Diffusion-weighted Imaging Lesion Volume Research Articles

Abstract TP135: Age-Related Differences in DWI Lesion Volume and Reversal in Patients With Recanalization After Mechanical Thrombectomy for Large Vessel Occlusion

Background and Purpose: With the development of mechanical thrombectomy (MT) for large vessel occlusion (LVO), post-treatment DWI lesion reversal (DWIR) has been reported. We aimed to retrospectively compare baseline and post-treatment DWI lesion volume and the incidence of DWIR between younger and elderly patients who received successful recanalization by MT for anterior LVO. Methods: A total of 177 patients who underwent successful recanalization with MT for occlusion of the anterior LVO between April 2011 and September 2022 were included in our hospital. Patients were divided into two groups: under 70 years of age and over 70 years of age. MRI was performed before and 24 hours after treatment. DWI lesion volume, apparent diffusion coefficient (ADC) value of DWI lesion, and the incidence of DWIR were examined between age groups. Factors associated with DWI lesion volumes were determined by multivariate analysis. Result: The median age of the patients was 78 years, 76 (42.9%) were female, 35 (19.8%) were in the <70 years group, and 142 (80.2%) were in the ≥70 years group. No significant differences existed between the age groups in the distribution of occluded vessels, NIHSS, and time from onset to recanalization. Baseline volume was significantly higher in the <70 years group than in the ≥70 years group (16.0ml vs 4.0ml p<0.001). There was no difference in the ADC value of DWI lesion between the two groups. There was no difference in DWIR between the two groups (65% vs. 55%), but the post-treatment DWI lesion was significantly smaller than the baseline lesion n the <70 years group. was Age being also independent of DWI lesion volume before and after treatment. Conclusions: In patients undergoing recanalization on MT for anterior LVO, baseline DWI lesions were significantly larger in young patients than in elderly patients. Although DWIR was present in over half of both groups, DWI lesion volume was significantly reduced after recanalization in younger patients.

Abstract TP126: Diffusion Weighted Image Lesion Dynamics in Acute Ischemic Stroke and Functional Recovery: Application of an Automated Software to 7000 Cases

Introduction: The change in DWI lesion volume in acute ischemic stroke has not been investigated in detail. We aimed to investigate the effect of DWI lesion growth or regression within seven days of onset on functional recovery after ischemic stroke. Methods: From a prospective stroke registry, we retrieved acute ischemic stroke cases who had more than two DWIs during in-hospital care between 2005 and 2022. The DWI lesion volume was automatically measured using JBS-01K (JLK Inc., South Korea), a fully automated and validated deep learning algorithm using 3D U-net. The association between categorized DWI lesion volume change (10, 25, 50, and 75 percentiles corresponding to -45%, 0%, 57%, and 220% of volume change) and functional recovery was assessed using multivariable ordinal logistic regression analysis taking lower modified Rankin scale (mRS) as a dependent variable, adjusting for relevant covariates. Results: A total of 7308 patients with ischemic stroke who underwent follow-up DWIs were included. A male was 62%, mean age of 67.5±13.5, and a median of initial NIHSS 4 [IQR 1-7]. The median of interval between the initial and follow-up DWI was 90 hours [IQR 68.25 - 112.20]. The median of the initial DW lesion volume was 1.00 ml [IQR 0.27-5.98], and the median of the follow-up DW lesion volume was 2.05 ml [IQR 0.27-5.98]. DWI lesion volume was regressed in 1844 cases (25%); 136 cases (13%) of EVT and 1708 cases (27%) of non-EVT cases. Compared with patients with 25-50 percentile strata, the adjusted odds ratios (OR) of having favorable functional recovery for < 10th, 10-25th, 50-75th, and ≥75th percentile were 1.25 [95% CI 1.05 - 1.48], 0.96 [0.83 - 1.11], 0.67 [0.59 - 0.76], and 0.63 [0.55 - 0.72], respectively (Figure). Conclusions: We found that approximately a quarter of patients with ischemic stroke had an interval regression of infarct volume on DWI, which is independently associated with favorable functional recovery.

Abstract 106: Circulating Interleukin-6 Levels Early During Active Stroke Estimate Time of Stroke Onset: Potential New Clinical Biomarker Tool From a Mobile Stroke Unit

Background: Circulating interleukin-6 (IL-6) concentrations are elevated in acute stroke but the timing of the IL-6 response in humans is unknown. We used a mobile stroke unit (MSU) to identify IL-6 levels within minutes of symptom onset. The results suggest a tool for estimating onset time for nearly 200,000 stroke patients annually in the U.S. in whom this is unknown. Methods: The study is a prospective, cohort investigation of ultra-early blood-derived IL-6 in acute stroke. Blood was obtained on the MSU, at 24 hours, and from hospital stroke patients and healthy controls. Plasma IL-6 was analyzed with ELISA. Confirmed strokes, mimics and controls were compared. Variables included demographics, DWI lesion volume, mRS, and NIHSS. Results: Forty-two adults were analyzed, including 28 patients treated on the MSU between August 2021 and May 2023, and 14 controls. Nineteen (68%) MSU patients were diagnosed as stroke, with 17 (61%) confirmed and 2 likely TIA or stroke averted by thrombolysis; 9 were stroke mimics. For confirmed stroke patients, median age was 72 (range 36-87) years, 47% were female, and 82% white. Median initial NIHSS score was 7 (range 1-22) and 12 (71%) received intravenous thrombolysis with tPA or TNK. Blood was obtained a median of 57 (range 26-158) minutes after symptom onset. IL-6 was elevated in all 17 confirmed stroke patients, a median of 3 times normal, as early as 26 minutes after symptom onset (median 6.4 pg/mL). In 15 (88%) cases, IL-6 increased over 24 hours, (median Δ 8.9 pg/mL). For mimics and healthy controls, median IL-6 was 5.9 and 2.3 pg/mL, respectively. Initial IL-6 in strokes was not associated with lesion volume (Spearman’s r= -0.035, p=894) or initial NIHSS (Spearman’s r=-0.043, p=869). Based on IL-6 trajectories observed, a cutoff for IL-6 set at 8 pg/mL had a sensitivity of 79% and specificity of 36% for estimating the stroke onset time was in the 4.5-hour thrombolysis window. Conclusions: This study found IL-6 was elevated in all confirmed strokes and increased in a linear fashion during the first 2.5 hours. IL-6 was independent of lesion volume and NIHSS. This suggests a rapid measurement of IL-6 from blood early in acute stroke may estimate onset time. The findings may aid development of immunomodulatory therapies for IL-6 in acute stroke.

Abstract WP129: Half of Acute Cortical Lesions in Minor Acute Ischemic Stroke Patients Persist on Flair at 30-day

Introduction: Ischemic lesions seen on acute DWI often result in chronic infarction on FLAIR. However, in minor stroke a proportion of cortical lesions seem to disappear. The objective of this study was to characterize the persistence rate of acute cortical lesions on FLAIR and associated imaging markers on 3DT1 at 30-day. Methods: Consented minor stroke patients (NIHSS<6) presented acutely (<24 hrs) received MRI at baseline, 5-day, and 30-day. One qualifying cortical lesion per patient was evaluated on baseline DWI for volume, white matter involvement, and on follow-up FLAIR for signal intensity ratio (SIR): comparison of lesion vs contralateral homologous tissue. Three independent raters blinded to hemisphere and exact location of the DWI lesion evaluated 3DT1 and FLAIR on follow-up (Figure). Results: Of 159 consented patients, 30 met criteria, and lesions of 28 patients (18%) evolved as hyperintense on FLAIR at 5-day. The 28 patients had a median age of 70 years, 54% female, median admit NIHSS of 2, and 32% were treated with IV alteplase. Of the 28 lesions, 17 (61%) had white matter involvement at baseline, and 14 (50%) were not evident on FLAIR at 30-day. Comparing those hyperintense vs not evident on FLAIR, raters identified 79% vs 21% (p<0.003) cavitation in white matter, 36% vs 0% (p<0.01) cavitation in gray matter, 57% vs 0% (p<0.001) laminar necrosis, and 100% vs 14% (p<0.001) cortical thinning on 3DT1. Lesions that persisted on FLAIR vs lesions not evident at 30-day had larger baseline DWI lesion volume: 2.2mL vs 0.3mL (p=0.024), and differences in SIR: 1.63 vs 1.3 (p=0.009) at 5-day, and 1.56 vs 1.1 (p=0.003) at 30-day. Conclusions: Half of the acute cortical lesions persisted on FLAIR at 30-day. Imaging markers on 3DT1 were more frequently associated with FLAIR evident lesions, but in ~1/3 of lesions not hyperintense, readers identified 3DT1 changes. Quantitative analysis is underway to confirm this observation.

Effect of Cerebral Small Vessel Disease Burden on Infarct Growth Rate and Stroke Outcomes in Large Vessel Occlusion Stroke Receiving Endovascular Treatment.

This study aimed to investigate the association between cerebral small vessel disease (CSVD) burden and infarct growth rate (IGR) in patients with large vessel occlusion (LVO) stroke who underwent endovascular treatment (EVT). A retrospective analysis was conducted on a cohort of 495 patients with anterior circulation stroke who received EVT. CSVD burden was assessed using a CSVD score based on neuroimaging features. IGR was calculated from diffusion-weighted imaging (DWI) lesion volumes divided by the time from stroke onset to imaging. Clinical outcomes included stroke progression and functional outcomes at 3 months. Multivariate analyses were performed to assess the relationship between CSVD burden, IGR, and clinical outcomes. The fast IGR group had a higher proportion of high CSVD scores than the slow IGR group (24.4% vs. 0.8%, p < 0.001). High CSVD burden was significantly associated with a faster IGR (odds ratio [95% confidence interval], 26.26 [6.26-110.14], p < 0.001) after adjusting for confounding factors. High CSVD burden also independently predicted stroke progression and poor functional outcomes. This study highlights a significant relationship between CSVD burden and IGR in LVO stroke patients undergoing EVT. High CSVD burden was associated with faster infarct growth and worse clinical outcomes.

Blood Oxygenation Level-Dependent Cerebrovascular Reactivity-Derived Steal Phenomenon May Indicate Tissue Reperfusion Failure After Successful Endovascular Thrombectomy.

In acute ischemic stroke due to large-vessel occlusion (LVO), the clinical outcome after endovascular thrombectomy (EVT) is influenced by the extent of autoregulatory hemodynamic impairment, which can be derived from blood oxygenation level-dependent cerebrovascular reactivity (BOLD-CVR). BOLD-CVR imaging identifies brain areas influenced by hemodynamic steal. We sought to investigate the presence of steal phenomenon and its relationship to DWI lesions and clinical deficit in the acute phase of ischemic stroke following successful vessel recanalization.From the prospective longitudinal IMPreST (Interplay of Microcirculation and Plasticity after ischemic Stroke) cohort study, patients with acute ischemic unilateral LVO stroke of the anterior circulation with successful endovascular thrombectomy (EVT; mTICI scale ≥ 2b) and subsequent BOLD-CVR examination were included for this analysis. We analyzed the spatial correlation between brain areas exhibiting BOLD-CVR-associated steal phenomenon and DWI infarct lesion as well as the relationship between steal phenomenon and NIHSS score at hospital discharge.Included patients (n = 21) exhibited steal phenomenon to different extents, whereas there was only a partial spatial overlap with the DWI lesion (median 19%; IQR, 8-59). The volume of steal phenomenon outside the DWI lesion showed a positive correlation with overall DWI lesion volume and was a significant predictor for the NIHSS score at hospital discharge.Patients with acute ischemic unilateral LVO stroke exhibited hemodynamic steal identified by BOLD-CVR after successful EVT. Steal volume was associated with DWI infarct lesion size and with poor clinical outcome at hospital discharge. BOLD-CVR may further aid in better understanding persisting hemodynamic impairment following reperfusion therapy.

Automated acute ischemic stroke lesion delineation based on apparent diffusion coefficient thresholds.

Automated lesion segmentation is increasingly used in acute ischemic stroke magnetic resonance imaging (MRI). We explored in detail the performance of apparent diffusion coefficient (ADC) thresholding for delineating baseline diffusion-weighted imaging (DWI) lesions. Retrospective, exploratory analysis of the prospective observational single-center 1000Plus study from September 2008 to June 2013 (clinicaltrials.org; NCT00715533). We built a fully automated lesion segmentation algorithm using a fixed ADC threshold (≤620 × 10-6 mm2/s) to delineate the baseline DWI lesion and analyzed its performance compared to manual assessments. Diagnostic capabilities of best possible ADC thresholds were investigated using receiver operating characteristic curves. Influential patient factors on ADC thresholding techniques' performance were studied by conducting multiple linear regression. 108 acute ischemic stroke patients were selected for analysis. The median Dice coefficient for the algorithm was 0.43 (IQR 0.20-0.64). Mean ADC values in the DWI lesion (β = -0.68, p < 0.001) and DWI lesion volumes (β = 0.29, p < 0.001) predicted performance. Optimal individual ADC thresholds differed between subjects with a median of ≤691 × 10-6 mm2/s (IQR ≤660-750 × 10-6 mm2/s). Mean ADC values in the DWI lesion (β = -0.96, p < 0.001) and mean ADC values in the brain parenchyma (β = 0.24, p < 0.001) were associated with the performance of individual thresholds. The performance of ADC thresholds for delineating acute stroke lesions varies substantially between patients. It is influenced by factors such as lesion size as well as lesion and parenchymal ADC values. Considering the inherent noisiness of ADC maps, ADC threshold-based automated delineation of very small lesions is not reliable.

Diffusion-Weighted Imaging Lesion Reversal in Older Patients With Stroke Treated With Mechanical Thrombectomy.

Diffusion-weighted imaging lesion reversal (DWIR) is frequently observed after mechanical thrombectomy for acute ischemic stroke, but little is known about age-related differences and impact on outcome. We aimed to compare, in patients <80 versus ≥80 years old, (1) the effect of successful recanalization on DWIR and (2) the impact of DWIR on functional outcome. We retrospectively analyzed data of patients treated for an anterior circulation acute ischemic stroke with large vessel occlusion in 2 French hospitals, who underwent baseline and 24-hour follow-up magnetic resonance imaging, with baseline DWI lesion volume ≥10 cc. The percentage of DWIR (DWIR%), was calculated as follows: DWIR%=(DWIR volume/baseline DWI volume)×100. Data on demographics, medical history, and baseline clinical and radiological characteristics were collected. Among 433 included patients (median age, 68 years), median DWIR% after mechanical thrombectomy was 22% (6-35) in patients ≥80, and 19% (interquartile range, 10-34) in patients <80 (P=0.948). In multivariable analyses, successful recanalization after mechanical thrombectomy was associated with higher median DWIR% in both ≥80 (P=0.004) and <80 (P=0.002) patients. In subgroup analyses performed on a minority of subjects, collateral vessels status score (n=87) and white matter hyperintensity volume (n=131) were not associated with DWIR% (P>0.2). In multivariable analyses, DWIR% was associated with increased rates of favorable 3-month outcomes in both ≥80 (P=0.003) and <80 (P=0.013) patients; the effect of DWIR% on outcome was not influenced by the age group (P interaction=0.185) Conclusions: DWIR might be an important and nonage-dependent effect of arterial recanalization, as it seems to beneficially impact 3-month outcomes of both younger and older subjects treated with mechanical thrombectomy for acute ischemic stroke and large vessel occlusion.

Predictors of Early Neurological Improvement and Its Relationship to Thrombolysis Treatment and Long-Term Outcome in the WAKE-UP Study

Introduction: The aims of this study were to evaluate the relationship of clinical and imaging baseline factors and treatment on the occurrence of early neurological improvement (ENI) in the WAKE-UP trial of MRI-guided intravenous thrombolysis in unknown onset stroke and to examine the association of ENI with long-term favorable outcome in patients treated with intravenous thrombolysis. Methods: We analyzed data from all patients with at least moderate stroke severity, reflected by an initial National Institutes of Health Stroke Scale (NIHSS) score ≥4 randomized in the WAKE-UP trial. ENI was defined as a decrease in NIHSS of ≥8 or a decline to zero or 1 at 24 h after initial presentation to the hospital. Favorable outcome was defined as a modified Rankin Scale score of 0–1 at 90 days. We performed group comparison and multivariable analysis of baseline factors associated with ENI and performed mediation analysis to evaluate the effect of ENI on the relationship between intravenous thrombolysis and favorable outcome. Results: ENI occurred in 93 out of 384 patients (24.2%) and was more likely to occur in patients who received treatment with alteplase (62.4% vs. 46.0%, p = 0.009), had smaller acute diffusion-weighted imaging lesion volume (5.51 mL vs. 10.9 mL, p ≤ 0.001), and less often large-vessel occlusion on initial MRI (7/93 [12.1%] versus 40/291 [29.9%], p = 0.014). In multivariable analysis, treatment with alteplase (OR 1.97, 95% confidence interval [CI] 0.954–1.100), lower baseline stroke volume (OR 0.965, 95% CI: 0.932–0.994), and shorter time from symptom recognition to treatment (OR 0.994, 95% CI: 0.989–0.999) were independently associated with ENI. Patients with ENI had higher rates of favorable outcome at 90-day follow-up (80.6% vs. 31.3%, p ≤ 0.001). The occurrence of ENI significantly mediated the association of treatment with a good outcome, with ENI at 24 h explaining 39.4% (12.9–96%) of the treatment effect. Conclusion: Intravenous alteplase increases the odds of ENI in patients with at least moderate stroke severity, especially when given early. In patients with large-vessel occlusion, ENI is rarely observed without thrombectomy. ENI represents a good surrogate early marker of treatment effect as more than a third of good outcome at 90 days is explained by ENI at 24 h.

Abstract TMP72: Multimodal Prediction Of Stroke Severity

Introduction: Predicting individual outcomes post-stroke with the highest possible accuracy is a crucial steppingstone in the realization of precision medicine. We here evaluated various types of lesion information in their capacity to predict stroke severity in a large cohort of patients with acute ischemic stroke. Methods: A total of 1,075 patients of the MRI-GENIE study [age: 64.2(14.7), 38% women] contributed to analyses (N=792 as train and N=283 as test sample). We employed ridge regression with hyperparameter optimization and nested five-fold cross-validation to predict acute NIHSS-based stroke severity. Our baseline model considered DWI lesion volume. Further models tested structural lesion location, indirect structural and functional lesion connectivity, individually and combined with lesion volume. Data was preprocessed by principal component analysis (PCA), retaining 95% of the variance of the original data. Model performance was compared in terms of explained variance (R-squared) and 95% confidence intervals in the outer loop of the training set and the test set. Results: Structural lesion connectivity enabled the highest prediction performance in the test set ( Figure 1 ). Prediction performance did not change notably with inclusion of lesion volume information. This contrasted with the combination of functional lesion connectivity and lesion volume that achieved a substantially higher prediction performance compared to functional lesion connectivity or lesion volume in isolation. Lesion location resulted in a prediction performance that was in the range of lesion volume alone and significantly lower than the ones of structural or functional connectivity with lesion volume. Conclusions: Structural connectivity facilitated the most convincing prediction of stroke severity. The capacity of functional lesion connectivity was substantially improved by the inclusion of lesion volume, indicating both represent complementary information.

Abstract TP84: Ring-like Pattern On Post-EVT MRI Is A Marker Of Perihematomal Edema

Introduction: Perihematomal edema is a consequence of primary intracerebral hemorrhage. On diffusion MRI, a corresponding heterogenous pattern of hypo- and hyper-intensity is visible on apparent diffusion coefficient (ADC), suggesting both cytotoxic and vasogenic edema. Analogously, endovascular therapy (EVT) for ischemic stroke can result in hemorrhagic transformation (HT) and a concomitant ring-like pattern, or “Rings” of mixed intensity on ADC. The objective of this study is to describe this pattern of secondary injury early after EVT. Methods: Patients were included if they consented to the prospective Natural History of Stroke GUARDS study from April 2018 to February 2022, were treated with EVT for anterior circulation LVO, achieved TICI 2b/3 reperfusion, and had early MRI, ~2h post-EVT. Two independent readers measured early and 24h DWI lesion volumes and 5d FLAIR lesion volumes using a semi-automated validated approach. Presence of any HT on GRE and Rings on ADC (Figure) on early, 24h, and 5d MRI were read independently by multiple readers who then reached consensus. The relationship of Rings with HT and lesion volume was explored. Results: Eighty-nine patients were included with median age 64y, 55% female, median admit NIHSS 18, 64% M1 LVO, and 47% IV tPA. On early MRI, 14 (16%) patients had Rings, 12 (86%) of whom also had HT (p&lt;0.001). At 24h, 42 (50%) patients had Rings with 33 (79%) also having HT (p&lt;0.001). There was a strong association between presence of Rings at 24h and 5d-FLAIR lesion volume, 56mL vs. 24mL in patients with vs. without Rings (p=0.002). Conclusions: Rings on ADC was seen in half of patients 24h post-EVT and appears to reflect peri-lesion edema associated with hemorrhagic transformation. This imaging marker was associated with larger lesion volumes at 5 days and may be able to serve as a target for adjunctive therapy post-EVT to mitigate edema formation.

FLAIR Vascular Hyperintensities as a Surrogate of Collaterals in Acute Stroke: DWI Matters.

FLAIR vascular hyperintensities are thought to represent leptomeningeal collaterals in acute ischemic stroke. However, whether all-FLAIR vascular hyperintensities or FLAIR vascular hyperintensities-DWI mismatch, ie, FLAIR vascular hyperintensities beyond the DWI lesion, best reflects collaterals remains debated. We aimed to compare the value of FLAIR vascular hyperintensities-DWI mismatch versus all-FLAIR vascular hyperintensities for collateral assessment using PWI-derived collateral flow maps as a reference. We retrospectively reviewed the registries of 6 large stroke centers and included all patients with acute stroke with anterior circulation large-vessel occlusion who underwent MR imaging with PWI before thrombectomy. Collateral status was graded from 1 to 4 on PWI-derived collateral flow maps and dichotomized into good (grades 3-4) and poor (grades 1-2). The extent of all-FLAIR vascular hyperintensities and FLAIR vascular hyperintensities-DWI mismatch was assessed on the 7 cortical ASPECTS regions, ranging from 0 (absence) to 7 (extensive), and associations with good collaterals were compared using receiver operating characteristic curves. Of the 209 included patients, 133 (64%) and 76 (36%) had good and poor collaterals, respectively. All-FLAIR vascular hyperintensity extent was similar between collateral groups (P = .76). Conversely, FLAIR vascular hyperintensities-DWI mismatch extent was significantly higher in patients with good compared with poor collaterals (P < .001). The area under the curve was 0.80 (95% CI, 0.74-0.87) for FLAIR vascular hyperintensities-DWI mismatch and 0.52 (95% CI, 0.44-0.60) for all-FLAIR vascular hyperintensities (P < .001 for the comparison), to predict good collaterals. Variables independently associated with good collaterals were smaller DWI lesion volume (P < .001) and larger FLAIR vascular hyperintensities-DWI mismatch (P = .02). In acute ischemic stroke with large-vessel occlusion, the extent of FLAIR vascular hyperintensities does not reliably reflect collateral status unless one accounts for DWI.

Differential Trajectory of Diffusion and Perfusion Magnetic Resonance Imaging of Rat Spinal Cord Injury.

Traumatic spinal cord injury causes rapid neuronal and vascular injury, and predictive biomarkers are needed to facilitate acute patient management. This study examined the progression of magnetic resonance imaging (MRI) biomarkers after spinal cord injury and their ability to predict long-term neurological outcomes in a rodent model, with an emphasis on diffusion-weighted imaging (DWI) markers of axonal injury and perfusion-weighted imaging of spinal cord blood flow (SCBF). Adult Sprague-Dawley rats received a cervical contusion injury of varying severity (injured = 30, sham = 9). MRI at 4 h, 48-h, and 12-weeks post-injury included T1, T2, perfusion, and DWI. Locomotor outcome was assessed up to 12 weeks post-injury. At 4 h, the deficit in SCBF was larger than the DWI lesion, and although SCBF partially recovered by 48 h, the DWI lesion expanded. At 4 h, the volume of the SCBF deficit (R2 = 0.56, padj < 0.01) was significantly correlated with 12-week locomotor outcome, whereas DWI (R2 = 0.30, padj < 0.01) was less predictive of outcome. At 48 h, SCBF (R2 = 0.41, padj < 0.01) became less associated with outcome, and DWI (R2 = 0.38, padj < 0.01) lesion volume became more closely related to outcome. Spinal cord perfusion has unique spatiotemporal dynamics compared with diffusion measures of axonal damage and highlights the importance of acute perfusion abnormalities. Perfusion and diffusion offer complementary and clinically relevant insight into physiological and structural abnormalities following spinal cord injury beyond those afforded by T1 or T2 contrasts.

Deep profiling of multiple ischemic lesions in a large, multi-center cohort: Frequency, spatial distribution, and associations to clinical characteristics.

Background purposeA substantial number of patients with acute ischemic stroke (AIS) experience multiple acute lesions (MAL). We here aimed to scrutinize MAL in a large radiologically deep-phenotyped cohort.Materials and methodsAnalyses relied upon imaging and clinical data from the international MRI-GENIE study. Imaging data comprised both Fluid-attenuated inversion recovery (FLAIR) for white matter hyperintensity (WMH) burden estimation and diffusion-weighted imaging (DWI) sequences for the assessment of acute stroke lesions. The initial step featured the systematic evaluation of occurrences of MAL within one and several vascular supply territories. Associations between MAL and important imaging and clinical characteristics were subsequently determined. The interaction effect between single and multiple lesion status and lesion volume was estimated by means of Bayesian hierarchical regression modeling for both stroke severity and functional outcome.ResultsWe analyzed 2,466 patients (age = 63.4 ± 14.8, 39% women), 49.7% of which presented with a single lesion. Another 37.4% experienced MAL in a single vascular territory, while 12.9% featured lesions in multiple vascular territories. Within most territories, MAL occurred as frequently as single lesions (ratio ∼1:1). Only the brainstem region comprised fewer patients with MAL (ratio 1:4). Patients with MAL presented with a significantly higher lesion volume and acute NIHSS (7.7 vs. 1.7 ml and 4 vs. 3, pFDR < 0.001). In contrast, patients with a single lesion were characterized by a significantly higher WMH burden (6.1 vs. 5.3 ml, pFDR = 0.048). Functional outcome did not differ significantly between patients with single versus multiple lesions. Bayesian analyses suggested that the association between lesion volume and stroke severity between single and multiple lesions was the same in case of anterior circulation stroke. In case of posterior circulation stroke, lesion volume was linked to a higher NIHSS only among those with MAL.ConclusionMultiple lesions, especially those within one vascular territory, occurred more frequently than previously reported. Overall, multiple lesions were distinctly linked to a higher acute stroke severity, a higher total DWI lesion volume and a lower WMH lesion volume. In posterior circulation stroke, lesion volume was linked to a higher stroke severity in multiple lesions only.

Association of Stroke Lesion Pattern and White Matter Hyperintensity Burden With Stroke Severity and Outcome.

To examine whether high white matter hyperintensity (WMH) burden is associated with greater stroke severity and worse functional outcomes in lesion pattern-specific ways. MR neuroimaging and NIH Stroke Scale data at index stroke and the modified Rankin Scale (mRS) score at 3-6 months after stroke were obtained from the MRI-Genetics Interface Exploration study of patients with acute ischemic stroke (AIS). Individual WMH volume was automatically derived from fluid-attenuated inversion recovery images. Stroke lesions were automatically segmented from diffusion-weighted imaging (DWI) images, parcellated into atlas-defined brain regions and further condensed to 10 lesion patterns via machine learning-based dimensionality reduction. Stroke lesion effects on AIS severity and unfavorable outcomes (mRS score >2) were modeled within purpose-built Bayesian linear and logistic regression frameworks. Interaction effects between stroke lesions and a high vs low WMH burden were integrated via hierarchical model structures. Models were adjusted for age, age2, sex, total DWI lesion and WMH volumes, and comorbidities. Data were split into derivation and validation cohorts. A total of 928 patients with AIS contributed to acute stroke severity analyses (age: 64.8 [14.5] years, 40% women) and 698 patients to long-term functional outcome analyses (age: 65.9 [14.7] years, 41% women). Stroke severity was mainly explained by lesions focused on bilateral subcortical and left hemispherically pronounced cortical regions across patients with both a high and low WMH burden. Lesions centered on left-hemispheric insular, opercular, and inferior frontal regions and lesions affecting right-hemispheric temporoparietal regions had more pronounced effects on stroke severity in case of high compared with low WMH burden. Unfavorable outcomes were predominantly explained by lesions in bilateral subcortical regions. In difference to the lesion location-specific WMH effects on stroke severity, higher WMH burden increased the odds of unfavorable outcomes independent of lesion location. Higher WMH burden may be associated with an increased stroke severity in case of stroke lesions involving left-hemispheric insular, opercular, and inferior frontal regions (potentially linked to language functions) and right-hemispheric temporoparietal regions (potentially linked to attention). Our findings suggest that patients with specific constellations of WMH burden and lesion locations may have greater benefits from acute recanalization treatments. Future clinical studies are warranted to systematically assess this assumption and guide more tailored treatment decisions.

Diffusion-Weighted Imaging and Fluid-Attenuated Inversion Recovery Quantification to Predict Diffusion-Weighted Imaging-Fluid-Attenuated Inversion Recovery Mismatch Status in Ischemic Stroke With Unknown Onset.

Visual rating of diffusion-weighted imaging (DWI)-fluid-attenuated inversion recovery (FLAIR) mismatch can be challenging. We evaluated quantification of DWI and FLAIR to predict DWI-FLAIR mismatch status in ischemic stroke. In screened patients from the WAKE-UP trial (Efficacy and Safety of Magnetic Resonance Imaging-Based Thrombolysis in Wake-Up Stroke), we retrospectively studied relative DWI (rDWI SI) and FLAIR signal intensity (rFLAIR SI). We defined the optimal mean rFLAIR SI and interquartile range of the rDWI SI in the DWI lesion to predict DWI-FLAIR mismatch status. We investigated agreement between each quantitative parameter and the DWI-FLAIR mismatch and the association between both quantitative parameters. We evaluated the predictive value of the quantitative parameters for excellent functional outcome by logistic regression, adjusted for DWI lesion volume, treatment, age, and National Institutes of Health Stroke Scale score. In the rFLAIR and rDWI SI analysis, 213/369 and 241/421 subjects respectively had a DWI-FLAIR mismatch. A mean rFLAIR SI cutoff of 1.09 and interquartile range rDWI SI cutoff of 0.47 were optimal to predict the DWI-FLAIR mismatch with a sensitivity and specificity of 77% (95% CI, 71%-83%) and 67% (95% CI, 59%-74%), and 76% (95% CI, 70%-81%) and 72% (95% CI, 65%-79%), respectively. For both quantitative parameters, agreement with the DWI-FLAIR mismatch was fair (73%, κ=0.44 [95% CI, 0.35-0.54] for rFLAIR and 74%, κ=0.48 [95% CI, 0.39-0.56] for rDWI). Both quantitative parameters correlated moderately (Pearson R=0.54 [95% CI, 0.46-0.61]; P<0.001, n=367). The interquartile range rDWI SI (n=188), but not the mean rFLAIR SI (n=172), was an independent predictor of excellent functional outcome (odds ratio, 0.67 per 0.1 unit increase of interquartile range rDWI SI, 95% CI, 0.51-0.89, P=0.01). Agreement between the quantitative and qualitative approach may be insufficient to advocate DWI or FLAIR quantification as alternative for visual rating.

Abstract WMP61: Simultaneous Cerebral Blood Flow And Blood Volume Thresholding Produces Consistent Volumes Between Computed Tomography Perfusion Deconvolution Algorithms

Introduction: Computed tomography perfusion (CTP) allows estimation of infarct volume in patients with acute ischemic stroke, but significant differences have been reported between CTP deconvolution algorithms. Hypothesis: We hypothesized that cerebral blood flow (CBF) and blood volume (CBV) dual thresholding estimates infarct volumes accurately and remain consistent between deconvolution algorithms. Methods: Data were from the open-source ISLES dataset, which comprised of patients with acute ischemic stroke who received admission CTP and infarct delineated from diffusion-weighted imaging (DWI) acquired &lt;3 hours of CTP and prior to treatment. CBF and CBV maps were calculated with a model-independent (filtered Fourier Transform) and a model-dependent (box-tail model) deconvolution algorithm using identical arterial input functions and Gaussian-filtered source images. Infarct was estimated using standard CBF&lt;30% relative to the contralateral hemisphere and a CBF&lt;30%+CBV&lt;38% dual threshold. Volume agreement between DWI and CTP lesions was determined by the mean difference ± standard deviation (DWI minus CTP). Consistency of CTP lesion volumes between deconvolution algorithms was characterized by the Pearson correlation (r) and a paired t-test. Results: Of 63 included patients, median DWI lesion volume was 28.0 (interquartile range: 13.3 to 57.2) ml. With model-independent and model-dependent deconvolution, respectively, mean differences were 35.7±40.4 ml and 10.9±47.6 ml using CBF&lt;30%, and 37.1±40.2 ml and 28.5±28.6 ml using CBF+CBV thresholding. Between model-independent and model-dependent CTP lesion volumes, Pearson correlation was moderate for CBF&lt;30% (r=0.645, p&lt;0.001) and excellent for CBF+CBV thresholding (r=0.903, p&lt;0.001). Paired t-tests were significant for both CBF&lt;30% and CBF+CBV thresholding (p&lt;0.001). Conclusions: CBF+CBV lesion volumes had improved consistency between deconvolution algorithms while achieving similar agreement to DWI lesion volumes compared to the standard CBF&lt;30% threshold. Further adjustment of CBF+CBV thresholds are required to improve accuracy to DWI lesion volumes but show promise in standardizing CTP lesion volumes across deconvolution algorithms.

Abstract WMP64: Multimodal Bayesian Modeling Of Stroke Severity

Introduction: Understanding the relations between lesions and outcomes is a particularly promising avenue to support tailored stroke care. We here employed a novel Bayesian framework integrating lesion location and functional lesion connectivity, i.e., lesion network mapping data, aiming to augment the prediction of stroke severity and the interpretability of lesion-symptom associations in a multi-center cohort of acute ischemic stroke (AIS) patients. Methods: Analyses relied on 1,077 AIS patients of the MRI-GENIE study [age: 64.2(14.7), 38%women]. NIHSS-based stroke severity was modeled via Bayesian linear regression. Structural location and functional connectivity information was represented by ten unique patterns each. We compared the out-of-sample predictive performances of structural vs. structural-functional models in Bayesian model comparisons. In ancillary analyses, we extracted functional connectivity pattern relevant for stroke severity and repeated analyses after stratifying for lesion size (50% of patients with larger lesions). Models were generally adjusted for age, sex, comorbidities and total DWI lesion volume. Results: Model comparison indicated a benefit of the combined structural-functional stroke severity prediction model compared to the structural one (model weights: 82% vs. 18%). This benefit of the combined model became even more apparent in case of patients with large lesions (97% vs. 3%). Positive lesion connectivity to the bilateral ventral attention (VA) and somatomotor networks, as well as temporal default mode network (DMN) predicted higher severity, while positive connectivity to more medial parts of the DMN and the visual network predicted lower severity. Additionally, negative lesion connectivity to the bilateral DMN, somatomotor, dorsal attention, and control networks predicted higher, and negative connectivity to the right control and bilateral VA networks predicted lower severity. Conclusions: Model comparisons indicated a benefit of integrating structural and functional information for the prediction of stroke severity, especially in case of larger lesions. Lesion connectivity data can enhance our understanding of why specific lesion locations can lead to symptoms post-stroke.

Collateral estimation by susceptibility-weighted imaging and prediction of functional outcomes after acute anterior circulation ischemic stroke

To determine the value of susceptibility-weighted imaging (SWI) for collateral estimation and for predicting functional outcomes after acute ischemic stroke. To identify independent predictors of favorable functional outcomes, age, sex, risk factors, baseline National Institutes of Health Stroke Scale (NIHSS) score, baseline diffusion-weighted imaging (DWI) lesion volume, site of steno-occlusion, SWI collateral grade, mode of treatment, and successful reperfusion were evaluated by multiple logistic regression analyses. A total of 152 participants were evaluated. A younger age (adjusted odds ratio (aOR), 0.42; 95% confidence interval (CI) 0.34 to 0.77; P < 0.001), a lower baseline NIHSS score (aOR 0.90; 95% CI 0.82 to 0.98; P = 0.02), a smaller baseline DWI lesion volume (aOR 0.83; 95% CI 0.73 to 0.96; P = 0.01), an intermediate collateral grade (aOR 9.49; 95% CI 1.36 to 66.38; P = 0.02), a good collateral grade (aOR 6.22; 95% CI 1.16 to 33.24; P = 0.03), and successful reperfusion (aOR 5.84; 95% CI 2.08 to 16.42; P = 0.001) were independently associated with a favorable functional outcome. There was a linear association between the SWI collateral grades and functional outcome (P = 0.008). Collateral estimation using the prominent vessel sign on SWI is clinically reliable, as it has prognostic value.

Clinical-CT mismatch defined NIHSS ≥ 8 and CT-ASPECTS ≥ 9 as a reliable marker of candidacy for intravenous thrombolytic therapy in acute ischemic stroke.

BackgroundClinical-diffusion mismatch between stroke severity and diffusion-weighted imaging lesion volume seems to identify stroke patients with penumbra. However, urgent magnetic resonance imaging is sometimes inaccessible or contraindicated. Thus, we hypothesized that using brain computed tomography (CT) to determine a baseline “clinical-CT mismatch” may also predict the responses to thrombolytic therapy.MethodsBrain CT lesions were measured using the Alberta Stroke Program Early CT Score (ASPECTS). A total of 104 patients were included: 79 patients with a baseline National Institutes of Health Stroke Scale (NIHSS) score ≥ 8 and a CT-ASPECTS ≥ 9 who were defined as clinical-CT mismatch-positive (P group) and 25 patients with an NIHSS score ≥ 8 and a CT-ASPECTS < 9 who were defined as clinical-CT mismatch-negative (the N group). We compared their clinical outcomes, including early neurological improvement (ENI), early neurological deterioration (END), delta NIHSS score (admission NIHSS—baseline NIHSS score), symptomatic intracranial hemorrhage (sICH), mortality, and favorable outcome at 3 months.ResultsPatients in the P group had a greater proportion of favorable outcome at 3 months (p = 0.032) and more frequent ENI (p = 0.038) and a greater delta NIHSS score (p = 0.001), as well as a lower proportion of END (p = 0.004) than those in the N group patients. There were no significant differences in the incidence rates of sICH and mortality between the two groups.ConclusionsClinical-CT mismatch may be able to predict which patients would benefit from intravenous thrombolysis.