Tensor-valued diffusion MRI of human acute stroke.

PURPOSE: Tensor-valued diffusion encoding can disentangle orientation dispersion and subvoxel anisotropy, potentially offering insight into microstructural changes after cerebral ischemia. The purpose was to evaluate tensor-valued diffusion MRI in human acute ischemic stroke, assess potential confounders from diffusion time dependencies, and compare to Monte Carlo diffusion simulations of axon beading. METHODS: Linear (LTE) and spherical (STE) b-tensor encoding with inherently different effective diffusion times were acquired in 21 acute ischemic stroke patients between 3 and 57 h post-onset at 3 T in 2.5 min. In an additional 10 patients, STE with 2 LTE yielding different effective diffusion times were acquired for comparison. Diffusional variance decomposition (DIVIDE) was used to estimate microscopic anisotropy (µFA), as well as anisotropic, isotropic, and total diffusional variance (MKA , MKI , MKT ). DIVIDE parameters, and diffusion tensor imaging (DTI)-derived mean diffusivity and fractional anisotropy (FA) were compared in lesion versus contralateral white matter. Monte Carlo diffusion simulations of various cylindrical geometries for all b-tensor protocols were used to interpret parameter measurements. RESULTS: MD was ˜40% lower in lesions for all LTE/STE protocols. The DIVIDE parameters varied with effective diffusion time: higher µFA and MKA in lesion versus contralateral white matter for STE with longer effective diffusion time LTE, whereas the shorter effective diffusion time LTE protocol yielded lower µFA and MKA in lesions. Both protocols, regardless of diffusion time, were consistent with simulations of greater beading amplitude and intracellular volume fraction. CONCLUSION: DIVIDE parameters depend on diffusion time in acute stroke but consistently indicate neurite beading and larger intracellular volume fraction.

Quantifying cerebral microbleeds using quantitative susceptibility mapping from magnetization-prepared rapid gradient-echo.

T1-weighted magnetization-prepared rapid gradient-echo (MPRAGE) is commonly included in brain studies for structural imaging using magnitude images; however, its phase images can provide an opportunity to assess microbleed burden using quantitative susceptibility mapping (QSM). This potential application for MPRAGE-based QSM was evaluated using in vivo and simulated measurements. Possible factors affecting image quality were also explored. Detection sensitivity was evaluated against standard multiecho gradient echo (MEGE) QSM using 3-T in vivo data of 15 subjects with a combined total of 108 confirmed microbleeds. The two methods were compared based on the microbleed size and susceptibility measurements. In addition, simulations explored the detection sensitivity of MPRAGE-QSM at different representative magnetic field strengths and echo times using microbleeds of different size, susceptibility, and location. Results showed that in vivo microbleeds appeared to be smaller (× 0.54) and of higher mean susceptibility (× 1.9) on MPRAGE-QSM than on MEGE-QSM, but total susceptibility estimates were in closer agreement (slope: 0.97, r2: 0.94), and detection sensitivity was comparable. In simulations, QSM at 1.5 T had a low contrast-to-noise ratio that obscured the detection of many microbleeds. Signal-to-noise ratio (SNR) levels at 3 T and above resulted in better contrast and increased detection. The detection rates for microbleeds of minimum one-voxel diameter and 0.4-ppm susceptibility were 0.55, 0.80, and 0.88 at SNR levels of 1.5, 3, and 7 T, respectively. Size and total susceptibility estimates were more consistent than mean susceptibility estimates, which showed size-dependent underestimation. MPRAGE-QSM provides an opportunity to detect and quantify the size and susceptibility of microbleeds of at least one-voxel diameter at B0 of 3 T or higher with no additional time cost, when standard T2*-weighted images are not available or have inadequate spatial resolution. The total susceptibility measure is more robust against sequence variations and might allow combining data from different protocols.

MR Susceptibility Separation for Quantifying Lesion Paramagnetic and Diamagnetic Evolution in Relapsing-Remitting Multiple Sclerosis.

BACKGROUND: Multiple sclerosis (MS) lesion evolution may involve changes in diamagnetic myelin and paramagnetic iron. Conventional quantitative susceptibility mapping (QSM) can provide net susceptibility distribution, but not the discrete paramagnetic and diamagnetic components. PURPOSE: To apply susceptibility separation (χ separation) to follow lesion evolution in MS with comparison to R2 */R2 ' /QSM. STUDY TYPE: Longitudinal, prospective. SUBJECTS: Twenty relapsing-remitting MS subjects (mean age: 42.5 ± 9.4 years, 13 females; mean years of symptoms: 4.3 ± 1.4 years). FIELD STRENGTH/SEQUENCE: Three-dimensional multiple echo gradient echo (QSM and R2 * mapping), two-dimensional dual echo fast spin echo (R2 mapping), T2 -weighted fluid attenuated inversion recovery, and T1-weighted magnetization prepared gradient echo sequences at 3 T. ASSESSMENT: Data were analyzed from two scans separated by a mean interval of 14.4 ± 2.0 months. White matter lesions on fluid-attenuated inversion recovery were defined by an automatic pipeline, then manually refined (by ZZ/AHW, 3/25 years' experience in MRI), and verified by a radiologist (MN, 25 years' experience in MS). Susceptibility separation yielded the paramagnetic and diamagnetic susceptibility content of each voxel. Lesions were classified into four groups based on the variation of QSM/R2 * or separated into positive/negative components from χ separation. STATISTICAL TESTS: Two-sample paired t tests for assessment of longitudinal differences. Spearman correlation coefficients to assess associations between χ separation and R2 */R2 ' /QSM. Significant level: P < 0.005. RESULTS: A total of 183 lesions were quantified. Categorizing lesions into groups based on χ separation demonstrated significant annual changes in QSM//R2 */R2 ' . When lesions were grouped based on changes in QSM and R2 *, both changing in unison yielded a significant dominant paramagnetic variation and both opposing yielded a dominant diamagnetic variation. Significant Spearman correlation coefficients were found between susceptibility-sensitive MRI indices and χ separation. DATA CONCLUSION: Susceptibility separation changes in MS lesions may distinguish and quantify paramagnetic and diamagnetic evolution, potentially providing additional insight compared to R2 * and QSM alone. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

High-resolution diffusion tensor imaging and T2 mapping detect regional changes within the hippocampus in multiple sclerosis.

Hippocampus demyelinating lesions in multiple sclerosis (MS) have been frequently observed in ex vivo histopathological studies; however, they are difficult to image and quantify in vivo. Diffusion tensor imaging (DTI) and T2 mapping could potentially detect such regional in vivo changes if acquired with sufficient spatial resolution. The goal here was to evaluate whether there are focal hippocampal abnormalities in 43 MS patients (35 relapsing-remitting, eight secondary progressive) with and without cognitive impairment (CI) versus 43 controls using high-resolution 1 mm isotropic DTI, as well as complementary methods of T2-weighted and T2 mapping at 3 T. Abnormal hippocampus regions were identified voxel-by-voxel by using mean diffusivity (MD)/T2 thresholds and avoiding voxels attributed to cerebrospinal fluid. When compared with controls, averaged left/right whole hippocampus MD was higher in both MS groups, while lower fractional anisotropy (FA) and volume, and higher T2 relaxometry and T2-weighted signal values, were only significant in CI MS. The hippocampal MD and T2 images/maps were not uniformly affected and focal regions of elevated MD/T2 were evident in MS patients. Both CI and not CI MS groups showed greater proportional areas of the hippocampus with elevated MD, whereas only the CI group showed a greater proportional area of elevated T2 relaxation times or T2-weighted signal. Higher T2 relaxometry and T2-weighted signal values of elevated regions correlated with greater disability and whole hippocampus FA negatively correlated with physical fatigue. High-resolution hippocampus DTI and T2 mapping with less partial volume effects showed whole hippocampus abnormalities with regional elevations of MD/T2 in MS, which could be interpreted as potentially from demyelination, neuron loss, and/or inflammation, and which overall were more extensive in the hippocampus of patients with larger total brain lesion volumes and CI.

A Normative Brain MRI Database of Neurotypical Participants from 5 to 90 Years of Age.

Brain magnetic resonance imaging (MRI) studies of clinical populations often require comparison to a normative 'control' cohort, usually of similar age/sex, scanned with the same protocol. The goal here was to create a normative brain MRI database of common quantitative methods to be used in comparisons with a variety of neurological disorders across the lifespan. 378 neurotypical controls (aged 5-90 years; median 31 years; 216 females, 162 males) completed brain MRI, cognitive testing, clinical assessment, and a demographics questionnaire. In addition, this large normative sample will yield novel insight into healthy brain development and aging.

Diffusion imaging of fornix and interconnected limbic deep grey matter is linked to cognitive impairment in multiple sclerosis.

Diffusion tensor imaging (DTI) and volumetric magnetic resonance imaging (MRI) have shown white matter (WM) and deep grey matter (GM) abnormalities in the limbic system of multiple sclerosis (MS) participants. Structures like the fornix have been associated with cognitive impairment (CI) in MS, but the diffusion metrics are often biased by partial volume effects from cerebrospinal fluid (CSF) due to its small bundle size and intraventricular location. These errors in DTI parameter estimation worsen with atrophy in MS. The goal here was to evaluate DTI parameters and volumes of the fornix, as well as associated deep GM structures like the thalamus and hippocampus, with high-resolution fluid-attenuated inversion recovery (FLAIR)-DTI at 3T in 43 MS patients, with and without CI, versus 43 controls. The fornix, thalamus and hippocampus displayed atrophy and/or abnormal diffusion metrics, with the fornix showing the most extensive changes within the structures studied here, mainly in CI MS. The affected fornix volumes and diffusion metrics were associated with thalamic atrophy and atypical diffusion metrics in interconnected limbic GM, larger total lesion volume and global brain atrophy. Lower fractional anisotropy (FA) and higher mean and radial diffusivity in the fornix, lower hippocampus FA and lower thalamus volume were strongly correlated with CI in MS. Hippocampus FA and thalamus atrophy were negatively correlated with fatigue and longer time since MS symptoms onset, respectively. FLAIR-DTI and volumetric analyses provided methodologically superior evidence for microstructural abnormalities and extensive atrophy of the fornix and interconnected deep GM in MS that were associated with cognitive deficits.

Distinct patterns of progressive gray and white matter degeneration in amyotrophic lateral sclerosis.

Progressive cerebral degeneration in amyotrophic lateral sclerosis (ALS) remains poorly understood. Here, three-dimensional (3D) texture analysis was used to study longitudinal gray and white matter cerebral degeneration in ALS from routine T1-weighted magnetic resonance imaging (MRI). Participants were included from the Canadian ALS Neuroimaging Consortium (CALSNIC) who underwent up to three clinical assessments and MRI at four-month intervals, up to 8 months after baseline (T0 ). Three-dimensional maps of the texture feature autocorrelation were computed from T1-weighted images. One hundred and nineteen controls and 137 ALS patients were included, with 81 controls and 84 ALS patients returning for at least one follow-up. At baseline, texture changes in ALS patients were detected in the motor cortex, corticospinal tract, insular cortex, and bilateral frontal and temporal white matter compared to controls. Longitudinal comparison of texture maps between T0 and Tmax (last follow-up visit) within ALS patients showed progressive texture alterations in the temporal white matter, insula, and internal capsule. Additionally, when compared to controls, ALS patients had greater texture changes in the frontal and temporal structures at Tmax than at T0 . In subgroup analysis, slow progressing ALS patients had greater progressive texture change in the internal capsule than the fast progressing patients. Contrastingly, fast progressing patients had greater progressive texture changes in the precentral gyrus. These findings suggest that the characteristic longitudinal gray matter pathology in ALS is the progressive involvement of frontotemporal regions rather than a worsening pathology within the motor cortex, and that phenotypic variability is associated with distinct progressive spatial pathology.

Nitroglycerin Is Not Associated with Improved Cerebral Perfusion in Acute Ischemic Stroke.

OBJECTIVE: The study was conducted to test the hypothesis that nitroglycerin (NTG) increases cerebral perfusion focally and globally in acute ischemic stroke patients, using serial perfusion-weighted imaging (PWI) magnetic resonance imaging measurements. PATIENTS AND METHODS: Thirty-five patients underwent PWI immediately before and 72 h after administration of a transdermal NTG patch or no treatment. Patients with baseline mean arterial pressure (MAP) > 100 mmHg (NTG group, n = 20) were treated with transdermal NTG (0.2 mg/h) for 72 h, without a nitrate-free interval. Patients with MAP ≤ 100 mmHg (untreated group, n = 15) were not treated. The primary outcome measure was absolute cerebral blood flow (CBF) in the hypoperfused region at 72 h. RESULTS: The mean baseline absolute CBF in the hypoperfused region was similar in the NTG group (33.3 ± 10.2 ml/100 g/min) and untreated (32.7 ± 8.4 ml/100 g/min, p = 0.4) groups. The median (IQR) baseline infarct volume was 10.4 (2.5-49.3) ml in the NTG group and 32.6 (8.6-96.7) ml in the untreated group (p = 0.09). MAP change in the NTG group was 1.2 ± 12.6 and 8 ± 20.7 mmHg at 2 h and 72 h, respectively. Mean absolute CBF in the hypoperfused region at 72 h was similar in the NTG (29.9 ± 12 ml/100 g/min) and untreated groups (24.1 ± 10 ml/100 g/min, p = 0.8). The median infarct volume increased in untreated (11.8 (5.7-44.2) ml) than the NTG group (3.2 (0.5-16.5) ml; p = 0.033) on univariate analysis, however, there was no difference on regression analysis. CONCLUSION: NTG was not associated with improvement in cerebral perfusion in acute ischemic stroke patients.

Rapid quantitative susceptibility mapping of intracerebral hemorrhage.

BACKGROUND: Quantitative susceptibility mapping (QSM) offers a means to track iron evolution in hemorrhage. However, standard QSM sequences have long acquisition times and are prone to motion artifact in hemorrhagic patients. PURPOSE: To minimize motion artifact and acquisition time by performing rapid QSM in intracerebral hemorrhage (ICH) using single-shot echo planar imaging (EPI). STUDY TYPE: Prospective method evaluation. POPULATION/SUBJECTS: Forty-five hemorrhages were analyzed from 35 MRI exams obtained between February 2016 and March 2019 from 27 patients (14 male / 13 female, age: 71 ± 12 years) with confirmed primary ICH. FIELD STRENGTH/SEQUENCE: 3T; susceptibility-weighted imaging (SWI) with 4.54-minute acquisition and 2D single-shot gradient EPI with 0.45-minute acquisition. ASSESSMENT: Susceptibility maps were constructed from both methods. Measurement of ICH area and mean magnetic susceptibility were made manually by three independent observers. Motion artifacts were quantified using the magnitude signal ratio of artifact-to-brain tissue to classify into three categories: mild or no artifact, moderate artifact, or severe artifact. The cutoff for each category was determined by four observers. STATISTICAL TESTS: Pearson's correlation coefficient and paired t-test using α = 0.05 were used to compare results. Inter- and intraclass correlation was used to assess observer variability. RESULTS: Using 45 hemorrhages, the ICH regions measured on susceptibility maps obtained from EPI and SWI sequences had high correlation coefficients for area (R2 ≥ 0.97) and mean magnetic susceptibility (R2 ≥ 0.93) for all observers. The artifact-to-tissue ratio was significantly higher (P < 0.01) for SWI vs. EPI, and the standard deviation for the SWI method (SD = 0.05) was much larger than EPI (SD = 0.01). All observers' measurements showed high agreement. DATA CONCLUSION: Single-shot EPI-QSM enabled rapid measurement of ICH area and mean magnetic susceptibility, with reduced motion as compared with more standard SWI. EPI-QSM requires minimal additional acquisition time and could be incorporated into iron tracking studies in ICH. LEVEL OF EVIDENCE: 2 Technical Efficacy Stage: 1 J. Magn. Reson. Imaging 2020;51:712-718.

Radiological Findings on Structural Magnetic Resonance Imaging in Fetal Alcohol Spectrum Disorders and Healthy Controls.

BACKGROUND: Fetal alcohol spectrum disorders (FASD) describe a range of physical, behavioral, and cognitive impairments stemming from prenatal alcohol exposure (PAE). Although case studies have demonstrated striking visible brain abnormalities in humans (enlargement of the lateral ventricles, thinning or absence of the corpus callosum, etc.), few studies have systematically determined how these radiological findings generalize to the wider population of individuals living with FASD. METHODS: This study examines rates of structural brain anomalies on magnetic resonance imaging (MRI) as determined by 2 radiologists in a retrospective blinded review of 163 controls and 164 individuals with PAE who were previously scanned as participants of past research studies. Incidental findings were categorized as normal variants, nonclinically significant incidental findings, or clinically significant incidental findings. Rates were compared between diagnostic subgroups using chi-square analysis. RESULTS: There was no significant difference in the overall rate of incidental findings between groups: 75% of controls and 73% of PAE participants had no incidental findings of any kind, and only 1% of controls and 3% of PAE participants had incidental finding of clinical significance (the remaining findings were considered nonsignificant anomalies or normal variants). When the PAE group was split by diagnosis, low-lying cerebellar tonsils, polymicrogyria, and ventricular asymmetry/enlargement were all most prevalent in subjects with fetal alcohol syndrome/partial fetal alcohol syndrome. In addition, the overall rate of incidental findings was higher (41%) in participants with FAS/pFAS, compared to 25% in controls. No participants in this relatively large sample had corpus callosum agenesis. CONCLUSIONS: Although advanced quantitative MRI research has uncovered a range of differences in brain structure associated with FASD, this qualitative radiological study suggests that routine clinical MRI does not reveal a consistent pattern of brain abnormalities that can be used diagnostically in this population.

Human pegivirus-1 associated leukoencephalitis: Clinical and molecular features.

Etiologic diagnosis is uncertain in 35% to 50% of patients with encephalitis, despite its substantial global prevalence and disease burden. We report on 2 adult female patients with fatal leukoencephalitis associated with human pegivirus-1 (HPgV-1) brain infection. Neuroimaging showed inflammatory changes in cerebral white matter. Brain-derived HPgV-1 RNA sequences clustered phylogenetically with other pegiviruses despite an 87-nucleotide deletion in the viral nonstructural (NS)2 gene. Neuropathology disclosed lymphocyte infiltration and gliosis predominantly in brain white matter. HPgV-1 NS5A antigen was detected in lymphocytes as well as in astrocytes and oligodendrocytes. HPgV-1 neuroadaptation should be considered in the differential diagnosis of progressive leukoencephalitis in humans. Ann Neurol 2018;84:789-795.

Quantitative Susceptibility Mapping for Following Intracranial Hemorrhage.

Purpose To follow the evolution of intracranial hemorrhage (ICH) by using quantitative susceptibility mapping (QSM). Materials and Methods Thirty-six patients with ICH confirmed at CT were enrolled to follow ICH evolution on day 2, 7, and 30 after symptom onset between August 2013 and April 2017. QSM was reconstructed from MRI gradient-echo phase images acquired at 1.5 T or 3.0 T. ICH regions were manually drawn on two-dimensional sections of co-registered CT and MR images independently by two raters. The ICH areas and mean values were compared between CT and MRI by using Bland-Altman plots and Pearson correlation. QSM time evolution of ICH was assessed by using paired t tests and was compared with conventional T2-weighted fluid-attenuated inversion recovery, or T1-weighted or T2*-weighted magnitude intensities. Results Significant reductions in ICH susceptibility were found between day 2 and day 7 (P < .001) and between day 7 and day 30 (P = .003), corresponding to different disease stages. The ICH areas measured at CT and QSM were linearly correlated (r2 = 0.98). The mean CT attenuation and mean susceptibility of ICH were linearly correlated (r2 = 0.29). Excellent intra- and interobserver reproducibility were found for QSM (intraclass correlation coefficient, 0.987 and 0.966, respectively). Conclusion Longitudinal evolution of intracranial hemorrhage (ICH) by using quantitative susceptibility mapping (QSM) demonstrated susceptibility differences in different disease stages, which was not found at conventional MRI; therefore, QSM may assist in quantitatively following ICH iron content.

The intracerebral hemorrhage acutely decreasing arterial pressure trial II (ICH ADAPT II) protocol.

BACKGROUND: Aggressively lowering blood pressure (BP) in acute intracerebral hemorrhage (ICH) may improve outcome. Although there is no evidence that BP reduction changes cerebral blood flow, retrospective magnetic resonance imaging (MRI) studies have demonstrated sub-acute ischemic lesions in ICH patients. The primary aim of this study is to assess ischemic lesion development in patients randomized to two different BP treatment strategies. We hypothesize aggressive BP reduction is not associated with ischemic injury after ICH. METHODS: The Intracerebral Hemorrhage Acutely Decreasing Blood Pressure Trial II (ICH ADAPT II) is a phase II multi-centre randomized open-label, blinded-endpoint trial. Acute ICH patients (N = 270) are randomized to a systolic blood pressure (SBP) target of <140 or <180 mmHg. Acute ICH patients within 6 h of onset and two SBP measurements ≥140 mmHg recorded >2 mins apart qualify. SBP is managed with a pre-defined treatment protocol. Patients undergo MRI at 48 h, Days 7 and 30, with clinical assessment at Day 30 and 90. The primary outcome is diffusion weighted imaging (DWI) lesion frequency at 48 h. Secondary outcomes include cumulative DWI lesion rate frequency within 30 days, absolute hematoma growth, prediction of DWI lesion incidence, 30-day mortality rates, day 90 functional outcome, and cognitive status. DISCUSSION: This trial will assess the impact of hypertensive therapies on physiological markers of ischemic injury. The findings of this study will provide evidence for the link, or lack thereof, between BP reduction and ischemic injury in ICH patients. TRIAL REGISTRATION: This study is registered with clinicaltrials.gov  ( NCT02281838 , first received October 29, 2014).

Early Rivaroxaban Use After Cardioembolic Stroke May Not Result in Hemorrhagic Transformation: A Prospective Magnetic Resonance Imaging Study.

BACKGROUND AND PURPOSE: Early anticoagulation after cardioembolic stroke remains controversial because of the potential for hemorrhagic transformation (HT). We tested the safety and feasibility of initiating rivaroxaban ≤14 days after cardioembolic stroke/transient ischemic attack. METHODS: A prospective, open-label study of patients with atrial fibrillation treated with rivaroxaban ≤14 days of transient ischemic attack or ischemic stroke (National Institute of Health Stroke Scale <9). All patients underwent magnetic resonance imaging <24 hours of rivaroxaban initiation and day 7. The primary end point was symptomatic HT at day 7. RESULTS: Sixty patients (mean±SD age 71±19 years, 82% stroke/18% transient ischemic attack) were enrolled. Median (interquartile range) time from onset to rivaroxaban was 3 (5) days. At treatment initiation, median National Institute of Health Stroke Scale was 2 (4), and median diffusion-weighted imaging volume was 7.9 (13.7) mL. At baseline, HT was present in 25 (42%) patients (hemorrhagic infarct [HI]1=19, HI2=6). On follow-up magnetic resonance imaging, no patients developed symptomatic HT. New asymptomatic HI1 developed in 3 patients, and asymptomatic progression from HI1 to HI2 occurred in 5 patients; otherwise, HT remained unchanged at day 7. CONCLUSIONS: These data support the safety of rivaroxaban initiation ≤14 days of mild-moderate cardioembolic stroke/transient ischemic attack. Magnetic resonance imaging evidence of petechial HT, which is common, does not appear to increase the risk of symptomatic HT.

Quantitative susceptibility mapping using a superposed dipole inversion method: Application to intracranial hemorrhage.

PURPOSE: To investigate gradient-echo phase errors caused by intracranial hemorrhage (ICH) of low signal magnitude, and propose methods to reduce artifacts from phase errors in quantitative susceptibility mapping (QSM) of ICH. METHODS: Two QSM methods are proposed: (1) mask-inversion that masks the phase of low signal magnitude regions, and (2) ICH magnetic dipole field isolation followed by susceptibility superposition using multiple boundaries for background field removal. The reconstruction methods were tested in eight subjects with ICH using standard single-echo susceptibility-weighted imaging at 1.5 Tesla with 40 ms echo time. Different phase unwrapping algorithms were also compared. RESULTS: Significant phase errors were evident inside ICHs with low signal magnitude. The mask-inversion method recovered susceptibility of ICH in numerical simulation and minimized phase error propagation in patients with ICH. The additional superposed dipole inversion process substantially suppressed and constrained streaking artifacts in all subjects. Using the proposed superposition method, ICH susceptibilities measured from long and short echo times were similar. Laplacian based phase unwrapping substantially underestimated the ICH dipole field as compared to a path-based method. CONCLUSION: The proposed methods of mask-inversion as well as ICH isolation and superposition can substantially reduce artifacts in QSM of ICH. Magn Reson Med 76:781-791, 2016. © 2015 Wiley Periodicals, Inc.

Microscopic Polyangiitis with Spinal Cord Involvement: A Case Report and Review of the Literature.

BACKGROUND: Microscopic polyangiitis (MPA) is an ANCA-associated vasculitis (AAV; ANCA denotes antineutrophil cytoplasmic antibody) that causes necrotizing inflammation of small blood vessels. Renal and pulmonary manifestations are common whereas central nervous system (CNS) involvement, and in particular spinal disease, is rare. METHODS: We reviewed a case of MPA presenting with spinal intradural hemorrhage and intracerebral hemorrhage. We also summarized all reported cases of AAV with spinal cord involvement in the literature (database search included MEDLINE, Embase, Scopus, and Proquest with no date or language restriction). RESULTS: We reviewed 20 cases of AAV with spinal cord involvement (12 granulomatosis with polyangiitis [GPA], 4 eosinophilic granulomatosis with polyangiitis, 2 MPA, and 2 cases diagnosed as AAV only) and reported demographic information, clinical features, methods of diagnosis, treatment, and patient outcome. Although CNS involvement has been associated with a poor prognosis, 14 of 18 cases that reported outcome data achieved remission during follow-up. Death occurred in 3 patients diagnosed with GPA and in 1 patient with MPA. Our patient with MPA deteriorated rapidly despite use of prednisone and died. CONCLUSIONS: AAV can present with brain and spinal cord involvement, even in the absence of systemic disease. CNS disease may be responsive to immunosuppressive therapy (e.g., steroids and cyclophosphamide) in several of the cases reviewed.

Reduction of Diffusion-Weighted Imaging Contrast of Acute Ischemic Stroke at Short Diffusion Times.

BACKGROUND AND PURPOSE: Diffusion-weighted imaging (DWI) of tissue water is a sensitive and specific indicator of acute brain ischemia, where reductions of the diffusion of tissue water are observed acutely in the stroke lesion core. Although these diffusion changes have been long attributed to cell swelling, the precise nature of the biophysical mechanisms remains uncertain. METHODS: The potential cause of diffusion reductions after stroke was investigated using an advanced DWI technique, oscillating gradient spin-echo DWI, that enables much shorter diffusion times and can improve specificity for alterations of structure at the micron level. RESULTS: Diffusion measurements in the white matter lesions of patients with acute ischemic stroke were reduced by only 8% using oscillating gradient spin-echo DWI, in contrast to a 37% decrease using standard DWI. Neurite beading has recently been proposed as a mechanism for the diffusion changes after ischemic stroke with some ex vivo evidence. To explore whether beading could cause such differential results, simulations of beaded cylinders and axonal swelling were performed, yielding good agreement with experiment. CONCLUSIONS: Short diffusion times result in dramatically reduced diffusion contrast of human stroke. Simulations implicate a combination of neuronal beading and axonal swelling as the key structural changes leading to the reduced apparent diffusion coefficient after stroke.

Ischemia in intracerebral hemorrhage is associated with leukoaraiosis and hematoma volume, not blood pressure reduction.

BACKGROUND AND PURPOSE: Diffusion-weighted imaging (DWI) lesions have been identified both inside and outside the perihematoma region. We tested the hypotheses that larger hematoma volumes and blood pressure reduction are associated with DWI lesions. METHODS: Hematoma and perihematoma edema volumes were measured using planimetric techniques in 117 intracerebral hemorrhage (ICH) patients who underwent DWI. Perihematoma and remote DWI lesion volumes were measured using apparent diffusion coefficient thresholds for moderate (<730×10(-6) mm/s) and severe (<550×10(-6) mm/s) ischemia. Acute blood pressure change over the first 24 hours was calculated. RESULTS: The median (interquartile range) time to magnetic resonance imaging was 2 (1-5) days. Median hematoma volume was 9.8 (2.6-23.0) mL, and median perihematoma edema volume was 7.0 (2.9-18.6) mL. A small portion of the perihematoma region contained tissue below the thresholds for moderate (8.0 [2.9-14.5]%) and severe ischemia (1.1 [0.3-3.5]%). Ischemic perihematoma tissue volumes were correlated with hematoma volumes (R=0.52, P<0.001), but not maximal systolic blood pressure drop at 24 hours (R=-0.09, P=0.38). Remote DWI lesions were found in 17 (14.5%) patients (mean volume=0.44±0.3 mL). Patients with remote DWI lesions had higher rates of antiplatelet use (P=0.01), prior ICH (P=0.03), lobar ICH (0.04), and larger leukoaraiosis volumes (P=0.02). Maximal systolic blood pressure drop at 24 hours was similar in patients with (-20.5 [-55, -10] mm Hg) and without remote DWI lesions (-27 [-46, -13] mm Hg, P=0.96). CONCLUSIONS: Small DWI lesions within and outside the perihematoma region are common in primary ICH. Perihematoma DWI lesions were independently associated with larger hematoma volumes. Remote DWI lesions may be an epiphenomenon associated with the underlying microvascular pathogenesis. These data do not support a hemodynamic mechanism of ischemic injury after primary ICH.

Blood-brain barrier compromise does not predict perihematoma edema growth in intracerebral hemorrhage.

BACKGROUND AND PURPOSE: There are limited data on the extent of blood-brain barrier (BBB) compromise in acute intracerebral hemorrhage patients. We tested the hypotheses that BBB compromise measured with permeability-surface area product (PS) is increased in the perihematoma region and predicts perihematoma edema growth in acute intracerebral hemorrhage patients. METHODS: Patients were randomized within 24 hours of symptom onset to a systolic blood pressure (SBP) treatment of <150 (n=26) or <180 mm Hg (n=27). Permeability maps were generated using computed tomographic perfusion source data acquired 2 hours after randomization, and mean PS was measured in the hematoma, perihematoma, and hemispheric regions. Hematoma and edema volumes were measured on noncontrast computed tomographic scans obtained at baseline, 2 hours and 24 hours after randomization. RESULTS: Patients were randomized at a median (interquartile range) time of 9.3 hours (14.1) from symptom onset. Treatment groups were balanced with respect to baseline SBP and hematoma volume. Perihematoma PS (5.1±2.4 mL/100 mL per minute) was higher than PS in contralateral regions (3.6±1.7 mL/100 mL per minute; P<0.001). Relative edema growth (0-24 hours) was not predicted by perihematoma PS (ß=-0.192 [-0.06 to 0.01]) or SBP change (ß=-0.092 [-0.002 to 0.001]). SBP was lower in the <150 target group (139.2±22.1 mm Hg) than in the <180 group (159.7±12.3 mm Hg; P<0.0001). Perihematoma PS was not different between groups (4.9±2.4 mL/100 mL per minute for the <150 group, 5.3±2.4 mL/100 mL per minute for the <180 group; P=0.51). CONCLUSIONS: BBB permeability is focally increased in the hematoma and perihematoma regions of acute intracerebral hemorrhage patients. BBB compromise does not predict acute perihematoma edema volume or edema growth. SBP reduction does not affect BBB permeability. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00963976.