Background and Purpose
In focal ischemic cortex, cerebral blood flow autoregulation is impaired, and perfusion passively follows blood pressure variations. Although it is generally agreed that profound hypotension is harmful in acute stroke, the hemodynamic and metabolic impact of increased blood pressure on the ischemic core and penumbra are less well understood. We, therefore, tested whether pharmacologically induced hypertension improves cerebral blood flow and metabolism and tissue outcome in acute stroke using optical imaging with high spatiotemporal resolution.
Cerebral blood flow, oxyhemoglobin, and cerebral metabolic rate of oxygen were measured noninvasively using simultaneous multispectral reflectance imaging and laser speckle flowmetry during distal middle cerebral artery occlusion in mice. Hypertension was induced by phenylephrine infusion starting 10 or 60 minutes after ischemia to raise blood pressure by 30% for the duration of ischemia; control groups received saline infusion.
Mild induced hypertension rapidly increased cerebral blood flow, oxyhemoglobin, and cerebral metabolic rate of oxygen in both the core and penumbra and prevented the expansion of cerebral blood flow deficit during 1 hour distal middle cerebral artery occlusion. Induced hypertension also diminished the deleterious effects of periinfarct depolarizations on cerebral blood flow, oxyhemoglobin, and cerebral metabolic rate of oxygen without altering their frequency. Consistent with this, mild induced hypertension reduced infarct volume by 48% without exacerbating tissue swelling when measured 2 days after 1 hour transient distal middle cerebral artery occlusion.
Our data suggest that mild induced hypertension increases collateral cerebral blood flow and oxygenation and improves cerebral metabolic rate of oxygen in the core and penumbra, supporting its use as bridging therapy in acute ischemic stroke until arterial recanalization is achieved.
cerebral metabolic rate of oxygen; laser speckle flowmetry; middle cerebral artery occlusion; multispectral reflectance imaging; stroke
Occlusions of bilateral common carotid arteries (bi-CCA) in mice are popular models for the investigation of transient forebrain ischemia. Currently available technologies for assessing cerebral blood flow (CBF) and oxygenation in ischemic mice have limitations. This study tests a novel near-infrared diffuse correlation spectroscopy (DCS) flow-oximeter for monitoring both CBF and cerebral oxygenation in mice undergoing repeated transient forebrain ischemia. Concurrent flow measurements in a mouse brain were first conducted for validation purposes; DCS measurement was found highly correlated with laser Doppler measurement (R2 = 0.94) and less susceptible to motion artifacts. With unique designs in experimental protocols and fiber-optic probes, we have demonstrated high sensitivities of DCS flow-oximeter in detecting the regional heterogeneity of CBF responses in different hemispheres and global changes of both CBF and cerebral oxygenation across two hemispheres in mice undergoing repeated 2-minute bi-CCA occlusions over 5 days. More than 75% CBF reductions were found during bi-CCA occlusions in mice, which may be considered as a threshold to determine a successful bi-CCA occlusion. With the progress of repeated 2-minute bi-CCA occlusions over days, a longitudinal decline in the magnitudes of CBF reduction was observed, indicating the brain adaptation to cerebral ischemia through the repeated preconditioning.
(170.0170) Medical optics and biotechnology; (170.3660) Light propagation in tissues; (170.3880) Medical and biological imaging; (170.6480) Spectroscopy, speckle
A pilot study explores relative contributions of extra-cerebral (scalp/skull) versus brain (cerebral) tissues to the blood flow index determined by diffuse correlation spectroscopy (DCS). Microvascular DCS flow measurements were made on the head during baseline and breath-holding/hyperventilation tasks, both with and without pressure. Baseline (resting) data enabled estimation of extra-cerebral flow signals and their pressure dependencies. A simple two-component model was used to derive baseline and activated cerebral blood flow (CBF) signals, and the DCS flow indices were also cross-correlated with concurrent Transcranial Doppler Ultrasound (TCD) blood velocity measurements. The study suggests new pressure-dependent experimental paradigms for elucidation of blood flow contributions from extra-cerebral and cerebral tissues.
(170.3880) Medical and biological imaging; (170.2655) Functional monitoring and imaging; (170.3660) Light propagation in tissues; (170.6480) Spectroscopy, speckle
Quantitative techniques have been derived for the measurement of global cerebral blood flow, cerebral blood volume, its response to changing arterial carbon dioxide tension and mixed cerebral venous saturation in the human newborn undergoing intensive care. Normal ranges have been established and significant disturbances of cerebral oxygenation and perfusion have been demonstrated in a variety of pathological conditions. Recently, absolute cerebral deoxyhaemoglobin concentration has been obtained in the newborn using second differential spectroscopy. When combined with the measurement of total cerebral haemoglobin concentration, the mean saturation of cerebral blood (SmcO2) may be obtained, allowing global cerebral oxygenation to be determined continuously in the intensive care unit. Marked changes in the concentrations of cerebral oxy- and deoxyhaemoglobin have been observed in foetuses undergoing labour. Measurements of SmcO2 from the foetal brain prior to delivery have shown the expected close correlation with acid-base status at birth. Although movement artefact remains a theoretical risk during uterine contractions, preliminary measurements of optical path length by intensity-modulated spectroscopy have demonstrated only small fluctuations. In future the clinical application of time, phase and spatially resolved spectroscopy is likely to improve both the quantitative accuracy and the regional specificity of physiological measurements in the foetal and neonatal brain.
Symptomatic ischemia following aneurysmal subarachnoid hemorrhage is common but poorly understood and inadequately treated. Severe constriction of the major arteries at the base of the brain, termed vasospasm, traditionally has been thought to be a proximal event underlying these ischemias, although microvascular changes also have been described. The vast majority of studies aimed at understanding the pathogenesis of ischemic deficits and vasospasm have focused on the interaction of the “spasmogen” of the extravasated blood with the smooth muscle and endothelium of the arteries. This has led to a comparative neglect of the contribution of the central nervous system to the maintenance of cerebral perfusion. In the present study, we focused on the role of the rostral ventromedial medulla (RVM) in modulating cerebral perfusion at rest and following an experimental subarachnoid hemorrhage in the rat. Changes in cerebral blood flow (CBF) were measured using laser-Doppler flowmetry and three-dimensional optical microangiography. Focal application of a GABAA receptor agonist and antagonist were used to respectively inactivate and activate the RVM. We show here that the RVM modulates cerebral blood flow under resting conditions, and further, contributes to restoration of cerebral perfusion following a high-grade subarachnoid hemorrhage. Failure of this brainstem compensatory mechanism could be significant for acute perfusion deficits seen in patients following subarachnoid hemorrhage.
cerebral blood flow; subarachnoid hemorrhage; brainstem; modulation
Moyamoya disease is characterized by a chronic stenoocclusive vasculopathy affecting the terminal internal carotid arteries. The clinical presentation and outcome of moyamoya disease remain varied based on angiographic studies alone, and much work has been done to study cerebral hemodynamics in this group of patients. The ability to measure cerebral blood flow (CBF) accurately continues to improve with time, and with it a better understanding of the pathophysiological mechanisms in patients with moyamoya disease. The main imaging techniques used to evaluate cerebral hemodynamics include PET, SPECT, xenon-enhanced CT, dynamic perfusion CT, MR imaging with dynamic susceptibility contrast and with arterial spin labeling, and Doppler ultrasonography. More invasive techniques include intraoperative ultrasonography. The authors review the current knowledge of CBF in this group of patients and the role each main quantitative method has played in evaluating them, both in the disease state and after surgical intervention.
moyamoya disease; cerebral blood flow; hemodynamics; xenon study; positron emission tomography; single-photon emission computed tomography; perfusion imaging
Chemotherapy may induce deleterious effects in normal tissues, leading to organ damage. Direct vascular injury is the least characterized side effect. Our aim was to establish a real-time, in vivo molecular imaging platform for evaluating the potential vascular toxicity of doxorubicin in mice.
Mice gonads served as reference organs. Mouse ovarian or testicular blood volume and femoral arterial blood flow were measured in real-time during and after doxorubicin (8 mg/kg intravenously) or paclitaxel (1.2 mg/kg) administration. Ovarian blood volume was imaged by ultrasound biomicroscopy (Vevo2100) with microbubbles as a contrast agent whereas testicular blood volume and blood flow as well as femoral arterial blood flow was imaged by pulse wave Doppler ultrasound. Visualization of ovarian and femoral microvasculature was obtained by fluorescence optical imaging system, equipped with a confocal fiber microscope (Cell-viZio).
Using microbubbles as a contrast agent revealed a 33% (P<0.01) decrease in ovarian blood volume already 3 minutes after doxorubicin injection. Doppler ultrasound depicted the same phenomenon in testicular blood volume and blood flow. The femoral arterial blood flow was impaired in the same fashion. Cell-viZio imaging depicted a pattern of vessels' injury at around the same time after doxorubicin injection: the wall of the blood vessels became irregular and the fluorescence signal displayed in the small vessels was gradually diminished. Paclitaxel had no vascular effect.
We have established a platform of innovative high-resolution molecular imaging, suitable for in vivo imaging of vessels' characteristics, arterial blood flow and organs blood volume that enable prolonged real-time detection of chemotherapy-induced effects in the same individuals. The acute reduction in gonadal and femoral blood flow and the impairment of the blood vessels wall may represent an acute universal doxorubicin-related vascular toxicity, an initial event in organ injury.
Because transcranial Doppler TCD is unable to measure arterial diameter, it remains unproven whether the changes in cerebral blood velocity it measures are representative of changes in cerebral blood flow. Our study was designed to compare velocity changes to flow changes measured by two MRI techniques, perfusion MRI and arterial spin labeling, using flavanol-rich cocoa to induce cerebral blood flow changes in healthy volunteers.
We enrolled 20 healthy subjects aged 62 to 80 years (mean 73 years). Each was studied at baseline and after consuming standardized servings of cocoa for 7–14 days.
Changes in middle cerebral artery flow by TCD were significantly correlated with changes in perfusion assessed by gadolinium MRI (r=0.63; p<0.03). Measures with arterial spin labeling showed a stronger correlation with borderline significance.
Changes in flow velocity in the middle cerebral artery associated with drinking cocoa were highly correlated with changes in cerebral blood flow measured by two MRI techniques, using the tracer gadolinium and arterial spin labeling. These results validate Doppler measures of cerebral blood flow velocity as representative assessments of cerebral blood flow.
TCD; cerebral blood flow; MRI; cocoa
Multimodal imaging improves the accuracy of the localization and the quantification of brain activation when measuring different manifestations of the hemodynamic response associated with cerebral activity. In this study, we incorporated cerebral blood flow (CBF) changes measured with arterial spin labeling (ASL), Diffuse Optical Tomography (DOT) and blood oxygen level-dependent (BOLD) recordings to reconstruct changes in oxy- (ΔHbO2) and deoxyhemoglobin (ΔHbR). Using the Grubb relation between relative changes in CBF and cerebral blood volume (CBV), we incorporated the ASL measurement as a prior to the total hemoglobin concentration change (ΔHbT). We applied this ASL fusion model to both synthetic data and experimental multimodal recordings during a 2-sec finger-tapping task. Our results show that the new approach is very powerful in estimating ΔHbO2 and ΔHbR with high spatial and quantitative accuracy. Moreover, our approach allows the computation of baseline total hemoglobin concentration (HbT0) as well as of the BOLD calibration factor M on a single subject basis. We obtained an average HbT0 of 71 μM, an average M value of 0.18 and an average increase of 13 % in cerebral metabolic rate of oxygen (CMRO2), all of which are in agreement with values previously reported in the literature. Our method yields an independent measurement of M, which provides an alternative measurement to validate the hypercapnic calibration of the BOLD signal.
fNIRS; fMRI; ASL; CMRO2; BOLD calibration; multimodal imaging
Optical microangiography (OMAG) and Doppler optical microangiography (DOMAG) are two non-invasive techniques capable of determining the tissue microstructural content, microvasculature angiography, and blood flow velocity and direction. These techniques were used to visualize the acute and chronic microvascular and tissue responses upon an injury in vivo. A tissue wound was induced using a 0.5 mm biopsy punch on a mouse pinna. The changes in the microangiography, blood flow velocity and direction were quantified for the acute (<30 min) wound response and the changes in the tissue structure and microangiography were determined for the chronic wound response (30 min–60 days). The initial wound triggered recruitment of peripheral capillaries, as well as redirection of main arterial and venous blood flow within 3 min. The complex vascular networks and new vessel formation were quantified during the chronic response using fractal dimension. The highest rate of wound closure occurred between days 8 and 22. The vessel tortuosity increased during this time suggesting angiogenesis. Taken together, these data signify that OMAG has the capability to track acute and chronic changes in blood flow, microangiography and structure during wound healing. The use of OMAG has great potential to improve our understanding of vascular and tissue responses to injury in order to develop more effective therapeutics.
Degeneration of cerebral white matter is commonly observed in aging, and the associated degradation in neural connectivity contributes to cognitive decline in older adults. Vascular dysfunction has been implicated as a potential mechanism for general age-related neural tissue deterioration; however, no prior study has examined the direct relationship between cortical vascular health and subcortical white-matter integrity. In this work, we aimed to determine whether blood supply to the brain is associated with microstructural integrity of connective tissue, and whether such associations are regionally specific and mainly accounted for by aging. We examined the association between cerebral blood flow (CBF) in the cortical mantle, measured using arterial spin labeling (ASL), and subcortical white-matter integrity, measured using diffusion tensor imaging (DTI), in a group of healthy adults spanning early to late adulthood. We found cortical CBF to be significantly associated with white-matter integrity throughout the brain. In addition, these associations were only partially tied to aging, as they remained even when statistically controlling for age, and when restricting the analyses to a young subset of the sample. Furthermore, vascular risk was not a prominent determinant of these effects. These findings suggest that the overall blood supply to the brain is an important indicator of white-matter health in the normal range of variations amongst adults, and that the decline in CBF with advancing age may potentially exacerbate deterioration of the connective anatomy of the brain.
Cerebral blood flow (CBF) during stepped hypercapnia was measured simultaneously
in the rat brain using near-infrared diffuse correlation spectroscopy (DCS) and
arterial spin labeling MRI (ASL). DCS and ASL CBF values agree very well, with
high correlation (R=0.86, p< 10-9), even when
physiological instability perturbed the vascular response. A partial volume
effect was evident in the smaller magnitude of the optical CBF response compared
to the MRI values (averaged over the cortical area), primarily due to the
inclusion of white matter in the optically sampled volume. The 8.2 and 11.7 mm
mid-separation channels of the multi-distance optical probe had the lowest
partial volume impact, reflecting ~75 % of the MR signal change. Using a
multiplicative correction factor, the ASL CBF could be predicted with no more
than 10% relative error, affording an opportunity for real-time relative
cerebral metabolism monitoring in conjunction with MR measurement of cerebral
blood volume using super paramagnetic contrast agents.
(170.2655) Functional monitoring and imaging; (170.1470) Blood or tissue constituent monitoring; (170.0170) Medical optics and biotechnology; (170.3340) Laser Doppler velocimetry
The capacity of the brain to regulate its blood flow in order to meet metabolic demands and to compensate for acute and chronic changes in cerebral perfusion pressure (cerebral autoregulation) is an essential protecting mechanism against cerebral ischemia.
We reviewed existing data on methods of assessing cerebral blood flow and autoregulation.
Cerebral autoregulation is mechanistically complex and depends on myogenic, neuronal, endothelial, and metabolic factors. There are numerous methods of estimating cerebrovascular reserve (CVR) non-invasively including Positive Emission Tomography (gold standard), Transcranial Doppler ultrasound, dynamic contrast-enhanced perfusion Magnetic Resonance Imaging, Single-Photon Emission Computed Tomography and Xenon Computed Tomography. Since each of these techniques has its advantages and disadvantages, selection of a specific method for CVR testing depends on availability, acquired experience in interpreting the study, required precision, and cost. Cerebral autoregulation may be impaired in patients with symptomatic or asymptomatic carotid stenosis or occlusion and is associated with a higher risk of stroke or transient ischemic attack (TIA) ipsilateral to the carotid artery disease.
Assessment of CVR can help stratify patients based on their risk of stroke or TIA and select patients who may benefit from revascularization therapies. Cerebral vasoreactivity testing may be useful to evaluate cerebral autoregulation after revascularization procedures as a surrogate endpoint of vascular events related to hypoperfusion or hyperperfusion.
Regional cerebral blood flow; autoregulation; cerebral ischemia; cerebral blood volume; cerebral perfusion pressure
It is unknown if impaired cerebral vasoreactivity recovers after ischemic stroke, and whether it compromises perfusion in regions surrounding infarct and other vascular territories. We investigated the regional differences in CO2 vasoreactivity (CO2VR) and their relationships to peri-infarct T2 hyperintensities (PIHs), chronic infarct volumes, and clinical outcomes.
We studied 39 subjects with chronic large middle cerebral artery territory infarcts and 48 matched controls. Anatomic and three-dimensional continuous arterial spin labeling imaging at 3-Tesla MRI were used to measure regional cerebral blood flow (CBF) and CO2VR during normocapnia, hypercapnia, and hypocapnia in main arteries distributions.
Stroke patients showed a significantly lower augmentation of blood flow at increased CO2 but greater reduction of blood flow with decreased CO2 than the control group. This altered vasoregulatory response was observed both ipsilateral and contralateral to the stroke. Lower CO2VR on the stroke side was associated with PIHs, greater infarct volume, and worse outcomes. The cases with PIHs (n = 27) had lower CBF during all conditions bilaterally (p < 0.0001) compared to cases with infarct only.
Perfusion augmentation is inadequate in multiple vascular territories in patients with large artery ischemic infarcts, but vasoconstriction is preserved. Peri-infarct T2 hyperintensities are associated with lower blood flow. Strategies aimed to preserve vasoreactivity after an ischemic stroke should be tested for their effect on long-term outcomes.
= anterior cerebral artery;
= apparent diffusion coefficient;
= blood pressure;
= continuous arterial spin labeling;
= cerebral blood flow;
= CO2 vasoreactivity;
= diffusion-weighted image;
= fluid-attenuated inversion recovery;
= field of view;
= gray matter;
= low-density lipoprotein;
= middle cerebral artery;
= magnetization prepared rapid gradient echo;
= modified Rankin Scale;
= NIH Stroke Scale;
= posterior cerebral artery;
= peri-infarct T2 hyperintensities;
= echo time;
= inversion time;
= repetition time;
= white blood cell;
= white matter.
Soluble epoxide hydrolase (sEH), a key enzyme in the metabolism of vasodilator eicosanoids called epoxyeicosatrienoic acids (EETs), is sexually dimorphic and suppressed by estrogen. We determined if the sex difference in blood flow during focal cerebral ischemia is linked to sEH. Soluble epoxide hydrolase expression in brain, hydrolase activity in cerebral vessels, and plasma 14,15-dihydroxyeicosatrienoic acid (14,15-DHET) were determined in male and female wild-type (WT) and sEH knockout (sEHKO) mice. Male, female, and ovariectomized female WT and sEHKO mice were subjected to 2-h middle cerebral artery occlusion (MCAO) and infarct size was measured at 24 h of reperfusion. Laser–Doppler cortical perfusion during MCAO was compared among groups and differences in cortical blood flow rates were confirmed using in vivo quantitative optical microangiography. Cerebrovascular expression and activity of sEH and plasma 14,15-DHET were lower in WT female than male mice, and blood flow during MCAO was higher and infarct size was smaller in WT female compared with male mice. Sex differences in cerebral blood flow and ischemic damage were abolished after ovariectomy and were absent in sEHKO mice. We conclude that sEH is an important mechanism underlying sex-linked differences in blood flow and brain damage after cerebral ischemia.
EETs; epoxide hydrolase; estrogen; ischemia; optical imaging
Four very low birth weight, very premature infants were monitored during a 12° postural elevation using diffuse correlation spectroscopy (DCS) to measure microvascular cerebral blood flow (CBF) and transcranial Doppler ultrasound (TCD) to measure macrovascular blood flow velocity in the middle cerebral artery. DCS data correlated significantly with peak systolic, end diastolic, and mean velocities measured by TCD (pA =0.036, 0.036, 0.047). Moreover, population averaged TCD and DCS data yielded no significant hemodynamic response to this postural change (p>0.05). We thus demonstrate feasibility of DCS in this population, we show correlation between absolute measures of blood flow from DCS and blood flow velocity from TCD, and we do not detect significant changes in CBF associated with a small postural change (12°) in these patients.
This study assesses the utility of a hybrid optical instrument for noninvasive transcranial monitoring in the neurointensive care unit. The instrument is based on diffuse correlation spectroscopy (DCS) for measurement of cerebral blood flow (CBF), and near-infrared spectroscopy (NIRS) for measurement of oxy- and deoxy-hemoglobin concentration. DCS/NIRS measurements of CBF and oxygenation from frontal lobes are compared with concurrent xenon-enhanced computed tomography (XeCT) in patients during induced blood pressure changes and carbon dioxide arterial partial pressure variation.
Seven neurocritical care patients were included in the study. Relative CBF measured by DCS (rCBFDCS), and changes in oxy-hemoglobin (ΔHbO2), deoxy-hemoglobin (ΔHb), and total hemoglobin concentration (ΔTHC), measured by NIRS, were continuously monitored throughout XeCT during a baseline scan and a scan after intervention. CBF from XeCT regions-of-interest (ROIs) under the optical probes were used to calculate relative XeCT CBF (rCBFXeCT) and were then compared to rCBFDCS. Spearman’s rank coefficients were employed to test for associations between rCBFDCS and rCBFXeCT, as well as between rCBF from both modalities and NIRS parameters.
rCBFDCS and rCBFXeCT showed good correlation (rs = 0.73, P = 0.010) across the patient cohort. Moderate correlations between rCBFDCS and ΔHbO2/ΔTHC were also observed. Both NIRS and DCS distinguished the effects of xenon inhalation on CBF, which varied among the patients.
DCS measurements of CBF and NIRS measurements of tissue blood oxygenation were successfully obtained in neurocritical care patients. The potential for DCS to provide continuous, noninvasive bedside monitoring for the purpose of CBF management and individualized care is demonstrated.
Near-infrared spectroscopy; Diffuse correlation spectroscopy; Cerebral blood flow; Xenon CT; Neurocritical care
In patients with unilateral internal carotid or middle cerebral artery (ICA or MCA) occlusive disease, the degree of crossed cerebellar hypoperfusion that is evident within a few months after the onset of stroke may reflect cerebral metabolic rate of oxygen in the affected cerebral hemisphere relative to that in the contralateral cerebral hemisphere. The aim of the present study was to determine whether the ratio of blood flow asymmetry in the cerebellar hemisphere to blood flow asymmetry in the cerebral hemisphere on positron emission tomography (PET) and single photon emission computed tomography (SPECT) correlates with oxygen extraction fraction (OEF) asymmetry in the cerebral hemisphere on PET in patients with chronic unilateral ICA or MCA occlusive disease and whether this blood flow ratio on SPECT detects misery perfusion in the affected cerebral hemisphere in such patients.
Brain blood flow and OEF were assessed using 15O-PET and N-isopropyl-p-[123I]iodoamphetamine (123I-IMP) SPECT, respectively. All images were anatomically standardized using SPM2. A region of interest (ROI) was automatically placed in the bilateral MCA territories and in the bilateral cerebellar hemispheres using a three-dimensional stereotaxic ROI template, and affected-to-contralateral asymmetry in the MCA territory or contralateral-to-affected asymmetry in the cerebellar hemisphere was calculated. Sixty-three patients with reduced blood flow in the affected cerebral hemisphere on 123I-IMP SPECT were enrolled in this study.
A significant correlation was observed between MCA ROI asymmetry of PET OEF and the ratio of cerebellar hemisphere asymmetry of blood flow to MCA ROI asymmetry of blood flow on PET (r = 0.381, p = 0.0019) or SPECT (r = 0.459, p = 0.0001). The correlation coefficient was higher when reanalyzed in a subgroup of 43 patients undergoing a PET study within 3 months after the last ischemic event (r = 0.541, p = 0.0001 for PET; r = 0.609, p < 0.0001 for SPECT). The blood flow ratio on brain perfusion SPECT in all patients provided 100 % sensitivity and 58 % specificity, with 43 % positive and 100 % negative predictive values for detecting abnormally elevated MCA ROI asymmetry of PET OEF.
The ratio of blood flow asymmetry in the cerebellar hemisphere to blood flow asymmetry in the cerebral hemisphere on PET and SPECT correlates with PET OEF asymmetry in the cerebral hemisphere, and this blood flow ratio on SPECT detects misery perfusion in the affected cerebral hemisphere.
Crossed cerebellar hypoperfusion; Misery perfusion; Oxygen extraction fraction; PET; SPECT
Multiple lines of evidence suggest cardiovascular co-morbidities hasten the onset of Alzheimer’s disease (AD) or accelerate its course.
To evaluate the utility of cerebral vascular physical function/condition parameters as potential systemic indicators of AD, we employed transcranial Doppler (TCD) ultrasound to assess cerebral blood flow and vascular resistance of the 16 arterial segments comprising the circle of Willis and its major tributaries.
Our study revealed decreased arterial mean flow velocity (MFV) and increased pulsatility index (PI) are associated with a clinical diagnosis of presumptive AD. Cerebral blood flow impairment revealed by these parameters reflects the global hemodynamic and structural consequences of a multifaceted disease process yielding diffuse congestive microvascular pathology, increased arterial rigidity, and decreased arterial compliance combined with putative age-associated cardiovascular output declines.
TCD evaluation offers direct physical confirmation of brain perfusion impairment and may ultimately provide a convenient, noninvasive means to assess the efficacy of medical interventions on cerebral blood flow or reveal incipient AD. In the near term, TCD-based direct assessments of brain perfusion may offer the prospect of preventing or mitigating AD simply by revealing patients who would benefit from interventions to improve circulatory system function.
Alzheimer’s disease; transcranial Doppler ultrasonography; cerebral blood flow; brain hypoperfusion; mean flow velocity; pulsatility index
Blood flow to the head and arms was measured by a new volumetric Doppler technique in 30 preterm infants and 10 full term infants. At least 80% of this blood flow is considered to perfuse the brain. At the same time mean blood velocity in the middle and anterior cerebral arteries was measured by Duplex Doppler scanning. While blood flow to the head and arms remained substantially constant in both groups over the first 48 hours of life (60 ml/100 g brain weight/min), blood velocity doubled in both cerebral arteries in the preterm group. The term infants had higher blood velocities in both arteries at all times, but the velocities also increased over 48 hours, although to a lesser extent than in the preterm group. These findings imply that the major intracranial arteries are themselves vasoactive, being dilated at birth and subsequently constricting, possibly as an autoregulatory response to rising arterial blood pressure. While vasodilated, the cerebral arteries will be less efficient at damping pressure transients, placing preterm infants at particular risk of periventricular haemorrhage during the early hours of life. The implications for possible approaches to the prevention of cerebral haemorrhage are discussed.
The microvasculature plays a vital part in the cardiovascular system. Any impairment to its function can lead to significant pathophysiological effects, particularly in organs such as the brain where there is a very tight coupling between structure and function. However, it is extremely difficult to quantify the health of the microvasculature in vivo, other than by assessing perfusion, using techniques such as arterial spin labelling. Recent work has suggested that the flow distribution within a voxel could also be a valuable measure. This can also be measured clinically, but as yet has not been related to the properties of the microvasculature due to the difficulties in modelling and characterizing these strongly inter-connected networks. In this paper, we present a new technique for characterizing an existing physiologically accurate model of the cerebral microvasculature in terms of its residue function. A new analytical mathematical framework for calculation of the residue function, based on the mass transport equation, of any arbitrary network is presented together with results from simulations. We then present a method for characterizing this function, which can be directly related to clinical data, and show how the resulting parameters are affected under conditions of both reduced perfusion and reduced network density. It is found that the residue function parameters are affected in different ways by these two effects, opening up the possibility of using such parameters, when acquired from clinical data, to infer information about both the network properties and the perfusion distribution. These results open up the possibility of obtaining valuable clinical information about the health of the microvasculature in vivo, providing additional tools to clinicians working in cerebrovascular diseases, such as stroke and dementia.
residue function; flow heterogeneity; ischaemic stroke
A new method of retinal blood flow measurement using Doppler optical coherence tomography was developed. It showed circulatory abnormalities in retinal and optic nerve diseases that correlated with disease location and severity.
To investigate blood flow changes in retinal and optic nerve diseases with Doppler Fourier domain optical coherence tomography (OCT).
Sixty-two participants were divided into five groups: normal, glaucoma, nonarteritic ischemic optic neuropathy (NAION), treated proliferative diabetic retinopathy (PDR), and branch retinal vein occlusion (BRVO). Doppler OCT was used to scan concentric circles of 3.4- and 3.75-mm diameters around the optic nerve head. Flow in retinal veins was calculated from the OCT velocity profiles. Arterial and venous diameters were measured from OCT Doppler and reflectance images.
Total retinal blood flow in normal subjects averaged 47.6 μL/min. The coefficient of variation of repeated measurements was 11% in normal eyes and 14% in diseased eyes. Eyes with glaucoma, NAION, treated PDR, and BRVO had significantly decreased retinal blood flow compared with normal eyes (P < 0.001). In glaucoma patients, the decrease in blood flow was highly correlated with the severity of visual field loss (P = 0.003). In NAION and BRVO patients, the hemisphere with more severe disease also had lower blood flow.
Doppler OCT retinal blood flow measurements showed good repeatability and excellent correlation with visual field and clinical presentations. This approach could enhance our understanding of retinal and optic nerve diseases and facilitate the development of new therapies.
Real-time ultrasound perfusion imaging (rt-UPI) allows visualization of microbubbles flowing through the cerebral microvasculature. We hypothesized that analysis of microbubble tissue replenishment would enable for characterization of perfusion deficits in acute middle cerebral artery (MCA) territory stroke. Twenty-three patients (mean age 70.2±13.2 years, 9 weeks) were included. Sequential images of bubble replenishment were acquired by transcranial rt-UPI at low mechanical index immediately after microbubble destruction. Different parameters were calculated from regions of interest (ROIs): real-time time to peak (rt-TTP), rise rate (β), and plateau (A) of acoustic intensity, and A × β was used as an index of blood flow. Results were compared with diffusion-weighted and perfusion magnetic resonance imaging. Parameters of rt-UPI had lower values in ROIs of ischemic as compared with normal tissue (β=0.58±0.40 versus 1.25±0.83; P=0.001; A=1.44±1.75 versus 2.63±2.31; P=0.05; A × β=1.14±2.25 versus 2.98±2.70; P=0.01). Real-time time to peak was delayed in ischemic tissue (11.43±2.67 versus 8.88±1.66 seconds; P<0.001). From the analysis of receiver operating characteristic curves, β and A × β had the largest areas under the curve with optimal cutoff values of β<0.76 and A × β<1.91. We conclude that rt-UPI with analysis of microbubble replenishment correctly identifies ischemic brain tissue in acute MCA stroke.
acute stroke; brain imaging; cerebral hemodynamics; neurosonology; ultrasound
Continuous arterial spin labeling (CASL) is a noninvasive magnetic resonance (MR) method for measuring cerebral perfusion. In its most widely used form, CASL incorporates a postlabeling delay to minimize the sensitivity of the technique to transit time effects, which otherwise corrupt cerebral blood flow (CBF) quantification. For this delay to work effectively, it must be longer than the longest transit time present in the system. In this work, CASL measurements were made in four coronal slices in the rat brain using a range of postlabeling delays. By doing this, direct estimation of both CBF and arterial transit time (δa) was possible. These measurements were performed in the normal brain and during hypoperfusion induced by occlusion of the common carotid arteries. It was found that, in the normal rat brain, significant regional variation exists for both CBF and δa. Mean values of CBF and δa in the selected gray matter regions of interest were 233 mL/100 g min and 266 ms, respectively, with the latter ranging from 100 to 500 ms. Therefore, use of a 500-ms postlabeling delay is suitable for any location in the normal rat brain. After common carotid artery occlusion, CBF decreased and δa increased by regionally dependent amounts. In the sensory cortex, δa increased to a mean value of 740 ms, significantly greater than 500 ms. These results highlight the importance of either (a) determining δa as part of the CASL measurement or (b) knowing the approximate range of values δa is likely to take for a given application, so that the parameters of the CASL sequence can be chosen appropriately.
arterial spin labeling; arterial transit time; cerebral hypoperfusion; magnetic resonance imaging; perfusion quantification; rat brain
We used a nonimpact inertial rotational model of a closed head injury in neonatal piglets to simulate the conditions following traumatic brain injury in infants. Diffuse optical techniques, including diffuse reflectance spectroscopy and diffuse correlation spectroscopy (DCS), were used to measure cerebral blood oxygenation and blood flow continuously and noninvasively before injury and up to 6 h after the injury. The DCS measurements of relative cerebral blood flow were validated against the fluorescent microsphere method. A strong linear correlation was observed between the two techniques (R = 0.89, p < 0.00001). Injury-induced cerebral hemodynamic changes were quantified, and significant changes were found in oxy- and deoxy-hemoglobin concentrations, total hemoglobin concentration, blood oxygen saturation, and cerebral blood flow after the injury. The diffuse optical measurements were robust and also correlated well with recordings of vital physiological parameters over the 6-h monitoring period, such as mean arterial blood pressure, arterial oxygen saturation, and heart rate. Finally, the diffuse optical techniques demonstrated sensitivity to dynamic physiological events, such as apnea, cardiac arrest, and hypertonic saline infusion. In total, the investigation corraborates potential of the optical methods for bedside monitoring of pediatric and adult human patients in the neurointensive care unit.
diffuse correlation spectroscopy (DCS); diffuse reflectance spectroscopy (DRS); cerebral hemodynamics; cerebral blood flow; traumatic brain injury; near—infrared spectroscopy (NIRS)