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R P Paczynski

Publications and source records attributed to R P Paczynski.

15 recordsLinked to original sources
PubMed2000

Absolute measurements of water content using magnetic resonance imaging: preliminary findings in an in vivo focal ischemic rat model.

Using a magnetic resonance (MR) imaging method, absolute measurements of in vivo brain water content were obtained in 15 male Long Evans rats that underwent a 90-min focal cerebral ischemia. A strong linear relationship (r = 0.80) with a slope of 1 was observed when correlating MR-measured water content to that obtained with the ex vivo wet/dry measurements. This effective spin-density-based method is the first-reported in vivo absolute quantification of brain tissue water content associated with a pathophysiological state and preliminary findings suggest that a noninvasive measurement of brain water content can be obtained with MRI.

Animals↗
PubMed2000

Effects of fluid management on edema volume and midline shift in a rat model of ischemic stroke.

BACKGROUND AND PURPOSE: The purpose of this study was to investigate the effects of fluid management on brain water content (BW) and midline shift (MLS) after a focal cerebral ischemic insult. METHODS: A suture model was used to induce focal cerebral ischemia for 90 minutes (n=44). The rats were randomly assigned to 3 groups 2. 5 hours after reperfusion: dehydration (n=24), control (n=8), or hydration (n=12). BW was obtained with the wet-dry weight method 24 hours after middle cerebral artery (MCA) occlusion. In addition, MRI were obtained (n=31) 24 hours after the onset of ischemia so that the ratio of hemispheric volumes ipsilateral (IH) and contralateral (CH) to the infarct and the extent of MLS could be obtained. RESULTS: Across the range from moderate dehydration to intravascular volume expansion with isotonic saline, BW of the IH increased linearly as a function of change in body weight (r(2)=0.89), whereas few changes in relation to body weight were observed in CH, indicating a preferential effect of fluid management on the infarcted hemisphere. Furthermore, the hemispheric volume ratio (IH/CH) and MLS also increased in relation to changes in body weight. However, paradoxical increases in BW, IH/CH, and extent of MLS were observed in comparison with controls when severe dehydration was produced with high-dose mannitol. CONCLUSIONS: Changes in ischemic BW by fluid management correlated closely with changes in body weight except when high-dose mannitol was used. Mannitol, as a dehydrating agent, may be associated with bimodal effects, with a high dose aggravating ischemic BW.

Animals↗
PubMed1999

Regional cerebral blood volume: a comparison of the dynamic imaging and the steady state methods.

Accurate assessment of regional cerebral blood volume (rCBV) is of critical importance in the study of cerebrovascular disease and other disorders of the central nervous system. Currently, magnetic resonance imaging (MRI) is able to measure rCBV non-invasively with two commonly used methods: the dynamic imaging (DI) and steady state (SS) approaches. In this study, two questions were investigated. First, how do partial volume effects between gray matter (GM) and white matter (WM) and between epicortical vessels and brain parenchyma affect the estimation of rCBV when using the SS approach? Second, how comparable are the ratios of rCBV in GM to rCBV in WM (rCBV GM/WM) obtained with the two methods? We used a paramagnetic contrast agent, OPTIMARK (Mallinckrodt, St. Louis, MO), at a dose of 0.2 mmol/kg in anesthetized pigs (n = 6) to obtain rCBV maps using both methods. When a 10% rCBV threshold was used to minimize effects from large epicortical vessels, and tissue segmentation was used to separate GM from WM, rCBV values of 4.8 +/- 0.3% and 3.3 +/- 0.5% were obtained for GM and WM, respectively, with the SS approach. Significantly higher rCBV values for both GM (P < 0.001) and WM (P < 0.01) were observed when the contribution from large epicortical vessels was not removed. When tissue segmentation and rCBV thresholding were used on SS data, an rCBV GM/WM ratio of 1.5 +/- 0.2 was obtained. This value did not differ significantly from the rCBV GM/WM ratio of 1.8 +/- 0.6 obtained using the DI approach.

Animals↗
PubMed1999

Quantitative magnetic resonance imaging in experimental hypercapnia: improvement in the relation between changes in brain R2 and the oxygen saturation of venous blood after correction for changes in cerebral blood volume.

Acute hypercapnia simultaneously induces increases in regional cerebral blood volume (rCBV) and the oxygen saturation of cerebral venous blood (Yv). Changes in both physiologic parameters may influence the changes in R2 (deltaR2) that can be measured in the brain with gradient echo magnetic resonance imaging. The authors examined the effect of incorporating independent measurements of the change in rCBV (deltarCBV) on the fidelity of the relation between deltaR2 and deltaYv in the setting of experimental hypercapnia. A two-dimensional T2-weighted gradient echo sequence was used to measure deltaR2 in the brain parenchyma of anesthetized rats in response to hypercapnia with respect to the control state. In parallel, estimates of rCBV were obtained using a three-dimensional steady-state approach in conjunction with a paramagnetic contrast agent during both control and hypercapnic states so that a deltarCBV could be calculated. Regional CBV values of 2.96 +/- 0.82% and 5.74 +/- 1.21% were obtained during the control and hypercapnic states, respectively, and linear relations between rCBV and CO2 tension in both arterial (r = 0.80) and jugular venous (r = 0.76) blood samples were obtained. When correlating deltaR2 directly with deltaYv, no clear relation was apparent, but a strong linear relation (r = 0.76) was observed when correction for deltarCBV was incorporated into the data analysis. These results are consistent with the current understanding of the mechanisms of blood oxygen level-dependent (BOLD) contrast and underscore the potential importance of taking into account deltarCBV when quantitative estimates of deltaYv from the "BOLD effect" are intended.

Animals↗
PubMed1998

Experimental hypoxemic hypoxia: changes in R2* of brain parenchyma accurately reflect the combined effects of changes in arterial and cerebral venous oxygen saturation.

A two-dimensional T2*-weighted gradient-echo sequence was used to image the rat brain before and during graded hypoxemia. Changes in R2* (deltaR2*) with respect to the control state were calculated for brain parenchyma and were compared with changes in hemoglobin saturation measured from both arterial and jugular venous blood samples. DeltaR2* was first correlated with the changes in arterial (deltaYa) and venous (deltaYv) hemoglobin saturations individually. Although a general trend toward a linear relationship with deltaR2* was observed for both deltaYa and deltaYv, neither alone was strong (correlation coefficients r=0.71 and 0.75 for deltaYa and deltaYv, respectively, and standard errors of the regression (SER)=0.52 and 0.48 for deltaYa and deltaYv, respectively). However, when an "effective" cerebral blood hemoglobin saturation change (deltaYb) was constructed that takes into account the approximate weighting of the contributions from the arterial and venous phases of the circulation (deltaYb = 0.75 x deltaYv + 0.25 x deltaYa), a stronger correlation with deltaR2* was obtained and there was less variance (r=0.87 and SER=0.35). It is concluded that an appropriate weighting of the contributions of arterial and venous phases of the circulation must be taken into account in modeling the volume susceptibility effects of deoxyhemoglobin on R2* of brain parenchyma. In this way, a more accurate relationship between deltaR2* and deltaYb can be obtained.

Analysis of Variance↗
PubMed1998

Effects of acute normovolemic hemodilution on T2*-weighted images of rat brain.

Acute normovolemic hemodilution (HD) was induced in anesthetized rats to assess the effect of changes in hematocrit (Hct) on signal intensity in T2*-weighted magnetic resonance (MR) images. Other relevant physiological parameters were maintained invariant. Two degrees of HD were induced: mild (Hct reduced from 42.6+/-2.2% to 33.4+/-2.1%) and moderate (Hct reduced from 44.6+/-2.7% to 26.2+/-1.7%). A two-dimensional gradient-echo sequence was used to monitor signal changes with high temporal resolution before, during, and after HD protocols. The time course of signal intensity change was closely related to that of changes in Hct. Corresponding changes in R2* (deltaR2*) with respect to the pre-HD state were calculated for the brain parenchyma. Average deltaR2* values of -0.24+/-0.06 s(-1) and -0.40+/-0.07 s(-1) were obtained for the mild and moderate HD groups, respectively, during the final 2 min of MR imaging (proximal to correlative measurements of Hct). MR measured deltaR2* values were in close agreement with the expected changes in R2* predicted from theory when the measured changes in Hct were used as independent variables. These data are in good agreement with the current understanding of the effects of changes in the intravascular concentration of deoxyhemoglobin on induced magnetic susceptibility and hold promise for quantitative measurement of brain oxygenation in vivo.

Analysis of Variance↗
PubMed1998

Experimental hypoxemic hypoxia: effects of variation in hematocrit on magnetic resonance T2*-weighted brain images.

T2*-weighted gradient echo magnetic resonance images of rat brain were obtained dynamically during acute hypoxemic hypoxia to investigate the relations between changes in cerebral blood oxygen saturation (deltaYb), blood hematocrit (Hct), and R2* (deltaR2*). Images from hypoxemic rats with normal Hct (42.8%+/-2.33%; n=12) were compared with those from hypoxemic rats with mild (33.4%+/-1.88%; n=8) or moderate (27.14%+/-2.7%; n=10) reduction of Hct. A linear relation between deltaYb and deltaR2* was obtained for all three groups. However, the slopes of the linear regressions were statistically different from one another (P < 0.001), with the slopes of the regression lines increasing inversely with Hct; that is, the slope for normal Hct is less than the slope for mildly reduced Hct, which is less than the slope for moderately reduced Hct. These data suggest that for any given reduction in the oxygen saturation of cerebral blood, the deltaR2* will be of a lesser magnitude when the hemoglobin concentration is reduced; the data are consistent with existing theoretical models of deoxyhemoglobin content-dependent effects in T2*-weighted magnetic resonance imaging.

Animals↗
PubMed1997

Quantitative regional brain water measurement with magnetic resonance imaging in a focal ischemia model.

Therapeutic approaches to cerebral edema require an understanding of both the magnitude and location of changes in brain water content. It is desirable to have a sensitive, accurate means of measuring brain water noninvasively so that effective therapies for cerebral edema in stroke, head trauma, and other conditions can be investigated. In this work, a three-dimensional magnetic resonance imaging technique that is able to provide both spin density and T1 simultaneously is described. This method was used to quantitate regional changes in brain water content in a rat model of focal cerebral ischemia. Brain water contents estimated from both relative spin density and relative T1 measurements made in vivo were compared with ex vivo measurements of relative tissue water content based on the wet-dry technique. Correlation coefficients of 0.95 and 0.98 were obtained between the wet-dry measurements and magnetic resonance measurements of T1 and spin density, respectively. Notably, the slope of the relationship between T1 and tissue water content changed dramatically after the injection of a paramagnetic contrast agent while precontrast and postcontrast spin density measurements remained essentially invariant. In addition, a plot of absolute spin density (obtained by normalizing spin density from agar gelatin phantoms of different water contents to the spin density of a sample of 100% water) was linearly related to wet-dry measurements with a slope of 0.99 (R2 = 0.99).

Animals↗
PubMed1997

Quantitative measurements of regional cerebral blood volume using MRI in rats: effects of arterial carbon dioxide tension and mannitol.

A three-dimensional (3D) T1-weighted sequence was used to acquire high spatial resolution whole brain images in rats before and after the injection of an intravascular contrast agent. These T1-weighted images were used to estimate regional cerebral blood volume (rCBV) as a percentage of blood volume in each voxel. Ventilation was manipulated to investigate the effects of altered arterial carbon dioxide tension (PaCO2) on rCBV. In addition, different doses of a hypertonic mannitol solution were used to investigate the sensitivity of the proposed method in a serial monitoring paradigm. An rCBV of 2.40% +/- 0.34% was obtained before any physiological manipulation, in good agreement with literature values using alternative techniques. Using this method, it was found that there exists a linear relationship between PaCO2 and rCBV (R2 = 0.77) and that rCBV increased in a dose and time dependent fashion in mannitol-treated rats. High signal-to-noise was available due to the substantial increase in blood signal from the intravascular contrast agent.

Animals↗
PubMed1997

Osmotherapy. Basic concepts and controversies.

Osmotherapy with compounds such as mannitol has become a mainstay of neurologic and neurosurgical intensive care. Elevated intracranial pressure is the most common indication. A substantive debate remains as to the appropriate timing of administration and the optimal fluid management protocol, and experts disagree about the clinically relevant mechanisms of action of osmotic diuretics. This article briefly summarizes the basic literature on the physical actions of mannitol, addresses commonly asked questions, and highlights some of the controversies that arise at the bedside.

Blood-Brain Barrier↗
PubMed1997

Multiple-dose mannitol reduces brain water content in a rat model of cortical infarction.

BACKGROUND AND PURPOSE: Repeated use of mannitol in the setting of ischemic infarction is a controversial and poorly defined therapeutic intervention. The purpose of this study was to examine the effects of repeated mannitol infusions on brain water content and tissue pressure in a well-defined rat model of focal ischemic stroke. METHODS: Mannitol infusions (0.5, 1.5, or 2.5 g/kg) were given by intravenous bolus 4 or 24 hours after 90-minute transient cortical ischemia in the territory of the right middle cerebral artery in rats and every 4 hours thereafter for a total of 24 hours. Fluid replacement was limited to 0.5 mL i.v. isotonic saline administered immediately after each mannitol dose. Control rats received 0.5 mL i.v. saline at the same intervals and were otherwise under ad libitum conditions. Water contents (percent H2O) of whole hemispheres and of cortical biopsies were measured with the wet-dry method, and blood samples were analyzed for plasma osmolality and chemistries. In a subgroup of rats, tissue pressure was also measured within the hemisphere ipsilateral to the infarct. RESULTS: Repeated mannitol infusions resulted in a dose-dependent increase in plasma osmolality and a dose-dependent decrease in the percent H2O of the ischemic middle cerebral artery cortex and ipsilateral hemisphere. In contrast, percent H2O of the contralateral cortex and hemisphere was significantly decreased only in the groups given the highest dose of mannitol (2.5 g/kg). Mannitol infusions at a dose of 1.5 g/kg begun 24 hours after reperfusion were also associated with a significant reduction of tissue pressure. CONCLUSIONS: In a rat model of ischemic cortical infarction, repeated mannitol infusions resulted primarily in a decrease in the percent H2O of the infarct and ipsilateral hemisphere, as well as decreased tissue pressure.

Animals↗
PubMed1996

Automated measurement of infarct size with scanned images of triphenyltetrazolium chloride-stained rat brains.

BACKGROUND AND PURPOSE: The extent of brain infarction after local cerebral ischemia is frequently assessed with the mitochondrial activity indicator 2,3,5-triphenyltetrazolium chloride (TTC). We describe an automated procedure for analysis of infarct size in TTC-stained rat brains. METHODS: Rats were subjected to middle cerebral artery occlusion and killed after 24 to 36 hours, and their brains were processed for TTC staining. Digital images of coronal sections from these brains (n > 50) were acquired with a desktop color scanner. The resulting images were divided into red, blue, and green component images. Total brain and infarct areas were automatically determined on the basis of total pixel intensity and area after segmentation of the red and green images, respectively. Automated measurements were compared with those made with a video camera-based image acquisition system that required manual tracing of lesion boundaries. RESULTS: The spatial resolution of scanned brain images (approximately equal to 200 microns) was comparable to that of the camera-based system and provided sufficient detail to recognize infarct boundaries and neuroanatomical features. Scanner-based acquisition and analysis were faster than with the camera-based method. The green component image accurately distinguished infarcted from normal brain, and the red component image represented total brain dimensions. Infarct measurements obtained by the automated method correlated closely with those from conventional apparatus (R2 = .89, P < .001). Intraobserver reliability with the automated method (R2 = 1.00) was higher than with the conventional method (R2 = .77). CONCLUSIONS: Infarct size after middle cerebral artery occlusion in the rat can be rapidly and reproducibly assessed with inexpensive scanning equipment and automated image analysis of TTC-stained brains.

Animals↗
PubMed1995

Experimental therapies to improve delivery of oxygen and substrate in acute stroke.

The results of large-scale clinical trials of hemodilution therapy and vasodilators for acute stroke have been disappointing. However, interventions involving the manipulation of whole blood viscosity, blood oxygen-carrying capacity, cardiac output, and the resistance properties of cerebral vessels are viable therapeutic modalities currently being investigated. The central aim of all of these therapies is the timely improvement of perfusion and substrate delivery to ischemic brain regions. Better understanding of cerebrovascular flow regulation and the physiology of microvessels may give rise to more effective therapies. In the past, overemphasis on hematocrit reduction and cerebral vasodilators has obscured the potential risks of reducing blood oxygen content and vascular resistance during acute stroke and the importance of optimizing oxygen delivery by other means, in particular by cardiac output augmentation and manipulation of plasma properties. A broader approach to therapeutic strategies for acute stroke includes not only increasing cerebral blood flow, but also interventions that will create favorable changes in the humoral microenvironment and promote overall substrate delivery to the brain.

Acute Disease↗
PubMedDate not supplied

Effects of the dihydropyridine Ca2+ channel antagonist nimodipine on kainic acid-induced limbic seizures.

The effects of the dihydropyridine Ca2+ channel antagonist nimodipine on kainic acid-induced seizures were studied in 30 0.5% halothane anesthetized Sprague-Dawley rats. Each animal received low dose kainic acid 0.5 mg/kg i.v. to allow study of the progression of neuronal excitability and epileptiform activity. Preadministration of nimodipine 1.0 mg/kg i.p. increased the latency but did not prevent kainic acid-induced epileptic activity. For example, the latency from kainic acid administration to the appearance of the first seizure and status epilepticus was 75.6 +/- 9.1 min and 85.9 +/- 9.4 min in controls vs. 117.3 +/- 9.3 min and 128.0 +/- 8.7 min in the nimodipine group (P less than 0.005). It is hypothesized that nimodipine attenuated excitability by blocking Ca2+ influx through voltage-dependent L-channels secondary to kainic acid-induced membrane depolarization.

Animals↗