve the diagnosis of NPSLE and contribute to the understanding of the underlying microstructural damage.

Background: Identifying in vivo the processes that determine lesion severity in multiple sclerosis (MS) remains a challenge. Objectives: To describe the dynamics of ultrasmall superparamagnetic iron oxide (USPIO) enhancement in MS lesions and the relationship between USPIO enhancement and microstructural changes over 3 years. Methods: Lesion development was assessed at baseline, Months 3, 6, and 9, using magnetic resonance imaging (MRI) with gadolinium and USPIO. Microstructural changes were assessed at baseline, Months 3, 6, 9, 12, 18, 24, and 36, using relaxometry, magnetization transfer, and diffusion-weighted imaging. Results: We included 15 patients with clinically isolated syndrome. In the 52 MRI scans acquired with USPIO, 22 lesions were USPIO and gadolinium positive, and 44 were USPIO negative but gadolinium positive. Lesions no longer exhibited sustained USPIO enhancement 3 months later. At baseline, lesions that were both USPIO and gadolinium positive had lower magnetization transfer ratio values (common language effect size = 0.84, p = 0.0005) and lower fractional anisotropy values (0.83, p = 0.001) than gadolinium-positive-only lesions. USPIO-positive lesions remained associated with greater damage than gadolinium-positive-only lesions throughout the 3-year follow-up. Conclusion: USPIO enhancement, mainly reflecting monocyte infiltration, is transient and is associated with persistent tissue damage after 3 years. [ABSTRACT FROM AUTHOR]

As the use of ultra-high field (UHF; ≥7 T) magnetic resonance (MR) imaging expands, there is an increasing need to establish high-resolution MR imaging protocols for patients with neurological disease. Magnetization transfer (MT) imaging has been used to provide information about changes in the magnitude of the restricted protons that are caused by tissue damages. Several studies have found that MTR has a good sensitivity to measure changes in myelin concentration within the brain. Because of the much higher specific absorption rate (SAR) of tissue and longer acquisition time required for UHF, however, in-vivo studies using conventional pulsed MT sequences at UHF have not been well utilized. In this study, we introduce a new MT data acquisition approach using a 7 T MR system, variable density magnetization transfer (vdMT) imaging, which can be reasonably included in a routine patient scan protocol with a much shorter scan time and reduced discomfort to the patient. To reduce SAR and scan time while maintaining at least similar MTR image quality to that obtained with the conventional method, a higher density of MT RF pulses was applied in the center of k-space, and sparsely applied MT RF pulses were used in the outer part of k-space. The fraction of k-space receiving 100% MT RF density and TR were optimized based on in-vivo ROI analysis, and results were confirmed with high-resolution MTR map using a vdMT approach from healthy controls and patients with multiple sclerosis (MS). The experimental results confirmed that vdMT imaging can cover a whole brain volume in an acceptable scan time for routine patient scans while providing MTR image quality at least similar to that obtained with conventional MT imaging (correlation coefficient=0.95 in an agar-gel phantom [MT offset frequency=1 kH], 0.90 in a postmortem MS brain, and 0.85 in the 4 healthy volunteers). MS lesions were associated with signal reductions in the postmortem MS brains and in the patients with MS. In this study, we have described a new approach for acquiring high-resolution MTR map of the whole brain volume using 7 T MR imaging. This vdMT method provides similar image quality to that obtained with the conventional method, and shortens the scan time by reducing SAR. These results suggest that vdMT approach is a method that could be used for UHF scans of patients with neurological disease. [ABSTRACT FROM AUTHOR]

In multiple sclerosis (MS), inflammatory lesions present a broad spectrum of histopathologic processes. For a better discrimination, lesions are visually defined into different lesion groups according to their appearance on conventional magnetic resonance imaging (MRI). The aim of this study was to investigate the properties of different MS lesion groups using multiparametric quantitative MRI. 35 patients diagnosed with relapsing-remitting MS received 3 Tesla MRI including magnetization-prepared 2 rapid acquisition gradient echo, diffusion tensor imaging and magnetization transfer imaging. Lesion segmentation was performed for T2 lesions, black holes and contrast-enhancing lesions. A subtraction mask was created including only T2 lesions that did not correspond to a black hole or contrast-enhancing lesion. T1 relaxation time (T1-RT), magnetization transfer ratio (MTR), mean diffusivity (MD) and fractional anisotropy (FA) were determined for every lesion and in normal-appearing white matter. Only MD differed significantly between all lesion groups and NAWM ( p < 0.05), while FA differed between all lesion groups but not NAWM. T1-RT and MTR were not useful imaging biomarkers to distinguish between lesion groups. A lack of sensitivity and specificity and unproportional alterations of quantitative MRI measures, due to heterogenous histopathologic processes within lesions, may be a possible explanation for missing discrimination. Thus, not only interpretation of visually defined MS lesion but also interpretation of quantitative MRI measures remains challenging and should be conducted carefully. [ABSTRACT FROM AUTHOR]

Purpose: To assess the use of functional magnetic resonance imaging (MRI), including diffusion-weighted MRI (DWI) and magnetization transfer MRI (MTI) in evaluating male infertility.Materials and Methods: Sixteen men with testicular spermatogenesis hypofunction confirmed by percutaneous testis biopsy and 31 volunteers (control group B, age range: 20-40 years) with normal semen analysis including younger (By, n = 15, age range: 20-30 years) and older (Bo, n = 16, age range: 31-40 years) men underwent pelvic 3T MRI, including DWI and MTI. Apparent diffusion coefficient (ADC) and magnetization transfer ratio (MTR) were compared.Results: The ADCs in 32 testes of 16 patients (0.497 ± 0.037 × 10-3 mm2 /s) were significantly (P < 0.001) higher than that of control group B (0.460 ± 0.031 × 10-3 mm2 /s), group By (0.453 ± 0.018 × 10-3 mm2 /s), and group Bo (0.461 ± 0.034 × 10-3 mm2 /s), whereas the MTRs were significantly lower than that of group B (16.14 ± 4.20), group By (17.88 ± 2.00), and group Bo (15.09 ± 4.28) (P < 0.001).Conclusion: Functional MRI, including DWI and MTI, appears promising for evaluating male infertility with higher ADC and lower MTR in testicular spermatogenesis hypofunction.Level Of Evidence: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:186-190. [ABSTRACT FROM AUTHOR]

Background and purposeHuntington’s disease (HD) is a chronic progressive neurodegenerative disorder with a long presymptomatic period that opens a window for potential therapies aimed at neuroprotection. Neuroimaging offers the potential to monitor disease-related progression of the disease burden (DB) using model-based magnetization transfer imaging.Materials and methodsWe have conducted a cross-sectional study to stratify healthy age-matched controls, premanifest and symptomatic HD patients (n = 30) according to their macromolecular depositions in the caudate nucleus. We employed a binary spin-bath magnetization transfer (MT) method for a quantitative description of macromolecule deposits and interactions with their adjacent environment.ResultsA region-of-interest based fuzzy clustering analysis identified representative clusters for several stages of the disease course related to its progression: one cluster represented subjects with a high DB 230 and healthy controls. Three further clusters represented transition zones between both DB levels (230–268) consisting of presymptomatic carriers with DB values increasing with decreasing distance from the cluster that indicated low DB and healthy age-matched controls.ConclusionThe proposed binary spin-bath MT method offers the potential to monitor DB and progression in HD. The method may augment qualitative MT techniques since it depicts tissue changes related to interactions between macromolecules and protons in disease specific brain regions that follow the neurodegenerative process.

ObjectiveQuantitative and semi-quantitative MRI (qMRI) metrics provide complementary specificity and differential sensitivity to pathological brain changes compatible with brain inflammation, degeneration, and repair. Moreover, advanced magnetic resonance imaging (MRI) metrics with overlapping elements amplify the true tissue-related information and limit measurement noise. In this work, we combined multiple advanced MRI parameters to assess focal and diffuse brain changes over 2 years in a group of early-stage relapsing-remitting MS patients.MethodsThirty relapsing-remitting MS patients with less than 5 years disease duration and nine healthy subjects underwent 3T MRI at baseline and after 2 years including T1, T2, T2* relaxometry, and magnetization transfer imaging. To assess longitudinal changes in normal-appearing (NA) tissue and lesions, we used analyses of variance and Bonferroni correction for multiple comparisons. Multivariate linear regression was used to assess the correlation between clinical outcome and multiparametric MRI changes in lesions and NA tissue.ResultsIn patients, we measured a significant longitudinal decrease of mean T2 relaxation times in NA white matter (p = 0.005) and a decrease of T1 relaxation times in the pallidum (p 0.4, p

Objective: Quantitative and semi-quantitative MRI (qMRI) metrics provide complementary specificity and differential sensitivity to pathological brain changes compatible with brain inflammation, degeneration, and repair. Moreover, advanced magnetic resonance imaging (MRI) metrics with overlapping elements amplify the true tissue-related information and limit measurement noise. In this work, we combined multiple advanced MRI parameters to assess focal and diffuse brain changes over 2 years in a group of early-stage relapsing-remitting MS patients. Methods: Thirty relapsing-remitting MS patients with less than 5 years disease duration and nine healthy subjects underwent 3T MRI at baseline and after 2 years including T1, T2, T2* relaxometry, and magnetization transfer imaging. To assess longitudinal changes in normal-appearing (NA) tissue and lesions, we used analyses of variance and Bonferroni correction for multiple comparisons. Multivariate linear regression was used to assess the correlation between clinical outcome and multiparametric MRI changes in lesions and NA tissue. results: In patients, we measured a significant longitudinal decrease of mean T2 relaxation times in NA white matter (p = 0.005) and a decrease of T1 relaxation times in the pallidum (p < 0.05), which are compatible with edema reabsorption and/or iron deposition. No longitudinal changes in qMRI metrics were observed in controls. In MS lesions, we measured a decrease in T1 relaxation time (p-value < 2.2e-16) and a significant increase in MTR (p-value < 1e-6), suggesting repair mechanisms, such as remyelination, increased axonal density, and/or a gliosis. Last, the evolution of advanced MRI metrics--and not changes in lesions or brain volume--were correlated to motor and cognitive tests scores evolution (Adj-R2 > 0.4, p < 0.05). In summary, the combination of multiple advanced MRI provided evidence of changes compatible with focal and diffuse brain repair at early MS stages as suggested by histopathological studies. [ABSTRACT FROM AUTHOR]

Background and purpose: Huntington's disease (HD) is a chronic progressive neurodegenerative disorder with a long presymptomatic period that opens a window for potential therapies aimed at neuroprotection. Neuroimaging offers the potential to monitor disease-related progression of the disease burden (DB) using model-based magnetization transfer imaging. Materials and methods: We have conducted a cross-sectional study to stratify healthy age-matched controls, premanifest and symptomatic HD patients (n = 30) according to their macromolecular depositions in the caudate nucleus. We employed a binary spinbath magnetization transfer (MT) method for a quantitative description of macromolecule deposits and interactions with their adjacent environment. Results: A region-of-interest based fuzzy clustering analysis identified representative clusters for several stages of the disease course related to its progression: one cluster represented subjects with a high DB <268 that encompassed all symptomatic HD patients and one presymptomatic gene carrier. The next cluster represented the presymptomatic gene carriers with a very low DB >230 and healthy controls. Three further clusters represented transition zones between both DB levels (230-268) consisting of presymptomatic carriers with DB values increasing with decreasing distance from the cluster that indicated low DB and healthy age-matched controls. Conclusion: The proposed binary spin-bath MT method offers the potential to monitor DB and progression in HD. The method may augment qualitative MT techniques since it depicts tissue changes related to interactions between macromolecules and protons in disease specific brain regions that follow the neurodegenerative process. [ABSTRACT FROM AUTHOR]

The increasing prevalence of tuberculosis in both immunocompetent and immunocompromised individuals in recent years makes the disease a topic of universal concern. It has insidious onset and can affect virtually any organ system in the body, including the central nervous system (CNS). CNS tuberculosis (TB) is becoming more and more complex and atypical with onset of multidrug-resistant TB. Routine diagnostic techniques using serology and body tissue are time consuming and may delay the definitive management. Hence, it is important to be familiar with various radiologic features of CNS TB to ensure early and accurate diagnosis, thereby reducing high morbidity and mortality associated with the disease. The newer imaging techniques further help to improve the characterization and diagnosis of atypical CNS TB. The authors review the imaging characteristics of different forms of CNS tuberculosis involving the brain and spine and discuss the role of advanced imaging modalities in differentiating CNS TB from other disease process. [ABSTRACT FROM AUTHOR]

The g-ratio, quantifying the ratio between the inner and outer diameters of a fiber, is an important microstructural characteristic of fiber pathways and is functionally related to conduction velocity. We introduce a novel method for estimating the MR g-ratio non-invasively across the whole brain using high-fidelity magnetization transfer (MT) imaging and single-shell diffusion MRI. These methods enabled us to map the MR g-ratio in vivo across the brain’s prominent fiber pathways in a group of 37 healthy volunteers and to estimate the inter-subject variability. Effective correction of susceptibility-related distortion artifacts was essential before combining the MT and diffusion data, in order to reduce partial volume and edge artifacts. The MR g-ratio is in good qualitative agreement with histological findings despite the different resolution and spatial coverage of MRI and histology. The MR g-ratio holds promise as an important non-invasive biomarker due to its microstructural and functional relevance in neurodegeneration.