Local Cerebral Hemodynamics Research Articles

Evaluation of Hemodynamic Change by Indocyanine Green-FLOW 800 Videoangiography Mapping: Prediction of Hyperperfusion Syndrome in Patients with Moyamoya Disease.

Objective Hyperperfusion syndrome (HPS) after bypass surgery for moyamoya disease (MMD) mainly results from redistribution of blood flow, which leads to poor outcomes, while effective methods to predict HPS are still lacking. Indocyanine green (ICG) videoangiography can assess regional cerebral blood flow changes semiquantitatively with the application of FLOW 800 software. The purpose of this study was to investigate whether the intraoperative evaluation of local hemodynamic changes around anastomotic sites using FLOW 800 videoangiography mapping can predict the incidence of HPS and clinical outcomes. Methods Of the patients who were diagnosed with MMD in our hospital between August 2018 and December 2019, who underwent superficial temporal artery-middle cerebral artery bypass surgeries, we investigated 65 hemispheres (in 62 patients) in which intraoperative ICG analysis was performed using FLOW 800 (Zeiss Meditec, Oberkochen, Germany) to evaluate the local cerebral hemodynamics before and after anastomosis. Regions of interest were set at more than 2 points on the brain surface according to the location and situation of recipient arteries in the surgical area. Peak cerebral blood volume (CBV), regional cerebral blood flow (CBF), and time to peak (TTP) were calculated from the selected points. As the data were available intraoperatively, anastomoses were performed in a suitable area. According to the occurrence of HPS, patients were divided into the asymptomatic and symptomatic groups, from which hemodynamic parameters were compared. Furthermore, ROC analysis was performed to determine the diagnostic accuracy of change rates in CBV, CBF, and TTP (i.e., ΔCBV, ΔCBF, and ΔTTP) for predicting HPS. Results Data from the 62 patients were analyzed, and all patients were closely assessed during hospitalization after the procedures. The values of ΔCBV and ΔCBF were significantly higher in the symptomatic group (p < 0.01), while ΔTTP is slightly lower in the symptomatic group with no statistical differences (p = 0.72). Hemodynamic parameters including ΔCBV and ΔCBF, calculated by FLOW 800, had high sensitivity and specificity according to the ROC curve (ΔCBV: AUC = 0.743, 95% CI, 0.605–0.881, p = 0.002; ΔCBF: AUC = 0.852, 95% CI, 0.750–0.954, p < 0.01), which could be used as predictors for HPS. Conclusions Intraoperative ICG-FLOW 800 videoangiography mapping is a safe method which can reflect hemodynamic characteristics in the surgical area for MMD, the findings of which correlate with the occurrence of HPS. Parameters including ΔCBV and ΔCBF are proven to be efficient in the prediction of HPS.

Local Cerebral Hemodynamics after Superficial Temporal Artery-Middle Cerebral Artery Bypass in Patients with Symptomatic Carotid Occlusions.

Context:Physiological insights into blood flow alterations in cortical vessels after superficial temporal artery-middle cerebral artery (STA-MCA) bypass surgery are important for the prognosis of bypass sustainability and hemodynamic patency.Aims:This study aims to assess the impact of STA-MCA bypass on local hemodynamics for patients with symptomatic carotid occlusions and Moyamoya disease.Settings and Design:This article presents a prospective nonrandomized study of intraoperative blood flow measurements in cortical branches of MCA and donor vessel before and after cerebral revascularization.Materials and Methods:Evaluation of local hemodynamic parameters was established for 112 patients with symptomatic carotid occlusive disease and cerebrovascular insufficiency during STA-MCA bypass surgery. We used intraoperative Doppler ultrasonography (89 patients – 72%), flowmetry (56 cases – 50%), and in 33 cases both methods. For physical justification of observed facts, we performed computational simulation with OpenFOAM CFD framework using Navier-Stokes nonstationary hemodynamic model.Statistical Analysis Used:All calculations were performed with IBM SPSS Statistics version 10.0 software. We used parametric (Z-test and Student's t-test) and nonparametric models (Wilcoxon, Mann–Whitney). For categorical values, we used Fisher's exact test.Results:Local cerebral hemodynamics after revascularization surgery significantly depended on initial perfusion deficit and the ability of bypass to reverse the blood flow in proximal parts of cortical artery (86 cases, 77%). Mechanism of cortical blood flow alteration was related to donor vessel cut flow value and potential consumption threshold of acceptor artery.Conclusions:Knowledge of hemodynamic principles of flow redistribution after STA-MCA bypass is important to improve bypass stainability and leads to better revascularization results.

Local cerebral hemodynamics following STA-MCA bypass in patients with symptomatic carotid occlusions

To assess changes in local hemodynamic parameters in patients with symptomatic ICA occlusions and moyamoya disease after placement of extracranial-intracranial bypass (EC-IC bypass). The study included 112 patients who underwent surgical treatment at the National Scientific and Practical Center for Neurosurgery in the period between 1999 and 2015. Of these, 105 patients had ICA occlusions, and 7 patients had moyamoya disease. During the main stage of EC-IC bypass placement, all patients were monitored for local hemodynamic parameters using intraoperative contact Doppler ultrasonography - 89 (72%) patients (72%) and flowmetry - 56 (50%)). In 33 (29%) cases, both techniques were used. Forty two patients underwent preoperative SCT perfusion to assess the degree of perfusion deficit. Grade 1 cerebrovascular insufficiency (acute oligemia) was detected in 6 patients; grade 2 perfusion deficit (persistent oligemia) was found in 25 patients; grade 3 perfusion deficit (chronic oligemia) was present in 11 patients. Measurements were performed before bypass placement: the blood flow direction and hemodynamic parameters in the cortical arteries were evaluated; and after bypass placement: blood flow values and directions in the cortical artery, proximal and distal to the bypass area, were assessed. A total of 112 EC-IC bypasses were placed without perioperative complications and deaths. Bypass functioning was confirmed in 108 (96.3%) cases; bypass thrombosis occurred in 4 (3.7%) cases. The distal blood flow direction was observed in patients with ICA occlusions (105 patients) in all cases before EC-IC bypass placement. Patients with moyamoya disease had more often the proximal blood flow direction - 5 (71%) out of 7 cases. The cerebral blood flow parameters obtained in this study differed significantly, depending on the baseline degree of perfusion deficit. The blood flow rate was minimal in patients with grade 1 cerebrovascular insufficiency. After revascularization, local hemodynamics in the cortical arteries was significantly dependent on the ability of EC-IC bypass to reverse blood flow in the proximal acceptor artery. A change in the blood flow direction was observed in 86 (77%) cases. The mean volumetric blood flow in EC-IC bypass was 34.2±5.7 mL/min. The knowledge of baseline hemodynamic parameters and their changes after revascularization plays an important role in choosing the correct surgical technique, further bypass functioning, and, as a result, improvement of the clinical outcome after surgery.

Intraoperative evaluation of local cerebral hemodynamic change by indocyanine green videoangiography: prediction of incidence and duration of postoperative transient neurological events in patients with moyamoya disease.

Transient neurological events (TNEs) occur frequently in the acute phase after direct bypass surgery for moyamoya disease (MMD), but there is currently no way to predict them. FlowInsight is a specialized software for analyzing indocyanine green (ICG) videoangiography taken with a surgical microscope. The purpose of this study was to investigate whether intraoperative evaluation of local hemodynamic changes around anastomotic sites using FlowInsight could predict the incidence and duration of TNEs. From patients who were diagnosed with MMD in our hospital between August 2014 and March 2017 and who underwent superficial temporal artery-middle cerebral artery bypass surgery, we investigated 25 hemispheres (in 22 patients) in which intraoperative ICG analysis was performed using FlowInsight. To evaluate the local cerebral hemodynamics before and after anastomosis, regions of interest were set at 3 locations on the brain surface around the anastomotic site, and the mean cerebral blood flow (CBF), mean gradation (Grad), mean transit time (MTT), and mean time to peak (TTP) were calculated from the 3 regions of interest. Furthermore, the change rate in CBF (ΔCBF [%]) was calculated using the formula (postanastomosis mean CBF - preanastomosis mean CBF)/preanastomosis mean CBF. ΔGrad (%), ΔMTT (%), and ΔTTP (%) were similarly calculated. Postoperative stroke without TNE occurred in 2 of the 25 hemispheres. These 2 hemispheres (in 2 patients) were excluded from the study, and data from the remaining 23 hemispheres (in 20 patients) were analyzed. For each parameter (ΔCBF, ΔGrad, ΔMTT, and ΔTTP) calculated by FlowInsight, the difference between the groups with and without TNEs was significant. The median values for ΔCBF and ΔGrad were significantly higher in the TNE group than in the no-TNE group (ΔCBF 30.13 vs 3.54, p = 0.0106; ΔGrad 62.05 vs 10.78, p = 0.00435), whereas the median values for ΔMTT and ΔTTP were significantly lower in the TNE group (ΔMTT -16.90 vs -7.393, p = 0.023; ΔTTP -29.07 vs -7.02, p = 0.00342). Comparison of the area under the curve (AUC) for each parameter showed that ΔTTP had the highest AUC and was the parameter with the highest diagnostic accuracy (AUC 0.857). The Youden index revealed that the optimal cutoff value of ΔTTP was -11.61 (sensitivity 77.8%, specificity 71.4%) as a predictor of TNEs. In addition, Spearman's rank correlation coefficients were calculated, and ΔCBF, ΔGrad, ΔMTT, and ΔTTP each showed a strong correlation with the duration of TNEs. The larger the change in each parameter, the longer the TNEs persisted. Intraoperative ICG videoangiography findings were correlated with the occurrence and duration of TNEs after direct bypass surgery for MMD. Screening for cases at high risk of TNEs can be achieved by ICG analysis using FlowInsight.

The significance of local cerebral hemodynamics in patients with acute brain injury

Objective To investigate the relevance between the seriousness of acute brain injury and regional cerebral blood flow (rCBF), regional cerebral blood volume (rCBV) or mean transition time (MTT); provide a possible method for the early diagnose and prognostic evaluation. Methods This study included 67 patients of acute brain injury and they were divided into mild, moderate and severe groups based on their glasgow coma scale (GCS) scores. They were examined to detect rCBF, rCBV and MTT by computed tomography perfusion (CTP) imaging after admitted to hospital. The prognoses of them after 6 months of follow-up were also recorded. The relations between the prognosis and rCBF, rCBV or MTT were analyzed. Results rCBV and rCBF of severe group were significantly lower than the mild group (P<0.05), and MTT of severe group was significantly higher than that of the mild group (P<0.05). The rCBV and the glasgow outcome scale (GOS) scores were significantly positively correlated(P<0.01), and MTT was significantly negatively correlated with the GOS score(P<0.01). Whereas there was no correlation between rCBF and the GOS score. Conclusion rCBF, rCBV and MTT were significantly correlated with the severity as well as the prognosis of patients with acute brain injury and they might be used as potential indicators of the severity and prognosis. Key words: Craniocerebral trauma; Regional cerebral blood flow; Regional cerebral blood volume; Mean transit time

Practical Steps for Applying a New Dynamic Model to Near-Infrared Spectroscopy Measurements of Hemodynamic Oscillations and Transient Changes: Implications for Cerebrovascular and Functional Brain Studies

Perturbations in cerebral blood volume (CBV), blood flow (CBF), and metabolic rate of oxygen (CMRO2) lead to associated changes in tissue concentrations of oxy- and deoxy-hemoglobin (ΔO and ΔD), which can be measured by near-infrared spectroscopy (NIRS). A novel hemodynamic model has been introduced to relate physiological perturbations and measured quantities. We seek to use this model to determine functional traces of cbv(t) and cbf(t) - cmro2(t) from time-varying NIRS data, and cerebrovascular physiological parameters from oscillatory NIRS data (lowercase letters denote the relative changes in CBV, CBF, and CMRO2 with respect to baseline). Such a practical implementation of a quantitative hemodynamic model is an important step toward the clinical translation of NIRS. In the time domain, we have simulated O(t) and D(t) traces induced by cerebral activation. In the frequency domain, we have performed a new analysis of frequency-resolved measurements of cerebral hemodynamic oscillations during a paced breathing paradigm. We have demonstrated that cbv(t) and cbf(t) - cmro2(t) can be reliably obtained from O(t) and D(t) using the model, and that the functional NIRS signals are delayed with respect to cbf(t) - cmro2(t) as a result of the blood transit time in the microvasculature. In the frequency domain, we have identified physiological parameters (e.g., blood transit time, cutoff frequency of autoregulation) that can be measured by frequency-resolved measurements of hemodynamic oscillations. The ability to perform noninvasive measurements of cerebrovascular parameters has far-reaching clinical implications. Functional brain studies rely on measurements of CBV, CBF, and CMRO2, whereas the diagnosis and assessment of neurovascular disorders, traumatic brain injury, and stroke would benefit from measurements of local cerebral hemodynamics and autoregulation.

Transcranial diffuse optical monitoring of microvascular cerebral hemodynamics after thrombolysis in ischemic stroke

The ultimate goal of therapeutic strategies for ischemic stroke is to reestablish the blood flow to the ischemic region of the brain. However, currently, the local cerebral hemodynamics (microvascular) is almost entirely inaccessible for stroke clinicians at the patient bed-side, and the recanalization of the major cerebral arteries (macrovascular) is the only available measure to evaluate the therapy, which does not always reflect the local conditions. Here we report the case of an ischemic stroke patient whose microvascular cerebral blood flow and oxygenation were monitored by a compact hybrid diffuse optical monitor during thrombolytic therapy. This monitor combined diffuse correlation spectroscopy and near-infrared spectroscopy. The reperfusion assessed by hybrid diffuse optics temporally correlated with the recanalization of the middle cerebral artery (assessed by transcranial-Doppler) and was in agreement with the patient outcome. This study suggests that upon further investigation, diffuse optics might have a potential for bed-side acute stroke monitoring and therapy guidance by providing hemodynamics information at the microvascular level.

Neuroprotection by a Central Nervous System–Type Prostacyclin Receptor Ligand Demonstrated in Monkeys Subjected to Middle Cerebral Artery Occlusion and Reperfusion

Recently, we found that a novel subtype of prostacyclin (PGI(2)) receptor clearly distinct from the peripheral subtype in terms of ligand specificity is expressed in the central nervous system (CNS). (15R)-16-m-tolyl-17,18,19,20-tetranorisocarbacyclin (15R-TIC) was synthesized and demonstrated to be a specific ligand for this CNS-type PGI(2) receptor. Previously, we demonstrated 15R-TIC to be neuroprotective in vivo during transient forebrain ischemia in gerbils and permanent middle cerebral artery occlusion (MCAO) in rats. Furthermore, this compound was shown to exert an anti-apoptotic effect on primary cultured hippocampal neurons, indicating its neuroprotective effect against ischemic insults occurs via direct action on CNS-type PGI(2) receptor. Local cerebral hemodynamics and oxygen metabolism were measured simultaneously by using positron emission tomography with the (15)O steady-state method, before and up to 18 hours after 3-hour transient MCAO reperfusion in cynomolgus monkeys. Methyl ester of 15R-TIC (50 microg/kg, n=4) or its vehicle (10% Intralipos, n=4) was injected intravenously within 5 minutes after onset of MCAO and continuously infused for 5 hours (50 microg/kg per hour). Neuropathology showed that 15R-TIC significantly reduced cortical damage after 3-hour MCAO. Positron emission tomography results showed 15R-TIC significantly reduced the volume of "infarct" region of interest and attenuated the decrease in cerebral metabolic rate of oxygen and oxygen extraction fraction, and these protective effects were not attributable to improvement of cerebral circulation. These results suggest that 15R-TIC has a potent neuroprotective effect against focal cerebral ischemia in a monkey MCAO via its direct action on CNS-type PGI(2) receptors.

Pial vessel permeability to tracers using cranial windows.

Many investigators, including numerous studies from our laboratory, have used fluorescence microscopy to directly examine changes in permeability of pial vessels in rats (, , , ), cats (, , ), mice (,), and hamsters (, , ) during basal and stimulated states. The use of cranial windows and fluorescence microscopy to examine the cerebral microcirculation has several advantages. First, the techniques allow the investigator to directly visualize cerebral microvessels. Thus, the investigator can visually examine changes in permeability of pial vessels during various stimuli and can visualize changes in reactivity of cerebral blood vessels during alterations in permeability of the blood-brain barrier (BBB). This allows the investigator to correlate changes in permeability of pial vessels with local cerebral hemodynamics. Second, the techniques allow the investigator to examine changes in permeability of pial vessels to differently sized and charged molecules. Thus, one can examine the effect of a specific stimuli on the selectivity of pial vessels. Third, the techniques allow the investigator to determine the precise sites, i.e., arteries, arterioles, capillaries, venules and/or veins, of disruption of the BBB during pathophysiologic conditions. This information may be of potential importance in the delivery of therapeutic agents to brain tissue during disease states. Fourth, the techniques allow the investigator to not only qualitatively, but quantitatively evaluate the permeability of pial vessels under basal conditions and during various conditions. With the calculation of clearance, the investigator can evaluate basal permeability of pial vessels and can determine the magnitude of disruption of the BBB in response to various stimuli.

Study of local cerebral hemodynamics by frequency-domain near-infrared spectroscopy and correlation with simultaneously acquired functional magnetic resonance imaging

The aim of our study was to explore the possibility of detecting hemodynamic changes in the brain using the phase of the intensity modulated optical signal. To obtain optical signals with the highest possible signal-to-noise ratio, we performed a series of simultaneous NIRS-fMRI measurements, with subsequent correlation of the time courses of both measurements. The cognitive paradigm used arithmetic calculations, with optical signals acquired with sensors placed on the forehead. Measurements were done on seven healthy subjects. In five subjects we demonstrated correlation between the hemodynamic signals obtained using NIRS and BOLD fMRI. In four subjects correlation was found for the hemodynamic signal obtained using the phase of the intensity modulated signal.

PET study of changes in local brain hemodynamics and oxygen metabolism after unilateral middle cerebral artery occlusion in baboons.

Local cerebral hemodynamics and oxygen metabolism were measured by positron emission tomography (PET) with the oxygen-15 (15O) steady-state method in baboons, immediately before (T0), 1 (T1), and 3-4 (T2) h after permanent middle cerebral artery occlusion (MCAO). At T1, there was a marked fall in both cerebral blood flow (CBF) and the CBF/cerebral blood volume (CBV) ratio in the occluded territory; these changes were sustained at T2, indicating stable reduction in cerebral perfusion pressure and lack of spontaneous reperfusion within this time range. Compared with preocclusion conditions, the oxygen extraction fraction (OEF) in the occluded territory was elevated at both T1 and T2, indicative of a persistent oligemia/ischemia for up to 3 h after MCAO. At T2, however, this OEF increase had lessened, concomitantly with a decline in cerebral metabolic rate of oxygen (CMRO2). This impairment of oxidative metabolism occurred earlier in the deep, compared with the cortical, MCA territories; in the latter, the CMRO2 was essentially preserved at T1 and only moderately reduced at T2, possibly suggesting prolonged viability. Finally, no significant changes in CBF or CMRO2 were observed in the contralateral MCA territory in this time range after MCAO. Despite methodological limitations (mainly partial volume effects related to PET imaging, which may have resulted in an underestimation of true changes and an overlooking of heterogeneous changes) our study demonstrates the feasibility of the combined PET-MCAO paradigm in baboons; this experimental approach should be valuable in investigating the pathophysiology and therapy of acute stroke.

Local cerebral hemodynamics in albino rats in the late stages after termination of neurotization (induction of neurosis).

1. The velocity of the local cerebral blood flow in rats with induced neurosis is distinguished 4–6 weeks after termination of exposure to stress by great instability, characteristic of disturbance of vascular tone. 2. A “rest” of 4–6 weeks abolishes the reduction of VLCBF observed in rats with induced neurosis but does not completely restore the local cerebral hemodynamics.

Effect of chronic middle cerebral artery stenosis on the local cerebral hemodynamics.

In 36 patients with angiographically proven middle cerebral artery (MCA) stenosis, local cerebral hemodynamics were studied employing angiography, 133Xe inhalation regional cerebral blood flow (rCBF) measurements and CT scans. They had transient ischemic attacks in 8 and completed stroke in 28. The patients with less than 50% stenosis (n = 16) had no hemodynamic abnormality in angiographical and rCBF examinations. The infarction in this group was small and located in the basal ganglia area. The patients with 50 to 74% stenosis (n = 9) often revealed a delayed filling of MCA branches in the angiography, however, they showed no significant rCBF reduction. The infarction in this group was also small and located in the basal ganglia area. The patients with 75 to 99% stenosis (n = 11) exhibited a significant flow depression both in angiographical and rCBF examinations. Three of them had large cerebral infarction in the watershed zone or the cerebral cortex. The results of the present study suggest that the hemodynamic effect of MCA stenosis begins to manifest at 50% in grade and becomes apparent at 75%. The danger of hemodynamic crisis as well as the risk of large cerebral infarction may increase when MCA stenosis exceeds 75% in grade.