Wijman, Christine A.C.

Background: Brain diffusion-weighted imaging MRI (DWI) holds promise as a prognostic tool in comatose post-cardiac arrest patients. In a preliminary study we found that more than 10% of whole brain volume with an ADC value of <650x10 -6 mm 2 /sec between 49-108 hours after the arrest identified poor outcome patients (death or vegetative state at 30 days) with 100% specificity and 81% sensitivity. We aimed to validate this threshold in an external dataset. Methods: This is an ongoing multicenter observational study of DWI MRIs of comatose post-cardiac arrest patients obtained between 1 and 5 days (i.e. 25-120 hours) after the arrest. Patient data are systematically recorded on a web-based data entry form and include baseline characteristics, serial neurological examinations, neurophysiological testing, and date and cause of death if applicable. Poor outcome is defined as in hospital death. Assuming a 40% survival rate, and 100% specificity of DWI for poor outcome, 250 patients are needed to achieve a 0% false positive rate for poor outcome with a 95% confidence interval of 0-5%. MRI scans were processed using MIPAV (Medical Image Processing, Analysis and Visualization program). The brain was semi-automatically outlined on the b0 images using a levelset algorithm that analyzes the intensity and then produces the contours of the boundary. If necessary, contours were adjusted manually. The created brain masks were then applied to the corresponding ADC maps, and the ADC values of voxels within the brain were saved for further analysis. We used the ADC maps that we received from the participating centers. If only the b0 and b1000 images were available, we recreated the brain ADC maps using MIPAV. Results: Data from 48 patients from three centers (Northwestern, Mayo Clinic Jacksonville, Stanford) were included in this preliminary analysis: mean age was 57±16 years, 33% female, arrest time 23±23 minutes, 88% of patients were treated with hypothermia. The MRIs were obtained at 73±22 hours after the arrest. Twenty patients (42%) survived to hospital discharge. The median (IQR) percentage of brain volume with ADC<650x10 -6 mm 2 /sec was 5% (3-6) in survivors and 30% (9-46) in non-survivors (P<0.001). Brain volume with an ADC<650x10 -6 mm 2 /sec > 10% was 100% (95%CI 80-100) specific and 68% (95%CI 48-83) sensitive for in hospital death with a positive predictive value of 100% (79-100), and a negative predictive value of 69% (49-84). The risk ratio (RR) of death if >10% of brain volume had an ADC<650x10 -6 mm 2 /sec was 3.2 (95%CI 1.9-5.5). Conclusion: The preliminary results of this multicenter study demonstrate that early quantitative DWI MRI in comatose post-cardiac arrest patients holds great promise as a prognostic adjunct in these patients in the era of hypothermia. Centers who frequently obtain brain DWI MRI in comatose post-cardiac arrest patients are encouraged to participate.

Background and Purpose— The ABC/2 score estimates intracerebral hemorrhage (ICH) volume, yet validations have been limited by small samples and inappropriate outcome measures. We determined accuracy of the ABC/2 score calculated at a specialized reading center (RC-ABC) or local site (site-ABC) versus the reference-standard computed tomography–based planimetry (CTP). Methods— In Minimally Invasive Surgery Plus Recombinant Tissue-Type Plasminogen Activator for Intracerebral Hemorrhage Evacuation-II (MISTIE-II), Clot Lysis Evaluation of Accelerated Resolution of Intraventricular Hemorrhage (CLEAR-IVH) and CLEAR-III trials. ICH volume was prospectively calculated by CTP, RC-ABC, and site-ABC. Agreement between CTP and ABC/2 was defined as an absolute difference up to 5 mL and relative difference within 20%. Determinants of ABC/2 accuracy were assessed by logistic regression. Results— In 4369 scans from 507 patients, CTP was more strongly correlated with RC-ABC ( r 2 =0.93) than with site-ABC ( r 2 =0.87). Although RC-ABC overestimated CTP-based volume on average (RC-ABC, 15.2 cm 3 ; CTP, 12.7 cm3), agreement was reasonable when categorized into mild, moderate, and severe ICH (κ=0.75; P <0.001). This was consistent with overestimation of ICH volume in 6 of 8 previous studies. Agreement with CTP was greater for RC-ABC (84% within 5 mL; 48% of scans within 20%) than for site-ABC (81% within 5 mL; 41% within 20%). RC-ABC had moderate accuracy for detecting ≥5 mL change in CTP volume between consecutive scans (sensitivity, 0.76; specificity, 0.86) and was more accurate with smaller ICH, thalamic hemorrhage, and homogeneous clots. Conclusions— ABC/2 scores at local or central sites are sufficiently accurate to categorize ICH volume and assess eligibility for the CLEAR-III and MISTIE III studies and moderately accurate for change in ICH volume. However, accuracy decreases with large, irregular, or lobar clots. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: MISTIE-II NCT00224770; CLEAR-III NCT00784134.