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

Purpose

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).

Methods

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.

Results

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.

Conclusions

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.     

An alternative viewpoint of the similarities and differences of SVD and FT deconvolution algorithms used for quantitative MR perfusion studies

Quantitative cerebral blood flow (CBF) values can be determined from residue function estimates obtained from magnetic resonance dynamic susceptibility contrast (DSC) perfusion studies using a variety of deconvolution approaches. However, there are significant differences between the CBF estimates obtained, differences that are not simply due to minor details of the implementation of the algorithms. The standard singular value decomposition (sSVD) shows a variation of CBF values with arterial-tissue delay (ATD) not present with the Fourier transform deconvolution algorithm. Fourier transform deconvolution and the newly suggested delay-invariant SVD algorithm implementations provide CBF estimates whose accuracy changes with tissue mean transit times (MTTs). Techniques combining sSVD with deliberate ATD manipulation have been proposed to compensate for this inaccuracy. Other studies indicate that CBF changes related to slice position in a multislice study, and other experimental factors, can be reduced using interpolative deconvolution algorithms. In this review, we use both time-domain and frequency-domain analysis to show the underlying theoretical relationships between these many approaches to obtain "the best" CBF estimate. This model allows us to better understand the similarities and differences, advantages and disadvantages between these variants of the deconvolution algorithms used in DSC perfusion studies.     

Model-free arterial spin labelling for cerebral blood flow quantification: introduction of regional arterial input functions identified by factor analysis

PURPOSE: To identify regional arterial input functions (AIFs) using factor analysis of dynamic studies (FADS) when quantification of perfusion is performed using model-free arterial spin labelling. MATERIAL AND METHODS: Five healthy volunteers and one patient were examined on a 3-T Philips unit using quantitative STAR labelling of arterial regions (QUASAR). Two sets of images were retrieved, one where the arterial signal had been crushed and another where it was retained. FADS was applied to the arterial signal curves to acquire the AIFs. Perfusion maps were obtained using block-circulant SVD deconvolution and regional AIFs obtained by FADS. In the volunteers, the ASL experiment was repeated within 24 h. The patient was also examined using dynamic susceptibility contrast MRI. RESULTS: In the healthy volunteers, CBF was 64+/-10 ml/[min 100 g] (mean+/-S.D.) in GM and 24+/-4 ml/[min 100 g] in WM, while the mean aBV was 0.94% in GM and 0.25% in WM. DISCUSSION: Good CBF image quality and reasonable quantitative CBF values were obtained using the combined QUASAR/FADS technique. We conclude that FADS may be a useful supplement in the evaluation of ASL data using QUASAR.     

Quantitative perfusion imaging in carotid artery stenosis using dynamic susceptibility contrast-enhanced magnetic resonance imaging

Quantitative, multislice dynamic susceptibility contrast-enhanced MRI perfusion measurements were used to determine the patterns of cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), and normalized first moment of the tissue deltaR2-time curve (N) in 11 subjects with carotid artery occlusion or stenosis. MTT correlated with degree of carotid stenosis, whereas a range of alterations in CBF and CBV were found presumably reflecting variables degrees of collateral flow. There was no significant correlation between MRI and SPET flow perfusion measurements, with increasing disparity between the two techniques at higher inter-hemispheric flow ratios. The effect of obtaining the arterial input function (AIF) from the middle cerebral artery (MCA) ipsilateral or contralateral to the stenosis was determined. Despite the use of an AIF from the MCA, which is distal to the circle of Willis, and hence the major sources of collateral supply, there was still some extra dispersion of the contrast agent bolus due to differences in arrival time.     

Deconvolution with simple extrapolation for improved cerebral blood flow measurement in dynamic susceptibility contrast magnetic resonance imaging during acute ischemic stroke

Magnetic resonance (MR) perfusion imaging is a clinical technique for measuring brain blood flow parameters during stroke and other ischemic events. Ischemia in brain tissue can be difficult to accurately measure or visualize when using MR-derived cerebral blood flow (CBF) maps. The deconvolution techniques used to estimate flow can introduce a mean transit time-dependent bias following application of noise stabilization techniques. The underestimation of the CBF values, greatest in normal tissues, causes a decrease in the image contrast observed in CBF maps between normally perfused and ischemic tissues; resulting in ischemic areas becoming less conspicuous. Through application of the proposed simple extrapolation technique, CBF biases are reduced when missing high-frequency signal components in the MR data removed during deconvolution noise stabilization are restored. The extrapolation approach was compared with other methods and showed a statistically significant increase in image contrast in CBF maps between normal and ischemic tissues for white matter (P<.05) and performed better than most other methods for gray matter. Receiver operator characteristic curve analysis demonstrated that extrapolated CBF maps better-detected penumbral regions. Extrapolated CBF maps provided more accurate CBF estimates in simulations, suggesting that the approach may provide a better prediction of outcome in the absence of treatment.     

Cerebral blood flow estimation from perfusion-weighted MRI using FT-based MMSE filtering method

INTRODUCTION: Perfusion-weighted MRI can be used for estimating blood flow parameters using bolus tracking technique based on dynamic susceptibility contrast MRI. In order to extract flow parameters, several deconvolution techniques have been proposed, of which the singular value decomposition (SVD) and Fourier transform (FT)-based techniques are more popular and widely used. In this work, an FT-based method has been proposed that involves derivation of an optimal shaped filter (defined as a filter function) estimated using minimum mean-squared error (MMSE) technique in the frequency domain. The proposed technique has been compared with the well-established SVD technique using simulation experiments. SIMULATION METHODS: Simulation was performed in multiple steps. An arterial input function (AIF) was first defined based on a certain blood flow value. The T2* signal change was then derived from this AIF, and noise was added to the signal. Then, a unique and optimal shaped filter function Phi(f) was derived in order to obtain the best estimate of scaled residue function. One way is by minimizing the mean-squared error between the noiseless and noisy scaled residue function, i.e., using an MMSE method. The effect of low and moderate noise and distorted AIF on cerebral blood flow (CBF) estimates was obtained by using FT-based MMSE method. Results were compared with the SVD technique. In this work, SVD technique was assumed to be the standard reference deconvolution technique. RESULTS AND DISCUSSION: For low-noise condition, the FT-based technique was more stable than the SVD technique, while for moderate noise, both techniques consistently underestimated CBF. SVD technique was found to be more stable in presence of AIF distortions. However, SVD technique was found to be unstable due to AIF delay compared to the FT-based MMSE method. The shaped filter function was found to be sensitive to effect of AIF distortions.     

Aspects on the accuracy of cerebral perfusion parameters obtained by dynamic susceptibility contrast MRI: a simulation study

Several studies have indicated that deconvolution based on singular value decomposition (SVD) is a robust concept for retrieval of cerebral blood flow in dynamic susceptibility contrast (DSC) MRI. However, the behavior of the technique under typical experimental conditions has not been completely investigated. In the present study, cerebral perfusion was simulated using different temporal resolutions, different signal-to-noise ratios (S/Ns), different shapes of the arterial input function (AIF), different signal drops, and different cut-off levels in the SVD deconvolution. Using Zierler's area-to-height relationship in combination with the central volume theorem, calculations of regional cerebral blood volume (rCBV), regional cerebral blood flow (rCBF), and regional mean transit time (rMTT) were accomplished, based on simulated DSC-MRI signal curves corresponding to artery, gray matter (GM), white matter (WM), and ischemic tissue. Gaussian noise was added to the noise-free signal curves to generate different S/Ns. We studied image time intervals of 0.5, 1.0, 1.5, 2.0, 2.5, and 3.0 s, as well as different degrees of signal decrease. The singular-value threshold in the SVD procedure and the shape of the AIF were also varied. Increased rCBF was seen when noise was added, especially for rCBF in WM at the larger image time intervals. The rCBF showed large standard deviations using a low threshold value. A prolonged time interval led to a lower absolute value of rCBF both in GM and WM, and a low/broad AIF also underestimated the rCBF. When a larger maximal signal decrease was assumed, smaller standard deviations were observed. No systematic change of the average rCBV was observed with increasing noise or with increasing image time interval. At S/N = 40, a low cut-off value resulted in an rCBF that was closer to the true value. Furthermore, at low S/N it was difficult to differentiate ischemic tissue from WM.     

Effects of blood ΔR2* non-linearity on absolute perfusion quantification using DSC-MRI: Comparison with Xe-133 SPECT

Purpose

To evaluate whether a non-linear blood ΔR₂*-versus-concentration relationship improves quantitative cerebral blood flow (CBF) estimates obtained by dynamic susceptibility contrast (DSC) MRI in a comparison with Xe-133 SPECT CBF in healthy volunteers.

Material and Methods

Linear as well as non-linear relationships between ΔR₂* and contrast agent concentration in blood were applied to the arterial input function (AIF) and the venous output function (VOF) from DSC-MRI. To reduce partial volume effects in the AIF, the arterial time integral was rescaled using a corrected VOF scheme.

Results

Under the assumption of proportionality between the two modalities, the relationship CBF(MRI) = 0.58CBF(SPECT) (r = 0.64) was observed using the linear relationship and CBF(MRI) = 0.51CBF(SPECT) (r = 0.71) using the non-linear relationship.

Discussion

A smaller ratio of the VOF time integral to the AIF time integral and a somewhat better correlation between global DSC-MRI and Xe-133 SPECT CBF estimates were observed using the non-linear relationship. The results did not, however, confirm the superiority of one model over the other, potentially because realistic AIF signal data may well originate from a combination of blood and surrounding tissue.     

Application of FT-based MMSE deconvolution method for cerebral blood flow measurement in patients with leukoaraiosis

Introduction

The bolus-tracking (BT) technique is the most popular perfusion-weighted (PW) dynamic susceptibility contrast MRI method used for estimating cerebral blood flow (CBF), cerebral blood volume and mean transit time. The BT technique uses a convolution model that establishes the input–output relationship between blood flow and the vascular tracer concentration. Singular value decomposition (SVD)- and Fourier transform (FT)-based deconvolution methods are popular and widely used for estimating PW MRI parameters. However, from the published literature, it appears that SVD is more widely accepted than other methods. In a previous article, an FT-based minimum mean-squared error (MMSE) technique was proposed and simulation experiments were performed to compare it with the well-established circular SVD (oSVD) method. In this study, the FT-based MMSE method has been used to estimate relative CBF (rCBF) in 13 patients with white matter lesions (WMLs) (leukoaraiosis), and results are compared with the widely used oSVD method.

Materials and Methods

Thirteen patients with leukoaraiosis were imaged on a 1.5-T Siemens whole-body scanner. After acquiring the localizer and structural scans consisting of FLAIR (fluid attenuated with inversion recovery), T₁-weighted and T₂-weighted images, perfusion study was implemented as part of the MRI protocol. For each patient and method, two values were calculated: (a) rCBF for normal white matter (NWM) ROI, obtained by dividing the average CBF value in NWM ROI with average CBF in gray matter (GM) ROI, and (b) rCBF for WML ROI, obtained by dividing the average CBF value in WML ROI with average CBF in GM ROI. Results for the two deconvolution methods were computed.

Results and Discussion

A significant (P<.05) decrease in estimated rCBF was observed in the WML in all the patients using the MMSE method, while for the oSVD method, the decrease was observed in all but one patient. Initial results suggest that the MMSE method is comparable to the oSVD method for estimating rCBF in NMW while it may be better than oSVD for estimating rCBF in lesions of low flow. Studies involving a larger patient population may be required to further validate the findings of this work.     

Reduced distortion artifact whole brain CBF mapping using blip-reversed non-segmented 3D echo planar imaging with pseudo-continuous arterial spin labeling

PurposeTo implement and evaluate interleaved blip-up, blip-down, non-segmented 3D echo planar imaging (EPI) with pseudo-continuous arterial spin labeling (pCASL) and post-processing for reduced susceptibility artifact cerebral blood flow (CBF) maps.Materials and methods3D EPI non-segmented acquisition with a pCASL labeling sequence was modified to include alternating k-space coverage along phase encoding direction (referred to as “blip-reversed”) for alternating dynamic acquisitions of control and label pairs. Eight volunteers were imaged on a 3T scanner. Images were corrected for distortion using spatial shifting transformation of the underlying field map. CBF maps were calculated and compared with maps obtained without blip reversal using matching gray matter (GM) images from a high resolution 3D scan. Additional benefit of using the correction for alternating blip-up and blip-down acquisitions was assessed by comparing to corrected blip-up only and corrected blip-down only CBF maps. Matched Student t-test of overlapping voxels for the eight volunteers was done to ascertain statistical improvement in distortion.ResultsMean CBF value in GM for the eight volunteers from distortion corrected CBF maps was 50.8 ± 9.9 ml/min/100 gm tissue. Corrected CBF maps had 6.3% and 4.1% more voxels in GM when compared with uncorrected blip up (BU) and blip down (BD) images, respectively. Student t-test showed significant reduction in distortion when compared with blip-up images and blip-down images (p < 0.001). When compared with corrected BU and corrected BD only CBF maps, BU and BD corrected maps had 2.3% and 1% more voxels (p = 0.006 and 0.04, respectively).ConclusionPseudo-continuous arterial spin labeling with non-segmented 3D EPI acquisition using alternating blip-reversed k-space traversal and distortion correction provided significantly better matching GM CBF maps. In addition, employing alternating blip-reversed acquisitions during pCASL acquisition resulted in statistically significant improvement over corrected blip-up and blip-down CBF maps.     

Cerebral perfusion alterations in epileptic patients during peri-ictal and post-ictal phase: PASL vs DSC-MRI

Non-invasive pulsed arterial spin labeling (PASL) MRI is a method to study brain perfusion that does not require the administration of a contrast agent, which makes it a valuable diagnostic tool as it reduces cost and side effects. The purpose of the present study was to establish the viability of PASL as an alternative to dynamic susceptibility contrast (DSC-MRI) and other perfusion imaging methods in characterizing changes in perfusion patterns caused by seizures in epileptic patients. We evaluated 19 patients with PASL. Of these, the 9 affected by high-frequency seizures were observed during the peri-ictal period (within 5 hours since the last seizure), while the 10 patients affected by low-frequency seizures were observed in the post-ictal period. For comparison, 17/19 patients were also evaluated with DSC-MRI and CBF/CBV. PASL imaging showed focal vascular changes, which allowed the classification of patients in three categories: 8 patients characterized by increased perfusion, 4 patients with normal perfusion and 7 patients with decreased perfusion. PASL perfusion imaging findings were comparable to those obtained by DSC-MRI. Since PASL is a) sensitive to vascular alterations induced by epileptic seizures, b) comparable to DSC-MRI for detecting perfusion asymmetries, c) potentially capable of detecting time-related perfusion changes, it can be recommended for repeated evaluations, to identify the epileptic focus, and in follow-up and/or therapy-response assessment.     

Intracranial vascular feature changes in time of flight MR angiography in patients undergoing carotid revascularization surgery

PurposeTo characterize the intracranial vascular features extracted from time of flight (TOF) images and their changes from baseline to follow-up in patients undergoing carotid revascularization, using arterial spin labeling (ASL) cerebral blood flow (CBF) measurement as a reference.MethodsIn this retrospective study, brain TOF and ASL images of 99 subjects, acquired before, within 48 h, and/or 6 months after, carotid revascularization surgery were analyzed. TOF images were analyzed using a custom software (iCafe) to quantify intracranial vascular features, including total vessel length, total vessel volume, and number of branches. Mean whole-brain CBF was calculated from ASL images. ASL scans showing low ASL signal in the entire flow territory of an internal carotid artery (ICA), which may be caused by labeling failure, were excluded. Changes and correlations between time points were analyzed separately for TOF intracranial vascular features and ASL CBF.ResultsSimilar to ASL CBF, TOF vascular features (i.e. total vessel length, total vessel volume and number of branches) increased dramatically from baseline to post-surgery, then returned to a level slightly higher than the baseline in long-term follow-up (All P < 0.05). Correlation between time points was observed for all three TOF vascular features but not for ASL CBF.ConclusionIntracranial vascular features, including total vessel length, total vessel volume and number of branches, extracted from TOF images are useful in detecting brain blood flow changes induced by carotid revascularization surgery.     

Reliability and reproducibility of perfusion MRI in cognitively normal subjects

Arterial spin labeling (ASL) magnetic resonance imaging (MRI) is becoming a popular method for measuring perfusion due to its ability of generating perfusion maps noninvasively. This allows for frequent repeat scanning, which is especially useful for follow-up studies. However, limited information is available regarding the reliability and reproducibility of ASL perfusion measurements. Here, the reliability and reproducibility of pulsed ASL was investigated in an elderly population to determine the variation in perfusion among cognitively normal individuals in different brain structures. Intraclass correlation coefficients (ICC) and within-subject variation coefficients (wsCV) were used to estimate reliability and reproducibility over a period of 1 year. Twelve cognitively normal subjects (75.5±5.3 years old, six male and six female) were scanned four times (at 0, 3, 6 and 12 months). No significant difference in cerebral blood flow (CBF) was found over this period. CBF values ranged from 46 to 53 ml/100 g per minute in the medial frontal gyrus (MFG) and from 40 to 44 ml/100 g per minute over all gray matter regions in the superior part of the brain. Data obtained from the first two scans were processed by two readers and showed high reliability (ICC >0.97) and reproducibility (wsCV <6%). However, over the total period of 1 year, reliability reduced to a moderate level (ICC=0.63–0.74) with wsCVs of gray matter, left MFG, right MFG of 13.5%, 12.3%, and 15.4%, respectively. In conclusion, measurement of CBF with pulsed ASL provided good agreement between inter-raters. A moderate level of reliability was obtained over a 1-year period, which was attributed to variance in slice positioning and coregistration. As such pulsed ASL has the potential to be used for CBF comparison in longitudinal studies.     

Adaptive total linear least square method for quantification of mean transit time in brain perfusion MRI

Absolute quantification of cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) are of great relevance for clinical applications. One of the widely used methods for quantification of these parameters is gamma-variate fitting. Traditional nonlinear regression methods for gamma-variate fitting are inaccurate and computationally demanding. In this study, we developed an adaptive total least square method (ATSSL) to fit a gamma-variate function to the delayed concentration-time course. For each concentration-time curve, the beginning and ending time point of the curve are adaptively determined online. After the curves were fitted, a robust method for automatically determination of arterial input function (AIF) from whole and region of interest (ROI) was developed. Using the obtained AIF and fitted gamma-variate concentration-time curve, the MTT, CBV, and CBF were calculated by utilizing singular value decomposition algorithm. Computer simulations show that the suggested method is adaptive, reliable, and insensitive to noise. Comparison with the traditional nonlinear regression method indicated that the presented method is more accurate and faster to determine the CBV, CBF and MTT.     

Impacts of dispersion maps on nonlinear distortion in distributed Raman amplified multi-span systems

The influences of dispersion maps on three major nonlinear effects (SPM, XPM and SRS) in distributed Raman amplified fiber transmission systems with periodic dispersion compensation are numerically investigated at identical nonlinear phase shift. The results show that compared with lumped amplification, distributed amplification tends to enhance the SPM/XPM induced penalties provided per span complete DC is used. However, these performance differences can be canceled out by means of optimal dispersion managements. Moreover, distributed Raman amplification can change the optimal dispersion maps for XPM effects. On the other hand, the impacts of SRS crosstalk are mainly determined by wavelength spacing and walk-off parameter, and the effects of dispersion management are quite limited. For a system with properly designed fiber dispersion characteristics, SRS induced waveform distortion can be well suppressed.     

Effects of echo time variation on perfusion assessment using dynamic susceptibility contrast MR imaging at 3 tesla

The implications of changing the echo time of a gradient-echo echo planar imaging sequence applied to dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) for perfusion imaging at 3T were investigated. Four echo times in the range of 21 to 45 ms were examined in a total of 17 patients who received a dose of 0.1 mmol/kg bodyweight Gadobutrol (Gadovist, 1.0 mmol/ml). As the primary optimization parameter, the concentration-to-noise ratio (SNRc) was selected as it takes effects of variations in baseline as well as in signal drop into account. In an analysis of gray matter, white matter and arterial regions of interest, SNRc showed the highest values for the shortest applied echo time in all cases. Maps of regional cerebral blood volume (rCBV) and blood flow (rCBF) were calculated using deconvolution based on singular value decomposition. The quality of rCBF and rCBV images was judged to be good or excellent in all cases, independent of the echo time. Calculated gray matter/white matter ratios of rCBF and rCBV displayed no significant dependence on the applied echo time. Considering the better SNRc and arterial signal saturation aspects, we found that the shortest investigated echo time was the superior one. We thus suggest that short echo times should be applied, taking technical limitations and clinical demands into consideration.     

Quantitative multi-modal functional MRI with blood oxygenation level dependent exponential decays adjusted for flow attenuated inversion recovery (BOLDED AFFAIR)

A magnetic resonance imaging (MRI) method is described that allows interleaved measurements of transverse (R(2)(*) and R(2)) and longitudinal (R(1)) relaxation rates of tissue water in conjunction with spin labeling. The image-contrasts are intrinsically blood oxygenation level dependent (BOLD) and cerebral blood flow (CBF) weighted, but each contrast is made quantitative by two echo time (TE) and inversion recovery time (TIR) acquisitions with gradient echo (GE) and spin echo (SE) weighted echo-planar imaging (EPI). The EPI data were acquired at 7 Tesla with nominal spatial resolution of 430 x 430 x 1000 microm(3) in rat brain in vivo. The method is termed as blood oxygenation level dependent exponential decays adjusted for flow attenuated inversion recovery (BOLDED AFFAIR) and allows acquisition of R(2)(*), R(2), and CBF maps in an interleaved manner within approximately 12 minute. The basic theory of the method, associated experimental/systematic errors, and temporal restrictions are discussed. The method is validated by comparison of multi-modal maps obtained by BOLDED AFFAIR (i.e., two TE and TIR values with GE and SE sequences) and conventional approach (i.e., multiple TE and TIR values with GE and SE sequences) during varied levels of whole brain activity. Preliminary functional data from a rat forepaw stimulation model demonstrate the feasibility of this method for functional MRI (fMRI) studies. It is expected that with appropriate precautions this method in conjunction with contrast agent-based MRI has great potential for quantitative fMRI studies of mammalian cortex.     

MRI based diffusion and perfusion predictive model to estimate stroke evolution.

In this study we present a novel automated strategy for predicting infarct evolution, based on MR diffusion and perfusion images acquired in the acute stage of stroke. The validity of this methodology was tested on novel patient data including data acquired from an independent stroke clinic. Regions-of-interest (ROIs) defining the initial diffusion lesion and tissue with abnormal hemodynamic function as defined by the mean transit time (MTT) abnormality were automatically extracted from DWI/PI maps. Quantitative measures of cerebral blood flow (CBF) and volume (CBV) along with ratio measures defined relative to the contralateral hemisphere (r(a)CBF and r(a)CBV) were calculated for the MTT ROIs. A parametric normal classifier algorithm incorporating these measures was used to predict infarct growth. The mean r(a)CBF and r(a)CBV values for eventually infarcted MTT tissue were 0.70 +/- 0.19 and 1.20 +/- 0.36. For recovered tissue the mean values were 0.99 +/- 0.25 and 1.87 +/- 0.71, respectively. There was a significant difference between these two regions for both measures (p < 0.003 and p < 0.001, respectively). Mean absolute measures of CBF (ml/100g/min) and CBV (ml/100g) for the total infarcted territory were 33.9 +/- 9.7 and 4.2 +/- 1.9. For recovered MTT tissue, the mean values were 41.5 +/- 7.2 and 5.3 +/- 1.2, respectively. A significant difference was also found for these regions (p < 0.009 and p < 0.036, respectively). The mean measures of sensitivity, specificity, positive and negative predictive values for modeling infarct evolution for the validation patient data were 0.72 +/- 0.05, 0.97 +/- 0.02, 0.68 +/- 0.07 and 0.97 +/- 0.02. We propose that this automated strategy may allow possible guided therapeutic intervention to stroke patients and evaluation of efficacy of novel stroke compounds in clinical drug trials.     

Validation study of a pulsed arterial spin labeling technique by comparison to perfusion computed tomography

Abnormalities in cerebral blood flow (CBF) are believed to play a significant role in the development of major neonatal neuropathologies. One approach that would appear ideal for measuring CBF in this fragile age group is arterial spin labeling (ASL) since ASL techniques are noninvasive and quantitative. The purpose of this study was to assess the accuracy of a pulsed ASL method implemented on a 3-T scanner dedicated to neonatal imaging. Cerebral blood flow was measured in nine neonatal piglets, the ASL–CBF measurements were acquired at two inversion times (TI) (1200 and 1700 ms), and CBF was measured by perfusion computed tomography (pCT) for validation. Perfusion CT also provided images of cerebral blood volume, which were used to identify large blood vessels, and contrast arrival time, which were used to assess differences in arterial transit times between gray and white matter. Good agreement was found between gray matter CBF values from pCT (76±1 ml/min per 100 g) and ASL at TI=1700 ms (73±1 ml/min per 100 g). At TI=1200 ms, ASL overestimated CBF (91±2 ml/min per 100 g), which was attributed to substantial intravascular signal. No significant differences in white matter CBF from pCT and ASL were observed (average CBF=60±1 ml/min per 100 g), nor was there any difference in contrast arrival times for gray and white matter (0.95±0.04 and 0.99±0.03 s, respectively), which suggests that the arterial transit times for ASL were the same in this animal model. This study verified the accuracy of the implemented ASL technique and showed the value of using pCT to study other factors that can affect ASL–CBF measurements.     

A comparison study between the saturation-recovery-T1 and CASL MRI methods for quantitative CBF imaging

The saturation-recovery (SR)-T₁ MRI method for quantitatively imaging cerebral blood flow (CBF) change (ΔCBF) concurrently with the blood oxygenation level dependence (BOLD) alteration has been recently developed and validated by simultaneous measurement of relative CBF change using laser Doppler flowmetry (LDF) in rats at 9.4T. In this study, ΔCBF induced by mildly transient hypercapnia and measured by the SR-T₁ MRI method was rigorously compared with an established perfusion MRI method—continuous arterial spin labeling (CASL) approach in normal and preclinical middle cerebral artery occlusion (MCAo) rat models. The results show an excellent agreement between ΔCBF values measured with these two imaging methods. Moreover, the intrinsic longitudinal relaxation rate (R₁^int) was experimentally determined in vivo in normal rat brains at 9.4T by comparing two independent measures of the apparent longitudinal relaxation rate (R₁^app) and CBF measured by the CSAL approach across a wide range of perfusion. In turn, the R₁^int constant can be employed to calculate the CBF value based on the R₁^app measurement in healthy brain. This comparison study validates the fundamental relationship for linking brain tissue water R₁^app and cerebral perfusion, demonstrates the feasibility of imaging and quantifying both CBF and its change using the SR-T₁ MRI method in vivo.