Showing papers in "Journal of Neuroimaging in 2018"

Cortical Thickness Estimations of FreeSurfer and the CAT12 Toolbox in Patients with Alzheimer's Disease and Healthy Controls

Abstract: Background and purpose Automated cortical thickness (CT) measurements are often used to assess gray matter changes in the healthy and diseased human brain. The FreeSurfer software is frequently applied for this type of analysis. The computational anatomy toolbox (CAT12) for SPM, which offers a fast and easy-to-use alternative approach, was recently made available. Methods In this study, we compared region of interest (ROI)-wise CT estimations of the surface-based FreeSurfer 6 (FS6) software and the volume-based CAT12 toolbox for SPM using 44 elderly healthy female control subjects (HC). In addition, these 44 HCs from the cross-sectional analysis and 34 age- and sex-matched patients with Alzheimer's disease (AD) were used to assess the potential of detecting group differences for each method. Finally, a test-retest analysis was conducted using 19 HC subjects. All data were taken from the OASIS database and MRI scans were recorded at 1.5 Tesla. Results A strong correlation was observed between both methods in terms of ROI mean CT estimates (R2 = .83). However, CAT12 delivered significantly higher CT estimations in 32 of the 34 ROIs, indicating a systematic difference between both approaches. Furthermore, both methods were able to reliably detect atrophic brain areas in AD subjects, with the highest decreases in temporal areas. Finally, FS6 as well as CAT12 showed excellent test-retest variability scores. Conclusion Although CT estimations were systematically higher for CAT12, this study provides evidence that this new toolbox delivers accurate and robust CT estimates and can be considered a fast and reliable alternative to FreeSurfer.

Spinal Cord Atrophy in Multiple Sclerosis: A Systematic Review and Meta-Analysis.

Abstract: BACKGROUND AND PURPOSE Spinal cord atrophy (SCA) is an important emerging outcome measure in multiple sclerosis (MS); however, there is limited consensus on the magnitude and rate of atrophy. The objective of this study was to synthesize the available data on measures of SCA in MS. METHODS Using published guidelines, relevant literature databases were searched between 1977 and 2017 for case-control or cohort studies reporting a quantitative measure of SCA in MS patients. Random-effects models pooled cross-sectional measures and longitudinal rates of SCA in MS and healthy controls (HCs). Student's t-test assessed differences between pooled measures in patient subgroups. Heterogeneity was assessed using DerSimonian and Laird's Q-test and the I 2 -index. RESULTS A total of 1,465 studies were retrieved including 94 that met inclusion and exclusion criteria. Pooled estimates of mean cervical spinal cord (SC) cross-sectional area (CSA) in all MS patients, relapsing-remitting MS (RRMS), all progressive MS, secondary progressive MS (SPMS), primary-progressive MS (PPMS), and HC were: 73.07 mm2 (95% CI [71.52-74.62]), 78.88 mm2 (95% CI [76.92-80.85]), 69.72 mm2 (95% CI [67.96-71.48]), 68.55 mm2 (95% CI [65.43-71.66]), 70.98 mm2 (95% CI [68.78-73.19]), and 80.87 mm2 (95% C I [78.70-83.04]), respectively. Pooled SC-CSA was greater in HC versus MS (P < .001) and RRMS versus progressive MS (P < .001). SCA showed moderate correlations with global disability in cross-sectional studies (r-value with disability score range [-.75 to -.22]). In longitudinal studies, the pooled annual rate of SCA was 1.78%/year (95%CI [1.28-2.27]). CONCLUSIONS The SC is atrophied in MS. The magnitude of SCA is greater in progressive versus relapsing forms and correlates with clinical disability. The pooled estimate of annual rate of SCA is greater than reported rates of brain atrophy in MS. These results demonstrate that SCA is highly relevant as an imaging outcome in MS clinical trials.

Role of FDG-PET/MRI, FDG-PET/CT, and Dynamic Susceptibility Contrast Perfusion MRI in Differentiating Radiation Necrosis from Tumor Recurrence in Glioblastomas.

Abstract: BACKGROUND AND PURPOSE To compare the utility of quantitative PET/MRI, dynamic susceptibility contrast (DSC) perfusion MRI (pMRI), and PET/CT in differentiating radiation necrosis (RN) from tumor recurrence (TR) in patients with treated glioblastoma multiforme (GBM). METHODS The study included 24 patients with GBM treated with surgery, radiotherapy, and temozolomide who presented with progression on imaging follow-up. All patients underwent PET/MRI and pMRI during a single examination. Additionally, 19 of 24 patients underwent PET/CT on the same day. Diagnosis was established by pathology in 17 of 24 and by clinical/radiologic consensus in 7 of 24. For the quantitative PET/MRI and PET/CT analysis, a region of interest (ROI) was drawn around each lesion and within the contralateral white matter. Lesion to contralateral white matter ratios for relative maximum, mean, and median were calculated. For pMRI, lesion ROI was drawn on the cerebral blood volume (CBV) maps and histogram metrics were calculated. Diagnostic performance for each metric was assessed using receiver operating characteristic curve analysis and area under curve (AUC) was calculated. RESULTS In 24 patients, 28 lesions were identified. For PET/MRI, relative mean ≥ 1.31 resulted in AUC of .94 with both sensitivity and negative predictive values (NPVs) of 100%. For pMRI, CBV max ≥3.32 yielded an AUC of .94 with both sensitivity and NPV measuring 100%. The joint model utilizing r-mean (PET/MRI) and CBV mode (pMRI) resulted in AUC of 1.0. CONCLUSION Our study demonstrates that quantitative PET/MRI parameters in combination with DSC pMRI provide the best diagnostic utility in distinguishing RN from TR in treated GBMs.

Neuroimaging of Dilated Perivascular Spaces: From Benign and Pathologic Causes to Mimics.

Abstract: Perivascular spaces (PVSs), also known as Virchow-Robin spaces, are pial-lined, fluid-filled structures found in characteristic locations throughout the brain. They can become abnormally enlarged or dilated and in rare cases can cause hydrocephalus. Dilated PVSs can pose a diagnostic dilemma for radiologists because of their varied appearance, sometimes mimicking more serious entities such as cystic neoplasms, including dysembryoplastic neuroepithelial tumor and multinodular and vacuolating neuronal tumor, or cystic infections including toxoplasmosis and neurocysticercosis. In addition, various pathologic processes, including cryptococcosis and chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids, can spread into the brain via PVSs, resulting in characteristic magnetic resonance imaging appearances. This review aims to describe the key imaging characteristics of normal and dilated PVSs, as well as cystic mimics and pathologic processes that directly involve PVSs.

MIMoSA: An Automated Method for Intermodal Segmentation Analysis of Multiple Sclerosis Brain Lesions.

Abstract: Background and purpose Magnetic resonance imaging (MRI) is crucial for in vivo detection and characterization of white matter lesions (WMLs) in multiple sclerosis. While WMLs have been studied for over two decades using MRI, automated segmentation remains challenging. Although the majority of statistical techniques for the automated segmentation of WMLs are based on single imaging modalities, recent advances have used multimodal techniques for identifying WMLs. Complementary modalities emphasize different tissue properties, which help identify interrelated features of lesions. Methods Method for Inter-Modal Segmentation Analysis (MIMoSA), a fully automatic lesion segmentation algorithm that utilizes novel covariance features from intermodal coupling regression in addition to mean structure to model the probability lesion is contained in each voxel, is proposed. MIMoSA was validated by comparison with both expert manual and other automated segmentation methods in two datasets. The first included 98 subjects imaged at Johns Hopkins Hospital in which bootstrap cross-validation was used to compare the performance of MIMoSA against OASIS and LesionTOADS, two popular automatic segmentation approaches. For a secondary validation, a publicly available data from a segmentation challenge were used for performance benchmarking. Results In the Johns Hopkins study, MIMoSA yielded average Sorensen-Dice coefficient (DSC) of .57 and partial AUC of .68 calculated with false positive rates up to 1%. This was superior to performance using OASIS and LesionTOADS. The proposed method also performed competitively in the segmentation challenge dataset. Conclusion MIMoSA resulted in statistically significant improvements in lesion segmentation performance compared with LesionTOADS and OASIS, and performed competitively in an additional validation study.

Atrophied Brain Lesion Volume: A New Imaging Biomarker in Multiple Sclerosis.

Abstract: BACKGROUND AND PURPOSE Lesion accrual in multiple sclerosis (MS) is an important and clinically relevant measure, used extensively as an imaging trial endpoint. However, lesions may also shrink or disappear entirely due to atrophy. Although generally ignored or treated as a nuisance, this phenomenon may actually be an important stand-alone imaging biomarker. Therefore, we investigated the rate of brain lesion loss due to atrophy (atrophied lesion volume) in MS subtypes compared to baseline lesion volume and to new and enlarging lesion volumes, and evaluated the independent predictive value of this phenomenon for clinical disability. METHODS A total of 192 patients (18 clinically isolated syndrome, 126 relapsing-remitting MS, and 48 progressive) received 3T magnetic resonance imaging at baseline and 5 years. Lesions were quantified at baseline, and new/enlarging lesion volumes were calculated over the study interval. Atrophied lesion volume was calculated by combining baseline lesion masks with follow-up SIENAX-derived cerebrospinal fluid partial volume maps. Measures were compared between disease subgroups, and correlations with disability change (Expanded Disability Status Scale [EDSS]) were evaluated. Hierarchical regression was employed to determine the unique additive value of atrophied lesion volume. RESULTS Atrophied lesion volume was different between MS subtypes (P = .02), and exceeded new lesion volume accumulation in progressive MS (298.1 vs. 75.5 mm3 ). Atrophied lesion volume was the only significant correlate of EDSS change (r = .192 relapsing, r = .317 progressive, P < .05), and explained significant additional variance when controlling for brain atrophy and new/enlarging lesion volume (R2 .092 vs. .045, P = .003). CONCLUSION Atrophied lesion volume is a unique and clinically relevant imaging marker in MS, with particular promise in progressive MS.

Reproducibility of Brain MRI Segmentation Algorithms: Empirical Comparison of Local MAP PSTAPLE, FreeSurfer, and FSL-FIRST.

Abstract: BACKGROUND AND PURPOSE Segmentation of human brain structures is crucial for the volumetric quantification of brain disease. Advances in algorithmic approaches have led to automated techniques that save time compared to interactive methods. Recently, the utility and accuracy of template library fusion algorithms, such as Local MAP PSTAPLE (PSTAPLE), have been demonstrated but there is little guidance regarding its reproducibility compared to single template-based algorithms such as FreeSurfer and FSL-FIRST. METHODS Eight repeated magnetic resonance imagings of 20 subjects were segmented using FreeSurfer, FSL-FIRST, and PSTAPLE. We reported the reproducibility of segmentation-derived volume measurements for brain structures and calculated sample size estimates for detecting hypothetical rates of tissue atrophy given the observed variances. RESULTS PSTAPLE had the most reproducible volume measurements for hippocampus, putamen, thalamus, caudate, pallidum, amygdala, Accumbens area, and cortical regions. FreeSurfer was most reproducible for brainstem. PSTAPLE was the most accurate algorithm in terms of several metrics include Dice's coefficient. The sample size estimates showed that a study utilizing PSTAPLE would require tens to hundreds less subjects than the other algorithms for detecting atrophy rates typically observed in brain disease. CONCLUSIONS PSTAPLE is a useful tool for automatic human brain segmentation due to its precision and accuracy, which enable the detection of the size of the effect typically reported for neurological disorders with a substantially reduced sample size, in comparison to the other tools we assessed. This enables randomized controlled trials to be executed with reduced cost and duration, in turn, facilitating the assessment of new therapeutic interventions.

Clinical and Neuroimaging Findings in Thalamic Territory Infarctions: A Review

Abstract: The thalamus is a part of the diencephalon, containing numerous connections between the forebrain and subcortical structures. It serves an important function as a relay center between the cerebral cortex and the subcortical regions, particularly with sensory information. The thalamus also plays a major role in regulating arousal and the levels of awareness. Distinct vascular distribution of the thalamus give rises to different syndromic presentation of thalamic nuclei infarcts. The clinical records and available imaging studies of patients with confirmed thalamic territory infarcts on magnetic resonance imaging (MRI) at the University Hospital of Rochester were reviewed and analyzed. This analysis was then used to provide an effective summary of thalamic vascular anatomy, the clinical symptoms, and syndromes associated with strokes in the affected territories. Specifically, we review the syndromes associated with classic vascular territories, including the anterior, paramedian, inferolateral, and posterior thalamic nuclei, that are supplied by the polar (tuberothalamic), paramedian, inferolateral (thalamogeniculate), and posterior choroidal arteries, respectively. In addition, we will also review the variant thalamic territories and associated infarction syndromes of the anteromedian, central, and posterolateral territories. This review article is aimed to better the clinical and radiologic understanding as well as the diagnosis of classic and variant thalamic territory infarcts. This article will also briefly touch on the recovery of function after thalamic infarcts.

Dual‐Sensitivity Multiple Sclerosis Lesion and CSF Segmentation for Multichannel 3T Brain MRI

Abstract: Background and purpose A pipeline for fully automated segmentation of 3T brain MRI scans in multiple sclerosis (MS) is presented. This 3T morphometry (3TM) pipeline provides indicators of MS disease progression from multichannel datasets with high-resolution 3-dimensional T1-weighted, T2-weighted, and fluid-attenuated inversion-recovery (FLAIR) contrast. 3TM segments white (WM) and gray matter (GM) and cerebrospinal fluid (CSF) to assess atrophy and provides WM lesion (WML) volume. Methods To address nonuniform distribution of noise/contrast (eg, posterior fossa in 3D-FLAIR) of 3T magnetic resonance imaging, the method employs dual sensitivity (different sensitivities for lesion detection in predefined regions). We tested this approach by assigning different sensitivities to supratentorial and infratentorial regions, and validated the segmentation for accuracy against manual delineation, and for precision in scan-rescans. Results Intraclass correlation coefficients of .95, .91, and .86 were observed for WML and CSF segmentation accuracy and brain parenchymal fraction (BPF). Dual sensitivity significantly reduced infratentorial false-positive WMLs, affording increases in global sensitivity without decreasing specificity. Scan-rescan yielded coefficients of variation (COVs) of 8% and .4% for WMLs and BPF and COVs of .8%, 1%, and 2% for GM, WM, and CSF volumes. WML volume difference/precision was .49 ± .72 mL over a range of 0-24 mL. Correlation between BPF and age was r = .62 (P = .0004), and effect size for detecting brain atrophy was Cohen's d = 1.26 (standardized mean difference vs. healthy controls). Conclusions This pipeline produces probability maps for brain lesions and tissue classes, facilitating expert review/correction and may provide high throughput, efficient characterization of MS in large datasets.

Effects of Aging on the Human Brain: A Proton and Phosphorus MR Spectroscopy Study at 3T.

Abstract: BACKGROUND AND PURPOSE To investigate accumulative aging effects on neurometabolism in human brain and to collect a reference dataset. METHODS Fifty-four healthy volunteers aged evenly between 22 and 73 years were studied using whole-brain 1 H-MR spectroscopic imaging in combination with 31 P-MRS at 3T. Global metabolite concentrations of brain N-acetylaspartate (NAA), total choline (tCho), and total creatine (tCr), as well as phosphocreatine (PCr), adenosine-5'-triphosphate (ATP), phosphomonoesters (PME), phosphodiesters (PDE), and inorganic phosphate (Pi) were determined. Fractional volumes of brain gray matter (FVGM), white matter (FVWM), and total tissue (FVTB, GM+WM) were also estimated. RESULTS With age, NAA, ATP, and PME, as well as FVTB and FVGM decreased and tCho and FVWM increased linearly. Positive correlations were found between FVGM and global concentrations of NAA, ATP, PME, and Pi. CONCLUSION Age-related accumulative metabolic changes in aging human brain correlated with reduced neuronal metabolic activity and density, reflected by decreased NAA, reduced mitochondrial activity by decreased ATP, and reduced membrane synthesis by decreased PME. These changes are associated with age-related decrease of neuronal volume. Global NAA and ATP might be used as surrogate biomarker for monitoring aging in human brain.

Early Blood-Brain Barrier Disruption after Mechanical Thrombectomy in Acute Ischemic Stroke.

Abstract: BACKGROUND AND PURPOSE The impact of blood-brain barrier (BBB) disruption can be detected by intraparenchymal hyperdense lesion on the computed tomography (CT) scan after endovascular stroke therapy. The purpose of this study was to determine whether early BBB disruption predicts intracranial hemorrhage and poor outcome in patients with acute ischemic stroke treated with mechanical thrombectomy. METHODS We analyzed patients with anterior circulation stroke treated with mechanical thrombectomy and identified BBB disruption on the noncontrast CT images immediately after endovascular treatment. Follow-up CT or magnetic resonance imaging scan was performed at 24 hours to assess intracranial hemorrhage. We dichotomized patients into those with moderate BBB disruption versus those with minor BBB disruption and no BBB disruption. We evaluated the association of moderate BBB disruption after mechanical thrombectomy with intracranial hemorrhage and clinical outcomes. RESULTS Moderate BBB disruption after mechanical thrombectomy was found in 56 of 210 patients (26.7%). Moderate BBB disruption was independently associated with higher rates of hemorrhagic transformation (OR 25.33; 95% CI 9.93-64.65; P < .001), parenchymal hematoma (OR 20.57; 95% CI 5.64-74.99; P < .001), and poor outcome at discharge (OR 2.35; 95% CI 1.09-5.07; P = .03). The association of BBB disruption with intracranial hemorrhage remained in patients with successful reperfusion after mechanical thrombectomy. The location of BBB disruption was not associated with intracranial hemorrhage and poor outcome. CONCLUSIONS Moderate BBB disruption is common after mechanical thrombectomy in a quarter of patients with acute ischemic stroke and increases the risk of intracranial hemorrhage and poor outcome.

MP2RAGE and Susceptibility-Weighted Imaging in Lesional Epilepsy at 7T.

Abstract: Background and purpose Surgery is the first choice therapeutic approach in case of drug-resistant epilepsy. Unfortunately, up to 43% of patients referred for presurgical assessment do not have a lesion detectable by routine 3T magnetic resonance imaging (MRI) (MRI-negative), although most of them likely have an underlying epileptogenic lesion. Thus, new MRI modalities with increased sensibility for epileptogenic lesions are required. This paper describes the magnetization-prepared two rapid acquisition gradient echoes (MP2RAGE) and susceptibility-weighted imaging (SWI) findings at 7T in a series of patients with drug-resistant epilepsy of different etiologies. Methods Prospective pilot study of 7 patients with drug-resistant lesional epilepsy and absence of contraindications for MRI underwent a research 7T head-only scanner. Qualitative analysis of the high-resolution MP2RAGE and SWI sequences is given for each case. This study was approved by the local ethics committee. Written informed consent was obtained from each participant. Results This study shows that such sequences at ultra-high field are new and valuable approaches to unravel and characterize epileptogenic lesions. Particularly, MP2RAGE shows a better delineation of lesions due to high gray-white matter contrast and structural resolution, and SWI reveals new imaging signs related to improved magnitude and phase contrast imaging. Conclusion MRI at ultra-high field is very promising for the detection of inconspicuous epileptogenic lesions and may facilitate epilepsy surgery of a great number of to-date MRI-negative patients.

Noninvasive PK11195-PET Image Analysis Techniques Can Detect Abnormal Cerebral Microglial Activation in Parkinson's Disease.

Abstract: Author(s): Kang, Yeona; Mozley, P David; Verma, Ajay; Schlyer, David; Henchcliffe, Claire; Gauthier, Susan A; Chiao, Ping C; He, Bin; Nikolopoulou, Anastasia; Logan, Jean; Sullivan, Jenna M; Pryor, Kane O; Hesterman, Jacob; Kothari, Paresh J; Vallabhajosula, Shankar | Abstract: BACKGROUND AND PURPOSE:Neuroinflammation has been implicated in the pathophysiology of Parkinson's disease (PD), which might be influenced by successful neuroprotective drugs. The uptake of [11 C](R)-PK11195 (PK) is often considered to be a proxy for neuroinflammation, and can be quantified using the Logan graphical method with an image-derived blood input function, or the Logan reference tissue model using automated reference region extraction. The purposes of this study were (1) to assess whether these noninvasive image analysis methods can discriminate between patients with PD and healthy volunteers (HVs), and (2) to establish the effect size that would be required to distinguish true drug-induced changes from system variance in longitudinal trials. METHODS:The sample consisted of 20 participants with PD and 19 HVs. Two independent teams analyzed the data to compare the volume of distribution calculated using image-derived input functions (IDIFs), and binding potentials calculated using the Logan reference region model. RESULTS:With all methods, the higher signal-to-background in patients resulted in lower variability and better repeatability than in controls. We were able to use noninvasive techniques showing significantly increased uptake of PK in multiple brain regions of participants with PD compared to HVs. CONCLUSION:Although not necessarily reflecting absolute values, these noninvasive image analysis methods can discriminate between PD patients and HVs. We see a difference of 24% in the substantia nigra between PD and HV with a repeatability coefficient of 13%, showing that it will be possible to estimate responses in longitudinal, within subject trials of novel neuroprotective drugs.

Interpretation of Brain CT Scans in the Field by Critical Care Physicians in a Mobile Stroke Unit.

Abstract: BACKGROUND AND PURPOSE In acute stroke, thromboembolism or spontaneous hemorrhage abruptly reduces blood flow to a part of the brain. To limit necrosis, rapid radiological identification of the pathological mechanism must be conducted to allow the initiation of targeted treatment. The aim of the Norwegian Acute Stroke Prehospital Project is to determine if anesthesiologists, trained in prehospital critical care, may accurately assess cerebral computed tomography (CT) scans in a mobile stroke unit (MSU). METHODS In this pilot study, 13 anesthesiologists assessed unselected acute stroke patients with a cerebral CT scan in an MSU. The scans were simultaneously available by teleradiology at the receiving hospital and the on-call radiologist. CT scan interpretation was focused on the radiological diagnosis of acute stroke and contraindications for thrombolysis. The aim of this study was to find inter-rater agreement between the pre- and in-hospital radiological assessments. A neuroradiologist evaluated all CT scans retrospectively. Statistical analysis of inter-rater agreement was analyzed with Cohen's kappa. RESULTS Fifty-one cerebral CT scans from the MSU were included. Inter-rater agreement between prehospital anesthesiologists and the in-hospital on-call radiologists was excellent in finding radiological selection for thrombolysis (kappa .87). Prehospital CT scans were conducted in median 10 minutes (7 and 14 minutes) in the MSU, and median 39 minutes (31 and 48 minutes) before arrival at the receiving hospital. CONCLUSION This pilot study shows that anesthesiologists trained in prehospital critical care may effectively assess cerebral CT scans in an MSU, and determine if there are radiological contraindications for thrombolysis.

Hematopoietic Stem Cell Transplantation in Late-Onset Krabbe Disease: No Evidence of Worsening Demyelination and Axonal Loss 4 Years Post-allograft.

Abstract: BACKGROUND AND PURPOSE Late-onset adult Krabbe disease is a very rare demyelinating leukodystrophy, affecting less than 1 in a million people. Hematopoietic stem cell transplantation (HSCT) strategies can stop the accumulation of toxic metabolites that damage myelin-producing cells. We used quantitative advanced imaging metrics to longitudinally assess the impact of HSCT on brain abnormalities in adult-onset Krabbe disease. METHODS A 42-year-old female with late-onset Krabbe disease and an age/sex-matched healthy control underwent annual 3T MRI (baseline was immediately prior to HSCT for the Krabbe subject). Imaging included conventional scans, myelin water imaging, diffusion tensor imaging, and magnetic resonance spectroscopy. RESULTS Brain abnormalities far beyond those visible on conventional imaging were detected, suggesting a global pathological process occurs in Krabbe disease with adult-onset etiology, with myelin being more affected than axons, and evidence of wide-spread gliosis. After HSCT, our patient showed clinical stability in all measures, as well as improvement in gait, dysarthria, and pseudobulbar affect at 7.5 years post-transplant. No MRI evidence of worsening demyelination and axonal loss was observed up to 4 years post-allograft. CONCLUSIONS Clinical evidence and stability of advanced MR measures related to myelin and axons supports HSCT as an effective treatment strategy for stopping progression associated with late-onset Krabbe disease.

The Role of Neuroimaging in the Determination of Brain Death.

Abstract: Background and purpose Brain death determination (BDD) is primarily a clinical diagnosis, where death is defined as the permanent loss of brainstem function. In scenarios where clinical examinations are inaccurate, ancillary imaging tests are required. The choice of ancillary imaging test is variable, but the common denominator for all of them is to establish a lack of cerebral blood flow. The purpose of this study was to compare the diagnostic accuracy and interrater reliability of different ancillary imaging tests used for BDD. Methods Archival data were retrospectively analyzed for all patients who underwent any ancillary imaging test for BDD at our institution. The results of ancillary imaging tests were compared with, the reference standard, the clinical checklist for declaration of brain death. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of different ancillary imaging tests for BDD were performed. Interobserver agreement between two observers was measured using kappa statistics for each of the imaging modalities. Results A total of 74 patients underwent 41 computer tomography perfusion (CTP), 54 CT angiogram, 15 radionuclide scans, 1 cerebral angiogram, 3 magnetic resonance imaging, and 71 nonenhanced CT (NECT) head for BDD. All ancillary tests (except NECT head) showed 100% specificity and PPV. CTP had the highest sensitivity and NPV. All ancillary imaging tests demonstrated very high interrater reliability. Conclusions The uses of ancillary imaging tests for BDD are increasing. Within this study's limitations, CTP followed by radionuclide scan were found to be the most accurate and reliable ancillary imaging test for BDD.

Clinical Neuroimaging Using 7 T MRI: Challenges and Prospects

Abstract: The aim of this article is to illustrate the principal challenges, from the medical and technical point of view, associated with the use of ultrahigh field (UHF) scanners in the clinical setting and to present available solutions to circumvent these limitations. We would like to show the differences between UHF scanners and those used routinely in clinical practice, the principal advantages, and disadvantages, the different UHFs that are ready be applied to routine clinical practice such as susceptibility-weighted imaging, fluid-attenuated inversion recovery, 3-dimensional time of flight, magnetization-prepared rapid acquisition gradient echo, magnetization-prepared 2 rapid acquisition gradient echo, and diffusion-weighted imaging, the technical principles of these sequences, and the particularities of advanced techniques such as diffusion tensor imaging, spectroscopy, and functional imaging at 7TMR. Finally, the main clinical applications in the field of the neuroradiology are discussed and the side effects are reported.

Evaluating the Association between Enlarged Perivascular Spaces and Disease Worsening in Multiple Sclerosis.

Abstract: Background and purpose Enlarged perivascular spaces (EPVSs) have been associated with relapses and brain atrophy in multiple sclerosis (MS). We investigated the association of EPVS with clinical and MRI features of disease worsening in a well-characterized cohort of relapsing-remitting MS patients prospectively followed for up to 10 years. Methods Baseline EPVSs were scored on 1.5T MRI in 30 converters to moderate-severe disability, and 30 nonconverters matched for baseline characteristics. Results EPVS scores were not significantly different between converters and nonconverters, nor associated with accrual of lesions or brain atrophy. Conclusions Our preliminary findings from a relatively small study sample argue against a potential use of EPVS as early indicator of risk for disease worsening in relapsing-remitting MS patients in a clinical setting. Although the small sample size and clinical 1.5T MRI may have limited our ability to detect a significant effect, we provided estimates of the association of EPVS with clinical and MRI indicators of disease worsening in a well-characterized cohort of MS patients.

Anomalies and Normal Variants of the Cerebral Arterial Supply: A Comprehensive Pictorial Review with a Proposed Workflow for Classification and Significance.

Abstract: Cerebral arteries may exhibit a wide range of variation from normal anatomy, which can be incidentally discovered during imaging. Knowledge of such variants is crucial to differentiate them from pathologies, to understand the etiology of certain pathologies directly related to a vascular variant, and to depict the changes in collateral circulation in patients with certain variants. Detection of particular variants may lead to the discovery of other nonvascular or vascular anomalies, especially aneurysms, and may also affect planning of endovascular or neurosurgical interventions. In this review, we summarize the variants and anomalies of cerebral arteries seen on cross-sectional imaging classified by a morphological approach and categorize their significance from a clinical perspective. This structured review is intended to serve as a guide for daily use in clinical practice.

Transorbital Sonography for Early Prognostication of Hypoxic‐Ischemic Encephalopathy After Cardiac Arrest

Abstract: BACKGROUND AND PURPOSE Early prognostication of the outcome in resuscitated post cardiac arrest (CA) patients remains challenging especially if treated with therapeutic hypothermia. Brain edema caused by hypoxic-ischemic encephalopathy (HIE) can indirectly be estimated by transorbital sonography (TOS) taking in account the optic nerve sheath diameter (ONSD). The prognostic value of this easy, safe, and reproducible technique was investigated in this study. METHODS A total of 49 patients, initially unconscious (Glasgow Coma Scale ≤6) after successful resuscitation, were enrolled into this prospective observational study. Sonographic ONSD measurements were performed twice on day of admission (day 0) and once on days 1 and 2 after CA. Beyond ONSD, established prognostic parameters like neuron specific enolase and gray-white matter ratios were assessed. Cerebral Performance Category (CPC) score served as outcome parameter. RESULTS A total of 15 (31.3%) patients had a good outcome (CPC-score 1-2), 8 patients (14.6%) had severe disability (CPC-score 3-4), and 26 (54.2%) had a fatal outcome (CPC-score 5). Already in the first measurement on day 0, nonsurvivors showed significantly higher ONSD values (P < .001). For predicting mortality, a threshold of 5.75 mm was calculated with a specificity of 100%. ONSD did not differ significantly depending on hypothermia (P = .7009). CONCLUSION Early and reliable prognostication of outcomes in patients with HIE can be simplified by ONSD values gathered with the use of TOS. Main advantages compared to other established markers are prognostication within the first 24 hours and independence from therapy with hypothermia. A higher level of accuracy can be reached by combining computed tomography (gray-to-white matter ratio values) and ONSD values.

An MRI Hyperintense Acute Reperfusion Marker Is Related to Elevated Peripheral Monocyte Count in Acute Ischemic Stroke.

Abstract: BACKGROUND AND PURPOSE Blood-brain barrier (BBB) disruption detected on magnetic resonance imaging (MRI) in acute ischemic stroke as a hyperintense acute reperfusion marker (HARM) is associated with upregulation of matrix metalloproteinase-9 (MMP-9). Although activated leukocytes, including monocytes, are the main source of MMPs, limited data exist to support relationship between leukocyte activation and BBB disruption in patients with acute ischemic stroke. The goal of this study is to investigate the relationship between neutrophils, lymphocytes, and monocytes with BBB disruption detected as HARM (+) in patients with acute ischemic stroke. METHODS We conducted a retrospective analysis of prospectively collected data in patients who did not receive any reperfusion therapy with acute (<12 hours) ischemic stroke. MRI scans were obtained at baseline, 24 hours, and 5 days. HARM was evaluated on the 24-hour follow-up scan. RESULTS Thirty-three patients were studied. HARM was detected in 27% of patients. Median volumes of baseline perfusion (mean transit time [MTT]) deficit (219.4 mL vs. 158.4 mL, P = .029) and DWI infarct growth at 24 hours (18.50 mL vs. .14 mL, P = .017), as well as the median absolute numbers (1 × 103 /mm3 ) of monocytes, were significantly higher in HARM (+) versus HARM (-) patients (0.9 vs. 0.6, p = 0.011). CONCLUSION Increased monocyte count associated with HARM supports importance of systemic inflammation in BBB disruption in acute ischemic stroke.

Hemodynamic Changes May Indicate Vessel Wall Injury After Stent Retrieval Thrombectomy for Acute Stroke.

Abstract: Background and purpose Stent retrievers have revolutionized endovascular treatment of acute ischemic stroke (AIS). Animal studies showed that mechanical thrombectomy (MT) may cause endothelial injury and intimal layer edema. Using transcranial color-coded duplex-sonography (TCCS) we observed postprocedural hemodynamic changes in the treated vessel. Methods We studied AIS patients with large intracranial artery occlusion in whom MT with stent retrievers was performed. Only those with complete recanalization (modified TICI-2b or 3) as assessed by postprocedural digital subtraction angiography (DSA) and in whom early control TCCS was performed were retained. Patients treated with intra-arterial thrombolysis or stenting were excluded. Results In 31 patients treated within a time period of 4 years (29 with middle cerebral artery [MCA] and 2 with basilar artery [BA] occlusion), postacute stroke brain-DSA confirmed complete recanalization without residual stenosis or vasospasm. However, in 27 (17 men, mean age 66.3 years) of them TCCS (mean 3.4 days after MT) showed very segmental acceleration of blood flow velocities in the affected arteries (MCA maximum peak systolic velocity [PSVmax] at least >35% as compared to the contralateral side at the same depth; BA PSVmax >40% as compared to velocities at different depths of the same vessel). None showed clinical deterioration. TCCS follow-up (mean 20 days) showed normalization in 14 of 16 cases. Conclusion Our TCCS study provides preliminary evidence of focal acceleration of blood flow velocities after MT. Without residual stenosis or vasospasm, this may be a sign of endothelial layer disruption/intimal injury. Further studies are needed to confirm our results.

Cerebral White Matter Maturation Patterns in Preterm Infants: An MRI T2 Relaxation Anisotropy and Diffusion Tensor Imaging Study

Abstract: BACKGROUND AND PURPOSE Preterm birth is associated with worse neurodevelopmental outcome, but brain maturation in preterm infants is poorly characterized with standard methods. We evaluated white matter (WM) of infant brains at term-equivalent age, as a function of gestational age at birth, using multimodal magnetic resonance imaging (MRI). METHODS Infants born very preterm (<32 weeks gestation) and late preterm (33-36 weeks gestation) were scanned at 3 T at term-equivalent age using diffusion tensor imaging (DTI) and T2 relaxometry. MRI data were analyzed using tract-based spatial statistics, and anisotropy of T2 relaxation was also determined. Principal component analysis and linear discriminant analysis were applied to seek the variables best distinguishing very preterm and late preterm groups. RESULTS Across widespread regions of WM, T2 is longer in very preterm infants than in late preterm ones. These effects are more prevalent in regions of WM that myelinate earlier and faster. Similar effects are obtained from DTI, showing that fractional anisotropy (FA) is lower and radial diffusivity higher in the very preterm group, with a bias toward earlier myelinating regions. Discriminant analysis shows high sensitivity and specificity of combined T2 relaxometry and DTI for the detection of a distinct WM development pathway in very preterm infants. T2 relaxation is anisotropic, depending on the angle between WM fiber and magnetic field, and this effect is modulated by FA. CONCLUSIONS Combined T2 relaxometry and DTI characterizes specific patterns of retarded WM maturation, at term equivalent age, in infants born very preterm relative to late preterm.

Cluster Confidence Index: A Streamline-Wise Pathway Reproducibility Metric for Diffusion-Weighted MRI Tractography.

Abstract: BACKGROUND Diffusion-weighted magnetic resonance imaging tractography can be used to create models of white matter fascicles Anatomical and pathological variability between subjects can drastically alter the tractography output, so standardizing results across a cohort is nontrivial Furthermore, tractography methods have inherently low reproducibility due to stochasticity (for probabilistic methods) and subjective decisions, since the final fascicle model often requires a manual intervention step performed by an expert human operator to control both outliers and systematic false-positive pathways, as defined by prior knowledge of anatomy METHODS We present an approach that computationally assigns a cluster confidence index (CCI) reflecting the reproducibility of that pathway in the context of a streamline dataset This metric is a tractography algorithm-agnostic tool that can be applied to any dataset of streamlines RESULTS Applications of this metric include systematic elimination of outlier streamlines using a CCI threshold and interactive filtering by CCI to facilitate manual segmentation of fascicle models CONCLUSIONS This method is intended to replace the application of a streamline density threshold so that outliers are eliminated based on low pathway density instead of voxel-wise density

Comparative Analysis of Markers of Mass Effect after Ischemic Stroke.

Abstract: BACKGROUND AND PURPOSE: Midline shift determined on magnetic resonance imaging (MRI) or computed tomography (CT) images is a well-validated marker of mass effect after large hemispheric infarction and associated with mortality. In this study, we targeted a population with moderately sized strokes. We compared midline shift to other imaging markers and determined their ability to predict long-term outcome. METHODS: MRI scans were studied from the Echoplanar Imaging Thrombolysis Evaluation Trial (EPITHET) cohort. Midline shift, acute stroke lesion volume, lesional swelling volume, change in ipsilateral hemisphere volume, the ratio of ipsilateral to contralateral hemisphere volume, and the reduction in lateral ventricle volume were measured. The relationships of these markers with poor outcome (modified Rankin scale score 3-6 at day 90) were assessed. Receiver-operating characteristic (ROC) curves were generated to compare the performance of each metric. RESULTS: Of the 71 included patients, 59.2% had a poor outcome that was associated with significantly larger values for midline shift, lesional swelling volume, and ratio of hemisphere volumes. Lesional swelling volume, change in hemisphere volume, ratio of hemisphere volumes, and lateral ventricle displacement were each correlated with midline shift (Spearman r = .60, .49, .61, and -.56, respectively; all P < .0001). ROC curve analysis showed that lesional swelling volume (area under the curve [AUC] = .791) predicted poor outcome better than midline shift (AUC = .682). For predicting mortality, ROC curve analysis showed that these three markers were equivalent. CONCLUSION: The ratio of ipsilateral to contralateral hemisphere volume, baseline lesion volume and lesional swelling volume best predicted poor outcome across a spectrum of stroke sizes.

Transcranial Doppler and Transcranial Color Duplex in Defining Collateral Cerebral Blood Flow.

Abstract: In an acute stroke setting, transcranial Doppler (TCD) and transcranial color-coded duplex (TCCD) have an important diagnostic utility in the monitoring of an arterial occlusion and microemboli detection. In addition, TCD has proven to be a very useful tool in the detection and progression of cerebral vasospasm in patients with subarachnoid hemorrhage. TCD/TCCD may have an important role in defining collateral blood flow (CF) in stroke patients. It is a noninvasive technique and can be utilized repeatedly allowing for changes in the blood flow dynamics as treatment is delivered. In this review, we outlined the evolving role of TCD/TCCD in defining CF in patients with an acute ischemic stroke, predicting clinical outcome and monitoring the treatment's efficacy of the CF augmentation.

Embryonal Tumor with Multilayered Rosettes, C19MC-Altered: Clinical, Pathological, and Neuroimaging Findings.

Abstract: Background and purpose Embryonal tumor with multilayered rosettes (ETMR), C19MC-altered, is a recently described, rare central nervous system tumor. To our knowledge, the imaging findings of this tumor have not been systematically evaluated in the neuroradiology literature. We present here the clinical, radiological, and pathological correlation of a case series of this very rare tumor, including the full range of anatomic compartment presentations (supratentorial, infratentorial, and spinal). Methods We retrospectively analyzed 7 (4M, 3F) pathologically-proven cases of ETMR referred to our institution between 2007 and 2017. We demonstrate the imaging characteristics of this tumor on CT and MRI with advanced imaging. Results All of the patients are children (ages 1-12). On MR imaging of ETMR, contrast enhancement is often heterogeneous and minimal if any, and there is no significant surrounding T2 fluid-attenuated inversion recovery (FLAIR) hyperintensity to suggest edema. The lesions were often expansile with no evidence of infiltration of the fiber tracks that were displaced by the tumor mass. Diffusion-weighted imaging often demonstrated restricted diffusion within ETMRs. On magnetic resonance spectroscopy (MRS), the choline/creatine (Cho/Cr) ratio is increased, with low N-acetylaspartate (NAA) or NAA/Cho ratio, typical of high-grade tumors. Conclusion We demonstrate the conventional and advanced imaging characteristics of ETMR, including MRS and diffusion tensor imaging, which, to our knowledge, have not been systematically evaluated in the radiology literature. The knowledge gained may potentially impact patient management, especially in inoperable cases and in locations where it is risky to perform a biopsy.

The CT-Defined Hyperdense Arterial Sign as a Marker for Acute Intracerebral Large Vessel Occlusion

Abstract: Background and Purpose To determine the sensitivity and specificity of the hyperdense artery sign (HAS) on thin-slice non-contrast computed tomography (NCCT), combined with brief clinical history, as an indicator for large vessel occlusion (LVO) in the setting of acute ischemic stroke. Methods Ninety-nine LVO and 102 non-LVO acute ischemic stroke patients were retrospectively identified from a prospective database at a single institution. After reviewing each patient's neurologic presentation based on his or her initial National Institute of Health Stroke Scale (NIHSS) and neurologic evaluation, all thin (1 mm) and thick (5 mm) NCCT scans were reviewed for the HAS. Analysis of sensitivity and specificity was conducted to determine the utility of the HAS sign as a reliable marker for LVO in acute ischemic stroke patients. Results Of the 99 LVO stroke patients, 66 HASs were identified on NCCT. Of the 102 non-LVO patients, 18 false-positive HASs were identified. The sensitivity and specificity of the HAS, respectively, was 67% and 82%. By anatomic distribution, the sensitivity of identifying basilar artery occlusions was 75%, and the sensitivity of identifying middle cerebral artery (MCA) M1 branch occlusions was 76%. Among patients with an NIHSS > 10, the sensitivity was 79%; whereas sensitivity was 50% if NIHSS was ≤ 10. Conclusions The HAS on thin-slice NCCT has a reasonably high sensitivity and specificity for identifying LVO in acute ischemic stroke patients presenting with an NIHSS > 10 and suspected MCA M1 or basilar artery occlusion.

I-123 DaTscan SPECT Brain Imaging in Parkinsonian Syndromes: Utility of the Putamen-to-Caudate Ratio

Abstract: Background and purpose Computer-based analysis of Dopamine transporter imaging (DaTscan) can aid in image interpretation. In this study, we examined the distribution of putamen-to-caudate ratios (PCRs) obtained by using a clinically available semiquantification method. Methods Medical records of 32 patients (M:16) with a diagnosis of Parkinson's disease (PD) (n = 22) or Parkinson's plus syndromes (PPS) (n = 10) based on clinical follow-up, were retrospectively reviewed. Single photon emission tomography (SPECT) imaging was performed 4 hours after intravenous injection of 3-5 mCi [I-123]-ioflupane. Semiquantitative evaluation using DaTQUANT software was performed. Utility of PCR with a cutoff of .7 and .8 in the diagnosis of nigrostriatal degeneration was assessed. PD and PPS groups based on clinical assessment and caudate-to-background ratio (CBR) were assessed separately. Results Minimum PCR for both hemispheres was .74 ± .09 (Mean ± SD, range: .58-.89), with 65.63% patients (21/32) having PCR > .7. Mean PCR in mild nigrostriatal degeneration was .77 ± .08 (range: .62-.89) and in advanced nigrostriatal degeneration was .73 ± .09 (range: .58-.89). Mean PCR in PD group was .73 ± .09 (range: .58-.89) and in PPS group was .75 ± .10 (range: .61-.88). Conclusions Although PCR can intrinsically be a useful indication of disease, this ratio obtained in our analysis by using one of the clinically available automatic semiquantitative methods has large variability and might not be a reliable numeric marker in interpretation of [I-123]ioflupane studies. This may be due to difficulty in separating caudate from putamen on SPECT images, as well as the nonuniform decreased Ioflupane uptake in both putamen and caudate.

Structural Complexity of the Cerebellum and Cerebral Cortex is Reduced in Spinocerebellar Ataxia Type 2

Abstract: BACKGROUND AND PURPOSE Fractal dimension (FD) is an index of structural complexity of cortical gray matter (GM) and white matter (WM). Application of FD to pontocerebellar degeneration has revealed cerebellar changes. However, so far, possible concurrent cerebral changes and progression of changes in brain complexity have not been investigated. METHODS We computed FD of cerebellar and cerebral cortex and WM derived from longitudinal brain MRI of patients with spinocerebellar ataxia type 2 (SCA2), which is an inherited cause of pontocerebellar degeneration. Nine SCA2 patients and 16 age-matched healthy controls were examined twice (3.6 ± .7 and 3.3 ± 1.0 years apart, respectively) on the same 1.5T MR scanner with T1-weighted imaging. Cortical GM and WM of the cerebrum and cerebellum were segmented using FreeSurfer and FD of these segmentations were computed. RESULTS At baseline, FD values of cerebellar GM and WM were significantly (P < .001) lower in SCA2 patients (2.48 ± .04 for GM and 1.74 ± .09 for WM) than in controls (2.56 ± .02 for GM and 2.22 ± .19 for WM). Also, FD values of cerebral GM were significantly (P < .05) lower in SCA2 patients (2.39 ± .03) than in controls (2.43 ± .02). No significant differences were observed for FD of the cerebral WM. The rate of change of FD values was not significantly different between SCA2 patients and controls. CONCLUSIONS The structural complexity of the cerebellum and cerebral cortex is reduced in SCA2 patients. Fractal analysis seems not to be able to demonstrate progression of changes associated with degeneration in SCA2.