rCBF Changes Research Articles

DL-3-n-butylphthalide improves cerebral hypoperfusion in patients with large cerebral atherosclerotic stenosis: a single-center, randomized, double-blind, placebo-controlled study

BackgroundDL-3-n-butylphthalide (NBP) was demonstrated to increase the cerebral blood flow (CBF) in the animal models, but there are no clinic studies to verify this. We aimed to explore the effect of NBP on improving cerebral hypoperfusion caused by cerebral large-vessel stenosis.MethodsIn this single-center, randomized, double-blind, placebo-controlled study, 120 patients with severe carotid atherosclerotic stenosis and cerebral hypoperfusion in the ipsilateral middle cerebral artery (MCA) were included and randomly assigned into NBP or placebo group as 1:1 radio. Patients in NBP or placebo group received 200 mg or 20 mg of NBP capsules three times daily for four weeks respectively. Single photon emission computed tomography (SPECT) was used to assess regional CBF (rCBF) in four regions of interest (ROIs) corresponding to MCA before and 12 weeks after the treatment. After therapy, the rCBF change for every ROI and the whole CBF change in MCA territory for every patient were classified into amelioration, stabilization and deterioration respectively.Results48 NBP patients (6 with bilateral stenosis) and 46 placebo patients (8 with bilateral stenosis) completed the trial. Overall, both groups had 54 stenotic carotid arteries and 216 ROIs for rCBF change analysis. After therapy, the rCBF in ROIs increased in NBP group (83.5% ± 11.4% vs. 85.8% ± 12.5%, p = 0.000), whereas no change was found in placebo group (86.9% ± 11.6% vs. 87.8% ± 11.7%, p = 0.331). Besides, there was higher percentages of ROIs with rCBF amelioration and stabilization in NBP group than in placebo group (93.1% vs. 79.2%, p = 0.000). Furthermore, ordinal regression analysis showed that compared with placebo, NBP independently made more patients to have whole CBF amelioration in ipsilateral MCA (Wald-χ2 = 5.247, OR = 3.31, p = 0.022).ConclusionsNBP might improve the cerebral hypoperfusion in the patients with carotid artery atherosclerotic stenosis.Trial registrationChinese Clinical Trial Registry, ChiCTR1900028005, registered December 8th 2019- Retrospectively registered (http://www.chictr.org.cn/index.aspx).

M143. REGIONAL CEREBRAL BLOOD FLOW IN INITIALLY ANTIPSYCHOTIC-NAïVE PATIENTS WITH SCHIZOPHRENIA OR PSYCHOSIS: EFFECTS OF PARTIAL D2 RECEPTOR AGONISM AND ASSOCIATION WITH SYMPTOM IMPROVEMENT

BackgroundSchizophrenia is suggested to stem from dysfunction of cortico-striato-thalamo-cortical networks. Supporting this, we have recently found increased glutamate levels in thalamus in antipsychotic-naïve patients with schizophrenia or psychosis. Moreover, higher baseline glutamate levels were related to less improvement of psychotic symptoms after treatment. Other groups have reported that striatal dopaminergic function in patients with psychosis is increased and associated with psychotic symptoms. Regional cerebral blood flow (rCBF) is considered a marker of neuronal activity and can be used to study the cortico-striato-thalamo-cortical networks.Here, we investigated rCBF in a large group of initially antipsychotic-naïve patients with schizophrenia or psychosis before and after treatment and related the findings to changes in psychotic symptoms.MethodsrCBF was acquired in 49 initially antipsychotic-naïve patients and 50 matched healthy controls at baseline, and in 32 patients and 53 healthy controls after 6 weeks with the pseudo-Continuous Arterial Spin Labelling (pCASL) sequence. Patients were treated with a partial dopamine D2 receptor agonist (aripiprazole) as monotherapy (mean dose: 10.6±5.4mg).Primary regions of interest of rCBF were thalamus, limbic- and associative striatum. In explorative analyses, we estimated rCBF in sensorimotor striatum, hippocampus-amygdala, and frontal lobe.Psychopathology was assessed with the positive and negative syndrome scale (PANSS).A linear mixed model was used to test if the change in rCBF was different in patients compared with healthy controls (significant interaction) with adjustment for age, sex, and whole brain rCBF. Post hoc tests evaluated possible group differences at baseline and after 6 weeks.In a general linear model, we investigated associations between baseline rCBF in striatum and thalamus and improvement in psychotic symptoms.ResultsrCBF changed over 6 weeks in all striatal regions (associative striatum: p=0.023; limbic striatum: p=0.004; sensorimotor striatum: p=0.004). Post hoc tests of associative striatum indicated no baseline group differences in rCBF (SCZ/HC: 63.4/65.1 mL/100g/min, p=0.59), however rCBF was higher in patients after 6 weeks (SCZ/HC: 68.8/63.2 mL/100g/min, p=0.049). Post hoc tests of limbic striatum indicated no baseline group differences in rCBF (SCZ/HC: 62.7/65.3 mL/100g/min, p=0.25) and no group differences rCBF after 6 weeks (SCZ/HC: 69.3/63.3 mL/100g/min, p=0.12).Post hoc tests of sensorimotor striatum indicated no baseline group differences in rCBF (SCZ/HC: 72.6/71.2 mL/100g/min, p=0.18), however, rCBF was significantly higher in patients after 6 weeks (SCZ/HC: 80.0/67.2 mL/100g/min, p<0.001).There were no group differences in the rCBF changes in thalamus (p=0.09), hippocampus-amygdala (p=0.24), frontal lobe (p=0.90), and the whole brain (p=0.14).In patients, higher baseline rCBF in limbic striatum was associated with less improvement in PANSS positive symptoms (p=0.025). We found no other associations between rCBF and psychopathy.DiscussionThe findings suggest that treatment with a partial dopamine D2 agonist increases rCBF in associative and sensorimotor striatum in initially antipsychotic-naïve patients and that higher rCBF in limbic striatum at baseline is related to poorer treatment outcome. Future studies should investigate the associations between different neurotransmitters and rCBF in vivo. This could further characterize disturbances in cortico-striato-thalamo-cortical networks in schizophrenia or psychosis as well as the effect of treatment.

Cerebral Hemodynamic Changes After Endovascular Recanalization of Symptomatic Chronic Intracranial Artery Occlusion.

Objective: We performed this study to evaluate the hemodynamic changes over time after successful endovascular recanalization in patients with symptomatic chronic intracranial artery occlusion (CIAO).Materials and Methods: We included 20 patients with symptomatic CIAO in a high-volume stroke center from June 2014 to June 2019. All subjects were evaluated with CT perfusion (CTP) studies before and after the recanalization. The relative cerebral blood flows (rCBFs) in perforating artery territory (PAT) and cortical artery territory (CAT) of occluded arteries were compared before and after the recanalization. The patients were categorized into subgroups based on the time interval from revascularization to post-procedural CTP, occlusion sites, and restenosis status. The proportion of rCBF change (rCBFc%) was compared in variable subgroups.Results: The rCBF increased significantly from 0.52 to 0.71 in PAT (P < 0.001) and from 0.59 to 0.85 in CAT (P < 0.001) after recanalization, and there were also statistical differences in variable subgroups except for those with restenosis. The median and interquartile range (IQR) of rCBFc% were 35.2 and 18.6–56.6%. For patients with short-term follow-up (55.2%), the rCBFc% was relatively higher than that in patients with mid-term (35.4%) and long-term follow-up (32.7%), although without statistical difference (P = 0.273). For patients with restenosis, the rCBFc% was significantly lower than that in patients without restenosis (18.5 vs. 37.3%, P = 0.008).Conclusions: In patients with symptomatic CIAO, the CBF may increase and be relatively stable over time after successful recanalization except for restenosis.

Transcranial Direct Current Stimulation for the Treatment of Parkinson's Disease: Clinical and Regional Cerebral Blood Flow SPECT Outcomes.

Over the course of treatment for Parkinson's disease (PD), the clinical effects of dopaminergic medication diminish and side effects emerge. Therefore, searching for new therapeutic alternatives or complementary treatments is required. Transcranial direct current stimulation (tDCS) could potentially complement the current therapeutic armamentarium, but only a few studies have investigated the therapeutic effects of tDCS in PD. The present pilot study aimed to investigate the effects of repeated tDCS treatment on motor symptoms and regional cerebral blood flow (rCBF) in patients with PD using single photon emission computed tomography (SPECT). Four patients with PD received tDCS to the dorsolateral prefrontal cortex two times per week (anode F3/cathode F4, 2mA for 30 minutes) over a period of 12 months. Patients underwent brain SPECT scans and clinical motor evaluation at baseline and 12-month follow-up. For SPECT data, voxel-wise changes in rCBF were analyzed. There was no significant change of the motor severity scale, but the follow-up SPECT showed significant hyperperfusion in the left superior frontal gyrus medial segment and left superior parietal lobule compared to baseline (P < .001). This study shows that tDCS application may improve rCBF in the frontal and parietal lobes in patients with PD, suggesting beneficial effects of tDCS on brain function. Our results are preliminary and further large-scale studies are needed to confirm our findings.

Neurovascular coupling in the developing neonatal brain at rest.

The neonatal brain is an extremely dynamic organization undergoing essential development in terms of connectivity and function. Several functional imaging investigations of the developing brain have found neurovascular coupling (NVC) patterns that contrast with those observed in adults. These discrepancies are partly due to that NVC is still developing in the neonatal brain. To characterize the vascular response to spontaneous neuronal activations, a multiscale multimodal noninvasive approach combining simultaneous electrical, hemodynamic, and metabolic recordings has been developed for preterm infants. Our results demonstrate that the immature vascular network does not adopt a unique strategy to respond to spontaneous cortical activations. NVC takes on different forms in the same preterm infant during the same recording session in response to very similar types of neural activation. This includes (a) positive stereotyped hemodynamic responses (increases in HbO, decreases in HbR together with increases in rCBF and rCMRO2), (b) negative hemodynamic responses (increases in HbR, decreases in HbO together with decreases in rCBF and rCMRO2), and (c) Increases and decreases in both HbO‐HbR and rCMRO2 together with no changes in rCBF. Age‐related NVC maturation is demonstrated in preterm infants, which can contribute to a better understanding/prevention of cerebral hemodynamic risks in these infants.

Efficacy of NMDA receptor antagonist on regional cerebral blood flow in Parkinson's disease with dementia

Although 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). A 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. The 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. Our findings implicate that memantine may delay the progression of brain perfusion deficits and clinical symptoms of PDD in the long term.

Is Precise Targeting of the Recipient Artery in a Superficial Temporal Artery-Middle Cerebral Artery Anastomosis Crucial?

To investigate the difference in treatment outcomes according to the method used to select the recipient artery in superficial temporal artery-middle cerebral artery (STA-MCA) anastomoses. We retrospectively analyzed the cases of 35 patients who underwent an STA-MCA anastomosis for internal carotid artery/MCA occlusion or stenosis. Patients were divided into two groups based on whether the recipient artery was precisely targeted by single-photon emission computed tomography (SPECT group) or less precisely targeted by visual assessment (Visual group). Then the bypass results in both groups were evaluated postoperatively based on changes in the regional cerebral blood flow (rCBF) and clinical outcomes. The delineated recipient artery in magnetic resonance angiography (MRA) matched the intraoperatively selected artery in 87.6% of the SPECT group cases and 83.3% of the Visual group cases. The SPECT group's digital subtraction angiography (DSA) findings coincided with the intraoperative selection in 76.9% of cases, and the MRA findings corresponded with the DSA findings in 92.3%. The postoperative areas with increased rCBF matched the perfused areas of intraoperatively selected arteries in 80.0% of the SPECT group cases and 77.8% of the Visual group cases. Postoperatively increased rCBF areas matching totally or partially with preoperative low-perfusion areas were observed in all cases. The present results revealed no significant differences in the change in rCBF in the low-perfusion area between the patients whose recipient arteries were selected by SPECT or visual assessment.

Neuroprotective Effects of Rasagiline in Parkinson's Disease: A Regional Cerebral Blood Flow Study.

Despite accumulating evidence for the clinical efficacy and neuroprotective properties of rasagiline in Parkinson's disease (PD), effects of rasagiline on brain perfusion in PD patients have not been elucidated. The present study aimed to investigate the effects of rasagiline on regional cerebral blood flow (rCBF) in patients with PD using single-photon emission computed tomography (SPECT). A total of 44 PD patients were recruited and treated with dopamine agonist, either alone or in combination with levodopa. Twenty-two of these patients (referred to as the rasagiline group) additionally received rasagiline (1mg/day). All patients underwent brain SPECT scans and clinical assessments at baseline and follow-up visits. The mean follow-up period was 2.2 years. Changes in rCBF were compared between the rasagiline group and the comparison group in a voxel-wise manner. Annual change in Unified Parkinson's Disease Rating Scale motor score was lower in the rasagiline group compared to the comparison group (P = .01). A significant group-by-time interaction effect on rCBF was found in the right precuneus (P = .001), where rCBF was decreased in the comparison group and remained stable in the rasagiline group. Our results show that adjunctive rasagiline treatment had beneficial effects on perfusion in the precuneus of PD patients, suggesting potential neuroprotective effects.

Efficacy of nicergoline treatment in Parkinson’s disease associated with dementia

Parkinson’s disease (PD) has a variable spectrum of cognitive impairment. However, there are no clear evident-based management guidelines for PD with dementia (PDD). Alternative treatments for PDD are therefore required. We conducted this longitudinal study to evaluate the efficacy of nicergoline in treating PDD by analyzing changes in regional cerebral blood flow (rCBF) and neuropsychological tests before and after nicergoline administration. A total of nine PDD patients who received nicergoline therapy (PDD + N) and 14 PD patients who did not receive nicergoline therapy (PDD − N) underwent single photon emission computed tomography (SPECT) and clinical assessments at baseline and 12-month follow-up visits. The PDD + N received nicergoline at 30 mg twice per day. Changes in rCBF were compared between the groups, and correlation analysis was performed to determine possible relationship between rCBF and clinical characteristics. There were no significant differences in rCBF between the two groups at baseline. Although changes in cognitive test scores and the motor severity scale were not significantly different between baseline and the 12-month follow-up within groups, rCBF was lower in both the temporal and inferior frontal restricted areas in the PDD − N group than the PDD + N at the 12-month follow-up visit. In conclusions, nicergoline appears to delay the speed of deterioration of cognitive function in patients with PDD based on our observation of decreased rCBF in the temporal regions and inferior frontal regions of PDD − N patients compared to PDD + N patients after 12-month of nicergoline therapy. Therefore, we cautiously suggest that nicergoline administration in PDD patients may slow progression of cognitive impairment in affected brain regions.

Cerebral Blood Flow Response During Bolus Normal Saline Infusion After Ischemic Stroke

Goals: We quantified cerebral blood flow response to a 500 cc bolus of 0.9%% normal saline (NS) within 96 hours of acute ischemic stroke (AIS) using diffuse correlation spectroscopy (DCS). Materials and Methods: Subjects with AIS in the anterior, middle, or posterior cerebral artery territory were enrolled within 96 hours of symptom onset. DCS measured relative cerebral blood flow (rCBF) in the bilateral frontal lobes for 15 minutes at rest (baseline), during a 30-minute infusion of 500 cc NS (bolus), and for 15 minutes after completion (post-bolus). Mean rCBF for each time period was calculated for individual subjects and median rCBF for the population was compared between time periods. Linear regression was used to evaluate for associations between rCBF and clinical features. Results: Among 57 subjects, median rCBF (IQR) increased relative to baseline in the ipsilesional hemisphere by 17% (−2.0%, 43.1%), P< 0.001, and in the contralesional hemisphere by 13.3% (−4.3%, 36.0%), P < .004. No significant associations were found between ipsilesional changes in rCBF and age, race, infarct size, infarct location, presence of large vessel stenosis, NIH stroke scale, or symptom duration. Conclusion: A 500 cc bolus of .9% NS produced a measurable increase in rCBF in both the affected and nonaffected hemispheres. Clinical features did not predict rCBF response.

Ketamine induced changes in regional cerebral blood flow, interregional connectivity patterns, and glutamate metabolism

Several imaging studies have attempted to characterize the contribution of glutamatergic dysfunction to functional dysconnectivity of large-scale brain networks using ketamine models. However, findings from BOLD imaging studies are conflicting, in part because the signal stems from a complex interaction between blood flow, blood volume, and oxygen consumption.We used arterial spin labelling imaging to measure regional cerebral blood flow (rCBF) in a group of healthy volunteers during a saline and during a ketamine infusion. We examined changes in rCBF and interregional connectivity patterns, as well as their associations with clinical symptom severity and Glx (glutamate + glutamine) assessed with magnetic resonance spectroscopy.We report a regionally selective pattern of rCBF changes following ketamine administration and complex changes in interregional connectivity patterns. We also found that the increase in rCBF in the bilateral putamen and left hippocampus was positively correlated with ketamine induced clinical symptom severity while anterior cingulate rCBF during the ketamine challenge was negatively correlated with change in hippocampal Glx.Our study adds to the efforts to empirically confirm putative links between an NMDA receptor blockage and dysconnectivity of large-scale brain networks, specifically the salience, executive control and default mode networks, suggesting that a glutamatergic imbalance may contribute to dysconnectivity. Development of glutamatergic compounds that alleviate disease burden, possibly through normalizing glutamate excess related increased rCBF, is direly needed.

Modulation of brain activity with transcranial direct current stimulation: Targeting regions implicated in impaired illness awareness in schizophrenia

BackgroundImpaired illness awareness or insight into illness (IIA) is a common feature of schizophrenia that contributes to medication nonadherence and poor clinical outcomes. Neuroimaging studies suggest IIA may arise from interhemispheric imbalance in frontoparietal regions, particularly in the posterior parietal area (PPA) and the dorsolateral prefrontal cortex (dlPFC). In this pilot study, we examined the effects of transcranial direct current stimulation (tDCS) on brain regions implicated in IIA. MethodsEleven patients with schizophrenia with IIA (≥3 PANSS G12) and 10 healthy controls were included. A crossover design was employed where all participants received single-session bi-frontal, bi-parietal, and sham stimulation in random order. For each condition, we measured (i) blood oxygen level-dependent (BOLD) response to an illness awareness task pre- and post-stimulation, (ii) regional cerebral blood-flow (rCBF) prior to and during stimulation, and (iii) changes in illness awareness. ResultsAt baseline, patients with schizophrenia showed higher BOLD-response to an illness awareness task in the left-PPA compared to healthy controls. Bi-parietal stimulation reduced the interhemispheric imbalance in the PPA compared to sham stimulation. Relatedly, bi-parietal stimulation increased rCBF beneath the anode (21% increase in the right-PPA), but not beneath the cathode (5.6% increase in the left-PPA). Bi-frontal stimulation did not induce changes in rCBF. We found no changes in illness awareness. ConclusionAlthough single-session tDCS did not improve illness awareness, this pilot study provides mechanistic justification for future investigations to determine if multi-session bi-parietal tDCS can induce sustained changes in brain activity in the PPA in association with improved illness awareness.

Effects of nicergoline treatment on regional cerebral blood flow in early Alzheimer's disease

AbstractAlzheimer's disease (AD) is associated with reduction of regional cerebral blood flow (rCBF) in various brain regions. Although nicergoline has been used to treat cognitive impairment in various types of dementia, the effect of nicergoline on brain perfusion in AD has not been elucidated. The aim of the study was to examine the effect of nicergoline on rCBF in patients with early AD using technetium‐99m hexamethylpropylene amine oxime single‐photon emission computed tomography (SPECT). For 1.7 years on average, 22 patients with early AD received nicergoline (30 mg twice daily) and acetylcholinesterase inhibitors (AChEI), whereas other 22 patients received AChEI only. All patients underwent assessment of dementia severity and SPECT scans at baseline and follow‐up. We compared baseline rCBF and annual percent change of rCBF between the two groups. There were no significant differences in rCBF between the groups at baseline. Although changes in dementia severity was not statistically different, the annual percent changes of rCBF were higher in the left temporal pole (−0.12 ± 3.95 vs −3.38 ± 3.30, P = 0.002) and middle cingulate gyrus (1.91 ± 3.58 vs −1.34 ± 3.17, P = 0.002) among the nicergoline group. Our study demonstrated that nicergoline treatment combined with AChEI either better preserves or further improves cerebral perfusion in the temporal and cingulate cortices in patients with early AD compared to AChEI treatment alone. These results may indicate potential beneficial effects of nicergoline on brain functions in AD.

Cerebral blood flow and Alzheimer's disease-related biomarkers in cerebrospinal fluid in idiopathic normal pressure hydrocephalus.

Alzheimer's disease (AD) pathology is highly prevalent in patients with idiopathic normal pressure hydrocephalus (iNPH), and the presence of AD pathology may involve regional cerebral blood flow (rCBF). In this study, we examined the relationship between rCBF and AD-related biomarkers in the cerebrospinal fluid of iNPH patients. Patients with iNPH (n = 39) were classified into groups with (iNPH/AD+) (n=15) and without (iNPH/AD-) (n=24) high biomarker probability of AD (i.e. combined low amyloid β 42 and high total tau in the cerebrospinal fluid). rCBF was quantified in 17 regions of interest by N-isopropyl-p-[123 I]iodoamphetamine single-photon emission computed tomography with the autoradiography method. We compared rCBF between the iNPH/AD- and iNPH/AD+ groups at baseline using a t-test and then compared changes in rCBF after shunt surgery between the groups using a paired t-test and two-way repeated measures ANOVA. At baseline, there were no significant differences in rCBF between the groups in most regions apart from the putamen. After shunt surgery, a significant increase in rCBF in the putamen, amygdala, hippocampus, and parahippocampal gyrus was observed in iNPH/AD- patients. In iNPH/AD+ patients, no significant improvement in rCBF was observed in any region. In repeated measures analysis of variance, a significant group × shunt interaction was observed in the parietal lobe, frontal lobe, posterior cingulate cortex, precuneus, lateral temporal lobe, amygdala, hippocampus, parahippocampal gyrus, and putamen. Improvement in rCBF after shunt surgery in iNPH/AD+ patients may be poorer than that in iNPH AD- patients.

Motor Improvement-Related Regional Cerebral Blood Flow Changes in Parkinson's Disease in Response to Antiparkinsonian Drugs.

Little is known about the relationship between regional cerebral blood flow (rCBF) change and clinical improvement in patients with Parkinson's disease (PD). Single-photon emission computed tomography (SPECT) measurement of cerebral blood flow allows evaluation of temporal changes in brain function, and using SPECT, we aimed to identify motor improvement-related rCBF changes in response to the administration of antiparkinsonian drugs. Thirty PD patients (16 without dementia; 14 with dementia) were scanned with technetium-99m labeled ethyl cysteinate dimer SPECT and were rated with the Movement Disorder Society-Unified Parkinson's Disease Rating Scale part III, both before and after a single administration of antiparkinsonian drugs. The SPECT data were processed using Statistical Parametric Mapping 2, the easy Z-score Imaging System, and voxel-based Stereotactic Extraction Estimation. The rCBF responses in the deep brain structures after administration of antiparkinsonian drugs tended to be larger than those in cortical areas. Among these deep brain structures, the rCBF increases in the substantia nigra (SN), lateral geniculate (LG) body, and medial geniculate (MG) body correlated with drug efficacy (p < 0.05, respectively). A subgroup analysis revealed that the motor improvement-related rCBF change in the MG was statistically significant, irrespective of cognitive function, but the significant changes in the LG and SN were not found in subjects with dementia. In conclusion, our SPECT study clearly exhibited drug-driven rCBF changes in PD patients, and we newly identified motor improvement-related rCBF changes in the LG and MG. These results suggest that rCBF changes in these regions could be considered as candidates for clinical indicators for objective evaluation of disease progression. Furthermore, functional studies focusing on the LG and MG, especially in relation to therapies using audio-visual stimuli, may bring some new clues to explain the pathophysiology of PD.

Cerebral blood flow in striatal regions is associated with apathy in patients with schizophrenia.

Striatal dysfunction has been proposed as a pathomechanism for negative symptoms in schizophrenia. There is consensus that negative symptoms can be grouped into 2 dimensions: apathy and diminished expression. Recent studies suggest that different neural mechanisms underlie these dimensions, but the relationship between regional resting-state cerebral blood flow (rCBF) and negative symptom dimensions has not been investigated. This study included 29 patients with schizophrenia and 20 healthy controls. We measured rCBF in the striatum using arterial spin labelling (ASL) MRI. We assessed negative symptoms using the Brief Negative Symptom Scale. In the ventral and dorsal striatum, rCBF was not different between patients with schizophrenia and controls. However, we did find a positive association between the severity of apathy and increased rCBF in the ventral and dorsal striatum in patients with schizophrenia. This effect was not present for diminished expression. All patients were taking atypical antipsychotics, so an effect of antipsychotic medication on rCBF could not be excluded, although we did not find a significant association between rCBF and chlorpromazine equivalents. The main finding of this study was a specific association between increased striatal rCBF and the negative symptom dimension of apathy. Our results further support the separate assessment of apathy and diminished expression when investigating the neural basis of negative symptoms. The ASL technique can provide a direct and quantitative approach to investigating the role of rCBF changes in the pathophysiology of negative symptoms.

Neuroimaging Characteristics of Frailty Status in Patients with Alzheimer's Disease.

Although frailty is closely linked to dementia, particularly Alzheimer's disease (AD), underlying pathophysiology of frailty associated with AD remains uncertain. This study aimed to investigate differences in structural and functional brain imaging abnormalities between AD with and without frailty. A total of 191 outpatients with probable AD (men: 91; women: 100; age: 80.7±6.3 years) who underwent both magnetic resonance imaging (MRI) and single-photon emission computed tomography (SPECT) were enrolled in this study. Frailty was determined in accordance with the Obu study Health Promotion for the Elderly. We compared numbers of small infarctions in the subcortical gray and white matter and severity of white matter abnormalities (periventricular hyperintensity [PVH] and deep white matter hyperintensity [DWMH]) on MRI, and regional cerebral blood flow (rCBF) changes on SPECT between AD with and without frailty. The prevalence of frailty was 43.4% in patients with AD. PVH and DWMH scores were significantly higher in AD with frailty compared to those without frailty. AD with frailty had a trend of decreased rCBF in the bilateral anterior cingulate gyrus, whereas those without frailty tend to have decreased rCBF in the left dominant parietal lobe and precuneus. Our MRI and SPECT imaging studies suggest different underlying pathophysiology in the brain between AD with frailty and without frailty.

Abstract TP90: Computed Tomography Perfusion Mismatch is Stable Over Time From Onset After Stroke Due to Underestimation of Core Infarct in Late Time Window

Background: Automated computed tomography perfusion (CTP) imaging is proven effective at selecting patients with acute large vessel occlusion (LVO) for endovascular intervention in the extended time window (&gt;6 hours after last known normal [LKN]). However, there are limited data on the likelihood of identifying core infarct-penumbral mismatch in the late time window. Hypothesis: Automated CTP mismatch ratios (Time-to-maximum residue function [T max ] &gt;6s: relative cerebral blood flow [rCBF] &lt;30%) using RAPID software will decrease as time from LKN increases. Methods: We reviewed a retrospective registry of consecutive patients with LVO who underwent CTP within 24h of LKN at 3 academic hospitals between 06/2017 - 12/2017. Unenhanced CT and CTP parameters were compared between patients who presented within 12h of LKN versus 12-24h of LKN. Results: Among 60 included patients, the median age was 78 years (IQR 64-84), 36 (60.0%) were female, and 39 (65.0%) underwent thrombectomy. Patients who presented at 12-24h had poorer ASPECTS scores than patients who presented &lt;12h from LKN (median score 7 [IQR 5-8] vs. 8 [IQR 6-9], p=0.092), but the mismatch ratios were not significantly different (median 5.95 [IQR 2.64-9.11] vs. 3.28 [IQR 2.19-7.70], p=0.509). Longer delay from LKN were associated with a lower ASPECTS score (adjusted β -0.12 points/hr, 95%CI -0.21 - -0.04, p=0.006), which was driven by patients with witnessed symptom onset (adjusted p=0.009; Figure), but no significant change in rCBF &lt;30% (adjusted p=0.360) irrespective of whether symptom onset was witnessed (adjusted p=0.847; Figure). Conclusions: As time progresses in acute anterior LVO, the unenhanced CT may be more sensitive than rCBF&lt;30% for detecting the volume of irreversibly damaged tissue. Figure caption: ASPECTS and rCBF &lt;30% over time. Blue dots indicate patients with witnessed onset (with fitted dashed line), red circles indicate patients with unwitnessed onset (with fitted solid line).

Brain Correlates of Continuous Pain in Rheumatoid Arthritis as Measured by Pulsed Arterial Spin Labeling.

Central nervous system pathways involving pain modulation shape the pain experience in patients with chronic pain. The aims of this study were to understand the mechanisms underlying pain in patients with rheumatoid arthritis (RA) and to identify brain signals that may serve as imaging markers for developing targeted treatments for RA-related pain. Patients with RA and matched control subjects underwent functional magnetic resonance imaging, using pulsed arterial spin labeling. The imaging conditions included 1) resting state, 2) low-intensity stimulus, and 3) high-intensity stimulus. Stimuli consisted of mechanical pressure applied to metacarpophalangeal (MCP) joints with an automated cuff inflator. The low-intensity stimulus was inflation to 30 mm Hg. The high-intensity stimulus was the amount of pressure required to achieve a pain intensity rating of 40 on a 100-point scale for each RA patient, with the same amount of pressure used in the matched control. Among RA patients, regional cerebral blood flow (rCBF) in the medial frontal cortex and dorsolateral prefrontal cortex increased during both low-pressure and high-pressure stimulation. No rCBF changes were observed in pain-free controls. Region-of-interest analyses in RA patients showed that baseline rCBF in the medial frontal cortex was negatively correlated with the pressure required for the high-intensity stimulus and positively correlated with pain induced by the low-intensity stimulus. Baseline rCBF was also marginally correlated with disease activity). Regional CBF during high pain was positively correlated with pain severity and pain interference. In response to clinically relevant joint pain evoked by pressure applied to the MCP joint, neural processing in the medial frontal cortex increases and is directly associated with clinical pain in patients with RA.

Increased cerebral blood flow after single dose of antipsychotics in healthy volunteers depends on dopamine D2 receptor density profiles

As a result of neuro-vascular coupling, the functional effects of antipsychotics in human brain have been investigated in both healthy and clinical populations using haemodynamic markers such as regional Cerebral Blood Flow (rCBF). However, the relationship between observed haemodynamic effects and the pharmacological action of these drugs has not been fully established. Here, we analysed Arterial Spin Labelling (ASL) rCBF data from a placebo-controlled study in healthy volunteers, who received a single dose of three different D2 receptor (D2R) antagonists and tested the association of the main effects of the drugs on rCBF against normative population maps of D2R protein density and gene-expression data. In particular, we correlated CBF changes after antipsychotic administration with non-displaceable binding potential (BPND) template maps of the high affinity D2-antagonist Positron Emission Tomography (PET) ligand [18F]Fallypride and with brain post-mortem microarray mRNA expression data for the DRD2 gene from the Allen Human Brain Atlas (ABA). For all antipsychotics, rCBF changes were directly proportional to brain D2R densities and DRD2 mRNA expression measures, although PET BPND spatial profiles explained more variance as compared with mRNA profiles (PET R2 range = 0.20–0.60, mRNA PET R2 range 0.04–0.20, pairwise-comparisons all pcorrected<0.05). In addition, the spatial coupling between ΔCBF and D2R profiles varied between the different antipsychotics tested, possibly reflecting differential affinities. Overall, these results indicate that the functional effects of antipsychotics as measured with rCBF are tightly correlated with the distribution of their target receptors in striatal and extra-striatal regions. Our results further demonstrate the link between neurotransmitter targets and haemodynamic changes reinforcing rCBF as a robust in-vivo marker of drug effects. This work is important in bridging the gap between pharmacokinetic and pharmacodynamics of novel and existing compounds.