Prevalence and the predictive performance of the dynamic CT-angiography spot sign in an observational cohort with intracerebral hemorrhage.

The CT-angiography (CTA) spot sign is a predictor of hematoma expansion (HE). We have previously reported on the use of dynamic CTA (dCTA) to detect spot sign, and to study its formation over the acquisition period. In this study, we report the frequency of dCTA spot sign in acute intracerebral hemorrhage, its sensitivity and specificity to predict HE, and explore the rate of contrast extravasation in relation to hematoma growth.We enrolled consecutive patients presenting with primary intracerebral hemorrhage within 4.5 hours. All patients underwent a dCTA protocol acquired over 60 seconds following contrast injection. We calculated frequency of the dCTA spot sign, predictive performance, and rate of contrast extravasation. We compared extravasation rates to the dichotomous definition of significant HE (defined as 6 mL or 33% growth).In 78 eligible patients, dCTA spot sign frequency was 44.9%. In 61 patients available for expansion analysis, sensitivity and specificity of dCTA spot sign was 65.4% and 62.9%, respectively. Contrast extravasation rate did not significantly predict HE (Odds Ratio 15.6 for each mL/min [95% confidence interval 0.30-820.25], P = .17). Correlation between extravasation rate and HE was low (r = 0.297, P= .11). Patients with significant HE had a higher rate of extravasation as compared to those without (0.12 mL/min vs 0.04 mL/min, P = .03).Dynamic CTA results in a higher frequency of spot sign positivity, but with modest sensitivity and specificity to predict expansion. Extravasation rate is likely related to HE, but a single measurement may be insufficient to predict the magnitude of expansion.

Distribution and predictive performance of the temporal phase of dynamic spot sign appearance in acute intracerebral hemorrhage.

BACKGROUND: Dynamic CT angiography (dCTA) contrast extravasation, known as the "dynamic spot sign", can predict hematoma expansion (HE) in intracerebral hemorrhage (ICH). Recent reports suggest the phase of spot sign appearance is related to the magnitude of HE. We used dCTA to explore the association between the phase of spot sign appearance and HE, clinical outcome, and contrast extravasation rates. METHODS: We assessed consecutive patients who presented with primary ICH within 4.5 hours from symptom onset who underwent a standardized dCTA protocol and were spot sign positive. The independent variable was the phase of spot sign appearance. The primary outcome was significant HE (either 6 mL or 33% growth). Secondary outcomes included total absolute HE, mortality, and discharge mRS. Mann-Whitney U, Fisher's exact test, and logistic regression were used, as appropriate. RESULTS: Of the 35 patients with spot signs, 27/35 (77%) appeared in the arterial phase and 8/35 (23%) appeared in the venous phase. Thirty patients had follow-up CT scans. Significant HE was seen in 14/23 (60.87%) and 3/7 (42.86%) of arterial and venous cohorts, respectively (p = 0.67). The sensitivity and specificity in predicting significant HE were 82% and 31% for the arterial phase and 18% and 69% for the venous phase, respectively. There was a non-significant trend towards greater total HE, in-hospital mortality, and discharge mRS of 4-6 in the arterial spot sign cohort. Arterial spot signs demonstrated a higher median contrast extravasation rate (0.137 mL/min) compared to venous spot signs (0.109 mL/min). CONCLUSION: Our exploratory analyses suggest that spot sign appearance in the arterial phase may be more likely associated with HE and poorer prognosis in ICH. This may be related to higher extravasation rates of arterial phase spot signs. However, further studies with larger sample sizes are warranted to confirm the findings.

Serial Quantitative Computed Tomography Perfusion in Aneurysmal Subarachnoid Hemorrhage.

PURPOSE: Computed tomography perfusion (CTP) has been performed to predict which patients with aneurysmal subarachnoid hemorrhage are at risk of developing delayed cerebral ischemia (DCI). Patients with severe arterial narrowing may have significant reduction in perfusion. However, many patients have less severe arterial narrowing. There is a paucity of literature evaluating perfusion changes which occur with mild to moderate narrowing. The purpose of our study was to investigate serial whole-brain CTP/computed tomography angiography in aneurysm-related subarachnoid hemorrhage (aSAH) patients with mild to moderate angiographic narrowing. METHODS: We retrospectively studied 18 aSAH patients who had baseline and follow-up whole-brain CTP/computed tomography angiography. Thirty-one regions of interest/hemisphere at six levels were grouped by vascular territory. Arterial diameters were measured at the circle of Willis. The correlation between arterial diameter and change in CTP values, change in CTP in with and without DCI, and response to intra-arterial vasodilator therapy in DCI patients was evaluated. RESULTS: There was correlation among the overall average cerebral blood flow (CBF; R=0.49, p<0.04), mean transit time (R=-0.48, p=0.04), and angiographic narrowing. In individual arterial territories, there was correlation between changes in CBF and arterial diameter in the middle cerebral artery (R=0.53, p=0.03), posterior cerebral artery (R=0.5, p=0.03), and anterior cerebral artery (R=0.54, p=0.02) territories. Prolonged mean transit time was correlated with arterial diameter narrowing in the middle cerebral artery territory (R=0.52, p=0.03). Patients with DCI tended to have serial worsening of CBF compared with those without DCI (p=0.055). CONCLUSIONS: Our preliminary study demonstrates there is a correlation between mild to moderate angiographic narrowing and serial changes in perfusion in patients with aSAH. Patients developing DCI tended to have progressively worsening CBF compared with those not developing DCI.

Effects of low-level alcohol use on cognitive interference: an fMRI study in young adults.

Alcohol consumption is widely known to adversely affect human health. Its neuropathology is largely evident in the cerebellum and frontal lobes, particularly in the immature brains of adolescents and young adults. It may also have a long-lasting impact on executive functioning. The Ottawa Prenatal Prospective Study (OPPS) has followed participants over 20 years, from birth to young adulthood, and has collected data on potentially confounding lifestyle variables, such as prenatal drug exposure and current drug use. The present study investigated the neural activity of 29 young adults from the OPPS using fMRI. The main objective was to discover the impact of regular low-level alcohol consumption on the cognitive interference of these participants, as they performed a Counting Stroop task. Results indicated that, despite a lack of performance differences, young adults who use alcohol on a regular basis differ significantly from non-users with respect to their neural activity as they perform this task. Areas that were significantly more activated in users compared to non-users included the cerebellum, thalamus, fusiform gyrus, prefrontal cortex, and precuneus. The observed activity suggests a significant impact of early alcohol use on neurocognitive functioning despite relatively low levels of alcohol consumption.

Data-driven classification of ventilated lung tissues using electrical impedance tomography.

Current methods for identifying ventilated lung regions utilizing electrical impedance tomography images rely on dividing the image into arbitrary regions of interest (ROI), manually delineating ROI, or forming ROI with pixels whose signal properties surpass an arbitrary threshold. In this paper, we propose a novel application of a data-driven classification method to identify ventilated lung ROI based on forming k clusters from pixels with correlated signals. A standard first-order model for lung mechanics is then applied to determine which ROI correspond to ventilated lung tissue. We applied the method in an experimental study of 16 mechanically ventilated swine in the supine position, which underwent changes in positive end-expiratory pressure (PEEP) and fraction of inspired oxygen (F(I)O(2)). In each stage of the experimental protocol, the method performed best with k = 4 and consistently identified 3 lung tissue ROI and 1 boundary tissue ROI in 15 of the 16 subjects. When testing for changes from baseline in lung position, tidal volume, and respiratory system compliance, we found that PEEP displaced the ventilated lung region dorsally by 2 cm, decreased tidal volume by 1.3%, and increased the respiratory system compliance time constant by 0.3 s. F(I)O(2) decreased tidal volume by 0.7%. All effects were tested at p < 0.05 with n = 16. These findings suggest that the proposed ROI detection method is robust and sensitive to ventilation dynamics in the experimental setting.

A Bayesian hierarchical correlation model for fMRI cluster analysis.

Data-driven cluster analysis is potentially suitable to search for, and discriminate between, distinct response signals in blood oxygenation level-dependent functional magnetic resonance imaging (BOLD fMRI), which appear during cerebrovascular disease. In contrast to model-driven methods, which test for a particular BOLD signal whose shape must be given beforehand, data-driven methods generate a set of BOLD signals directly from the fMRI data by clustering voxels into groups with correlated time signals. Here, we address the problem of selecting only the clusters that represent genuine responses to the experimental stimulus by modeling the correlation structure of the clustered data using a Bayesian hierarchical model. The model is empirically justified by demonstrating the hierarchical organization of the voxel correlations after cluster analysis. BOLD signal discrimination is demonstrated using: 1) simulations that contain multiple pathological BOLD response signals; and 2) fMRI data acquired during an event-related motor task. These demonstrations are compared with results from a model-driven method based on the general linear model. Our simulations show that the data-driven method can discriminate between the BOLD response signals, while the model-driven method only finds one signal. For fMRI, the data-driven method distinguishes between the BOLD signals appearing in the sensorimotor cortex and those in basal ganglia and putamen, while the model-driven method combines these signals into one activation map. We conclude that the proposed data-driven method provides an objective framework to identify and discriminate between distinct BOLD response signals.

Effects of marijuana on visuospatial working memory: an fMRI study in young adults.

OBJECTIVES: The effects of marijuana use on visuospatial working memory were investigated in 19-21-year-olds using functional magnetic resonance imaging (fMRI). METHODS: Participants were members of the Ottawa Prenatal Prospective Study, a longitudinal study that collected a unique body of information on participants from infancy to young adulthood including: prenatal drug history, detailed cognitive/behavioral performance, and current and past drug usage. This information allowed for the measurement of an unprecedented number of potentially confounding drug exposure variables including: prenatal marijuana, nicotine, alcohol, and caffeine exposure and offspring alcohol, marijuana, and nicotine use. Ten marijuana users and 14 nonusing controls performed a visuospatial 2-back task while fMRI blood oxygen level-dependent response was examined. RESULTS: Despite similar task performance, marijuana users had significantly greater activation in the inferior and middle frontal gyri, regions of the brain normally associated with visuospatial working memory. Marijuana users also had greater activation in the right superior temporal gyrus, a region of the brain not typically associated with visuospatial working memory tasks. CONCLUSIONS: These results suggest that marijuana use leads to altered neural functioning during visuospatial working memory after controlling for other prenatal and current drug use. This alteration appears to be compensated for by the recruitment of blood flow in additional brain regions. It is possible that this compensation may not be sufficient in more real-life situations where this type of processing is required and thus deficits may be observed. Awareness of these neural physiological effects of marijuana in youth is critical.

Determination of the venous output function from MR signal phase: feasibility for quantitative DCE-MRI in human brain.

For dynamic contrast-enhanced MRI studies in the human brain, it is useful to measure the venous output function (VOF). The purpose of this work was to explore the feasibility of measuring the VOF using the MR signal phase (in absolute units of gadolinium concentration) in the superior sagittal sinus. Phantom experiments were performed to validate the technique for different superior sagittal sinus angles (theta = 0-48 degrees relative to the main magnetic field), different curvatures (straight or radius = 45 mm), and different spatial resolutions (2.2-5.5 mm, to study partial-volume effects). Additionally, the technique was tested on three patients. The phantom experimental results (echo time = 5.5 ms, theta

Toward a functional neuroanatomy of dysthymia: a functional magnetic resonance imaging study.

BACKGROUND: Dysthymia is a common mood disorder. Recent studies have confirmed the neurobiological and treatment response overlap of dysthymia with major depression. There are no previous published studies of functional magnetic resonance imaging (fMRI) in dysthymia. METHOD: fMRI was used to compare neural processing of 17 unmedicated dysthymic patients with 17 age, sex, and education-matched control subjects in a mood induction paradigm using the International Affective Pictures System (IAPS). RESULTS: Using a random effects analysis to compare the groups, the results revealed that the dysthymic patients had significantly reduced activation in the dorsolateral prefrontal cortex compared to controls. The dysthymic patients exhibited increased activation in the amygdala, anterior cingulate and insula compared to controls and these differences were more evident when processing negative than positive images. LIMITATIONS: This study included both early and late subtypes of dysthymia, and participants were only imaged at one time point, which may limit the generalizability of the results. CONCLUSIONS: The findings suggest the involvement of the prefrontal cortex, anterior cingulate, amygdala, and insula in the neural circuitry underlying dysthymia. It is suggested that altered activation in some of these neural regions may be a common substrate for depressive disorders in general while others may relate specifically to symptom characteristics and the chronic course of dysthymia. These findings are particularly striking given the history of this deceptively mild disorder which is still confused by some with character pathology.

fMRI investigation of disinhibition in cognitively impaired patients with multiple sclerosis.

UNLABELLED: Although deficits in executive functioning are well known cognitive sequelae of multiple sclerosis (MS), less is known about patients' performance on response inhibition tasks in particular. Behavioural observation of cognitively impaired MS patients often reveals impulsivity. However, knowledge about associated neural activity during response inhibition measurable with functional magnetic resonance imaging (fMRI) is lacking. In the current study the performance and fMRI activation patterns of patients with MS on a response inhibition task (Go/No-Go) were investigated. METHODS: Ten cognitively impaired patients with MS (with little or no physical disability) and 10 sex-, age- and education-matched healthy controls performed a Go/No-Go task while in the MR scanner. RESULTS: MS patients had significantly more commission errors than controls but did not demonstrate longer reaction times. Controlling for this difference, whole brain random effects analyses revealed that patients demonstrated more activation than controls in the fusiform gyrus, cingulate gyrus (including the anterior cingulate gyrus), cerebellum and putamen. Patients demonstrated less activity than controls in the supramarginal gyrus. CONCLUSIONS: MS patients exhibited significant neural compensation during response inhibition when compared with controls. The specific results provide new insight into the neural processing underlying the impulsivity often observed in cognitively impaired individuals with MS.

Selection criteria for the analysis of data-driven clusters in cerebral FMRI.

Functional MRI (fMRI) may be possible without a priori models of the cerebral hemodynamic response. First, such data-driven fMRI requires that all cerebral territories with distinct patterns be identified. Second, a systematic selection method is necessary to prevent the subjective interpretation of the identified territories. This paper addresses the second point by proposing a novel method for the automated interpretation of identified territories in data-driven fMRI. Selection criteria are formulated using: 1) the temporal cross-correlation between each identified territory and the paradigm and 2) the spatial contiguity of the corresponding voxel map. Ten event-design fMRI data sets are analyzed with one prominent algorithm, fuzzy c-means clustering, before applying the selection criteria. For comparison, these data are also analyzed with an established, model-based method: statistical parametric mapping. Both methods produced similar results and identified potential activation in the expected territory of the sensorimotor cortex in all ten data sets. Moreover, the proposed method classified distinct territories in separate clusters. Selected clusters have a mean temporal correlation coefficient of 0.39+/-0.07 (n=19) with a mean 2.7+/-1.4 second response delay. At most, four separate contiguous territories were observed in 87% of these clusters. These results suggest that the proposed method may be effective for exploratory fMRI studies where the hemodynamic response is perturbed during cerebrovascular disease.

White matter thresholds for ischemic penumbra and infarct core in patients with acute stroke: CT perfusion study.

PURPOSE: To prospectively determine the parameters derived at admission computed tomographic (CT) perfusion imaging admission that best differentiate ischemic white matter that recovers from that which infarcts, with the latter retrospectively defined at a CT examination performed without contrast material (unenhanced CT) 5-7 days after the event. MATERIALS AND METHODS: Ethics committee approval and informed consent were obtained. Thirty patients with stroke underwent unenhanced CT, CT angiography, and CT perfusion studies at admission. Additionally, CT angiography was performed 24 hours after the stroke, and an unenhanced CT study was performed 5-7 days after the stroke. Five patients were excluded; the remaining patients (10 men, 15 women; mean age, 70 years +/- 13 [standard deviation]) were separated into those with recanalization (n = 16) and those without recanalization (n = 9) at 24 hours. For patients with recanalization, the final infarct was outlined on unenhanced CT images obtained 5-7 days after the event and was superimposed on coregistered maps from the CT perfusion study performed at admission. Ischemic white matter tissue (cerebral blood flow [CBF] < 14 mL/min/100 g) was identified at the admission CT perfusion study, and the penumbra was defined as the difference between the ischemic region and the infarct region. RESULTS: Infarct regions showed a matched decrease in CBF and cerebral blood volume (CBV) at admission, whereas penumbra regions showed a significant (P < .05) decrease in CBF but no change in CBV (P > .05) from contralateral values. A threshold CBF . CBV value of 8.14 was the most sensitive (95%, 20 of 21 regions) and specific (94%, 32 of 34 regions) parameter for differentiating between regions of ischemic white matter that recovered and regions of ischemic white matter that infarcted. CONCLUSION: The product of CBF and CBV derived from CT perfusion data provided the best differentiation between regions of ischemic white matter that infarcted and regions of ischemic white matter that recovered 5-7 days after a stroke.

Acute anterior circulation stroke: recanalization using clot angioplasty.

BACKGROUND AND PURPOSE: Different strategies have been employed to recanalize acutely occluded middle cerebral and internal carotid arteries (ICA) in the setting of acute stroke including intravenous and intra-arterial tPA. However, pharmaceutical thrombolysis alone, may not be effective in patients with a large amount of clot volume (complete M1, terminal internal carotid artery). We report our initial experience with endovascular clot disruption using a soft silicone balloon in addition to intravenous or intra-arterial thrombolysis with tPA. METHODS: This is a retrospective review of nine patients with symptoms of acute stroke from clot in the middle cerebral or internal carotid territories who were treated with intracranial balloon angioplasty. All patients presented with symptoms of acute anterior circulation stroke less than six hours from onset. Patients in whom computed tomography (CT) angiography confirmed the presence of large vessel clot (terminal ICA, M1 or proximal M2) were included in the study. A CT perfusion was performed providing maps of cerebral blood volume, flow and mean transit time. If the patient presented less than three hours from onset then intravenous tissue plasminogen activator (tPA) was also administered. Intra-arterial tPA was delivered into the clot. If the volume of clot was judged to be significant by the treating neurointerventionist, then a limited trial of tPA was administered intra-arterially followed by balloon angioplasty of persistant clot. The time from imaging to vessel recanalization was recorded. Clinical outcomes were assessed using the modified Rankin scale and Barthel Index. RESULTS: Diagnostic CT perfusion studies were performed in 7 (78%), all of which showed a significant amount of salvageable tissue as judged by the treating neurointerventionist and neurologist. Recanalization (TIMI 2 or 3) was possible in 8 (89%). There were no cases of symptomatic intracranial hemorrhage and 2 (22%) asymptomatic hemorrhages. The average time from performance of the initial emergency CT to vessel recanalization was 2.1 hours with mean time from symptom onset to vessel recanalization of 4.1 hours. Five (56%) patients had good outcomes, 1 (11%) had mild and 3 (33%) had moderate to severe disability. CONCLUSION: Clot angioplasty can potentially shorten recanalization times in well-selected patients and can be an effective complimentary procedure in patients with tPA resistant clot. Angioplasty can be performed with a very low complication rate using the technique described and may be associated with good outcomes.

Effects of prenatal marijuana on visuospatial working memory: an fMRI study in young adults.

The long lasting neurophysiological effects of prenatal marijuana exposure on visuospatial working memory were investigated in 18-22 year olds using functional magnetic resonance imaging (fMRI). The participants are members of the Ottawa Prenatal Prospective Study (OPPS), a longitudinal study that provides a unique body of information collected from each participant over 20 years, including prenatal drug history, detailed cognitive/behavioral performance from infancy to young adulthood, and current and past drug usage. This information allowed for the control of potentially confounding drug exposure variables in the statistical analyses. Thirty-one offspring from the OPPS (16 prenatally exposed and 15 nonexposed) performed a visuospatial 2-back task while neural activity was imaged with fMRI. Cognitive performance data were also collected. No significant performance differences were observed when comparing controls versus exposed participants. Multiple regression analyses (including controls with no exposure) revealed that as the amount of prenatal marijuana exposure increased, there was significantly more neural activity in the left inferior and middle frontal gyri, left parahippocampal gyrus, left middle occipital gyrus and left cerebellum. There was also significantly less activity in right inferior and middle frontal gyri. These results suggest that prenatal marijuana exposure alters neural functioning during visuospatial working memory processing in young adulthood.

Acute bilateral opercular strokes causing loss of emotional facial movements.

UNLABELLED: The classic anterior opercular syndrome of Foix-Chavany-Marie presents with loss of voluntary facial, pharyngeal, lingual, and mastication movements, with preservation of emotional and automatic movements. Most commonly, sequential strokes affecting bilateral opercula cause this syndrome. The inverse clinical presentation, with selective loss of emotional facial movements, has only rarely been reported, and is less well-localized. CASE REPORT: We report a case of selective loss of emotional facial movements which resulted from bilateral acute infarcts. No etiology was discovered, and the syndrome was reversible. DISCUSSION: The available literature, and findings in this case, suggest that voluntary and automatic facial movements have distinct pathways, and damage to the insula bilaterally may lead to the selective loss of emotional facial movements. The clinical presentation of this inverse automatic/voluntary dissocation needs to be recognized as a rare syndrome with bilateral localization, so that patients at higher risk of further stroke can quickly be identified.

Sodium T2*-weighted MR imaging of acute focal cerebral ischemia in rabbits.

Changes in T2*-weighted tissue sodium (23Na) signal following acute ischemia may help to identify necrotic tissue and estimate the duration of ischemia. Sodium signal was monitored in a rabbit model of acute (0-4 h) focal cerebral ischemia, using gradient echo 23Na MR images (echo time = 3.2 ms) acquired continuously in 20-min intervals on a 4-Tesla MRI. 2,3,5-Triphenyl-tetrazolium chloride staining was used to identify regions of necrosis. In necrotic tissue, average 23Na image signal intensity decreased by 11% +/- 8% during the first 40 min of ischemia followed by a linear increase (0.19%/min) to 25% +/- 14% greater than baseline after 4 h of ischemia. The time course of 23Na signal change observed in necrotic tissue following focal ischemia in this rabbit model is consistent with an initial decrease in 23Na T2* relaxation time followed by an increase in tissue sodium concentration and provides further evidence that tissue 23Na signal may offer unique information regarding tissue viability that is complementary to other MR imaging techniques.

Effects of prenatal marijuana on response inhibition: an fMRI study of young adults.

The neurophysiological effects of prenatal marijuana exposure on response inhibition were assessed in 18- to 22-year-olds. Thirty-one participants from the Ottawa Prenatal Prospective Study (OPPS) performed a blocked design Go/No-Go task while neural activity was imaged with functional magnetic resonance imaging (fMRI). The OPPS is a longitudinal study that provides a unique body of information collected from each participant over 20 years, including prenatal drug history, detailed cognitive/behavioral performance from infancy to young adulthood, and current and past drug usage. The fMRI results showed that with increased prenatal marijuana exposure, there was a significant increase in neural activity in bilateral prefrontal cortex and right premotor cortex during response inhibition. There was also an attenuation of activity in left cerebellum with increased prenatal exposure to marijuana when challenging the response inhibition neural circuitry. Prenatally exposed offspring had significantly more commission errors than nonexposed participants, but all participants were able to perform the task with more than 85% accuracy. These findings were observed when controlling for present marijuana use and prenatal exposure to nicotine, alcohol and caffeine, and suggest that prenatal marijuana exposure is related to changes in neural activity during response inhibition that last into young adulthood.