Stroke mismatch volume with the use of ABC/2 is equivalent to planimetric stroke mismatch volume.

BACKGROUND AND PURPOSE: In the clinical setting, there is a need to perform mismatch measurements quickly and easily on the MR imaging scanner to determine the specific amount of treatable penumbra. The objective of this study was to quantify the agreement of the ABC/2 method with the established planimetric method. MATERIALS AND METHODS: Patients (n = 193) were selected from the NINDS Natural History Stroke Registry if they 1) were treated with standard intravenous rtPA, 2) had a pretreatment MR imaging with evaluable DWI and PWI, and 3) had an acute ischemic stroke lesion. A rater placed the linear diameters to measure the largest DWI and MTT lesion areas in 3 perpendicular axes-A, B, and C-and then used the ABC/2 formula to calculate lesion volumes. A separate rater measured the planimetric volumes. Multiple mismatch thresholds were used, including MTT volume - DWI volume ≥50 mL versus ≥60 mL and (MTT volume - DWI volume)/MTT volume ≥20% versus MTT/DWI = 1.8. RESULTS: Compared with the planimetric method, the ABC/2 method had high sensitivity (0.91), specificity (0.90), accuracy (0.91), PPV (0.90), and NPV (0.91) to quantify mismatch by use of the ≥50 mL definition. The Spearman correlation coefficients were 0.846 and 0.876, respectively, for the DWI and MTT measurements. The inter-rater Bland-Altman plots demonstrated 95%, 95%, and 97% agreement for the DWI, MTT, and mismatch measurements. CONCLUSIONS: The ABC/2 method is highly reliable and accurate for quantifying the specific amount of MR imaging-determined mismatch and therefore is a potential tool to quickly calculate a treatable mismatch pattern.

Blood-brain barrier disruption after cardiac surgery.

BACKGROUND AND PURPOSE: CNS complications are often seen after heart surgery, and postsurgical disruption of the BBB may play an etiologic role. The objective of this study was to determine the prevalence of MR imaging-detected BBB disruption (HARM) and DWI lesions after cardiac surgery. MATERIALS AND METHODS: All patients had an MRI after cardiac surgery. For half the patients (group 1), we administered gadolinium 24 hours after surgery and obtained high-resolution DWI and FLAIR images 24-48 hours later. We administered gadolinium to the other half (group 2) at the time of the postoperative scan, 2-4 days after surgery. Two stroke neurologists evaluated the images. RESULTS: Of the 19 patients we studied, none had clinical evidence of a stroke or delirium at the time of the gadolinium administration or the scan, but 9 patients (47%) had HARM (67% in group 1; 30% in group 2; P = .18) and 14 patients (74%) had DWI lesions (70% in group 1; 78% in group 2; P = 1.0). Not all patients with DWI lesions had HARM, and not all patients with HARM had DWI lesions (P = .56). CONCLUSIONS: Almost half the patients undergoing cardiac surgery have evidence of HARM, and three-quarters have acute lesions on DWI after surgery. BBB disruption is more prevalent in the first 24 hours after surgery. These findings suggest that MR imaging can be used as an imaging biomarker to assess therapies that may protect the BBB in patients undergoing heart surgery.

Hyperintense vessel sign on fluid-attenuated inversion recovery MR imaging is reduced by gadolinium.

The HVS on FLAIR imaging is a useful marker of acute ischemic stroke. We investigated whether prior administration of gadolinium-based contrast hindered detection of this sign on images from subjects with acute nonlacunar ischemic stroke <4.5 hours after onset. Both blinded and comparative unblinded analyses showed significantly reduced HVS detection on postcontrast images. We suggest that assessment for this sign should be performed on images acquired prior to contrast administration.

Hyperacute injury marker (HARM) in primary hemorrhage: a distinct form of CNS barrier disruption.

OBJECTIVE: The objective of the study was to characterize a previously unreported form of CNS barrier disruption in intracerebral hemorrhage (ICH): hyperacute injury marker (HARM). METHODS: In this retrospective cohort analysis of patients presenting with primary ICH, precontrast and postcontrast MRI scans obtained within 5 days of symptom onset were analyzed. The presence of CNS barrier disruption was defined by (1) perihematomal or intrahematomal enhancement visualized on postcontrast T1-weighted MRI or (2) HARM: sulcal or ventricular hyperintensity visualized on postcontrast fluid-attenuated inversion recovery sequences (graded on a 5-point scale). RESULTS: Forty-six patients were included in the analysis. Mean age was 65 years, median NIH Stroke Scale score was 7, and mean ICH volume was 12.2 mL (range 0.3-46.9 mL). HARM was visualized in 85% of patients, and this was moderate to severe in 50%. In all cases, the sulcal enhancement was noncontiguous with the hematoma. Of those patients with postcontrast T1-weighted imaging, perihematomal or intrahematomal contrast enhancement was visualized in 75% of patients. CONCLUSIONS: This study demonstrates that HARM occurs in intracerebral hemorrhage and that it likely represents a second type of CNS barrier disruption distinct from parenchymal postcontrast T1-weighted enhancement. Similar to T1 enhancement, this phenomenon may serve as a clinically useful biomarker to test therapies aimed at stabilizing acute ICH and CNS barrier disruption. Future studies are needed to further define the time course and prognostic implications of this finding.

Endothelial progenitor cells correlate with lesion volume and growth in acute stroke.

OBJECTIVES: Circulating endothelial progenitor cells (EPC) are markers of vascular injury and their numbers decrease in acute stroke. However, the relation of EPC levels to stroke severity has not been quantified. MRI measurements of lesion volume provide an objective method for stroke severity assessment and outcome prediction. This cross-sectional study aims to determine whether EPC are correlated with lesion volume at baseline, lesion growth, and final lesion volume. METHODS: Seventeen patients (median age 63 years, NIH Stroke Scale score 7) were selected from 175 patients with imaging-confirmed acute ischemic stroke. EPC were quantified by flow cytometry using CD34, CD133, and VEGFR2 surface markers. Brain MRI was performed at baseline and at days 1 and 5 after the stroke onset. Stroke lesion volumes were quantified. RESULTS: Larger lesion volumes measured on diffusion-weighted images (DWI) at baseline were associated with low EPC levels, while smaller lesion volumes and less lesion growth were linked with high levels of EPC subsets (CD34+CD133+, CD133+VEGFR2+, and CD34+ CD133+VEGFR2+). Similar results were observed with DWI lesion volumes and EPC (CD34+CD133+) on day 1. Lesion growth volume, represented as a difference between final lesion volume and baseline DWI, was larger in patients with lower day 1 EPC (CD133+VEGFR2+). After adjustments for age and admission glucose (model 1), mean arterial pressure and white blood cells (model 2), INR and hematocrit (model 3), the CD34+CD133+ subset remained predictive of baseline and day 1 lesion volumes, while CD133+VEGFR2+ predicted baseline lesion volume and growth of lesion volume. CONCLUSIONS: Higher EPC levels were indicative of smaller volumes of acute lesion, final lesion, and lesion growth, and may serve as markers of acute phase stroke severity. However, a larger prospective study is needed to confirm our findings.

Distal hyperintense vessels on FLAIR: an MRI marker for collateral circulation in acute stroke?

BACKGROUND: Hyperintense vessels (HV) on fluid-attenuated inversion recovery imaging are frequently observed in acute ischemic stroke patients. However, the exact mechanism and clinical implications of this sign have not yet been clearly defined. The features of HV and its relevance to other imaging factors are presented here. METHODS: Prominence and location of HV were documented in 52 consecutive patients with middle cerebral artery (MCA) territory infarction, before treatment with IV recombinant tissue plasminogen activator. Pretreatment ischemic lesion volume, perfusion lesion volume, and vessel occlusion were determined in addition to recanalization status and ischemic lesion volume on follow-up imaging. NIH Stroke Scale (NIHSS) was used as a measure of clinical severity. RESULTS: HV distal to arterial occlusion was observed in 73% of patients; more frequent in proximal than distal MCA occlusion patients. Among the 38 patients with proximal MCA occlusion, initial perfusion lesion volume was comparable among patients with different grade distal HV. However, patients with more prominent distal HV had smaller initial, 24-hour, and subacute ischemic lesion volumes and lower initial NIHSS scores. CONCLUSIONS: The presence of distal hyperintense vessels before thrombolytic treatment is associated with large diffusion-perfusion mismatch and smaller subacute ischemic lesion volumes in patients with proximal middle cerebral artery occlusion. DWI = diffusion-weighted imaging; FLAIR = fluid-attenuated inversion recovery; GRE = gradient recalled echo; HV = hyperintense vessels; MCA = middle cerebral artery; MRA = magnetic resonance angiography; MTT = mean transit time; NIHSS = NIH Stroke Scale; PWI = perfusion-weighted imaging; rt-PA = recombinant tissue plasminogen activator; TE = echo time; TI = inversion time; TIMI = thrombolysis in myocardial infarction; TR = repetition time.

Higher prevalence of cortical lesions observed in patients with acute stroke using high-resolution diffusion-weighted imaging.

Ischemic lesion conspicuity on routine diffusion-weighted imaging (DWI, 30 seconds) was compared with an improved sequence (high-resolution DWI [DWI-HR], 256 seconds) having increased spatial resolution and signal to noise and decreased eddy current artifact in 42 patients with acute ischemic stroke. Total lesion volumes were similar; however, twice as many lesions were identified on DWI-HR, predominately in cortical gray matter. Modest improvements to imaging resulted in increased conspicuity, potentially affecting diagnosis, suspected pathogenic mechanism, and therapeutic decision.

Assessment of CE-MRA for the rapid detection of supra-aortic vascular disease.

BACKGROUND: Contrast-enhanced MR angiography (CE-MRA) using a combined head and neck coil permits non-invasive imaging of the vasculature from the aortic arch through to the Circle of Willis in less than 2 minutes. OBJECTIVE: To determine the accuracy of CE-MRA for the detection of vascular pathology, in particular vascular stenoses, using digital subtraction angiography (DSA) as the gold standard. METHODS: In a prospective study of 81 patients referred for DSA, CE-MRA and DSA studies were performed within 72 hours of each other. CE-MRA was performed on a 1.5 Tesla clinical MRI scanner using a five-channel neurovascular array (head and neck coil), with dynamic tracking of the IV gadolinium bolus. CE-MRAs and DSA films were read by two interventional neuroradiologists blinded to the clinical presentation of the patient. RESULTS: On DSA, there were 77 vascular stenoses > or =50% identified, 51 extracranial and 26 intracranial. The overall sensitivity of CE-MRA using the neurovascular array for the detection of vascular stenoses > or =50% was 57% (95% CI: 46 to 68%) with a specificity of 98% (97 to 99%). The sensitivity for the detection of extracranial vascular stenoses > or =50% was 82% (72 to 93%) with a specificity of 97% (96 to 98%). However, the sensitivity for the detection of intracranial vascular stenoses > or =50% was only 8% (0 to 18%), with a specificity of 99% (98 to 100%). CONCLUSIONS: At this stage Contrast-enhanced MR angiography using a neurovascular coil shows promise as a rapid, specific, and noninvasive screening method for extracranial vascular disease, but not for intracranial vascular disease.

Early and late recurrence of ischemic lesion on MRI: evidence for a prolonged stroke-prone state?

BACKGROUND: Based on previous observations of a high rate of ischemic lesion recurrence on diffusion-weighted imaging (DWI) within 1 week after an acute ischemic stroke, the authors hypothesized that silent new ischemic lesions are common between 1 week and 90 days after index stroke and that early lesion recurrence may be associated with late lesion recurrence. METHODS: The authors studied 80 acute ischemic stroke patients who had initial MRI performed within 48 hours, and follow-up scans at 5 days and at 30 or 90 days after onset. Early lesion recurrences were defined as new ischemic lesions on 5-day DWI, and late lesion recurrences were defined as those on 30- or 90-day DWI or fluid attenuation inversion recovery image. Early lesion recurrence occurring outside the initial perfusion deficit was termed distant lesion recurrence. RESULTS: Late lesion recurrence occurred in 26%, more frequently observed on 30-day MRI than 90-day MRI (p = 0.016). Early lesion recurrence (OR 4.0; 95% CI 1.3 to 11.7) and distant early lesion recurrence (OR 6.9; 95% CI 1.5 to 32.2) were independently associated with late lesion recurrence by multiple logistic regression analyses. CONCLUSIONS: There may be a continued risk for recurrent ischemic lesions in the weeks following the clinically symptomatic stroke. Future studies are needed to investigate whether MRI-defined ischemic lesion recurrences predict subsequent clinical recurrence and thus may be a potential surrogate endpoint in stroke secondary prevention trials.

Determination of the MRI contrast agent concentration time course in vivo following bolus injection: effect of equilibrium transcytolemmal water exchange.

For bolus-tracking studies, it is commonly assumed that CR concentration bears a linear relationship with the measured (usually longitudinal) (1)H(2)O relaxation rate constant, R*(1) identical with(T(1) *)(-1). This requires that equilibrium transcytolemmal water exchange be in the fast exchange limit (FXL). However, though systems remain in fast exchange, the FXL will not usually obtain. Here, the consequences are considered: 1) the measurement of R(1) * itself can be affected, 2) the resultant non-linear [CR]-dependence causes significant error by assuming FXL, 3) the thermodynamic [CR] (based on the space in which CR is actually distributed) can be determined, 4) transcytolemmal water permeability may be estimated, and 5) the pharmacokinetic parameters can be factored. For a 30-sec, 0.17 mmol/kg dose of GdDTPA(2-), the FXL assumption underestimates the [CR] maximum in rat thigh muscle by a factor of almost two. Similar results are obtained for a rat brain GS-9L gliosarcoma tumor model.

Iron absorption and cellular transport: the mobilferrin/paraferritin paradigm.

Dietary inorganic iron is mostly ferric iron. This is solubilized at the acid pH level of the stomach where it chelates mucins and certain dietary constituents to keep them soluble and available for absorption in the more alkaline duodenum. Mucosal uptake of iron is facilitated by a beta 3 integrin and a 56 kDa protein known as mobilferrin. In the cytosol of the absorptive cell, iron is associated with a 520-kDa complex known as paraferritin which contains integrin, mobilferrin, and flavin monooxygenase. This complex serves as a ferrireductase to reduce iron to the ferrous state so that it is available for formation of end products such as heme proteins. The large complex has other constituents, such as beta 2 microglobulin, whose functions remain to be delineated. We postulate that the basolateral membranes of absorptive cells possess both holo-transferrin and apotransferrin receptors that regulate the ingress and egress of cellular iron, respectively. Unlike absorptive cells, nonintestinal cells appear to possess three pathways for uptake of inorganic iron: (1) the classical transferrin-transferrin receptor pathway, (2) the transferrin-associated transferrin receptor independent pathway (TRIP), and (3) the transferrin-independent mobilferrin-integrin pathway (MIP) observed in intestinal absorptive cells. The TRIP is used when transferrin receptors become saturated at physiological concentrations of iron and transferrin. The MIP may only be used efficiently for mucosal uptake of iron and iron-overloaded individuals with fully saturated transferrin. Alternatively, it may facilitate iron uptake from the TRIP after degradation of transferrin near the surface of the cell. However, both transferrin-associated pathways donate iron to a common intracellular iron pathway for ferri-reduction and probably other functions.

The alternate iron transport pathway: mobilferrin and integrin in reticulocytes.

Iron transport in reticulocytes is known to occur via the well-described transferrin-receptor-endosome pathway. An alternative pathway for iron transport independent of transferrin has been postulated in reticulocytes and other cells. Transport of iron into reticulocytes from ferric citrate solutions was shown to be saturable and independent of transferrin. During transport of iron from ferric citrate, both cell surface integrins, and a soluble protein, mobilferrin, were labelled. This demonstrated that the reticulocyte transferrin independent pathway for iron transport involved integrins and mobilferrin similar to intestinal absorptive cells. This pathway would be expected to transport iron into cells under conditions of iron overload and was capable of providing iron for haemoglobin synthesis. Mobilferrin was also radiolabelled when radioiron labelled transferrin was incubated with reticulocytes and this occurred with a different time course than was observed following reticulocyte exposure to radiolabelled ferric citrate. This suggested that mobilferrin may serve as an intermediary in both pathways.

Rapid progression of acquired amegakaryocytic thrombocytopenia to aplastic anemia.

Acquired amegakaryocytic thrombocytopenia is a rare disorder characterized by severe thrombocytopenia and selective, marked decrease or absence of megakaryocytes. Although immunosuppressive therapy (prednisone and/or antithymocyte globulin) has been shown to induce remissions in a subset of patients, most patients do not respond, and progression to aplastic anemia occurs in some cases. We report a case of acquired amegakaryocytic thrombocytopenia which, despite aggressive immunosuppressive treatment, rapidly progressed to aplastic anemia. Clinical, laboratory, and immunologic features of our patient's case are described and compared to those of the previously reported six cases that progressed from amegakaryocytic thrombocytopenia to aplastic anemia.

Severe transient hypoglycemia causes reversible change in the apparent diffusion coefficient of water.

BACKGROUND AND PURPOSE: The aim of this study was to determine the effects of temporary severe hypoglycemia on the apparent diffusion coefficient (ADC) acquired by diffusion-weighted MRI of brain water with the use of serial multislice ADC mapping in rats. Severe hypoglycemia reduces the extracellular space volume, as does ischemia. Demonstrating a reduction of ADC with hypoglycemia should increase our understanding of the mechanisms underlying ADC changes in ischemia and other conditions. METHODS: Fasted rats were given regular insulin (15 IU/kg IP). Rats were subjected to 15 minutes (n = 5) and 50 minutes (n = 5) of temporary severe hypoglycemia, causing a transiently isoelectric electroencephalogram (EEG). ADC mapping was performed every 30 seconds beginning at the onset of isoelectricity for 8.5 minutes. ADC maps were also obtained later during the isoelectric EEG period and 10, 20, 30, and 40 minutes after glucose infusion. Control images were obtained from a separate group of animals suffering cardiac arrest (n = 5). RESULTS: Abnormal ADC values were not observed before the onset of cerebral isoelectricity, except for isolated areas in the cortex and periventricular regions. Cortical ADC values globally declined at the onset of EEG isoelectricity. The ADC decline spread to subcortical regions within a few minutes. During the isoelectric period, significant declines of ADC values (27% to 45%) occurred in the entire brain. Glucose infusion normalized most of the ADC changes, even after a 50-minute period of isoelectricity. CONCLUSIONS: ADC mapping during hypoglycemia clearly demonstrates changes likely related to energy depletion. Most of these ADC declines were reversible. Hypoglycemia is a condition known to be associated with shrinkage of the extracellular space. These observations support the hypothesis that ADC reductions observed in ischemia are also related to shifts of water from the extracellular to the intracellular compartment.

A new design for a three-channel surface gradient coil employing a three-dimensional finite element model.

A new design of a three-channel surface gradient coil (SGC) is presented. The optimal objective of this design is to minimize parasitic field gradients by modifying the wire arrangement in the individual coils. A 3D finite element (FE) model is employed to analyze the SGC's field predictions. The numerical analysis results of the new SGC design indicate improved field behaviors when compared with those of a previously reported SGC designed by Cho and Yi (J. Magn. Reson. 94, 471-485 (1991)). To confirm the predicted improvement, two Gy (Y-axis) gradient coils, based on the old and new designs, have been constructed and installed in a General Electric CSI 2 Tesla MRI system with a 15-cm bore. Based on the resulting MR images, the new gradient coil configuration provides more uniform field gradients and less parasitic field gradients, which results in higher quality images than the previously reported SGC design. This paper also demonstrates the remarkable accuracy of the 3D FE simulation model.

The role of spreading depression in focal ischemia evaluated by diffusion mapping.

This study investigated the role of spontaneous and induced spreading depression (SD) on the evolution of focal ischemia in vivo. We induced focal ischemia in 12 rats using the middle cerebral artery suture occlusion (MCAO) method. Chemical stimulation of nonischemic ipsilateral cortex by potassium chloride application (KCl group; n = 7) and saline (NaCl group; n = 5) was performed at 15, 30, 45, and 60 minutes following MCAO, and SD was detected electrophysiologically. Ischemic lesion volumes assessed over 15-minute intervals, evaluated by continuous apparent diffusion coefficient (ADC) of water mapping, demonstrated that the ischemic region increased significantly during 15-minute time epochs with a single SD episode (36.5 +/- 12.9 mm3, mean +/- SD) or multiple SD episodes (39.8 +/- 22.3) compared with those without SD (13.9 +/- 11.5) (p = 0.0009). Infarct volume at postmortem 24 hours after MCAO was significantly larger in the KCl group, with more total SDs (237.8 +/- 13.8) than the NaCl group (190.5 +/- 12.6) (p = 0.0001). This study demonstrates that ischemia-related and induced SDs increase significantly ischemic lesion volume in vivo, supporting the hypothesis for a causative role of SD in extending focal ischemic injury.

Spreading waves of a reduced diffusion coefficient of water in normal and ischemic rat brain.

Using echo planar diffusion-weighted magnetic resonance imaging, we measured three-dimensional changes in the apparent diffusion coefficient (ADC) of water in eight contiguous coronal slices, encompassing the entire rat brain, before and after local cortical stimulation. We applied chemical (potassium chloride application; n = 6) and mechanical (needle stab; n = 4) stimulations to the right posterior parietal rat cortex. In all animals in which potassium chloride or the needle stab was applied, a region of decreased ADC values to a mean of 0.45 +/- 0.03 x 10(-5)cm2/s occurred. These reduced ADC levels appeared in the posterior parietal cortex within 1 min after cortical stimulation and the change recovered within 1 min. Then a ripple-like movement of similar changes developed across the unilateral cortex. This change was localized to the cortex and no significant ADC changes occurred in subcortical structures. The propagating speed of this movement was 3.4 +/- 0.5 mm/min. These findings are compatible with spreading depression as observed electrophysiologically. Similar ADC changes occurred in areas distinct from the ischemic lesion in 3 of 12 animals subjected to focal cerebral ischemia. This magnetic resonance method could detect spreading ADC decline if it occurred in human diseases including brain ischemia.

Multislice diffusion mapping for 3-D evolution of cerebral ischemia in a rat stroke model.

Diffusion-weighted magnetic resonance imaging (DWI) can quantitatively demonstrate cerebral ischemia within minutes after the onset of ischemia. The use of a DWI echo-planar multislice technique in this study and the mapping of the apparent diffusion coefficient (ADC) of water, a reliable indicator of ischemic regions, allow for the detection of the three-dimensional (3-D) evolution of ischemia in a rat stroke model. We evaluated 13 time points from 5 to 180 minutes after occlusion of the middle cerebral artery (MCA) and monitored the 3-D spread of ischemia. Within 5 minutes after the onset of ischemia, regions with reduced ADC values occurred. The core of the lesion, with the lowest absolute ADC values, first appeared in the lateral caudoputamen and frontoparietal cortex, then spread to adjacent areas. The volume of ischemic tissue was 224 +/- 48.5 mm3 (mean +/- SEM) after 180 minutes, ranging from 92 to 320 mm3, and this correlated well with the corrected infarct volume at postmortem (194 +/- 23.1 mm3, r = 0.72, p < 0.05). This experiment demonstrated that 3-D multislice diffusion mapping can detect ischemic regions noninvasively 5 minutes after MCA occlusion and follow the development of ischemia. The distribution of changes in absolute ADC values within the ischemic region can be followed over time, giving important information about the evolution of focal ischemia.

MRI diffusion mapping of reversible and irreversible ischemic injury in focal brain ischemia.

The reduction of the apparent diffusion coefficient (ADC) of water shortly after a focal ischemic insult is thought to reflect intracellular water accumulation (cytotoxic edema) related to high-energy metabolism failure and loss of ion homeostasis. We attempted to clarify whether varying ranges of ADC measurements in ischemic brain tissue can be used to differentiate between reversible and irreversible ischemic lesions before reperfusion in a temporary ischemia model. We induced 45 minutes of temporary ischemia in 12 rats using the middle cerebral artery suture occlusion method. Regional changes of ADC values were serially measured in seven regions of interest in each hemisphere and evaluated by delta ADC, defined as the difference between ADC value in an ischemic region and that in a contralateral homologous region. We acquired dynamic contrast-enhanced perfusion images 2 minutes before and after reperfusion to document reduced perfusion and its restoration. We confirmed the infarct area by 2,3,5-triphenyltetrazolium chloride staining 24 hours after occlusion and correlated this with the MRI studies. Recovery of initially reduced ADC values occurred only in ischemic regions where delta ADC values were not below -0.25 x 10(-5) cm2/sec. Although the extent of infarction at postmortem examination varied in regions with moderately decreased prereperfusion ADC values, more than 70% of regions of interest with slight declines of prereperfusion ADC values exhibited no infarction. ADC values progressively decreased after reperfusion in regions that initially had severely decreased prereperfusion ADC values, and postmortem examination always demonstrated infarction in such regions.(ABSTRACT TRUNCATED AT 250 WORDS)

Spreading waves of decreased diffusion coefficient after cortical stimulation in the rat brain.

A method is demonstrated for the noninvasive detection and study of spreading cortical depression. Spreading depression (SD) was elicited in rats by topical application of potassium chloride to the exposed cortex. The apparent diffusion coefficient (Dapp) of water in a region of the cortex, measured using a PFG-NMR spin echo sequence with an observation time of 40 ms, declines 35% within 30 s and recovers to the normal value within the next 30 s. The region of decreased Dapp was shown to be 2 mm in size and to move in the cortex, away from the point of application, with a uniform velocity of 3.3 +/- 0.5 mm/min. The behavior of the affected region is consistent with other reports of the behavior of SD as monitored by electrophysiological means. The technique can be implemented on currently available MRI equipment and makes possible the noninvasive study of SD in animal models of neurological disorders, their therapeutic intervention, and possibly the study of SD in humans.