State Cerebral Blood Flow Research Articles

P02-159 - Magnetic resonance imaging of baseline brain perfusion in major depressive disorder

IntroductionContinuous arterial spin labelling (cASL) is a non-invasive magnetic resonance imaging method increasingly used to study human brain function and perfusion physiology.ObjectivesIn this study, we investigated distinct patterns of cerebral blood flow (CBF) in MDD patients by means of resting state cASL.Methods11 healthy controls and 11 patients with MDD according to DSM-IV criteria were included. The individual cASL images underwent data preprocessing steps including the generation of perfusion-weighted images, followed by conversion to quantified CBF. An analysis of temporally coherent CBF patterns was performed using a spatial Independent Component Analysis.ResultsBoth groups showed distinct blood flow patterns in a medial frontoparietal and lateral temporal component (“default mode” network), a medial temporal and anterior cingulate component (“limbic” network) and bilateral prefrontal and parietal component (“cognitive” network). Within the “limbic” network, MDD patients showed a pattern of increased CBF in the bilateral ventrolateral prefrontal, cingulate, striatal and hippocampal regions. Within the “cognitive” network, MDD patients showed a pattern of increased CBF in left dorsolateral prefrontal and the inferior parietal areas. Decreased perfusion in MDD patients was found in the right precuneus, the right inferior parietal cortex, the left posterior cingulate and the left lateral temporal cortex.ConclusionsThese preliminary data demonstrate the sensitivity of cASL techniques for detecting resting state CBF changes in MDD patients. Thus, cASL studies in MDD could provide valuable information with regard to neurobiologically characterized endophenotypes, while resting state CBF measures could serve as objective predictors of treatment response in future studies.

Static and dynamic characteristics of cerebral blood flow during the resting state

In this study, the static and dynamic characteristics of cerebral blood flow (CBF) in the resting state were investigated using an arterial spin labeling (ASL) perfusion imaging technique. Consistent with previous PET results, static CBF measured by ASL was significantly higher in the posterior cingulate cortex (PCC), thalamus, insula/superior temporal gyrus (STG) and medial prefrontal cortex (MPFC) than the average CBF of the brain. The dynamic measurement of CBF fluctuations showed high correlation (functional connectivity) between components in the default mode network. These brain regions also had high local temporal synchrony and high fluctuation amplitude, as measured by regional homogeneity (ReHo) and amplitude of low-frequency fluctuation (ALFF) analyses. The spatial pattern of the static CBF correlated well with that of the dynamic indices. The high static and dynamic activities in the PCC, MPFC, insula/STG and thalamus suggest that these regions play a vital role in maintaining and facilitating fundamental brain functions.

Static Cerebral Blood Flow Autoregulation in Humans

Static cerebral blood flow (CBF) autoregulation maintains a constant CBF despite changes in cerebral perfusion pressure (CPP) within certain limits; this is achieved through adaptive responses in the cerebrovascular resistance, i.e. arteriolar vasoconstriction and vasodilation. This system may protect the brain from hyper- and hypoperfusion upon CPP challenges. CBF autoregulation appears to be mediated through myogenic and metabolic feedback systems, which may involve the vasoconstrictor 20-hydroxyeicosatetraenoic acid as well as an oxygen-sensing mechanism that may involve nitric oxide signalling. Static CBF autoregulation is modulated or impaired in various pathological conditions. In chronic arterial hypertension, both the lower and upper limit of CBF autoregulation are shifted towards higher CPPs; however, CBF autoregulation may be readapted to normal by antihypertensive therapy. Furthermore, CBF autoregulation is impaired in a wide range of clinical conditions, including cerebral ischaemia, traumatic brain injury, intracranial space-occupying processes, subarachnoid haemorrhage, acute bacterial meningitis, fulminant hepatic failure and diabetes. In some of these conditions, CBF autoregulation may be restored by means of hyperventilation and/or induced hypothermia. At present, the clinical impact of CBF autoregulation impairment and of treatment strategies that aim to restore CBF autoregulation remains unclear.

Differential responses in CBF and CBV to cocaine as measured by fMRI: Implications for pharmacological MRI signals derived oxygen metabolism assessment

Introduction Cognitive performance-induced brain oxygen metabolism has been successfully measured by functional magnetic resonance imaging (fMRI) in human studies. The measurement of the cerebral metabolic rate of oxygen consumption (CMRO 2) is typically achieved by assuming a fixed coupling of cerebral blood flow (CBF) and cerebral blood volume (CBV) and by performing a separate experiment to assess the vascular response to a hypercapnic challenge. Psychoactive drugs may have directly effect on the cerebral vasculature, potentially confounding the interpretation of pharmacological MRI (phMRI) data. In this study, we tested the assumptions of the standard CMRO 2 calculation following the administration of cocaine, in order to test the validity of this measurement in phMRI studies. The initial transient state and later steady state CBF and CBV responses to a hypercapnic challenge were measured. Methods CBF and CBV responses were directly measured by fMRI using continuous arterial spin-labeling (ASL) and contrast-enhanced fMRI, respectively. The coupling between changes in CBF and CBV during a hypercapnic challenge was examined under normal conditions and following the administration of cocaine. Results A decoupling of changes in CBF and CBV was observed during the transient state immediately following the administration of cocaine, and an altered coupling of CBF and CBV was found during the steady state after cocaine injection. Discussion These data suggest caution in interpreting CMRO 2 measurements from phMRI studies and may also lead to an improved understanding of the complex neuronal and vascular mechanisms of drug action.

Dexmedetomidine Weakens Dynamic Cerebral Autoregulation as Assessed by Transfer Function Analysis and the Thigh Cuff Method

Dexmedetomidine, which is often used in intensive care units in patients with compromised circulation, might induce further severe decreases in cerebral blood flow (CBF) with temporal decreases in arterial pressure induced by various stimuli if dynamic cerebral autoregulation is not improved. Therefore, the authors hypothesized that dexmedetomidine strengthens dynamic cerebral autoregulation. Fourteen healthy male subjects received placebo, low-dose dexmedetomidine (loading, 3 microg x kg(-1) x h(-1) for 10 min; maintenance, 0.2 microg x kg(-1) x h(-1) for 60 min), and high-dose dexmedetomidine (loading, 6 microg x kg(-1) x h(-1) for 10 min; maintenance, 0.4 microg x kg(-1) x h(-1) for 60 min) infusions in a randomized, double-blind, crossover study. After 70 min of drug administration, dynamic cerebral autoregulation was estimated by transfer function analysis between arterial pressure variability and CBF velocity variability, and the thigh cuff method. Compared with placebo, steady state CBF velocity and mean blood pressure significantly decreased during administration of dexmedetomidine. Transfer function gain in the very-low-frequency range increased and phase in the low-frequency range decreased significantly, suggesting alterations in dynamic cerebral autoregulation in lower frequency ranges. Moreover, the dynamic rate of regulation and percentage restoration in CBF velocity significantly decreased when a temporal decrease in arterial pressure was induced by thigh cuff release. Contrary to the authors' hypothesis, the current results of two experimental analyses suggest together that dexmedetomidine weakens dynamic cerebral autoregulation and delays restoration in CBF velocity during conditions of decreased steady state CBF velocity. Therefore, dexmedetomidine may lead to further sustained reductions in CBF during temporal decreases in arterial pressure.

Hemodynamic response following neuronal activity in cases with severe stenosis of the cervical internal carotid artery and its serial change through carotid artery stenting

●Abstract● Objective: Regional cerebral blood flow (CBF) increasing focally at sites of neural activity is called hemodynamic response (HDR). In cases with severe cerebral ischemia, HDR may be disturbed and cause disruption of normal neuro-vascular coupling. HDR was measured during a motor task using functional near infrared spectroscopy (fNIRS) in cases with severe cervical internal carotid artery (ICA) stenosis before and after carotid artery stenting (CAS). Ischemia and the influence of therapy for it on HDR was analyzed. Methods: Seventeen right-handed patients with severe cervical ICA stenosis admitted for CAS were examined. fNIRS during a motor task was performed and concentration changes in oxygenated hemoglobin (HbO2), deoxygenated hemoglobin (HbR), and total hemoglobin (tHb) were calculated in these patients in addition to routine evaluations. The same measurements were repeated after CAS and serial data were evaluated. In order to analyze the relevance of HDR to CBF status, Xenon-enhanced computed tomography (Xe-CT) was performed before and after CAS. Results: Some abnormalities in the HDR curve and its recovery after CAS were detected, including a delay in peak time of tHb concentration, of more than 10 seconds during the 20 second stimulation, in 9 cases. TTP 0.7 (time to peak) value, defined as the time to reach seventy percent of maximum tHb concentration, was observed to be higher in patients with low CBF at rest before CAS. In the group with a high TTP 0.7 value, CBF at rest before CAS was lower than 35mL/100g/min., significantly lower than the group without a high TTP 0.7 value (P<0.01). Additionally, in the group with a high TTP 0.7 value, CBF increase after CAS was significantly higher than the group with a lower TTP 0.7 value (P<0.01).

Rehabilitation of Unilateral Spatial Neglect: New Insights From Magnetic Resonance Perfusion Imaging

Hillis AE. Rehabilitation of unilateral spatial neglect: new insights from magnetic resonance perfusion imaging. Objective To illustrate how magnetic resonance perfusion imaging has provided insights regarding rehabilitation of different forms of hemispatial neglect. Data Sources Recent studies of different types of neglect and their neural substrates and of rehabilitation strategies that might be differentially effective for different types of neglect. Study Selection Author selected all articles on PubMed that were identified with the key words reference frame or perfusion-weighted imaging plus neglect plus rehabilitation and other relevant articles that were cited therein. Data Extraction An independent reviewer determined if the data presented provided evidence relevant to planning or developing rehabilitation for stroke patients with distinct forms of neglect. Data Synthesis Results from a number of studies converge on the hypothesis that hypoperfusion and/or infarct of right angular gyrus and intraparietal sulcus can cause viewer-centered neglect, whereas hypoperfusion and/or infarct of right superior temporal gyrus can lead to left stimulus-centered neglect. Distinct forms of rehabilitation might be differentially useful for distinct types of spatial neglect, even though an individual patient may have 2 or more types of neglect. Magnetic resonance perfusion imaging has also shown that fluctuations in neglect in the acute-subacute period after stroke are often due to changes in blood flow caused by changes in blood pressure. Conclusions Consideration of neglect type and status of cerebral blood flow can be useful in planning strategies to ameliorate each individual’s deficits.

Assessing success after cerebral revascularization for ischemia.

Cerebral revascularization continues to evolve as an option in the setting of ischemia. The potential to favorably influence stroke risk and the natural history of cerebrovascular occlusive disease is being evaluated by the ongoing Carotid Occlusion Surgery Study and the Japanese Extracranial-Intracranial Bypass Trial. For those patients who undergo bypass in the setting of ischemia, four key areas of follow-up include functional neurological status, neurocognitive status, bypass patency, and status of cerebral blood flow and perfusion. Several stroke scales that can be used to assess functional status include the National Institutes of Health Stroke Scale, Bathel Index, Modified Rankin Scale, and Stroke Specific Quality of Life. Neurocognition can be checked using the Repeatable Battery for the Assessment of Neuropsychological Status, among other tests. Bypass patency is checked intraoperatively using various flow probes and postoperatively using magnetic resonance angiography (MRA) or computed tomographic angiography (CTA). Cerebral blood flow and perfusion can be assessed using a host of modalities that include positron emission tomography (PET), xenon CT, single photon emission computed tomography (SPECT), transcranial Doppler (TCD), CT, and MR. Paired blood flow studies after a cerebral vasodilatory stimulus using one of these modalities can determine the state of autoregulatory vasodilation (Stage 1 hemodynamic compromise). However, only PET with oxygen extraction fraction measurements can reliably assess for Stage 2 compromise (misery perfusion). This article discusses the various clinical, neuropsychological, and radiographic techniques available to assess a patient's clinical state and cerebral blood flow before and after cerebral revascularization.

Comparison of Conventional Region of Interest and Statistical Mapping Method in Brain Single-photon Emission Computed Tomography for Prediction of Hyperperfusion after Carotid Endarterectomy

Hyperperfusion after carotid endarterectomy (CEA) has been proposed as the main mechanism of intracerebral hemorrhage, which is a disastrous complication. The aim of this study was to compare the predictive value of cerebral blood flow (CBF) abnormalities for hyperperfusion after CEA with the conventional region of interest (ROI) analysis and statistical brain mapping analysis. For 46 patients with unilateral carotid stenosis of 70% or more, CBF and cerebral vasoreactivity were investigated with resting and acetazolamide-challenge single-photon emission computed tomography before CEA and 1 day after CEA. Three-dimensional stereotactic surface projection (3-D-SSP) analysis of CBF changes was performed by automatic quantification with a predefined template. Logistic regression analysis demonstrated CBF reduction (z-score) to be the only significant variable for postoperative hyperperfusion on 3-D-SSP with thalamic normalization but no significant variable with the ROI method. Receiver operating characteristic (ROC) analysis demonstrated significant improvement in the predictive value of CBF reduction (z-score) on 3-D-SSP (area under the ROC curve = 0.93) in comparison with the ROI method (area under the ROC curve = 0.78) (P = 0.049). According to the optimal cutoff values provided by ROC analysis, patients were categorized into two groups: Type I (CBF decrease < 20%, n = 23) and Type II (CBF decrease > or = 20%, n = 23) on ROI analysis and Type A (z-score < or = 2, n = 40) and Type B (z-score > 2, n = 6) on 3-D-SSP. There was a significant difference in incidence of hyperperfusion between Type A (1 of 40) and Type B (5 of 6) on 3-D-SSP (P = 0.00003) but not between Type I (1 of 23) and Type II (5 of 23) on ROI analysis. Cerebral vasoreactivity did not show significant value in the prediction of hyperperfusion with either the ROI or the 3-D-SSP method. Objective assessment of CBF status, especially baseline CBF reduction (z-score), with automatic quantification by 3-D-SSP with normalization had a higher diagnostic value than conventional ROI analysis to identify patients at risk for hyperperfusion after CEA.

Perfusion–diffusion compartmental models describe cerebral helium kinetics at high and low cerebral blood flows in sheep

This study evaluated the relative importance of perfusion and diffusion mechanisms in compartmental models of blood:tissue helium exchange in the brain. Helium has different physiochemical properties from previously studied gases, and is a common diluent gas in underwater diving where decompression schedules are based on theoretical models of inert gas kinetics. Helium kinetics across the cerebrum were determined during and after 15 min of helium inhalation, at separate low and high steady states of cerebral blood flow in seven sheep under isoflurane anaesthesia. Helium concentrations in arterial and sagittal sinus venous blood were determined using gas chromatographic analysis, and sagittal sinus blood flow was monitored continuously. Parameters and model selection criteria of various perfusion-limited or perfusion-diffusion compartmental models of the brain were estimated by simultaneous fitting of the models to the sagittal sinus helium concentrations for both blood flow states. Purely perfusion-limited models fitted the data poorly. Models that allowed a diffusion-limited exchange of helium between a perfusion-limited tissue compartment and an unperfused deep compartment provided better overall fit of the data and credible parameter estimates. Fit to the data was also improved by allowing countercurrent diffusion shunt of helium between arterial and venous blood. These results suggest a role of diffusion in blood:tissue helium equilibration in brain.

Outcome of severe traumatic brain injury: comparison of three monitoring approaches

The determination of cerebral perfusion pressure (CPP) is regarded as vital in monitoring patients with severe traumatic brain injury. Besides indicating the status of cerebral blood flow (CBF), it also reveals the status of intracranial pressure (ICP). The abnormal or suboptimal level of CPP is commonly correlated with high values of ICP and therefore with poor patient outcomes. Eighty-two patients were divided into three groups of patients receiving treatment based on CPP and CBF, ICP alone, and conservative methods during two different observation periods. The characteristics of these three groups were compared based on age, sex, time between injury and hospital arrival, Glasgow Coma Scale score, pupillary reaction to light, surgical intervention, and computerized tomography scanning findings according to the Marshall classification system. Only time between injury and arrival (p = 0.001) was statistically significant. There was a statistically significant difference in the proportions of good outcomes between the multimodality group compared with the group of patients that underwent a single intracranial-based monitoring method and the group that received no monitoring (p = 0.003) based on a disability rating scale after a follow up of 12 months. Death was the focus of outcome in this study in which the multimodality approach to monitoring had superior results.

Diffusion-limited, but not perfusion-limited, compartmental models describe cerebral nitrous oxide kinetics at high and low cerebral blood flows.

This study aimed to evaluate the relative importance of diffusion-limited vs. perfusion-limited mechanisms in compartmental models of blood-tissue inert gas exchange in the brain. Nitrous oxide concentrations in arterial and brain efferent blood were determined using gas chromatographic analysis during and after 15 min of nitrous oxide inhalation, at separate low and high steady states of cerebral blood flow (CBF) in five sheep under halothane anesthesia. Parameters and model selection criteria of various perfusion- or diffusion-limited structural models of the brain were estimated by simultaneous fitting of the models to the mean observed brain effluent nitrous oxide concentration for both blood flow states. Perfusion-limited models returned precise, credible estimates of apparent brain volume but fit the low CBF data poorly. Diffusion-limited models provided better overall fit of the data, which was best described by exchange of nitrous oxide between a perfusion-limited brain compartment and an unperfused compartment. In individual animals, during the low CBF state, nitrous oxide kinetics displayed either fast, perfusion-limited behavior or slow, diffusion-limited behavior. This variability was exemplified in the different parameter estimates of the diffusion limited models fitted to the individual animal data sets. Results suggest that a diffusion limitation contributes to cerebral nitrous oxide kinetics.

Long-term effects of bifemelane hydrochloride on post-stroke deterioration of cognitive function and cerebral blood flow

Cognitive function and cerebral blood flow (CBF) often decrease gradually in stroke patients in the chronic phase. We studied the long-term effects of bifemelane hydrochloride, a cholinergic system accelerator, on cognitive function and CBF in 18 elderly stroke patients. Nine patients were treated with bifemelane for 37.1 ± 5.4 months (mean ± SD), and the other nine patients received no psychotropic drugs for 38.0 ± 5.1 months. Before the study, there were no significant differences between the two groups in Mini-Mental State Examination (MMSE) scores and CBF. After the long-term follow-ups, MMSE scores and CBF decreased significantly in the control group, whereas MMSE scores and CBF were not altered significantly in the treated group. Bifemelane can prevent ischemia-induced decrease in acetylcholine levels and enhance choline acetyl transferase activity and muscarinic receptor binding in the aged brain. Bifemelane also may prevent post-stroke deterioration of cognitive function and CBF through its cholinergic actions.

Cerebral blood flow changes induced by CO 2 in anxiety

Cerebral blood flow (CBF) was measured twice with the 133Xenon inhalation technique, under resting conditions and during 5% CO 2 inhalation, in 13 patients with generalized anxiety disorder and a group of normal volunteers of comparable age and sex distribution. CO 2 inhalation was associated with similar increases in end-tidal CO 2 (PECO 2) and CBF. Neither group showed statistically significant increases in state anxiety. However, when subjects (both patients and controls) who became anxious during CO 2 inhalation were compared with those who did not, on associated CBF changes, significant differences emerged. The former showed less marked CBF increase as compared to the latter in the absence of any significant differences between the two groups on PECO 2 during the second measurement. Changes in state anxiety and CBF showed a statistically significant inverse correlation for the entire group.

Effect of cerebrospinal fluid removal on cerebral blood flow and metabolism in the baboon: influence of tyrosine infusion and cerebral embolism on cerebrospinal fluid pressure autoregulation.

Cerebral blood flow (CBF) and metabolism were measured before and after withdrawal of 5 to 6 ml of cerebrospinal fluid (CSF) in 17 baboons. The measurements were made before and after infusion of tyrosine, the precursor amino acid of the putative neurotransmitters, dopamine and norepinephrine, in the brain. The same observations were made in another experimental group, i.e., before and after acute cerebral multiembolization induced by microfil emboli. In the steady state CBF was unaltered following reduction of intracranial pressure by removal of CSF. After infusion of tyrosine, CBF was decreased, and cerebrovascular resistance increased significantly on removal of CSF. Cerebral embolization did not influence changes in CBF at reduced intracranial pressure. It appears that the cerebral resistance vessels constrict following reduction of intracranial pressure by removal of CSF and that cerebrospinal fluid pressure-CBF autoregulatory mechanisms are resistant to cerebral ischemia induced by middle cerebral artery embolization.

Cerebral blood flow in patients with subarachnoid haemorrhage studied with an intravenous isotope technique. Its clinical significance in the timing of surgery of cerebral arterial aneurysm

The cerebral blood flow state has been evaluated in a series of 207 patients suffering from subarachnoid haemorrhage and with proved arterial aneurysms. Particular interest was focussed on 160 in grade I or II according to Botterell. An intravenous isotope method was used with 131-I Hippuran or 99-Tc pertechnetate as indicators. 133 of the 160 patients were operated on. 78 were also examined postoperatively. The radioactivity was recorded by two gamma detectors place bilaterally over the skull. The heights of the curves were taken as an index of the cerebral blood flow. Transit time was determined by dividing the area of the curve by its height. The results showed that even patients with no or slight neurological symptoms could have a depressed cerebral blood flow. Alterations in the blood flow seemed to precede a change in the clinical picture. Postoperatively, most patients had a further decrease in flow, but some others remained unchanged or even improved. With a normal or only slightly disturbed cerebral blood flow in the preoperative period, the morbidity and mortality of intracranial aneurysm surgery was estimated at 8%. For patients with a low preoperative blood flow value, i.e. more than a 40% reduction, the morbidity and mortality was much higher, about 30%. The results indicate that an analysis of the cerebral blood flow status represents an additional diagnostic parameter of great clinical significance, increasing the possibility of predicting to outcome of the operative treatment of an intracranial arterial aneurysm.

Transient responses of cerebral blood flow and ventilation to changes in PaCO2 in normal subjects and patients with cerebrovascular disease.

In the present study, the dynamics of the cerebral blood flow (CBF) and ventilatory response to hypercapnia was investigated in a group of patients with a cerebrovascular disease and compared to responses measured in a group of normal volunteers. There was a significant correlation between the rapidity of the transient CBF and ventilatory responses and the severity of the cerebrovascular disease. While the steady state CBF response showed no such correlation, the steady state ventilatory response was reduced in patients with severe cerebrovascular disease. Various explanations for the differences in the dynamic responses of CBF and ventilation in patients with mild or severe cerebrovascular disease compared to normal subjects are considered. Measurement of these circulatory and ventilatory responses may be sensitive means for assessing the changing statls of patients with cerebrovascular disease.

Clinical and experimental studies on cranial impedance rheography.

Summary 1. Measurement of the changes in cerebral blood flow, especially the degree of cerebral arteriosclerosis was made possible to some extent by the use of a rheogram which recorded changes in impedance due to the pulsation of the blood flow in the head, especially in the brain. 2. The conclusion made by the amplitude, and time between Q of the electrocardiogram and the point of maximum amplitude (Q-β) was more advantageous than that by detailed analysis of the wave form. 3. Investigation of the distribution of the electric current in the head revealed that 2/3–3/4 of the current passed intracerebrally. 4. The state of cerebral blood flow has so far been clinically grasped to some extent by the application of simple and continuous rheography to the scalp without causing any invasion on the patient.

Cardiovascular responses to experimental cerebral concussion in the rhesus monkey; discussion of similarity of responses to electroconvulsive shock and cerebral concussion in dogs, monkeys, and man.

IN PREVIOUS papers we have reported that when the dog is used as an experimental animal the common carotid blood flow and arterial pressure responses to electroconvulsive shock and experimental concussion are similar.* Under the conditions of these experiments we inferred that the observed changes in common carotid blood flow were indicative of cerebral blood flow variations. 2 To test this hypothesis, a series of experiments were performed with electroconvulsive shock on rhesus macaque monkeys. 3 Measurement of the internal carotid blood flow in these animals indicates the status of cerebral blood flow. 4 The pattern of flow and pressure changes following electroconvulsive shock in the monkeys was similar to that obtained in dogs. 3 Furthermore, the pattern of arterial pressure responses following electroconvulsive shock therapy in psychotic patients is similar in time and direction of change to the pattern observed in dogs and monkeys after such stimuli. 5 The