Stroke penumbra defined by an MRI-based oxygen challenge technique: 2. Validation based on the consequences of reperfusion

Magnetic resonance imaging (MRI) with oxygen challenge (T2* OC) uses oxygen as a metabolic biotracer to define penumbral tissue based on CMRO2 and oxygen extraction fraction. Penumbra displays a greater T2* signal change during OC than surrounding tissue. Since timely restoration of cerebral blood flow (CBF) should salvage penumbra, T2* OC was tested by examining the consequences of reperfusion on T2* OC-defined penumbra. Transient ischemia (109±20 minutes) was induced in male Sprague-Dawley rats (n=8). Penumbra was identified on T2*-weighted MRI during OC. Ischemia and ischemic injury were identified on CBF and apparent diffusion coefficient maps, respectively. Reperfusion was induced and scans repeated. T2 for final infarct and T2* OC were run on day 7. T2* signal increase to OC was 3.4% in contralateral cortex and caudate nucleus and was unaffected by reperfusion. In OC-defined penumbra, T2* signal increased by 8.4%±4.1% during ischemia and returned to 3.25%±0.8% following reperfusion. Ischemic core T2* signal increase was 0.39%±0.47% during ischemia and 0.84%±1.8% on reperfusion. Penumbral CBF increased from 41.94±13 to 116.5±25 mL per 100 g per minute on reperfusion. On day 7, OC-defined penumbra gave a normal OC response and was located outside the infarct. T2* OC-defined penumbra recovered when CBF was restored, providing further validation of the utility of T2* OC for acute stroke management

Error Disclosure Training and Organizational Culture

Objective. Our primary objective was to determine whether, after training was offered to participants, those who indicated they had received error disclosure training previously were more likely to disclose a hypothetical error and have more positive perceptions of their organizational culture pertaining to error disclosure, safety, and teamwork. Methods. Across a 3-year span, all clinical faculty from six health institutions (four medical schools, one cancer center, and one health science center) in The University of Texas System were offered the opportunity to anonymously complete an electronic survey focused on measuring error disclosure culture, safety culture, teamwork culture, and intention to disclose a hypothetical error at two time points—both before (baseline) and after (follow-up) disclosure training was conducted for a subset of faculty. Results. There were significant improvements (all p-values \u3c .05) in the follow-up surveys compared with the baseline surveys for the following domains (percent refers to percent positives before and after, respectively): minor error disclosure culture (33 percent vs. 52 percent), serious error disclosure (53 percent vs. 70 percent), safety culture (50 percent vs. 63 percent), and teamwork culture (62 percent vs. 73 percent). Follow-up survey data revealed significant differences (all p-values \u3c .001) between faculty who had previously received any error disclosure training (n = 472) and those who had not (n = 599). Specifically, we found significant differences in culture (all p-values \u3c .001) between those who received any error disclosure training and those who did not for all culture domains: minor error disclosure (61 percent vs. 41 percent), serious error disclosure (79 percent vs. 58 percent), trust-based error disclosure (61 percent vs. 51 percent), safety (73 percent vs. 51 percent), and teamwork (78 percent vs. 66 percent). Significant differences also existed for intent to disclose an error (t = 4.1, p \u3c .05). We also found that error disclosure culture was significantly associated with intent to disclose for those who received previous error disclosure training, whereas all types of culture we measured were significantly associated with intent to disclose for those who did not receive error disclosure training. Conclusions. Error disclosure, teamwork, and safety culture all improved over a 3-year period during which disclosure training was provided to key faculty in these six institutions. Self‑reported likelihood to disclose errors also improved. The precise impact of the training on these improvements cannot be determined from this study; nevertheless, we present an approach to measuring error disclosure culture and providing training that may be useful to other institutions

Stroke penumbra defined by an MRI-based oxygen challenge technique: 1. validation using [14C]2-deoxyglucose autoradiography

Accurate identification of ischemic penumbra will improve stroke patient selection for reperfusion therapies and clinical trials. Current magnetic resonance imaging (MRI) techniques have limitations and lack validation. Oxygen challenge T2* MRI (T2* OC) uses oxygen as a biotracer to detect tissue metabolism, with penumbra displaying the greatest T2* signal change during OC. [14C]2-deoxyglucose (2-DG) autoradiography was combined with T2* OC to determine metabolic status of T2*-defined penumbra. Permanent middle cerebral artery occlusion was induced in anesthetized male Sprague-Dawley rats (n=6). Ischemic injury and perfusion deficit were determined by diffusion- and perfusion-weighted imaging, respectively. At 147±32 minutes after stroke, T2* signal change was measured during a 5-minute 100% OC, immediately followed by 125 μCi/kg 2-DG, intravenously. Magnetic resonance images were coregistered with the corresponding autoradiograms. Regions of interest were located within ischemic core, T2*-defined penumbra, equivalent contralateral structures, and a region of hyperglycolysis. A T2* signal increase of 9.22%±3.9% (mean±s.d.) was recorded in presumed penumbra, which displayed local cerebral glucose utilization values equivalent to contralateral cortex. T2* signal change was negligible in ischemic core, 3.2%±0.78% in contralateral regions, and 1.41%±0.62% in hyperglycolytic tissue, located outside OC-defined penumbra and within the diffusion abnormality. The results support the utility of OC-MRI to detect viable penumbral tissue follow

Potential use of oxygen as a metabolic biosensor in combination with T2*-weighted MRI to define the ischemic penumbra

We describe a novel magnetic resonance imaging technique for detecting metabolism indirectly through changes in oxyhemoglobin:deoxyhemoglobin ratios and T2* signal change during ‘oxygen challenge’ (OC, 5 mins 100% O2). During OC, T2* increase reflects O2 binding to deoxyhemoglobin, which is formed when metabolizing tissues take up oxygen. Here OC has been applied to identify tissue metabolism within the ischemic brain. Permanent middle cerebral artery occlusion was induced in rats. In series 1 scanning (n=5), diffusion-weighted imaging (DWI) was performed, followed by echo-planar T2* acquired during OC and perfusion-weighted imaging (PWI, arterial spin labeling). Oxygen challenge induced a T2* signal increase of 1.8%, 3.7%, and 0.24% in the contralateral cortex, ipsilateral cortex within the PWI/DWI mismatch zone, and ischemic core, respectively. T2* and apparent diffusion coefficient (ADC) map coregistration revealed that the T2* signal increase extended into the ADC lesion (3.4%). In series 2 (n=5), FLASH T2* and ADC maps coregistered with histology revealed a T2* signal increase of 4.9% in the histologically defined border zone (55% normal neuronal morphology, located within the ADC lesion boundary) compared with a 0.7% increase in the cortical ischemic core (92% neuronal ischemic cell change, core ADC lesion). Oxygen challenge has potential clinical utility and, by distinguishing metabolically active and inactive tissues within hypoperfused regions, could provide a more precise assessment of penumbra

Patient safety and the ageing physician: a qualitative study of key stakeholder attitudes and experiences

Background Unprecedented numbers of physicians are practicing past age 65. Unlike other safety-conscious industries, such as aviation, medicine lacks robust systems to ensure late-career physician (LCP) competence while promoting career longevity. Objective To describe the attitudes of key stakeholders about the oversight of LCPs and principles that might shape policy development. Design Thematic content analysis of interviews and focus groups. Participants 40 representatives of stakeholder groups including state medical board leaders, institutional chief medical officers, senior physicians (\u3e65 years old), patient advocates (patients or family members in advocacy roles), nurses and junior physicians. Participants represented a balanced sample from all US regions, surgical and non-surgical specialties, and both academic and non-academic institutions. Results Stakeholders describe lax professional self-regulation of LCPs and believe this represents an important unsolved challenge. Patient safety and attention to physician well-being emerged as key organising principles for policy development. Stakeholders believe that healthcare institutions rather than state or certifying boards should lead implementation of policies related to LCPs, yet expressed concerns about resistance by physicians and the ability of institutions to address politically complex medical staff challenges. Respondents recommended a coaching and professional development framework, with environmental changes, to maximise safety and career longevity of physicians as they age. Conclusions Key stakeholders express a desire for wider adoption of LCP standards, but foresee significant culture change and practical challenges ahead. Participants recommended that institutions lead this work, with support from regulatory stakeholders that endorse standards and create frameworks for policy adoption

Quantitative histopathologic assessment of perfusion MRI as a marker of glioblastoma cell infiltration in and beyond the peritumoral edema region

Background: Conventional MRI fails to detect regions of glioblastoma cell infiltration beyond the contrast‐enhanced T1 solid tumor region, with infiltrating tumor cells often migrating along host blood vessels. Purpose: To quantitatively and qualitatively analyze the correlation between perfusion MRI signal and tumor cell density in order to assess whether local perfusion perturbation could provide a useful biomarker of glioblastoma cell infiltration. Study Type: Animal model. Subjects: Mice bearing orthotopic glioblastoma xenografts generated from a patient‐derived glioblastoma cell line. Field Strength/Sequences: 7T perfusion images acquired using a high signal‐to‐noise ratio (SNR) multiple boli arterial spin labeling sequence were compared with conventional MRI (T1/T2 weighted, contrast‐enhanced T1, diffusion‐weighted, and apparent diffusion coefficient). Assessment: Immunohistochemistry sections were stained for human leukocyte antigen (probing human‐derived tumor cells). To achieve quantitative MRI‐tissue comparison, multiple histological slices cut in the MRI plane were stacked to produce tumor cell density maps acting as a “ground truth.” Statistical Tests: Sensitivity, specificity, accuracy, and Dice similarity indices were calculated and a two‐tailed, paired t‐test used for statistical analysis. Results: High comparison test results (Dice 0.62–0.72, Accuracy 0.86–0.88, Sensitivity 0.51–0.7, and Specificity 0.92–0.97) indicate a good segmentation for all imaging modalities and highlight the quality of the MRI tissue assessment protocol. Perfusion imaging exhibits higher sensitivity (0.7) than conventional MRI (0.51–0.61). MRI/histology voxel‐to‐voxel comparison revealed a negative correlation between tumor cell infiltration and perfusion at the tumor margins (P = 0.0004). Data Conclusion: These results demonstrate the ability of perfusion imaging to probe regions of low tumor cell infiltration while confirming the sensitivity limitations of conventional imaging modalities. The quantitative relationship between tumor cell density and perfusion identified in and beyond the edematous T2 hyperintensity region surrounding macroscopic tumor could be used to detect marginal tumor cell infiltration with greater accuracy