Short-term outcome after stenting versus endarterectomy for symptomatic carotid stenosis: a preplanned meta-analysis of individual patient data.

BACKGROUND: Results from randomised controlled trials have shown a higher short-term risk of stroke associated with carotid stenting than with carotid endarterectomy for the treatment of symptomatic carotid stenosis. However, these trials were underpowered for investigation of whether carotid artery stenting might be a safe alternative to endarterectomy in specific patient subgroups. We therefore did a preplanned meta-analysis of individual patient data from three randomised controlled trials. METHODS: Data from all 3433 patients with symptomatic carotid stenosis who were randomly assigned and analysed in the Endarterectomy versus Angioplasty in Patients with Symptomatic Severe Carotid Stenosis (EVA-3S) trial, the Stent-Protected Angioplasty versus Carotid Endarterectomy (SPACE) trial, and the International Carotid Stenting Study (ICSS) were pooled and analysed with fixed-effect binomial regression models adjusted for source trial. The primary outcome event was any stroke or death. The intention-to-treat (ITT) analysis included all patients and outcome events occurring between randomisation and 120 days thereafter. The per-protocol (PP) analysis was restricted to patients receiving the allocated treatment and events occurring within 30 days after treatment. FINDINGS: In the first 120 days after randomisation (ITT analysis), any stroke or death occurred significantly more often in the carotid stenting group (153 [8·9%] of 1725) than in the carotid endarterectomy group (99 [5·8%] of 1708, risk ratio [RR] 1·53, [95% CI 1·20-1·95], p=0·0006; absolute risk difference 3·2 [1·4-4·9]). Of all subgroup variables assessed, only age significantly modified the treatment effect: in patients younger than 70 years (median age), the estimated 120-day risk of stroke or death was 50 (5·8%) of 869 patients in the carotid stenting group and 48 (5·7%) of 843 in the carotid endarterectomy group (RR 1·00 [0·68-1·47]); in patients 70 years or older, the estimated risk with carotid stenting was twice that with carotid endarterectomy (103 [12·0%] of 856 vs 51 [5·9%] of 865, 2·04 [1·48-2·82], interaction p=0·0053, p=0·0014 for trend). In the PP analysis, risk estimates of stroke or death within 30 days of treatment among patients younger than 70 years were 43 (5·1%) of 851 patients in the stenting group and 37 (4·5%) of 821 in the endarterectomy group (1·11 [0·73-1·71]); in patients 70 years or older, the estimates were 87 (10·5%) of 828 patients and 36 (4·4%) of 824, respectively (2·41 [1·65-3·51]; categorical interaction p=0·0078, trend interaction p=0·0013]. INTERPRETATION: Stenting for symptomatic carotid stenosis should be avoided in older patients (age ≥70 years), but might be as safe as endarterectomy in younger patients. FUNDING: The Stroke Association.

Abciximab is a safe rescue therapy in thromboembolic events complicating cerebral aneurysm coil embolization: single center experience in 42 cases and review of the literature.

BACKGROUND AND PURPOSE: The purpose of this study was to estimate the safety and efficacy of abciximab treatment in combination with prophylactic heparin, acetylsalicylic acid (ASA), and clopidogrel application in cases of thrombus formation complicating endovascular coil embolization in cerebral aneurysms. METHODS: Thromboembolic incidents during endovascular management of 515 consecutive cerebral aneurysms were observed in 48 cases (9.3%). Eight incidents were observed during embolization of incidental aneurysms (8/174; 4.6%, 95% CI: 2.0 to 8.9%). All patients underwent anticoagulation with heparin and platelet-inhibition with ASA during treatment procedure. In addition, clopidogrel orally was applied 3 days preoperatively in patients with incidental aneurysms. In case of thrombus formation, glycoprotein IIb-IIIa inhibitor abciximab was given in 42 cases. No coagulation-effective rescue treatment was conducted in 5 cases. One patient was treated with r-tPA. End points were infarction on follow-up cranial CT and the rate of intracranial hemorrhages. RESULTS: No infarcts on follow-up CT were observed after treatment with abciximab in 29/42 patients (69.0%, 95% CI: 52.9 to 82.4%). No coagulant rescue therapy was applied in 5 patients because of a small nonocclusive thrombus or good collateral blood supply, showing consecutive infarction on follow-up CT in 3 cases as did the 1 patient treated with r-tPA. No periprocedural bleedings or rebleedings were observed in any case. CONCLUSIONS: Abciximab was safe as rescue treatment in cases of thrombus formation during endovascular aneurysm coiling. In our study the use of Abciximab, in combination with prophylactic anticoagulation and antiaggregation, does not lead to additional intracranial hemorrhages or any extracranial bleeding complications.

Microstructural callosal abnormalities in normal-appearing brain of children with developmental delay detected with diffusion tensor imaging.

Callosal fibres play an important role in psychomotor and cognitive functions. The purpose of this study was to investigate possible microstructural abnormalities of the corpus callosum in children with developmental delay, who have normal conventional brain MR imaging results. Seventeen pediatric patients (aged 1-9 years) with developmental delay were studied. Quantitative T2 and fractional anisotropy (FA) values were measured at the genu and splenium of the corpus callosum (CC). Fibre tracking, volumetric determination, as well as fibre density calculations of the CC were also carried out. The results were compared with those of the age-matched healthy subjects. A general elevation of T2 relaxation times (105 ms in patients vs. 95 ms in controls) and reduction of the FA values (0.66 in patients vs. 0.74 in controls) at the genu of the CC were found in patients. Reductions of the fibre numbers (5,464 in patients vs. 8,886 in controls) and volumes (3,415 ml in patients vs. 5,235 ml in controls) of the CC were found only in patients older than 5 years. The study indicates that despite their inconspicuous findings in conventional MRI microstructural brain abnormalities are evident in these pediatric patients suffering from developmental delay.

Cerebral embolism during carotid artery stenting: role of carotid plaque echolucency.

BACKGROUND: Carotid artery stenting (CAS) is associated with the risk of intraprocedural stroke. A better understanding of specific risk factors could help to improve the procedure and to reduce the overall risk of CAS. We addressed the role of carotid plaque echolucency as potential risk factor for cerebral embolism during CAS. METHODS: We prospectively evaluated carotid plaque echolucency by use of a computer-assisted measure of echogenicity, the gray scale median (GSM), in 31 consecutive patients with symptomatic high-grade carotid stenosis that were scheduled to undergo CAS. Dual-frequency transcranial Doppler ultrasound was used to detect solid cerebral microemboli during CAS. RESULTS: 27 of the 31 patients met all inclusion/exclusion criteria.Solid cerebral microemboli were detected during 17 of 27 CAS procedures. The GSM of the target plaques was lower in subjects with intraprocedural embolism (37.9 +/- 20.8) than in those without (58.2 +/- 25.7) (p = 0.040). A receiver-operating characteristic analysis showed that the GSM that gave the greatest separation between plaques with a higher and a lower probability of intraprocedural embolism was 50: the proportion of subjects with intraprocedural embolism was 85% in CAS of echolucent plaques (GSM <50) and 42% in CAS of echogenic plaques (GSM > or =50) (p = 0.031). CONCLUSIONS: CAS of both echolucent and echogenic carotid plaques may be associated with cerebral embolism, particularly CAS of echolucent plaques. Plaque echolucency alone does not reliably identify patients at particularly high risk of intraprocedural embolism, but should be considered as one of a broad panel of risk factors of CAS.

Results of the Stent-Protected Angioplasty versus Carotid Endarterectomy (SPACE) study to treat symptomatic stenoses at 2 years: a multinational, prospective, randomised trial.

BACKGROUND: The SPACE trial is a multinational, prospective, randomised study to test the hypothesis that carotid artery stenting is not inferior to carotid endarterectomy for treating patients with severe symptomatic carotid artery stenosis. We did not prove non-inferiority of carotid artery stenting compared with carotid endarterectomy for the 30-day complication rate, and we now report the results at 2 years. METHODS: Between March, 2001, and February, 2006, patients with symptomatic, severe (>or=70%) carotid artery stenosis were recruited to this non-inferiority trial and randomly assigned with a block randomisation design to have carotid artery angioplasty with stenting or carotid artery endarterectomy. 2-year endpoints include several clinical endpoints and the incidence of recurrent carotid stenosis of at least 70%. Clinical and vascular follow-up was done by a certified neurologist. Analyses were by intention to treat and per protocol. This trial is registered with ISRCTN, number 57874028.12. FINDINGS: 1 214 patients were randomly assigned (613 were randomly assigned to carotid angioplasty with stenting and 601 were randomly assigned to carotid endarterectomy). In both the intention-to-treat and per-protocol analyses the Kaplan-Meier estimates of ipsilateral ischaemic strokes up to 2 years after the procedure and any periprocedural stroke or death do not differ between the carotid artery stenting and the carotid endarterectomy groups (intention to treat 9.5%vs 8.8%; hazard ratio (HR) 1.10, 95%CI 0.75 to 1.61; log-rank p=0.62; per protocol 9.4%vs 7.8%; HR 1.23, 95%CI 0.82 to 1.83; log-rank p=0.31). In both the intention-to-treat and per-protocol populations, recurrent stenosis of 70% or more is significantly more frequent in the carotid artery stenting group compared with the carotid endarterectomy group, with a life-table estimate of 10.7% versus 4.6% (p=0.0009) and 11.1% versus 4.6% (p=0.0007), respectively. Only two incidences of recurrent stenoses after carotid artery stenting led to neurological symptoms. INTERPRETATION: After 2 years' follow-up, the rate of recurrent ipsilateral ischaemic strokes reported in the SPACE trial is similar for both treatment groups. The incidence of recurrent carotid stenosis at 2 years, as defined by ultrasound, is significantly higher after carotid artery stenting. However, it cannot be excluded that the degree of in-stent stenosis is slightly overestimated by conventional ultrasound criteria.

Clinical applications of quantitative T2 determination: a complementary MRI tool for routine diagnosis of suspected myelination disorders.

BACKGROUND AND AIMS: Though magnetic resonance imaging (MRI) plays an important role in studying pathological changes in central nervous system, a quantitative measure of contrast variance on MRI, allowing the detection of subtle signal variances in pathological processes, is not readily available for routine imaging. We report on the first experiences with evaluation of routine T2 relaxation time measurement as a diagnostic tool in routine imaging of suspected myelination disorders. METHODS: Twenty patients suffering from defined or suspected myelination disorders were examined by MRI. T2 relaxation time maps of the brain were derived from a triple spin echo sequence. T2 values were measured for each patient by regions of interest (ROI) analysis. As references age-dependent T2 prediction values in normal maturating brains were calculated by using a biexponentional function reported earlier. Deviations from these prediction values were used as an assisting tool both for detection of pathology and for monitoring of changes over time. These quantitative results were compared to conventional visual inspections by two independent neuroradiologists. RESULTS: In 18 patients with single diagnostic MRI, the T2 measurements were more graduated or definite in 9/18 cases, confirmatory in 9/18 cases. In two patients with MRI follow up, the dynamic clinical course of the disease had no correlate in visual inspection of the images but was associated with the quantitative T2 values. CONCLUSIONS: Quantitative T2 measurement is a promising tool for routine imaging as a complementary method in detecting and monitoring of suspected myelination disorders.

Management of cerebral arteriovenous malformations associated with symptomatic congestive intracranial hypertension.

We report on management strategies and clinical outcomes in 4 cases of acute symptomatic congestive intracranial hypertension associated with cerebral arteriovenous malformations (AVMs). Congestion resulted from high-volume shunts exhausting the drainage capacity of the cerebral venous system in 3 patients, and from sudden venous outflow obstruction in 1 patient. Two AVMs were suggested to be surgically accessible, whereas two AVMs were deemed to be inoperable. Surgically accessible AVMs were treated with embolization followed by complete surgical resection. Inoperable AVMs were treated with partial embolization. Both AVM embolization followed by surgical resection and partial AVM embolization effectively reduced intracranial pressure and achieved sustained patient recovery. Hence, an endovascular approach may be considered to manage AVM-related congestive intracranial hypertension either in combination with surgical AVM removal, or as a palliative approach in inoperable AVMs.

Intravenous administration of acetylsalicylic acid during endovascular treatment of cerebral aneurysms reduces the rate of thromboembolic events.

BACKGROUND AND PURPOSE: The purpose of this study is to analyze the effect of a modified intraoperative anticoagulation strategy including acetylsalicylic acid (ASA) on complication rates during endovascular coil embolization. METHODS: Two hundred and sixty-one cerebral aneurysms were treated in 247 patients by endovascular coil embolization from January 2001 to September 2004. Additional intravenous administration of 250 mg ASA was applied since January 2003. Patients treated before (-ASA; n=102 aneurysms) and after that date (+ASA; n=159 aneurysms) were compared. End points were rates of thromboembolism and severity of hemorrhages after intraoperative aneurysm rupture. RESULTS: Thromboembolic events during the procedure were observed more often in the -ASA group (18/102 aneurysms, 17.6%) in comparison with the +ASA group (14/159 aneurysms, 8.8%; P=0.028; Fisher exact test). Aneurysm perforation events occurring during or immediately after the procedure were observed equally often in the -ASA group (7/102 aneurysms, 6.9%) in comparison with the +ASA group (10/159 aneurysms, 6.3%). CONCLUSIONS: Intravenous application of ASA is feasible and safe during interventional aneurysm embolization. ASA seems to be associated with a significant reduction in the rate of thromboembolic events without increase in the rate or severity of intraoperative bleedings.

Blood-oxygen-level-dependent MRI allows metabolic description of tissue at risk in acute stroke patients.

BACKGROUND AND PURPOSE: The delineation of the "penumbra" is of particular interest in acute stroke imaging. The "mismatch concept" applying perfusion-weighted imaging (PWI) and diffusion-weighted imaging (DWI) appears to be an oversimplification of the underlying electrophysiological tissue status. An additional parameter reflecting the metabolic state of the threatened brain tissue would improve our ability to describe the penumbra. One candidate is deoxyhemoglobin (deoxy-Hb) as an indicator of the oxygen extraction fraction that can be visualized by T2*-based blood oxygen level-dependent (BOLD) imaging. METHODS: We analyzed data from 32 patients with acute stroke in the territory of the middle cerebral artery. MRI included fluid-attenuated inversion recovery, DWI, PWI, time-of-flight angiography, and quantitative T2 and T2* (qT2, qT2*) imaging. Follow-up was performed on day 1 and days 5 to 8. We calculated 1/T2'=1/qT2*-1/qT2. Changes of T2', representing the deoxy-Hb effect, were analyzed by 3D regions of interest (ROIs): apparent diffusion coefficient lesion day 0 (L0), time-to-peak-lesion day 0 (T0), final infarct size days 5 to 8 (F5-8), lesion growth (LG; F5-8-L0), and surviving tissue (ST; T0-F5-8). RESULTS: We observed a clear decrease of T2' in the infarcted hemisphere compared with the unaffected control ROIs. The mean value showed the most pronounced loss of T2' signal intensity in L0 (-15.7%), followed by LG (-10.5%) and ST (-8.0%). CONCLUSIONS: The implementation of BOLD imaging in acute stroke MRI offers a noninvasive estimation of the O2 utilization and is able to add additional information concerning the present metabolic state of the threatened brain tissue. The changes in T2' intensity are visually noticeable in the reconstructed T2' images and provide a better estimation of the real penumbra.

Outcome and symptomatic bleeding complications of intravenous thrombolysis within 6 hours in MRI-selected stroke patients: comparison of a German multicenter study with the pooled data of ATLANTIS, ECASS, and NINDS tPA trials.

BACKGROUND AND PURPOSE: We compared outcome and symptomatic bleeding complications of intravenous tissue plasminogen activator (IV-tPA) within 6 hours of symptom onset in MRI-selected patients with acute middle cerebral artery infarction with the pooled data of the large stroke tPA trials. METHODS: Patients were examined by perfusion-weighted and diffusion-weighted imaging < or =6 hours. Within 3 hours, patients were treated according to Second European-Australasian Acute Stroke Study (ECASS II) criteria. After 3 to 6 hours, treatment with IV-tPA was performed based on MRI findings. Favorable outcome was assessed after 90 days using a dichotomized modified Rankin scale score of 0 to 1. Intracerebral bleeding complications were assessed on follow-up MRI or computed tomography. Data were compared with the pooled placebo and pooled tPA patients of the ATLANTIS, ECASS, and National Institute of Neurological Disorders and Stroke (NINDS) tPA trials. RESULTS: From 174 MRI-selected tPA patients, 62% (n=108) were treated in < or =3 hours and 38% (n=66) after 3 to 6 hours. Favorable outcome was more frequent in MRI-selected tPA patients (48% [95% CI, 39 to 54]) compared with pooled placebo (33% [95% CI, 31 to 36]; P<0.001) and pooled tPA patients (40% [95% CI, 37 to 42]; P=0.046). Odds ratios for favorable outcome in the MRI-selected tPA group were 1.82 (1.32 to 2.51) compared with the pooled placebo and 1.39 (1.01 to 1.92) compared with the pooled tPA group. The rate of symptomatic intracerebral hemorrhage in MRI-selected tPA patients (3% [95% CI, 0 to 5]) was lower than in the pooled tPA group (8% [95% CI, 7 to 10]; P=0.012) and comparable to the pooled placebo group (2% [95% CI, 1 to 3]; P=0.392). CONCLUSIONS: This study supports that it is safe and effective to expand the time window for IV-tPA up to 6 hours in patients with tissue at risk as defined by MRI.

Emergency carotid artery stenting in persistent hemodynamic deficit associated with severe carotid stenosis.

MR imaging in a 73-year-old man presenting with hemispheric stroke revealed a subcortical diffusion-weighted imaging lesion associated with a high-grade stenosis of the proximal internal carotid artery, which suggested hemodynamic infarction. Collateral supply was absent. After failure of conservative therapy, successful unprotected carotid artery stent placement (CAS) was performed followed by a complete neurologic recovery. Emergency CAS should be considered in acute stroke patients with severe hemodynamic impairment if conservative treatment options are not successful.

Vascular occlusion sites determine differences in lesion growth from early apparent diffusion coefficient lesion to final infarct.

BACKGROUND AND PURPOSE: Occlusion of major cerebral arteries is the primary source of tissue damage in ischemic stroke and the target of thrombolytic therapy. We hypothesized that large infarcts in more proximal vascular occlusions correspond with substantially increased ischemic lesions shown on initial apparent diffusion coefficient (ADC) maps. METHODS: Initial ADC lesions in 120 patients with acute ischemic stroke were analyzed within 6 hours of stroke onset. Patients were categorized on the basis of vascular occlusion, as shown on MR angiography. Lesion volumes were determined by using manual delineation (ADC(man)) and a threshold method for ADC values (<550 x 10(-9) mm(2)/s(-1), ADC(<550)). Infarct volumes were analyzed by using T2-weighted (n = 109) or CT (n = 11) images obtained on days 5-8. RESULTS: Median lesion volumes for ADC(<550), ADC(man), and infarcts, respectively, were as follows: proximal internal carotid artery (ICA)/middle cerebral artery (MCA) occlusions, 10, 23, and 32 cm(3); carotid-T occlusions, 11, 37, and 138 cm(3); MCA trunk occlusions, 11, 27, and 44 cm(3)); and MCA branch occlusions 8, 27, and 21 cm(3). Initial ADC lesion volumes were different only between the carotid T and the MCA branch (P < .05). On days 5-8, infarct volumes decreased from proximal to distal sites (P < .05), with the exception of MCA trunk versus proximal ICA/MCA occlusions. Recanalization rate in carotid-T occlusion was significantly lower than those of all other occlusion types. CONCLUSION: Initial ADC lesions can be small, even in patients with proximal vascular occlusions. These patients develop considerably large infarctions, suggesting a high potential for infarct growth. This growth might be averted with improved early recanalization of proximal vascular occlusions.

Tissue at risk is overestimated in perfusion-weighted imaging: MR imaging in acute stroke patients without vessel recanalization.

BACKGROUND AND PURPOSE: The volume of decreased cerebral blood flow (CBF) in acute stroke perfusion-weighted imaging frequently overestimates final infarct volume. We hypothesized that surviving tissue exists even in patients without recanalization and tried to determine perfusion thresholds from initial MR imaging. METHODS: Stroke MR imaging including MR angiography was carried out at days 0, 1, and 7 after stroke onset in 19 patients without recanalization at least until day 1. The following lesions were defined: L0 = diffusion restriction at day 0; LG1 = lesion growth until day 1; LG7 = lesion growth until day 7; ST7 = initially hypoperfused, but surviving tissue. These lesions were transferred on initial MR imaging within 4.7 hours and perfusion values at day 0 were determined. RESULTS: Median lesion volume L0 at day 0 was 18.2 mL and increased to 39.4 and 43.8 mL at days 1 and 7. Volume of decreased rCBF not progressing to infarction was 148.5 mL (ST7). Mean ST7 perfusion values were different from L0 and LG1, but only mean relative cerebral blood volume (rCBV) was different from LG7, discriminating survival against death of tissue. A threshold value of 0.82 CBV for death versus survival was determined with a sensitivity of 0.56 and specificity of 0.95. Carotid T occlusions showed the greatest potential of lesion growth. CONCLUSION: Even when vessel occlusion persists, hypoperfused tissue on MR imaging does not necessarily progress toward infarction. The most conclusive inferences can be drawn from CBV images. The site of arterial occlusion also determines progression to infarction.

Are there time-dependent differences in diffusion and perfusion within the first 6 hours after stroke onset?

BACKGROUND AND PURPOSE: Stroke heterogeneity in computed tomography-based studies has been attributed as main cause for missing efficacy of intravenous tissue plasminogen activator (tPA) therapy within 3 to 6 hours. We investigated early time-dependent differences in acute stroke pathophysiology by multiparametric magnetic resonance imaging (MRI). METHODS: Stroke MRI of 112 acute ischemic stroke patients within <6 hours were dichotomized into a <3-hour group (n=52) and a 3- to 6-hour group (n=60). Infarct volume was determined on days 5 to 8. Lesion volumes were determined for apparent diffusion coefficient (ADC_man) and the subregion with ADC values <550x10(-9) mm/s2 (ADC <550), and for the time-to-peak (TTP) delay of 2 to 4 seconds, 4 to 6 seconds, 6 to 8 seconds, and >8 seconds. A subsample analysis was performed for occlusions of the middle carotid artery (MCA) trunk (n=36) and MCA branches (n=30), and for all patients treated by intravenous tPA (n=70). RESULTS: ADC and TTP lesion volumes were not different within <3 hours compared with volumes at 3 to 6 hours. In patients receiving intravenous tPA (n=70), there were no significant differences in ADC_man, TTP >2 seconds, and infarct volume (days 5 to 8) between the 2 groups. There was a greater proportion of ADC <550/ADC_man, which was most pronounced in patients with MCA trunk occlusions after 3 to 6 hours and a larger mismatch in the <3-hour group compared with that of the 3- to 6-hour group. In MCA branch occlusions, there was a less severe TTP delay after 3 to 6 hours. However, all differences missed the significance level (P=0.05) after correction for multiple testing. CONCLUSIONS: We observed no significant time-dependent differences within 6 hours after stroke onset in degree and volume of diffusion and perfusion impairment. An exclusion from intravenous tPA solely based on a rigid 3-hour time window seems unjustified in MRI-confirmed ischemic stroke.

Predictors of apparent diffusion coefficient normalization in stroke patients.

BACKGROUND AND PURPOSE: We sought to describe the frequency of normalization of apparent diffusion coefficient (ADC) values that are decreased in hyperacute stroke and to identify characteristics of tissue demonstrating normalization. METHODS: Sixty-eight acute ischemic stroke patients underwent MRI examination (including diffusion/perfusion imaging and MR angiography) within 6 hours (mean, 2.8 hours) after symptom onset, after 24 hours, and again 4 to 7 days later. Lesion volumes with decreased ADC and delayed time to peak in perfusion imaging were determined. In patients showing ADC normalization, volumes with ADC decrease graded as <50%, 50% to 60%, 60% to 70%, and 70% to 80% of the contralateral value were determined by thresholding. Patients were categorized as normalizers (demonstrating ADC normalization in >5 mL tissue with initially decreased ADC) or nonnormalizers (demonstrating ADC normalization in <5 mL tissue). RESULTS: Fourteen patients (19.7%) were classified as normalizers. Eleven of 31 patients (35.5%) initially imaged <3 hours after stroke onset and 3 of 37 (7.5%) of those imaged 3 to 6 hours after onset were normalizers. ADC normalization occurred predominantly in the basal ganglia and white matter after thrombolytic therapy in patients with more distal vessel occlusions. All normalizers demonstrated at least partial tissue reperfusion. Tissue with more severe initial decrease in ADC was less likely to demonstrate normalization. CONCLUSIONS: ADC normalization is not a rare event in acute stroke after tissue reperfusion. Brain tissue with initially decreased ADC, especially within 3 hours after stroke onset, may include "tissue at risk."

Severe ADC decreases do not predict irreversible tissue damage in humans.

BACKGROUND AND PURPOSE: A mismatch between diffusion- and perfusion-weighted MRI is thought to define tissue at risk of infarction. This concept is based on the assumption that diffusion slowing of and decreases in the apparent diffusion coefficient (ADC) serve as indicator of tissue proceeding to infarction. We tested this hypothesis. METHODS: MRI (diffusion weighted, perfusion weighted, MRA, T2 weighted) was performed in 15 patients with acute stroke within 2.9+/-0.8 hours (mean+/-SD) of onset and on days 1 and 7. After intraindividual realignment of the ADC maps, the development of ADC range volumes and ADC values was determined. RESULTS: An increase (354%, group A1) in the total ADC-based lesion volume below a threshold of < 80% occurred in 4 patients on day 1, persisting on day 7 with a pronounced increase of ADC range volumes with low ADC values. An increase in total ADC-based lesion volume (201%, group A2) followed by a secondary drop to day 7 was found in 7 patients. A significant reduction in total ADC-based lesion volume (14%, group B) was found in 4 patients. ADC-based lesion volume increase was associated with persistent vessel occlusion in group A, whereas recanalization in group B resulted in ADC volume decrease. ADC normalization was observed independently from the degree of the initial ADC decrease on days 1 and 7 in group B. CONCLUSIONS: In line with results from animal experiments, ADC decreases do not reliably indicate tissue infarction Even severely decreased ADC values may normalize in human stroke, and it seems likely that ADC normalization depends on the duration and severity of ischemia rather than the absolute value.

Correlation of apparent diffusion coefficient and computed tomography density in acute ischemic stroke.

BACKGROUND AND PURPOSE: Diffusion-weighted MR imaging is very sensitive for the detection of restricted molecular water diffusion in acute ischemic stroke. CT is sensitive to net water uptake in ischemic edema. We compared the decrease in the apparent diffusion coefficient (ADC) in diffusion-weighted MR imaging with CT density changes to study the correlation between diffusion restriction and water uptake in acute stroke patients. METHODS: Twenty-five patients with acute ischemic stroke of the anterior cerebral circulation underwent MR and CT imaging 1.3 to 5.4 hours after symptom onset. ADC and CT data were transferred into a common 3-dimensional space, and regions of decreased ADC (dADC) were superimposed onto the corresponding CT. Mean values of ADC and Hounsfield units (HU) were determined in comparison with the nonaffected hemisphere. RESULTS: Mean decrease in ADC (dADC) was 170+/-53x 10(-6) mm2/s and corresponded to a decrease (dCT) in CT density of 1.3+/-0.7 HU. dCT showed a continuous linear decrease of 0.4 HU/h (r=0.55, P<0.01), whereas the decrease is ADC was almost complete after 1.5 hours. A correlation between the decrease in ADC and dCT was found (r=0.41, P=0.04). CONCLUSIONS: The severity of diffusion restriction correlates with net water uptake in acute ischemic stroke. However, the underlying pathophysiology and different time courses indicate a common reason rather than a direct causality for both phenomena. The time delay and low value of CT density changes provide a reasonable explanation for the higher sensitivity of MR imaging in ischemic stroke.

Cerebral blood flow predicts lesion growth in acute stroke patients.

BACKGROUND AND PURPOSE: We sought to study the role of MRI-derived cerebral blood flow (CBF) measurements for the prediction of lesion development in acute stroke patients. METHODS: Thirty-two patients were treated with tissue plasminogen activator. Diffusion-weighted (DWI) and perfusion-weighted MRI, T2-weighted imaging, and MR angiography were performed before treatment (2.8+/-0.9 hours after symptom onset) and on follow-up (days 1 and 7). CBF thresholds (12 and 22 mL/100 g per minute) were applied to bolus tracking MRI maps to determine predictive cutoff levels. RESULTS: In 21 patients (group A), the terminal lesion volume (T2-weighted imaging) was larger than the initial DWI lesion volume (89+/-93 versus 21+/-38 mL). In 11 patients (group B), the terminal lesion volume was smaller than the initial DWI lesion volume (7+/-27 versus 15+/-29 mL). The initial DWI lesion volume did not differ between both groups. The presence of a tissue volume > or =50 mL with a CBF value < or =12 mL/100 g per minute was predictive for lesion enlargement to day 7 in T2-weighted imaging (positive predictive value, 0.80). CONCLUSIONS: The presence of a tissue volume > or =50 mL with a CBF value < or =12 mL/100 g per minute predicts further lesion growth in hyperacute stroke patients. MRI-derived CBF values, with all their present limitations, are valuable in early estimation of prognosis of stroke patients.

Normal brain maturation characterized with age-related T2 relaxation times: an attempt to develop a quantitative imaging measure for clinical use.

OBJECTIVES: We studied age-related changes in T2 relaxation times from the normal maturating human brain under routine clinical MR examination conditions. MATERIALS AND METHODS: In 70 healthy subjects aged between 3 weeks and 39 years, T2 maps of the brain in which the intensity of each pixel corresponded to T2 relaxation times were generated based on magnetic resonance imaging data collected with a triple spin echo sequence. T2 relaxation times in white matter (WM) and gray matter (GM) were measured in 6 distinctive regions of interest of the T2 maps. The age dependence of the T2 values was mathematically simulated using a biexponential function. RESULTS: T2 values were largest at the age of 3 weeks (maximum: approximately 400 milliseconds for WM and 200 milliseconds for GM) and decreased continuously with increasing age, faster in the first few months and slower thereafter, until values achieved between 95 and 110 milliseconds for WM and 88 and 95 milliseconds for GM in adults. The relationship between T2 values and age could be well simulated using a biexponential function (R > 0.92). CONCLUSIONS: T2 relaxation time correlates well with the progress of brain maturation. The used biexponential function reflects the dynamic development of myelination in newborns and young children as well as the maturation of myelination during adolescence and could be used to develop a "normal" reference for neuroradiological diagnoses.

Histological findings in ruptured aneurysms treated with GDCs: six examples at varying times after treatment.

BACKGROUND AND PURPOSE: A novel plastic embedding approach was used to histologically evaluate inflammatory changes and scar formation over time and to better visualize the mesh attenuation within the aneurysm lumen of acutely ruptured aneurysms after treatment with GDCs. METHODS: Autopsies were performed on six patients with acute subarachnoid hemorrhage who had died between 5 and 272 days after GDC treatment. The aneurysms containing the platinum coils were embedded in plastic along with the intact parent vessels, were sliced, and were ground to a thickness of 5 to 10 micro m. In addition, 250- micro m-thick sections were prepared. Histologic examinations were performed. Three exemplary cases representing the time lapse from treatment to death are discussed in detail. RESULTS: At the three exemplary time periods (5, 13, and 272 days) after coiling, a continuing healing process could be observed. At 5 days after placement of GDCs, a blood clot consisting of erythrocytes and fibrin was found throughout the cavity. Thirteen days after the procedure, large foamy macrophages were observed near the coils in the aneurysm cavity. Two hundred seventy-two days after the intervention, scar formation within the aneurysm appeared to be completed, with vascularized connective tissue filling the cavity and embedding the coils. Large foreign body giant cells were found adjacent to the coils. A layer of long slender cells, resembling endothelium, sealed the aneurysm neck. CONCLUSION: We postulate that within days after GDC treatment, blood clotting and thrombus formation prevent rebleeding and that solid scar formation covered by a layer of long slender cells, resembling endothelium, seals the aneurysm over time.