Lower Magnetization Transfer Ratio Research Articles

Optic chiasm involvement in multiple sclerosis, aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder and myelin oligodendrocyte glycoprotein–associated disease

Background: Optic neuritis (ON) is a common feature of inflammatory demyelinating diseases (IDDs) such as multiple sclerosis (MS), aquaporin 4-antibody neuromyelitis optica spectrum disorder (AQP4 + NMOSD) and myelin oligodendrocyte glycoprotein antibody–associated disease (MOGAD). However, the involvement of the optic chiasm (OC) in IDD has not been fully investigated. Aims: To examine OC differences in non-acute IDD patients with (ON+) and without ON (ON−) using magnetisation transfer ratio (MTR), to compare differences between MS, AQP4 + NMOSD and MOGAD and understand their associations with other neuro-ophthalmological markers. Methods: Twenty-eight relapsing-remitting multiple sclerosis (RRMS), 24 AQP4 + NMOSD, 28 MOGAD patients and 32 healthy controls (HCs) underwent clinical evaluation, MRI and optical coherence tomography (OCT) scan. Multivariable linear regression models were applied. Results: ON + IDD patients showed lower OC MTR than HCs (28.87 ± 4.58 vs 31.65 ± 4.93; p = 0.004). When compared with HCs, lower OC MTR was found in ON + AQP4 + NMOSD (28.55 ± 4.18 vs 31.65 ± 4.93; p = 0.020) and MOGAD (28.73 ± 4.99 vs 31.65 ± 4.93; p = 0.007) and in ON− AQP4 + NMOSD (28.37 ± 7.27 vs 31.65 ± 4.93; p = 0.035). ON+ RRMS had lower MTR than ON− RRMS (28.87 ± 4.58 vs 30.99 ± 4.76; p = 0.038). Lower OC MTR was associated with higher number of ON (regression coefficient (RC) = −1.15, 95% confidence interval (CI) = −1.819 to −0.490, p = 0.001), worse visual acuity (RC = −0.026, 95% CI = −0.041 to −0.011, p = 0.001) and lower peripapillary retinal nerve fibre layer (pRNFL) thickness (RC = 1.129, 95% CI = 0.199 to 2.059, p = 0.018) when considering the whole IDD group. Conclusion: OC microstructural damage indicates prior ON in IDD and is linked to reduced vision and thinner pRNFL.

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).

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.

Smoking, cardiovascular risk factors and LRP2 gene variation: Associations with disease severity, cognitive function and brain structure in primary progressive multiple sclerosis

BackgroundSmoking, cardiovascular risk factors, and genetic factors can have adverse effects in MS. ObjectiveTo determine if smoking after disease onset, cardiovascular risk factors, and genetic variants influence primary progressive MS (PPMS). MethodIn this cross-sectional study, smoking habits, Framingham Risk Score (FRS), genetic variants, including the low-density lipoprotein receptor-related protein 2 (LRP2) SNP rs12988804 and MRI were collected in 60 PPMS trial participants. Disability and cognition were assessed with the Age-Related Multiple Sclerosis Severity (ARMSS) score, the Progressive-Onset MS Multiple Sclerosis Severity Score, and the Brief International Cognitive Assessment for MS. ResultsSmoking after PPMS onset was significantly associated with higher ARMSS (95% CI 0.8–2.4, p = 0.00016) statistically significant after Bonferroni correction. Lower magnetization transfer ratio in lesions was also significantly associated with smoking after onset of PPMS after correction (95% CI -0.9–-4.4, p = 0.0035). Pack-years in people who smoked after onset was likewise significantly associated with higher ARMSS score (b = 0.06 95% CI 0.02–0.09, p = 0.0021) as well as lower Symbol Digit Modalities Test scores (b = -0.40; 95% CI -0.66–-0.13, p = 0.0037), both statistically significant after Bonferroni correction. The LRP2 risk allele was associated with decreased performance on the California Verbal Learning Test 2 after correction (CC vs. CT+TT 95% CI -14.2–-3.4, p = 0.0018). ConclusionIf validated, these findings suggest that intervention regarding smoking may be beneficial in PPMS. If confirmed, assessment of the LRP2 gene variant may aid in the understanding of underlying pathological mechanisms in PPMS.

Magnetisation transfer imaging revealed microstructural changes related to apathy symptoms after ischaemic stroke.

Apathy after stroke is common and has a negative impact on functional recovery. Neuroimaging correlates of poststroke apathy remain unclear. We aimed to investigate microstructural changes associated with the severity of poststroke apathy symptoms. We assessed 67 patients with cerebral ischaemia who underwent magnetisation transfer brain imaging 12-15 months after stroke. We used magnetisation transfer ratio (MTR) to represent microstructural integrity. We performed whole-brain voxel-based analysis and subsequent region of interest analysis to investigate the association between MTR and symptoms of poststroke apathy. To assess apathy symptoms, we used clinician-reported version of the Apathy Evaluation Scale. Voxel-based analysis showed the association between symptoms of apathy and decreased MTR in areas overlapping with structures located in both hemispheres: left thalamus, bilateral hippocampus, bilateral fornix/stria terminalis, right amygdala, splenium of the corpus callosum, the retrolenticular part of left internal capsule and left sagittal stratum. In the region of interest analysis, only lower MTR in right fornix/stria terminalis was associated with greater poststroke apathy symptoms in a multivariate logistic model (odds ratio: 1.25, 95% CI: 1.09-1.46, p=0.003). These associations were independent of depressive symptoms. Magnetisation transfer brain imaging 12-15 months after stroke revealed changes in microstructural integrity associated with apathy symptoms in brain areas related to processing emotional information and reward valuation.

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.

Magnetization transfer and diffusion tensor imaging in dogs with intervertebral disk herniation.

BackgroundQuantitative magnetic resonance imaging (QMRI) techniques of magnetization transfer ratio (MTR) and diffusion tensor imaging (DTI) provide microstructural information about the spinal cord.ObjectiveCompare neurologic grades using the modified Frankel scale with MTR and DTI measurements in dogs with thoracolumbar intervertebral disk herniation (IVDH).AnimalsFifty‐one dogs with thoracolumbar IVDH.MethodsProspective cohort study. Quantitative MRI measurements of the spinal cord were obtained at the region of compression. A linear regression generalized estimating equations model was used to compare QMRI measurements between different neurological grades after adjusting for age, weight, duration of clinical signs, and lesion location.ResultsGrade 5 (.79 × 10−3 mm2/s [median], .43−.91 [range]) and axial (1.47 × 10−3 mm2/s, .58−1.8) diffusivity were lower compared to grades 2 (1.003, .68−1.36; P = .02 and 1.81 × 10−3 mm2/s, 1.36−2.12; P < .001, respectively) and 3 (1.07 × 10−3 mm2/s, .77−1.5; P = .04 and 1.92 × 10−3 mm2/s, 1.83−2.37;P < .001, respectively). Compared to dogs with acute myelopathy, chronic myelopathy was associated with higher mean (1.02 × 10−3 mm2/s, .77−1.36 vs. .83 × 10−3 mm2/s, .64−1.5; P = .03) and radial diffusivity (.75 × 10−3 mm2/s, .38−1.04 vs. .44 × 10−3 mm2/s, .22−1.01; P = .008) and lower MTR (46.76, 31.8−56.43 vs. 54.4, 45.2−62.27; P = .004) and fractional anisotropy (.58, .4−0.75 vs. .7, .46−.85; P = .02). Fractional anisotropy was lower in dogs with a T2‐weighted intramedullary hyperintensity compared to those without (.7, .45−.85 vs. .54, .4−.8; P = .01).Conclusion and Clinical RelevanceMean diffusivity and AD could serve as surrogates of severity of spinal cord injury and are complementary to the clinical exam in dogs with thoracolumbar IVDH.

Pathologic correlates of the magnetization transfer ratio in multiple sclerosis.

To identify pathologic correlates of magnetization transfer ratio (MTR) in multiple sclerosis (MS) in an MRI-pathology study. We acquired MTR maps at 3T from 16 fixed MS brains and 4 controls, and immunostained 100 tissue blocks for neuronal neurofilaments, myelin (SMI94), tissue macrophages (CD68), microglia (IBA1), B-lymphocytes, T-lymphocytes, cytotoxic T-lymphocytes, astrocytes (glial fibrillary acidic protein), and mitochondrial damage (COX4, VDAC). We defined regions of interest in lesions, normal-appearing white matter (NAWM), and cortical normal-appearing gray matter (NAGM). Associations between MTR and immunostaining intensities were explored using linear mixed-effects models (with cassettes nested within patients) and interaction terms (for differences between regions of interest and between cases and controls); a multivariate linear mixed-effects model identified the best pathologic correlates of MTR. MTR was the lowest in white matter (WM) lesions (23.4 ± 9.4%) and the highest in NAWM (38.1 ± 8.7%). In MS brains, lower MTR was associated with lower immunostaining intensity for myelin (coefficient 0.31; 95% confidence interval [CI] 0.07-0.55), macrophages (coefficient 0.03; 95% CI 0.01-0.07), and astrocytes (coefficient 0.51; 95% CI 0.02-1.00), and with greater mitochondrial damage (coefficient 0.31; 95% CI 0.07-0.55). Based on interaction terms, MTR was more strongly associated with myelin in WM (coefficient 1.58; 95% CI 1.09-2.08) and gray matter (GM) lesions (coefficient 0.66; 95% CI 0.13-1.20), and with macrophages (coefficient 1.40; 95% CI 0.56-2.25), astrocytes (coefficient 2.66; 95% CI 1.31-4.01), and mitochondrial damage (coefficient -12.59; 95% CI -23.16 to -2.02) in MS brains than controls. In the multivariate model, myelin immunostaining intensity was the best correlate of MTR (coefficient 0.31; 95% CI 0.09-0.52; p = 0.004). Myelin was the strongest correlate of MTR, especially in WM and cortical GM lesions, but additional correlates should be kept in mind when designing and interpreting MTR observational and experimental studies in MS.

Quantitative MRI of cerebral white matter hyperintensities: A new approach towards understanding the underlying pathology

Interest in white matter hyperintensities (WMH), a radiological biomarker of small vessel disease, is continuously increasing. This is, in most part, due to our better understanding of their association with various clinical disorders, such as stroke and Alzheimer’s disease, and the overlapping pathology of WMH with these afflictions. Although post-mortem histological studies have reported various underlying pathophysiological substrates, in vivo research has not been specific enough to fully corroborate these findings. Furthermore, post-mortem studies are not able to capture which pathological processes are the driving force of the WMH severity. The current study attempts to fill this gap by non-invasively investigating the influence of WMH on brain tissue using quantitative MRI (qMRI) measurements of the water content (H2O), the longitudinal (T1) and effective transverse relaxation times (T2∗), as well as the semi-quantitative magnetization transfer ratio (MTR), and bound proton fraction (ƒbound). In total, seventy subjects (age range 50–80 years) were selected from a population-based aging cohort study, 1000BRAINS. Normal appearing grey (NAGM) and white matter (NAWM), as well as deep (DWMH) and periventricular (PWMH) white matter hyperintensities, were segmented and characterized in terms of their quantitative properties. The subjects were then further divided into four grades according to the Fazekas rating scale of severity. Groupwise analyses of the qMRI values in each tissue class were performed. All five qMRI parameters showed significant differences between WMH and NAWM (p < 0.001). Importantly, the parameters differed between DWMH and PWMH, the latter having higher H2O, T1, T2∗ and lower MTR and ƒbound values (p < 0.001). Following grading according to the Fazekas scale, DWMH showed an increase in the water content, T1 and a decrease in bound proton fraction corresponding to severity, exhibiting significant changes in grade 3 (p < 0.001), while NAWM revealed significantly higher H2O values in grade 3 compared to grade 0 (p < 0.001). PWMH demonstrated an increase in T2∗ values (significant in grade 3, P < 0.001). These results are in agreement with previous histopathological studies and support the interpretation that both edema and myelin loss due to a possible breakdown of the blood-brain barrier and inflammation are the major pathological substrates turning white matter into DWMH. Edema being an earlier contributing factor to the pathology, as expressed in the elevated water content values in NAWM with increasing severity. In the case of PWMH, an altered fluid dynamic and cerebrospinal fluid leakage exacerbate the changes. It was also found that the pathology, as monitored by qMRI, evolves faster in DWMH than in the PWMH following the severity.

Handedness Side and Magnetization Transfer Ratio in the Primary Sensorimotor Cortex Central Sulcus.

Left-handers show lower asymmetry in manual ability when compared to right-handers. Unlike right-handers, left-handers do not show larger deactivation of the ipsilateral primary sensorimotor (SM1) cortex on functional magnetic resonance imaging when moving their dominant than their nondominant hand. However, it should be noted that morphometric MRI studies have reported no differences between right-handers and left-handers in volume, thickness, or surface area of the SM1 cortex. In this regard, magnetization transfer (MT) imaging is a technique with the potential to provide information on microstructural organization and macromolecular content of tissue. In particular, MT ratio index of the brain gray matter is assumed to reflect the variable content of afferent or efferent myelinated fibers, with higher MT ratio values being associated with increased fibers number or degree of myelination. The aim of this study was hence to assess, for the first time, through quantitative MT ratio measurements, potential differences in microstructural organization/characteristics of SM1 cortex between left- and right-handers, which could underlay handedness side. Nine left-handed and 9 right-handed healthy subjects, as determined by the Edinburgh handedness inventory, were examined with T1-weighted and MT-weighted imaging on a 3 T scanner. The hands of subjects were kept still during all acquisitions. Using FreeSurfer suite and the automatic anatomical labeling parcellations defined by the Destrieux atlas, we measured MT ratio, as well as cortical thickness, in three regions of interests corresponding to the precentral gyrus, the central sulcus, and the postcentral gyrus in the bilateral SM1 cortex. No significant difference between left- and right-handers was revealed in the thickness of the three partitions of the SM1 cortex. However, left-handers showed a significantly (p = 0.007) lower MT ratio (31.92% ± 0.96%) in the right SM1 central sulcus (i.e., the hand representation area for left-handers) as compared to right-handers (33.28% ± 0.94%). The results of this preliminary study indicate that quantitative MT imaging, unlike conventional morphometric MRI measurements, can be a useful tool to reveal, in SM1 cortex, potential microstructural correlates of handedness side.

Magnetic resonance imaging of noradrenergic neurons

Noradrenaline is a neurotransmitter involved in general arousal, selective attention, memory, inflammation, and neurodegeneration. The purpose of this work was to delineate noradrenergic neurons in vivo by T1-weighted MRI with magnetization transfer (MT). In the brainstem of human and mice, MRI identified the locus coeruleus, dorsal motor vagus nucleus, and nucleus tractus solitarius. Given (1) the long T1 and low magnetization transfer ratio for the noradrenergic cell groups compared to other gray matter, (2) significant correlation between MT MRI signal intensity and proton density, and (3) no correlation between magnetization transfer ratio (or R1) and iron, copper, or manganese in human brain, the high MRI signal of the noradrenergic neurons must be attributed to abundant water protons interacting with any T1-shortening paramagnetic ions in active cells rather than to specific T1-shortening molecules. The absence of a high MRI signal from the locus coeruleus of Ear2(−/−) mice lacking noradrenergic neurons confirms that cell bodies of noradrenergic neurons are the source of the bright MRI appearance. The observation of this high signal in DBH(−/−) mice, in 3-week-old mice, and in mice under hyperoxia/hypercapnia/hypoxia together with the general absence of neuromelanin (NM) in noradrenergic neurons of young rodents further excludes that it is due to NM, dopamine β-hydroxylase, their binding to paramagnetic ions, blood inflow, or hemoglobin. Instead, these findings indicate a high density of water protons whose T1 is shortened by paramagnetic ions as the relevant source of the high MRI signal. In the brain of APP/PS1/Ear2(−/−) mice, a transgenic model of Alzheimer’s disease, MRI detected noradrenergic neuron loss in the locus coeruleus. Proton magnetic resonance spectroscopy revealed that a 60–75% reduction of noradrenaline is responsible for a reduction of N-acetylaspartate and glutamate in the hippocampus as well as for a shortening of the water proton T2 in the frontal cortex. These results suggest that a concurrent shortage of noradrenaline in Alzheimer’s disease accelerates pathologic processes such as inflammation and neuron loss.

Evaluation of normal cadaveric Achilles tendon and enthesis with ultrashort echo time (UTE) magnetic resonance imaging and indentation testing.

Entheses are regions where tendons and ligaments attach to bone, and are the primary target in seronegative and other diseases of the musculoskeletal (MSK) system. MRI has been widely used for visualizing features of inflammatory and degenerative MSK disease; however, normal tendons and entheses have short transverse relaxation times (T2 ), and show little or no signal with conventional clinical MRI pulse sequences, making it difficult to investigate their MR properties. In this study we examined the normal MR morphology of the cadaveric Achilles tendon and enthesis at 3T using novel three-dimensional ultrashort echo time (3D UTE) Cones sequences, and at 11.7T using conventional MRI sequences. We also studied the MR properties of the Achilles tendon and enthesis including T2 *, T1 , and magnetization transfer ratio (MTR). In addition, MT modeling of macromolecular proton fractions was investigated using 3D UTE Cones sequences at 3T. Indentation testing was performed to investigate the mechanical properties of the tendons and entheses, and this was followed by histological examination. In total five specimens (<50years) were investigated. On average, tendons and entheses respectively had T2 * values of 0.93±0.48ms and 2.77±0.79ms, T1 values of 644±22ms and 780±55ms, MTRs of 0.373±0.03 and 0.244±0.009 with an MT power of 1000° and frequency offset of 2kHz, and macromolecular proton fractions of 18.0±2.2% and 13.9±1.9%. Compared with the tendon, the enthesis generally had a longer T2 *, a longer T1 , a lower MTR, and a lower macromolecular proton fraction as well as both a higher Young's modulus and stiffness. Results from this study are likely to provide a useful baseline for identifying deviations from the normal in seronegative arthritis and other disease of the entheses.

Impaired biophysical integrity of macromolecular protein pools in the uncinate circuit in late-life depression

Major depressive disorder is a common mood disorder in the elderly. Although the neuroanatomical abnormalities have been identified in patients with late-life depression (LLD), the precise biological basis of LLD remains largely unknown. The purpose of this study was to examine the biophysical integrity of macromolecular protein pools in the nodal regions of the "uncinate circuit," a component of fronto-limbic circuitry that is connected by the uncinate fasciculus and is critical in the regulation of mood and emotions, using novel magnetization transfer (MT) imaging. Twenty-four patients with LLD and 27 non-depressed healthy control subjects (HCs) of comparable age, sex, and race were recruited from the communities of the greater Chicago Area. The nodal regions of the uncinate circuit, i.e., bilateral amygdala, hippocampus, and lateral and medial orbitofrontal cortices (OFCs), were examined. Compared with HCs, patients with LLD had significantly lower magnetization transfer ratio (MTR), a measure of the biophysical integrity of macromolecular protein pools, in bilateral amygdala and hippocampus. The lower MTR was negatively correlated with the depression score. Moreover, the MTR of these regions decreased with age and positively correlated with neuropsychological performance in the LLD group but not in the HC group. These findings suggest that LLD is associated with compromised biophysical integrity of macromolecular protein pools in nodal regions of the uncinate circuit, and that major depression may accentuate age-related attenuation of the biophysical integrity of macromolecular protein pools in this circuit. These findings provide important new insights into the neurobiological mechanisms of the pathophysiology of LLD.

High-resolution magnetization transfer MRI in patients with cervical spondylotic myelopathy

Magnetization transfer (MT) contrast has been established as a marker of myelin integrity, and cervical spondylotic myelopathy is known to cause demyelination. Ten patients with clinical and magnetic resonance imaging (MRI) manifestations of cervical spondylotic myelopathy (CSM) were compared to the MRIs of seven historic healthy controls, using the magnetization transfer ratio (MTR) and Nurick scores as the primary metrics. Transverse slices through the intervertebral discs of the cervical spine were acquired using a gradient echo sequence (MEDIC) with and without an MT saturation pulse on a 3 Tesla Siemens Prisma scanner (TR = 300 ms, TEeff = 17 ms, flip angle = 30°, in-plane resolution = 0.47 × 0.47 mm2). The CSM patients tended to have a lower mean MTR (30.4 ± 6.5) than the controls (34.8 ± 3.8), but the difference was not significant (independent samples t-test, p = 0.110, Cohen’s d = 0.80). The mean MTR across all intervertebral disc levels was not significantly correlated to the Nurick score (Spearman’s ρ = −0.489, p = 0.151). The intervertebral level with the lowest MTR in each cohort was not significantly different between groups (equal variances not assumed, t = 1.965, dof = 14.8, p = 0.068, Cohen’s d = 0.88), but the CSM patients tended to have a lower MTR. The mean MTR at this level was negatively correlated to the Nurick score among CSM patients (Spearman’s ρ = −0.725, p = 0.018). CSM patients tended to have decreased MTR indicating myelin degradation compared to our healthy subjects, and MTR was negatively correlated with the severity of CSM.

Diffusion-Weighted and Magnetization Transfer Imaging in Testicular Spermatogenic Function Evaluation: Preliminary Results.

To assess the use of functional magnetic resonance imaging (MRI), including diffusion-weighted MRI (DWI) and magnetization transfer MRI (MTI) in evaluating male infertility. 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. 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). Functional MRI, including DWI and MTI, appears promising for evaluating male infertility with higher ADC and lower MTR in testicular spermatogenesis hypofunction. 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:186-190.

GABA and glutamate levels correlate with MTR and clinical disability: Insights from multiple sclerosis

Converging areas of research have implicated glutamate and γ-aminobutyric acid (GABA) as key players in neuronal signalling and other central functions. Further research is needed, however, to identify microstructural and behavioral links to regional variability in levels of these neurometabolites, particularly in the presence of demyelinating disease. Thus, we sought to investigate the extent to which regional glutamate and GABA levels are related to a neuroimaging marker of microstructural damage and to motor and cognitive performance. Twenty-one healthy volunteers and 47 people with multiple sclerosis (all right-handed) participated in this study. Motor and cognitive abilities were assessed with standard tests used in the study of multiple sclerosis. Proton magnetic resonance spectroscopy data were acquired from sensorimotor and parietal regions of the brains’ left cerebral hemisphere using a MEGA-PRESS sequence. Our analysis protocol for the spectroscopy data was designed to account for confounding factors that could contaminate the measurement of neurometabolite levels due to disease, such as the macromolecule signal, partial volume effects, and relaxation effects. Glutamate levels in both regions of interest were lower in people with multiple sclerosis. In the sensorimotor (though not the parietal) region, GABA concentration was higher in the multiple sclerosis group compared to controls. Lower magnetization transfer ratio within grey and white matter regions from which spectroscopy data were acquired was linked to neurometabolite levels. When adjusting for age, normalized brain volume, MTR, total N-acetylaspartate level, and glutamate level, significant relationships were found between lower sensorimotor GABA level and worse performance on several tests, including one of upper limb motor function. This work highlights important methodological considerations relevant to analysis of spectroscopy data, particularly in the afflicted human brain. These findings support that regional neurotransmitter levels are linked to local microstructural integrity and specific behavioral abilities that can be affected in diseases such as multiple sclerosis.

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

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

Cortical Damage and Disability in Multiple Sclerosis: Relation to Intracortical Inhibition and Facilitation.

Multimodal research combining biomarkers of intracortical activity and cortical damage could shed light on pathophysiological and adaptive neural processes related to the clinical severity of neurological conditions such as multiple sclerosis (MS). Among people with relapsing-remitting and progressive forms of MS, we assessed the extent to which transcranial magnetic stimulation (TMS)-based biomarkers of excitatory and inhibitory cortical activity are related to cortical damage and clinical impairment. Participants included 18 healthy individuals and 36 people with MS who had a relapsing-remitting or progressive clinical course. Using TMS, intracortical facilitation (ICF), short-interval intracortical inhibition (SICI), long-interval intracortical inhibition (LICI), and cortical silent period (CSP) were obtained. Cortical volume and cortical magnetization transfer ratio (MTR) were quantified. Disability was assessed with Multiple Sclerosis Functional Composite (MSFC). Lower mean MTR within the cerebral cortex correlated with shorter CSP among MS participants with a progressive, but not a relapsing-remitting, clinical course. Within the cortical hand knob region targeted with TMS, lower MTR was correlated with lower SICI only among individuals with relapsing-remitting MS. Longer CSP, higher ICF, lower cortical MTR, and sex were all independent significant predictors of poor upper extremity motor performance, while only cortical MTR was a significant independent predictor of total MSFC score among people with MS. Cortical damage and cortical activity (both inhibitory and excitatory) may contribute to the severity of motor disability experienced by people with MS. When interpreting TMS-based outcomes, cortical integrity, clinical course, and symptom type should be considered.

Reduced skeletal muscle quantity and quality in patients with diabetic polyneuropathy assessed by magnetic resonance imaging.

The aim of this study was to determine whether diabetic polyneuropathy (DPN) is associated with reduced muscle quality using MRI. MRIs of the tibialis anterior (TA) muscle were recorded from 9 individuals (5 men) with DPN (∼65 years) and 8 (4 men) age- and gender-matched controls. A magnetization transfer ratio (MTR) and T2 relaxation times of the TA were calculated. Despite equal voluntary activation, the DPN group was ∼37% weaker than controls, with a significantly lower proportion (∼8%) of contractile tissue and lower MTR (0.28 ± 0.03 vs. 0.32 ± 0.02 percent units). T2 relaxation time was significantly longer in the DPN group (77 ± 16 ms) compared with controls (63 ± 6 ms). These findings indicate a reduction in the structural integrity and myocellular protein density in the TA of those with DPN. Thus, muscle weakness in DPN is likely due to both a loss of muscle mass and a reduction in contractile quality.

Quantitative magnetic resonance imaging in patients with cirrhosis: a cross-sectional study.

Cerebral magnetic resonance imaging was undertaken, at 3 Tesla field strength, employing magnetization transfer (MT) and diffusion-weighted imaging (DWI) sequences, in 26 patients with well-compensated cirrhosis, free of overt hepatic encephalopathy. Results were compared to those from 18 aged-matched healthy volunteers. Cerebral magnetization transfer ratios (MTR) were reduced in the frontal white matter, caudate, putamen and globus pallidus in patients with cirrhosis, compared to healthy controls, while the apparent diffusion coefficients (ADC) on DWI were significantly increased in the genu and body of the corpus callosum. An association between previous excessive alcohol consumption and both MTR and ADCs was noted, but this association was lost when controls were exercised for the severity of liver disease and psychometric impairment on multivariate analysis. Eight (31%) of the 26 patients had impaired psychometric performance consistent with a diagnosis of minimal hepatic encephalopathy. No statistically significant difference in regional cerebral MTRs or ADCs was found in relation to neuropsychiatric status, although there was a trend towards lower MTRs in patients with impaired psychometric performance. The alterations in MTR and ADC in the patients with functionally compensated cirrhosis are compatible with theories governing the genesis of hepatic encephalopathy, including changes in astrocyte membrane permeability, with subsequent redistribution of macromolecules.