Regional Cerebral Blood Volume Research Articles

Neutral sphingomyelinase controls acute and chronic alcohol effects on brain activity

Alcohol consumption is a widespread phenomenon throughout the world. However, how recreational alcohol use evolves into alcohol use disorder (AUD) remains poorly understood. The Smpd3 gene and its coded protein neutral sphingomyelinase (NSM) are associated with alcohol consumption in humans and alcohol-related behaviors in mice, suggesting a potential role in this transition.Using multiparametric magnetic resonance imaging, we characterized the role of NSM in acute and chronic effects of alcohol on brain anatomy and function in female mice.Chronic voluntary alcohol consumption (16 vol% for at least 6 days) affected brain anatomy in WT mice, reducing regional structure volume predominantly in cortical regions. Attenuated NSM activity prevented these anatomical changes. Functional MRI linked these anatomical adaptations to functional changes: Chronic alcohol consumption in mice significantly modulated resting state functional connectivity (RS FC) in response to an acute ethanol challenge (i.p. bolus of 2 g kg−1) in heterozygous NSM knockout (Fro), but not in WT mice. Acute ethanol administration in alcohol-naïve WT mice significantly decreased RS FC in cortical and brainstem regions, a key finding that was amplified in Fro mice. Regarding direct pharmacological effects, acute ethanol administration increased the regional cerebral blood volume (rCBV) in many brain areas. Here, chronic alcohol consumption otherwise attenuated the acute rCBV response in WT mice but enhanced it in Fro mice. Altogether, these findings suggest a differential role for NSM in acute and chronic functional brain responses to alcohol. Therefore, targeting NSM may be useful in the prevention or treatment of AUD.

Longitudinal Imaging of Tumor Perfusion After Preoperative Endovascular Embolization in Meningiomas: Surgical Time Window Selecting, Clinical Consideration, and Outcomes

ObjectiveTo quantitatively investigate the longitudinal computed tomography perfusion (CTP) imaging in meningiomas preoperatively embolized using microcatheters. MethodsThis retrospective monocentric study included 27 patients with symptomatic supratentorial meningiomas. Quantitative CTP images before and post-embolization were evaluated and correlated with angiographic, immunohistochemical, and clinical data. ResultsThe mean age of the patients was 45±18 years, with a female-to-male ratio of 1.45:1. After embolization, both the embolized (Eb) and unembolized (UEb) regions showed hypoperfusion. A steady state was achieved on days 4-6 post-embolization, during which differences in regional cerebral blood volume (rCBV) (Eb 0.5±0.3 ml/100mg, UEb 3.3±1.4 ml/100mg; P<0.05), and mean transit time (MTT) (Eb 3.5 ±1.8 s, UEb 3.1±0.4 s) were observed. The cerebral blood flow (rCBF) and time to the peak (TTP) exhibited opposite patterns between Eb and UEb. A steady state was reached in rCBF (Eb 1.7± 1.2 ml/100 g/min, UEb 30± 5.4 ml/100 g/min; P<0.01), and TTP (Eb 5± 4.8 s, UEb 1.8± 1.5 s; P<0.01) within 4-6 days. Estimated blood loss (EBL) showed significant association with the surgical time interval among the three groups (p<0.05). Tissue necrosis predominated over 7 days post-embolization, indicating a correlation with the devascularization process. The overall incidence of post-embolized headache, seizures, extremity weakness/paralysis, and post-operational headache was 11.1%, 7.4%, 3.7%; and 7.4%, respectively. All symptoms resolved by the last follow-up (3 months). ConclusionPreoperative embolization of meningiomas using N-butyl cyanoacrylate effectively induced significant and sustained tissue transformation and decreased EBL over 7 days. Hemodynamic fluctuations tended to stabilize within 4-6 days.

Mapping cerebral perfusion in mice under various anesthesia levels using highly sensitive BOLD MRI with transient hypoxia.

Cerebral perfusion is critical for the early detection of neurological diseases and for effectively monitoring disease progression and treatment responses. Mouse models are widely used in brain research, often under anesthesia, which can affect vascular physiology. However, the impact of anesthesia on regional cerebral blood volume and flow in mice has not been thoroughly investigated. In this study, we have developed a whole-brain perfusion MRI approach by using a 5-second nitrogen gas stimulus under inhalational anesthetics to induce transient BOLD dynamic susceptibility contrast (DSC). This method proved to be highly sensitive, repeatable within each imaging session, and across four weekly sessions. Relative cerebral blood volumes measured by BOLD DSC agree well with those by contrast agents. Quantitative cerebral blood volume and flow metrics were successfully measured in mice under dexmedetomidine and various isoflurane doses using both total vasculature-sensitive gradient-echo and microvasculature-sensitive spin-echo BOLD MRI. Dexmedetomidine reduces cerebral perfusion, while isoflurane increases cerebral perfusion in a dose-dependent manner.

Imaging Role in Diagnosis, Prognosis, and Treatment Response Prediction Associated with High-grade Glioma

Abstract Background: Glioma is one of the most drug and radiation-resistant tumors. Gliomas suffer from inter- and intratumor heterogeneity which makes the outcome of similar treatment protocols vary from patient to patient. This article is aimed to overview the potential imaging markers for individual diagnosis, prognosis, and treatment response prediction in malignant glioma. Furthermore, the correlation between imaging findings and biological and clinical information of glioma patients is reviewed. Materials and Methods: The search strategy in this study is to select related studies from scientific websites such as PubMed, Scopus, Google Scholar, and Web of Science published until 2022. It comprised a combination of keywords such as Biomarkers, Diagnosis, Prognosis, Imaging techniques, and malignant glioma, according to Medical Subject Headings. Results: Some imaging parameters that are effective in glioma management include: ADC, FA, Ktrans, regional cerebral blood volume (rCBV), cerebral blood flow (CBF), ve, Cho/NAA and lactate/lipid ratios, intratumoral uptake of 18F-FET (for diagnostic application), RD, ADC, ve, vp, Ktrans, CBFT1, rCBV, tumor blood flow, Cho/NAA, lactate/lipid, MI/Cho, uptakes of 18F-FET, 11C-MET, and 18F-FLT (for prognostic and predictive application). Cerebral blood volume and Ktrans are related to molecular markers such as vascular endothelial growth factor (VEGF). Preoperative ADCmin value of GBM tumors is associated with O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status. 2-hydroxyglutarate metabolite and dynamic 18F-FDOPA positron emission tomography uptake are related to isocitrate dehydrogenase (IDH) mutations. Conclusion: Parameters including ADC, RD, FA, rCBV, Ktrans, vp, and uptake of 18F-FET are useful for diagnosis, prognosis, and treatment response prediction in glioma. A significant correlation between molecular markers such as VEGF, MGMT, and IDH mutations with some diffusion and perfusion imaging parameters has been identified.

Correlation of oxidative stress and vascular endothelial dysfunction with hippocampal perfusion in atrial fibrillation patients with cognitive impairment.

To evaluate the correlation of oxidative stress and vascular endothelial dysfunction with hippocampal perfusion in patients with atrial fibrillation and cognitive impairment. In total, 41 atrial fibrillation patients with cognitive impairment were compared to 45 atrial fibrillation patients without cognitive impairment. Oxidative stress, vascular endothelial dysfunction, hippocampal perfusion, and cognitive function were measured. Serum level of oxidized low-density lipoprotein was significantly higher in the atrial fibrillation + cognitive impairment group than in the atrial fibrillation group. Serum levels of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 were significantly higher, and nitric oxide was lower, in the atrial fibrillation + cognitive impairment group than in the atrial fibrillation group. The regional cerebral blood volume, mean transit time, and time to peak were significantly higher in the atrial fibrillation + cognitive impairment group than in the atrial fibrillation group. Moreover, regional cerebral blood flow was significantly lower in the atrial fibrillation + cognitive impairment group than in the atrial fibrillation group. Age, left atrial diameter, and regional cerebral blood volume were negatively correlated with the cognitive function score in the atrial fibrillation + cognitive impairment group. Serum levels of oxidized low-density lipoprotein, regional cerebral blood volume, regional cerebral blood flow, mean transit time, and time to peak were significantly correlated with cognitive impairment in atrial fibrillation patients after multivariate logistic regression analysis. Hippocampal perfusion and oxidative stress were significantly correlated with cognitive impairment in atrial fibrillation patients.

Concurrent functional ultrasound imaging with graphene-based DC-coupled electrophysiology as a platform to study slow brain signals and cerebral blood flow under control and pathophysiological brain states.

Current methodology used to investigate how shifts in brain states associated with regional cerebral blood volume (CBV) change in deep brain areas, are limited by either the spatiotemporal resolution of the CBV techniques, and/or compatibility with electrophysiological recordings; particularly in relation to spontaneous brain activity and the study of individual events. Additionally, infraslow brain signals (<0.1 Hz), including spreading depolarisations, DC-shifts and infraslow oscillations (ISO), are poorly captured by traditional AC-coupled electrographic recordings; yet these very slow brain signals can profoundly change CBV. To gain an improved understanding of how infraslow brain signals couple to CBV we present a new method for concurrent CBV with wide bandwidth electrophysiological mapping using simultaneous functional ultrasound imaging (fUS) and graphene-based field effect transistor (gFET) DC-coupled electrophysiological acquisitions. To validate the feasibility of this methodology visually-evoked neurovascular coupling (NVC) responses were examined. gFET recordings are not affected by concurrent fUS imaging, and epidural placement of gFET arrays within the imaging window did not deteriorate fUS signal quality. To examine directly the impact of infra-slow potential shifts on CBV, cortical spreading depolarisations (CSDs) were induced. A biphasic pattern of decreased, followed by increased CBV, propagating throughout the ipsilateral cortex, and a delayed decrease in deeper subcortical brain regions was observed. In a model of acute seizures, CBV oscillations were observed prior to seizure initiation. Individual seizures occurred on the rising phase of both infraslow brain signal and CBV oscillations. When seizures co-occurred with CSDs, CBV responses were larger in amplitude, with delayed CBV decreases in subcortical structures. Overall, our data demonstrate that gFETs are highly compatible with fUS and allow concurrent examination of wide bandwidth electrophysiology and CBV. This graphene-enabled technological advance has the potential to improve our understanding of how infraslow brain signals relate to CBV changes in control and pathological brain states.

BIOM-51. IDENTIFICATION OF A LOW-FLIP ANGLE BASED CBV THRESHOLD FOR FRACTIONAL TUMOR BURDEN (FTB) MAPPING IN RECURRENT GLIOBLASTOMA

Abstract INTRODUCTION Differentiation of glioblastoma recurrence from post treatment radiation effects (PTRE) would improve patient management. Dynamic susceptibility contrast (DSC) MRI can be used to generate fractional tumor burden (FTB) maps, via application of regional cerebral blood volume (RCBV) thresholds, to spatially differentiate recurrence from PTRE. FTB maps derived from a DSC-MRI protocol that includes a contrast agent preload in addition to the bolus injection and a moderate-flip angle (MFA) been histologically validated. Recently, a single-dose, low-flip angle (LFA) protocol was shown to provide RCBV measurements consistent with the MFA protocol and has been recommended as a consensus protocol. This study aims to identify the RCBV thresholds for the single-dose, LFA protocol that generates FTB maps, concordant with those obtained from the reference double-dose, MFA protocol. METHODS Two sets of DSC-MRI data were collected sequentially from 52 patients using a single-dose, low-flip angle (30o) protocol and a double-dose, moderate flip angle (60o) protocol using TR = 1.5s and TE = 30ms. Standardized RCBV maps (sRCBV) were obtained and co-registered with the post-contrast T1-weighted images using the FDA-approved clinical software, IB Neuro™ and IB Delta Suite™, respectively. The ground truth MFA-based FTB maps were computed using multiple sRCBV thresholds (1.0 and 1.75). An ROC analysis was conducted to identify the optimal, voxel-wise LFA sRCBV thresholds to produce FTB maps that best match the reference maps. RESULTS/ CONCLUSIONS The ROC analysis identified a lower LFA threshold of 1.0 to accurately distinguish PTRE from tumor recurrence and an upper threshold of 1.55 to differentiate aggressive tumor regions. The single-dose, LFA protocol eliminates variations in the contrast agent incubation time between the preload and bolus injection. This study provides motivation for the use of the single-dose LFA protocol in the management of patients with glioblastoma and is a reliable method for distinguishing tumor from PTRE.

P19.06.B T2/FLAIR MISMATCH, SPECIFIC RADIOGENOMIC MARKER FOR A DIFFUSE LOW GRADE ASTROCYTOMA

Abstract A 36-year-old woman presented with recurring episodes of generalized tonic clonic seizures. An MRI from an outside institution demonstrated an intra-axial brain mass suspicious for a primary brain tumor. Repeat conventional and advanced MRI imaging revealed a primary brain mass centred on the left postcentral gyrus involving cortex and subcortical white matter. The lesion was homogenously hyperintense on T2-weighted imaging, and centrally iso-to hypointense on FLAIR with a rim of hyperintense signal on the FLAIR sequence. There was no significant peritumoral edema or minimal effacement of the central sulcus. No abnormal enhancement was seen post-contrast. The lesion demonstrated no reduced diffusivity on diffusion-weighted imaging. MR perfusion showed no elevation in regional cerebral blood volume or flow. Findings are most compatible with a low grade glioma. Patient underwent total surgical resection and biopsy for histopathology. Genetic sequencing revealed an IDH mutant, non 1P,19q codeleted grade II astrocytoma. The diagnosis of adult infiltrating gliomas is predicted using imaging, and confirmed by histopathology, and molecular diagnostic methods. Regardless of grade the 1st phase in glioma diagnosis and management is IDH status. A multidisciplinary approach to the diagnosis of low grade and high grade glioma including genetic and molecular analysis is essential, as different genetic and molecular subtypes have different management and prognostic implications. Conventional MRI still represents a mandatory and extremely important step in the diagnostic workflow of neuro oncological patients for preoperative diagnosis, treatment planning, and subsequent follow up. The T2/FLAIR mismatch sign describes the MRI appearance of an IDH-mutant astrocytoma that is non 1p19q codeleted, and it is considered a preoperative novel specific MRI marker for this type of diffuse astrocytoma. In this case, the MRI findings were used preoperatively as a noninvasive tool to diagnose the patient`s low grade glioma which was confirmed by subsequent histological and genetic analysis. TEACHING POINTS1. T2/FLAIR mismatch allows for pre-operative diagnosis of IDH-mutant astrocytomas with a high level of specificity.2. It is particularly helpful in distinguishing diffuse astrocytoma from an oligodendroglioma3. Conventional MR sequences can suggest the diagnosis of IDH mutant gliomas which can assist neurosurgeons in presurgical planning and can help neuro-oncologists with treatment planning including potential clinical trials.

Quantitative Analysis of Brain CT Perfusion in Healthy Beagle Dogs: A Pilot Study.

Brain computed tomography (CT) perfusion is a technique that allows for the fast evaluation of cerebral hemodynamics. However, quantitative studies of brain CT perfusion in veterinary medicine are lacking. The purpose of this study was to investigate the normal range of perfusion determined via CT in brains of healthy dogs and to compare values between white matter and gray matter, differences in aging, and each hemisphere. Nine intact male beagle dogs were prospectively examined using dynamic CT scanning and post-processing for brain perfusion. Regional cerebral blood volume (rCBV), regional cerebral blood flow (rCBF), mean transit time, and time to peak were calculated. Tissue ROIs were drawn in the gray matter and white matter of the frontal, temporal, parietal, and occipital lobes; caudate nucleus; thalamus; piriform lobe; hippocampus; and cerebellum. Significant differences were observed between the white matter regions and gray matter regions for rCBV and rCBF (p < 0.05). However, no significant differences were identified between hemispheres and between young and old groups in brain regions. The findings obtained in this study involving healthy beagle dogs might serve as a reference for regional CT perfusion values in specific brain regions. These results may aid in the characterization of various brain diseases in dogs.

NEIM-07 DIFFERENTIAL DIAGNOSIS OF TUMOR RECURRENCE AND RADIATION NECROSIS AFTER STEREOTACTIC RADIOTHERAPY FOR BRAIN METASTASES WITH 320-ROW ADCT PERFUSION IMAGE AND T1/T2 MATCH: RADIOLOGICAL AND PATHOLOGICAL ANALYSIS

BACKGROUND AND PURPOSERadiation necrosis occurs from 6 months to several years following stereotactic irradiation (STI) for brain metastases when tumor recurrences are also most likely. Conventional MR imaging does not provide sufficient information to differentiate between radiation necrosis and tumor recurrence. Methionine-PET, FDG-PET and MR spectroscopy sometimes lead to false positive findings. We applied 320-row area detector CT perfusion imaging for the differentiation because it shows vascularity of lesions in the whole brain. MR T1/T2 match sign also evaluate because it is convenient diagnostic method. METHODBetween October 2006 and September 2021, 48 lesions enlarged in 46 patients 3 to 122 months (median: 11 months) after STI. Differential diagnosis was performed with CT perfusion imaging and MR T1/T2 match sign. To calculate the regional cerebral blood volume (rCBV), the regions of interest (ROIs) were located in the enhanced areas. The lesions progressively increased in size or became symptomatic were resected and diagnosed by pathological examination. RESULTSMean age was 63 years, and 60% were male. Primary were lung 31, breast 9, kidney 3, colon 2, melanoma 2, and uterus 1. Mean time to progression from STI was 11 months (range; 3-122). Pathological diagnosis revealed 38 lesions (79%) had tumor recurrence, and 10 (21%) had radiation necrosis. A cut off value rCBV of greater than 3.0 analyzed by ROC curve provided the best sensitivity and specificity for identifying recurrent metastatic tumors, at 89% and 100%, respectively. T1/T2 match sign was provided sensitivity and specificity for identifying recurrent tumors, at 84% and 90%, respectively. To estimate intralesional pathological heterogeneity, contradistinction of CBV map and T1/T2 match sign is useful for the choice of intraoperative maneuver. CONCLUSIONPerfusion CT imaging and T1/T2 match sign demonstrated reliable methods for differentiating tumor recurrence from radiation necrosis after STI.

Assessing the diagnostic accuracy and interobserver agreement of MRI perfusion in differentiating disease progression and pseudoprogression following treatment for glioblastoma in a tertiary UK centre

To assess the local diagnostic accuracy and interobserver agreement of dynamic susceptibility contrast-enhanced magnetic resonance perfusion (DSC MRP) reporting in differentiating between disease progression and pseudoprogression (PP) at a tertiary UK centre. This retrospective study included adults with histology-proven glioblastoma who underwent an index DSC MRP examination following treatment. Each index examination was evaluated by three reporters independently, including qualitative assessment and measurement of mean regional cerebral blood volume (rCBVmean) ratios. Consensus opinion was used as the reference standard and considered clinical, radiological and histological follow-up information. Examination reports were compared to each other and to the consensus opinion. Thirty-two cases were included (19 progression, 13 pseudoprogression). Interobserver agreement was fair for qualitative opinion (κ=0.58, 95% confidence interval [CI] 0.40-0.76) and good for rCBVmean ratio measurement (intraclass correlation coefficient [ICC, two-way random effects model] 0.63, 95% CI=0.43-0.78). Qualitative opinion showed diagnostic accuracies of 77.1% (95% CI=67.4-85.1) for progression and 75% (95% CI=65.1-83.3) for pseudoprogression. rCBVmean ratios were higher for progression (6.85±3.98) than pseudoprogression (3.71±3.40); a 3.0 threshold value maximised the sum of sensitivity (91.1%) and specificity (69.7%) on receiver operating characteristic analysis. DSC MRP and rCBVmean ratio measurement aid differentiation between progression and pseudoprogression following treatment for glioblastoma. Measurement of the rCBVmean ratio shows good interobserver agreement and can change opinion and improve confidence in DSC MRP reporting. Individual centres should validate their own threshold rCBVmean ratio values to optimise diagnostic accuracy.

Chronic Cognitive and Cerebrovascular Function after Mild Traumatic Brain Injury in Rats.

Severe traumatic brain injury (TBI) results in cognitive dysfunction in part due to vascular perturbations. In contrast, the long-term vasculo-cognitive pathophysiology of mild TBI (mTBI) remains unknown. We evaluated mTBI effects on chronic cognitive and cerebrovascular function and assessed their interrelationships. Sprague-Dawley rats received midline fluid percussion injury (n = 20) or sham (n = 21). Cognitive function was assessed (3- and 6-month novel object recognition [NOR], novel object location [NOL], and temporal order object recognition [TOR]). Six-month cerebral blood flow (CBF) and cerebral blood volume (CBV) using contrast magnetic resonance imaging (MRI) and ex vivo circle of Willis artery endothelial and smooth muscle-dependent function were measured. mTBI rats showed significantly impaired NOR, with similar trends (non-significant) in NOL/TOR. Regional CBF and CBV were similar in sham and mTBI. NOR correlated with CBF in lateral hippocampus, medial hippocampus, and primary somatosensory barrel cortex, whereas it inversely correlated with arterial smooth muscle-dependent dilation. Six-month baseline endothelial and smooth muscle-dependent arterial function were similar among mTBI and sham, but post-angiotensin 2 stimulation, mTBI showed no change in smooth muscle-dependent dilation from baseline response, unlike the reduction in sham. mTBI led to chronic cognitive dysfunction and altered angiotensin 2-stimulated smooth muscle-dependent vasoreactivity. The findings of persistent pathophysiological consequences of mTBI in this animal model add to the broader understanding of chronic pathophysiological sequelae in human mild TBI.

Impaired brain activity in patients with persistent atrial fibrillation assessed by near-infrared spectroscopy and its changes after catheter ablation

Although the prevalence of cognitive impairment and depression is higher in patients with atrial fibrillation (AF) than in the general population, the mechanism has not been fully examined and impact of catheter ablation (CA) of AF also remains unclear. Recently, the development of near-infrared spectroscopy (NIRS) has enabled noninvasive measurements of regional cerebral blood volume and brain activity, in terms of cerebral oxyhemoglobin in the cerebral cortex. We assessed brain activities by NIRS, depressive symptoms by the Center for Epidemiologic Studies Depression Scale (CES-D) and cognitive function by Mini-Mental State Examination (MMSE). We then compared the results between AF patients (paroxysmal AF n = 18 and persistent AF n = 14) and control subjects (n = 29). Next, we also followed up persistent AF patients who kept sinus rhythm at 3 months after CA (n = 8) and measured their brain activities using NIRS, CES-D and MMSE after CA to investigate the associations of changes in brain activities with changes in both CES-D and MMSE. Our results showed that (1) frontal and temporal brain activities were lower in patients with persistent AF than both in control subjects and paroxysmal AF patients (P < 0.01), (2) frontal and temporal brain activities were improved in more than half of the persistent AF patients who kept sinus rhythm at 3 months after CA, especially in those who presented impaired brain activity before CA, and (3) improvement of frontal brain activity was associated with improvement of CES-D (R = − 0.793, P = 0.019), whereas improvement of temporal brain activity was associated with improvement of MMSE (R = 0.749, P = 0.033). NIRS measurement showed reduced frontal and temporal brain activities in the persistent AF patients, CA improved frontal and temporal brain activities in some of these patients, and associated with improvement of depressive state and/or improvement of cognitive function.

Differences in cerebral blood flow measurement using arterial spin labeling MRI between patients with moyamoya disease and patients with arteriosclerotic cerebrovascular disease.

It is unclear whether the accuracy of arterial spin labeling (ASL) magnetic resonance imaging (MRI) is the same between moyamoya disease (MMD), which is known to have markedly elevated cerebral blood volume (CBV), and atherosclerotic intracranial arterial stenosis (AS), which has relatively less elevated CBV. To investigate how the differences in hemodynamics affect measurement of ASL-cerebral blood flow (CBF) using ASL for patients with MMD and AS. Fourteen MMD and ten AS patients were evaluated with ASL-MRI, magnetic resonance angiography (MRA), and 15O-gas positron emission computed tomography (PET). The regional CBF values of ASL using two post-labeling delays (PLDs; 1525 ms and 2525 ms) were compared with the PET-derived CBF, CBV, and mean transit time (MTT). Corresponding anterior circulation results were evaluated by flow territory map-based analysis. The correlation between the ASL-CBF values (2525 ms) and PET-CBF declined in the MMD group (r = 0.28; P < 0.01), while the AS group showed good correlation (r = 0.77; P < 0.01). In the MMD group, the ASL-CBF values (2525 ms) overestimated the PET-CBF values as the regional CBV values increased (r = 0.35; P < 0.01). When the regions of interest were divided into two subgroups according to the degree of arterial stenosis by MRA, the correlation coefficient between the ASL-CBF (2525 ms) and PET-CBF values improved (mild stenosis: r = 0.36; P = 0.06; severe stenosis: r = 0.51; P < 0.01). The accuracy of CBF measurements using ASL-MRI differed between patients with MMD and AS. The prominent increase of CBV and the degree of arterial stenosis may have affected the accuracy of ASL-CBF in patients with MMD.

Abstract 9565: Quantitative Assessment of Neonatal Brain Perfusion by Ultrafast Power Doppler in the Operating Room

Introduction: The main challenge with cardiopulmonary bypass (CPB) surgery in newborns with congenital heart disease is to prevent ischemic brain injury impacting on the long-term neurodevelopmental outcomes. To date, no quantitative method is available to adapt the CBP parameters for optimal per-operative cerebral perfusion. Ultrafast power Doppler (UPD) is a new portative bedside technique to map and quantify cerebral perfusion. Our objective was to evaluate UPD for quantifying the variation of cerebral perfusion in neonates during CBP surgery. Methods: UPD was performed in 5 newborns with hypoplastic left heart syndrome undergoing a Norwood procedure and 5 age-matched healthy newborns. Using a 6.9 MHz linear array probe (11L, General Electric) connected to a programmable and portable ultrafast ultrasound scanner (Vantage 256, Verasonics Inc.), via a transfontanellar approach, six pre-defined brain imaging planes were acquired in sagittal and coronal views. Assessments were performed pre-operatively, during various perfusions states intra-operatively and 24-48 hours post-operatively. Global and regional cerebral blood volume (CBV) and resistivity index (RI) maps from UPD were obtained. Results: The baseline brain perfusion was the same for both groups (p=0.62). During CPB, whole brain and regional CBV decreases more than 50% compared to baseline and reaching approximately 25% of initial CBV during selective brain perfusion and during the final stages of bypass (Figure). RI maps shows intermittent overall decrease of vascular resistivities below 0.5 on bypass and selective brain perfusion before returning to baseline in post-op, reflecting an overall decrease of the cerebral vascular resistance during CPB. Conclusions: UPD demonstrates variation in cerebral vascular resistance and blood volume in neonates undergoing CPB surgery. UPD paves the road for optimization of CPB parameters in neonates undergoing cardiac surgery.

Characterization of cortical hemodynamic changes following sensory, visual, and speech activation by intraoperative optical imaging utilizing phase-based evaluation methods.

Alterations within cerebral hemodynamics are the intrinsic signal source for a wide variety of neuroimaging techniques. Stimulation of specific functions leads due to neurovascular coupling, to changes in regional cerebral blood flow, oxygenation and volume. In this study, we investigated the temporal characteristics of cortical hemodynamic responses following electrical, tactile, visual, and speech activation for different stimulation paradigms using Intraoperative Optical Imaging (IOI). Image datasets from a total of 22 patients that underwent surgical resection of brain tumors were evaluated. The measured reflectance changes at different light wavelength bands, representing alterations in regional cortical blood volume (CBV), and deoxyhemoglobin (HbR) concentration, were assessed by using Fourier‐based evaluation methods. We found a decrease of CBV connected to an increase of HbR within the contralateral primary sensory cortex (SI) in patients that were prolonged (30 s/15 s) electrically stimulated. Additionally, we found differences in amplitude as well as localization of activated areas for different stimulation patterns. Contrary to electrical stimulation, prolonged tactile as well as prolonged visual stimulation are provoking increases in CBV within the corresponding activated areas (SI, visual cortex). The processing of the acquired data from awake patients performing speech tasks reveals areas with increased, as well as areas with decreased CBV. The results lead us to the conclusion, that the CBV decreases in connection with HbR increases in SI are associated to processing of nociceptive stimuli and that stimulation type, as well as paradigm have a nonnegligible impact on the temporal characteristics of the following hemodynamic response.

Inverse correlation of fluctuations of cerebral blood and water concentrations in humans

Near-infrared spectroscopy (fNIRS) measures concentrations of oxygenated (HbO) and deoxygenated (HbR) hemoglobin in the brain. Recently, we demonstrated its potential also for measuring concentrations of cerebral water (hbox {cH}_{2}hbox {O}). We performed fNIRS measurements during rest to study fluctuations in concentrations of hbox {cH}_{2}hbox {O}, HbO and HbR in 33 well-rested healthy control subjects (HC) and 18 acutely sleep-deprived HC. Resting-state fNIRS signal was filtered in full-band, cardiac, respiratory, low-, and very-low-frequency bands. The sum of HbO and HbR constitutes the regional cerebral blood volume (CBV). CBV and hbox {cH}_{2}hbox {O} concentrations were analyzed via temporal correlation and phase synchrony. Fluctuation in concentrations of hbox {cH}_{2}hbox {O} and CBV was strongly anti-correlated across all frequency bands in both frontal and parietal cortices. Fluctuation in concentrations of {hbox {cH}}_{2}{hbox {O}} and CBV showed neither a completely synchronous nor a random phase relationship in both frontal and parietal cortices. Acutely sleep-deprived subjects did not show significant differences in temporal correlation or phase synchrony between fluctuations in {hbox {cH}}_{2}{hbox {O}} and CBV concentrations compared with well-rested HC. The reciprocal interrelation between fluctuations in CBV and {hbox {cH}}_{2}{hbox {O}} concentrations is consistent with the Munro–Kellie doctrine of constant intracranial volume. This coupling may constitute a functional mechanism underlying glymphatic circulation, which persists despite acutely disturbed sleep patterns.

Altered regional cerebral blood flow in obstructive sleep apnea is associated with sleep fragmentation and oxygen desaturation

Altered cerebral perfusion has been reported in obstructive sleep apnea (OSA). Using dynamic susceptibility contrast MRI, we compared cerebral perfusion between male OSA patients and male healthy reference subjects and assessed correlations of perfusion abnormalities of OSA patients with sleep parameters and neuropsychological deficits at 3 T MRI, polysomnography and neuropsychological tests in 68 patients with OSA and 21 reference subjects. We found lower global and regional cerebral blood flow and cerebral blood volume, localized mainly in bilateral parietal and prefrontal cortices, as well as multiple focal cortical and deep structures related to the default mode network and attention network. In the correlation analysis between regional hypoperfusion and parameters of polysomnography, different patterns of regional hypoperfusion were distinctively associated with parameters of intermittent hypoxia and sleep fragmentation, which involved mainly parietal and orbitofrontal cortices, respectively. There was no association between brain perfusion and cognition in OSA patients in areas where significant association was observed in reference subjects, largely overlapping with nodes of the default mode network and attention network. Our results suggest that impaired cerebral perfusion in important areas of functional networks could be an important pathomechanism of neurocognitive deficits in OSA.

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.

Minute changes of cerebral parenchymal non-contrast computed tomography attenuation reflect cerebral volume alterations of blood.

Non-infarcted acute cerebral ischaemic areas appear hypo-attenuated on non-contrast narrow-window computed tomography images. We aimed to determine the mechanism underlying minute computed tomography hypo-attenuation and visualise these attenuation changes on non-contrast computed tomography images. The cerebral parenchyma was defined by pixels with attenuation of 20-50 Hounsfield units. We calculated the mean cerebral parenchymal attenuation in non-contrast computed tomography images. We analysed the correlation of complete blood counts with corresponding mean cerebral parenchymal attenuation values using linear regression analysis. Moreover, we developed an image processing method that involved pixel colorisation based on the noise-reduced attenuation value for minute cerebral parenchymal attenuation visualisation. Haemoglobin, haematocrit and red blood cell counts positively correlated with mean cerebral parenchymal attenuation values. The cerebral haematocrit is correlated with the blood haematocrit; therefore, cerebral parenchymal attenuation correlated linearly with cerebral haemoglobin concentration. Haemoglobin contents in a pixel partially determine the X-ray absorption dose and attenuation value. Pixel haemoglobin contents are determined by the cerebral volume of blood in a pixel. Image processed computed tomography images reflected cerebral volume of blood and showed the same alterations with regional cerebral blood volume maps of perfusion computed tomography. Cerebral parenchymal attenuation correlated with cerebral haemoglobin concentration and cerebral volume of blood. Infarcted cerebral parenchyma shows about 5 Hounsfield units gray matter attenuation decrease. Attenuation decrease by less than 5 Hounsfield units means decreased cerebral volume of blood, indicating a reversible functional change. One cannot recognise minute hypo-attenuation (<5 Hounsfield units) in routine computed tomography images. However, it can be visualised through an image processing method on non-contrast computed tomography images. It may detect pre-infarction cerebral volume of blood and regional cerebral blood volume alterations.