Resting quantitative cerebral blood flow in schizophrenia measured by pulsed arterial spin labeling perfusion MRI

Department of Psychology, Southern Methodist University, Dallas, TX, USA.
Psychiatry Research (Impact Factor: 2.47). 08/2011; 194(1):64-72. DOI: 10.1016/j.pscychresns.2011.06.013
Source: PubMed

ABSTRACT Arterial spin labeling (ASL) perfusion MRI is a relatively novel technique that can allow for quantitative measurement of cerebral blood flow (CBF) by using magnetically labeled arterial blood water as an endogenous tracer. Available data on resting CBF in schizophrenia primarily come from invasive and expensive nuclear medicine techniques that are often limited to small samples and yield mixed results. The noninvasive nature of ASL offers promise for larger-scale studies. The utility of this approach was examined in 24 healthy controls and 30 patients with schizophrenia. Differences between groups in quantitative CBF were assessed, as were relationships between CBF and psychiatric symptoms. Group comparisons demonstrated greater CBF for controls in several regions including bilateral precuneus and middle frontal gyrus. Patients showed increased CBF in left putamen/superior corona radiata and right middle temporal gyrus. For patients, greater severity of negative symptoms was associated with reduced CBF in bilateral superior temporal gyrus, cingulate gyrus, and left middle frontal gyrus. Increased severity of positive symptoms was related to both higher CBF in cingulate gyrus and superior frontal gyrus and decreased CBF in precentral gyrus/middle frontal gyrus. These findings support the feasibility and utility of implementing ASL in schizophrenia research and expand upon previous results.

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Available from: Ruben Gur, Jan 27, 2014
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    • "An extensive review done by Fusar-Poli et al. (2007) reported notable alterations in brain activation, coupled with decreased performance in respect to controls, and an involvement of various cerebral regions. Perfusion has been found altered in patients with schizophrenia using dynamic susceptibility contrast MRI (Loeber et al., 1999; Brambilla et al., 2007; Bellani et al., 2011; Peruzzo et al., 2011) or arterial spin labeling (Pinkham et al., 2011; Wolf et al., 2012) or positron emission tomography (Faget-Agius et al., 2012). Also patients with Schizophrenia Research 165 (2015) 38–44 ⁎ Corresponding author at: Dipartimento di Salute Mentale e Neuroscienze, Università degli Studi di Milano, U.O.C. Psichiatria, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milano, Italy. "
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    ABSTRACT: Hemodynamic changes in the brain have been reported in major psychosis in respect to healthy controls, and could unveil the basis of structural brain modifications happening in patients. The study of first episode psychosis is of particular interest because the confounding role of chronicity and medication can be excluded. The aim of this work is to automatically discriminate first episode psychosis patients and normal controls on the basis of brain perfusion employing a support vector machine (SVM) classifier. 35 normal controls and 35 first episode psychosis underwent dynamic susceptibility contrast magnetic resonance imaging, and cerebral blood flow and volume, along with mean transit time were obtained. We investigated their behavior in the whole brain and in selected regions of interest, in particular the left and right frontal, parietal, temporal and occipital lobes, insula, caudate and cerebellum. The distribution of values of perfusion indexes were used as features in a support vector machine classifier. Mean values of blood flow and volume were slightly lower in patients, and the difference reached statistical significance in the right caudate, left and right frontal lobes, and in left cerebellum. Linear SVM reached an accuracy of 83% in the classification of patients and normal controls, with the highest accuracy associated with the right frontal lobe and left parietal lobe. In conclusion, we found evidence that brain perfusion could be used as a potential marker to classify patients with psychosis, who show reduced blood flow and volume in respect to normal controls. Copyright © 2015 Elsevier B.V. All rights reserved.
    Schizophrenia Research 04/2015; 165(1). DOI:10.1016/j.schres.2015.03.017 · 3.92 Impact Factor
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    • "Abnormal CBF has been reported in a variety of neurological diseases and disorders [3-6]. While the majority of CBF related studies have focused on gray matter, aberrant white matter perfusion has been observed in schizophrenia [7], normal pressure hydrocephalus [8], and multiple sclerosis [9]. Although the physiological and pathophysiological mechanisms underlying these findings are not yet fully understood, reliable and quantitative measurement of CBF is desirable for its potential of facilitating clinical diagnosis/prognosis, treatment formulation, and neuroscience investigation. "
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    ABSTRACT: This study was aimed to experimentally and numerically investigate the feasibility of measuring cerebral white matter perfusion using pseudocontinuous arterial spin labeling (PCASL) 3T magnetic resonance imaging (MRI) at a relatively fine resolution to mitigate partial volume effect from gray matter. The Institutional Research Ethics Committee approved this study. On a clinical 3T MR system, ten healthy volunteers (5 females, 5 males, age = 28±3 years) were scanned after providing written informed consent. PCASL imaging was performed with varied combinations of labeling duration (τ = 1000, 1500, 2000, and 2500 ms) and post-labeling delay (PLD = 1000, 1400, 1800, and 2200 ms), at a spatial resolution (1.56x1.56x5 mm(3)) finer than commonly used (3.5x3.5 mm(2), 5-8 mm in thickness). Computer simulations were performed to calculate the achievable perfusion-weighted signal-to-noise ratio at varied τ, PLD, and transit delay. Based on experimental and numerical data, the optimal τ and PLD were found to be 2000 ms and 1500-1800 ms, respectively, yielding adequate SNR (~2) to support perfusion measurement in the majority (~60%) of white matter. The measurement variability was about 9% in a one-week interval. The measured white matter perfusion and perfusion ratio of gray matter to white matter were 15.8-27.5 ml/100ml/min and 1.8-4.0, respectively, depending on spatial resolution as well as the amount of deep white matter included. PCASL 3T MRI is able to measure perfusion in the majority of cerebral white matter at an adequate signal-to-noise ratio by using appropriate tagging duration and post-labeling delay. Although pixel-wise comparison may not be possible, region-of-interest based flow quantification is feasible.
    PLoS ONE 12/2013; 8(12):e82679. DOI:10.1371/journal.pone.0082679 · 3.23 Impact Factor
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    • "Since the introduction of ASL, and despite its low SNR, a large number of studies have demonstrated its usefulness in identifying patterns of abnormal perfusion at the group level (e.g. [34]). "
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    ABSTRACT: In this paper, patient-specific perfusion abnormalities in Arterial Spin Labeling (ASL) were identified by comparing a single patient to a group of healthy controls using a mixed-effect hierarchical General Linear Model (GLM). Two approaches are currently in use to solve hierarchical GLMs: (1) the homoscedastic approach assumes homogeneous variances across subjects and (2) the heteroscedastic approach is theoretically more efficient in the presence of heterogeneous variances but algorithmically more demanding. In practice, in functional magnetic resonance imaging studies, the superiority of the heteroscedastic approach is still under debate. Due to the low signal-to-noise ratio of ASL sequences, within-subject variances have a significant impact on the estimated perfusion maps and the heteroscedastic model might be better suited in this context. In this paper we studied how the homoscedastic and heteroscedastic approaches behave in terms of specificity and sensitivity in the detection of patient-specific ASL perfusion abnormalities. Validation was undertaken on a dataset of 25 patients diagnosed with brain tumors and 36 healthy volunteers. We showed evidence of heterogeneous within-subject variances in ASL and pointed out an increased false positive rate of the homoscedastic model. In the detection of patient-specific brain perfusion abnormalities with ASL, modeling heterogeneous variances increases the sensitivity at the same specificity level.
    NeuroImage 05/2013; 81. DOI:10.1016/j.neuroimage.2013.04.079 · 6.36 Impact Factor
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