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G Zaharchuk

Publications and source records attributed to G Zaharchuk.

10 recordsLinked to original sources

Comparative overview of brain perfusion imaging techniques.

Numerous imaging techniques have been developed and applied to evaluate brain hemodynamics. Among these are: Positron Emission Tomography (PET), Single Photon Emission Computed Tomography (SPECT), Xenon-enhanced Computed Tomography (XeCT), Dynamic Perfusion-computed Tomography (PCT), Magnetic Resonance Imaging Dynamic Susceptibility Contrast (DSC), Arterial Spin-Labeling (ASL), and Doppler Ultrasound. These techniques give similar information about brain hemodynamics in the form of parameters such as cerebral blood flow (CBF) or volume (CBV). All of them are used to characterize the same types of pathological conditions. However, each technique has its own advantages and drawbacks. This article addresses the main imaging techniques dedicated to brain hemodynamics. It represents a comparative overview, established by consensus among specialists of the various techniques. For clinicians, this paper should offers a clearer picture of the pros and cons of currently available brain perfusion imaging techniques, and assist them in choosing the proper method in every specific clinical setting.

Cerebrovascular Circulation↗

Is all perfusion-weighted magnetic resonance imaging for stroke equal? The temporal evolution of multiple hemodynamic parameters after focal ischemia in rats correlated with evidence of infarction.

Although perfusion-weighted imaging techniques are increasingly used to study stroke, no particular hemodynamic variable has emerged as a standard marker for accumulated ischemic damage. To better characterize the hemodynamic signature of infarction. the authors have assessed the severity and temporal evolution of ischemic hemodynamics in a middle cerebral artery occlusion model in the rat. Cerebral blood flow (CBF) and total and microvascular cerebral blood volume (CBV) changes were measured with arterial spin labeling and steady-state susceptibility contrast magnetic resonance imaging (MRI), respectively, and analyzed in regions corresponding to infarcted and spared ipsilateral tissue, based on 2,3,5-triphenyltetrazolium chloride histology sections after 24 hours ischemia. Spin echo susceptibility contrast was used to measure microvascular-weighted CBV, which had a maximum sensitivity for vessels with radii between 4 and 30 microm. Serial measurements between 1 and 3 hours after occlusion showed no change in CBF (22 +/- 20% of contralateral, mean +/- SD) or in total CBV (78 +/- 13% of contralateral) in regions destined to infarct. However, microvascular CBV progressively declined from 72 +/- 5% to 64 +/- 11% (P < 0.01) during this same period. Microvascular CBV changes with time were entirely due to decreases in subcortical infarcted zones (from 73 +/- 9% to 57 +/- 14%. P < 0.001) without changes in the cortical infarcted territory. The hemodynamic variables showed differences in magnitude and temporal response, and these changes varied based on histologic outcome and brain architecture. Such factors should be considered when designing imaging studies for human stroke.

Animals↗

Delivery of imaging agents into brain.

Delivery of diagnostic agents to the central nervous system (CNS) poses several challenges as a result of the special features of CNS blood vessels and tissue fluids. Diffusion barriers exist between blood and neural tissue, in the endothelium of parenchymal vessels (blood-brain barrier, BBB), and in the epithelia of the choroid plexuses and arachnoid membrane (blood-CSF barriers), which severely restrict penetration of several diagnostic imaging agents. The anatomy of large vessels can be imaged using bolus injection of X-ray contrast agents to identify sites of malformation or occlusion, and blood flow measured using MRI and CT, while new techniques permit analysis of capillary perfusion and blood volume. Absolute quantities can be derived, although relative measures in different CNS regions may be as useful in diagnosis. Local blood flow, blood volume, and their ratio (mean transit time) can be measured with high speed tomographic imaging using MRI and CT. Intravascular contrast agents for MRI are based on high magnetic susceptibility agents such as gadolinium, dysprosium and iron. Steady-state imaging using agents that cross the BBB including (123)I- and (99m)Tc-labelled lipophilic agents with SPECT, gives a 'snapshot' of perfusion at the time of injection. Cerebral perfusion can also be measured with PET, using H(2)(15)O, (11)C- or (15)O-butanol, and (18)F-fluoromethane, and cerebral blood volume measured with C(15)O. Recent advances in MRI permit the non-invasive 'labelling' of endogenous water protons in flowing blood, with subsequent detection as a measure of blood flow. Imaging the BBB most commonly involves detecting disruptions of the barrier, allowing contrast agents to leak out of the vascular system. Gd-DTPA is useful in imaging leaky vessels as in some cerebral tumors, while the shortening of T(1) by MR contrast agents can be used to detect more subtle changes in BBB permeability to water as in cerebral ischemia. Techniques for imaging the dynamic activity of the brain parenchyma mainly involve PET, using a variety of radiopharmaceuticals to image glucose transport and metabolism, neurotransmitter binding and uptake, protein synthesis and DNA dynamics. PET methods permit detailed analysis of regional function by comparing resting and task-related images, important in improving understanding of both normal and pathological brain function.

Journal Article↗

Multislice perfusion and perfusion territory imaging in humans with separate label and image coils.

An arterial spin labeling technique using separate RF labeling and imaging coils was used to obtain multislice perfusion images of the human brain at 3 T. Continuous RF irradiation at a peak power of 0.3 W was applied to the carotid arteries to adiabatically invert spins. Labeling was achieved without producing magnetization transfer effects since the B1 field of the labeling coil did not extend into the imaging region or couple significant power into the imaging coil. Eliminating magnetization transfer allowed the acquisition of multislice perfusion images of arbitrary orientation. Combining surface coil labeling with a reduced RF duty cycle permitted significantly lower SAR than single coil approaches. The technique was also found to allow selective labeling of blood in either carotid, providing an assessment of the artery's perfusion territory. In normal subjects, these territories were well-defined and localized to the ipsilateral hemisphere.

Artifacts↗

Evidence of a cerebrovascular postarteriole windkessel with delayed compliance.

A pronounced temporal mismatch was observed between the responses of relative cerebral blood volume (rCBV) measured by magnetic resonance imaging and relative cerebral blood flow measured by laser-Doppler flowmetry in rat somatosensory cortex after electrical forepaw stimulation. The increase of relative cerebral blood flow after stimulus onset and decrease after stimulus cessation were accurately described with a single exponential time constant of 2.4 +/- 0.8 seconds. In contrast, rCBV exhibited two distinct and nearly sequential processes after both onset and cessation of stimulation. A rapid change of rCBV (1.5 +/- 0.8 seconds) occurring immediately after onset and cessation was not statistically different from the time constant for relative cerebral blood flow. However, a slow phase of increase (onset) and decrease (cessation) with an exponential time constant of 14 +/- 13 seconds began approximately 8 seconds after the rapid phase of CBV change. A modified windkessel model was developed to describe the temporal evolution of rCBV as a rapid elastic response of capillaries and veins followed by slow venous relaxation of stress. Venous delayed compliance was suggested as the mechanism for the poststimulus undershoot in blood oxygen-sensitive magnetic resonance imaging signal that has been observed in this animal model and in human data.

Algorithms↗

Cerebrovascular dynamics of autoregulation and hypoperfusion. An MRI study of CBF and changes in total and microvascular cerebral blood volume during hemorrhagic hypotension.

BACKGROUND AND PURPOSE: To determine how cerebral blood flow (CBF), total and microvascular cerebral blood volume (CBV), and blood oxygenation level-dependent (BOLD) contrast change during autoregulation and hypotension using hemodynamic MRI. METHODS: Using arterial spin labeling and steady-state susceptibility contrast, we measured CBF and changes in both total and microvascular CBV during hemorrhagic hypotension in the rat (n=9). RESULTS: We observed CBF autoregulation for mean arterial blood pressure (MABP) between 50 and 140 mm Hg, at which average CBF was 1.27+/-0.44 mL. g(-1). min(-1) (mean+/-SD). During autoregulation, total and microvascular CBV changes were small and not significantly different from CBF changes. Consistent with this, no significant BOLD changes were observed. For MABP between 10 and 40 mm Hg, total CBV in the striatum increased slightly (+7+/-12%, P<0.05) whereas microvascular CBV decreased (-15+/-17%, P<0.01); on the cortical surface, total CBV increases were larger (+21+/-18%, P<0.01) and microvascular CBV was unchanged (3+/-22%, P>0.05). With severe hypotension, both total and microvascular CBV decreased significantly. Over the entire range of graded global hypoperfusion, there were increases in the CBV/CBF ratio. CONCLUSIONS: Parenchymal CBV changes are smaller than those of previous reports but are consistent with the small arteriolar fraction of total blood volume. Such measurements allow a framework for understanding effective compensatory vasodilation during autoregulation and volume-flow relationships during hypoperfusion.

Animals↗

Measurement of changes in cerebral blood volume in spontaneously hypertensive rats following L-arginine infusion using dynamic susceptibility contrast MRI.

To understand whether the NO-dependent vasodilator L-arginine was effective upon a chronically hypertensive cerebral capillary endothelium, dynamic susceptibility contrast MRI was used to measure the relative cerebral blood volume (rCBV) changes in nonischemic spontaneously hypertensive rats (SHRs). rCBV was measured in 11 rats at 4.7 T using fast gradient echo imaging with intravenous injection of Gd-DTPA. Images were acquired before, immediately after, and up to 90 min after the infusion of 300 mg/kg L-arginine (n = 7) or of an equivalent volume of saline (n = 4). L-arginine increased rCBV in cortex beginning 10 min after infusion and reached significance after 30 min (P < 0.01), reached a peak of 1.24 +/- 0.06 (mean +/- SEM) times pre-injection level after 50 min, and was sustained throughout the 90 min observation period. In contrast, the rCBV in the deeper gray matter (striatum) showed no statistically significant change over the 90 min observation period. While this is consistent with previous studies showing that L-arginine infusion can directly modulate vascular tone and cerebral hemodynamics, it demonstrates that the effect is present only in cortex, and that it can occur also in the setting of a disturbed capillary endothelium.

Animals↗

Continuous assessment of perfusion by tagging including volume and water extraction (CAPTIVE): a steady-state contrast agent technique for measuring blood flow, relative blood volume fraction, and the water extraction fraction.

A new technique, CAPTIVE, that is a synthesis of arterial spin labeling (ASL) blood flow and steady-state susceptibility contrast relative blood volume imaging is described. Using a single injection of a novel, long half-life intravascular magnetopharmaceutical with a high tissue:blood susceptibility difference (deltachi) to deltaR1 ratio, changes in tissue transverse relaxivity (deltaR2 or deltaR2*) that arise from changes in blood volume were measured, while preserving the ability to measure blood flow using traditional T1-based ASL techniques. This modification permits the continuous measurement of both blood flow and blood volume. Also, because the contrast agent can be used to remove the signal from intravascular spins, it is possible to measure the first-pass water extraction fraction. Contrast-to-noise is easily traded off with repetition rate, allowing the use of non-EPI scanners and more flexible imaging paradigms. The basic theory of these measurements, several experimental scenarios, and validating results are presented. Specifically, the PaCO2-reactivity of microvascular and total relative cerebral blood volume (rCBV), cerebral blood flow (CBF), and the water extraction-flow product (EF) in rats with the new contrast agent MPEG-PL-DyDTPA is measured, and the values are concordant with those of previous literature. As an example of one possible application, continuous flow and volume measurements during transient focal ischemia are presented. It is believed that CAPTIVE imaging will yield a more complete picture of the hemodynamic state of an organ, and has further application for understanding the origins of the BOLD effect.

Animals↗

Mismatch between cerebral blood volume and flow index during transient focal ischemia studied with MRI and GD-BOPTA.

We investigated the regional and temporal changes in cerebral blood volume (CBV), cerebral blood flow (CBF), and vascular transit time in seven mongrel cats during 30 min transient focal ischemia, caused by occlusion of the middle cerebral artery. Dynamic susceptibility contrast magnetic resonance imaging was done at 4.7 T, using fast gradient echo T2* weighted imaging and intravenous injection of gadolinium-BOPTA/Dimeglumine. During occlusion, the areas showing a blood volume change were predominantly within the middle cerebral artery territory and could be divided into areas showing either CBV increases or decreases. The area with decreased blood volume also had decreased blood flow as measured by our flow-based index (p < 0.05) and was located in the central territory of the middle cerebral artery. Peripheral to this region was an area showing increased blood volume but without significant CBF changes (p > 0.05). During reperfusion, the CBF increased in the entire zone showing changes in blood volume during occlusion, and remained significantly elevated until 45 min post-occlusion, while CBV remained elevated in the hyperemic rim for at least 2 h. The presence of a peri-ischemic zone showing flow/volume mismatch identified a region wherein baseline CBF is maintained by means of compensatory vasodilatation, but where the ratio of CBF to CBV is decreased. Dynamic susceptibility contrast magnetic resonance imaging with gadolinium-BOPTA/Dimeglumine may be a valuable technique for the investigation of regional and temporal perturbations of hemodynamics during ischemia and reperfusion.

Animals↗

Neuronal nitric oxide synthase mutant mice show smaller infarcts and attenuated apparent diffusion coefficient changes in the peri-infarct zone during focal cerebral ischemia.

Diffusion-weighted MRI at 2 T was used to monitor and assess tissue damage after permanent middle cerebral artery occlusion (MCAO) in wild-type (WT) and mice deficient in nitric oxide synthase gene expression (nNOS-). The ischemic lesion was evaluated 3 h after occlusion and subdivided into the lesion core and peri-infarct zone based on the magnitude of the apparent diffusion coefficient (ADC) change. Infarct volume, measured by using histochemical staining 24 h after MCA occlusion, correlated best with MRI infarct volume as assessed by an ADC threshold of 25% decrease from baseline at 3 h. For ADC thresholds of greater than 25% decrease, lesion size was not significantly different in nNOS- and WT mice. However, brain tissue showing ADC decreases of 10-25% was significantly smaller in the ipsilateral hemisphere of mutants (27 +/- 2% and 21 +/- 2% in WT and nNOS-, respectively; P < 0.05). These findings occurred independently of infarct volume and are consistent with a smaller peri-infarct zone in nNOS- mice. We postulate that the smaller peri-infarct zone is a reflection of less severe metabolic disturbance after ischemia in nNOS- mice, possibly related to diminished production of nitric oxide (NO) or a related product. We conclude that magnetic resonance techniques previously used to assess ischemic damage in larger animals can be extended to the mouse, raising the possibility that the molecular mechanisms leading to ischemic damage can be examined by using genetically engineered mice.

Animals↗