Biomedical subjects

R M Dijkhuizen

Publications and source records attributed to R M Dijkhuizen.

At least 19 recordsLinked to original sources

PubMed2001

Functional magnetic resonance imaging of reorganization in rat brain after stroke.

Functional recovery after stroke has been associated with brain plasticity; however, the exact relationship is unknown. We performed behavioral tests, functional MRI, and histology in a rat stroke model to assess the correlation between temporal changes in sensorimotor function, brain activation patterns, cerebral ischemic damage, and cerebrovascular reactivity. Unilateral stroke induced a large ipsilateral infarct and acute dysfunction of the contralateral forelimb, which significantly recovered at later stages. Forelimb impairment was accompanied by loss of stimulus-induced activation in the ipsilesional sensorimotor cortex; however, local tissue and perfusion were only moderately affected and cerebrovascular reactivity was preserved in this area. At 3 days after stroke, extensive activation-induced responses were detected in the contralesional hemisphere. After 14 days, we found reduced involvement of the contralesional hemisphere, and significant responses in the infarction periphery. Our data suggest that limb dysfunction is related to loss of brain activation in the ipsilesional sensorimotor cortex and that restoration of function is associated with biphasic recruitment of peri- and contralesional functional fields in the brain.

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PubMed2001

Diffusion NMR spectroscopy.

MR offers unique tools for measuring molecular diffusion. This review focuses on the use of diffusion-weighted MR spectroscopy (DW-MRS) to non-invasively quantitate the translational displacement of endogenous metabolites in intact mammalian tissues. Most of the metabolites that are observed by in vivo MRS are predominantly located in the intracellular compartment. DW-MRS is of fundamental interest because it enables one to probe the in situ status of the intracellular space from the diffusion characteristics of the metabolites, while at the same time providing information on the intrinsic diffusion properties of the metabolites themselves. Alternative techniques require the introduction of exogenous probe molecules, which involves invasive procedures, and are also unable to measure molecular diffusion in and throughout intact tissues. The length scale of the process(es) probed by MR is in the micrometer range which is of the same order as the dimensions of many intracellular entities. DW-MRS has been used to estimate the dimensions of the cellular elements that restrict intracellular metabolite diffusion in muscle and nerve tissue. In addition, it has been shown that DW-MRS can provide novel information on the cellular response to pathophysiological changes in relation to a range of disorders, including ischemia and excitotoxicity of the brain and cancer.

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PubMed2001

Delayed rt-PA treatment in a rat embolic stroke model: diagnosis and prognosis of ischemic injury and hemorrhagic transformation with magnetic resonance imaging.

The authors characterized effects of late recombinant tissue plasminogen activator (rt-PA) administration in a rat embolic stroke model with magnetic resonance imaging (MRI), to assess potential MRI correlates, or predictors, or both, of rt-PA-induced hemorrhage. Diffusion-, perfusion-, and postcontrast T1-weighted MRI were performed between 4 and 9 hours and at 24 hours after embolic stroke in spontaneously hypertensive rats. Treatment with either rt-PA or saline was started 6 hours after stroke. A spectrophotometric hemoglobin assay quantified hemorrhage severity. Before treatment, relative cerebral blood flow index (rCBFi) and apparent diffusion coefficient (ADC) in the ischemic territory were 30% +/- 23% and 60% +/- 5% (of contralateral), respectively, which increased to 45% +/- 39% and 68% +/- 4% 2 hours after rt-PA. After 24 hours, rCBFi and ADC were 27% +/- 27% and 59 +/- 5%. Hemorrhage volume after 24 hours was significantly greater in rt-PA-treated animals than in controls (8.7 +/- 3.7 microL vs. 5.1 +/- 2.4 microL, P < 0.05). Before rt-PA administration, clear postcontrast T1-weighted signal intensity enhancement was evident in areas of subsequent bleeding. These areas had lower rCBFi levels than regions without hemorrhage (23% +/- 22% vs. 36% +/- 29%, P < 0.05). In conclusion, late thrombolytic therapy does not necessarily lead to successful reperfusion. Hemorrhage emerged in areas with relatively low perfusion levels and early blood-brain barrier damage. Magnetic resonance imaging may be useful for quantifying effects of thrombolytic therapy and predicting risks of hemorrhagic transformation.

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PubMed2000

In vivo glucose detection by homonuclear spectral editing.

A frequency-selective multiple-quantum-coherence spectral editing pulse sequence, Ssel-MQC, was implemented for the detection of the betaH1-glucose resonance at 4.63 ppm in rat brain in vivo. Unwanted signal suppression and glucose coherence transfer pathway selection were performed with magnetic field gradients. To optimize sensitivity, the sequence was executed with surface coil signal reception and adiabatic RF pulse transmission. The glucose editing capabilities of Ssel-MQC were first evaluated in vitro. Ssel-MQC achieved excellent water suppression (suppression factor >10(5)), at the expense of an approximately 60% loss of the glucose signal due to incomplete coherence transfer pathway selection. Next, the sequence was used for in vivo glucose detection in normal rat brain during D-glucose infusion and in the brain of diabetic rats prior to and following insulin infusion.

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PubMed1999

Correlation between tissue depolarizations and damage in focal ischemic rat brain.

Ischemia-induced depolarizations may play a key role in the development of cerebral ischemic injury. Our goal was to assess the relationship between tissue depolarizations and tissue damage in focal ischemia. We performed multi-electrode cortical direct current (DC) potential recording and, subsequently, diffusion-weighted and T(2)-weighted magnetic resonance imaging (MRI) in rats after i) cortical application of KCl, and ii) permanent and transient middle cerebral artery (MCA)-occlusion in rats. Cortical KCl application induced 10.0+/-2.2 transient negative DC potential shifts per h on the ipsilateral hemisphere (i.e. cortical spreading depressions) (n=4). During 6 h of permanent MCA-occlusion (n=9) 1-10 DC potential shifts were observed, dependent on the brain location. Anoxic depolarization developed in the ischemic core. Outside ischemic areas DC potential shifts resembled cortical spreading depressions. Depolarizations in cortical ischemic borderzones were also transient, but generally long-lasting. Reperfusion induced 1 (n=5) or 3 h (n=6) after MCA-occlusion resulted in repolarization in 2.9+/-1.5 min. Ischemic lesion volumes after 7 h, calculated from diffusion-weighted and T(2)-weighted MR images, correlated significantly with total depolarization time in cortical perifocal zones (R=0.741, p<0.05), but not with the number of depolarizations. The extent of ischemic damage, as measured from alterations in the water diffusion coefficient and T(2), was also significantly related to the total time of depolarization (R=0.762 and 0.738, respectively, p<0.01). We conclude that early ischemic tissue injury is related to the total duration of tissue depolarization and not to the frequency of depolarizations.

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PubMed1999

Changes in the diffusion of water and intracellular metabolites after excitotoxic injury and global ischemia in neonatal rat brain.

The reduction of the apparent diffusion coefficient (ADC) of brain tissue water in acute cerebral ischemia, as measured by diffusion-weighted magnetic resonance imaging, is generally associated with the development of cytotoxic edema. However, the underlying mechanism is still unknown. Our aim was to elucidate diffusion changes in the intracellular environment in cytotoxic edematous tissue. The ADC of intracellular metabolites was measured by use of diffusion-weighted 1H-magnetic resonance spectroscopy after (1) unilateral N-methyl-D-aspartate (NMDA) injection and (2) cardiac arrest-induced global ischemia in neonatal rat brain. The distinct water ADC drop early after global ischemia was accompanied by a significant reduction of the ADC of all measured metabolites (P < 0.01, n = 8). In the first hours after excitotoxic injury, the ADC of water and the metabolites taurine and N-acetylaspartate dropped significantly (P < 0.05, n = 8). At 24 and 72 hours after NMDA injection brain metabolite levels were diminished and metabolite ADC approached contralateral values. Administration of the NMDA-antagonist MK-801 1.5 hours after NMDA injection completely normalized the water ADC but not the metabolite ADC after 1 to 2 hours (n = 8). No damage was detected 72 hours later and, water and metabolite ADC had normal values (n = 8). The contribution of brain temperature changes (calculated from the chemical shift between the water and N-acetylaspartate signals) and tissue deoxygenation to ischemia-induced intracellular ADC changes was minor. These data lend support to previous suggestions that the ischemia-induced brain water ADC drop may partly be caused by reduced diffusional displacement of intracellular water, possibly involving early alterations in intracellular tortuosity, cytoplasmic streaming, or intracellular molecular interactions.

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PubMed1999

Spatial assessment of the dynamics of lactate formation in focal ischemic rat brain.

Early identification of the potentially salvageable penumbra is critical for the determination of therapeutic intervention strategies in acute focal cerebral ischemia. This study differentiates the ischemic penumbra from the core on the basis of the dynamics of lactate formation. This was tested in a rat model of focal cerebral ischemia by infusion of [1-13C]-glucose, using lactate-edited magnetic resonance spectroscopic imaging techniques. The authors detected essentially no enrichment of lactate with 13C-label from the infused 13C-glucose in the ischemic core. However, in borderzone areas, 13C was incorporated into lactate, which could point toward compromised but potentially viable tissue. The authors' findings suggest that this combination of 13C-glucose infusion with the proposed magnetic resonance methods may aid in differentiating the penumbra from the core in cerebral ischemia.

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PubMed1998

Suppression of cortical spreading depressions after magnesium treatment in the rat.

The aim of this study was to investigate whether the neuroprotective properties of magnesium in cerebral ischaemia involve suppression of repetitive tissue depolarizations. Cortical spreading depressions (CSDs), evoked by cortical KCl application, and cardiac arrest-induced anoxic depolarization (AD) were measured by extracellular DC recording on intact rat brain. At 90 min after onset of CSDs saline, MK-801 (3 mg/kg) or MgSO4 (90 mg/kg) was given i.v. Latency time to AD was measured after 4 h. The frequency of CSDs was significantly reduced in animals treated with MgSO4 or MK-801. AD was significantly delayed by MgSO4 but not by MK-801. Our results suggest that suppression of depolarization by magnesium may play a role in its neuroprotective properties in cerebral ischaemia.

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PubMed1998

Dynamics of cerebral tissue injury and perfusion after temporary hypoxia-ischemia in the rat: evidence for region-specific sensitivity and delayed damage.

BACKGROUND AND PURPOSE: Selective regional sensitivity and delayed damage in cerebral ischemia provide opportunities for directed and late therapy for stroke. Our aim was to characterize the spatial and temporal profile of ischemia-induced changes in cerebral perfusion and tissue status, with the use of noninvasive MRI techniques, to gain more insight in region-specific vulnerability and delayed damage. METHODS: Rats underwent 20 minutes of unilateral cerebral hypoxia-ischemia (HI). We performed combined repetitive quantitative diffusion-weighted, T2-weighted, and dynamic susceptibility contrast-enhanced MRI from before HI to 5 hours after HI. Data were correlated with parallel blood oxygenation level-dependent MRI and laser-Doppler flowmetry. Finally, MRI and histology were done 24 and 72 hours after HI. RESULTS: Severe hypoperfusion during HI caused acute reductions of the apparent diffusion coefficient (ADC) of tissue water in the ipsilateral hemisphere. Reperfusion resulted in dynamic perfusion alterations that varied spatially. The ADC recovered completely within 1 hour in the hippocampus (from 0.68 +/- 0.07 to 0.83 +/- 0.09 x 10[-3] mm2/s), cortex (from 0.56 +/- 0.06 to 0.77 +/- 0.07 x 10[-3] mm2/s), and caudate putamen (from 0.58 +/- 0.06 to 0.75 +/- 0.06 x 10[-3] mm2/s) but only partially or not at all in the thalamus (from 0.65 +/- 0.07 to 0.68 +/- 0.12 x 10[-3] mm2/s) and substantia nigra (from 0.80 +/- 0.08 to 0.76 +/- 0.10 x 10[-3] mm2/s). Secondary ADC reductions, accompanied by significant T2 elevations and histological damage, were observed after 24 hours. Initial and secondary ADC decreases were observed invariably in the hippocampus, cortex, and caudate putamen and in approximately 70% of the animals in the thalamus and substantia nigra. CONCLUSIONS: Region-specific responses and delayed ischemic damage after transient HI were demonstrated by MRI. Acute reperfusion-induced normalization of ADCs appeared to poorly predict ultimate tissue recovery since secondary, irreversible damage developed eventually.

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PubMed1997

Cerebral ischemia and white matter edema in experimental hydrocephalus: a combined in vivo MRI and MRS study.

T2 and diffusion weighted MRI, as well as 31P and 1H MRS were performed in kaolin-induced hydrocephalic rats. Extracellular white matter edema was detected in the early stages of progressive hydrocephalus. Phosphocreatine (PCr)/inorganic phosphate (Pi) ratios in hydrocephalic animals were decreased compared to controls, and lactate was detected during the acute and chronic stages of hydrocephalus. These MR spectroscopic results are indicative of a compromised energy metabolism and suggest the occurrence of cerebral ischemia in experimental hydrocephalus.

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PubMed1997

Regional assessment of tissue oxygenation and the temporal evolution of hemodynamic parameters and water diffusion during acute focal ischemia in rat brain.

We assessed the temporal and spatial correlation between perfusion deficits and tissue damage in the first hours of focal cerebral ischemia in the rat. Repetitive dynamic susceptibility contrast-enhanced ('bolus track') and diffusion-weighted (DW) MRI, performed from ca. 0.5 up to 6 h after intraluminal middle cerebral artery occlusion (MCA-O), allowed the determination of the time course of various hemodynamic parameters and ischemic tissue damage in specific brain regions. In addition, blood oxygenation level dependent (BOLD) MRI combined with a respiratory challenge provided complementary information on brain hemodynamics. Within the territory of reduced blood flow, the degree of the hemodynamic disturbances was heterogeneous. Interestingly, the spatial pattern of perfusion deficiencies remained essentially the same from ca. 0.5 to 6 h post-MCA-O. However, the area and the extent of ischemic tissue damage, as expressed by reductions in the apparent diffusion coefficient (ADC) of tissue water, tended to progress with increasing occlusion time. Different ADC profiles correlated with different degrees of hemodynamic disturbances. In the ischemic core, which showed severely compromized perfusion, the ADC dropped significantly within 1 h. In perifocal areas, ADC reductions were delayed and less pronounced. Data from the bolus track and BOLD MRI experiments revealed the existence of residual flow, particularly in perifocal regions. Our data point to a time-dependent change in the relationship between ADC reductions and hemodynamic alterations and, therefore, agree with the concept of a progressively increasing perfusion threshold for ischemic tissue damage as a function of time of ischemia.

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PubMed1996

Status of the neonatal rat brain after NMDA-induced excitotoxic injury as measured by MRI, MRS and metabolic imaging.

Intrastriatal injection of the excitotoxin N-methyl-D-aspartate (NMDA) in neonatal rat brain resulted in an acute ipsilateral decrease of the apparent diffusion coefficient (ADC) of brain tissue water, as measured with diffusion-weighted MRI. The early diffusion changes were accompanied by only mild changes in the overall metabolic status as measured by in vivo 1H MRS and 31P MRS and metabolic imaging of brain sections. Minimal decreases in the high-energy phosphate levels and a small hemispheric acidosis were observed in the first 6 h after NMDA administration. In addition, there was very modest lactate accumulation. Twenty-four hours after the induction of the excitotoxic injury the tissue energy status was still only moderately affected, whereas an overall decrease of 1H MRS-detected brain metabolites was found. Treatment with the non-competitive NMDA-antagonist MK-801 given within 90 min after NMDA injection rapidly reversed the NMDA-induced changes in the entire ipsilateral hemisphere. The effect of the competitive NMDA-antagonist D-CPPene was restricted to the cortical areas and was accomplished on a slower time scale. Our results indicate that; (i) early excitotoxicity in the neonatal rat brain does not lead to profound changes in the metabolic status; and (ii) brain tissue water ADC changes are not necessarily associated with a metabolic energy failure.

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PubMed1996

Dynamic changes in water ADC, energy metabolism, extracellular space volume, and tortuosity in neonatal rat brain during global ischemia.

To obtain a better understanding of the mechanisms underlying early changes in the brain water apparent diffusion coefficient (ADC) observed in cerebral ischemia, dynamic changes in the ADC of water and in the energy status were measured at postnatal day 8 or 9 in neonatal rat brains after cardiac arrest using 1H MRS/MRI and 31P MRS, respectively. The time courses of the MR parameters were compared with changes in the extracellular space (ECS) volume fraction (alpha) and tortuosity (lambda), determined from concentration-time profiles of tetramethylammonium applied by iontophoresis. The data show a decrease of the ADC of tissue water after induction of global ischemia of which the time course strongly correlates with the time course of the decrease in the ECS volume fraction and the increase in ECS tortuosity. This indicates that cell swelling is an important cause for the ADC decrease of water.

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PubMed1996

Biexponential diffusion attenuation in various states of brain tissue: implications for diffusion-weighted imaging.

Diffusion-weighted single voxel experiments conducted at b-values up to 1 x 10(4) smm-2 yielded biexponential signal attenuation curves for both normal and ischemic brain. The relative fractions of the rapidly and slowly decaying components (f1, f2) are f1 = 0.80 +/- 0.02, f2 = 0.17 +/- 0.02 in healthy adult rat brain and f1 = 0.90 +/- 0.02, f2 = 0.11 +/- 0.01 in normal neonatal rat brain, whereas the corresponding values for the postmortem situation are f1 = 0.69 +/- 0.02, f2 = 0.33 +/- 0.02. It is demonstrated that the changes in f1 and f2 occur simultaneously to those in the extracellular and intracellular space fractions (fex, f(in)) during: (i) cell swelling after total circulatory arrest, and (ii) the recovery from N-methyl-D-aspartate induced excitotoxic brain edema evoked by MK-801, as measured by changes in the electrical impedance. Possible reasons for the discrepancy between the estimated magnitude components and the physiological values are presented and evaluated. Implications of the biexponential signal attenuation curves for diffusion-weighted imaging experiments are discussed.

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PubMed1996

Diffusion of metabolites in normal and ischemic rat brain measured by localized 1H MRS.

The apparent diffusion coefficient (ADC) of choline-containing compounds (Cho), creatine and phosphocreatine (Cre), N-acetyl-aspartate (NAA), lactate, and water was measured in normal rat brain, and in the ischemic and contralateral region of rat brain approximately 3 and 24 h after induction of focal cerebral ischemia. After 3 h of ischemia, the ADC of Cre and NAA in the ischemic region had significantly decreased by 29% and 19%, respectively (P < 0.05). Lactate ADC was also obtained in the ischemic region. After 24 h of focal ischemia, no ADC values could be measured for NAA, Cre and Cho in the ischemic region because their concentrations had become too low. The ADCs of lactate and water in the ischemic volume were virtually identical at 3 and 24 h after occlusion. The experiments suggest that the ADC decrease of water after induction of ischemia is partly caused by changes in the diffusion characteristics of the intracellular compartment.

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PubMed1996

Mechanical lesions of the fimbria fornix in rat brain studied by 1H-magnetic resonance imaging. Evidence for long-lasting dynamic alterations in the ipsilateral ventricular system.

In vivo 1H-NMR imaging was employed to study dynamic changes in the status of tissue water as a function of time after mechanical brain injury induced by partial unilateral transection of the fimbria fornix (FF) in the rat brain and was correlated with histology. Changes in the brain tissue were reproducibly found in distinct regions which were exclusively located in the lesioned hemisphere. The most pronounced changes concerned the lateral ventricle. Ventricular enlargement became evident posterior to the site of transection after a few hours and was maximal after 2-4 days. At later time points the posterior ventricular expansion was reduced. The lateral ventricle anterior to the site of transection was significantly enlarged from day 1 and continued to expand for up to 7 months. Tissue response at the site of transection, mainly involving the hippocampal formation and the thalamus, was first manifested after 24 h, while signs of progressive tissue degeneration were apparent in the long term.

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PubMed1995

T1 and T2 relaxation times of the major 1H-containing metabolites in rat brain after focal ischemia.

The relaxation properties of water and metabolites were measured in rat brain following the occlusion of the middle cerebral artery (MCA) with localized 1H MRS. The PRESS sequence was employed to select volumes of 39 microL in the ischemic and the contralateral hemisphere. T1 and T2 relaxation times and peak intensities of water, choline containing compounds (Cho), creatine and phosphocreatine (Cre) and N-acetyl aspartate (NAA) in both hemispheres were determined at 3-6 h, 1 day and 3 or 4 days after occlusion. Lactate in the ischemic hemisphere was also quantified. The relaxation properties and peak intensities of NAA, Cre and Cho remained unchanged in the ischemic volume during the first 3-6 h of ischemia as compared to the contralateral volume. Water T2 was slightly increased in the ischemic volume. After 24 h the T1 and T2 of water and Cre and the T1 of Cho had increased significantly in the ischemic volume, while the peak intensities of Cho, Cre and NAA were reduced. It appears therefore that tissue changes which occur in the early phase of ischemia have no significant effects on the relaxation behaviour of the metabolites. However, ischemic brain damage affects the relaxation behaviour and concentration of the metabolites and water at later stages.

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PubMed1992

1H-NMR imaging of fimbria fornix lesions in the rat brain.

Mechanical lesions of the fimbria fornix (FF) have been widely used as a model to investigate the recovery of damaged brain tissue. 1H-NMR imaging was employed to non-invasively measure changes in the brain after unilateral FF transection. Rats were subjected to NMR imaging at various times after the lesions were made. The experimental protocol included (multislice) T2-weighted and diffusion-weighted imaging thereby allowing the construction of two-dimensional maps of the relaxation time T2 (transverse or spine-spin relaxation time) and the apparent diffusion coefficient (ADC) of water. FF transection induced considerable changes in the status of the brain tissue at a number of different locations which were exclusively present in the affected hemisphere. At 1 day post-lesion the region of the lateral ventricle and hippocampus started to display pronounced changes in that T2- and diffusion-weighted images showed a hyperintensity and a hypointensity, respectively. These effects were maximal around day 2 to 4 whereafter a slow recovery towards the control situation was observed. Immediately after transection the FF lesion itself could be visualized. These early images pointed to an aspecific disruption of the tissue due to the mechanical intervention. Interestingly, however, from day 2 post-lesion a number of changes became evident in this region which seemed to be localized to specific structures, including the ventricle and hippocampus. After one month the presumably ventricle effect dominated and was predominantly localized to the anterior side of the FF lesion.(ABSTRACT TRUNCATED AT 250 WORDS)

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