Admission computed tomography radiomic signatures outperform hematoma volume in predicting baseline clinical severity and functional outcome in the ATACH-2 trial intracerebral hemorrhage population.

BACKGROUND AND PURPOSE: Radiomics provides a framework for automated extraction of high-dimensional feature sets from medical images. We aimed to determine radiomics signature correlates of admission clinical severity and medium-term outcome from intracerebral hemorrhage (ICH) lesions on baseline head computed tomography (CT). METHODS: We used the ATACH-2 (Antihypertensive Treatment of Acute Cerebral Hemorrhage II) trial dataset. Patients included in this analysis (n = 895) were randomly allocated to discovery (n = 448) and independent validation (n = 447) cohorts. We extracted 1130 radiomics features from hematoma lesions on baseline noncontrast head CT scans and generated radiomics signatures associated with admission Glasgow Coma Scale (GCS), admission National Institutes of Health Stroke Scale (NIHSS), and 3-month modified Rankin Scale (mRS) scores. Spearman's correlation between radiomics signatures and corresponding target variables was compared with hematoma volume. RESULTS: In the discovery cohort, radiomics signatures, compared to ICH volume, had a significantly stronger association with admission GCS (0.47 vs. 0.44, p = 0.008), admission NIHSS (0.69 vs. 0.57, p < 0.001), and 3-month mRS scores (0.44 vs. 0.32, p < 0.001). Similarly, in independent validation, radiomics signatures, compared to ICH volume, had a significantly stronger association with admission GCS (0.43 vs. 0.41, p = 0.02), NIHSS (0.64 vs. 0.56, p < 0.001), and 3-month mRS scores (0.43 vs. 0.33, p < 0.001). In multiple regression analysis adjusted for known predictors of ICH outcome, the radiomics signature was an independent predictor of 3-month mRS in both cohorts. CONCLUSIONS: Limited by the enrollment criteria of the ATACH-2 trial, we showed that radiomics features quantifying hematoma texture, density, and shape on baseline CT can provide imaging correlates for clinical presentation and 3-month outcome. These findings couldtrigger a paradigm shift where imaging biomarkers may improve current modelsfor prognostication, risk-stratification, and treatment triage of ICH patients.

Physician moral injury in the context of moral, ethical and legal codes.

After 40 years of attributing high rates of physician career dissatisfaction, attrition, alcoholism, divorce and suicide to 'burnout', there is growing recognition that these outcomes may instead be caused by moral injury. This has led to a debate about the relative diagnostic merits of these two terms, a recognition that interventions designed to treat burnout may be ineffective, and much perplexity about how-if at all-this changes anything.The current research seeks to develop the construct of moral injury outside military contexts, generate more robust validity tests and more fully describe and measure the experiences of persons exposed to moral harms. Absent from the literature is a mechanism through which to move from the collective moral injury experience of physicians to a systematic change in the structure of medical practice. To address this, after providing a brief history, definitions and contrasts between burnout, moral distress and moral injury, we review the interplay of moral and ethical codes in the context of moral injury. We conclude by suggesting that professional associations can potentially prevent moral injury by providing protections for physicians within their codes of ethics.

Impact of Telerehabilitation for Stroke-Related Deficits.

Background: Stroke is the leading cause of serious long-term disability in the United States. Barriers to rehabilitation include cost, transportation, lack of trained personnel, and equipment. Telerehabilitation (TR) has emerged as a promising modality to reduce costs, improve accessibility, and retain patient independence. TR allows providers to remotely administer therapy, potentially increasing access to underserved regions. Objectives: To describe types of stroke rehabilitation therapy delivered through TR and to evaluate whether TR is as effective as traditional in-person outpatient therapy in improving satisfaction and poststroke residual deficits such as motor function, speech, and disability. Methods: A literature search of the term "telerehabilitation and stroke" was conducted across three databases. Full-text articles with results pertaining to TR interventions were reviewed. Articles were scored for methodological quality using the PEDro scale. Results: Thirty-four articles with 1,025 patients were included. Types of TR included speech therapy, virtual reality (VR), robotic, community-based, goal setting, and motor training exercises. Frequently measured outcomes included motor function, speech, disability, and satisfaction. All 34 studies reported improvement from baseline after TR therapy. PEDro scores ranged from 2 to 8 with a mean of 4.59 ± 1.94 (on a scale of 0-10). Studies with control interventions, randomized allocation, and blinded assessment had significantly higher PEDro scores. All 15 studies that compared TR with traditional therapy showed equivalent or better functional outcomes. Home-based robotic therapy and VR were less costly than in-person therapy. Patient satisfaction with TR and in-person clinical therapy was similar. Conclusions: TR is less costly and equally as effective as clinic-based rehabilitation at improving functional outcomes in stroke patients. TR produces similar patient satisfaction. TR can be combined with other therapies, including VR, speech, and robotic assistance, or used as an adjuvant to direct in-person care.

Poor Outcomes Related to Anterior Extension of Large Hemispheric Infarction: Topographic Analysis of GAMES-RP Trial MRI Scans.

BACKGROUND: We aimed to assess the correlation of lesion location and clinical outcome in patients with large hemispheric infarction (LHI). METHODS: We analyzed admission MRI data from the GAMES-RP trial, which enrolled patients with anterior circulation infarct volumes of 82-300 cm3 within 10 hours of onset. Infarct lesions were segmented and co-registered onto MNI-152 brain space. Voxel-wise general linear models were applied to assess location-outcome correlations after correction for infarct volume as a co-variate. RESULTS: We included 83 patients with known 3-month modified Rankin scale (mRS). In voxel-wise analysis, there was significant correlation between admission infarct lesions involving the anterior cerebral artery (ACA) territory and its middle cerebral artery (MCA) border zone with both higher 3-month mRS and post-stroke day 3 and 7 National Institutes of Health Stroke Scale (NIHSS) total score and arm/leg subscores. Higher NIHSS total scores from admission through poststroke day 2 correlated with left MCA infarcts. In multivariate analysis, ACA territory infarct volume (P = .001) and admission NIHSS (P = .005) were independent predictors of 3-month mRS. Moreover, in a subgroup of 36 patients with infarct lesions involving right MCA-ACA border zone, intravenous (IV) glibenclamide (BIIB093; glyburide) treatment was the only independent predictor of 3-month mRS in multivariate regression analysis (P = .016). CONCLUSIONS: Anterior extension of LHI with involvement of ACA territory and ACA-MCA border zone is an independent predictor of poor functional outcome, likely due to impairment of arm/leg motor function. If confirmed in larger cohorts, infarct topology may potentially help triage LHI patients who may benefit from IV glibenclamide. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01794182.

Modeling health and well-being measures using ZIP code spatial neighborhood patterns.

Individual-level assessment of health and well-being permits analysis of community well-being and health risk evaluations across several dimensions of health. It also enables comparison and rankings of reported health and well-being for large geographical areas such as states, metropolitan areas, and counties. However, there is large variation in reported well-being within such large spatial units underscoring the importance of analyzing well-being at more granular levels, such as ZIP codes. In this paper, we address this problem by modeling well-being data to generate ZIP code tabulation area (ZCTA)-level rankings through spatially informed statistical modeling. We build regression models for individual-level overall well-being index and scores from five subscales (Physical, Financial, Social, Community, Purpose) using individual-level demographic characteristics as predictors while including a ZCTA-level spatial effect. The ZCTA neighborhood information is incorporated by using a graph Laplacian matrix; this enables estimation of the effect of a ZCTA on well-being using individual-level data from that ZCTA as well as by borrowing information from neighboring ZCTAs. We deploy our model on well-being data for the U.S. states of Massachusetts and Georgia. We find that our model can capture the effects of demographic features while also offering spatial effect estimates for all ZCTAs, including ones with no observations, under certain conditions. These spatial effect estimates provide community health and well-being rankings of ZCTAs, and our method can be deployed more generally to model other outcomes that are spatially dependent as well as data from other states or groups of states.

Radiomic markers of intracerebral hemorrhage expansion on non-contrast CT: independent validation and comparison with visual markers.

Objective: To devise and validate radiomic signatures of impending hematoma expansion (HE) based on admission non-contrast head computed tomography (CT) of patients with intracerebral hemorrhage (ICH). Methods: Utilizing a large multicentric clinical trial dataset of hypertensive patients with spontaneous supratentorial ICH, we developed signatures predictive of HE in a discovery cohort (n = 449) and confirmed their performance in an independent validation cohort (n = 448). In addition to n = 1,130 radiomic features, n = 6 clinical variables associated with HE, n = 8 previously defined visual markers of HE, the BAT score, and combinations thereof served as candidate variable sets for signatures. The area under the receiver operating characteristic curve (AUC) quantified signatures' performance. Results: A signature combining select radiomic features and clinical variables attained the highest AUC (95% confidence interval) of 0.67 (0.61-0.72) and 0.64 (0.59-0.70) in the discovery and independent validation cohort, respectively, significantly outperforming the clinical (pdiscovery = 0.02, pvalidation = 0.01) and visual signature (pdiscovery = 0.03, pvalidation = 0.01) as well as the BAT score (pdiscovery < 0.001, pvalidation < 0.001). Adding visual markers to radiomic features failed to improve prediction performance. All signatures were significantly (p < 0.001) correlated with functional outcome at 3-months, underlining their prognostic relevance. Conclusion: Radiomic features of ICH on admission non-contrast head CT can predict impending HE with stable generalizability; and combining radiomic with clinical predictors yielded the highest predictive value. By enabling selective anti-expansion treatment of patients at elevated risk of HE in future clinical trials, the proposed markers may increase therapeutic efficacy, and ultimately improve outcomes.

Brain Tumor Imaging: Applications of Artificial Intelligence.

Artificial intelligence has become a popular field of research with goals of integrating it into the clinical decision-making process. A growing number of predictive models are being employed utilizing machine learning that includes quantitative, computer-extracted imaging features known as radiomic features, and deep learning systems. This is especially true in brain-tumor imaging where artificial intelligence has been proposed to characterize, differentiate, and prognostication. We reviewed current literature regarding the potential uses of machine learning-based, and deep learning-based artificial intelligence in neuro-oncology as it pertains to brain tumor molecular classification, differentiation, and treatment response. While there is promising evidence supporting the use of artificial intelligence in neuro-oncology, there are still more investigations needed on a larger, multicenter scale along with a streamlined and standardized image processing workflow prior to its introduction in routine clinical decision-making protocol.

The coronal plane maximum diameter of deep intracerebral hemorrhage predicts functional outcome more accurately than hematoma volume.

BACKGROUND: Among prognostic imaging variables, the hematoma volume on admission computed tomography (CT) has long been considered the strongest predictor of outcome and mortality in intracerebral hemorrhage. AIMS: To examine whether different features of hematoma shape are associated with functional outcome in deep intracerebral hemorrhage. METHODS: We analyzed 790 patients from the ATACH-2 trial, and 14 shape features were quantified. We calculated Spearman's Rho to assess the correlation between shape features and three-month modified Rankin scale (mRS) score, and the area under the receiver operating characteristic curve (AUC) to quantify the association between shape features and poor outcome defined as mRS>2 as well as mRS > 3. RESULTS: Among 14 shape features, the maximum intracerebral hemorrhage diameter in the coronal plane was the strongest predictor of functional outcome, with a maximum coronal diameter >∼3.5 cm indicating higher three-month mRS scores. The maximum coronal diameter versus hematoma volume yielded a Rho of 0.40 versus 0.35 (p = 0.006), an AUC[mRS>2] of 0.71 versus 0.68 (p = 0.004), and an AUC[mRS>3] of 0.71 versus 0.69 (p = 0.029). In multiple regression analysis adjusted for known outcome predictors, the maximum coronal diameter was independently associated with three-month mRS (p < 0.001). CONCLUSIONS: A coronal-plane maximum diameter measurement offers greater prognostic value in deep intracerebral hemorrhage than hematoma volume. This simple shape metric may expedite assessment of admission head CTs, offer a potential biomarker for hematoma size eligibility criteria in clinical trials, and may substitute volume in prognostic intracerebral hemorrhage scoring systems.

Imaging of Spontaneous Intracerebral Hemorrhage.

Primary or nontraumatic spontaneous intracerebral hemorrhage (ICH) comprises approximately 15% to 20% of all stroke. ICH has a mortality of approximately 40% within the first month, and 75% mortality and morbidity rate within the first year. Despite reduction in overall stroke incidence, hemorrhagic stroke incidence has remained steady since 1980. Neuroimaging is critical in detection of ICH, determining the underlying cause, identification of patients at risk of hematoma expansion, and directing the treatment strategy. This article discusses the neuroimaging methods of ICH, imaging markers for clinical outcome prediction, and future research directions with attention to the latest evidence-based guidelines.

P2Y12 inhibitors in neuroendovascular surgery: An opportunity for precision medicine.

INTRODUCTION: Dual antiplatelet therapy (DAPT), primarily the combination of aspirin with a P2Y12 inhibitor, in patients undergoing intravascular stent or flow diverter placement remains the primary strategy to reduce device-related thromboembolic complications. However, selection, timing, and dosing of DAPT is critical and can be challenging given the existing significant inter- and intraindividual response variations to P2Y12 inhibitors. METHODS: Assessment of indexed, peer-reviewed literature from 2000 to 2020 in interventional cardiology and neuroendovascular therapeutics with critical, peer-reviewed appraisal and extraction of evidence and strategies to utilize DAPT in cardio- and neurovascular patients with endoluminal devices. RESULTS: Both geno- and phenotyping for DAPT are rapidly and conveniently available as point-of-care testing at a favorable cost-benefit ratio. Furthermore, systematic inclusion of a quantifying clinical risk score combined with an operator-linked, technical risk assessment for potential adverse events allows a more precise and individualized approach to new P2Y12 inhibitor therapy. CONCLUSIONS: The latest evidence, primarily obtained from cardiovascular intervention trials, supports that combining patient pharmacogenetics with drug response monitoring, as part of an individually tailored, precision medicine approach, is both predictive and cost-effective in achieving and maintaining individual target platelet inhibition levels. Indirect evidence supports that this gain in optimizing drug responses translates to reducing main adverse events and overall treatment costs in patients undergoing DAPT after intracranial stent or flow diverting treatment.

A case of post angiography subdural collection contrast enhancement: Time course of attenuation reduction.

The leakage of contrast material into the subdural space following intra-arterial or intravenous administration can present as hyperattenuating subdural collections on noncontrast head computed tomography (CT) scan, mimicking subdural hematomas. Such a finding can potentially initiate erroneous intervention or hinder thromboprophylaxis treatment. We report the time course of attenuation changes in enhancing subdural collections of a patient with suspected stroke following percutaneous coronary intervention. The patient had simple fluid attenuation subdural collections (hygromas) on preprocedure head CT scan, which showed gradually increasing attenuation on 2- and 10-hours post angiography CT scans. On delayed follow-up head CT scan, at 24 and 31 hours after the percutaneous coronary intervention, the subdural collection attenuation returned to preprocedural levels. In this patient, findings on an MRI obtained 9 hours after the procedure, were not in favor of a subdural hematoma. This case highlights the likelihood of contrast leakage into subdural space, mimicking extra-axial hemorrhage on head CT scans, and the time needed for normalization of subdural collection attenuation.

Pharmacy-Mediated Antiplatelet Management Protocol Compared to One-time Platelet Function Testing Prior to Pipeline Embolization of Cerebral Aneurysms: A Propensity Score-Matched Cohort Study.

BACKGROUND: There is ongoing controversy regarding the optimal antiplatelet regimen, and extent or even need for platelet function testing surrounding Pipeline flow diverter (Medtronic Inc, Dublin, Ireland) embolization of cerebral aneurysms. OBJECTIVE: To compare a unique pharmacy-mediated antiplatelet medication management protocol to a 1-time platelet function testing strategy prior to Pipeline placement. METHODS: A retrospective review of patients with cerebral aneurysms who underwent Pipeline embolization at 2 academic institutions was performed. The first line antiplatelet regimen consisted of aspirin and clopidogrel at both institutions. At institution A, the pharmacy-mediated antiplatelet medication management protocol consisted of repeat platelet function testing using VerifyNow (Accriva Diagnostics, San Diego, California), and dosing adjustments prior to and after Pipeline placement. At institution B, a 1-time platelet function test using light transmission aggregometry was obtained prior to Pipeline placement. Both strategies were compared using propensity score matching. RESULTS: A total of 63 and 165 Pipeline embolization procedures were performed at institutions A and B, respectively. Baseline characteristics differed in aneurysm location and aneurysm maximal diameter. Propensity score matching resulted in 25 matched pairs and demonstrated that the number of procedures in which the patient was switched to an alternative platelet agent was significantly smaller at institution A. There were no differences between the sites with regard to aneurysm occlusion rate, the incidence of thromboembolic and hemorrhagic complications, and modified Rankin scale at last follow-up after propensity score matching. CONCLUSION: Pharmacy-mediated antiplatelet management using VerifyNow is a safe and efficacious alternative to a more traditional approach, and significantly reduces the need to utilize other, potentially more expensive antiplatelet agents.

Evaluation of Radiological Features of the Posterior Communicating Artery and Their Impact on Efficacy of Saccular Aneurysm Treatment with the Pipeline Embolization Device: A Case Series Study.

BACKGROUND: Posterior communicating artery segment aneurysms are one of the most frequent intracranial aneurysms. Currently, limited data have described the use of the pipeline embolization device (PED) in these aneurysms. METHODS: We conducted a multicenter retrospective review of 3 prospectively collected databases of patients treated with the PED from January 2013 to December 2017. The primary objective was to assess the efficacy and safety of the PED in the treatment of saccular posterior communicating artery (PComA) aneurysms. We also assessed the effect of anatomical variations on the angiographic and clinical outcomes, including the presence of fetal PComA, vessel origin relationship to the aneurysm, and patency after PED placement. RESULTS: We identified 57 patients with 60 saccular aneurysms; Their mean age was 60.5 years, and 49 were female (86.0%). A total of 55 aneurysms (91.7%) were unruptured. The median imaging follow-up duration was 8.5 months. Complete occlusion at the last imaging follow-up study was 84.0%. At the last follow-up examination, 94.5% of patients had a modified Rankin scale score of ≤2. The presence of fetal PComA, origin type, and patency during follow-up did have a significant effect on aneurysm occlusion (P = 0.61, P = 0.40, and P = 0.14, respectively). CONCLUSIONS: PED use for treatment of PComA aneurysms resulted in acceptable occlusion rates. The present study did not find that fetal PComA, its origin, or its patency during follow-up had an effect on aneurysm occlusion.

Predictive factors of incomplete aneurysm occlusion after endovascular treatment with the Pipeline embolization device.

OBJECTIVE: The Pipeline embolization device (PED) is a routine choice for the endovascular treatment of select intracranial aneurysms. Its success is based on the high rates of aneurysm occlusion, followed by near-zero recanalization probability once occlusion has occurred. Therefore, identification of patient factors predictive of incomplete occlusion on the last angiographic follow-up is critical to its success. METHODS: A multicenter retrospective cohort analysis was conducted on consecutive patients treated with a PED for unruptured aneurysms in 3 academic institutions in the US. Patients with angiographic follow-up were selected to identify the factors associated with incomplete occlusion. RESULTS: Among all 3 participating institutions a total of 523 PED placement procedures were identified. There were 284 procedures for 316 aneurysms, which had radiographic follow-up and were included in this analysis (median age 58 years; female-to-male ratio 4.2:1). Complete occlusion (100% occlusion) was noted in 76.6% of aneurysms, whereas incomplete occlusion (≤ 99% occlusion) at last follow-up was identified in 23.4%. After accounting for factor collinearity and confounding, multivariable analysis identified older age (> 70 years; OR 4.46, 95% CI 2.30-8.65, p < 0.001); higher maximal diameter (≥ 15 mm; OR 3.29, 95% CI 1.43-7.55, p = 0.005); and fusiform morphology (OR 2.89, 95% CI 1.06-7.85, p = 0.038) to be independently associated with higher rates of incomplete occlusion at last follow-up. Thromboembolic complications were noted in 1.4% and hemorrhagic complications were found in 0.7% of procedures. CONCLUSIONS: Incomplete aneurysm occlusion following placement of a PED was independently associated with age > 70 years, aneurysm diameter ≥ 15 mm, and fusiform morphology. Such predictive factors can be used to guide individualized treatment selection and counseling in patients undergoing cerebrovascular neurosurgery.

Comparison of Pipeline Embolization Device and Flow Re-Direction Endoluminal Device Flow Diverters for Internal Carotid Artery Aneurysms: A Propensity Score-Matched Cohort Study.

BACKGROUND: Flow diversion has become an accepted endovascular treatment modality for intracranial aneurysms. Studies comparing different types of flow diverters are currently lacking. OBJECTIVE: To perform a propensity score-matched cohort study comparing the Pipeline Embolization Device (PED; Medtronic, Dublin, Ireland) and Flow Redirection Endoluminal Device (FRED; MicroVention, Aliso Viejo, California). METHODS: Aneurysms of the internal carotid artery proximal to the communicating segment treated with PED at 2 neurovascular centers in the United States were matched with aneurysms treated in the European FRED study using propensity scoring. Aneurysms treated in the setting of subarachnoid hemorrhage were excluded from matching. Occlusion rates and complications were evaluated. RESULTS: Two hundred twenty-one internal carotid artery aneurysms were treated with PED and 282 with FRED. Propensity score matching controlling for age, sex, aneurysm size, location, number of flow diverters, and adjunctive coiling resulted in 55 matched pairs. Median angiographic follow-up was nonsignificantly longer for FRED compared to PED (12.2 vs 7.5 mo, P = .28). The rate of complete occlusion did not differ between flow diverters (80% vs 80%, P > .99). Functional outcome and complications were comparable for PED and FRED. CONCLUSION: Propensity score-matched analysis of PED and FRED for internal carotid artery aneurysms revealed comparable angiographic complete occlusion and complication rates. Whether FRED has an advantage in terms of near complete aneurysm occlusion warrants further investigation. Limitations include the retrospective design and lack of an independent assessment of radiographic outcome in a core-laboratory and functional outcomes, among others, and the results should be interpreted as such.

Neuroprotection in traumatic brain injury.

Traumatic brain injury (TBI) has a high incidence worldwide and is associated with significant morbidity and mortality. TBI has enduring implications in several domains and limits overall quality of life even in the survivors. Assessment of failures of different strategies attempted at improving outcomes in traumatic brain injury is required. Several neuroprotective strategies have been studied to limit the morbidity and mortality associated with TBI. Various approaches, both pharmacologic and surgical, have been tried. In this article, we will review the epidemiology of TBI, the impact of secondary brain injury on outcomes and different strategies in traumatic brain injury. Furthermore, discussion into failure of different strategies and necessary future approach will be discussed. TBI remains a challenging condition to intervene on due to its heterogeneity. Future work should incorporate a multi-disciplinary as well as multi-center approach to target specific subset of patient population.

Proposal of a follow-up imaging strategy following Pipeline flow diversion treatment of intracranial aneurysms.

OBJECTIVE: There is currently no standardized follow-up imaging strategy for intracranial aneurysms treated with the Pipeline embolization device (PED). Here, the authors use follow-up imaging data for aneurysms treated with the PED to propose a standardizable follow-up imaging strategy. METHODS: A retrospective review of all patients who underwent treatment for ruptured or unruptured intracranial aneurysms with the PED between March 2013 and March 2017 at 2 major academic institutions in the US was performed. RESULTS: A total of 218 patients underwent treatment for 259 aneurysms with the PED and had undergone at least 1 follow-up imaging session to assess aneurysm occlusion status. There were 235 (90.7%) anterior and 24 posterior (9.3%) circulation aneurysms. On Kaplan-Meier analysis, the cumulative incidences of aneurysm occlusion at 6, 12, 18, and 24 months were 38.2%, 77.8%, 84.2%, and 85.1%, respectively. No differences in the cumulative incidence of aneurysm occlusion according to aneurysm location (p = 0.39) or aneurysm size (p = 0.81) were observed. A trend toward a decreased cumulative incidence of aneurysm occlusion in patients 70 years or older was observed (p = 0.088). No instances of aneurysm rupture after PED treatment or aneurysm recurrence after occlusion were noted. Sixteen (6.2%) aneurysms were re-treated with the PED; 11 of these had imaging follow-up data available, demonstrating occlusion in 3 (27.3%). CONCLUSIONS: The authors propose a follow-up imaging strategy that incorporates 12-month digital subtraction angiography and 24-month MRA for patients younger than 70 years and single-session digital subtraction angiography at 12 months in patients 70 years or older. For recurrent or persistent aneurysms, re-treatment with the PED or use of an alternative treatment modality may be considered.