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BACKGROUND AND PURPOSE: Recently, there has been growing interest in the glymphatic system (the functional waste clearance pathway for the central nervous system and its role in flushing solutes (such as amyloid s and tau), metabolic, and other cellular waste products in the brain. Herein, we investigate a recent potential biomarker for glymphatic activity (the diffusion tensor imaging along the perivascular space [DTI-ALPS] parameter) using diffusion MRI imaging in an elderly cohort comprising 10 cognitively normal, 10 mild cognitive impairment (MCI), and 16 Alzheimer's disease (AD). METHODS: All 36 participants imaged on a Siemens 3.0T Tim Trio. Single-SE diffusion weighted Echo-planar imaging scans were acquired as well as T1 magnetization prepared rapid gradient echo, T2 axial, and susceptibility weighted imaging. Three millimeter regions of interest were drawn in the projection and association fibers adjacent to the medullary veins at the level of the lateral ventricle. The DTI-ALPS parameter was calculated in these regions and correlated with cognitive status, Mini-Mental State Examination (MMSE), and ADASCog11 measures. RESULTS: Significant correlations were found between DTI-ALPS and MMSE and ADASCog11 in the right hemisphere adjusting for age, sex, and APoE e4 status. Significant differences were also found in the right DTI-ALPS indices between cognitively normal and AD groups (P < .026) and MCI groups (P < .025) in a univariate general linear model corrected for age, sex, and APoE e4. Significant differences in apparent diffusion coefficient between cognitively normal and AD groups were found in the right projection fibers (P = .028). CONCLUSION: Further work is needed to determine the utility of DTI-ALPS index in larger elderly cohorts and whether it measures glymphatic activity.

Objective The posterior cingulate cortex (PCC)/precuneus is a key hub of the default mode network, whose function is known to be altered in epilepsy. Glutamate and γ-aminobutyric acid (GABA) are the main excitatory and inhibitory neurotransmitters in the central nervous system, respectively. Glutathione (GSH) is the most important free radical scavenging compound in the brain. Quantification of these molecules by magnetic resonance spectroscopy (MRS) up to 4 T is limited by overlapping resonances from other molecules. In this study, we used ultra-high-field (7 T) MRS to quantify their concentrations in patients with different epilepsy syndromes. Methods Nineteen patients with temporal lobe epilepsy (TLE) and 16 with idiopathic generalized epilepsy (IGE) underwent magnetic resonance imaging scans using a 7-T research scanner. Single-voxel (8 cm3 ) MRS, located in the PCC/precuneus, was acquired via stimulated echo acquisition mode. Their results were compared to 10 healthy volunteers. Results Mean concentrations of glutamate, GABA, and the glutamate/GABA ratio did not differ between the IGE, TLE, and healthy volunteer groups. The mean ± SD concentration of GSH was 1.9 ± 0.3 mmol·L-1 in healthy controls, 2.0 ± 0.2 mmol·L-1 in patients with TLE, and 2.2 ± 0.4 mmol·L-1 in patients with IGE. One-way analysis of variance with post hoc Tukey-Kramer test revealed a significant difference in the concentration of GSH between patients with IGE and controls (P = .03). Short-term seizure freedom in patients with epilepsy was predicted by an elevated concentration of glutamate in the PCC/precuneus (P = .01). In patients with TLE, the concentration of GABA declined with age (P = .03). Significance Patients with IGE have higher concentrations of GSH in the PCC/precuneus than healthy controls. There is no difference in the concentrations of glutamate and GABA, or their ratio, in the PCC/precuneus between patients with IGE, patients with TLE, and healthy controls. Measuring the concentration of glutamate in the PCC/precuneus may assist with predicting drug response.

Background and purpose Quantitative susceptibility mapping (QSM) of the brain has become highly reproducible and has applications in an expanding array of diseases. To translate QSM from bench to bedside, it is important to automate its reconstruction immediately after data acquisition. In this work, a server system that automatically reconstructs QSM and exchange images with the scanner using the DICOM standard is demonstrated using a multi-site, multi-vendor reproducibility study and a large, single-site, multi-scanner image quality review study in a clinical environment. Methods A single healthy subject was scanned with a 3D multi-echo gradient echo sequence at nine sites around the world using scanners from three manufacturers. A high-resolution (HiRes, .5 × .5 × 1 mm3 reconstructed) and standard-resolution (StdRes, .5 × .5 × 3 mm3 ) protocol was performed. ROI analysis of various white matter and gray matter regions was performed to investigate reproducibility across sites. At one institution, a retrospective multi-scanner image quality review was carried out of all clinical QSM images acquired consecutively in 1 month. Results Reconstruction times using a GPU were 29 ± 22 seconds (StdRes) and 55 ± 39 seconds (HiRes). ROI standard deviation across sites was below 24 ppb (StdRes) and 17 ppb (HiRes). Correlations between ROI averages across sites were on average .92 (StdRes) and .96 (HiRes). Image quality review of 873 consecutive patients revealed diagnostic or excellent image quality in 96% of patients. Conclusion Online QSM reconstruction for a variety of sites and scanner platforms with low cross-site ROI standard deviation is demonstrated. Image quality review revealed diagnostic or excellent image quality in 96% of 873 patients.

OBJECTIVE: We investigated the relationship between the interictal metabolic patterns, the extent of resection of 18 F-fluorodeoxyglucose positron emission tomography (18 FDG-PET) hypometabolism, and seizure outcomes in patients with unilateral drug-resistant mesial temporal lobe epilepsy (MTLE) following anterior temporal lobe (TL) resection. METHODS: Eighty-two patients with hippocampal sclerosis or normal magnetic resonance imaging (MRI) findings, concordant 18 FDG-PET hypometabolism, and at least 2 years of postoperative follow-up were included in this 2-center study. The hypometabolic regions in each patient were identified with reference to 20 healthy controls (p < 0.005). The resected TL volume and the volume of resected TL PET hypometabolism (TLH) were calculated from the pre- and postoperative MRI scans coregistered with interictal 18 FDG-PET. RESULTS: Striking differences in metabolic patterns were observed depending on the lateralization of the epileptogenic TL. The extent of the ipsilateral TLH was significantly greater in left MTLE patients (p < 0.001), whereas right MTLE patients had significantly higher rates of contralateral (CTL) TLH (p = 0.016). In right MTLE patients, CTL hypometabolism was the strongest predictor of an unfavorable seizure outcome, associated with a 5-fold increase in the likelihood of seizure recurrence (odds ratio [OR] = 4.90, 95% confidence interval [CI] = 1.07-22.39, p = 0.04). In left MTLE patients, greater extent of resection of ipsilateral TLH was associated with lower rates of seizure recurrence (p = 0.004) in univariate analysis; however, its predictive value did not reach statistical significance (OR = 0.96, 95% CI = 0.90-1.02, p = 0.19). INTERPRETATION: The difference in metabolic patterns depending on the lateralization of MTLE may represent distinct epileptic networks in patients with right versus left MTLE, and can guide preoperative counseling and surgical planning. Ann Neurol 2019; 1-10 ANN NEUROL 2019;85:241-250.

BACKGROUND AND PURPOSE: Degeneration of gray matter and subcortical structures after ischemic stroke has been well described. However, little is known about white matter degeneration after stroke. It is unclear whether white matter degeneration occurs throughout the whole brain, or whether patterns of degeneration occur more in specific brain areas. METHODS: We prospectively collected National Institutes of Health Stroke Scale (NIHSS) scores and diffusion tensor imaging (DTI) in patients with acute ischemic stroke within the first week after onset (baseline), and at 1 and 3 months. DTI was processed to produce maps of fractional anisotropy, apparent diffusion coefficients, and axial and radial diffusivity. DTI parameters in specified regions-of-interest corresponding to items on the NIHSS were calculated and changes over time were assessed using linear mixed-effect modeling. RESULTS: Seventeen patients were included in the study. Mean age (SD) was 71 (11.7) years, and median (IQR) baseline NIHSS 9 (5-13.3). Changes over time were observed in both visual cortices, contralesional primary motor cortex, premotor cortex, and superior temporal gyrus (P < .05). Changes in the ipsilesional motor cortex and inferior parietal lobule were only seen in patients with scores on the respective NIHSS-items (P .05). CONCLUSION: White matter changes after stroke may be localized rather than a global phenomenon.

There is increasing scrutiny from healthcare organizations towards the utility and associated costs of imaging. MRI has traditionally been used as a high-end modality, and although shown extremely important for many types of clinical scenarios, it has been suggested as too expensive by some. This editorial will try and explain how value should be addressed and gives some insights and practical examples of how value of MRI can be increased. It requires a global effort to increase accessibility, value for money, and impact on patient management. We hope this editorial sheds some light and gives some indications of where the field may wish to address some of its research to proactively demonstrate the value of MRI. Level of Evidence: 5. Technical Efficacy: Stage 5. J. Magn. Reson. Imaging 2019;49:e14–e25.

Purpose To investigate whether there are any white matter changes in a 6‐month follow‐up of mild‐moderate Alzheimer's patients using diffusion tensor imaging (DTI). Materials and Methods We recruited 18 mild‐moderate Alzheimer's disease patients and they underwent magnetic resonance imaging (MRI) at recruitment and at 6‐month follow‐up. Diffusion MRI images were processed using DTI‐ToolKit to create a population‐based tensor template. This template was integrated with a voxel‐wise and atlas‐based analysis in FSL to determine the magnitude and location of change in diffusion metrics over the 6‐month follow‐up period. Results There were significant widespread changes in diffusion metrics across the entire white matter skeleton (P

Background To evaluate a new semi-automated segmentation method for calculating hippocampal volumes and to compare results with standard software tools in a cohort of people with subjective memory complaints (SMC) and mild cognitive impairment (MCI). Methods Data from 58 participants, 39 with SMC (17 male, 22 female, mean age 72.6) and 19 with MCI (6 male, 13 female, mean age 74.3), were analyzed. For each participant, T1-weighted images were acquired using an MPRAGE sequence on a 3 Tesla MRI system. Hippocampal volumes (left, right, and total) were calculated with a new, age appropriate registration template, based on older people and using the advanced software tool ANTs (Advanced Normalization Tools). The results were compared with manual tracing (seen as the reference standard) and two widely accepted automated software tools (FSL, FreeSurfer). Results The hippocampal volumes, calculated by using the age appropriate registration template were significantly (P

Background: Increased physical activity (PA) is associated with better cognitive function. We investigated whether individuals with memory problems and additional cerebrovascular risk factors (CVD) could increase PA in the short-term and maintain adherence to a PA program in the long-term. We also examined factors influencing PA adherence. Methods: The AIBL Active trial recruited participants with mild cognitive impairment (MCI) or subjective memory complaints (SMC) and at least 1 CVD risk factor from The Australian Imaging Biomarkers and Lifestyle Flagship Study of Aging (AIBL). They were randomly assigned to a control or PA group. The control group continued their usual PA throughout the study. The PA group was given a 24-month home-based program with a target of 150 minutes/week of moderate PA and a behavioral intervention. Scheduled group-specific phone calls (nｼ18) and newsletters (nｼ17) were administered to both groups over 24 months. The PA group recorded sessions in diaries and adherence was calculated from the number of sessions recorded expressed as the percentage of the sessions prescribed. At baseline, 6, 12 and 24 months participants completed fitness (6-minute walk distance); PA and PA self-efficacy (one痴 confidence to be physically active) questionnaires; cognitive and health assessments. Results: The adherence results for the PA group (nｼ55) comprising of 53% women are reported. At baseline 24% were defined as inactive; men were significantly older than women; 74.7(6SD 5.6) versus 70.1(4.8) years respectively. Five participants did not start the intervention. After 24 months 96% were still in the study. After 6 months mean PA adherence was 83.5% and declined over the trial with mean 24-month adherence being 75.2%. Age, gender and MCI did not significantly influence adherence. Higher baseline self-effi- cacy (p

This study aimed to evaluate and validate chemical shift imaging (CSI) for in vivo glutamate (Glu) quantification in patients with supratentorial gliomas. If validated, CSI could become an extremely useful tool to investigate metabolic dysfunction of Glu in excitotoxic neuropathologies. Quantitative CSI estimates of Glu concentrations were compared with known concentrations of Glu in aqueous phantom solutions. Forty-one patients with known or likely supratentorial gliomas underwent preoperative CSI. The spectra obtained were analyzed for Glu concentrations and Glu to creatine (Cr) ratios. These in vivo measurements were correlated against ex vivo Glu content quantified by high performance liquid chromatography (HPLC) measured in 65 resected brain tumor and peritumoral brain specimens. For the phantom solutions the CSI estimates of Glu concentration and the Glu/Cr ratios were highly correlated with known Glu concentration (r² = 0.95, p = 0.002, and r² = 0.97, p

Transverse myelitis is an acute inflammatory disease of the spinal cord, characterized by rapid onset of bilateral neurological symptoms. Weakness, sensory disturbance, and autonomic dysfunction evolve over hours or days, most progressing to maximal clinical severity within 10 days of onset. At maximal clinical severity, half will have a paraparesis, and almost all patients have sensory disturbance and bladder dysfunction. Residual disability is divided equally between severe, moderate and minimal or none. The causes of transverse myelitis are diverse; etiologies implicated include demyelinating conditions, collagen vascular disease, and parainfectious causes, however, despite extensive diagnostic work-up many cases are considered idiopathic. Due to heterogeneity in pathogenesis, and the similarity of its clinical presentation with those of various noninflammatory myelopathies, transverse myelitis has frequently been viewed as a diagnostic dilemma. However, as targeted therapies to optimize patient outcome develop, timely identification of the underlying etiology is becoming increasingly important. In this review, we describe the imaging and clinical features of idiopathic and disease-associated transverse myelitis and its major differentials, with discussion of how MR imaging features assist in the identification of various sub-types of transverse myelitis. We will also discuss the potential for advanced MR techniques to contribute to diagnosis and prognostication.

Objective Very low cerebral blood volume (VLCBV), diffusion, and hypoperfusion lesion volumes have been proposed as predictors of hemorrhagic transformation following stroke thrombolysis. We aimed to compare these parameters, validate VLCBV in an independent cohort using DEFUSE study data, and investigate the interaction of VLCBV with regional reperfusion. Methods The EPITHET and DEFUSE studies obtained diffusion and perfusion magnetic resonance imaging (MRI) in patients 3 to 6 hours from onset of ischemic stroke. EPITHET randomized patients to tissue plasminogen activator (tPA) or placebo, and all DEFUSE patients received tPA. VLCBV was defined as cerebral blood volume2 ml VLCBV threshold defined in EPITHET predicted PH with 100% sensitivity, 72% specificity, 35% positive predictive value, and 100% negative predictive value. Pooling EPITHET and DEFUSE (163 patients, including 23 with PH), regression models using VLCBV (p 8 seconds lesion volumes. Excluding VLCBV in regions without reperfusion improved specificity from 61 to 78% in the pooled analysis. Interpretation VLCBV predicts PH after stroke thrombolysis and appears to be a more powerful predictor than baseline diffusion or hypoperfusion lesion volumes. Reperfusion of regions of VLCBV is strongly associated with post-thrombolysis PH. VLCBV may be clinically useful to identify patients at significant risk of hemorrhage following reperfusion. ANN NEUROL 2013;73:510–519

Recanalization of arterial obstruction is associated with improved clinical outcomes. There are no controlled data demonstrating whether arterial obstruction status predicts the treatment effect of intravenous (IV) tissue plasminogen activator (tPA). We aimed to determine if the presence of arterial obstruction improves the treatment effect of IV tPA over placebo in attenuating infarct growth.We analyzed 175 ischemic stroke patients treated in the 3-6 hour time window from the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET) trial (randomized to IV tPA or placebo) and Diffusion and perfusion imaging Evaluation For Understanding Stroke Evolution (DEFUSE) study (all treated with IV tPA). Infarct growth was calculated as the difference between baseline diffusion-weighted imaging (DWI) and final T2 lesion volumes. Baseline arterial obstruction of large intracranial arteries was graded on magnetic resonance angiography (MRA).Among the 116 patients with adequate baseline MRA and final lesion assessment, 72 had arterial obstruction (48 tPA, 24 placebo) and 44 no arterial obstruction (33 tPA, 11 placebo). Infarct growth was lower in the tPA than placebo group (median difference 26ml, 95% confidence interval [CI], 1-50) in patients with arterial obstruction, but was similar in patients with no arterial obstruction (median difference 5ml, 95%CI, -3 to 9). Infarct growth attenuation with tPA over placebo treatment was greater among patients with arterial obstruction than those without arterial obstruction by a median of 32ml (95%CI, 21-43, p0.001).The treatment effect of IV tPA over placebo was greater with baseline arterial obstruction, supporting arterial obstruction status as a consideration in selecting patients more likely to benefit from IV thrombolysis.

Background and Purpose. The authors used serial magnetic resonance perfusion-weighted imaging (PWI) and diffusionweighted imaging (DWI) to determine whether major reperfusion and the attenuation of infarct expansion are associated with improved stroke outcome. Methods. Forty-nine patients were studied with serial magnetic resonance imaging within 6 hours of stroke onset and again at 4 days (subacute studies) and 3 months (outcome studies). Two imaging parameters were examined: infarct expansion between acute and outcome studies and major reperfusion between acute and subacute studies. Results. Patients with major reperfusion (45% of those with acute PWI lesions) were more likely to have little or no disability at outcome (National Institutes of Health Stroke Scale [NIHSS] score = 4, P= .0176; Barthel Index [BI] score = 90, P= .0547)fter adjustment for baseline differences. In contrast, patients with infarct expansion (48%) were more likely to be dead or dependent at outcome (BI 2, P< .0001). These measures were used to generate sample size calculations based on hypothetical treatment effects. Therapies postulated to double the proportion of patients with major reperfusion from one third to two thirds would require 41 patients in each group (treated and untreated) to be sufficiently powered to show a difference. Interventions postulated to halve the number of patients with infarct expansion from 50% to 25% would require 66 patients in each group to show a difference. Conclusions. Infarct expansion and major reperfusion are associated with clinically meaningful changes in stroke outcome. These measures could be used as surrogate markers of outcome in late phase II proof-of-concept stroke studies designed to provide efficacy signals before embarking on large phase III studies with definitive clinical endpoints.

Objective: To investigate whether patients with first-episode psychosis or chronic schizophrenia have an increased incidence of magnetic resonance imaging (MRI) brain abnormalities compared with control subjects. Method: Totally 340 clinical MRI reports [Controls (n = 98), first-episode psychoses (n = 152), chronic schizophrenia (n = 90)] were reported by a neuroradiologist blind to diagnosis and subsequently categorized using referral criteria (immediate, urgent, routine or no referral). Results: Thirty percent of all scans were reported by a neuroradiologist as abnormal, but the majority required no referral. Patients with chronic schizophrenia were more likely to have clinically significant abnormal scans than patients with first episode psychosis or control subjects. In four patients the MRI findings led to the discovery of previously unsuspected pathology. Conclusion: Patients with chronic schizophrenia have an increased prevalence of incidental brain abnormalities. A small proportion of patients with chronic schizophrenia and first-episode psychosis benefitted directly from MRI scanning.

the words produced by younger adults and older adults. Nine of the categories (3 living categories, 3 non-living categories and 3 mixed categories) least influenced by normal ageing were then selected to be administered to patients with MCI prodromal to AD. Conclusions: Performance on the altered version of the CFT is unaffected by normal ageing effects and will further help in understanding the automatic and executive semantic impairment in pathological ageing due to AD. It may also be more sensitive to the earliest preclinical and presymptomatic changes caused byADwhen applied in patients with MCI. The practical implications for diagnosis of this modified neuropsychological instrument are important since it will improve the identification of people at risk during the earliest stage of the disease before irreversible neural damage occurs. This will allow for timely therapeutic intervention should disease modifying drugs become available in the future.

pants imaged with 11 C-PiB (PiB). e4 was present in 43% of the PiB cohort and 26% of the flute cohort while 54% of the PIB and 65% flute HC were classed as SMC by an affirmative answer to the question "Do you have difficulty with your memory?" and normal for age psychometric scores. PET images were acquired 90-110 mins post-injection of 18 F-flutemetamol and 40-70 minutes post-injection of 11 C-PiB. Neocortical SUVR were calculated using the pons as reference region for flutemetamol and a cutoff of 0.62 to define scans as low (Ab -) or high (Ab +) Ab burden. PiB was normalized to cerebellar cortex and a cut-off of 1.5 was used. Results: Compared to HC without memory complaint, SMC in both cohorts had significantly higher anxiety scores. Only in the flute cohort did the SMC have lower composite memory scores and have a higher prevalence of Ab + cases (OR 6.25, p1⁄40.002). However, in both cohorts a significantly increased prevalence of Ab + cases was present in, and confined to, the e4 carriers with SMC (66% vs 30% in e4 carriers without complaint in the PiB cohort; 63% vs 10% in the flute cohort). Conclusions: Subjective memory complaint is only associated with increased risk of preclinical AD in e4 carriers. Screening for SMC e4 carriers will provide amyloid positive scans in over 60% of subjects and may reduce the cost of amyloid imaging to identify individuals for preclinical AD trials.

Objective To investigate the neuroradiological correlates of age-related cognitive decline in the elderly. Design A sample of healthy control subjects underwent magnetic resonance imaging (MRI) scanning and cognitive testing. Setting Melbourne, Australia. Participants 40 volunteers over the age of 55 who were spouses of subjects seen in a hospital memory clinic, subjects from a register of normal volunteer subjects (not staff) kept for research purposes or residents of a retirement hostel. Measures Hippocampal and amygdala (HA) atrophy, periventricular lesions (PVL) and deep white matter lesions (DWML) were rated by two radiologists blind to cognitive test score results. Cognitive assessment was by the Cambridge Cognitive Examination (CAMCOG). Results After controlling for age and education, lower scores on the memory subscale of the CAMCOG were associated with the presence of HA atrophy, but not with DWML or PVL. Conclusions HA atrophy on MRI is associated with impaired memory performance in the healthy elderly, while PVL and DWML are not. Further study should determine whether HA atrophy is a risk factor for developing dementia.

andTaiwanese). Thuswe performedan epidemiology study inTaiwan to study the relationship between bilingualism and dementia.Methods: In this study, we investigate the language profile, MMSE, AD8 of 499 people in a local community (Taishan) of Taiwan. People in Taishan who are older than 70 years old were recruited since February, 2011 to December, 2011. 73 (14.6%) of them are bilinguals, 426 (85.4%) are monolinguals. Clinical neurologist confirms the diagnosis of dementia in all subjects. Results: The results reveal no significant difference in dementia prevalence between bilingual (16.4%) and monolingual (15.0%) population. But age of bilinguals is older than monolinguals (78.4 v.s. 73.4). Bilinguals show significant higher MMSE results (mean: 24.5) compare to monolinguals (mean: 22.7). Conclusions: Although the dementia prevalence didn’t show significant difference between the 2 groups, there is 5 years difference between age of bilinguals and monolinguals in this study. This suggests s that bilingualism may still have some protective effects on dementia. Besides, bilingualism itself does have advantage on MMSE scores, especially in sub-items of attention and constructional praxis. More research works have to be done to demonstrate the meaning and possible implication of language effects on dementia.

This paper proposes an inexpensive means of assessing radiofrequency (RF) power deposition in a magnet. This is particularly important at 3T where sequences approach Food and Drug Administration approved RF limits. It will also be of interest to operators at 1.5 T as part of their ongoing quality assurance programs. At 3T, we found that the RF power deposited in the magnet was less than that read by the MR power monitor.

The objective of this paper is to describe clinical applications of magnetic resonance angiography. The data used were obtained from recent articles on vascular and flow magnetic resonance imaging retrieved from Index Medicus 1988-91. Other contributions were from the 19th Annual Meeting of the American Society of Neuroradiology held in Washington DC in June 1991 and the 10th Annual Conference of the Society of Magnetic Resonance in Medicine in August 1991. The data are presented in such a way as to give the reader unfamiliar with magnetic resonance a basic insight into some of the new imaging techniques. Magnetic resonance imaging is advancing at a rapid rate. Magnetic resonance angiography is already finding many areas of clinical use with concomitant reduction in conventional angiographic and duplex Doppler ultrasound procedures.