Determining T2 relaxation time and stroke onset relationship in ischaemic stroke within apparent diffusion coefficient-defined lesions. A user-independent method for quantifying the impact of stroke in the human brain.

BACKGROUND AND OBJECTIVE: In hyperacute ischaemic stroke, T2 of cerebral water increases with time. Quantifying this change may be informative of the extent of tissue damage and onset time. Our objective was to develop a user-unbiased method to measure the effect of cerebral ischaemia on T2 to study stroke onset time-dependency in human acute stroke lesions. METHODS: Six rats were subjected to permanent middle cerebral occlusion to induce focal ischaemia, and a consecutive cohort of acute stroke patients (n = 38) were recruited within 9 hours from symptom onset. T1-weighted structural, T2 relaxometry, and diffusion MRI for apparent diffusion coefficient (ADC) were acquired. Ischaemic lesions were defined as regions of lowered ADC. The median T2 difference (ΔT2) between lesion and contralateral non-ischaemic control region was determined by the newly-developed spherical reference method, and data compared to that obtained by the mirror reference method. Linear regressions and receiver operating characteristics (ROC) were compared between the two methods. RESULTS: ΔT2 increases linearly in rat brain ischaemia by 1.9 ± 0.8 ms/h during the first 6 hours, as determined by the spherical reference method. In patients, ΔT2 linearly increases by 1.6 ± 1.4 and 1.9 ± 0.9 ms/h in the lesion, as determined by the mirror reference and spherical reference method, respectively. ROC analyses produced areas under the curve of 0.83 and 0.71 for the spherical and mirror reference methods, respectively. CONCLUSIONS: Data from the spherical reference method showed that the median T2 increase in the ischaemic lesion is correlated with stroke onset time in a rat as well as in a human patient cohort, opening the possibility of using the approach as a timing tool in clinics.

Quantifying T 2 relaxation time changes within lesions defined by apparent diffusion coefficient in grey and white matter in acute stroke patients.

The apparent diffusion coefficient (ADC) of cerebral water, as measured by diffusion MRI, rapidly decreases in ischaemia, highlighting a lesion in acute stroke patients. The MRI T 2 relaxation time changes in ischaemic brain such that T 2 in ADC lesions may be informative of the extent of tissue damage, potentially aiding in stratification for treatment. We have developed a novel user-unbiased method of determining the changes in T 2 in ADC lesions as a function of clinical symptom duration based on voxel-wise referencing to a contralateral brain volume. The spherical reference method calculates the most probable pre-ischaemic T 2 on a voxel-wise basis, making use of features of the contralateral hemisphere presumed to be largely unaffected. We studied whether T 2 changes in the two main cerebral tissue types, i.e. in grey matter (GM) and white matter (WM), would differ in stroke. Thirty-eight acute stroke patients were accrued within 9 h of symptom onset and scanned at 3 T for 3D T 1-weighted, multi b-value diffusion and multi-echo spin echo MRI for tissue type segmentation, quantitative ADC and absolute T 2 images, respectively. T 2 changes measured by the spherical reference method were 1.94 ± 0.61, 1.50 ± 0.52 and 1.40 ± 0.54 ms h-1 in the whole, GM, and WM lesions, respectively. Thus, T 2 time courses were comparable between GM and WM independent of brain tissue type involved. We demonstrate that T 2 changes in ADC-delineated lesions can be quantified in the clinical setting in a user unbiased manner and that T 2 change correlated with symptom onset time, opening the possibility of using the approach as a tool to assess severity of tissue damage in the clinical setting.

Do Clinicians Overestimate the Severity of Intracerebral Hemorrhage?

Background and Purpose- Intracerebral hemorrhage (ICH) has a poorer prognosis than acute ischemic stroke (AIS). However, clinician perception of prognosis may influence treatment decisions and adversely affect outcome. On acute CT, the conspicuity of ICH compared with AIS may lead clinicians to overestimate severity and influence prognostic evaluation. We investigated whether clinicians' estimates of volume, severity, and prognosis from acute imaging differed between ICH and AIS. Methods- CT scans from participants with acute ICH or ischemic stroke were reviewed. Volume was calculated using the ABC/2 method and automated volumetric analysis via specialized imaging software. ICH cases were matched with AIS cases for lesion volume, based on acute (<6 hours) CT for ICH, and 24-hour CT for AIS. Blind to clinical information, clinicians estimated lesion volume to the nearest 5 mL, graded lesion severity from 1 (mild) to 5 (very severe), and estimated 30-day prognosis using the modified Rankin Scale. Results- We compared 33 ICH cases with 33 volume-matched AIS cases. Clinicians overestimated ICH volume and underestimated AIS volumes: mean differences (estimated-actual volume) were +8 mL (±30) for ICH and -8 mL (±27) for AIS ( P<0.001). Observers rated ICH to be of greater severity and poorer prognosis compared with AIS cases: 109 of 265 (41%) ICH cases rated severity categories 4 or 5 compared with 36 of 257 (14%) AIS, P<0.001; estimated modified Rankin Scale of 0 to 2 in 125 of 265 (47%) ICH compared with 190 of 257 (74%) AIS, P<0.001. Results were unaffected by presence of intraventricular blood. Estimated severity and prognosis for ICH remained significantly worse compared with AIS after adjustment for estimated volumes. Conclusions- Clinicians overestimated ICH volume and severity compared with AIS of equivalent volume and also assigned significantly worse prognosis independent of volume estimates.

Observer Agreement on Computed Tomography Perfusion Imaging in Acute Ischemic Stroke.

Background and Purpose- Computed tomography (CT) perfusion (CTP) provides potentially valuable information to guide treatment decisions in acute stroke. Assessment of interobserver reliability of CTP has, however, been limited to small, mostly single center studies. We performed a large, internet-based study to assess observer reliability of CTP interpretation in acute stroke. Methods- We selected 24 cases from the IST-3 (Third International Stroke Trial), ATTEST (Alteplase Versus Tenecteplase for Thrombolysis After Ischaemic Stroke), and POSH (Post Stroke Hyperglycaemia) studies to illustrate various perfusion abnormalities. For each case, observers were presented with noncontrast CT, maps of cerebral blood volume, cerebral blood flow, mean transit time, delay time, and thresholded penumbra maps (dichotomized into penumbra and core), together with a short clinical vignette. Observers used a structured questionnaire to record presence of perfusion deficit, its extent compared with ischemic changes on noncontrast CT, and an Alberta Stroke Program Early CT Score for noncontrast CT and CTP. All images were viewed, and responses were collected online. We assessed observer agreement with Krippendorff-α. Intraobserver agreement was assessed by inviting observers who reviewed all scans for a repeat review of 6 scans. Results- Fifty seven observers contributed to the study, with 27 observers reviewing all 24 scans and 17 observers contributing repeat readings. Interobserver agreement was good to excellent for all CTP. Agreement was higher for perfusion maps compared with noncontrast CT and was higher for mean transit time, delay time, and penumbra map (Krippendorff-α =0.77, 0.79, and 0.81, respectively) compared with cerebral blood volume and cerebral blood flow (Krippendorff-α =0.69 and 0.62, respectively). Intraobserver agreement was fair to substantial in the majority of readers (Krippendorff-α ranged from 0.29 to 0.80). Conclusions- There are high levels of interobserver and intraobserver agreement for the interpretation of CTP in acute stroke, particularly of mean transit time, delay time, and penumbra maps.

Penumbra and re-canalization acute computed tomography in ischemic stroke evaluation: PRACTISE study protocol.

Rationale Multimodal imaging, including computed tomography angiography and computed tomography perfusion imaging, yields additional information on intracranial vessels and brain perfusion and can differentiate between ischemic core and penumbra which may affect patient selection for intravenous thrombolysis. Hypothesis The use of multimodal imaging will increase the number of patients receiving intravenous thrombolysis and lead to better treatment outcomes. Sample size 400 patients. Methods and design PRACTISE is a prospective, multicenter, randomized, controlled trial in which patients presenting within 4.5 h of symptom onset are randomized to either the current evidence-based imaging (NCCT alone) or additional multimodal computed tomography imaging (NCCT + computed tomography angiography + computed tomography perfusion). Clinical decisions on intravenous recombinant tissue plasminogen activator are documented. Total imaging time in both arms and time to initiation of treatment delivery in those treated with intravenous recombinant tissue plasminogen activator, is recorded. Follow-up will include brain imaging at 24 h to document infarct size, the presence of edema and the presence of intra-cerebral hemorrhage. Clinical evaluations include NIHSS score at baseline, 24 h and day 7 ± 2, and mRS at day 90 to define functional outcomes. Study outcomes The primary outcome is the proportion of patients receiving intravenous recombinant tissue plasminogen activator. Secondary end-points evaluate times to decision-making, comparison of different image processing software and clinical outcomes at three months. Discussion Multimodal computed tomography is a widely available tool for patient selection for revascularization therapy, but it is currently unknown whether the use of additional imaging in all stroke patients is beneficial. The study opened for recruitment in March 2015 and will provide data on the value of multimodal imaging in treatment decisions for acute stroke.

PARK11 gene (GIGYF2) variants Asn56Ser and Asn457Thr are not pathogenic for Parkinson's disease.

The GIGYF2 (Grb10-Interacting GYF Protein-2) gene has recently been proposed to be the responsible gene for the PARK11 locus. Ten different putative pathogenic variants were identified in cohorts of Parkinson's disease (PD) patients from Italy and France. Among these variants Asn56Ser and Asn457Thr were found repeatedly. In the present study we screened 669 PD patients (predominantly of central European origin) and 1051 control individuals for the presence of these two variants. Asn56Ser was found in one patient with a positive family history of the disease and in one control individual. The affected sister of the patient did not carry this variant. Asn457Thr was found in one patient, who was exceptional for his Egyptian origin and in three control individuals. This variant was not found in 50 control individuals from Egypt. We conclude that neither of these two variants plays a major role in the pathogenesis of PD in our study population.