Serial magnetic resonance imaging in experimental primate stroke: validation of MRI for pre-clinical cerebroprotective trials

Precise assessment of stroke outcome is critical for pre-clinical testing of cerebroprotective strategies. Differences in stroke volume measured by various magnetic resonance imaging (MRI) techniques are documented in humans, but not well described in experimental primate stroke. This study characterizes changes in stroke volume using serial MRI scans in a baboon model of reperfused cerebral ischemia. The location/area of hyperintensity on MRI corresponded with the TTC-stained infarct region. T2-weighted fast spin echo (T2W FSE), fluid attenuated inversion recovery (FLAIR), and diffusion weighted imaging (DWI) showed a decrease in infarct volume between 72 h and nine days post-ischemia (p = ns, p = 0.029, and p = 0.006). T2W FSE and FLAIR demonstrated an increase in infarct volume from 24 h to nine days post-ischemia, while DWI displayed a decrease over the same period. While early T2W FSE, FLAIR, and DWI all correlated with late infarct volume (p < 0.001), 72 h T2W FSE was the best direct measure (2.39% +/- 1.40% unity deviation). Serial MRI in a nonhuman primate model of focal cerebral ischemia recapitulates findings in clinical stroke. MRI at 72 h accurately predicts late infarct volume.     

Infarct volume on apparent diffusion coefficient maps correlates with length of stay and outcome after middle cerebral artery stroke

BACKGROUND: Diffusion-weighted MRI (DWI) can depict acute ischemia based on decreased apparent diffusion coefficient (ADC) values. ADC maps, unlike DWI (which have contributions from T2 properties), solely reflect diffusion properties. Recent studies indicate that severity of neurological deficit corresponds with degree of ADC alteration. PURPOSE: To determine whether infarct volume on ADC maps correlates with length of hospitalization and clinical outcome in patients with acute ischemic middle cerebral artery (MCA) stroke. STUDY POPULATION: Forty-five consecutive patients with acute (3 SDs below the average ADC value of a contralateral control region. Infarct volume was correlated with length of hospitalization and 6-month outcome assessed with Glasgow Outcome Scale (GOS), Modified Rankin Score (mRS), Barthel Index (BI) and a dichotomized outcome status with favorable outcome defined as GOS 1, mRS or=95. RESULTS: Infarct volume on ADC maps ranged from 0.2 to 187 cm(3) and was significantly correlated with length of hospitalization (p < 0.001, r = 0.67). Furthermore, ADC infarct volume was significantly correlated with GOS (r = 0.73), mRS (r = 0.68), BI (r = 0.67) and outcome status (r = 0.65) (each p < 0.001). Multiple logistic regression revealed a statistically significant correlation between ADC infarct volume and outcome status (p < 0.05), but none for Canadian Neurological Scale score, age and gender (p >0.05 each). CONCLUSION: Infarct volume measured by using a quantitative definition for infarcted tissue on ADC maps correlated significantly with length of hospitalization (as a possible surrogate marker for short-term outcome) and functional outcome after 6 months. ADC infarct volume may provide prognostic information for patients with acute ischemic MCA stroke.     

Diffusion- and perfusion-weighted magnetic resonance imaging of focal cerebral ischemia and cortical spreading depression under conditions of mild hypothermia

In a model of experimental stroke, we characterize the effects of mild hypothermia, an effective neuroprotectant, on fluid shifts, cerebral perfusion and spreading depression (SD) using diffusion- (DWI) and perfusion-weighted MRI (PWI). Twenty-two rats underwent 2 h of middle cerebral artery (MCA) occlusion and were either kept normothermic or rendered mildly hypothermic shortly after MCA occlusion for 2 h. DWI images were obtained 0.5, 2 and 24 h after MCA occlusion, and maps of the apparent diffusion coefficient (ADC) were generated. SD-like transient ADC decreases were also detected using DWI in animals subjected to topical KCl application (n=4) and ischemia (n=6). Mild hypothermia significantly inhibited DWI lesion growth early after the onset of ischemia as well as 24 h later, and improved recovery of striatal ADC by 24 h. Mild hypothermia prolonged SD-like ADC transients and further decreased the ADC following KCl application and immediately after MCA occlusion. Cerebral perfusion, however, was not affected by temperature changes. We conclude that mild hypothermia is neuroprotective and suppresses infarct growth early after the onset of ischemia, with better ADC recovery. The ADC decrease during SD was greater during mild hypothermia, and suggests that the source of the ADC is more complex than previously believed.     

Comparison of diffusion-weighted MRI and CT in acute stroke

OBJECTIVE: To compare diffusion-weighted MRI (DWI) and CT with respect to accuracy of localizing acute cerebral infarction; sensitivity, specificity, and interrater reliability for identifying more than one-third middle cerebral artery (MCA) territory involvement; and correlation of acute lesion volume with final infarct volume. METHOD: Nineteen consecutive stroke patients underwent CT and DWI within 7 hours of stroke onset and a follow-up DWI examination 36 hours after symptom onset, which served as the "gold standard" for lesion location and extent of MCA involvement. Each scan was evaluated for acute ischemic lesions by two experienced observers. After 30 days, T2-weighted MRI was obtained for assessment of the final infarct volume. RESULTS: The acute CT and DWI scans were obtained on average 2.6 and 5.1 hours after symptom onset. On DWI the acute lesion was identified correctly in all instances and on CT it was identified correctly in 42 to 63% of patients. Sensitivity for detection of more than 33% MCA involvement was better for DWI (57 to 86%) than for CT (14 to 43%), whereas specificity was excellent for both. Interrater reliability was moderately good for both (kappa, 0.6 for DWI; 0.5 for CT). A positive correlation (r = 0.79; p = 0.001) existed between lesion volume on acute DWI and final infarct volume, whereas no correlation was found between CT volume and final infarct volume. CONCLUSION: When compared with CT, DWI was more accurate for identifying acute infarction and more sensitive for detection of more than 33% MCA involvement. In addition, lesion volume on acute DWI, but not on acute CT, correlated strongly with final infarct volume. Additional studies are required to demonstrate whether these advantages of DWI are clinically relevant in the management of patients with acute stroke.     

Neuroprotective effect of hyperbaric oxygen therapy monitored by MR-imaging after embolic stroke in rats

The potential neuroprotective effects of hyperbaric oxygen (HBO) were tested in an embolic model of focal cerebral ischemia with partially spontaneous reperfusion. Rats (n = 10) were subjected to embolic middle cerebral artery occlusion (MCAO) and diffusion weighted MRI (DWI) was performed at baseline, 1, 3, and 6 h after MCAO to determine the ADC viability threshold yielding the lesion volumes that best approximated the 2,3,5-triphenyltetrazolium chloride (TTC) infarct volumes at 24 h (experiment 1). For assessment of neuroprotective effects, rats were treated with 100% oxygen at 2.5 atmospheres absolute (ATA, n = 15) or normobaric room air (n = 15) for 60 min beginning 180 min after MCAO (experiment 2). DWI-, perfusion (PWI)- and T2-weighted MRI (T2WI) started within 0.5 h after MCAO and was continued 5 h, 24 h (PWI and T2WI only), and 168 h (T2WI only). Infarct volume was calculated based on TTC-staining at 24 h (experiment 1) or 168 h (experiment 2) post-MCAO. ADC-lesion evolution was maximal between 3 and 6 h. In experiment 2, the relative regional cerebral blood volume (rCBV) of both groups showed similar incomplete spontaneous reperfusion in the ischemic core. HBO reduced infarct volume to 145.3 +/- 39.6 mm3 vs. 202.5 +/- 58.3 mm3 (control, P = 0.029). As shown by MRI and TTC, HBO treatment demonstrated significant neuroprotection at 5 h after embolic focal cerebral ischemia that lasted for 168 h.     

A modified rabbit model of stroke: evaluation using clinical MRI scanner

Abstract

Objective: Occluding the middle cerebral artery of small animals with an intraluminal filament to build a stroke model has gained increasing acceptance. In light of the growing demand for magnetic resonance imaging (MRI) studies using the clinical MRI scanner, large animal models can be superior to small animal models. In this work, we developed a modified rabbit model of stroke, which was assessed using clinical MRI scanner and compared with a most commonly silicone-coated filament model.

Methods: We presented a focal cerebral ischemia in rabbits. The key feature of this modified method is the use of a guide wire as a 'nylon suture'. At 3 days after ischemia, the percentage of brain infarct volume, neurobehavioral score, intracranial hemorrhagic incidence and dynamic changes of T₂ and apparent diffusion coefficient values were assessed respectively and compared between the focal cerebral models.

Results: Wire-induced models had more severe brain infarct size with less dispersion (32.7 ± 6.5%, coefficient of variation=0.20) than that with filament models (25.4 ± 8.9%, coefficient of variation=0.31; p<0.05). There were more significant MRI changes in the early stage, higher rate of technique success (wire, 20/20; filament, 17/20) and less intracranial hemorrhage (wire, 0/20; filament, 3/20) in wire-induced models than in filament-induced rabbits (p<0.05).

Conclusion: Our data suggest that wire-induced method can provide a useful tool for the earlier research of ischemia.     

Co-registration of radiographic and pathologic infarct territory in a non-human primate model of stroke

OBJECTIVES: Infarct volume correlation using magnetic resonance imaging (MRI) and pathology specimens enables exact tissue localization of cerebral injury following experimental stroke. We describe a protocol that enables co-registration of radiographic signal change and histologic ischemia in a non-human primate model of stroke.METHODS: One male baboon underwent left middle cerebral artery territory occlusion/reperfusion. MRI [5 mm axial T2 weighted (T2W) slices] was carried out 9 days post-ischemia after which the animal was killed. Immediately post-mortem, the whole brain was perfused and fixed in paraformaldehyde and sliced into 5 mm axial sections that corresponded to those demonstrated on MRI. Slices (40 microm) were obtained from each section and were then stained using Luxol hematoxylin and eosin.RESULTS: The relative area of hyperintensity demonstrated on T2W MRI approximates, in size and location, the region of infarct on gross pathology. This was confirmed microscopically.DISCUSSION: With the use of advanced imaging modalities, this co-registration technique affords the capacity to differentiate ischemic core, penumbra, and uninjured cortex following experimental stroke. Such a precise delineation enables immunohistochemical analysis of a wide variety of substrates in each of the aforementioned regions.     

Neuroprotective effects of erythromycin on ischemic injury following permanent focal cerebral ischemia in rats

Objective: This study aims to determine if erythromycin provides neuroprotective effects against ischemic injury following permanent focal cerebral ischemia.

Methods: Sprague–Dawley rats were subjected to middle cerebral artery occlusion (MCAO). Each animal received a single subcutaneous injection of erythromycin lactobionate (EM, 50 mg/kg) or vehicle immediately after ischemia. The infarct volume, edema index and neurological performance were evaluated at 24 and 72 h after MCAO. The cerebral blood flow (CBF) was measured with an MRI system at 30 min after MCAO. TUNEL staining and immunohistochemical analyses for oxidative stress (4-HNE, 8-OHdG) and inflammation (Iba-1, TNF-α) in the cortex were conducted at 24 and 72 h after MCAO.

Results: The CBF did not differ between the EM-treated and vehicle-treated groups. The EM treatment significantly reduced the infarct volume (p < 0.01) at 24 and 72 h after MCAO and significantly reduced the edema index (p < 0.01) at 24 h. The EM treatment significantly improved the neurological deficit scores (p < 0.05) at 24 and 72 h. EM also significantly suppressed the accumulation of 4-HNE (p < 0.01) and 8-OHdG (p < 0.01) and markedly reduced Iba-1 (p < 0.01) and TNF-α expression (p < 0.05) at both time points. The EM treatment significantly reduced TUNEL-positive cells (p < 0.01) at both time points.

Conclusion: These findings suggest that EM can protect against the neuronal damage caused by cerebral ischemia by alleviating inflammation and reducing oxidant stress.     

Nitric oxide synthase inhibitorN-nitro-l-arginine methyl ester decreases ischemic damage in reversible focal cerebral ischemia in hyperglycemic rats

We tested the hypothesis that the exacerbation of post-ischemic brain tissue injury associated with hyperglycemia in rats is due to toxic metabolism of nitric oxide. We used magnetic resonance imaging (MRI) techniques to measure neuronal and cerebrovascular injury in a 2-h transient focal cerebral ischemia model in normoglycemic and hyperglycemic rats at 3 and 24 h post-ischemia onset. We determined the effect of low dose (3 mg/kg i.p.) treatment with the nitric oxide synthase inhibitorN^G-nitro-l-arginine methyl ester (l-NAME). Compared to normoglycemia, preexisting hyperglycemia increased the volume of brain tissue exhibiting hyperintensity in diffusion weighted MRI (DWI) by factors of 5.6 and 6.2 at 3 h and 24 h post-ischemia, respectively. A similar increase in tissue volumes exhibiting hyperintense signal in T2-weighted MRI (T2WI) (3.3-fold and 5.6-fold) was observed. Cerebral blood volume MRI indicated a large focal no-reflow zone in hyperglycemic rats. Treatment withl-NAME eliminated the no-reflow zone in the hyperglycemic rats, and reduced tissue volumes of DWI hyperintensity by 86% and 93% at 3 h and 24 h, respectively. Similarly, tissue volumes of T2WI hyperintensity were reduced by 80% and 94% at 3 h and 24 h, respectively. Thus, nitric oxide is an important mediator in the exacerbation of post-ischemic brain injury in hyperglycemic rats. Inhibition of nitric oxide synthase limits edema formation, improves perfusion and reduces infarct volume.     

Nitric oxide synthase inhibitorN-nitro-l-arginine methyl ester decreases ischemic damage in reversible focal cerebral ischemia in hyperglycemic rats

We tested the hypothesis that the exacerbation of post-ischemic brain tissue injury associated with hyperglycemia in rats is due to toxic metabolism of nitric oxide. We used magnetic resonance imaging (MRI) techniques to measure neuronal and cerebrovascular injury in a 2-h transient focal cerebral ischemia model in normoglycemic and hyperglycemic rats at 3 and 24 h post-ischemia onset. We determined the effect of low dose (3 mg/kg i.p.) treatment with the nitric oxide synthase inhibitorN^G-nitro-l-arginine methyl ester (l-NAME). Compared to normoglycemia, preexisting hyperglycemia increased the volume of brain tissue exhibiting hyperintensity in diffusion weighted MRI (DWI) by factors of 5.6 and 6.2 at 3 h and 24 h post-ischemia, respectively. A similar increase in tissue volumes exhibiting hyperintense signal in T2-weighted MRI (T2WI) (3.3-fold and 5.6-fold) was observed. Cerebral blood volume MRI indicated a large focal no-reflow zone in hyperglycemic rats. Treatment withl-NAME eliminated the no-reflow zone in the hyperglycemic rats, and reduced tissue volumes of DWI hyperintensity by 86% and 93% at 3 h and 24 h, respectively. Similarly, tissue volumes of T2WI hyperintensity were reduced by 80% and 94% at 3 h and 24 h, respectively. Thus, nitric oxide is an important mediator in the exacerbation of post-ischemic brain injury in hyperglycemic rats. Inhibition of nitric oxide synthase limits edema formation, improves perfusion and reduces infarct volume.     

Fluid–attenuated inversion recovery (FLAIR) sequences for the assessment of acute stroke

Background and purpose Diffusion–weighted magnetic resonance (MR) imaging (DWI), and three–dimensional (3D) time–of–flight (TOF) MR angiography (MRA), are highly sensitive for the early detection of stroke and arterial occlusion. However, only a few studies have evaluated the sensitivity of conventional MR sequences that are usually included in the imaging protocol. The aim of this study was to evaluate interobserver and intertechnique reproducibility of Fluid–Attenuated Inversion Recovery (FLAIR) sequences for the diagnosis of early brain ischemia and arterial occlusion. Methods Over a 30–month period, brain MR examinations were performed in 34 patients within 12 hours after stroke onset. Imaging protocol included FLAIR sequences, DWI and 3D TOF MRA. Ten observers including radiologists and neurologists, performed separately a visual interpretation of FLAIR images for the detection of brain ischemia and arterial occlusion seen as an arterial high signal. DWI and 3D TOF MRA were used as reference and interpreted independently by two senior radiologists. Interobserver agreement was assessed for image quality, detectability and conspicuity of lesions whereas intertechnique agreement was only judged for lesion detectability. Results On FLAIR sequences, interobserver agreement for the detection of brain ischemia and arterial occlusion was excellent (κ = 0.81 and 0.87 respectively). The concordance between FLAIR and DWI sequences for the detection of brain ischemia and between FLAIR and 3D TOF MRA for the detection of arterial occlusion were judged as excellent for all observers (κ = 0.91 and 0.89 respectively). Conclusion Although DWI is the most sensitive technique with which to detect acute stroke, FLAIR imaging may also be useful to demonstrate both acute ischemia and arterial occlusion with an excellent interobserver reproducibility.     

Significance of hyperintense vessels on FLAIR MRI in acute stroke

OBJECTIVE: To describe hyperintense vessels sign (HVS) in patients with acute stroke on fluid-attenuated inversion recovery (FLAIR) MRI and determine its clinical significance and utility. BACKGROUND: Enhancement of vessels on postcontrast MRI in patients with acute stroke is considered an indicator of early brain ischemia. Recently, the FLAIR technique has shown promise in earlier and better detection of ischemic brain parenchymal lesions. METHODS: Two observers retrospectively reviewed 304 MRI of patients with stroke and identified 30 patients with acute middle cerebral artery stroke and HVS on FLAIR obtained within 24 hours of symptom onset. These patients were evaluated with contrast-enhanced MRI (n = 9), MR angiography of carotid and intracranial circulation (n = 30), cerebral angiography (n = 8), transcranial Doppler (n = 17), and SPECT (n = 16). The extent of HVS was compared with final infarct size and NIH Stroke Scale score. RESULTS: HVS on FLAIR was seen in 10% of the patients with acute stroke. HVS was associated with large vessel occlusion or severe stenosis (>90%). Intravascular enhancement on contrast MRI was observed in vessels that were hyperintense on FLAIR. Both cortical and subcortical infarcts demonstrated HVS. MR angiographic and cerebral angiographic findings of large vessel occlusion or severe stenosis (>90%), slow flow, low velocities by transcranial Doppler, and hypoperfusion on SPECT correlated with HVS. HVS was the earliest ischemic change in three patients scanned within 3 hours of ictus. Final infarct size was smaller than the area showing HVS in all patients. CONCLUSION: HVS on FLAIR MRI is an indicator of slow flow and early ischemia as a result of large vessel occlusion or stenosis and inadequacy of collateral circulation. HVS does not mean that infarction has occurred but indicates brain tissue at risk of infarction. It should prompt consideration of revascularization and flow augmentation strategies.     

Combined diffusion and perfusion MRI with correlation to single-photon emission CT in acute ischemic stroke. Ischemic penumbra predicts infarct growth.

BACKGROUND AND PURPOSE: More effective imaging methods are needed to overcome the limitations of CT in the investigation of treatments for acute ischemic stroke. Diffusion-weighted MRI (DWI) is sensitive in detecting infarcted brain tissue, whereas perfusion-weighted MRI (PWI) can detect brain perfusion in the same imaging session. Combining these methods may help in identifying the ischemic penumbra, which is an important concept in the hemodynamics of acute stroke. The purpose of this study was to determine whether combined DWI and PWI in acute (<24 hours) ischemic stroke can predict infarct growth and final size. METHODS: Forty-six patients with acute ischemic stroke underwent DWI and PWI on days 1, 2, and 8. No patient received thrombolysis. Twenty-three patients underwent single-photon emission CT in the acute phase. Lesion volumes were measured from DWI, SPECT, and maps of relative cerebral blood flow calculated from PWI. RESULTS: The mean volume of infarcted tissue detected by DWI increased from 46.1 to 75.6 cm(3) between days 1 and 2 (P<0.001; n=46) and to 78.5 cm(3) after 1 week (P<0.001; n=42). The perfusion-diffusion mismatch correlated with infarct growth (r=0. 699, P<0.001). The volume of hypoperfusion on the initial PWI correlated with final infarct size (r=0.827, P<0.001). The hypoperfusion volumes detected by PWI and SPECT correlated significantly (r=0.824, P<0.001). CONCLUSIONS: Combined DWI and PWI can predict infarct enlargement in acute stroke. PWI can detect hypoperfused brain tissue in good agreement with SPECT in acute stroke.     

Imaging of the spinal cord and brain in multiple sclerosis: a comparative study between fast flair and fast spin echo

Recent reports have suggested that fluid attenuated inversion recovery (FLAIR) is a technique superior to conventional (CSE) or fast spin echo (FSE) T2-weighted sequences in detecting intrinsic lesions both in the brain and spinal cord. We report our experience of an inversion recovery prepared FSE, which we refer to as fast FLAIR, in a comparative study of ten patients with clinically definite multiple sclerosis (MS) who underwent cervical cord and brain imaging with both FSE and fast FLAIR. The results showed that in the cerebral hemispheres fast FLAIR detected more lesions than FSE (P < 0.001). However, FSE detected more lesions than fast FLAIR in the posterior fossa (P = 0.02) and in the cord fast FLAIR was much inferior detecting only 2 of 33 lesions seen on FSE. Estimating the T2 relaxation times of lesions in each of three areas (periventricular, posterior fossa, cervical cord) showed that the T2 value of posterior fossa and cervical cord lesions was significantly lower than that of periventricular lesions, suggesting that the lesion composition is different and consequently their imaging appearances are different. In conclusion, although fast FLAIR improves the detection of MS lesions in the cerebral hemispheres, its substantially lower sensitivity in the posterior fossa and spinal cord is a potentially important limitation to its use as a tool for the diagnosis of MS and for monitoring therapies. Further studies are needed to elucidate the mechanisms underlying the loss of sensitivity. Received: 23 March 1992 Received in revised form: 1 July 1996 Accepted: 5 August 1996     

Plasmatic level of neuroinflammatory markers predict the extent of diffusion-weighted image lesions in hyperacute stroke.

Sixteen patients with acute middle cerebral artery stroke were studied to correlate neuroinflammatory markers with perfusion- and diffusion-weighted magnetic resonance imaging (MRI) lesion volumes (PWI and DWI). At arrival (less than 6 hours), plasmatic matrix metalloproteinase (MMP)-9, MMP-2, interleukin (IL)-6, IL-8, intercellular adhesion molecule (ICAM)-1, and tumor necrosis factor (TNF)-alpha were serially measured (by ELISA), and MRI was performed. In cerebral ischemia, tissue destruction seems related to matrix metalloproteinases expression because baseline MMP-9 was the only predictor of the infarct volume measured as a DWI lesion (lineal regression: b = 0.50, 0.25-0.74; P < 0.001). Moreover, the extent of hypoperfused brain area (PWI) was associated with a proinflammatory cytokine release in the next hours (TNF-alpha and IL-6).     

Cerebral magnetic resonance imaging within 6 hours of stroke onset: inter- and intra-observer reproducibility

BACKGROUND: Magnetic resonance imaging (MRI) provides valuable pathophysiological information during the very first hours of cerebral ischemia. However, the reliability of prime-time MRI in the setting of emergency care remains unknown. AIM: To evaluate the reproducibility between and within observers of the assessment of MRI scans in stroke patients. METHOD: We performed a MRI scan within 6 h of stroke onset, with time-of-flight (TOF), T2* gradient echo, FLAIR, diffusion- (DWI) and perfusion- (PWI) weighted images, in 17 consecutive patients. Four observers, blinded to the clinical history, separately performed a visual assessment of all scans, and repeated the assessment 2-8 days later. Two neuroradiologists made volumetric measures of diffusion and perfusion abnormalities using a semi-automatic technique 2 weeks after the 2nd visual assessment. We evaluated: (i) in the whole set of MRI scans, the quality of scans and their ability to identify primary hemorrhages on T2* gradient echo sequences; (ii) in patients with acute cerebral ischemia only, the inter- and intra-observer agreement for the presence of arterial occlusion and cerebral abnormalities on TOF sequences, and (iii) on DWI and PWI sequences, the relationship between visual and automatic assessments for the presence of a mismatch (defined as the difference between the perfusion and diffusion abnormalities) of >20%. Statistics used the kappa (kappa) method. RESULTS: The median delay between clinical onset and MRI was 285 min. Two patients had primary cerebral hemorrhages, 1 a post-ictal deficit, and 14 cerebral ischemia. The quality of the scans was judged as appropriate for all scans in all sequences except for FLAIR. All observers identified the 2 patients with hemorrhages. The inter- and intra-observer reliability was substantial to excellent (kappa values ranging from 0.63 to 1.00) for all sequences. The agreement between visual and automatic assessments for the presence of a mismatch of >20% was excellent in all observers. CONCLUSION: The visual assessment of T2* gradient echo, TOF, diffusion and perfusion sequences at the acute stage of stroke is reproducible between and within observers. The visual assessment is as good as the volumetric assessment to detect a mismatch of >20%.     

Comparing diffusion-weighted and T2-weighted MR imaging for the quantification of infarct size in a neonatal rat hypoxic–ischemic model at 24 h post-injury

PURPOSE: In a neonatal rat model of hypoxic-ischemic (HI) brain injury, using T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI), we aim to determine the best MRI method of lesion quantification that reflects infarct size. MATERIALS AND METHODS: Twenty 7-day-old rats underwent MRI 24h after HI brain injury was induced. Lesion size relative to whole brain was measured using T2WI and apparent diffusion coefficient (ADC) maps, applying thresholds of 60%, 70% and 80% contralateral control hemisphere mean ADC, and at day 10 post-HI on pathology with TTC staining. Multiple linear regression analysis was used to study the relationships between lesion size at MRI and pathology. RESULTS: Lesion size measurement using all MRI methods significantly correlated with infarct size at pathology; using T2WI, r=0.808 (p<0.001), using 80% ADC, 70% ADC and 60% ADC thresholds, r=0.888 (p<0.001), 0.761, (p<0.001) and 0.569 (p=0.014), respectively. Eighty percent ADC threshold was found to be the only significant independent predictor of final infarct volume (adjusted R(2)=0.775). CONCLUSION: At 24h post-HI, lesion size on DWI, using 80% ADC threshold is the best predictor of final infarct volume. Although T2WI performed less well, it has the advantage of superior spatial resolution and is technically less demanding. These are important considerations for experiments which utilize MRI as a surrogate method for lesion quantification in the neonatal rat HI model.     

Prediction of infarct growth and neurologic deterioration in patients with positive perfusion-diffusion mismatch

Background

To assess the value of baseline clinical severity and perfusion–diffusion mismatch as predictors for further infarct growth and clinical outcome.

Methods

Patients with acute ischemic stroke and initial perfusion–diffusion mismatch within 72 h were enrolled. Baseline perfusion defects on time-to-peak (TTP) and cerebral blood volume (CBV) maps were measured. Infarct volume and stroke severity were assessed by diffusion-weighted image (DWI) and NIHSS, and were repeatedly assessed 7 days later. The predictive value of baseline NIHSS and perfusion defects on further infarct growth and neurologic deterioration was determined.

Results

Fifty-two patients (mean age 68.3 ± 12.8 years, 42% women) were enrolled. CBV defects were significantly associated with infarct growth (CBV, p = 0.02). Initial stroke severity, but not TTP and CBV mismatch (p = 0.65 and 0.76, respectively), significantly inversely correlated with neurologic deterioration (p = 0.001).

Conclusions

In patients with mismatch, those with severe symptoms initially are more likely to have infarct growth, while those with minor symptoms tend to suffer from larger extent of neurologic deterioration within 1 week. CBV is associated with further infarct growth but not clinical deterioration.     

Distal hyperintense vessels alleviate insula infarction in proximal middle cerebral artery occlusion

Purpose: Insula involvement in acute cerebral ischemia more likely causes penumbral loss and poor clinical outcome than infarct-sparing insula. Our objective was to prove the hypothesis that abundant collateral circulation represented by distal hyperintense vessels (HV) on MRI alleviates insula infarction and facilitates prognosis. Material and Methods: One hundred and fourteen stroke cases with M1 totally occlusion on MR angiography were documented consecutively from 2012 to 2014. The degree of HV was graded as absent, subtle or prominent. Clinical data were recorded retrospectively by reviewing the medical records. The infarct volume on diffusion-weighted image, along with National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS), was used to evaluate the clinical severity and prognosis. Results: The degree of HV was more abundant in insula-uninvolved stroke compared with stroke involving insula infarction (p = 0.026). Insula-involved stroke patients were older (p = 0.039) with a higher percentage of atrial fibrillation history (p = 0.042). Univariate analysis revealed that insula infarction, age, infarct volume and NIHSS predicted unfavorable prognosis of stroke, whereas HV had a favorable effect. The protective effect of HV was confirmed by multivariate analysis. Conclusion: HV is a protective barrier between insula infarction and severity of clinical symptoms among stroke patients.     

MAP2 immunostaining in thick sections for early ischemic stroke infarct volume in non-human primate brain

The delineation of early infarction in large gyrencephalic brain cannot be accomplished with triphenyl-tetrazolium chloride (TTC) due to its limitations in the early phase, nor can it be identified with microtubule-associated protein 2 (MAP2) immunohistochemistry, due to the fragility of large thin sections. We hypothesize that MAP2 immunostaining of thick brain sections can accurately identify early ischemia in the entire monkey brain.Using ischemic brains of one rat and three monkeys, a thick-section MAP2 immunostaining protocol was developed to outline the infarct region over the entire non-human primate brain. Comparison of adjacent thick and thin sections in a rat brain indicated complete correspondence between ischemic regions (100.4 mm³ ± 1.2%, n = 7, p = 0.44). Thick sections in monkey brain possessed the increased structural stability necessary for the extensive MAP2 immunostaining procedure permitting quantification of the ischemic region as a percent of total monkey brain, giving infarct volumes of 11.4, 16.3, and 19.0% of total brain. Stacked 2D images of the intact thick brain tissue sections provided a 3D representation for comparison to MRI images. The infarct volume of 16.1 cm³ from the MAP2 sections registered with MRI images agreed well with the volume calculated directly from the stained sections of 16.6 cm³.Thick brain tissue section MAP2 immunostaining provides a new method for determining infarct volume over the entire brain at early time points in a non-human primate model of ischemic stroke.