Association between Carotid Plaque Features on CTA and Cerebrovascular Ischemia: A Systematic Review and Meta-Analysis.

BACKGROUND: CTA is a widely available imaging examination that may allow the evaluation of high-risk carotid plaque features. PURPOSE: Our aim was to evaluate the association between specific carotid plaque features on CTA and ipsilateral cerebrovascular ischemia. DATA SOURCES: We performed a systematic review of Ovid MEDLINE, Ovid Embase, Scopus, and the Cochrane Library from inception to March 2016 for articles that evaluated the relationship between CTA-detected carotid plaque features and ischemic events, defined as ipsilateral ischemic stroke or transient ischemic attack. STUDY SELECTION: Sixteen studies were ultimately included after screening 12,557. DATA ANALYSIS: Two readers recorded data from each study and assessed the study quality with all disagreements resolved by a third reader. A random-effects OR was used to evaluate the association between cerebrovascular ischemia and each of the evaluated plaque features. DATA SYNTHESIS: We found significant positive relationships with cerebrovascular ischemia for the presence of soft plaque (OR, 2.9; 95% CI, 1.4-6.0), plaque ulceration (OR, 2.2; 95% CI, 1.4-3.4), and increased common carotid artery wall thickness (OR, 6.2; 95% CI, 2.5-15.6). We found a significant negative relationship between calcified plaque and ipsilateral ischemia (OR, 0.5; 95% CI, 0.4-0.7). LIMITATIONS: We found heterogeneity in the existing literature secondary to lack of standardized plaque features and clinical definitions. CONCLUSIONS: Soft plaque, plaque ulceration, and increased common carotid artery wall thickness on CTA are associated with ipsilateral cerebrovascular ischemia, while calcified plaque is negatively associated with downstream ischemic events.

Association between Intracranial Atherosclerotic Calcium Burden and Angiographic Luminal Stenosis Measurements.

BACKGROUND AND PURPOSE: Calcification of the intracranial vasculature is an independent risk factor for stroke. The relationship between luminal stenosis and calcium burden in the intracranial circulation is incompletely understood. We evaluated the relationship between atherosclerotic calcification and luminal stenosis in the intracranial ICAs. MATERIALS AND METHODS: Using a prospective stroke registry, we identified patients who had both NCCT and CTA or MRA examinations as part of a diagnostic evaluation for ischemic stroke. We used NCCTs to qualitatively (modified Woodcock Visual Score) and quantitatively (Agatston-Janowitz Calcium Score) measure ICA calcium burden and used angiography to measure arterial stenosis. We calculated correlation coefficients between the degree of narrowing and calcium burden measures. RESULTS: In 470 unique carotid arteries (235 patients), 372 (79.1%) had atherosclerotic calcification detectable on CT compared with 160 (34%) with measurable arterial stenosis on CTA or MRA (P < .001). We found a weak linear correlation between qualitative (R = 0.48) and quantitative (R = 0.42) measures of calcium burden and the degree of luminal stenosis (P < .001 for both). Of 310 ICAs with 0% luminal stenosis, 216 (69.7%) had measurable calcium scores. CONCLUSIONS: There is a weak correlation between intracranial atherosclerotic calcium scores and luminal narrowing, which may be explained by the greater sensitivity of CT than angiography in detecting the presence of measurable atherosclerotic disease. Future studies are warranted to evaluate the relationship between stenosis and calcium burden in predicting stroke risk.

Quantifying Intracranial Internal Carotid Artery Stenosis on MR Angiography.

BACKGROUND AND PURPOSE: Intracranial atherosclerosis is a common cause of ischemic stroke. Intracranial stenosis is most commonly quantified by the Warfarin-Aspirin Symptomatic Intracranial Disease method, which involves calculating a ratio of luminal diameter measurements on conventional angiography. Our purpose was to determine whether a single linear measurement of the narrowest caliber of the intracranial ICA on MRA can accurately predict Warfarin-Aspirin Symptomatic Intracranial Disease stenosis measurements. MATERIALS AND METHODS: We identified patients from a prospective stroke registry who had undergone head MRAs to quantitatively evaluate the degree of Warfarin-Aspirin Symptomatic Intracranial Disease-derived stenosis in each intracranial ICA. We also made a single linear millimeter measurement at the site of maximal narrowing of the ICA. We calculated a correlation coefficient between the lumen diameter in millimeters and percentage Warfarin-Aspirin Symptomatic Intracranial Disease stenosis. We performed receiver operating characteristic analysis to determine optimal luminal diameter cutoff values. RESULTS: In 386 unique intracranial ICAs, we found a strong linear relationship between single lumen measurements and Warfarin-Aspirin Symptomatic Intracranial Disease-style stenosis measurements (R = -0.84, P < .0001). We found that ICA lumen diameters of ≤2.1 and ≤1.3 mm were optimal cutoffs for identifying patients with ≥50% stenosis and ≥70% stenosis, respectively (area under the curve = 0.96 and 0.99, respectively). CONCLUSIONS: There is a strong linear relationship between the narrowest lumen diameter of the intracranial ICA and percentage stenosis. Our results suggest that a single lumen diameter measurement on MRA allows accurate estimation of Warfarin-Aspirin Symptomatic Intracranial Disease stenosis, which may affect risk stratification and treatment decisions.

Application of Blood-Brain Barrier Permeability Imaging in Global Cerebral Edema.

BACKGROUND AND PURPOSE: Blood-brain barrier permeability is not routinely evaluated in the clinical setting. Global cerebral edema occurs after SAH and is associated with BBB disruption. Detection of global cerebral edema using current imaging techniques is challenging. Our purpose was to apply blood-brain barrier permeability imaging in patients with global cerebral edema by using extended CT perfusion. MATERIALS AND METHODS: Patients with SAH underwent CTP in the early phase after aneurysmal rupture (days 0-3) and were classified as having global cerebral edema or nonglobal cerebral edema using established noncontrast CT criteria. CTP data were postprocessed into blood-brain barrier permeability quantitative maps of PS (permeability surface-area product), K(trans) (volume transfer constant from blood plasma to extravascular extracellular space), Kep (washout rate constant of the contrast agent from extravascular extracellular space to intravascular space), VE (extravascular extracellular space volume per unit of tissue volume), VP (plasmatic volume per unit of tissue volume), and F (plasma flow) by using Olea Sphere software. Mean values were compared using t tests. RESULTS: Twenty-two patients were included in the analysis. Kep (1.32 versus 1.52, P < .0001), K(trans) (0.15 versus 0.19, P < .0001), VP (0.51 versus 0.57, P = .0007), and F (1176 versus 1329, P = .0001) were decreased in global cerebral edema compared with nonglobal cerebral edema while VE (0.81 versus 0.39, P < .0001) was increased. CONCLUSIONS: Extended CTP was used to evaluate blood-brain barrier permeability in patients with SAH with and without global cerebral edema. Kep is an important indicator of altered blood-brain barrier permeability in patients with decreased blood flow, as Kep is flow-independent. Further study of blood-brain barrier permeability is needed to improve diagnosis and monitoring of global cerebral edema.

Evaluating Permeability Surface-Area Product as a Measure of Blood-Brain Barrier Permeability in a Murine Model.

BACKGROUND AND PURPOSE: Permeability surface-area product has been suggested as a marker for BBB permeability with potential applications in clinical care and research. However, few studies have demonstrated its correlation with actual quantitative measurements of BBB permeability. Our aim was to demonstrate the correlation of quantitative permeability surface-area product and BBB permeability in a murine model by histologic confirmation. MATERIALS AND METHODS: Coronal MR imaging was performed on mice treated with mannitol (n = 6) for disruption of the BBB and controls treated with saline (n = 5). Permeability surface-area product was determined by ROI placement and was compared between saline- and mannitol-treated mice. Correlation was made with contrast-enhancement measurements and immunohistologic-stained sections of tripeptidyl peptidase-1 distribution in mice treated with mannitol and saline followed by injection of a viral vector containing the CLN2 gene, which directs production of tripeptidyl peptidase-1. RESULTS: Significantly increased permeability surface-area product was seen in mannitol- compared with saline-treated mice in the whole brain (P = .008), MCA territory (P = .014), and mixed vascular territories (P = .008). These findings were compared with contrast-enhancement measurements of BBB permeability and were correlated with immunohistologic-stained sections demonstrating BBB permeability to a large vector. CONCLUSIONS: Permeability surface-area product is increased in situations with known disruptions of the BBB, as evidenced by immunologic staining of large-vector passage through the BBB and concordance with contrast-enhancement measurements in a murine model. Quantitative permeability surface-area product has potential as an imaging marker of BBB permeability.

Automated calcium burden measurement in internal carotid artery plaque with CT: a hierarchical adaptive approach.

AIM: Calcium burden measurement in internal carotid artery (ICA) plaque could play an important role in assessing stroke risk and stenosis quantification in the ICA. We propose an automatic method for labelling calcified plaques in ICA in CT images. METHODS: Our approach builds upon the mean shift paradigm via an adaptive thresholding strategy. The data consists of single CT slices from 75 patients, with variety of plaque sizes and number of calcium regions. The manual measurements were carried out by a neuroradiologist for benchmarking. The calcium burden was measured as the area of the labelled plaque. Various metrics were employed to compare manual and automated measurements including correlation coefficient (CC), dice similarity (DS), Jacard Index (JI), polyline distance metric (PDM) and precision of merit (PoM). RESULTS: We found that our automated method of calcium area characterization performed accurately compared to manual measurements with CC=0.978, and PoM=0.915. The PDM, DS, and JI, also indicate a good performance with a mean DS=0.85 (SD=0.085), a mean JI=0.747 (SD=0.12), and a mean PDM=0.195 (SD=0.177). CONCLUSION: The proposed approach for calcium burden measurement, yields reasonably accurate labelling of calcified plaque when benchmarked against manual measurements. The approach is independent of the number and size of calcium regions, and the prototype design shows encouraging results to be adaptable to clinical practice.

CT angiographic features of symptom-producing plaque in moderate-grade carotid artery stenosis.

BACKGROUND AND PURPOSE: Emerging evidence indicates that plaque imaging can improve stroke risk stratification in patients with carotid artery atherosclerosis. We studied the association between soft and hard (calcified) plaque thickness measurements on CTA and symptomatic disease status (ipsilateral stroke or TIA) in patients with moderate-grade carotid artery stenosis. MATERIALS AND METHODS: We measured soft-plaque and hard-plaque thickness on CTA axial source images in each carotid artery plaque in subjects with NASCET 50%-69% ICA stenosis. We used logistic regression and receiver operating characteristic analyses to assess the strength of the association between thickness measurements and prior stroke or TIA. RESULTS: Twenty of 72 vessels studied (27.7%) had ischemic symptoms ipsilateral to the side of moderate-grade carotid stenosis. Each 1-mm increase in soft plaque resulted in a 3.7 times greater odds of a prior ipsilateral ischemic event (95% CI, 1.9-7.2). Conversely, for each 1-mm increase in hard plaque, the odds of being symptomatic decreased by approximately 80% (OR, 0.22; 95% CI, 0.10%-0.48%). Receiver operating characteristic analysis showed an area under the curve of 0.88 by using soft-plaque thickness measurements to discriminate between asymptomatic and symptomatic plaques. Sensitivity and specificity were optimized by using a maximum soft-plaque thickness of 2.2 mm, which provided a sensitivity of 85% and a specificity of 83%. CONCLUSIONS: Simple CTA plaque-thickness measurements might differentiate symptomatic and asymptomatic moderate-grade carotid artery plaque. With further prospective validation, CTA plaque measures could function as an easily implementable tool for risk stratification in carotid artery disease.

FAC1, a novel gene identified with the monoclonal antibody Alz50, is developmentally regulated in human brain.

The monoclonal antibody Alz50 recognizes both neurofibrillary pathology associated with Alzheimer's disease and subplate neurons in the developing human brain. To attempt to identify Alz50 antigens expressed during development, a human fetal brain cDNA library was immunoscreened. A positive clone was isolated and sequenced. The clone represents a novel gene named FAC1 (Fetal Alz-50-Reactive Clone 1). The FAC1 gene is located on human chromosome 17 and is conserved across species. In the human fetal brain, the FAC1 gene product is abundantly expressed and the protein is located both in the nucleus and the cytoplasm of cells throughout the developing cortex. Decreased levels of FAC1 protein are observed in adult brain by immunoblot analysis. By immunocytochemistry, the FAC1 protein is almost exclusively localized in the nucleus of neurons in the adult neocortex. Therefore, expression of the FAC1 gene is developmentally regulated and the cellular localization of the protein product is altered during development.

Two methods of single-dose ampule opening and their influence upon glass particulate contamination.

Contamination of glass ampules by glass fragments can occur following ampule opening. The intravenous administration of these glass fragments in animal experiments has resulted in insult to the brain, pulmonary, hepatic, renal, and splenic systems of these animals. Thus, it is of clinical importance to determine quantitatively the extent of glass particulate contamination by examining the different methods of glass ampule opening. Twenty, 2-mL single-dose glass ampules were examined for glass fragments following opening. Ten of the ampules were snapped open by hand while 10 were snapped open with the use of a commercial ampule opener. The contents of the ampules were aspirated into a 5-mL glass syringe, attached to an 18-gauge nonfilter needle. The contents of the syringe were filtered, then examined for glass fragments under a microscope. The size and number of glass particles were recorded using a calibrated ocular micrometer. Analysis of variance for repeated measures and Duncan's test showed no significant difference between the two groups. Thus, no significant difference existed in the number and size of glass particles aspirated when comparing these two ampule opening methods.