Quantification Of Cerebral Blood Flow Research Articles

Reduction of errors in ASL cerebral perfusion and arterial transit time maps using image de‐noising

In this work, the performance of image de-noising techniques for reducing errors in arterial spin labeling cerebral blood flow and arterial transit time estimates is investigated. Simulations were used to show that the established arterial spin labeling cerebral blood flow quantification method exhibits the bias behavior common to nonlinear model estimates, and as a result, the reduction of random errors using image de-noising can improve accuracy. To assess the effect on precision, multiple arterial spin labeling data sets acquired from the rat brain were processed using a variety of common de-noising methods (Wiener filter, anisotropic diffusion filter, gaussian filter, wavelet decomposition, and independent component analyses). The various de-noising schemes were also applied to human arterial spin labeling data to assess the possible extent of structure degradation due to excessive spatial smoothing. The animal experiments and simulated data show that noise reduction methods can suppress both random and systematic errors, improving both the precision and accuracy of cerebral blood flow measurements and the precision of transit time maps. A number of these methods (and particularly independent component analysis) were shown to achieve this aim without compromising image contrast.

The Concept of the Penumbra: can it be Translated to Stroke Management?

The 'penumbra' is a concept coined in animal experiments suggesting that functionally impaired tissue can survive and recover if sufficient reperfusion is re-established within a limited time period, which depends on the level of residual flow. In an ischaemic territory, irreversible damage progresses over time from the centre of the most severe flow reduction to the periphery with less disturbed perfusion. This centrifugal progression of irreversible tissue damage is characterised by a complex cascade of interconnected electrophysiological, molecular, metabolic and perfusion disturbances. Waves of depolarisations, the peri infarct spreading depressions, inducing activation of ion pumps and liberation of excitatory transmitters play an important role in the drastically increased metabolic demand during reduced oxygen supply causing hypoxic tissue changes and lactacidosis, which further damage the tissue. Positron emission tomography allows the quantification of regional cerebral blood flow, the regional metabolic rate for oxygen and the regional oxygen extraction fraction, which can be used to identify regions with a critical reduction in these physiologic variables as indicators of penumbra and irreversible damage within ischaemic territories in animal models and patients with stroke. These positron emission tomography methods require arterial blood sampling and due to the complex logistics involved, are limited for routine application. Therefore, newer tracers were developed for the noninvasive detection of irreversible tissue damage (flumazenil) and of hypoxic tissue changes (fluoromisonidazole). As a widely applicable clinical tool, diffusion/perfusion-weighted magnetic resonance imaging is used; the 'mismatch' between perfusion and diffusion changes serves as a surrogate marker of the penumbra. However, in comparative studies of magnetic resonance imaging and positron emission tomography, diffusion-weighted imaging showed a high false-positive rate of irreversible damage, and the perfusion-weighted-diffusion-weighted mismatch overestimated the penumbra as defined by positron emission tomography. Advanced analytical procedures of magnetic resonance imaging data may improve the reliability of these surrogate markers but should be validated with quantitative procedures.

Estimation of 123I-IMP arterial blood activity from dynamic planar imaging of the chest using a graph plot method for the quantification of regional cerebral blood flow

I-123-labeled N-isopropyl-p-iodoamphetamine ((123)I-IMP) is used for the measurement of regional cerebral blood flow (rCBF). A continuous or single arterial blood sampling (ABS) is necessary to estimate an integral of arterial input function (AIF) for the measurement of rCBF by using a microsphere model analysis. Therefore, a method of measuring rCBF without any blood sampling is desired. The aim of this study was to establish a method to estimate the AIF from the time-activity curve of the lungs after an injection of (123)I-IMP, using a regression analysis for the measurement of rCBF without any blood sampling. Thirty-seven prospective studies in 10 consecutive patients were enrolled. A chest planar dynamic imaging for 3 min and continuous ABS for 5 min after a bolus injection of 167MBq (123)I-IMP were performed in all studies. Data from the chest imaging were analyzed in comparison with ABS data (AIF(5)) in the first 10 studies, and an equation for estimation yielding accurate AIF(5) from the total counts cleared from the lungs, during 5 min after injection of (123)I-IMP (TCL(5)), was derived. The validity of the proposed method was evaluated in the subsequent 27 studies. A good correlation was obtained between the AIF and TCL by regression analysis in the first 10 studies (r = 0.94, P < 0.001). An equation for the estimation of AIF by the regression analysis in the first 10 studies was defined as follows: estimated AIF = 2147 + 4.174 x TCL(5). In the subsequent 27 studies, a good linear correlation was obtained between the measured and the estimated AIF(5) by using the equation (r = 0.79, P < 0.001). AIF(5) can be accurately estimated from TCL(5). Therefore, estimated AIF(5) can be used for the measurement of rCBF instead of ABS data.

Estimation of labeling efficiency in pseudocontinuous arterial spin labeling

Pseudocontinuous arterial spin labeling MRI is a new arterial spin labeling technique that has the potential of combining advantages of continuous arterial spin labeling and pulsed arterial spin labeling. However, unlike continuous arterial spin labeling, the labeling process of pseudocontinuous arterial spin labeling is not strictly an adiabatic inversion and the efficiency of labeling may be subject specific. Here, three experiments were performed to study the labeling efficiency in pseudocontinuous arterial spin labeling MRI. First, the optimal labeling position was determined empirically to be approximately 84 mm below the anterior commissure-posterior commissure line in order to achieve the highest sensitivity. Second, an experimental method was developed to utilize phase-contrast velocity MRI as a normalization factor and to estimate the labeling efficiency in vivo, which was founded to be 0.86 +/- 0.06 (n = 10, mean +/- standard deviation). Third, we compared the labeling efficiency of pseudocontinuous arterial spin labeling MRI under normocapnic and hypercapnic (inhalation of 5% CO(2)) conditions and showed that a higher flow velocity in the feeding arteries resulted in a reduction in the labeling efficiency. In summary, our results suggest that labeling efficiency is a critical parameter in pseudocontinuous arterial spin labeling MRI not only in terms of achieving highest sensitivity but also in quantification of absolute cerebral blood flow in milliliters per minute per 100 g. We propose that the labeling efficiency should be estimated using phase-contrast velocity MRI on a subject-specific basis.

Wisconsin Card Sorting Test and Brain Perfusion Imaging in Early Dementia

Background/Aims: The presence of frontal or executive deficits in patients even at early stages of dementia is now widely recognized. We investigated the relationship between the scores of the Wisconsin card sorting test (WCST) and brain perfusion in patients with early dementia. Methods: A total of 77 subjects participated in this study. They underwent the WCST and brain single photon emission computed tomography with 99mTc-ethylcisteinate dimer. We analyzed the data using a regional cerebral blood flow (rCBF) quantification software program, 3DSRT. Results: The number of categories achieved (CA) scores of the WCST had a weakly positive correlation with regional cerebral blood flow in the bilateral precentral, bilateral callosomarginal, bilateral pericallosal, right thalamus, left central and left parietal segments. The number of perseverative errors of the Nelson type (PEN) scores had a weakly negative correlation with rCBF in the right thalamus. Conclusion: The results in this study suggest that CA scores mainly reflect the function of the precentral segments, especially the left side, and that PEN scores correlate with rCBF in the right thalamus. The results suggest that CA scores and PEN scores should be differentially estimated in the WCST.

Absolute quantification of perfusion using dynamic susceptibility contrast MRI: pitfalls and possibilities

Absolute quantification of cerebral blood flow, cerebral blood volume and mean transit time is desirable in the determination of tissue viability thresholds and tissue at risk in acute ischaemic stroke, as well as in cases where a global reduction in cerebral blood flow is expected, for example, in patients with dementia or depressive disorders. Absolute values are also useful when comparing sequential examinations of tissue perfusion parameters, for example, in the monitoring and follow-up of various kinds of therapy. Regardless of the method employed, a number of assumptions and approximations must be made to obtain absolute measures of perfusion. Furthermore, the different stages of data acquisition and processing are associated with various degrees of uncertainty. In this review, the problems of particular relevance to absolute quantification of cerebral perfusion parameters using dynamic susceptibility contrast magnetic resonance imaging are discussed, and possible solutions are outlined.

Arterial transit time effects in pulsed arterial spin labeling CBF mapping: Insight from a PET and MR study in normal human subjects

Arterial transit time (ATT), a key parameter required to calculate absolute cerebral blood flow in arterial spin labeling (ASL), is subject to much uncertainty. In this study, ASL ATTs were estimated on a per-voxel basis using data measured by both ASL and positron emission tomography in the same subjects. The mean ATT increased by 260 +/- 20 (standard error of the mean) ms when the imaging slab shifted downwards by 54 mm, and increased from 630 +/- 30 to 1220 +/- 30 ms for the first slice, with an increase of 610 +/- 20 ms over a four-slice slab when the gap between the imaging and labeling slab increased from 20 to 74 mm. When the per-slice ATTs were employed in ASL cerebral blood flow quantification and the in-slice ATT variations ignored, regional cerebral blood flow could be significantly different from the positron emission tomography measures. ATT also decreased with focal activation by the same amount for both visual and motor tasks (approximately 80 ms). These results provide a quantitative relationship between ATT and the ASL imaging geometry and yield an assessment of the assumptions commonly used in ASL imaging. These findings should be considered in the interpretation of, and comparisons between, different ASL-based cerebral blood flow studies. The results also provide spatially specific ATT data that may aid in optimizing the ASL imaging parameters.

Absolute quantification of cerebral blood flow: correlation between dynamic susceptibility contrast MRI and model-free arterial spin labeling

To compare absolute cerebral blood flow (CBF) estimates obtained by model-free arterial spin labeling (ASL) and dynamic susceptibility contrast MRI (DSC-MRI), corrected for partial volume effects (PVEs). CBF was measured using DSC-MRI and model-free ASL (quantitative signal targeting with alternating radiofrequency labeling of arterial regions) at 3 T in 15 subjects with brain tumor, and the two modalities were compared with regard to CBF estimates in normal gray matter (GM) and DSC-to-ASL CBF ratios in selected tumor regions. The DSC-MRI CBF maps were calculated using a global arterial input function (AIF) from the sylvian-fissure region, but, in order to minimize PVEs, the AIF time integral was rescaled by a venous output function time integral obtained from the sagittal sinus. In GM, the average DSC-MRI CBF estimate was 150+/-45 ml/(min 100 g) (mean+/-SD) while the corresponding ASL CBF was 44+/-10 ml/(min 100 g). The linear correlation between GM CBF estimates obtained by DSC-MRI and ASL was r=.89, and observed DSC-to-ASL CBF ratios differed by less than 3% between GM and tumor regions. A satisfactory positive linear correlation between the CBF estimates obtained by model-free ASL and DSC-MRI was observed, and DSC-to-ASL CBF ratios showed no obvious tissue dependence.

Partial volume effect (PVE) on the arterial input function (AIF) in T1‐weighted perfusion imaging and limitations of the multiplicative rescaling approach

The partial volume effect (PVE) on the arterial input function (AIF) remains a major obstacle to absolute quantification of cerebral blood flow (CBF) using MRI. This study evaluates the validity and performance of a commonly used multiplicative rescaling of the AIF to correct for the PVE. In a group of six patients, perfusion imaging was performed using a T(1)-weighted approach that minimizes confounding susceptibility artifacts. Various degrees of PVE were induced on the AIF and subsequently corrected using four different schemes of multiplicative AIF rescaling. Our results show that a multiplicative rescaling is not always applicable and can introduce a CBF bias. An easily measurable quantity denoted the tissue signal fraction (TSF) is proposed as a measure of the applicability of a multiplicative rescaling. For the present CBF quantification method, a TSF of <0.4 results in a CBF bias <15% after AIF rescaling.

Characterizing the Origin of the Arterial Spin Labelling Signal in MRI Using a Multiecho Acquisition Approach

Arterial spin labelling (ASL) can noninvasively isolate the MR signal from arterial blood water that has flowed into the brain. In gray matter, the labelled bolus is dispersed within three main compartments during image acquisition: the intravascular compartment; intracellular tissue space; and the extracellular tissue space. Changes in the relative volumes of the extracellular and intracellular tissue space are thought to occur in many pathologic conditions such as stroke and brain tumors. Accurate measurement of the distribution of the ASL signal within these three compartments will yield better understanding of the time course of blood delivery and exchange, and may have particular application in animal models of disease to investigate the relationship between the source of the ASL signal and pathology. In this study, we sample the transverse relaxation of the ASL perfusion weighted and control images acquired with and without vascular crusher gradients at a range of postlabelling delays and tagging durations, to estimate the tricompartmental distribution of labelled water in the rat cortex. Our results provide evidence for rapid exchange of labelled blood water into the intracellular space relative to the transit time through the vascular bed, and provide a more solid foundation for cerebral blood flow quantification using ASL techniques.

The QUASAR reproducibility study, Part II: Results from a multi-center Arterial Spin Labeling test–retest study

Arterial Spin Labeling (ASL) is a method to measure perfusion using magnetically labeled blood water as an endogenous tracer. Being fully non-invasive, this technique is attractive for longitudinal studies of cerebral blood flow in healthy and diseased individuals, or as a surrogate marker of metabolism. So far, ASL has been restricted mostly to specialist centers due to a generally low SNR of the method and potential issues with user-dependent analysis needed to obtain quantitative measurement of cerebral blood flow (CBF).Here, we evaluated a particular implementation of ASL (called Quantitative STAR labeling of Arterial Regions or QUASAR), a method providing user independent quantification of CBF in a large test–retest study across sites from around the world, dubbed “The QUASAR reproducibility study”. Altogether, 28 sites located in Asia, Europe and North America participated and a total of 284 healthy volunteers were scanned. Minimal operator dependence was assured by using an automatic planning tool and its accuracy and potential usefulness in multi-center trials was evaluated as well.Accurate repositioning between sessions was achieved with the automatic planning tool showing mean displacements of 1.87±0.95 mm and rotations of 1.56±0.66°. Mean gray matter CBF was 47.4±7.5 [ml/100 g/min] with a between-subject standard variation SDb=5.5 [ml/100 g/min] and a within-subject standard deviation SDw=4.7 [ml/100 g/min]. The corresponding repeatability was 13.0 [ml/100 g/min] and was found to be within the range of previous studies.

Arterial spin-labeled perfusion MRI in basic and clinical neuroscience

Arterial spin labeling (ASL) provides an endogenous and completely noninvasive tracer for the quantification of regional cerebral blood flow (CBF) with magnetic resonance imaging (MRI). Although the measurement of CBF has obvious utility in cerebrovascular disorders, because CBF is closely coupled to neural metabolism, ASL perfusion MRI has a broad range of potential applications as a biomarker of regional brain function in basic and clinical neuroscience. Over the past few years, ASL technology has improved considerably and the utility of ASL perfusion MRI as a diagnostic and research tool has been demonstrated. This review briefly covers ASL methodologies and clinical applications, while expanding on the use of ASL in human neuroscience research to elucidate patterns of resting brain function that correlate with genotype or phenotype (trait effects), or in response to exogenous manipulations of brain function with pharmacological agents or psychological tasks (state effects). ASL perfusion MRI provides a versatile biomarker of regional brain function that can be acquired as part of a multimodal MRI examination. Because ASL quantifies a physiological parameter, it should be useful for multisite or longitudinal studies.

Quantification of cerebral blood flow, cerebral blood volume, and blood–brain‐barrier leakage with DCE‐MRI

Dynamic susceptibility contrast MRI (DSC-MRI) is the current standard for the measurement of Cerebral Blood Flow (CBF) and Cerebral Blood Volume (CBV), but it is not suitable for the measurement of Extraction Flow (EF) and may not allow for absolute quantification. The objective of this study was to develop and evaluate a methodology to measure CBF, CBV, and EF from T1-weighted dynamic contrast-enhanced MRI (DCE-MRI). A two-compartment modeling approach was developed, which applies both to tissues with an intact and with a broken Blood-Brain-Barrier (BBB). The approach was evaluated using measurements in normal grey matter (GM) and white matter (WM) and in tumors of 15 patients. Accuracy and precision were estimated with simulations of normal brain tissue. All tumor and normal tissue curves were accurately fitted by the model. CBF (mL/100 mL/min) was 82 +/- 21 in GM and 23 +/- 14 in WM, CBV (mL/100 mL) was 2.6 +/- 0.8 in GM and 1.3 +/- 0.4 in WM. EF (mL/100 mL/min) was close to zero in GM (-0.009 +/- 0.05) and WM (-0.03 +/- 0.08). Simulations show an overlap between CBF values of WM and GM, which is eliminated when Contrast-to-Noise (CNR) is improved. The model provides a consistent description of tracer kinetics in all brain tissues, and an accurate assessment of perfusion and permeability in reference tissues. The measurement sequence requires optimization to improve CNR and the precision in the perfusion parameters. With this approach, DCE-MRI presents a promising alternative to DSC-MRI for quantitative bolus-tracking in the brain.

Absolute quantification of cerebral blood flow in neurologically normal volunteers: Dynamic‐susceptibility contrast MRI‐perfusion compared with computed tomography (CT)‐perfusion

To improve the reproducibility of arterial input function (AIF) registration and absolute cerebral blood flow (CBF) quantification in dynamic-susceptibility MRI-perfusion (MRP) at 1.5T, we rescaled the AIF by use of a venous output function (VOF). We compared CBF estimates of 20 healthy, elderly volunteers, obtained by computed tomography (CT)-perfusion (CTP) and MRP on two consecutive days. MRP, calculated without the AIF correction, did not result in any significant correlation with CTP. The rescaled MRP showed fair to moderate correlation with CTP for the central gray matter (GM) and the whole brain. Our results indicate that the method used for correction of partial volume effects (PVEs) improves MRP experiments by reducing AIF-introduced variance at 1.5T.

Frontal Assessment Battery and Brain Perfusion Imaging in Early Dementia

Background/Aims: The frontal assessment battery (FAB) is reported to be a useful tool for screening frontal function. However, the neural substrates involved remain to be elucidated. The aim of the present study was to identify the brain regions responsible for FAB performance in patients with early dementia. We sought a correlation between FAB scores and brain perfusion. Methods: A total of 117 subjects participated in this study (Alzheimer’s disease = 51, frontotemporal dementia = 14, vascular dementia = 13, dementia with Lewy bodies = 7, psychiatric disease = 7, mild cognitive impairment = 11, controls = 14). They underwent brain single photon emission computed tomography with ^99mTc-ethylcisteinate dimer, and we analyzed the data, using a regional cerebral blood flow (rCBF) quantification software program, 3DSRT (3-dimensional stereotaxic region of interest template). Results: FAB scores had a moderately positive correlation with left callosomarginal and precentral rCBF. Comparison of rCBF between high- and low-scoring FAB groups revealed that the latter showed significantly lower rCBF in the bilateral callosomarginal and left precentral regions. Conclusion: The results in this study suggest that the FAB mainly reflects the function of the callosomarginal and precentral segments, especially the left side, and that it might be a valid frontal lobe function test.

Variation in the shape of pulsed arterial spin labeling kinetic curves across the healthy human brain and its implications for CBF quantification

Arterial spin labeling (ASL) uses proximally inverted blood water spins as an endogenous contrast agent to measure blood perfusion in tissue. In this work pulsed ASL was used to measure the kinetic curves of cerebral blood flow (CBF) across eight anatomically based regions of interest (ROIs) in five normal healthy subjects. CBF estimates based on these data were compared when obtained using a single inversion time versus fitting a kinetic model to all 10 measured inversion times. CBF estimates were also compared when fitting to the 10 inversion time data using a standard two-parameter approach (CBF and bolus arrival time) or a more recently proposed three-parameter model (CBF, bolus arrival time, and arrival time dispersion). Variations in the shape of the kinetic curve were found across the brain that were consistent across subjects. The arrival time in the occipital ROI was found to be long enough to lead to underestimation of the CBF when using a single inversion time of 1.5 s. In four out of the eight ROIs there was significant underestimation of CBF using the standard two-parameter model compared to the three-parameter approach. These results have important implications for the development of a robust, quantitative ASL protocol.

Reference-based Maximum Upslope: A CBF Quantification Method without Using Arterial Input Function in Dynamic Susceptibility Contrast MRI

We assessed errors in cerebral blood flow (CBF) obtained from our proposed reference-based method without using arterial input function (AIF) indices in dynamic susceptibility contrast (DSC) magnetic resonance imaging (MRI). We calculated CBF and the referential tissue-related ratio (CBFratio) using numerical simulation and 3 nondeconvolution methods and a deconvolution method of block-circulant singular value decomposition (cSVD). We compared errors with and without simulated noise as parameters of mean transit time (MTT), AIF delay and temporal resolution, and clinical DSC-MRI maps. The errors in CBF obtained using maximum upslope (US) were smallest among the nondeconvolution methods and almost equivalent to errors in the cSVD method under practical imaging conditions. In addition, errors in the CBFratio obtained using reference-based US (Ref-US) referring to white matter were smallest, even compared to all errors in CBF and CBFratio. The Ref-US method introduced less error than the cSVD method, especially at low flow rates, was further robust against AIF noise and coarse temporal resolution, and was comparably robust against transit delay. In pixel-by-pixel correlations between absolute value maps for US and for cSVD-CBF in clinical DSC-MRI, those correlation coefficients (r) between the 2 maps were stable, r > 0.9, despite variation in the slopes of the linear regression line, so the 2 CBFratio maps were visually well correlated in any case. The Ref-US technique without AIF measurement can become a practical perfusion methodology for DSC-MRI in patients even with acute stroke because it balances robustness with systematic and random errors and it is simply performed.

The Use of Quantitative Magnetic Resonance Perfusion for Assessment of CBF in The Perioperative Management of Carotid Stenosis: Case Illustration

Objective and Importance: Internal Carotid Artery (ICA) stenosis is a common condition with a high preva- lence in the normal population and carries a high risk of stroke. Hemodynamic impairment has been proven to be a power- ful and independent risk factor for stroke. Understanding the hemodynamics beyond a stenosis may play a role in select- ing patients who would benefit from treatment, determining the success of the treatment, and monitoring for disease recur- rence. Our group has developed a unique quantitative approach to MR perfusion. We report on the use of Quantitative Magnetic Resonance Perfusion (MRP) for assessment of Cerebral Blood Flow (CBF) pre- and post- Carotid Angioplasty and Stenting for symptomatic ICA stenosis. Clinical Presentation: A 71-year-old female with significant comorbidities presented with two episodes of left transient ischemic attacks (TIAs) over the course of one month related to high grade left ICA stenosis. Preoperative quantitative MRP showed asymmetry in CBF between the two hemispheres. Carotid angioplasty and stenting was recommended. Intervention: Left ICA angioplasty and stenting was performed and reduced the stenosis to <10%. Quantitative MRP done after the procedure revealed improved CBF to the affected side and normalization in the asymmetry of perfusion between the two hemispheres. Quantitative MRP values showed that affected regions were hypoperfused, but flow was sufficiently maintained so as to avoid infarct. Conclusion: Relative MRP images allowed us to elucidate improvement in perfusion resulting form carotid angioplasty and stenting. This novel quantitative MRP allows quantification of CBF and the potential to provide additional informa- tion on the degree of hemodynamic compromise.

Arterial spin‐labeled perfusion combined with segmentation techniques to evaluate cerebral blood flow in white and gray matter of children with sickle cell anemia

Changes in cerebral perfusion are an important feature of the pathophysiology of sickle cell anemia (SCA); cerebrovascular ischemia occurs frequently and leads to neurocognitive deficits, silent infarcts, and overt stroke. Non-invasive MRI methods to measure cerebral blood flow (CBF) by arterial spin labeling (ASL) afford new opportunities to characterize disease- and therapy-induced changes in cerebral hemodynamics in patients with SCA. Recent studies have documented elevated gray matter (GM) CBF in untreated children with SCA, but no measurements of white matter (WM) CBF have been reported. Pulsed ASL with automated brain image segmentation-classification techniques were used to determine the CBF in GM, WM, and abnormal white matter (ABWM) of 21 children with SCA, 18 of whom were receiving hydroxyurea therapy. GM and WM CBF were highly associated (R(2) = 0.76, P < 0.0001) and the GM to WM CBF ratio was 1.6 (95% confidence interval: 1.43-1.83). Global GM CBF in our treated cohort was 87 +/- 24 mL/min/100 g, a value lower than previously reported in untreated patients with SCA. CBF was elevated in normal appearing WM (43 +/- 14 mL/min/100 g) but decreased in ABWM (6 +/- 12 mL/min/100 g), compared to published normal pediatric controls. Hemispheric asymmetry in CBF was noted in most patients. These perfusion measurements suggest that hydroxyurea may normalize GM CBF in children with SCA, but altered perfusion in WM may persist. This novel combined approach for CBF quantification will facilitate prospective studies of cerebral vasculopathy in SCA, particularly regarding the effects of treatments such as hydroxyurea.

Neuroimaging in Ischemia and Infarction

The authors provide an overview of current clinical neuroimaging techniques for acute ischemic stroke. The pathophysiology of ischemic stroke is briefly reviewed, especially as it pertains to cerebral blood flow. There are three important goals that must be met in the imaging of an acute ischemic stroke: (1) to quantitate the extent of infarction already present; (2) to quantitate the amount of salvageable brain remaining; and (3) to identify the presence of arterial stenosis or occlusion that is both responsible for the stroke and potentially amenable to treatment. Methods of quantifying the degree of infarction, by magnetic resonance imaging or computed tomography, are compared. Techniques for measuring cerebral blood flow, to quantify tissue at risk, are detailed and compared. The quantification of cerebral blood flow is discussed in detail. Methods of visualizing the cerebral circulation are illustrated.