[DoNTRuN a neurosurgical trainee network; network for the advancement of clinical research]. / DoNTRuN, een neurochirurgisch assistentennetwerk.

There is a lot of research into the effectiveness of interventions, but good evidence for many interventions is missing. This is very true of simple and frequently performed treatments. These interventions are often done by trainees in the course of their specialist training, and for this reason they are in a unique position to carry out research into them. There are far fewer high-quality, multicentre clinical trials in the surgical specialisations than in any other specialisation. As trainee neurosurgeons, we are of the opinion that this can be improved upon. With the establishment of the Dutch Neurosurgical Trainee Research Network (DoNTRuN), a national network, we are aiming to initiate and carry out new clinical trials. This initiative, which is currently unique in the Netherlands, will not only enable us to set up multicentre clinical trials relatively simply, but will also educate trainees in the carrying out of thorough clinical research, an area neglected in the current training program.

Preventing ventriculostomy-related infections with antibiotic-impregnated drains in hospitals: a two-centre Dutch study.

This observational cohort study assessed the effect of the introduction of antibiotic-impregnated external ventricular drains (AI-EVDs), as opposed to plain silicone EVDs, on the occurrence of ventriculostomy-related infections (VRIs) in two Dutch hospitals, with no other changes to their clinical practice. VRI was defined using the criteria of the Centers for Disease Control and Prevention, and with a culture-based definition. A propensity-score-adjusted competing risks survival analysis showed that introduction of AI-EVDs did not significantly decrease the risk of VRIs in routine care, nor affect the bacterial aetiology, even after adjustment for confounding and competing events.

Familial occurrence of brain arteriovenous malformations: a systematic review.

BACKGROUND: Brain arteriovenous malformations (BAVMs) are thought to be sporadic developmental vascular lesions, but familial occurrence has been described. We compared the characteristics of patients with familial BAVMs with those of patients with sporadic BAVMs. METHODS: We systematically reviewed the literature on patients with familial BAVMs. Three families that were found in our centre were added. Age, sex distribution and clinical presentation of the identified patients were compared with those in population based series of patients with sporadic BAVMs. Furthermore, we calculated the difference in mean age at diagnosis of parents and children to study possible anticipation. RESULTS: We identified 53 patients in 25 families with BAVMs. Mean age at diagnosis of patients with familial BAVMs was 27 years (range 9 months to 58 years), which was younger than in the reference population (difference between means 8 years, 95% CI 3 to 13 years). Patients with familial BAVMs did not differ from the reference populations with respect to sex or mode of presentation. In families with BAVMs in successive generations, the age of the child at diagnosis was younger than the age of the parent (difference between means 22 years, 95% CI 13 to 30 years), which suggests clinical anticipation. CONCLUSIONS: Few patients with familial BAVMs have been described. These patients were diagnosed at a younger age than sporadic BAVMs whereas their mode of presentation was similar. Although there are indications of anticipation, it remains as yet unclear whether the described families represent accidental aggregation or indicate true familial occurrence of BAVMs.

Frameless stereotactic subcaudate tractotomy for intractable obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is a chronic, disabling disorder. Psychosurgery may be indicated for a subset of patients for whom no conventional treatment is satisfactory. This paper focuses on the stereotactic subcaudate tractotomy (SST). Thus far, these procedures have been carried out using frame-based stereotactic techniques. However, modern - highly accurate - frameless stereotactic procedures have successfully been introduced in neurosurgical practice. We developed a novel frameless stereotactic subcaudate tractotomy procedure with promising initial results in a patient suffering from intractable OCD. This is the first report on frameless SST. Future studies should examine whether other ablative stereotactic psychosurgery procedures can be done using frameless stereotactic methods.

Frameless stereotactic placement of ventriculoperitoneal shunts in undersized ventricles: a simple modification to free-hand procedures.

The aim of this report is to introduce a simple modification to the free-hand frameless stereotactic placement of ventriculoperitoneal shunts in undersized ventricles. In this technical note, we describe our experience with ventricular catheter placement in two children suffering from shunt dependent idiopathic intracranial hypertension using an image-guided instrument holder with a catheter guide. In both patients, the surgical procedure proved to be easy and accurate, with good initial clinical results. The use of an image-guided instrument holder is a modification to the free-hand frameless stereotactic placement of ventriculoperitoneal shunts in undersized ventricles.

Clinical evaluation of stereotactic brain biopsies with an MKM-mounted instrument holder.

OBJECT: The aim of this study was to assess the clinical usefulness and accuracy of robot-assisted frameless stereotactic brain biopsies with a recently introduced MKM-mounted instrument holder. METHODS: Twenty-three patients with intracranial lesions participated in this study. Depending on the size of the intracranial lesion, fiducials for image-to-patient co-ordinate transformation consisted either of bone screws or adhesive markers. Shortly after surgery, postoperative MRI-imaging was performed to demonstrate the location of the biopsy site. These images were compared with the preoperative images to assess the biopsy localisation error. RESULTS: Postoperative biopsy sites could be demonstrated in six patients with bone screws and in 14 with adhesive markers. These two subgroups yielded average biopsy localisation errors of 3.3 mm (SD 1.7 mm) and 4.5 mm (SD 2.0 mm) respectively. This difference was not statistically significant. One biopsy was located in a liquefied haematoma. All others yielded pathological tissue. There were two postoperative haemorrhages, of which only one was temporarily symptomatic. There was no mortality in the first 30 days after surgery. CONCLUSIONS: Robot-assisted frameless point-stereotactic techniques represent an alternative to frame-based techniques for the performance of stereotactic biopsies.

Magnesium therapy after aneurysmal subarachnoid haemorrhage a dose-finding study for long term treatment.

BACKGROUND: Magnesium is a neuroprotective agent which might prevent or reverse delayed cerebral ischemia (DCI) after aneurysmal subarachnoid haemorrhage (SAH). Although the dosage for short-term magnesium therapy is well established, there is lack of knowledge on the dosage for extended use of magnesium. Our aim was to find a dosage schedule of magnesium sulphate to maintain a serum magnesium level of 1.0-2.0 mmol/L for 14 days to cover the period of DCI. METHODS: We prospectively studied 14 patients admitted within 48 hours after aneurysmal subarachnoid haemorrhage (SAH) to our hospital. Magnesium sulphate was administrated intravenously for 14 days, using 3 different dosage schedules. Group A (n=3) received a bolus injection of 16 mmol magnesium sulphate followed by a continuous infusion of 16 mmol/daily; group B (n=6) a continuous infusion of 30 mmol/daily; and group C (n=5) a continuous infusion of 64 mmol/daily. Serum magnesium was measured at least every two days and all patients were under continuous observation during magnesium treatment. Renal magnesium excretion was measured only in group C. FINDINGS: In treatment group A the mean serum magnesium level during treatment was 1.03+/-0.14 (range 0.82-1.34) mmol/L, in group B 1.10+/-0.15 (range 0.87-1.43) mmol/L, and in group C 1.38+/-0.18 (range 1.11-1.98) mmol/L. The renal magnesium excretion in group C was equal to the administrated doses within 48 hours after treatment had started. All patients in group A reported a flushing sensation during the bolus injection; no other side effects were noted. INTERPRETATION: With a continuous intravenous dosage of 64 mmol/L per day, serum magnesium levels maintained within the range of 1.0-2.0 mmol/L for 14 days.

An MKM-mounted instrument holder for frameless point-stereotactic procedures: a phantom-based accuracy evaluation.

To enable the use of the Mehrkoordinaten Manipulator (MKM) robotic navigation system for frameless point stereotactic procedures, a new instrument holder is presented. A phantom-based accuracy study was performed in which this new method was compared with frame-based procedures performed using the Brown-Roberts-Wells (BRW) stereotactic frame. The authors acquired computerized tomography scans of a test phantom, consisting of 19 acrylic plastic target rods on a circular base. These images were used in frame-based (BRW) and frameless (MKM) localization experiments. In both cases the authors calculated the distances between the actual target positions and the positions reached stereotactically. The mean application accuracy (target registration error) was 0.68 mm when the BRW frame was used and 0.96 mm when the MKM system was used after manual repositioning of the microscope (p < 0.001). Positioning accomplished using robotics only demonstrated a slightly larger inaccuracy: 1.47 mm (p < 0.005). Because the surgeon is concerned with the largest error in an individual case rather than the mean error in a large number of cases, the mean + three standard deviations was also compared. This value differed very little between the manually positioned MKM system and the BRW frame (2.04 mm and 1.84 mm, respectively). Although repeatability per target appeared to be slightly better when the BRW frame was used, accuracy was more homogeneous over the phantom volume when the MKM system was used (both differences were not significant). In conclusion, the accuracy of point stereotactic procedures performed using an instrument holder attached to the system is comparable with the accuracy of procedures involving a stereotactic frame. Moreover, the frameless techniques and robotic features of the MKM enable a more surgeon- and patient-friendly stereotactic procedure.

Surgical anatomy of the cerebral arteries in patients with subarachnoid hemorrhage: comparison of computerized tomography angiography and digital subtraction angiography.

OBJECT: The purpose of this study was to compare computerized tomography (CT) angiography and digital subtraction (DS) angiography studies in patients with subarachnoid hemorrhage (SAH) to assess their vascular anatomy relevant to cerebral aneurysm surgery. METHODS: From a prospective series of 100 patients with SAH, the authors selected 73 patients whose CT angiography studies were of adequate quality and in whom DS angiography of both carotid arteries had been performed. Eleven patients with no DS angiographic studies of the vertebrobasilar artery were only evaluated for the anterior half of the circle of Willis. Anterior communicating arteries (ACoAs), both precommunicating anterior cerebral arteries (A1 segments), both posterior communicating arteries (PCoAs), and both precommunicating posterior cerebral arteries (P1 segments) were assessed on CT angiography and DS angiography by two independent observers. CONCLUSIONS: Computerized tomography angiography compares well with DS angiography for visualizing normal-sized arteries, and is superior for visualizing ACoAs and hypoplastic A1 and P, segments. Important preoperative aspects such as dominant A1 segments and PCoAs are equally well seen using either modality. Neither method enabled the authors to visualize more than 50% of PCoAs. Use of CT angiography can provide the required preoperative anatomical information for aneurysm surgery in most patients with SAH.

Randomized pilot trial of postoperative aspirin in subarachnoid hemorrhage.

OBJECTIVE: To assess the safety and feasibility of a clinical trial on the effectiveness of acetylsalicylic acid (ASA) in subarachnoid hemorrhage (SAH). BACKGROUND: Several studies have indicated that increased platelet activity might be involved in the pathogenesis of delayed cerebral ischemia (DCI) after SAH. METHOD: Fifty patients who had early surgery (< or =4 days) for a ruptured aneurysm were enrolled in this randomized, double-blind, placebo-controlled trial. Trial medication, consisting of suppositories with 100 mg ASA versus placebo, was started immediately after surgical clipping of the aneurysm and continued for 21 days. End points were functional outcome and quality of life at 4 months, clinical deterioration after operation, development of DCI, hypodense lesion on postoperative CT, and hemorrhagic complications. RESULTS: One-third of all patients with aneurysmal SAH were eligible for the trial. Fifteen of 26 patients receiving placebo deteriorated clinically versus 10 of 24 patients receiving ASA; 4 patients in each group deteriorated from DCI. Postoperative hypodensities on CT were observed in 27 patients, distributed equally in both groups. Functional outcome and quality-of-life scores were slightly in favor of patients who had received ASA, but not to a significant degree (p = 0.22). Two patients in the ASA group had an asymptomatic hemorrhagic complication, and one patient in the placebo group had a fatal and another a symptomatic hemorrhagic complication. CONCLUSION: This pilot study shows that a clinical trial of acetylsalicylic acid (ASA) in subarachnoid hemorrhage (SAH) is feasible and probably safe. The effectiveness of ASA on functional outcome and delayed cerebral ischemia has to be studied in a larger trial.

Computerized tomography angiography in patients with subarachnoid hemorrhage: from aneurysm detection to treatment without conventional angiography.

OBJECT: The purpose of this study was to determine prospectively whether and to what extent computerized tomography (CT) angiography can serve as the sole imaging method for a preoperative workup in patients with ruptured intracranial aneurysms. METHODS: During a 1-year period, all patients who presented to the authors' hospital with subarachnoid hemorrhage demonstrated by unenhanced CT scanning or lumbar puncture underwent CT angiography. Two radiologists evaluated the CT angiography source images and maximum intensity projection slabs and arrived at a consensus. They categorized the quality of the CT angiography as adequate or inadequate and classified aneurysms that were detected as definitely or possibly present. The parent artery of anterior communicating artery aneurysms was identified by asymmetrical anterior cerebral artery size and asymmetrical aneurysm location. The parent artery was indicated by the larger A1 segment in cases of asymmetrical A1 size. Only CT angiograms of adequate quality that revealed aneurysms classified as definitely present and with an unequivocal parent artery were presented to the neurosurgeons, who decided whether preoperative digital subtraction (DS) angiography should still be performed. Forty-nine of the 100 studied patients did not undergo surgery because of poor clinical condition, nonaneurysmal cause of the hemorrhage, or endovascular treatment of the ruptured aneurysm. Of the 51 patients who underwent surgery, radiologists required DS angiography in 17 patients; the imaging technique provided greater certainty in 13 instances. The neurosurgeons required DS angiography 11 times; this provided additional information in two instances. Twenty-three (45%) of the 51 patients were surgically treated successfully on the basis of CT angiography findings alone. CONCLUSIONS: Computerized tomography angiography can replace DS angiography as the preoperative neuroimaging technique in a substantial proportion of patients with ruptured intracranial aneurysms.

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.

Subarachnoid hemorrhage: aneurysm detection and preoperative evaluation with CT angiography.

PURPOSE: To evaluate if computed tomographic (CT) angiography can replace digital subtraction angiography (DSA) for aneurysm detection and as preoperative work-up in patients with subarachnoid hemorrhage (SAH). MATERIALS AND METHODS: Prospectively, 100 patients with SAH underwent CT angiography; 80 also underwent DSA. Two observers independently evaluated CT angiographic source images and maximum intensity projection slabs. Neurosurgeons compared CT angiograms and DSA images for presurgical evaluation. RESULTS: On CT angiograms, the observers detected 73 and 70 of 75 symptomatic aneurysms; 96% of the detected aneurysms were classified as definitely present. Of 16 incidental aneurysms, 12 and 10 were detected by the observers. With adequate CT angiographic quality, parent artery side of anterior communicating aneurysms was correctly predicted in 100% (95% confidence interval [CI]: 87%, 100%). Neurosurgeons assessed CT angiography as equal or superior to DSA in 83% (95% CI: 73%, 90%) of 87 aneurysms, and in 74% (95% CI: 63%, 82%) operation might have been based on CT angiographic findings alone. CONCLUSION: CT angiography depicted 90% of all aneurysms, and 90% were classified as definitely present. CT angiography must be of high quality with adequate depiction of the aneurysm and the parent artery for surgery to be performed on the basis of CT angiographic findings alone.

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.

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.

Dynamic magnetic resonance imaging and spectroscopie of experimental brain injury.

This article describes the use of non-invasive magnetic resonance (MR) methods for the characterization and monitoring of the pathophysiology of experimental brain injury in laboratory animals as a function of time and treatment. The impact of MR in brain research is primarily due to its non-invasive nature, thereby enabling repeated measurements in long-term studies, and due to the type of information that it provides. MR imaging (MRI) enables the measurement of the morphology/anatomy as well as the functional status of tissues under in vivo conditions. Compared to other in vivo imaging modalities, MRI has a high spatial resolution and allows for a remarkable soft tissue differentiation. MR spectroscopy (MRS) provides information on the biochemical/metabolic status of tissues. MR methods which have proven valuable in animal studies, can be readily translated to the clinical situation where MR-based diagnosis and treatment planning play a rapidly increasing role. After a short introduction into the principles of MR, we will illustrate the remarkable versatility of MR in research on brain injury from recent animal studies. Examples will be mainly drawn from experiments on early injury in focai cerebral ischemia and from research on mechanical brain trauma and excitotoxic lesions. The article ends with a brief description of the perspectives of MR in neuropsychiatry.

Changes in metabolites and tissue water status after focal ischemia in cat brain assessed with localized proton MR spectroscopy.

Localized proton spectroscopy was used to monitor changes in metabolism and the biophysical status of tissue water in cat brain induced by occlusion of the middle cerebral artery. Changes in the intensity of N-acetyl-aspartate (NAA), total creatine (tCr), and lactate (Lac) signals in localized volumes of interest in the ischemic hemisphere were quantified relative to the preischemic signal. Changes in the apparent diffusion coefficient (ADC), T1- and T2-relaxation times of water in those volumes were also quantified. Lactate was shown to increase rapidly in the first 0.5-2.0 h of ischemia and stabilized afterwards. The ADC of water started to decrease from 0.64 x 10(-9) m2/s to 0.54 x 10(-9) m2/s in the first minutes following occlusion, as was shown in two cases where ADC was measured with high temporal resolution, and stabilized after approximately 3 h at 0.38 x 10(-9) m2/s (n = 6). NAA and tCr decreased by 35% (P < 0.0001) and 30% (P < 0.005), respectively, in the first 8 h of ischemia in comparison with the preischemic control levels. T1 and T2 gradually increased with 0.3 s (P < 0.0001) and 5.2 ms (P < 0.0001), respectively, during the same time span.

Comparison of diffusion-weighted MRI with changes in cell volume in a rat model of brain injury.

The precise mechanisms that underlie acute changes in tissue water diffusion following cerebral ischemia or related insults such as glutamate exposure remain unexplained, but it has been suggested that these may be caused by cell swelling due to water uptake. This study was undertaken to compare the changes observed in diffusion-weighted MR images with changes in the cellular volume measured by electrical impedance in a model of N-methyl-D-aspartate-induced brain injury in perinatal rats. The results show that the temporal course of the intensity changes in the diffusion-weighted images parallelled the progressive shrinkage of the extracellular space measured from the electrical impedance. After administration of the N-methyl-D-aspartate antagonist MK-801 the signal enhancement in the images was reversed, which paralleled the normalization of the extracellular space observed by the impedance measurements. It was estimated that the extracellular space decreased from 24 to 12% while the apparent diffusion coefficient of water decreased from 0.89 x 10(-9) in normal tissue to 0.42 x 10(-9) m2/s in tissue exposed to N-methyl-D-aspartate. These data indicate that changes in tissue water diffusion are related to changes in cell volume.

Temporal evolution of NMDA-induced excitoxicity in the neonatal rat brain measured with 1H nuclear magnetic resonance imaging.

The aim of this study is to characterize the evolution of excitotoxic damage in neonatal rat brain by diffusion-weighted and T2-weighted magnetic resonance imaging. Results are compared with histological findings. Magnetic resonance imaging was performed at various times (15 min, 24 h, 3 days and 5 days) after intrastriatal microinjection of N-methyl-D-aspartate (NMDA) at postnatal day 8. The transverse relaxation time (T2) and apparent diffusion coefficient of water were determined. The results show an acute reduction of the apparent diffusion coefficient, reflected by an ipsilateral hyperintensity in the diffusion-weighted images, within 15 min after intrastriatal NMDA injection. At this time no changes in the T2-weighted images were apparent. The volume of the hyperintensity was relatively large with a radius of approximately 2 mm and coincided with histological signs of pronounced karyo-dendritic swelling. Subcutaneous administration of MK-801 25 min after the intracerebral NMDA injection readily reversed the hyperintensity and resulted in complete protection as verified by histology. Areas with increased T2 values were observed 1 day after NMDA microinjection and corresponded to regions with obvious cell necrosis. Five days after NMDA injection the lesion was evident using both diffusion- and T2-weighted images and coincided with an overt lesion comprising areas of cell loss and dilatation of the ipsilateral ventricle. In conclusion, this study illustrates the possibility of using diffusion-weighted imaging as a tool to monitor efficacy of treatment strategies at an early stage of excitotoxic injury.

Temporal evolution of focal cerebral ischemia in the rat assessed by T2-weighted and diffusion-weighted magnetic resonance imaging.

The present study was undertaken to characterize the formation of ischemic brain edema using diffusion-weighted and T2-weighted magnetic resonance imaging in a rat model of focal ischemia. The extent of edema formation was measured from multislice diffusion-weighted and T2-weighted spin-echo images acquired at various times after ischemia. The spin-spin relaxation time (T2) and the apparent diffusion coefficient in normal and ischemic tissue were also determined. The results show that on the diffusion-weighted images the lesion was clearly visible at 30 minutes after ischemia, while on the T2-weighted images it became increasingly evident after 2-3 hours. On both types of images the hyperintense area increased in size over the first 48 hours. After 1 week the hyperintensity on the diffusion-weighted images rapidly disappeared and evolved as a hypointense lesion in the chronic phase. These results confirm the high sensitivity of diffusion-weighted MRI for the detection of early ischemia. The temporal course of the edema observed on T2W-images is in agreement with the reported increase of total water content occurring in this model. The increase of the lesion observed on the diffusion-weighted images during the first 2 days points to an aggravation of cytotoxic edema that parallels the changes in free water shown by the T2-weighted images. It is shown that the highly elevated T2's of the infarcted area several days after ischemia can substantially contaminate the diffusion-weighted images.