Background and Objectives: To investigate the relationship between baseline blood-brain barrier (BBB) permeability and the kinetics of circulating inflammatory markers in a cohort of acute ischemic stroke (AIS) patients treated with mechanical thrombectomy. Methods: The HIBISCUS-STROKE cohort includes AIS patients treated with mechanical thrombectomy following admission MRI, and undergoing a sequential assessment of circulating inflammatory markers. Baseline dynamic-susceptibility perfusion MRI was post-processed with arrival time correction to provide K2 maps reflecting BBB permeability. After co-registration of apparent-diffusion-coefficient and K2 maps, 90^th percentile of K2 value was extracted within baseline ischemic core and expressed as a percentage change compared to contralateral normal appearing white matter. Population was dichotomized according to median K2 value. Uni- and multiple variable logistic regressions analyses were performed to investigate factors associated with increased pretreatment BBB permeability in the whole population and in patients with symptoms onset <6h. Results: In the whole population (n=105 patients, median K2=1.59), patients with increased BBB permeability had higher serum levels of MMP-9 at H48 (p=0.02), higher CRP serum level at H48 (p=0.01), poorer collateral status (p=0.01), and larger baseline ischemic core (p<0.001). They were more likely to have hemorrhagic transformation (p=0.008), larger final lesion volume (p=0.02), and worst neurologic outcome at 3-months (p=0.04). The multiple variable logistic regression indicated that increased BBB permeability was only associated with ischemic core volume (Odds Ratio (OR)= 1.04; 95% Confidence Interval (CI): [1.01; 1.06], p<0.0001). Restricting analysis to patients with symptoms onset < 6h (n=72, median K2=1.27), subjects with increased BBB permeability had higher serum levels of MMP-9 at both H0 (p=0.005), H6 (p=0.004), H24 (p=0.02) and H48 (p=0.01), higher CRP levels at H48 (p=0.02) and larger baseline ischemic core (p<0.0001). The multiple variable logistic analysis showed that increased BBB permeability was independently associated with higher H0 MMP-9 levels (OR=1.33; 95% CI: [1.12; 1.65]; p=0.01) and larger ischemic core (OR=1.27; 95% CI: [1.08; 1.59]; p=0.04). Discussion: In AIS patients, increased BBB permeability is associated with larger ischemic core. In the subgroup of patients with symptoms onset <6h, increased BBB permeability is independently associated with higher H0-MMP-9 levels and larger ischemic core.

After radiochemotherapy, 30% of patients with early worsening MRI experience pseudoprogression (Psp) which is not distinguishable from early progression (EP). We aimed to assess the diagnostic value of radiomics in patients with suspected EP or Psp. Radiomics features (RF) of 76 patients (53 EP and 23 Psp) retrospectively identified were extracted from conventional MRI based on four volumes-of-interest. Subjects were randomly assigned into training and validation groups. Classification model (EP versus Psp) consisted of a random forest algorithm after univariate filtering. Overall (OS) and progression-free survivals (PFS) were predicted using a semi-supervised principal component analysis and, forecasts were evaluated using C index and integrated Brier scores (IBS). Using 11 RFs, radiomics classified patients with 75.0% and 76.0% accuracy, 81.6% and 94.1% sensitivity, 50.0% and 37.5% specificity, respectively in training and validation phases. Addition of MGMT promoter status improved accuracy to 83% and 79.2% and, specificity to 63.6% and 75%. OS model included 14 RFs and stratified low- and high-risk patients both in the training (hazard ratio (HR), 3.63, p=0.002) and the validation (HR, 3.76, p=0.001) phases. Similarly, PFS model stratified patients during training (HR, 2.58, p=0.005) and validation (HR, 3.58, p=0.004) phases using 5 RF. OS and PFS forecasts had C index of 0.65 and 0.69 and, IBS of 0.122 and 0.147, respectively. Conventional MRI radiomics has promising diagnostic value, especially when combined with MGMT promoter status, but with moderate specificity. In addition, our results suggest a potential for predicting OS and PFS.

BACKGROUND: In acute stroke, diffusion-weighted imaging (DWI) is used to assess the ischemic core. Dynamic-susceptibility contrast perfusion magnetic resonance imaging allows an estimation of the oxygen extraction fraction (OEF), but the outcome of DWI lesions with increased OEF postrecanalization is unclear. This study investigated the impact of OEF on the fate of DWI lesions in patients achieving recanalization after thrombectomy. METHODS: This was a retrospective analysis of the HIBISCUS-STROKE cohort (Cohort of Patients to Identify Biological and Imaging Markers of Cardiovascular Outcomes in Stroke; NCT: 03149705), a single-center observational study that prospectively enrolled patients who underwent magnetic resonance imaging triage for thrombectomy and a day-6 T2-fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging. Automated postprocessing of admission dynamic-susceptibility contrast perfusion magnetic resonance imaging generated OEF maps. At visual analysis, the OEF status within DWI lesions was assessed in comparison to the contralateral side and correlated with volume changes (difference of ischemic lesion between admission DWI and registered day-6 T2-FLAIR). At voxel-based analysis, recovered DWI regions (lesions present on the admission DWI but absent on the registered day-6 T2-FLAIR) and nonrecovered regions were segmented to extract semiquantitative OEF values. RESULTS: Of the participants enrolled from 2016 to 2022, 134 of 321 (41.7%) were included (median age, 71.0 years; 58.2% male; median baseline National Institutes of Health Scale score, 15.0). At visual analysis, 46 of 134 (34.3%) patients had increased OEF within DWI lesions. These patients were more likely to show a reduction in ischemic lesion volumes compared with those without increased OEF (median change, −4.0 versus 4.8 mL; P <0.0001). Multivariable analysis indicated that increased OEF within DWI lesions was associated with a reduction in ischemic lesion volumes from admission DWI to day-6 T2-FLAIR (odds ratio, 0.68 [95% CI, 0.49–0.87]; P =0.008). At voxel-based analysis, recovered DWI regions had increased OEF, while nonrecovered regions had decreased OEF (median, 126.9% versus −27.0%; P <0.0001). CONCLUSIONS: Increased OEF within hyperacute DWI lesions was associated with ischemic lesion recovery between admission DWI and day-6 T2-FLAIR in patients achieving recanalization after thrombectomy. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03149705.