rCBF Changes Research Articles

Cholinergic enhancement increases regional cerebral blood flow to the posterior cingulate cortex in mild Alzheimer's disease.

The brain region that shows reductions in regional cerebral blood flow (rCBF) earliest is the posterior cingulate cortex (PCC), which is thought to have a relationship with cognitive function. We made a hypothesis that the PCC hypoperfusion is a result of cholinergic dysfunction and can be restored by cholinergic enhancement. This present longitudinal study aimed to detect the restoration of PCC rCBF in response to donepezil, an acetylcholine esterase inhibitor. We evaluated rCBF changes in the PCC, precuneus and anterior cingulate cortex using perfusion single-photon emission computed tomography (SPECT), statistical analysis and region of interest analysis, prospectively. We allocated 36 patients with mild AD to either the responder or non-responder groups based on changes in Mini-Mental State Examination scores. The patients were followed up for 18 months. The PCC rCBF significantly increased in responders after 6 months of donepezil therapy. Statistical maps at baseline showed a typical decreased pattern of mild AD and obvious rCBF restoration in the bilateral PCC at 6 months in responders. Changes in Mini-Mental State Examination scores and the AD assessment scale cognitive scores significantly correlated with rCBF changes in the PCC of responders. Cholinergic enhancement restored PCC rCBF under the three conditions of mild AD, responders and short follow-up interval, and that increase correlated with improved cognitive function. These findings support our hypothesis that PCC rCBF reflects cholinergic function in AD patients. Geriatr Gerontol Int 2017; 17: 951-958.

Effect of continuous positive airway pressure on regional cerebral blood flow in patients with severe obstructive sleep apnea syndrome

ObjectivesObstructive sleep apnea (OSA) is commonly associated with neural and cognitive deficits induced by recurrent hypoxemia and sleep fragment. The aims of this study were to use statistical parametric mapping (SPM) to analyze changes in regional cerebral blood flow (rCBF) in untreated patients with severe OSA before and after nasal continuous positive airway pressure (CPAP) treatment, examine the impact of OSA-related variables on rCBF, and assess the therapeutic effect of nasal CPAP treatment. MethodsThirty male patients with severe OSA underwent brain single photon emission computed tomography (SPECT) scans twice before and after nasal CPAP treatment for ≥6 months, whereas 26 healthy controls underwent a single SPECT scan. The rCBF differences were compared between two OSA sub-groups (untreated and treated) and the control group, and correlations between rCBF differences and clinical parameters were analyzed. ResultsCompared with the controls, the untreated OSA patients showed a significantly lower rCBF in multiple brain areas. After the treatment, partial reversal of the rCBF decreases was observed in the limbic and prefrontal areas. Moreover, complete reversal of the rCBF decreases was observed in the medial orbitofrontal, angular and cerebellar areas. Significant improvements in some clinical and polysomnographic variables (Epworth Sleepiness Scale, apnea–hypopnea index, CPAP duration, and arousal index) paralleled the rCBF changes after the treatment. ConclusionsDecreased rCBF in severe OSA was significantly reversible by CPAP treatment and correlated with the improvements in the apnea–hypopnea index, arousal index, CPAP duration and Epworth Sleepiness Scale. These results suggest that long-term CPAP treatment improves rCBF in areas responsible for executive, affective, and memory function.

A new method for evaluating regional cerebral blood flow changes: Laser speckle contrast imaging in a C57BL/6J mouse model of photothrombotic ischemia.

The present study aimed to improve the processing of data acquired from laser speckle contrast imaging (LSCI) to provide a standardization method to explore changes in regional cerebral blood flow (rCBF) and to determine the correlations among rCBF, cerebral ischemic lesion volume and microvascular density over time in a focal ischemic region. C57BL/6J mice were subjected to focal photothrombotic (PT) ischemia. rCBF was measured using LSCI at different time points before and after PT ischemia through an intact skull. Standardized rCBF (SrCBF), defined as the ratio of rCBF measured in the ipsilateral region of interest (ROI) to that in the corresponding contralateral region, was calculated to evaluate potential changes. In addition, the volume of the ischemic lesion and the microvascular density were determined using Nissl staining and immunofluorescence, respectively. The relationships among the ischemic lesion volume, microvascular density and SrCBF were analyzed over time. The results showed that the cortical rCBF measured using LSCI following PT ischemia in the C57BL/6J mice gradually increased. Changes in the cerebral ischemic lesion volume were negatively correlated with SrCBF in the ischemic region. Changes in the microvascular density were similar to those observed in SrCBF. Our findings indicate that LSCI is a practical technique for observing changes in murine cortical rCBF without skull opening and for analyzing the relationships among the ischemic lesion volume, microvascular density and SrCBF following focal cerebral ischemia. Preliminary results also suggest that the use of LSCI to observe the formation of collateral circulation is feasible.

Acute deep brain stimulation changes in regional cerebral blood flow in obsessive-compulsive disorder.

OBJECTIVE Deep brain stimulation (DBS) is a reversible, nonlesion-based treatment for patients with intractable obsessive-compulsive disorder (OCD). The first studies on DBS for OCD stimulating the ventral capsule/ventral striatum (VC/VS) yielded encouraging results for this neuroanatomical site's therapeutic efficacy. This investigation was conducted to better understand which regions of the cortico-striatal-thalamic-cortical network were acutely affected by VC/VS DBS for OCD. Furthermore, the objective was to identify which brain regions demonstrated changes in perfusion, as stimulation was applied across a dorsoventral lead axis that corresponded to different anatomical locations in the VC/VS. METHODS Six patients receiving VC/VS DBS for OCD underwent oxygen-15 positron emission tomography (15O-PET) scanning. Monopolar DBS was delivered at each of the 4 different electrodes on the stimulating lead in the VC/VS. The data were analyzed using SPM5. Paired t-tests were run in SPSS to identify significant changes in regional cerebral blood flow (rCBF) between stimulation conditions. Pearson's r correlations were run between these significant changes in rCBF and changes in OCD and depressive symptom severity. RESULTS Perfusion in the dorsal anterior cingulate cortex (dACC) significantly increased when monopolar DBS was turned on at the most ventral DBS contact, and this increase in dACC activity was correlated with reductions in depressive symptom severity (r(5) = -0.994, p = 0.001). Perfusion in the thalamus, striatum, and globus pallidus significantly increased when DBS was turned on at the most dorsal contact. CONCLUSIONS DBS of the VC/VS appears to modulate activity in the regions implicated in the pathophysiology of OCD. Different regions in the cortico-striatal-thalamic-cortical circuit showed increased perfusion based on whether the stimulation was more ventral or dorsal along the lead axis in the VC/VS. Evidence was found that DBS at the most ventral site was associated with clinical changes in depressive symptom severity, but not OCD symptom severity.

Changes in the regional cerebral blood flow detected by arterial spin labeling after 6-week escitalopram treatment for major depressive disorder

BackgroundA few studies have used pseudo-continuous arterial spin labeling (pCASL) to assess the regional cerebral blood flow (rCBF) in patients with major depressive disorder (MDD). However, rCBF changes during treatment with escitalopram have not been studied in detail. We used pCASL to investigate the effect of 6-week escitalopram treatment on the rCBF in MDD patients. MethodsWe subjected 53 MDD patients and 36 controls to pCASL (T1, baseline). The patients then received treatment with escitalopram for 6 weeks and 27 were scanned again (T2). We used selected regions of interest that exhibited differences between the controls and patients at T1 and compared the T2 rCBF in the patients with the T1 rCBF of the controls. We also compared the T1 and T2 rCBF in the patients to assess their response to escitalopram. ResultsAfter 6-week treatment with escitalopram, the rCBF in the patients' left inferior temporal gyri, the middle- and inferior frontal gyri, and the subgenual anterior cingulate, which had been higher at T1 than in the controls, was decreased. Their rCBF in the right lingual gyrus remained significantly lower at T2. LimitationWe did not have a placebo-control group and the number of patients available at T2 was small. ConclusionIn MDD patients, 6-week escitalopram treatment elicited significant rCBF changes toward normalization in most of the areas that had shown significant differences between the patients and the controls at T1. The persistence of rCBF anomalies in the right lingual gyrus may be a trait marker of MDD.

Long-Term Efficacy of Memantine in Parkinson' Disease Dementia: An 18-Month Prospective Perfusion Single Photon Emission Computed Tomography Preliminary Study.

Background and PurposeAlthough the treatment efficacy of memantine in Parkinson's disease dementia (PDD) has been reported after several weeks of administration, the long-term effects on brain perfusion and clinical symptoms remain unclear. The current study aimed to follow-up PDD patients after 18 months of memantine treatment using 99mTc hexamethylpropylene amine oxime single photon emission computed tomography (SPECT).MethodsA total of 15 patients with PDD and 11 healthy participants were recruited into this study and they were assessed with brain SPECT, Mini-Mental State Examination (MMSE), Clinical Dementia Rating (CDR), Global Deterioration Scale (GDS), and Neuropsychiatric Inventory (NPI). Differences in regional cerebral blood flow (rCBF) between the two groups were evaluated at baseline. After 18 months of memantine administration, changes in brain perfusion, severity of dementia, cognition, and neuropsychiatric disturbances were examined in the patients with PDD.ResultsThe PDD group showed hypoperfusion in most of the cortical, subcortical, and cerebellar areas compared to healthy controls at baseline. At the follow-up, changes in rCBF, CDR (p=0.32), sum of box of CDR (p=0.49), MMSE (p=0.61), GDS (p=0.79), and NPI (p=0.23) were not significant in the PDD patients.ConclusionsOur findings implicate that memantine may delay the progression of brain perfusion deficits and clinical symptoms of PDD in the long term.

In Search of Baseline: Absolute and Relative Measures of Blood Flow and Oxidative Metabolism in Visual Cortex Stimulated at Three Levels of Complexity

Objective: Functional imaging of regional cerebral blood flow (rCBF) or the blood-oxygenation-level dependent (BOLD) signal is based on the premise that changes of flow and energy metabolism are linked to the same incremental excitation of neurons. The baseline conjecture holds that a single default mode of brain function gives rise to coupled changes of blood flow and oxidative metabolism that raise oxygen’s extraction fraction, when activity falls, and lower the extraction fraction when activity rises. To locate the hypothetical baseline in visual cortex in relation to functional demands, we compared increments of (rCBF) and oxidative metabolism (rCMRO2) during stimulation of visual cortex at three different levels of complexity. Materials and Methods: Healthy volunteers underwent positron emission tomography (PET) with [15O] water and [15O] oxygen while they viewed three stimuli in random order; a cross-hair fixation stimulus without color or spatial frequency (FX), an achromatic white disc stimulus with an 8 Hz on-off rate (WD), and a circular yellow-blue chromatic checkerboard with an 8 Hz color-reversing frequency (YB). For the baseline conjecture to hold, the sum of any pair of contrasts must equal the third at any site of significant change, such that the sum of the contrasts [YB-WD] and [WD-FX] must equal the contrast [YB-FX]. Results: The rCMRO2 and rCBF changes averaged 21% and 52% of the whole-brain average, implying excitation by increasing stimulus complexity. The color reversal contrast ([YB-WD]) revealed bilateral sites of significant change of rCMRO2 and a single left hemisphere site of significant rCBF change in the general region of Brodmann’s areas (BA) 17 and 18 of the lingual gyrus. The spatial frequency contrasts ([YB-FX] and [WD-FX]) revealed single sites of significant change of rCMRO2 and rCBF also in the lingual gyrus but close to the midline. For the midline sites, the [YB-FX] and [WD-FX] contrasts were identical and revealed a baseline between the FX and WD/YB stimulus conditions. For the lateral sites, the [YB-WD] stimulus contrast revealed a baseline between the YB and WD stimulus conditions. Conclusion: The intermediate positions of the baselines indicated the existence in BA 17/18 of at least two populations of cells, a lateral group responding to the absence and presence of color reversal in the presence of a spatial frequency, and a midline group responding only to the absence and presence of spatial frequency.

Application of cerebral MR perfusion imaging using pulsed arterial spin labeling technique in patients with amnestic-type mild cognitive impairment and mild Alzheimer disease

Objective To study the value of relative cerebral blood flow (rCBF) changes in patients with amnestic-type mild cognitive impairment (aMCI) and mild Alzheimer disease (AD) using MRI pulsed arterial spin labeling (PASL). Methods A prospective study recruited 37 aMCI patients (aMCI group) , 30 mild AD patients (mild AD group) and 30 healthy volunteers (normal control group) from March 2011 to December 2013, MRI using PASL for cerebral perfusion imaging was performed and data of rCBF were collected. Taking age as covariate, analysis of variance (ANONA) was carried out to assess the difference of rCBF among all the three groups, then Bonferroni was done between every two groups. A follow-up examination using PASL was performed in the seventeen patients of the aMCI group. And paired t-test was used for comparing the longitudinal change of their rCBF data. Results Compared with the normal control group, the aMCI group showed significant increase of rCBF in bilateral posterior cingulate cortices and precuneus (cluster number 2 785, P<0.05). While the mild AD group showed decrease of rCBF in the left inferior and superior parietal lobes, the angular, middle frontal lobe, as well as the right superior temporal lobe (cluster number 3 459-5 206, P<0.05). When compared with the aMCI group, the mild AD group showed regional hypoperfusion in bilateral middle frontal lobes, the left precuneus, the right postcentral and inferior parietal lobe (cluster number 3 236-19 863, P<0.05). In the longitudinal study of the 17 aMCI patients, an increased rCBF was found to coexist with reduced rCBF in the left inferior frontal and lateral occipital cortex, bilateral frontal poles and paracingulate gyrus, with hyperperfusion dominated. Increased rCBF was also detected in the left temporal lobe, the angular gyrus and precuneus, while decreased rCBF was present in the left putamen, the operculum and right corpus callosum (P<0.05). Conclusions ASL perfusion imaging is a valuable method for dynamic monitoring of the cerebral perfusion changes in aMCI and AD patients. PASL will assist in finding a useful imaging biomarker for early diagnosis of AD. Key words: Cognition disorders; Alzheimer disease; Magnetic resonance imaging

The Comparative Study of NIRS and Eastern Medicine Phenomenon in the Meridian Point Commonly Used for Pain Relief

We showed that the brain areas such as the thalamus, insula and anterior cingulate cortex were activated by heating the tail of monkeys in 47 C water and those activations were suppressed by electroacupuncture (EA) at ST36 and LI4 acupoints, and that histamine and dopamine release was increased after pain stimulus in rats and the changes were completely abolished by EA at ST36 and ST37 acupoints and that different manual acupuncture at ST36 appear to change the neural coding of electrical signals in the spinal dorsal horn through WDR neurons in rats. In this meeting we will show with Near-infrared Spectroscopy and the interview sheet about the Eastern medicine complaint that the subjects whose center-of-gravity value are lighter than a standard value are “blood deficiency”, the subjects whose center-of-gravity value is heavier than a standard value are “blood stasis”, the subjects whose integration value are higher than a standard value are “qi stagnancy” or normal, and the subjects whose integration value are lower than a standard value are “qi deficiency” and that acupunture stimulation on SP6 or on ST36 balanced regional cerebral blood flow (rCBF) but that on LU6 decreased rCBF, and that the simultaneous acupunture stimulation on DU20 and Ex-HN4 reduced rCBF at the frontal cortex. However, independent acupunture stimulation on DU20 or Ex-HN4 failed to change rCBF. We would like to also report change of rCBF by pain and painkilling.

Voxel-wise meta-analyses of brain blood flow and local synchrony abnormalities in medication-free patients with major depressive disorder.

Published meta-analyses of resting-state regional cerebral blood flow (rCBF) studies of major depressive disorder (MDD) have included patients receiving antidepressants, which might affect brain activity and thus bias the results. To our knowledge, no meta-analysis has investigated regional homogeneity changes in medication-free patients with MDD. Moreover, an association between regional homogeneity and rCBF has been demonstrated in some brain regions in healthy controls. We sought to explore to what extent resting-state rCBF and regional homogeneity changes co-occur in the depressed brain without the potential confound of medication. Using the effect-size signed differential mapping method, we conducted 2 meta-analyses of rCBF and regional homogeneity studies of medication-free patients with MDD. Our systematic search identified 14 rCBF studies and 9 regional homogeneity studies. We identified conjoint decreases in resting-state rCBF and regional homogeneity in the insula and superior temporal gyrus in medication-free patients with MDD compared with controls. Other changes included altered resting-state rCBF in the precuneus and in the frontal-limbic-thalamic-striatal neural circuit as well as altered regional homogeneity in the uncus and parahippocampal gyrus. Meta-regression revealed that the percentage of female patients with MDD was negatively associated with resting-state rCBF in the right anterior cingulate cortex and that the age of patients with MDD was negatively associated with rCBF in the left insula and with regional homogeneity in the left uncus. The analysis techniques, patient characteristics and clinical variables of the included studies were heterogeneous. The conjoint alterations of rCBF and regional homogeneity in the insula and superior temporal gyrus may be core neuropathological changes in medication-free patients with MDD and serve as a specific region of interest for further studies on MDD.

Regional cerebral blood flow in late-onset schizophrenia: a SPECT study using 99mTc-ECD

Progressive disability in schizophrenia has been considered to be associated with onset-age. The objective of this study was to evaluate age onset-related degeneration in rCBF in patients with schizophrenia. We evaluated characteristic changes in brain perfusion by age, gender, medication and clinical symptoms in medicated patients with early-onset (EOS: developed at younger than 40 years old: n = 44) and late-onset (LOS: developed at older than 40 years old: n = 19) schizophrenia and control subjects matched for age and gender (n = 37) using statistical parametric mapping (SPM8) applied to 99mTc-ECD SPECT. We performed SPECT with 99mTc-ECD on the brains of subjects. A voxel-by-voxel group analysis was performed using SPM 8 and ANOVA. rCBF in EOS was found to be reduced in the precentral and inferior frontal gyri; on the other hand, rCBF was reduced in the bilateral postcentral gyrus in LOS. This study revealed a significant difference in brain perfusion between EOS and LOS. The present study might suggest that the characteristic changes in rCBF are related to onset-age in schizophrenia.

Using arterial spin labeling to examine mood states in youth.

IntroductionLittle is known about the neural correlates of mood states and the specific physiological changes associated with their valence and duration, especially in young people. Arterial spin labeling (ASL) imaging is particularly well-suited to study sustained cerebral states in young people, due to its robustness to low-frequency drift, excellent interscan reliability, and noninvasiveness. Yet, it has so far been underutilized for understanding the neural mechanisms underlying mood states in youth.MethodsIn this exploratory study, 21 healthy adolescents aged 16 to 18 took part in a mood induction experiment. Neutral, sad, and happy mood states were induced using film clips and explicit instructions. An ASL scan was obtained following presentation of each film clip.ResultsMood induction led to robust changes in self-reported mood ratings. Compared to neutral, sad mood was associated with increased regional cerebral blood flow (rCBF) in the left middle frontal gyrus and anterior prefrontal cortex, and decreased rCBF in the right middle frontal gyrus and the inferior parietal lobule. A decrease in self-reported mood from neutral to sad condition was associated with increased rCBF in the precuneus. Happy mood was associated with increased rCBF in medial frontal and cingulate gyri, the subgenual anterior cingulate cortex, and ventral striatum, and decreased rCBF in the inferior parietal lobule. The level of current self-reported depressive symptoms was negatively associated with rCBF change in the cerebellum and lingual gyrus following both sad and happy mood inductions.ConclusionsArterial spin labeling is sensitive to experimentally induced mood changes in healthy young people. The effects of happy mood on rCBF patterns were generally stronger than the effects of sad mood.

Quantification of blood flow-dependent component in estimates of beta-amyloid load obtained using quasi-steady-state standardized uptake value ratio.

Longitudinal positron emission tomography (PET) imaging of beta-amyloid is used in basic research and in drug efficacy trials in Alzheimer's disease (AD). However, the extent of amyloid accumulation after clinical onset is not fully known. Importantly, regional PET data are typically quantified using the standardized uptake value ratio (SUVR), which according to simulations is sensitive to changes in regional cerebral blood flow (rCBF). We aimed to better understand the potentials of longitudinal amyloid imaging by disentangling the influence of blood flow on SUVR using experimental data. [18F]AV-45 PET data from 101 subjects, ranging from cognitively normal to AD patients, in the Alzheimer's Disease Neuroimaging Initiative were extracted. The relationship between global cortical distribution volume ratio, indicator of rCBF (R1), and SUVR was examined using multilinear regression. There was a significant effect of rCBF on SUVR. The effect increased by disease severity. Results suggest that changes in rCBF can produce apparent changes in SUVR in AD. Therefore, future longitudinal studies should measure amyloid changes in a way not sensitive to this effect, ideally using quantitative PET imaging. Furthermore, the results suggest no true accumulation beyond clinical onset and highlight the risks of longitudinal amyloid imaging in drug trials in AD.

Abstract W P60: Blood Pressure Reduction In Acute Ischemic Stroke Does Not Affect Ischemic Core Tissue Perfusion

Introduction: Blood pressure (BP) reduction in acute ischemic stroke patients can potentially decrease cerebral blood flow (CBF) in ischemic tissue due to disrupted autoregulation, particularly in the ischemic core. We tested this hypothesis using a 3 group non-randomized controlled study of serial CBF measurements in ischemic stroke patients. Methods: Patients with acute ischemic stroke ≤72h of symptom onset were recruited. Groups were assigned according to baseline mean arterial blood pressure (MAP): patients with MAP &gt;120mmHg were treated with intravenous labetalol and sublingual (SL) nitroglycerin and those with MAP 100-120 mmHg were treated with SL nitroglycerin. The BP reduction target was 10% of the baseline MAP. Patients with MAP&lt;100 mmHg formed the control group. Patients underwent MR perfusion-weighted imaging (PWI) and diffusion-weighted imaging (DWI) before and after BP reduction. Blinded planimetric assessment was done to determine PWI deficits and DWI lesion volumes in the ischemic core region. Results: A total of 48 patients with mean±SD age of 65.4±13.2 years were enrolled at 23.4±15.3h after symptom onset. The mean time difference between perfusion scans was 25.6±9.5 min.Median(IQR) DWI volume was 11.1 (96.8) ml. Mean MAP was 126±7.5 mmHg in the MAP&gt;120 group(n=13), 109.9±4.9 mmHg in the MAP 100-120 group (n=16), and 89.9±6.2 mmHg in the controls (n=19). Mean BP reduction in the treated patients was 11.9±6.7 mmHg (95% CI 15.6-3; p=0.04). Baseline mean relative CBF (rCBF) in ischemic core tissue was 1.1±0.47 in the MAP &gt;120 group, 0.87±0.35 in the MAP 100-120 group and 0.78±0.32 in controls. The mean change in rCBF following BP reduction did not differ between the MAP &gt;120 group (0.03±0.17), MAP 100-120 group (0.06±0.17) and controls (0.08±0.25) (p=0.28). Similarly, there was no difference in the mean relative cerebral blood volume (p=0.3) and relative mean transit time (p=0.58) before and after BP reduction. In patients treated with SL nitroglycerin (n=17), there was no improvement in mean lesional rCBF (0.04±0.17 vs.-0.02±0.18, p=0.25). Conclusion: Modest BP reduction does not lead to an immediate decrease in CBF, within the ischemic core. Acute antihypertensive therapy may be less directly harmful than has been postulated.

Hyperperfusion counteracted by transient rapid vasoconstriction followed by long-lasting oligemia induced by cortical spreading depression in anesthetized mice.

Cortical spreading depression (CSD) involves mass depolarization of neurons and glial cells accompanied with changes in regional cerebral blood flow (rCBF) and energy metabolism. To further understand the mechanisms of CBF response, we examined the temporal diametric changes in pial arteries, pial veins, and cortical capillaries. In urethane-anesthetized mice, the diameters of these vessels were measured while simultaneously recording rCBF with a laser Doppler flowmeter. We observed a considerable increase in rCBF during depolarization in CSD induced by application of KCl, accompanied by a transient dip of rCBF with marked vasoconstriction of pial arteries, which resembled the response to pin-prick-induced CSD. Arterial constriction diminished or disappeared during the second and third passages of CSD, whereas the rCBF increase was maintained without a transient dip. Long-lasting oligemia with a decrease in the reciprocal of mean transit time of injected dye and mild constriction of pial arteries was observed after several passages of the CSD wave. These results indicate that CSD-induced rCBF changes consist of initial hyperemia with a transient dip and followed by a long-lasting oligemia, partially corresponding to the diametric changes of pial arteries, and further suggest that vessels other than pial arteries, such as intracortical vessels, are involved.

In Patients With Idiopathic Normal Pressure Hydrocephalus Postoperative Cerebral Perfusion Changes Measured by Dynamic Susceptibility Contrast Magnetic Resonance Imaging Correlate With Clinical Improvement.

To explore relationships between clinical improvement and relative cerebral blood flow (rCBF) changes after shunt-insertion in idiopathic normal pressure hydrocephalus (iNPH) as measured by dynamic susceptibility contrast magnetic resonance imaging. In 20 idiopathic normal pressure hydrocephalus patients rCBF was measured preoperatively and 3 months postoperatively. Because of shunt-induced right-sided artefacts, evaluation was restricted to 12 left-sided cortical, subcortical, and periventricular regions of interest. Correlations between rCBF and clinical symptoms were analyzed in shunt responders. In responders, the postoperative regions of interest-based rCBF increase of 2% to 9% was significant in the parenchyma, the hippocampus, and the anterior periventricular white matter. Perfusion improvement in the cingulus, caudate head, and thalamus correlated with decreased disturbance in one or more of the domains neuropsychology, gait, balance, and total performance. Apparently, dynamic susceptibility contrast magnetic resonance imaging can measure postoperative perfusion changes in responders. Postoperatively, perfusion increase in some grey matter structures seems to determine the degree of clinical improvement.

Efficacy of an NMDA receptor antagonist for Parkinson's disease dementia: A brain perfusion SPECT study

ABSTRACTMemantine's efficacy has been demonstrated in patients with moderate to severe Alzheimer's disease. However, memantine therapy is not typically used in treating Parkinson's disease dementia (PDD), although the deviating glutamatergic pattern evidenced in neuropathological findings suggests that N‐methyl D‐aspartate receptor antagonists in patients with Lewy‐body disorder may be effective. Therefore, we conducted this longitudinal study to confirm the efficacy of memantine for PDD by analyzing comparative changes in regional cerebral blood flow (rCBF) and neuropsychological tests before and after memantine administration in PDD. A total of 18 patients with PDD were enrolled in this study. All patients underwent technetium‐99m hexamethylpropyleneamine oxime single photon emission computed tomography and completed neuropsychological tests before and 12 months after memantine administration. This study showed that there was no significant difference in cognitive functioning before and after memantine administration. No significant difference in rCBF was observed in any regions at baseline compared to 12 months after memantine administration. Our results suggest that memantine delays the speed of deterioration in cognitive functioning and behavioral symptoms in PDD because we found no significant changes in rCBF and cognition after memantine treatment.

A Spatiotemporal Profile of In Vivo Cerebral Blood Flow Changes Following Intranasal Oxytocin in Humans

BackgroundAnimal and human studies highlight the role of oxytocin in social cognition and behavior and the potential of intranasal oxytocin (IN-OT) to treat social impairment in individuals with neuropsychiatric disorders such as autism. However, extensive efforts to evaluate the central actions and therapeutic efficacy of IN-OT may be marred by the absence of data regarding its temporal dynamics and sites of action in the living human brain. MethodsIn a placebo-controlled study, we used arterial spin labeling to measure IN-OT-induced changes in resting regional cerebral blood flow (rCBF) in 32 healthy men. Volunteers were blinded regarding the nature of the compound they received. The rCBF data were acquired 15 min before and up to 78 min after onset of treatment onset (40 IU of IN-OT or placebo). The data were analyzed using mass univariate and multivariate pattern recognition techniques. ResultsWe obtained robust evidence delineating an oxytocinergic network comprising regions expected to express oxytocin receptors, based on histologic evidence, and including core regions of the brain circuitry underpinning social cognition and emotion processing. Pattern recognition on rCBF maps indicated that IN-OT-induced changes were sustained over the entire posttreatment observation interval (25–78 min) and consistent with a pharmacodynamic profile showing a peak response at 39–51 min. ConclusionsOur study provides the first visualization and quantification of IN-OT-induced changes in rCBF in the living human brain unaffected by cognitive, affective, or social manipulations. Our findings can inform theoretical and mechanistic models regarding IN-OT effects on typical and atypical social behavior and guide future experiments (e.g., regarding the timing of experimental manipulations).

Prominent hypointense veins on susceptibility weighted image in the cat brain with acute infarction: DWI, SWI, and PWI

The multiple prominent hypointense veins on susceptibility-weighted imaging (SWI) have been found in the ischemic territory of patients with acute ischemic stroke. Venous side is the unknown area in the hemodynamics of brain infarction. To evaluate the venous aspect in acute brain infarction through an animal study. The acute infarction in cat brains was induced with a bolus infusion of 0.25 mL of triolein through one side of the common carotid artery. The magnetic resonance (MR) images, including diffusion-weighted imaging (DWI), apparent diffusion coefficient (ADC) map, SW, and perfusion-weighted (PWI) images, were obtained serially at 2 h (n = 17), 1 day (n = 11), and 4 days (n = 4) after triolein infusion. The obtained MR images were evaluated qualitatively and quantitatively. For qualitative assessment, the signal intensity of the serial MR images was evaluated. The presence or absence and the location with serial changes of infarction were identified on DWI and ADC map images. The presence or absence of prominent hypointense veins and the serial changes of cortical veins were also evaluated on SWI. Quantitative assessment was performed by comparing the relative cerebral blood volume (rCBV), cerebral blood flow (rCBF), and mean transit times (MTT) of the lesions with those of the contralateral normal side calculated on PWI. The serial changes of rCBV, rCBF, and MTT ratio were also evaluated. Acute infarction in the first and second medial gyrus of lesion hemisphere was found by qualitative evaluation of DWI and ADC map images. On the serial evaluation of SWI, the cortical veins of cat brain with infarction were obscured at 2 h and then re-appeared at 1 day. The hemorrhage transformation and prominent hypointense veins were seen at 4 days on SWI. The quantitative evaluation revealed increased MTT ratios and decreased rCBV and rCBF ratios on PWIs in the acute infarction of cat brain. The prominent hypointense veins on SWI were seen in the half of the acute infarction at 4 days. The prominent hypointense veins on SWI may have good agreement with the increased MTT ratio.

Blood-brain barrier permeability change and regulation mechanism after subarachnoid hemorrhage.

We aimed to investigate the blood brain barrier (BBB) change caused by subarachnoid hemorrhage (SAH) and to explore the molecular mechanisms of acute brain injury after SAH. The SD rat model of SAH was firstly established by endovascular filament perforation technique. The changes of regional cerebral blood flow (rCBF), BBB permeability and ultrastructure of brain tissue at different time points after SAH were respectively observed by Doppler flowmetry, evans blue extravasation and transmission electron microscopy. Meanwhile, the expression changes of Claudin-5, Occludin, Zo-1 and Caveolin-1 were detected by immunohistochemistry and Western blot. Furthermore, the expressions of Akt, P-Akt and Foxo1A were also measured by Western blot. The change of BBB permeability showed two peaks at 3 and 72 h after SAH, corresponding to the change of rCBF. The BBB tight junction opening can be observed after SAH, and the largest opening was occurred at 3 h and 72 h. There was no significant change in Caveolin-1, Claudin-5 and Akt expressions after SAH (P > 0.05), while Zo-1 and Occludin were significantly down-regulated (P < 0.05). The expression of P-Akt was obviously reduced at 30 min and then increased at 1 and 24 h, while Foxo1A was up-regulated at 1 and 24 h after SAH (P < 0.05). Down-regulated Zo-1 and Occludin, as well as Akt/FOXO signaling pathway may be involved in the regulation of tight junction opening and the BBB permeability in the early stage after SAH.