Association of Cortical Lesions With Regional Glutamate, GABA, N-Acetylaspartate, and Myoinositol Levels in Patients With Multiple Sclerosis.

BACKGROUND AND OBJECTIVES: Cortical lesions contribute to disability in multiple sclerosis (MS), but their impact on regional neurotransmitter levels remains to be clarified. We tested the hypothesis that cortical lesions are associated with regional glutamate and gamma-aminobutyric acid (GABA) concentrations within the affected cortical region. METHODS: In this cross-sectional study, we used structural 7T MRI to segment cortical lesions and 7T proton MR-spectroscopy of the bilateral sensorimotor hand areas to quantify regional GABA, glutamate, N-acetylaspartate, and myoinositol concentrations in patients with MS (inclusion criteria: diagnosis of relapsing-remitting [RR] or secondary progressive MS [SPMS]; age 18-80 years) and age and sex-matched healthy controls. Data were collected at a single center between August 2018 and September 2020. Linear mixed-effects models were used to test for associations between metabolite concentrations and cortical lesion volumes within the same MR-spectroscopy voxel. RESULTS: Forty-seven patients with MS (34 RRMS, 13 SPMS; 45.1 ± 12.5 years; 31 women) and 23 healthy controls (44.4 ± 13 years, 15 women) were studied. In patients, higher regional glutamate and lower regional GABA concentrations were associated with larger cortical lesion volume within the MR-spectroscopy voxel [glutamate: 0.61 (95% CI 0.19-1.03) log(mm3), p = 0.005, GABA: -0.71 (-1.24 to -0.18) log(mm3), p = 0.01]. In addition, lower N-acetylaspartate levels [-0.37 (-0.67 to -0.07) log(mm3), p = 0.016] and higher myoinositol levels [0.48 (0.03-0.93) log(mm3), p = 0.037] were associated with a larger regional cortical lesion volume. Furthermore, glutamate concentrations were reduced in patients with SPMS compared with healthy participants [-0.75 (-1.3 to -0.19) mM, p = 0.005] and patients with RRMS [-0.55 (-1.07 to -0.02) mM, p = 0.04]. N-acetylaspartate levels were lower in both patients with RRMS [-0.81 (-1.39 to -0.24) mM, p = 0.003] and SPMS [-1.31 (-2.07 to -0.54) mM, p < 0.001] when compared with healthy controls. Creatine-normalized N-acetylaspartate levels were associated with performance in the 9-hole peg test of the contralateral hand [-0.004 (-0.007 to -0.002) log(s), p = 0.002], and reduced mean creatine-normalized glutamate was associated with increased Expanded Disability Status Scale (R = -0.39, p = 0.02). DISCUSSION: Cortical lesions are associated with local increases in glutamate and a reduction in GABA concentration within the lesional or perilesional tissue. Further studies are needed to investigate the causal relationship between cortical lesions and changes in neurotransmitter concentrations.

Quantitative magnetic resonance imaging reflects different levels of histologically determined myelin densities in multiple sclerosis, including remyelination in inactive multiple sclerosis lesions.

Magnetic resonance imaging (MRI) of focal or diffuse myelin damage or remyelination may provide important insights into disease progression and potential treatment efficacy in multiple sclerosis (MS). We performed post-mortem MRI and histopathological myelin measurements in seven progressive MS cases to evaluate the ability of three myelin-sensitive MRI scans to distinguish different stages of MS pathology, particularly chronic demyelinated and remyelinated lesions. At 3 Tesla, we acquired two different myelin water imaging (MWI) scans and magnetisation transfer ratio (MTR) data. Histopathology included histochemical stainings for myelin phospholipids (LFB) and iron as well as immunohistochemistry for myelin proteolipid protein (PLP), CD68 (phagocytosing microglia/macrophages) and BCAS1 (remyelinating oligodendrocytes). Mixed-effects modelling determined which histopathological metric best predicted MWF and MTR in normal-appearing and diffusely abnormal white matter, active/inactive, inactive, remyelinated and ischemic lesions. Both MWI measures correlated well with each other and histology across regions, reflecting the different stages of MS pathology. MTR data showed a considerable influence of components other than myelin and a strong dependency on tissue storage duration. Both MRI and histology revealed increased myelin densities in inactive compared with active/inactive lesions. Chronic inactive lesions harboured single scattered myelin fibres indicative of low-level remyelination. Mixed-effects modelling showed that smaller differences between white matter areas were linked to PLP densities and only to a small extent confounded by iron. MWI reflects differences in myelin lipids and proteins across various levels of myelin densities encountered in MS, including low-level remyelination in chronic inactive lesions.

Brain Imaging Abnormalities in Mixed Alzheimer's and Subcortical Vascular Dementia.

BACKGROUND: A large proportion of Alzheimer's disease (AD) patients have coexisting subcortical vascular dementia (SVaD), a condition referred to as mixed dementia (MixD). Brain imaging features of MixD presumably include those of cerebrovascular disease and AD pathology, but are difficult to characterize due to their heterogeneity. OBJECTIVE: To perform an exploratory analysis of conventional and non-conventional structural magnetic resonance imaging (MRI) abnormalities in MixD and to compare them to those observed in AD and SVaD. METHODS: We conducted a cross-sectional, region-of-interest-based analysis of 1) hyperintense white-matter signal abnormalities (WMSA) on T2-FLAIR and hypointense WMSA on T1-weighted MRI; 2) diffusion tensor imaging; 3) quantitative susceptibility mapping; and 4) effective transverse relaxation rate (R2*) in N = 17 participants (AD:5, SVaD:5, MixD:7). General linear model was used to explore group differences in these brain imaging measures. RESULTS: Model findings suggested imaging characteristics specific to our MixD group, including 1) higher burden of WMSAs on T1-weighted MRI (versus both AD and SVaD); 2) frontal lobar preponderance of WMSAs on both T2-FLAIR and T1-weighted MRI; 3) higher fractional anisotropy values within normal-appear white-matter tissues (versus SVaD, but not AD); and 4) lower R2* values within the T2-FLAIR WMSA areas (versus both AD and SVaD). CONCLUSION: These findings suggest a preliminary picture of the location and type of brain imaging characteristics associated with MixD. Future imaging studies may employ region-specific hypotheses to distinguish MixD more rigorously from AD or SVaD.

Linking lesions in sensorimotor cortex to contralateral hand function in multiple sclerosis: a 7†T MRI study.

Cortical lesions constitute a key manifestation of multiple sclerosis and contribute to clinical disability and cognitive impairment. Yet it is unknown whether local cortical lesions and cortical lesion subtypes contribute to domain-specific impairments attributable to the function of the lesioned cortex. In this cross-sectional study, we assessed how cortical lesions in the primary sensorimotor hand area relate to corticomotor physiology and sensorimotor function of the contralateral hand. Fifty relapse-free patients with relapsing-remitting or secondary-progressive multiple sclerosis and 28 healthy age- and sex-matched participants underwent whole-brain 7 T MRI to map cortical lesions. Brain scans were also used to estimate normalized brain volume, pericentral cortical thickness, white matter lesion fraction of the corticospinal tract, infratentorial lesion volume and the cross-sectional area of the upper cervical spinal cord. We tested sensorimotor hand function and calculated a motor and sensory composite score for each hand. In 37 patients and 20 healthy controls, we measured maximal motor-evoked potential amplitude, resting motor threshold and corticomotor conduction time with transcranial magnetic stimulation and the N20 latency from somatosensory-evoked potentials. Patients showed at least one cortical lesion in the primary sensorimotor hand area in 47 of 100 hemispheres. The presence of a lesion was associated with worse contralateral sensory (P = 0.014) and motor (P = 0.009) composite scores. Transcranial magnetic stimulation of a lesion-positive primary sensorimotor hand area revealed a decreased maximal motor-evoked potential amplitude (P < 0.001) and delayed corticomotor conduction (P = 0.002) relative to a lesion-negative primary sensorimotor hand area. Stepwise mixed linear regressions showed that the presence of a primary sensorimotor hand area lesion, higher white-matter lesion fraction of the corticospinal tract, reduced spinal cord cross-sectional area and higher infratentorial lesion volume were associated with reduced contralateral motor hand function. Cortical lesions in the primary sensorimotor hand area, spinal cord cross-sectional area and normalized brain volume were also associated with smaller maximal motor-evoked potential amplitude and longer corticomotor conduction times. The effect of cortical lesions on sensory function was no longer significant when controlling for MRI-based covariates. Lastly, we found that intracortical and subpial lesions had the largest effect on reduced motor hand function, intracortical lesions on reduced motor-evoked potential amplitude and leucocortical lesions on delayed corticomotor conduction. Together, this comprehensive multilevel assessment of sensorimotor brain damage shows that the presence of a cortical lesion in the primary sensorimotor hand area is associated with impaired corticomotor function of the hand, after accounting for damage at the subcortical level. The results also provide preliminary evidence that cortical lesion types may affect the various facets of corticomotor function differentially.

Imaging cortical multiple sclerosis lesions with ultra-high field MRI.

BACKGROUND: Cortical lesions are abundant in multiple sclerosis (MS), yet difficult to visualize in vivo. Ultra-high field (UHF) MRI at 7 T and above provides technological advances suited to optimize the detection of cortical lesions in MS. PURPOSE: To provide a narrative and quantitative systematic review of the literature on UHF MRI of cortical lesions in MS. METHODS: A systematic search of all literature on UHF MRI of cortical lesions in MS published before September 2020. Quantitative outcome measures included cortical lesion numbers reported using 3 T and 7 T MRI and between 7 T MRI sequences, along with sensitivity of UHF MRI towards cortical lesions verified by histopathology. RESULTS: 7 T MRI detected on average 52 ± 26% (mean ± 95% confidence interval) more cortical lesions than the best performing image contrast at 3 T, with the largest increase in type II-IV intracortical lesion detection. Across all studies, the mean cortical lesion number was 17 ± 6 per patient. In progressive MS cohorts, approximately four times more cortical lesions were reported than in CIS/early RRMS, and RRMS. Yet, there was no difference in lesion type ratio between these MS subtypes. Furthermore, superiority of one MRI sequence over another could not be established from available data. Post-mortem lesion detection with UHF MRI agreed only modestly with pathological examinations. Mean pro- and retrospective sensitivity was 33 ± 6% and 71 ± 10%, respectively, with the highest sensitivity towards type I and type IV lesions. CONCLUSION: UHF MRI improves cortical lesion detection in MS considerably compared to 3 T MRI, particularly for type II-IV lesions. Despite modest sensitivity, 7 T MRI is still capable of visualizing all aspects of cortical lesion pathology and could potentially aid clinicians in diagnosing and monitoring MS, and progressive MS in particular. However, standardization of acquisition and segmentation protocols is needed.

In vivo investigation of the multi-exponential T2 decay in human white matter at 7 T: Implications for myelin water imaging at UHF.

INTRODUCTION: Multi-component T2 mapping using a gradient- and spin-echo (GraSE) acquisition has become standard for myelin water imaging at 3 T. Higher magnetic field strengths promise signal-to-noise ratio benefits but face specific absorption rate limits and shortened T2 times. This study investigates compartmental T2 times in vivo and addresses advantages and challenges of multi-component T2 mapping at 7 T. METHODS: We acquired 3D multi-echo GraSE data in seven healthy adults at 7 T, with three subjects also scanned at 3 T. Stimulated echoes arising from B1+ inhomogeneities were accounted for by the extended phase graph (EPG) algorithm. We used the computed T2 distributions to determine T2 times that identify different water pools and assessed signal-to-noise and fit-to-noise characteristics of the signal estimation. We compared short T2 fractions and T2 properties of the intermediate water pool at 3 T and 7 T. RESULTS: Flip angle mapping confirmed that EPG accurately determined the larger B1+ inhomogeneity at 7 T. Multi-component T2 analysis demonstrated shortened T2 times at 7 T compared with 3 T. Fit-to-noise and signal-to-noise ratios were improved at 7 T but depended on B1+ homogeneity. Adjusting the shortest T2 to 8 ms and the T2 threshold that separates different water compartments to 20 ms yielded short T2 fractions at 7 T that conformed to 3 T data. Short T2 fractions in myelin-rich white matter regions were lower at 7 T than at 3 T, and higher in iron-rich structures. DISCUSSION: Adjusting the T2 compartment boundaries was required due to the shorter T2 relaxation times at 7 T. Shorter echo spacing would better sample the fast decaying signal but would increase peripheral nerve stimulation. Multi-channel transmission will improve T2 measurements at 7 T. CONCLUSION: We used a multi-echo 3D GraSE sequence to characterize the multi-exponential T2 decay at 7 T. We adapted T2 parameters for evaluation of the short T2 fraction. Obtained 7 T multi-component T2 maps were in good agreement with 3 T data.

Multi-spin echo T2 relaxation imaging with compressed sensing (METRICS) for rapid myelin water imaging.

PURPOSE: Myelin water imaging (MWI) provides a valuable biomarker for myelin, but clinical application has been restricted by long acquisition times. Accelerating the standard multi-echo T2 acquisition with gradient echoes (GRASE) or by 2D multi-slice data collection results in image blurring, contrast changes, and other issues. Compressed sensing (CS) can vastly accelerate conventional MRI. In this work, we assessed the use of CS for in vivo human MWI, using a 3D multi spin-echo sequence. METHODS: We implemented multi-echo T2 relaxation imaging with compressed sensing (METRICS) and METRICS with partial Fourier acceleration (METRICS-PF). Scan-rescan data were acquired from 12 healthy controls for assessment of repeatability. MWI data were acquired for METRICS in 9 m:58 s and for METRICS-PF in 7 m:25 s, both with 1.5 × 2 × 3 mm3 voxels, 56 echoes, 7 ms ΔTE, and 240 × 240 × 170 mm3 FOV. METRICS was compared with a novel multi-echo spin-echo gold-standard (MSE-GS) MWI acquisition, acquired for a single additional subject in 2 h:2 m:40 s. RESULTS: METRICS/METRICS-PF myelin water fraction had mean: repeatability coefficient 1.5/1.1, coefficient of variation 6.2/4.5%, and intra-class correlation coefficient 0.79/0.84. Repeatability metrics comparing METRICS with METRICS-PF were similar, and both sequences agreed with reference values from literature. METRICS images and quantitative maps showed excellent qualitative agreement with those of MSE-GS. CONCLUSION: METRICS and METRICS-PF provided highly repeatable MWI data without the inherent disadvantages of GRASE or 2D multi-slice acquisition. CS acceleration allows MWI data to be acquired rapidly with larger FOV, higher estimated SNR, more isotropic voxels and more echoes than with previous techniques. The approach introduced here generalizes to any multi-component T2 mapping application.

Myelin Damage in Normal Appearing White Matter Contributes to Impaired Cognitive Processing Speed in Multiple Sclerosis.

BACKGROUND AND PURPOSE: Cognitive impairment is a core symptom in multiple sclerosis (MS). Damage to normal appearing white matter (NAWM) is likely involved. We sought to determine if greater myelin heterogeneity in NAWM is associated with decreased cognitive performance in MS. METHODS: A total of 27 participants with MS and 13 controls matched for age, sex, and education underwent myelin water imaging (MWI) from which the myelin water fraction (MWF) was calculated. Corpus callosum, superior longitudinal fasciculus, and cingulum were chosen as regions of interest (ROIs) a priori based on their involvement in MS-related cognitive impairment. Cognitive performance was assessed using the Symbol Digit Modalities Test (SDMT). Pearson ́s product moment correlations were performed to assess relationships between cognitive performance and myelin heterogeneity (variance of MWF within an ROI). RESULTS: In MS, myelin heterogeneity in all three ROIs was significantly associated with performance on the SDMT. These correlations ranged from moderate (r = -.561) to moderately strong (r = -.654) and were highly significant (P values ranged from .001 to .0002). Conversely, myelin heterogeneity was not associated with SDMT performance in controls in any ROI (P > .108). CONCLUSION: Increased myelin heterogeneity in NAWM is associated with decreased cognitive processing speed performance in MS.

Cartilage recovery in runners with and without knee osteoarthritis: A pilot study.

OBJECTIVE: Running is an easy way of meeting physical activity recommendations for individuals with knee osteoarthritis (KOA); however, it remains unknown how their cartilage reacts to running. The objective of this pilot study was to compare the effects of 30 min of running on T2 and T1ρ relaxation times of tibiofemoral cartilage in female runners with and without KOA. METHODS: Ten female runners with symptomatic KOA (mean age 52.6 ±â€¯7.6 years) and 10 without KOA (mean age 52.5 ±â€¯7.8 years) ran for 30 min on a treadmill. Tibiofemoral cartilage T2 and T1ρ relaxation times were measured using magnetic resonance imaging prior to and immediately after the bout of running. Repeated-measures analyses of covariance (ANCOVA) were conducted to examine between-group differences across scanning times. RESULTS: No Group × Time interactions were found for T2 (P ≥ 0.076) or T1ρ (P ≥ 0.288) relaxation times. However, runners with KOA showed increased T2 values compared with pre-running in the medial and lateral femur 55 min post-running (5.4 to 5.5%, P < 0.022) and in all four tibiofemoral compartments 90 min post-running (6.9 to 11.1%, P < 0.01). A significant group effect was found for T1ρ in the medial femur, with greater values in those with KOA compared with controls. CONCLUSION: While Group × Time interactions in T2 and T1ρ relaxation times remained statistically insignificant, the observed significant increases in T2 in runners with tibiofemoral osteoarthritis TFOA may suggest slower and continuing changes in the cartilage and thus a need for longer recovery after running. Future research should investigate the effects of repeated exposure to running.

The role of iron and myelin in orientation dependent R2* of white matter.

Brain myelin and iron content are important parameters in neurodegenerative diseases such as multiple sclerosis (MS). Both myelin and iron content influence the brain's R2* relaxation rate. However, their quantification based on R2* maps requires a realistic tissue model that can be fitted to the measured data. In structures with low myelin content, such as deep gray matter, R2* shows a linear increase with increasing iron content. In white matter, R2* is not only affected by iron and myelin but also by the orientation of the myelinated axons with respect to the external magnetic field. Here, we propose a numerical model which incorporates iron and myelin, as well as fibre orientation, to simulate R2* decay in white matter. Applying our model to fibre orientation-dependent in vivo R2* data, we are able to determine a unique solution of myelin and iron content in global white matter. We determine an averaged myelin volume fraction of 16.02 ± 2.07% in non-lesional white matter of patients with MS, 17.32 ± 2.20% in matched healthy controls, and 18.19 ± 2.98% in healthy siblings of patients with MS. Averaged iron content was 35.6 ± 8.9 mg/kg tissue in patients, 43.1 ± 8.3 mg/kg in controls, and 47.8 ± 8.2 mg/kg in siblings. All differences in iron content between groups were significant, while the difference in myelin content between MS patients and the siblings of MS patients was significant. In conclusion, we demonstrate that a model that combines myelin-induced orientation-dependent and iron-induced orientation-independent components is able to fit in vivo R2* data.

Longitudinal advanced MRI case report of white matter radiation necrosis.

Radiation necrosis mostly occurs in and near the radiation field. We used magnetic resonance imaging to study radiation-induced necrosis of atypical onset, severity, and extent following stereotactic radiosurgery for a symptomatic arteriovenous malformation. Susceptibility-sensitive imaging, T1-relaxation, myelin water imaging, and magnetic resonance spectroscopy were acquired three times up to 52 months postradiosurgery. Increasing water content outside the radiation field, contralateral neuronal loss, and gliosis were detected over time. Our findings suggest that radiation-induced vasculopathic changes spread more diffusely than previously described. An autoimmune response to brain antigens could underlie white matter changes outside the initial radiation field.

Increased mean R2* in the deep gray matter of multiple sclerosis patients: Have we been measuring atrophy?

BACKGROUND: Magnetic resonance relaxometry studies in multiple sclerosis (MS) have suggested that iron accumulates within deep gray matter (DGM) structures early in the disease course. However, the commonly utilized mean R2* and magnetic susceptibility measures reflect regional iron concentration but not a structure's total iron content. Thus, tissue atrophy could impact mean R2* and magnetic susceptibility estimates. PURPOSE: To demonstrate that both average iron concentration and total iron content need to be reported in order to distinguish between atrophy-related and definite magnetic susceptibility changes. STUDY TYPE: Observational. POPULATION: The study was performed on 30 healthy controls (HCs) and 39 people with definite MS. FIELD STRENGTH/SEQUENCE: 3T Philips Achieva using an 8-channel SENSE head coil. R2* data were acquired using a multiecho gradient echo sequence and diffusion tensor imaging data were acquired using an echo-planar sequence. ASSESSMENT: Total iron content in DGM structures was assessed by calculating the sum of all R2* values within a region (denoted as R2mass* ) and compared to the mean R2* as a measure of iron concentration. STATISTICAL TEST: Significant group differences were investigated in a linear regression model. All DGM structures were assessed individually and the significance threshold was adjusted using the Bonferroni-Holm correction for multiple comparisons. RESULTS: There was an increased mean DGM R2* in MS patients compared to HCs (significant in the pallidus, P = 0.0051). In contrast, R2mass* in patients was found to be lower in the thalamus and the caudate (P = 0.0011) compared to HCs, and similar between the two cohorts in the other DGM regions. DATA CONCLUSION: An increase in mean R2* may not necessarily reflect increased iron accumulation. We propose R2mass* as an additional metric to account for the effects of tissue atrophy when assessing tissue content changes, such as iron deposition or loss. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;50:201-208.

Rapid two-step dipole inversion for susceptibility mapping with sparsity priors.

Quantitative susceptibility mapping (QSM) is a post-processing technique of gradient echo phase data that attempts to map the spatial distribution of local tissue magnetic susceptibilities. To obtain these maps, an ill-posed field-to-source inverse problem must be solved to remove non-local magnetic field perturbations. Current state-of-the-art algorithms which aim to solve the dipole inversion problem are plagued by the trade-off between reconstruction speed and accuracy. A two-step dipole inversion algorithm is proposed to bridge this gap. Our approach first addresses the well-conditioned k-space region, which is reconstructed using a Krylov subspace solver. Then the ill-conditioned k-space region is reconstructed by solving a constrained l1-minimization problem. The proposed pipeline does not incorporate a priori information, but utilizes sparsity constraints in the second step. We compared our method to well-established QSM algorithms with respect to COSMOS in in vivo volunteer datasets. Compared to MEDI and HEIDI the proposed algorithm produces susceptibility maps with a lower root-mean-square error and a higher coefficient of determination, with respect to COSMOS, while being 50 times faster. Our two-step dipole inversion algorithm without a priori information yields improved QSM reconstruction quality at reduced computation times compared to current state-of-the-art methods.

Susceptibility-sensitive MRI of multiple sclerosis lesions and the impact of normal-appearing white matter changes.

Susceptibility-sensitive magnetic resonance imaging (MRI) has gained importance in multiple sclerosis (MS) research because of its versatility, high resolution and excellent sensitivity to changes in tissue structure and composition. In particular, mapping of the resonance frequency of the MR signal and quantitative susceptibility mapping (QSM) have been explored for the description of MS lesions. Many current studies utilizing these techniques attribute increases in the MR frequency or QSM to elevated tissue iron content, in addition to myelin loss. However, this common interpretation is inconsistent with recent histopathological studies. Here, we investigate the nature of MR frequency shifts related to MS lesions by comparing post-mortem MRI data with histology, and contrast them with numerical simulations of the MR signal. We demonstrate that iron accumulation is not the driving source of the MR frequency or QSM image contrast in our sample; rather, most chronic MS lesions are characterized by advanced loss of both myelin and iron. Moreover, our results suggest that the appearance of MS lesions on MR frequency maps and QSM depends on changes in the non-lesional white matter surrounding the lesions. Understanding and accounting for these changes is essential for the quantitative interpretation of MR frequency or QSM data in white matter.

Anisotropic cerebral vascular architecture causes orientation dependency in cerebral blood flow and volume measured with dynamic susceptibility contrast magnetic resonance imaging.

Measurements of cerebral perfusion using dynamic susceptibility contrast magnetic resonance imaging rely on the assumption of isotropic vascular architecture. However, a considerable fraction of vessels runs in parallel with white matter tracts. Here, we investigate the effects of tissue orientation on dynamic susceptibility contrast magnetic resonance imaging. Tissue orientation was measured using diffusion tensor imaging and dynamic susceptibility contrast was performed with gradient echo planar imaging. Perfusion parameters and the raw dynamic susceptibility contrast signals were correlated with tissue orientation. Additionally, numerical simulations were performed for a range of vascular volumes of both the isotropic vascular bed and anisotropic vessel components, as well as for a range of contrast agent concentrations. The effect of the contrast agent was much larger in white matter tissue perpendicular to the main magnetic field compared to white matter parallel to the main magnetic field. In addition, cerebral blood flow and cerebral blood volume were affected in the same way with angle-dependent variations of up to 130%. Mean transit time and time to maximum of the residual curve exhibited weak orientation dependency of 10%. Numerical simulations agreed with the measured data, showing that one-third of the white matter vascular volume is comprised of vessels running in parallel with the fibre tracts.

Multi-echo GRE imaging of knee cartilage.

PURPOSE: To visualize healthy and abnormal articular cartilage, we investigated the potential of using the 3D multi-echo gradient echo (GRE) signal's magnitude and frequency and maps of T2* relaxation. MATERIALS AND METHODS: After optimizing imaging parameters in five healthy volunteers, 3D multi-echo GRE magnetic resonance (MR) images were acquired at 3T in four patients with chondral damage prior to their arthroscopic surgery. Average magnitude and frequency information was extracted from the GRE images, and T2* maps were generated. Cartilage abnormalities were confirmed after arthroscopy and were graded using the Outerbridge classification scheme. Regions of interest were identified on average magnitude GRE images and compared to arthroscopy. RESULTS: All four patients presented with regions of Outerbridge Grade I and II cartilage damage on arthroscopy. One patient had Grade III changes. Grade I, II, and III changes were detectable on average magnitude and T2* maps, while Grade II and higher changes were also observable on MR frequency maps. For average magnitude images of healthy volunteers, the signal-to-noise ratio of the magnitude image averaged over three echoes was 4.26 ± 0.32, 12.26 ± 1.09, 14.31 ± 1.93, and 13.36 ± 1.13 in bone, femoral, tibial, and patellar cartilage, respectively. CONCLUSION: This proof-of-principle study demonstrates the feasibility of using different imaging contrasts from the 3D multi-echo GRE scan to visualize abnormalities of the articular cartilage. © 2016 International Society for Magnetic Resonance in Medicine Level of Evidence: 1 J. MAGN. RESON. IMAGING 2017;45:1502-1513.

Orientation Dependent MR Signal Decay Differentiates between People with MS, Their Asymptomatic Siblings and Unrelated Healthy Controls.

R2* relaxometry of the brain is a quantitative magnetic resonance technique which is influenced by iron and myelin content across different brain regions. Multiple sclerosis (MS) is a common inflammatory, demyelinating disease affecting both white and grey matter regions of the CNS. Using R2*, increased iron deposition has been described in deep gray matter of MS patients. Iron accumulation might promote oxidative stress in the brain, which can lead to cell death and neurodegeneration. However, recent histological work indicates that iron may be reduced within the normal appearing white matter (WM) in MS. In the present study we analyzed the R2* signal across the white matter in 39 patients with MS, 31 asymptomatic age matched siblings of patients and 30 age-matched controls. The measurement of R2* in white matter is affected by the signal's dependency on white matter fibre orientation with respect to the main magnetic field which can be accounted using diffusion tensor imaging. We observed a clear separation of the three study groups in R2*. The values in the MS group were significantly lower compared to the siblings and controls, while the siblings group presented with significantly higher R2* values than both unrelated healthy controls and patients. Furthermore, we found significantly decreased normal-appearing white matter R2* values in patients with more severe disease course. Angle resolved analysis of R2* improves the sensitivity for detecting subtle differences in WM R2* compared to standard histogram based analyses. Our findings suggest that the decreased R2* values in MS are due to diffuse tissue damage and decreased myelin in the normal appearing and diffusely abnormal WM. The increased R2* in unaffected siblings may identify a predisposition to increased iron and the potential for oxidative stress as a risk factor for developing MS.

Magnetic resonance frequency shifts during acute MS lesion formation.

OBJECTIVE: We investigated the evolution of new multiple sclerosis (MS) lesions over time using frequency shifts of the magnetic resonance (MR) signal. METHODS: Twenty patients with relapsing-remitting MS were serially scanned for 6 months at 1-month intervals. Maps of MR frequency shifts were acquired using susceptibility-weighted imaging. New lesions were identified by enhancement with gadolinium (Gd). RESULTS: Forty new lesions were identified as areas of signal increase on Gd-enhanced scans. Up to 3 months before lesion appearance, the frequency in areas of future Gd enhancement was not detectably different from the frequency in normal-appearing white matter. Rapid increase in MR frequency was observed between 1 month before and 1 month after Gd enhancement. Two months postenhancement and later, the frequency stabilized and remained at a constantly increased level. CONCLUSIONS: These findings suggest that an increase in MR frequency does not simply reflect blood-brain barrier disruption or edema; rather, it reflects a change of tissue architecture as a consequence of new lesion formation. The data demonstrate that the MR frequency of focal MS lesions is increased before the lesions appear on conventional MRI. Unlike many other advanced imaging techniques, the images for frequency mapping can be rapidly acquired at high spatial resolution and standardized on most clinical scanners.