Campbell, B. C.V. et al. (2019) Penumbral imaging and functional outcome in patients with anterior circulation ischaemic stroke treated with endovascular thrombectomy versus medical therapy: a meta-analysis of individual patient-level data.ABSTRACT Background: CT-perfusion (CTP) and MRI may assist patient selection for endovascular thrombectomy. We aimed to establish whether imaging assessments of ischaemic core and penumbra volumes were associated with functional outcomes and treatment effect.

BACKGROUND AND PURPOSE: Mechanical thrombectomy (MT) has helped many patients achieve functional independence. The effect of time-to-treatment based in specific epochs and as related to Alberta Stroke Program Early CT Score (ASPECTS) has not been established. The goal of the study was to evaluate the association between last known normal (LKN)-to-puncture time and good functional outcome. METHODS: We conducted a retrospective cohort study of prospectively collected acute ischemic stroke patients undergoing MT for large vessel occlusion. We used binary logistic regression models adjusted for age, Modified Treatment in Cerebral Ischemia score, initial National Institutes of Health Stroke Scale, and noncontrast CT ASPECTS to assess the association between LKN-topuncture time and favorable outcome defined as Modified Rankin Score 0-2 on discharge. RESULTS: Among 421 patients, 328 were included in analysis. Increased LKN-to-puncture time was associated with decreased probability of good functional outcome (adjusted odds ratio [aOR] ratio per 15-minute delay = .98; 95% confidence interval [CI], .97-.99; P = .001). This was especially true when LKN-puncture time was 0-6 hours (aOR per 15-minute delay = .94; 95% CI, .89-.99; P = .05) or ASPECTS 8-10 (aOR = .98; 95% CI, .97-.99; P = .002) as opposed to when LKN-puncture time was 6-24 hours (aOR per 15-minute delay = .99; 95% CI, .97-1.00; P = .16) and ASPECTS <8 (aOR = .98; 95% CI, .93-1.03; P = .37). CONCLUSION: Decreased LKN-groin puncture time improves outcome particularly in those with good ASPECTS presenting within 6 hours. Strategies to decrease reperfusion times should be investigated, particularly in those in the early time window and with good ASPECTS.

BACKGROUND AND PURPOSE To assess the sensitivity of non-localized, whole-head 1H-MRS to an individual’s serial changes in total-brain NAA, Glx, Cr and Cho concentrations – metabolite metrics often used as surrogate markers in neurological pathologies. MATERIALS AND METHODS In this prospective study, four back-to-back (single imaging session) and three serial (successive sessions) non-localizing, ~3 minute 1H-MRS (TE/TR/TI= 5/104/940 ms) scans were performed on 18 healthy young volunteers: 9 women, 9 men: 29.9±7.6 [mean±standard deviation (SD)] years old. These were analyzed by calculating a within-subject coefficient of variation (CV=SD/mean) to assess intra- and inter-scan repeatability and prediction intervals. This study was Health Insurance Portability and Accountability Act-compliant. All subjects gave Institutional Review Board-approved written, informed consent. RESULTS The intra-scan CVs for the NAA, Glx, Cr and Cho were: 3.9±1.8%, 7.3±4.6%, 4.0±3.4% and 2.5±1.6%, and the corresponding inter-scan (longitudinal) values were: 7.0±3.1%, 10.6±5.6%, 7.6±3.5% and 7.0±3.9%. This method is shown to have 80% power to detect changes of 14%, 27%, 26% and 19% between two serial measurements in a given individual. CONCLUSIONS Subject to the assumption that in neurological disorders NAA, Glx, Cr and Cho changes represent brain-only pathology and not muscles, bone marrow, adipose tissue or epithelial cells, this approach enables us to quantify them, thereby adding specificity to the assessment of the total disease load. This will facilitate monitoring diffuse pathologies with faster measurement, more extensive (~90%) spatial coverage and sensitivity than localized 1H-MRS.

SUMMARY NAA, Cr and Cho 1H-MRS signals are often used as surrogate markers in diffuse neurological pathologies, but spatial coverage of this methodology is limited to 1%–65% of the brain. Here we wish to demonstrate that non-localized, WH 1H-MRS, captures just the brain’s contribution to the Cho and Cr signals, ignoring all other compartments. Towards this end 27 young healthy adults (18 men, 9 women), 29.9±8.5 years old, were recruited and underwent T1-weighted MRI for tissue segmentation, non-localizing, ~3 minute WH 1H-MRS (TE/TR/TI= 5/104/940 ms) and 30 min 1HMRSI (TE/TR=35/2100 ms) in a 360 cm3 VOIs at the brain's center. The VOI absolute NAA and Cr and Cho concentrations: 7.7±0.5, 5.5±0.4 and 1.3±0.2 mM, were all within 10% of the WH: 8.6±1.1, 6.0±1.0 and 1.3±0.2 mM. The mean NAA/Cr and NAA/Cho ratios in the WH were only slightly higher than the “brain-only” VOI: 1.5 versus 1.4 (7%) and 6.6 versus 5.9 (11%); Cho/Cr were not different (0.2 for both). The brain/WH volume ratio was 0.31±0.03 (brain ≈30% of WH volume). Air-tissue susceptibility-driven local magnetic field changes going from the brain outwards showed sharp ›100 Hz/cm (1 ppm/cm) gradients, explaining the skull’s Cr and Cho signal losses through, resonance shifts, line broadening and destructive interference. The similarity of non-localized WH and localized VOI NAA, Cr and Cho concentrations and their ratios, suggest that their signals originate predominantly from the brain. Therefore, the fast, comprehensive WH-1H-MRS method may facilitate quantification of these metabolites, which are common surrogate markers in neurological disorders.

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