Regional Cerebral Blood Flow Values Research Articles

A 3D pseudo-continuous arterial spin labeling study of altered cerebral blood flow correlation networks in mild cognitive impairment and Alzheimer's disease.

To investigate the abnormalities of the three-dimensional pseudo-continuous arterial spin labeling (3D PCASL) based cerebral blood flow (CBF) correlation networks in mild cognitive impairment (MCI) and Alzheimer's disease (AD). 3D PCASL images of 53 cognitive normal (CN) subjects, 43 subjects with MCI, and 30 subjects with AD were acquired from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Whole-brain CBF maps were calculated using PCASL and proton density-weighted images (PDWI). The 246 regional CBF values, including the cortex and subcortex, were obtained after registering the Brainnetome Atlas to the individual CBF maps. The Pearson correlation coefficient between every two regions across subjects was calculated to construct the CBF correlation network. Then the topologies of CBF networks with regard to global properties (global network efficiency, clustering coefficient, characteristic path length, and small-world properties), hub regions, nodal properties (betweenness centrality, BC), and connections were compared among CN, MCI, and AD. Significant changes in the global and nodal properties were observed in the permutation tests, and connections with significant differences survived after the z-statistic and false discovery rate (FDR) correction. The CBF correlation networks of CN, MCI, and AD all showed small-world properties. Compared with CN, global efficiency decreased significantly in AD. Significant differences in nodal properties and a loss of hub regions are noted in the middle temporal lobe in both MCI and AD. In the frontal lobe, BC is reduced in MCI while it is increased in the occipital lobe in AD. The identified altered hub regions with significant differences in MCI and AD were mainly distributed in the hippocampus and entorhinal cortex. In addition, disrupted hub regions in AD with significantly decreased connections were mainly found in the precuneus/posterior cingulate cortex (PCC) and hippocampus-cortical cortex. Noninvasive 3D PCASL-based CBF correlation networks are capable of showing changes in topological organization in subjects with MCI and AD, and the observed disruption in the topological organization may underlie cognitive decline in MCI and AD.

Proposal for diagnosis using FLAIR image aimed for pediatric MELAS with recurrent stroke-like episodes on MRI system cannot take ASL imaging

BackgroundArterial spin-labeling (ASL) imaging is currently the most useful method for diagnosing mitochondrial encephalomyopathy, lactic acidosis, and stroke-like attack syndrome (MELAS). However, ASL is often an optional feature of standard MRI systems. Therefore, not all MRI systems can perform ASL imaging. In contrast, fluid-attenuated inversion recovery (FLAIR) imaging is one of the common sequences in brain MRI because FLAIR imaging can be performed regardless of the specifications of the equipment. This study aimed to compare the diagnostic performance of quantitative analysis of signal intensity obtained from fluid-attenuated inversion recovery (FLAIR) images with ASL images for MELAS with recurrent stroke-like episodes (SLEs). A total of 68 cases with normal magnetic resonance imaging findings and 25 cases diagnosed MELAS with recurrent SLEs were included. We evaluated the frontal lobe and cuneus as target areas and compared the regional cerebral blood flow (rCBF) values obtained from ASL images with the normalized signal intensity (nSI) obtained from FLAIR images.ResultsThe sensitivity and specificity for diagnosing MELAS from linear discriminant analysis (LDA) obtained from the rCBF values were 0.84 and 0.941, respectively, and those of nSI were 0.8 and 0.897, respectively. The area under the ROC curves (AUC) calculated from the receiver operating characteristic (ROC) curve analysis using rCBF values and nSI were 0.889 and 0.804, respectively.ConclusionQuantitative analysis using the signal intensity of the FLAIR image could have a diagnostic performance equivalent to that of rCBF values obtained from ASL images.

Altered cerebral blood flow and white matter during wakeful rest in patients with obstructive sleep apnea: a population-based retrospective study.

To explore changes in cerebral blood flow (CBF) and white matter during wakeful rest in patients with obstructive sleep apnea (OSA). The subjects comprised OSA patients and age- and sex-matched non-sleep apnea (NSA) subjects from December 2020 to December 2021. All subjects underwent structural and arterial spin labeling MRI examinations using a 3.0 T MRI scanner. Intergroup differences in regional and global CBF and white matter hyperintensities (WMHs) were analyzed. In this study, 100 (74 males) of 750 (439 males) subjects were diagnosed with OSA, so the prevalence of OSA in the general population was 13.3% (100/750), with 16.9% (74/439) in males and 8.4% (26/311) in females. Excluding four patients with incomplete imaging data, 96 OSA patients and 103 age- and sex-matched NSA subjects were included. At global level, OSA patients showed significantly decreased CBF values in gray matter and whole brain compared to NSA subjects (gray matter: p = 0.010; whole brain: p = 0.021). No significant difference in CBF values was found in WM between the two groups (p = 0.250). At regional level, compared with NSA subjects, patients with OSA exhibited significantly decreased regional CBF values mainly in right parietal lobe and right temporal lobe. Moreover, OSA patients had significantly higher WMHs burden than NSA subjects (p = 0.017). OSA patients exhibit decreased global and regional CBF values and increased WMHs burden. These findings provide a basis for exploring neuropathological changes of OSA and for early and appropriate treatment.

A diagnostic index based on pseudo-continuous arterial spin labeling and T1-mapping improves efficacy in discriminating Alzheimer's disease from normal cognition.

BackgroundPseudo-continuous arterial spin labeling (pCASL) is widely used to quantify cerebral blood flow (CBF) abnormalities in patients with Alzheimer’s disease (AD). T1-mapping techniques assess microstructural characteristics in various pathologic changes, but their application in AD remains in the exploratory stage. We hypothesized that combining quantitative CBF and T1 values would generate diagnostic results with higher accuracy than using either method alone in discriminating AD patients from cognitively normal control (NC) subjects.Materials and methodsA total of 45 patients diagnosed with AD and 33 NC subjects were enrolled, and cognitive assessment was performed for each participant according to the Chinese version of the Mini-Mental State Examination (MMSE). T1-weighted magnetization-prepared 2 rapid acquisition gradient echo (MP2RAGE) and pCASL sequence were scanned on a 3T MR scanner. A brain morphometric analysis was integrated into prototype sequence, providing tissue classification and morphometric segmentation results. Quantitative CBF and T1 values of each brain region were automatically generated inline after data acquisition. Independent samples t-test was used to compare regional CBF and T1 values controlled by false discovery rate correction (corrected p < 0.01). The model with combined CBF and T1 values was compared with the individual index by performing receiver operating characteristic curves analysis. The associations between the MMSE score and CBF and T1 values of the brain were investigated using partial correlations.ResultsCerebral blood flow of the right caudate nucleus (RCc) and left hippocampus (LHc) was significantly lower in the AD group compared with the NC group, while the T1 values of the right caudate nucleus (RCt) and left hippocampus (LHt) increased in the AD group. Prediction accuracies of 73.1, 77.2, 75.9, and 81.3% were achieved for each of the above parameters, respectively. In distinguishing patients from controls using the corresponding optimized cut-off values, most combinations of parameters were elevated (area under curve = 0.775–0.894). The highest area under curve value was 0.944, by combining RCc, LHc, RCt, and LHt.ConclusionIn this preliminary study, the combined model based on pCASL and T1-mapping improved the diagnostic performance of discriminating AD and NC groups. T1-mapping may become a competitive technique for quantitatively measuring pathologic changes in the brain.

Arterial spin labeling imaging for the detection of cerebral blood flow asymmetry in patients with corticobasal syndrome.

Corticobasal syndrome (CBS) and Parkinson's disease (PD) both present with asymmetrical extrapyramidal symptoms, often leading to a diagnostic dilemma. Patients with CBS frequently show cerebral blood flow (CBF) asymmetry alongside asymmetrical cortical atrophy. This study aimed to evaluate the clinical utility of arterial spin labeling (ASL) magnetic resonance imaging (MRI) to detect CBF asymmetry in patients with CBS. We retrospectively investigated asymmetries of regional CBF and cortical volume, measured using ASL and T1-weighted MRI, in 13 patients with CBS and 22 age-matched patients with PD. Regional CBF and cortical volume values were derived from nine brain regions on each side. CBF and volume asymmetries were calculated as %difference in each region, respectively. CBF asymmetry showed significantly greater differences in seven of nine regions, such as the perirolandic area (- 8.7% vs. - 1.4%, p < 0.001) and parietal cortex (- 9.7% vs. - 1.3%, p < 0.001) in patients with CBS compared with patients with PD. In contrast, significant differences in volume asymmetry were observed in three regions included within the seven regions showing CBF asymmetry, which indicated that CBF asymmetry has greater sensitivity than volume asymmetry to detect asymmetricity in CBS. ASL imaging showed significant CBF asymmetry in a wider range of brain regions in patients with CBS, which suggests that noninvasive MRI with ASL imaging is a promising tool for the diagnosis of CBS, with advantages that include the simultaneous evaluation of asymmetrical hypoperfusion in addition to focal atrophy.

Using Perfusion Contrast for Spatial Normalization of ASL MRI Images in a Pediatric Craniosynostosis Population.

Spatial normalization is an important step for group image processing and evaluation of mean brain perfusion in anatomical regions using arterial spin labeling (ASL) MRI and is typically performed via high-resolution structural brain scans. However, structural segmentation and/or spatial normalization to standard space is complicated when gray-white matter contrast in structural images is low due to ongoing myelination in newborns and infants. This problem is of particularly clinical relevance for imaging infants with inborn or acquired disorders that impair normal brain development. We investigated whether the ASL MRI perfusion contrast is a viable alternative for spatial normalization, using a pseudo-continuous ASL acquired using a 1.5 T MRI unit (GE Healthcare). Four approaches have been compared: (1) using the structural image contrast, or perfusion contrast with (2) rigid, (3) affine, and (4) nonlinear transformations – in 16 healthy controls [median age 0.83 years, inter-quartile range (IQR) ± 0.56] and 36 trigonocephaly patients (median age 0.50 years, IQR ± 0.30) – a non-syndromic type of craniosynostosis. Performance was compared quantitatively using the real-valued Tanimoto coefficient (TC), visually by three blinded readers, and eventually by the impact on regional cerebral blood flow (CBF) values. For both patients and controls, nonlinear registration using perfusion contrast showed the highest TC, at 17.51 (CI 6.66–49.38) times more likely to have a higher rating and 17.45–18.88 ml/100 g/min higher CBF compared with the standard normalization. Using perfusion-based contrast improved spatial normalization compared with the use of structural images, significantly affected the regional CBF, and may open up new possibilities for future large pediatric ASL brain studies.

Assessment of regional cerebral blood flow by ct perfusion in patients of Alzheimer’s disease

Background: Alzheimer’s disease is a neurodegenerative disorder and is characterized by progressive cognitive decline which starts with an impairment in the ability to recollect recent memories, but eventually affects all the intellectual functions and finally leads to a total dependence for basic functions of daily life culminating into premature death. Dementia can be defined as a clinical syndrome characterized by a cluster of symptoms and signs manifested by difficulties in memory, disturbances in language and other cognitive functions, changes in behavior, and impairments in activities of daily living. Alzheimer is an age-associated degenerative disorder. The burden of Alzheimer’s disease and that of dementia per se is dependent on age. With increasing life expectancy, the proportion of elderly is increasing and so is the number of patients with Alzheimer’s disease associated dementia. Material and Method: This cross-sectional study was carried out for duration of 18 months at Department of Radiodiagnosis, Era's Lucknow Medical College, Lucknow with an aim to study the parameters viz. cerebral blood flow and cerebral blood volume and to correlate the finding of CT perfusion with the clinical score of dementia. The Patients attending adult psychiatry OPD diagnosed as a case of Alzheimer's as per DSM 4 criteria by fulfilling the inclusion criteria and giving informed consent were taken up for study. They were also evaluated for socio-demographic details and illness related variables. After obtaining an informed consent, demographic information, duration and nature of complaints was noted. All the patients were then subjected to CT Perfusion evaluation. Dementia severity was assessed using Clinical Dementia Rating Scale (CDRS).Result: Age of patients ranged from 60 to 75 years with a mean of 66±4.03 years. Majority of cases were aged between 60 and 69 years (77.5%). There were only 9 patients aged >70 years (22.5%).Forgetfulness (40%), difficulty in thinking (27.5%) and mental confusion (27.5%) were the three most common presenting complaints followed by loneliness (22.5%), agitation (17.5%), depression and mental decline (15% each). Inability to recognize (10%) and hallucinations (7.5%) were among the least common presenting complaints. According to clinical dementia score, a total of 16 (40%) patients were categorized as mild dementia, 20 (50%) as moderate dementia and 4 (10%) as severe dementia respectively. Mean regional cerebral blood flow values for right frontal, left frontal, left temporal, right occipital, right lenticular nucleus and left lenticular nucleus were 39.46±3.82, 39.33±3.87, 45.59±4.66, 45.51±5.02, 45.59±4.76, 45.65±4.49, 42.57±4.23 and 42.87±4.81 ml/100 g/min respectively. Mean global CBF was calculated as 43.32±4.29 ml/100 g/min. Mean regional cerebral blood volume values for right frontal, left frontal, left temporal, right occipital, right lenticular nucleus and left lenticular nucleus were 2.56±0.49, 2.62±0.54, 2.97±0.50, 3.03±0.56, 2.95±0.48, 2.92±0.52, 3.13±0.55 and 3.13±0.55 ml/100 g respectively. Mean global CBF was calculated as 2.91±0.49 ml/100 g/min.Conclusion: A total of 40 patients of Alzheimer’s disease aged 60 to 75 years (Mean age 66±4.03 years; 65% males) were enrolled and subjected to clinical and CT evaluation. According to clinical dementia score, a total of 16 (40%) patients were categorized as mild dementia, 20 (50%) as moderate dementia and 4 (10%) as severe dementia respectively. Mean cerebral blood flow (CBF) ranged from 39.33±3.87 ml/100 g/min (Left frontal region) to 45.65±4.49 ml/100 g/min (Left occipital region) among different brain regions. Mean global CBF was 43.32±4.29 ml/100 g/min.

Arterial Spin Labeling Magnetic Resonance Imaging in Healthy Adults: Mathematical Model Fitting to Assess Age-Related Perfusion Pattern.

ObjectiveTo investigate the age-dependent changes in regional cerebral blood flow (CBF) in healthy adults by fitting mathematical models to imaging data.Materials and MethodsIn this prospective study, 90 healthy adults underwent pseudo-continuous arterial spin labeling imaging of the brain. Regional CBF values were extracted from the arterial spin labeling images of each subject. Multivariable regression with the Akaike information criterion, link test, and F test (Ramsey's regression equation specification error test) was performed for 7 models in every brain region to determine the best mathematical model for fitting the relationship between CBF and age.ResultsOf all 87 brain regions, 68 brain regions were best fitted by cubic models, 9 brain regions were best fitted by quadratic models, and 10 brain regions were best fitted by linear models. In most brain regions (global gray matter and the other 65 brain regions), CBF decreased nonlinearly with aging, and the rate of CBF reduction decreased with aging, gradually approaching 0 after approximately 60. CBF in some regions of the frontal, parietal, and occipital lobes increased nonlinearly with aging before age 30, approximately, and decreased nonlinearly with aging for the rest of life.ConclusionIn adults, the age-related perfusion patterns in most brain regions were best fitted by the cubic models, and age-dependent CBF changes were nonlinear.

Application of 3D-Arterial Spin Labeling Brain Perfusion Imaging in the Preoperative Diagnosis and Grading of Glioma

To explore the value of three-dimensional arterial spin labeling brain perfusion imaging in the preoperative diagnosis and grading of glioma. A total of 128 patients with preoperative and postoperative intracranial occupying lesions and glioma between January 2018 and December 2020, including 76 preoperative patients and 52 postoperative patients. Routine magnetic resonance imaging and three-dimensional arterial spin labeling perfusion examinations were performed in all patients, and the cerebral blood flow values and the area size of the lesions were measured preoperatively and postoperatively, and the ratio of the two was calculated to standardize the regional cerebral blood flow. The perfusion of three-dimensional arterial spin labeling in glioma was characterized by high perfusion in solid areas of high-grade glioma and low perfusion in solid areas of low-grade glioma. The correct diagnostic rate of perfusion grading in threedimensional arterial spin labeling was found to be 93.21 %, while the accuracy rate of magnetic resonance imaging was only 84.33 %, using pathological diagnostic results as the standard. The difference between the two was statistically significant (p 0.05). In the diagnosis of postoperative recurrence, the cerebral blood flow values of lesions in the glioma recurrence group were significantly higher than those in the glioma non-recurrence group. The regional cerebral blood flow values of lesions in the glioma recurrence group were significantly higher than those in the glioma non-recurrence group, and the differences between the two groups were statistically different (p<0.05). Three-dimensional arterial spin labeling can provide a more comprehensive and accurate assessment of glioma, which provides a new theoretical basis for preoperative grading of glioma, prediction of postoperative recurrence and assessment of surgical planning.

Cerebral Blood Flow Is Associated with Diagnostic Class and Cognitive Decline in Alzheimer's Disease.

Reliable cerebral blood flow (CBF) biomarkers using a noninvasive imaging technique are sought to facilitate early diagnosis and intervention in early Alzheimer's disease (AD). We aim to identify brain regions in which CBF values are affected and related to cognitive decline in early AD using a large cohort. Perfusion MRIs using continuous arterial spin labeling were acquired at 1.5 T in 58 normal controls (NC), 50 mild cognitive impairments (MCI), and 40 AD subjects from the Cardiovascular Health Study Cognition Study. Regional absolute CBF and normalized CBF (nCBF) values, without and with correction of partial volume effects, were compared across three groups. Association between regional CBF values and Modified Mini-Mental State Examination (3MSE) were investigated by multiple linear regression analyses adjusted for cardiovascular risk factors. After correcting for partial volume effects and cardiovascular risk factors, ADs exhibited decreased nCBF with the strongest reduction in the bilateral posterior cingulate & precuneus region (p < 0.001) compared to NCs, and the strongest reduction in the bilateral superior medial frontal region (p < 0.001) compared to MCIs. MCIs exhibited the strongest nCBF decrease in the left hippocampus and nCBF increase in the right inferior frontal and insular region. The 3MSE scores within the symptomatic subjects were significantly associated with nCBF in the bilateral posterior and middle cingulate and parietal (p < 0.001), bilateral superior medial frontal (p < 0.001), bilateral temporoparietal (p < 0.02), and right hippocampus (p = 0.02) regions. Noninvasive perfusion MRI can detect functional changes across diagnostic class and serve as a staging biomarker of cognitive status.

0011 The Influence of Obstructive Sleep Apnea Severity and Sex on Cerebral Perfusion

Abstract Introduction Obstructive Sleep Apnea (OSA) has been shown to initiate a pathological cascade negatively affecting the cardiovascular system, including cerebral circulation. There is limited data on OSA effects on regional brain function, though reduced global cerebral blood flow (CBF) has been observed among patients with OSA. However, there are few precise assessments. We hypothesized that regional CBF values are altered in OSA, and that sex influences the hypothesized relationship. Methods Participants from the NYU Center for Brain Health cohort (n=68; 57.4% female; mean age=66.32±6.84), representing cognitively healthy volunteers with OSA (AHI4% &amp;gt; 5/hr) and without, from several NIA-supported studies, completed evaluations including clinical, structural &amp; functional high-resolution arterial spin labeling 3 tesla MRI scans. Hippocampal and temporal cortex CBF was assessed at baseline and after CO2 challenge using a rebreathing protocol. Analyses were completed using one-way ANCOVA controlling for age and BMI. Results More men had OSA (82.8% vs 56.4%). Men without OSA showed a larger change in CBF after challenge in left (t=2.6, p=0.014) and right (t=2.4, p=0.021) hippocampus. Although the main analyses by severity level only boarded significance, pairwise comparisons indicated men with severe OSA (AHI4%&amp;gt;30/hr) exhibited a larger change in CBF after challenge in the hippocampus overall compared to those with mild OSA (AHI4%5–15/hr; p=0.015) and without OSA (p=0.017). Women with severe OSA showed a reduced change in CBF after challenge in the right hippocampus compared to those with mild (p=0.016), moderate (AHI4%16–29/hr; p=0.008), and without OSA (p=0.015). Conclusion This study suggests a possible differential effect of OSA severity and sex on regional CBF in response to a CO2 challenge, specifically in the hippocampus. Further studies will examine cognitive consequences of these sex-specific hippocampal perfusion abnormalities in OSA. Support NIH/NIA (1R01HL118624) Osorio, RS 07/01/13-04/30/17 Sleep Disordered Breathing in normal elderly and risk for Alzheimer’s disease (AD).NIH/NIA (R01AG056031S1) Osorio, RS 8/01/2019-7/31/2020 Sleep Aging and Risk for Alzheimer’s disease - Research Supplement to Promote Diversity in Health-Related Research

M18. REDUCED CORTICAL CEREBRAL BLOOD FLOW IN FIRST EPISODE PSYCHOSIS PATIENTS

BackgroundAbnormal Cerebral Blood Flow (CBF) has been found in patients with chronic schizophrenia (SCZ), first-episode psychosis patients (FEP) and individuals at clinical high-risk (CHR). In particular, previous studies using Arterial Spin Labelling (ASL) found that SCZ have a global reduction of CBF in the cortex and increased CBF in the basal ganglia, the hippocampus, and the amygdala as compared with controls. To date, only one study investigated CBF using ASL in a small cohort of medicated FEP reporting increased CBF in the striatum and reduced frontal CBF as compared with controls. However, it is still not clear whether these abnormalities are related to antipsychotic treatment or rather they reflect a disease state independent from medication. Critically, clinical and pre-clinical evidence suggests that antipsychotics increase CBF, especially in the basal ganglia through dopamine D2 receptors blockade. Here, we assessed CBF differences between FEP and controls in a larger cohort of unmedicated or minimally treated patients. In addition, we tested the association between CBF abnormalities and clinical features.Methods26 FEP (13 medication-free, 9 antipsychotics naïve, 4 minimally treated) and 22 healthy controls (HC) were recruited. FEP and HC were matched for age and gender. Among FEP, 11 had a diagnosis of affective psychosis and 15 of non-affective psychosis. MRI scans were acquired using a GE MR750 3T scanner and a 12-channel head coil. ASL data was acquired using a pseudo-continuous ASL sequence (pCASL). Four control-label pairs were used. Quantification of the CBF data was made using a coil sensitivity map and a proton density image. CBF maps were normalized using non-linear registration and smoothed using a 6 mm full width at half maximum (FWHM) kernel. Grey matter CBF and regional CBF values in each Region of Interest (ROI) were extracted using individual grey matter images and WFU-Pickatlas ROIs with the MarsBar toolbox. Based on previous studies the following ROIs were selected: right and left hippocampus, right and left striatum, right and left frontal cortex. Whole-brain voxel-wise analysis was performed using a non-parametric independent t-test as implemented in FSL randomize (Threshold Free Cluster Enhancement, TFCE, and 5000 permutations). Bonferroni method was used to correct ROI analysis for multiple comparisons (alpha = 0.05, n = 7).ResultsSignificantly reduced CBF was found in FEP as compared with controls in total grey matter CBF (p = 0.004). Whole-brain voxel-wise analysis FEP-HC comparison revealed a widespread cortical reduction in large cortical clusters that encompass the occipital, parietal and frontal cortices (pFWE TFCE corrected < 0.05). ROI analysis revealed a significant reduction in CBF in the right frontal cortex (p = 0.002). A nominal significant reduction was also detected in the left frontal cortex (p = 0.014). No statistically significant differences were found in the other ROI considered (all p > 0.1). Sub-analysis after removing minimally treated patients did not change the results. Both global grey matter CBF and right frontal CBF were reduced in both affective and non-affective psychosis as compared with controls (p < 0.05), whereas no differences were detected between the two clinical groups.DiscussionOur results confirm earlier evidence on reduction of cortical perfusion in FEP. However, in contrast with previous studies, we did not detect any difference in striatal perfusion in our cohort of unmedicated/minimally treated patients. Hence, our results support the hypothesis that alteration in striatal perfusion are likely due to medication. Finally, our results suggest that CBF alterations might have a trans-diagnostic role in the pathophysiology of psychosis.

P3714Cerebral blood flow and cognitive functioning in the heart-brain axis

Abstract Background Recent studies suggest that cardiovascular disease and dementia are closely related, which led to the concept of a “heart-brain axis”. Dysfunction in any component of the heart-brain axis could be a risk factor for the development of brain damage and consequently to the development of cognitive impairment. In the Heart-Brain study, we focus on vascular cognitive impairment (VCI), symptomatic carotid occlusive disease (COD) and heart failure (HF) as three extreme phenotypes of haemodynamic dysfunction in different components of the heart-brain axis (i.e. heart – carotids – brain). We compared values of cerebral blood flow (CBF), measured with arterial spin labeling (ASL) between patients with HF, COD and VCI and investigated the association between CBF and cognitive functioning. Methods We included 442 participants (129 VCI; 75 COD; 124 HF; and 114 controls) from the Heart-Brain Study (67±9 yrs; 38% F; MMSE 28±2). We used 3T pseudo-continuous ASL to estimate whole-brain and regional partial volume-corrected CBF. Using a standardized neuropsychological assessment, we measured global cognitive functioning and four cognitive domains. Compound z-scores were constructed for each cognitive domain. We investigated associations using linear regression analyses, adjusted for age, sex, education, center and diagnosis. Subsequently, we stratified for diagnosis. Results Whole-brain and regional CBF values were lowest in patients with COD, followed by VCI and HF, compared to controls. Global cognitive functioning was lowest in patients with VCI, followed by COD and HF, compared to controls. Overall, we found hardly any association between whole-brain or regional CBF values and cognitive functioning (standardized beta [stb] = 0.00–0.10, p&gt;0.05). Subsequent stratification for diagnosis showed no association between whole-brain or regional CBF and cognitive functioning in any participant group. Conclusions Our results suggest that reduced CBF is not the major explanatory factor underlying impaired cognitive functioning in patients with disorders along the heart-brain axis. The predisposition of cognitive impairment in these patients is likely to be driven by other (haemodynamic) mechanisms than CBF. Acknowledgement/Funding We acknowledge the support of the Netherlands CardioVascular Research Initiative: the Dutch Heart Foundation (CVON 2012-06 Heart Brain Connection), Du

Arterial spin-labeling magnetic resonance imaging of brain maturation in early childhood: Mathematical model fitting to assess age-dependent change of cerebral blood flow

PurposeTo determine the trajectory of age-dependent cerebral blood flow (CBF) change in infants and young children by fitting mathematical models to the imaging data. MethodsIn this retrospective study, we reviewed the arterial spin-labeling imaging studies of 49 typically developing infants and young children at postmenstrual age (PMA) ranging from 38 to 194 weeks. All patients had normal structural MR imaging. Coregistration and gray matter segmentation were performed to extract whole-brain CBF values. Regional CBF values were obtained using manual region-of-interest placement. Curve estimation regression procedures with the corrected Akaike information criterion (AICc) were performed to determine the mathematical model best fitting the relationship between the CBF (whole-brain and regional measurements) and PMA of the patients. ResultsWhole-brain CBF trajectory was best fitted by a cubic model (AICc = 215.95; R2 = 0.566; P < .001). Whole-brain CBF at 1, 6, 12, and 24 months was estimated to be 36, 52, 58, and 55 mL/100 g/min, respectively. Regional CBF trajectory was also best fitted by a cubic model in the frontal (AICc = 233.63; R2 = 0.442; P < .001), parietal (AICc = 229.18; R2 = 0.614; P < .001), basal ganglion (AICc = 239.39; R2 = 0.178; P = .043), temporal (AICc = 236.01; R2 = 0.441; P < .001), and occipital (AICc = 236.46; R2 = 0.475; P < .001) regions. ConclusionsIn early childhood, the trajectory of CBF change was nonlinear and best fitted by the cubic model for the whole brain and all brain regions.

Regional cerebral hypoperfusion after acute sleep deprivation: A STROBE-compliant study of arterial spin labeling fMRI.

Previous neuroimaging studies have shown that functional changes occur after acute sleep deprivation, which suggest detrimental effects of a lack of sleep on the intrinsic functional architecture of the brain. We aimed to identify regional resting perfusion changes in subjects with acute sleep deprivation.Thirty-three healthy subjects with habitual good sleep participated in 36 hours (2 days and 1 night) of sleep deprivation and then underwent the attention network test and pseudo-continuous arterial spin labeling scanning. Regional cerebral blood flow was used to compare cerebral perfusion before and after sleep deprivation. Correlation analyses of regional perfusion changes and scores on the attention network test were performed.Compared with the baseline (n = 20) scans, the scans of subjects after sleep deprivation (n = 26) revealed a slower response time (549.99 milliseconds vs 603.36 milliseconds; t = −2.301; P = .028) and a significantly higher lapse rate (0.88% vs 22.85%; t = −2.977; P = .006). The sleep deprivation subjects showed lower cerebral blood flow (CBF) in the left parahippocampal gyrus/fusiform cortex (pHipp/Fus), right pHipp/Fus, and right prefrontal cortex (PFC) relative to the baseline subjects (Gaussian random field correction, voxel level P < .01, and cluster level P < .05). Although no significant relationships were observed between the altered regional CBF (rCBF) values and the attention network test scores, the receiver-operating characteristic and leave-one-out cross-validation analyses revealed that significant decreases in rCBF in the bilateral pHipp/Fus and right PFC could discriminate between sleep deprivation and good sleep status.We observed that rCBF was reduced after 36 hours (2 days and 1 night) of sleep deprivation. Our preliminary findings suggest an acute vulnerability to hypoperfusion due to lack of sleep.

Assessment of regional cerebral blood flow in patients with early and late onset alcohol dependence: a SPECT study

Aim: Alcohol dependence has negative effects on the structure and functionality of the brain. The age of onset of alcohol is an important parameter in the grouping of alcoholics. The aim of this study is to compare whether regional cerebral blood flow (r-CBF) values differ between early (EO) versus late onset (LO) alcoholic patients.Methods: A total of 33 male patients with alcohol dependence as per DSM-IV criteria and 13 healthy controls were enrolled for the study. Regional measures of cortical cerebral blood flow were assessed using a high resolution Tc-99m-HMPAO single photon emission computed tomography (SPECT). Alcoholic subjects were divided into two groups according to onset of problematic alcohol drinking age. Results: When three groups were compared, r-CBF differences were obtained in inferior frontal, inferior temporal, inferior left occipital and middle left frontal regions. Decreased r-CBF values were found in LO group when they compared to controls in both lower frontal and temporal regions (p&lt;0.05). LO group showed significant reduced r-CBF values in regions of inferior frontal and temporal, inferior left occipital and middle left frontal when compared with EO. Conclusion: Our findings revealed that, there were differences in r-CBF values in EO and LO alcoholics at early abstinence period. These findings suggest that frontal lobes have a key role in alcoholism neurobiology, as noted in previous studies. Repeating the measurements after a long-term abstinence will be useful in revealing differences among the alcoholic groups.

A Simple Non-invasive I-123-IMP Autoradiography Method Developed by Modifying the Simple Non-invasive I-123-IMP Microsphere Method.

Objective(s):We developed a simple non-invasive I-123-N-isopropyl-p-iodoamphetamine (123I-IMP) quantification method by analyzing chest RI-angiography and single photon emission computed tomography (SPECT) images based on the microsphere model (SIMS method). Theoretically, the SIMS method could be changed to the simple non-invasive ARG (SIARG) method by modifying the integrated washout ratio (WR) to one-point WR. If the regional cerebral blood flow (rCBF) values derived from the SIARG and ARG methods correlate well, the facilities employing the ARG method can easily switch to the SIARG method. The purpose of this study was to develop the SIARG method by modifying the SIMS method, and to confirm the feasibility of this method.Methods:The correlation between the input counts of the SIARG method and the blood counts was determined by linear regression analysis. The rCBF values determined by the SIARG method were compared with the values obtained with the ARG and SIMS methods.Results:There was a good linear correlation between the SIARG counts and the arterial blood counts obtained by the ARG method (r=0.85, P<0.001, n=29). The rCBF values obtained by the ARG and SIARG methods (n=29, 696 ROIs) correlated well (y=1.01x – 3.6, r=0.85, P<0.001). Similarly, the rCBF values obtained by the SIARG and SIMS methods (n=29, 696 ROIs) correlated well (y=0.98x – 15.2, r=0.90, P<0.001). rCBF values obtained by the SIARG method were almost the same as the values obtained by the ARG method, and values of the SIMS method were 15 ml/100g/min higher that of those obtained by the SIARG method.Conclusion:The rCBF values obtained by the ARG, SIARG, and SIMS methods correlated very well. Therefore, the SIARG method is potentially useful for examinations in routine clinical practice.

Evaluaton of regional cerebral blood flow alterations by limbic activation in patients with schizophrenia

The aim of study is to evaluate the functions of limbic system in schizophrenia by performing procaine administration and using single photon emission computed tomography (SPECT). 22 patients and 19 controls were included in the study. Patients were evaluated with Positive and Negative Syndrome Scale (PANSS), Brief Psychiatric Rating Scale (BPRS), Hamilton Rating Scale for Depression (HAM-D) and Hamilton Rating Scale for Anxiety (HAM-A), Calgary Depression Rating Scale for Schizophrenia (CDSS) and the controls were evaluated with BPRS, HAM-D and HAM-A. The regional cerebral blood flow (rCBF) values were measured by SPECT. The rCBF following placebo and the alteration ratios of the rCBF following procaine of patients compared to controls. The rCBF following placebo in bilateral frontal, bilateral superior temporal, bilateral parahippocampus, thalamus, insula and alteration ratios of rCBF following procaine in bilateral anterior cingulate cortex (ACC) and left thalamus of patients were lower. Poor limbic activation to procaine was observed in the ACC and left thalamus of patients with schizophrenia. These findings support that the ACC and thalamus are crucial role in pathophysiology of schizophrenia.

Quantifying the Cerebral Hemodynamic Changes in Hypertensive Patients Using 3D Pseudo-continuous Arterial Spin Labeling.

Objective To investigate the cerebral hemodynamic changes in hypertensive patients using 3D pseudo-continuous arterial spin labeling(3D pCASL).Methods Fifty-eight hypertensive subjects and thirty-four age-matched healthy volunteers were recruited and scanned using the 3D whole-brain pCASL sequence.The regional cerebral blood flow(CBF)values were achieved based on 3D pCASL with SPM8 technique and were manually drawn. Results Compared with healthy volunteers,hypertensive patients had significantly lower CBF values in various regions,with statistical difference at the bilateral centrum semiovale(P=0.000,P=0.000),periventricular white matter(P=0.001,P=0.002),splenium of corpus callosum(P=0.003),frontal lobe(P=0.003),parietal lobe(P=0.014),occipital lobe(P=0.002),temporal lobe(P=0.006),medulla(P=0.012),pons(P=0.016),midbrain(P=0.034),cerebellum(P=0.000),and gray matter(P=0.001).Nevertheless,the CBF values in the thalami,globus pallidus,putamen,and genu of corpus callosum demonstrated no significant inter-group difference(all P>0.05).Conclusions 3D pCASL can be used to detect the subtle hemodynamic abnormalities even at the early stage of hypertension.The observed decrease in CBF in these regions may suggest an increased risk of cerebral small vessel diseases.

Functional assessment of prefrontal lobes in patients with major depression disorder using a dual-mode technique of 3D-arterial spin labeling and 18F-fluorodeoxyglucose positron emission tomography/computed tomography.

The aim of this study was to explore the functions of cerebral blood perfusion and glucose metabolism in the prefrontal lobe of patients with major depression disorder (MDD), and to analyze the correlations between these functional changes and depressive symptoms. 3D-arterial spin labeling (ASL) and 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) were successfully performed in 17 patients with MDD and 16 healthy controls in a resting state. The depressive symptoms of the patients were classified into seven factors and scored with the Hamilton Depression Rating Scale. Regional cerebral blood flow (CBF) values and standardized uptake values (SUV) of 18F-FDG in the whole brain were respectively compared between the patients and healthy controls using a two-sample t-test, and the correlations between the CBF and SUV in the prefrontal cerebral regions with the patients' Hamilton scores were evaluated using Pearson correlation analysis. Decreased regional CBF was indicated in the bilateral middle and the right superior frontal gyri, and decreased regional SUV was indicated in the bilateral superior, middle and inferior frontal gyri in the MDD patients compared with the controls. Positive correlations were observed between CBF values and aggregate Hamilton scores in the left middle and right middle frontal gyri of the patients. Positive correlations were also observed between SUVs and aggregate Hamilton scores in the left middle and right middle frontal gyri. 18F-FDG PET/CT was indicated to be more sensitive than 3D-ASL in identifying the functional abnormalities in the prefrontal lobe. Decreased CBF and SUV in the prefrontal lobe were closely correlated with Hamilton score. The left middle frontal gyrus may be a key functional region in MDD.