Quantification of blood-brain barrier water exchange and permeability with multidelay diffusion-weighted pseudo-continuous arterial spin labeling.

PURPOSE: To present a pulse sequence and mathematical models for quantification of blood-brain barrier water exchange and permeability. METHODS: Motion-compensated diffusion-weighted (MCDW) gradient-and-spin echo (GRASE) pseudo-continuous arterial spin labeling (pCASL) sequence was proposed to acquire intravascular/extravascular perfusion signals from five postlabeling delays (PLDs, 1590-2790 ms). Experiments were performed on 11 healthy subjects at 3 T. A comprehensive set of perfusion and permeability parameters including cerebral blood flow (CBF), capillary transit time (τc ), and water exchange rate (kw ) were quantified, and permeability surface area product (PSw ), total extraction fraction (Ew ), and capillary volume (Vc ) were derived simultaneously by a three-compartment single-pass approximation (SPA) model on group-averaged data. With information (i.e., Vc and τc ) obtained from three-compartment SPA modeling, a simplified linear regression of logarithm (LRL) approach was proposed for individual kw quantification, and Ew and PSw can be estimated from long PLD (2490/2790 ms) signals. MCDW-pCASL was compared with a previously developed diffusion-prepared (DP) pCASL sequence, which calculates kw by a two-compartment SPA model from PLD = 1800 ms signals, to evaluate the improvements. RESULTS: Using three-compartment SPA modeling, group-averaged CBF = 51.5/36.8 ml/100 g/min, kw = 126.3/106.7 min-1 , PSw = 151.6/93.8 ml/100 g/min, Ew = 94.7/92.2%, τc = 1409.2/1431.8 ms, and Vc = 1.2/0.9 ml/100 g in gray/white matter, respectively. Temporal SNR of MCDW-pCASL perfusion signals increased 3-fold, and individual kw maps calculated by the LRL method achieved higher spatial resolution (3.5 mm3 isotropic) as compared with DP pCASL (3.5 × 3.5 × 8 mm3 ). CONCLUSION: MCDW-pCASL allows visualization of intravascular/extravascular ASL signals across multiple PLDs. The three-compartment SPA model provides a comprehensive measurement of blood-brain barrier water dynamics from group-averaged data, and a simplified LRL method was proposed for individual kw quantification.

caliPER: A software for blood-free parametric Patlak mapping using PET/MRI input function.

Routine clinical use of absolute PET quantification techniques is limited by the need for serial arterial blood sampling for input function and more importantly by the lack of automated pharmacokinetic analysis tools that can be readily implemented in clinic with minimal effort. PET/MRI provides the ability for absolute quantification of PET probes without the need for serial arterial blood sampling using image-derived input functions (IDIFs). Here we introduce caliPER, a modular and scalable software for simplified pharmacokinetic modeling of PET probes with irreversible uptake or binding based on PET/MR IDIFs and Patlak Plot analysis. caliPER generates regional values or parametric maps of net influx rate (Ki) using reconstructed dynamic PET images and anatomical MRI aligned to PET for IDIF vessel delineation. We evaluated the performance of caliPER for blood-free region-based and pixel-wise Patlak analyses of [18F] FDG by comparing caliPER IDIF to serial arterial blood input functions and its application in imaging brain glucose hypometabolism in Frontotemporal dementia. IDIFs corrected for partial volume errors including spill-out and spill-in effects were similar to arterial blood input functions with a general bias of around 6-8%, even for arteries <5 mm. The Ki and cerebral metabolic rate of glucose estimated using caliPER IDIF were similar to estimates using arterial blood sampling (<2%) and within limits of whole brain values reported in literature. Overall, caliPER is a promising tool for irreversible PET tracer quantification and can simplify the ability to perform parametric analysis in clinical settings without the need for blood sampling.

Using simultaneous PET/MRI to compare the accuracy of diagnosing frontotemporal dementia by arterial spin labelling MRI and FDG-PET.

PURPOSE: The clinical utility of FDG-PET in diagnosing frontotemporal dementia (FTD) has been well demonstrated over the past decades. On the contrary, the diagnostic value of arterial spin labelling (ASL) MRI - a relatively new technique - in clinical diagnosis of FTD has yet to be confirmed. Using simultaneous PET/MRI, we evaluated the diagnostic performance of ASL in identifying pathological abnormalities in FTD (FTD) to determine whether ASL can provide similar diagnostic value as FDG-PET. METHODS: ASL and FDG-PET images were compared in 10 patients with FTD and 10 healthy older adults. Qualitative and quantitative measures of diagnostic equivalency were used to determine the diagnostic utility of ASL compared to FDG-PET. Sensitivity, specificity, and inter-rater reliability were calculated for each modality from scores of subjective visual ratings and from analysis of regional mean values in thirteen a priori regions of interest (ROI). To determine the extent of concordance between modalities in each patient, individual statistical maps generated from comparison of each patient to controls were compared between modalities using the Jaccard similarity index (JI). RESULTS: Visual assessments revealed lower sensitivity, specificity and inter-rater reliability for ASL (66.67%/62.12%/0.2) compared to FDG-PET (88.43%/90.91%/0.61). Across all regions, ASL performed lower than FDG-PET in discriminating patients from controls (areas under the receiver operating curve: ASL = 0.75 and FDG-PET = 0.87). In all patients, ASL identified patterns of reduced perfusion consistent with FTD, but areas of hypometabolism exceeded hypoperfused areas (group-mean JI = 0.30 ± 0.22). CONCLUSION: This pilot study demonstrated that ASL can detect similar spatial patterns of abnormalities in individual FTD patients compared to FDG-PET, but its sensitivity and specificity for discriminant diagnosis of a patient from healthy individuals remained unmatched to FDG-PET. Further studies at the individual level are required to confirm the clinical role of ASL in FTD management.

Water Exchange across the Blood-Brain Barrier in Obstructive Sleep Apnea: An MRI Diffusion-Weighted Pseudo-Continuous Arterial Spin Labeling Study.

BACKGROUND AND PURPOSE: Obstructive sleep apnea (OSA) subjects show brain injury in sites that control autonomic, cognitive, and mood functions that are deficient in the condition. The processes contributing to injury may include altered blood-brain barrier (BBB) actions. Our aim was to examine BBB function, based on diffusion-weighted pseudo-continuous arterial spin labeling (DW-pCASL) procedures, in OSA compared to controls. METHODS: We performed DW-pCASL imaging in nine OSA and nine controls on a 3.0-Tesla MRI scanner. Global mean gray and white matter arterial transient time (ATT, an index of large artery integrity), water exchange rate across the BBB (Kw, BBB function), DW-pCASL ratio, and cerebral blood flow (CBF) values were compared between OSA and control subjects. RESULTS: Global mean gray and white matter ATT (OSA vs. controls; gray matter, 1.691 ± .120 vs. 1.658 ± .109 second, P = .49; white matter, 1.700 ± .115 vs. 1.650 ± .114 second, P = .44), and CBF values (gray matter, 57.4 ± 15.8 vs. 58.2 ± 10.7 ml/100 g/min, P = .67; white matter, 24.2 ± 7.0 vs. 24.6 ± 6.7 ml/100 g/min, P = .91) did not differ significantly, but global gray and white matter Kw (gray matter, 158.0 ± 28.9 vs. 220.8 ± 40.6 min(-1) , P = .002; white matter, 177.5 ± 57.2 vs. 261.1 ± 51.0 min(-1) , P = .006), and DW-pCASL ratio (gray matter, .727 ± .076 vs. .823 ± .069, P = .011; white matter, .722 ± .144 vs. .888 ± .100, P = .004) values were significantly reduced in OSA over controls. CONCLUSIONS: OSA subjects show compromised BBB function, but intact large artery integrity. The BBB alterations may introduce neural damage contributing to abnormal functions in OSA, and suggest a need to repair BBB function with strategies commonly used in other fields.

Impaired Cerebrovascular Function in Coronary Artery Disease Patients and Recovery Following Cardiac Rehabilitation.

Coronary artery disease (CAD) poses a risk to the cerebrovascular function of older adults and has been linked to impaired cognitive abilities. Using magnetic resonance perfusion imaging, we investigated changes in resting cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) to hypercapnia in 34 CAD patients and 21 age-matched controls. Gray matter volume (GMV) images were acquired and used as a confounding variable to separate changes in structure from function. Compared to healthy controls, CAD patients demonstrated reduced CBF in the superior frontal, anterior cingulate (AC), insular, pre- and post-central gyri, middle temporal, and superior temporal regions. Subsequent analysis of these regions demonstrated decreased CVR in the AC, insula, post-central and superior frontal regions. Except in the superior frontal and precentral regions, regional reductions in CBF and CVR were identified in brain areas where no detectable reductions in GMV were observed, demonstrating that these vascular changes were independent of brain atrophy. Because aerobic fitness training can improve brain function, potential changes in regional CBF were investigated in the CAD patients after completion of a 6-months exercise-based cardiac rehabilitation program. Increased CBF was observed in the bilateral AC, as well as recovery of CBF in the dorsal aspect of the right AC, where the magnitude of increased CBF was roughly equal to the reduction in CBF at baseline compared to controls. These exercise-related improvements in CBF in the AC is intriguing given the role of this area in cognitive processing and regulation of cardiovascular autonomic control.

Feasibility of simultaneous whole-brain imaging on an integrated PET-MRI system using an enhanced 2-point Dixon attenuation correction method.

PURPOSE: To evaluate a potential approach for improved attenuation correction (AC) of PET in simultaneous PET and MRI brain imaging, a straightforward approach that adds bone information missing on Dixon AC was explored. METHODS: Bone information derived from individual T1-weighted MRI data using segmentation tools in SPM8, were added to the standard Dixon AC map. Percent relative difference between PET reconstructed with Dixon+bone and with Dixon AC maps were compared across brain regions of 13 oncology patients. The clinical potential of the improved Dixon AC was investigated by comparing relative perfusion (rCBF) measured with arterial spin labeling to relative glucose uptake (rPETdxbone) measured simultaneously with (18)F-flurodexoyglucose in several regions across the brain. RESULTS: A gradual increase in PET signal from center to the edge of the brain was observed in PET reconstructed with Dixon+bone. A 5-20% reduction in regional PET signals were observed in data corrected with standard Dixon AC maps. These regional underestimations of PET were either reduced or removed when Dixon+bone AC was applied. The mean relative correlation coefficient between rCBF and rPETdxbone was r = 0.53 (p < 0.001). Marked regional variations in rCBF-to-rPET correlation were observed, with the highest associations in the caudate and cingulate and the lowest in limbic structures. All findings were well matched to observations from previous studies conducted with PET data reconstructed with computed tomography derived AC maps. CONCLUSION: Adding bone information derived from T1-weighted MRI to Dixon AC maps can improve underestimation of PET activity in hybrid PET-MRI neuroimaging.

Turbo-FLASH based arterial spin labeled perfusion MRI at 7 T.

Motivations of arterial spin labeling (ASL) at ultrahigh magnetic fields include prolonged blood T1 and greater signal-to-noise ratio (SNR). However, increased B0 and B1 inhomogeneities and increased specific absorption ratio (SAR) challenge practical ASL implementations. In this study, Turbo-FLASH (Fast Low Angle Shot) based pulsed and pseudo-continuous ASL sequences were performed at 7T, by taking advantage of the relatively low SAR and short TE of Turbo-FLASH that minimizes susceptibility artifacts. Consistent with theoretical predictions, the experimental data showed that Turbo-FLASH based ASL yielded approximately 4 times SNR gain at 7T compared to 3T. High quality perfusion images were obtained with an in-plane spatial resolution of 0.85×1.7 mm(2). A further functional MRI study of motor cortex activation precisely located the primary motor cortex to the precentral gyrus, with the same high spatial resolution. Finally, functional connectivity between left and right motor cortices as well as supplemental motor area were demonstrated using resting state perfusion images. Turbo-FLASH based ASL is a promising approach for perfusion imaging at 7T, which could provide novel approaches to high spatiotemporal resolution fMRI and to investigate the functional connectivity of brain networks at ultrahigh field.

Model-independent dynamic constraint to improve the optical reconstruction of regional kinetic parameters.

Optical dye-dilution techniques can quantify kinetic parameters in a region of tissue, but currently rely on a two-step process-spatial reconstruction of the dye concentration, repeated at every time-point, and subsequent kinetic analysis of the time-dependent change in dye concentration. Inaccuracies, in this approach, are due mainly to the ill-posed nature of the spatial reconstruction problem, which propagates into kinetic analysis and result in errors in extracted dynamic parameters. We present a hybrid kinetic deconvolution optical reconstruction algorithm, effectively combining optical reconstruction and model-independent kinetic analysis into a single inverse problem that is better posed. Kinetic parameters of multiple tissue regions can be quantified simultaneously. As proof of principle, we provide numerical experiments in reflectance-based and fluorescence molecular tomography scenarios.

Measuring the neural response to continuous intramuscular infusion of hypertonic saline by perfusion MRI.

PURPOSE: To determine the extent to which arterial spin labeling (ASL), a functional magnetic resonance imaging technique that directly measures cerebral blood flow (CBF), is able to measure the neural activation associated with prolonged experimental muscle pain. MATERIALS AND METHODS: Hypertonic saline (HS) (5% NaCl) was infused into the brachioradialis muscle of 19 healthy volunteers for 15 min. The imaging volume extended from the dorsal side of the pons to the primary somatosensory cortices, covering most of the cortical and subcortical regions associated with pain perception. RESULTS: Using a numerical scale from 0 to 10, ratings of pain intensity peaked at 5.9 ± 0.5 (mean ± SE). Group activation maps showed that the slow infusion of HS evoked CBF increases primarily in bilateral insula, with additional activation in right frontal regions. In the activated areas, CBF gradually increased at the onset of HS infusion and was maintained at relatively constant levels throughout the remainder of the infusion period. However, the level and extent of activation were smaller than observed in previous studies involving acute muscle pain. CONCLUSION: This study demonstrates the ability of ASL to measure changes in CBF over extended periods of time and that the neural activation caused by muscle pain is paradigm specific.

A two-stage approach for measuring vascular water exchange and arterial transit time by diffusion-weighted perfusion MRI.

Changes in the exchange rate of water across the blood-brain barrier, denoted k(w), may indicate blood-brain barrier dysfunction before the leakage of large-molecule contrast agents is observable. A previously proposed approach for measuring k(w) is to use diffusion-weighted arterial spin labeling to measure the vascular and tissue fractions of labeled water, because the vascular-to-tissue ratio is related to k(w). However, the accuracy of diffusion-weighted arterial spin labeling is affected by arterial blood contributions and the arterial transit time (τ(a)). To address these issues, a two-stage method is proposed that uses combinations of diffusion-weighted gradient strengths and post-labeling delays to measure both τ(a) and k(w). The feasibility of this method was assessed by acquiring diffusion-weighted arterial spin labeling data from seven healthy volunteers. Repeat measurements and Monte Carlo simulations were conducted to determine the precision and accuracy of the k(w) estimates. Average grey and white matter k(w) values were 110 ± 18 and 126 ± 18 min(-1), respectively, which compare favorably to blood-brain barrier permeability measurements obtained with positron emission tomography. The intrasubject coefficient of variation was 26% ± 23% in grey matter and 21% ± 17% in white matter, indicating that reproducible k(w) measurements can be obtained.

Quantification of renal perfusion: comparison of arterial spin labeling and dynamic contrast-enhanced MRI.

PURPOSE: To provide the first comparison of absolute renal perfusion obtained by arterial spin labeling (ASL) and separable compartment modeling of dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI). Moreover, we provide the first application of the dual bolus approach to quantitative DCE-MRI perfusion measurements in the kidney. MATERIALS AND METHODS: Consecutive ASL and DCE-MRI acquisitions were performed on six rabbits on a 1.5 T MRI system. Gadolinium (Gd)-DTPA was administered in two separate injections to decouple measurement of the arterial input function and tissue uptake curves. For DCE perfusion, pixel-wise and mean cortex region-of-interest tissue curves were fit to a separable compartment model. RESULTS: Absolute renal cortex perfusion estimates obtained by DCE and ASL were in close agreement: 3.28 ± 0.59 mL/g/min (ASL), 2.98 ± 0.60 mL/g/min (DCE), and 3.57 ± 0.96 mL/g/min (pixel-wise DCE). Renal medulla perfusion was 1.53 ± 0.35 mL/g/min (ASL) but was not adequately described by the separable compartment model. CONCLUSION: ASL and DCE-MRI provided similar measures of absolute perfusion in the renal cortex, offering both noncontrast and contrast-based alternatives to improve current renal MRI assessment of kidney function.

Noninvasive MRI measures of microstructural and cerebrovascular changes during normal swine brain development.

The swine brain is emerging as a potentially valuable translational animal model of neurodevelopment and offers the ability to assess the impact of experimentally induced neurological disorders. The goal for this study was to characterize swine brain development using noninvasive MRI measures of microstructural and cerebrovascular changes. Thirteen pigs at various postnatal ages (2.3-43.5 kg) were imaged on a 1.5-Tesla MRI system. Microstructural changes were assessed using diffusion tensor imaging measures of mean diffusivity and fractional anisotropy. Cerebrovascular changes were assessed using arterial spin labeling measures of baseline cerebral blood flow (CBF) and the cerebrovascular reactivity (CVR) of the blood-oxygen level dependent (BOLD) MRI signal to CO2. We found a positive logarithmic relationship for regional tissue volumes and fractional anisotropy with body weight, which is similar to the pattern reported in the developing human brain. Unlike in the maturing human brain, no consistent changes in mean diffusivity or baseline CBF with development were observed. Changes in BOLD CVR exhibited a positive logarithmic relationship with body weight, which may impact the interpretation of functional MRI results at different stages of development. This animal model can be validated by applying the same noninvasive measures in humans.

Feasibility and precision of cerebral blood flow and cerebrovascular reactivity MRI measurements using a computer-controlled gas delivery system in an anesthetised juvenile animal model.

PURPOSE: To demonstrate the feasibility and repeatability of cerebrovascular reactivity (CVR) imaging using a controlled CO(2) challenge in mechanically ventilated juvenile pigs. MATERIALS AND METHODS: Precise end-tidal partial pressure CO(2) (PETCO(2)) control was achieved via a computer-controlled model-driven prospective end-tidal targeting (MPET) system integrated with mechanical ventilation using a custom-built secondary breathing circuit. Test-retest blood-oxygen level dependent (BOLD) CVR images were collected in nine juvenile pigs by quantifying the BOLD response to iso-oxic square-wave PETCO(2) changes. For comparison, test-retest baseline arterial spin labeling (ASL) cerebral blood flow (CBF) images were collected. Repeatability was quantified using the intra-class correlation coefficient (ICC) and coefficient of variation (CV). RESULTS: The repeatability of the PETCO(2) (CV < 2%) step changes resulted in BOLD CVR ICC > 0.94 and CV < 6% for cortical brain regions, which was similar to ASL CBF repeatability (ICC > 0.96 and CV < 4%). CONCLUSION: This study demonstrates the feasibility and precision of CVR imaging with an MPET CO(2) challenge in mechanically ventilated subjects using an animal model. Translation of this method into clinical imaging protocols may enable CVR imaging in young children with cerebrovascular disease who require general anesthesia.

Quantification issues in arterial spin labeling perfusion magnetic resonance imaging.

Arterial spin labeling (ASL) perfusion magnetic resonance imaging has gained wide acceptance for its value in clinical and neuroscience applications during recent years. Its capability for noninvasive and absolute perfusion quantification is a key characteristic that makes ASL attractive for many clinical applications. In the present review, we discuss the main parameters or factors that affect the reliability and accuracy of ASL perfusion measurements. Our secondary goal was to outline potential solutions that may improve the reliability and accuracy of ASL in clinical settings. It was found that, through theoretical analyses, flow quantification is most sensitive to tagging efficiency and estimation of the equilibrium magnetization of blood signal (M(0b)). Variations of blood T1 have a greater effect on perfusion quantification than variations of tissue T1. Arterial transit time becomes an influential factor when it is longer than the postlabeling delay time. The T2's of blood and tissue impose minimal effects on perfusion calculation at field strengths equal to or lower than 3.0 T. Subsequently, we proposed various approaches for in vivo estimation or calibration of the above parameters, such as the use of phase-contrast magnetic resonance imaging for calibration of the labeling efficiency as well as the use of inversion recovery TrueFISP (true fast imaging with steady-state precession) sequence for blood T1 mapping. We also list representative clinical cases in which implicit assumptions for ASL perfusion quantification may be violated, such as the venous outflow effect in children with sickle cell disease. Finally, an optimal imaging protocol including in vivo measurements of several critical parameters was recommended for clinical ASL studies.

Using perfusion MRI to measure the dynamic changes in neural activation associated with tonic muscular pain.

Knowledge regarding neural pain processing is primarily the result of studies involving models of brief cutaneous pain; however, clinical pain generally originates in deep tissue and is prolonged. This study measured the dynamic neural activation associated with a muscular pain model incorporating both acute and tonic states. Hypertonic saline (5% NaCl) was infused into the brachioradialis muscle of eleven healthy volunteers for 15min after an initial bolus of 0.5mL. Ten controls followed the same protocol with normal saline (0.9% NaCl). Magnetic resonance images of cerebral blood flow (CBF) were acquired using an arterial spin labelling method. The imaging volume extended from the thalamus to the primary somatosensory cortices, but did not include the brainstem and cerebellum. Using a numerical scale from 0 to 10, ratings of pain intensity peaked at 5.9+/-0.6 and remained near 5 for the remainder of the trial. Controls experienced minimal pain, reporting a peak value of 1.8+/-0.4. Significant CBF increases in rostral and caudal anterior insula bilaterally, anterior mid-cingulate cortex (aMCC), bilateral thalamus, and contralateral posterior insula were observed. The time courses of CBF revealed significant differences in the activation pattern during tonic pain. In particular, a more rapid return to baseline in aMCC versus insula was interpreted as a preferential decrease in the affective component of pain. This conclusion was supported by the strong correlation between pain intensity ratings and CBF in the contralateral insula (R(2)=0.911, p<0.01), which is a region believed to be responsible for pain intensity processing.

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) (1,200 and 1,700 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=1,700 ms (73+/-1 ml/min per 100 g). At TI=1,200 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.

When perfusion meets diffusion: in vivo measurement of water permeability in human brain.

Quantification of water permeability can improve the accuracy of perfusion measurements obtained with arterial spin labeling (ASL) methods, and may provide clinically relevant information regarding the functional status of the microvasculature. The amount of labeled water in the vascular and tissue compartments in an ASL experiment can be estimated based on their distinct diffusion characteristics, and in turn, water permeability determined from the relative vascular and tissue contributions. In the present study, a hybrid magnetic resonance imaging technique was introduced by marrying a continuous ASL method with a twice-refocused spin-echo diffusion sequence. Series of diffusion-weighted ASL signals were acquired with systematically varied b values. The signals were modeled with fast and slow decaying components that were associated with the vascular and tissue compartments, respectively. The relative amount of labeled water in the tissue compartment increased from 61% to 74% and to 86% when the postlabeling delay time was increased from 0.8 to 1.2 and to 1.5 secs. With a b value of 50 secs/mm2, the capillary contribution (fast component) of the ASL signal could be effectively minimized. Using the single-pass approximation model, the water permeability of gray matter in the human brain was estimated based on the derived relative water fractions in the tissue and microvasculature. The potential for in vivo magnetic resonance mapping of water permeability was showed using two diffusion weighted ASL measurements with b=0 and 50 secs/mm2 in both healthy subjects and a case of brain tumor.

Measurement of cerebral oxidative metabolism with near-infrared spectroscopy: a validation study.

Predicting the onset of secondary energy failure after a hypoxic-ischemic insult in newborns is critical for providing effective treatment. Measuring reductions in the cerebral metabolic rate of oxygen (CMRO(2)) may be one method for early detection, as hypoxia-ischemia is believed to impair oxidative metabolism. We have developed a near-infrared spectroscopy (NIRS) technique based on the Fick Principle for measuring CMRO(2). This technique combines cerebral blood flow (CBF) measurements obtained using the tracer indocyanine green with measurements of the cerebral deoxy-hemoglobin (Hb) concentration. In this study, NIRS measurements of CMRO(2) were compared with CMRO(2) determined from the product of CBF and the cerebral arteriovenous difference in oxygen measured from blood samples. The blood samples were collected from a peripheral artery and the sagittal sinus. Eight piglets were subjected to five cerebral metabolic states created by varying the plane of anesthesia. No significant difference was found between CMRO(2) measurements obtained with the two techniques at any anesthetic level (P>0.5). Furthermore, there was a strong correlation when concomitant CMRO(2) values from the two techniques were compared (R(2)=0.88, P<0.001). This work showed that CMRO(2) can be determined accurately by combining NIRS measurements of CBF and Hb. Since NIRS is safe and measurements can be obtained at the bedside, it is believed that this technique could assist in the early diagnosis of cerebral energy dysfunction after hypoxia-ischemia.

A model of blood-brain barrier permeability to water: accounting for blood inflow and longitudinal relaxation effects.

A noninvasive technique for measuring the permeability of the blood-brain barrier (BBB) to water could help to evaluate changes in the functional integrity of the BBB that occur in different pathologies, such as multiple sclerosis or growth of brain tumor. Recently, Schwarzbauer et al. (Magn Reson Med 1997;37:769-777) proposed an MR method to measure this permeability based on the T(1) reductions induced by injecting various doses of paramagnetic contrast agent. However, this method may be difficult to implement in a clinical environment. Described here is a two-point technique, in which a spatially selective inversion is used to measure T(1) prior to and after injection of an intravascular contrast agent. Measurements made in the rat brain are compared to numerical simulations generated with a physiological model that accounts for blood flow and includes two different blood volumes: nonexchanging and exchanging blood volumes. Our results suggest that BBB permeability could be evaluated from the change in T(1) caused by the vascular contrast agent. This technique might provide an approach for monitoring changes in BBB permeability to water in clinical studies.

Effects of indomethacin on cerebral blood flow at rest and during hypercapnia: an arterial spin tagging study in humans.

PURPOSE: To investigate using an arterial spin tagging (AST) approach the effect of indomethacin on the cerebral blood flow (CBF) response to hypercapnia. MATERIALS AND METHODS: Subjects inhaled a gas mixture containing 6% CO(2) for two 5-minute periods, which were separated by a 10-minute interval, in which subjects inhaled room air. In six subjects, indomethacin (i.v., 0.2 mg/kg) was infused in the normocapnic interval between the two hypercapnic periods. RESULTS: Indomethacin reduced normocapnic gray matter CBF by 36 +/- 5% and reduced the CBF increase during hypercapnia from 43 +/- 9% to 16 +/- 5% in gray matter (P < 0.001) and from 48 +/- 11% to 35 +/- 9% in white matter (P < 0.025). CONCLUSION: The results demonstrate that an AST approach can measure the effects of indomethacin on global CBF increases during hypercapnia and suggest that an AST approach could be used to investigate pharmacological effects on focal CBF increases during functional activation.