Meta-Analysis of the Use of Head Impulse Test and Head Impulse Test with Direction Changing Nystagmus and Test of Skew Deviation in the Diagnosis of Peripheral Vertigo and Stroke.

INTRODUCTION: The head impulse test (HIT) and HIT combined with direction-changing Nystagmus-Test of Skew deviation (HINTS) have been proposed as bedside tests to differentiate between peripheral and central causes of vertigo in the emergency department (ED). We conducted a meta-analysis of the HIT and HINTS tests to diagnose peripheral vertigo (PV) and central vertigo. METHODS: Pubmed, Google Scholar, EmBase, and articles references published in English up to July 2021 were searched for keywords "vertigo" or "acute vestibular syndrome" or "dizziness" and "head impulse" and "stroke." The bivariate method for meta-analysis was used to calculate positive (PLR) and negative likelihood ratios (NLR) and summary receiver operating characteristics area under the curve (AUC). RESULTS: A total of 11 studies were included analysing both HIT (8 studies, N = 417) and HINTS (6 studies, N = 405). HIT and HINTS were performed within 24 h in 4 of 11 studies. PLR and NLR for HIT in PV was 4.85 (95% CI: 2.83-8.08) and 0.19 (95% CI: 0.12-0.29, I2 63.25%), respectively. The AUC for HIT the diagnosis of PV and stroke was 0.90 and 0.92, respectively. PLR and NLR for a negative HIT in stroke was 5.85 (95% CI: 3.07-10.6) and 0.17 (95% CI: 0.08-0.30), respectively. PLR and NLR for peripheral HINTS pattern for PV was 17.3 (95% CI: 8.38-32.1) and 0.15 (95% CI: 0.07-0.26), respectively. PLR and NLR for central HINTS pattern for stroke: 5.61 (95% CI: 4.19-7.7) and 0.06 (95% CI: 0.03-0.12). In all included studies, HIT and HINTS exams were administered by neurology residents or neurology specialists with additional neuro-otology or neuro-ophthalmology subspeciality experience, and two studies included ED physicians. Raters reported high degree of bias and high concern regarding applicability in most domains of the quality assessment of diagnostic accuracy studies (QUADAS-2) tool. Meta-regression did not demonstrate a statistically significant effect of publication year, time to test, and type of assessor on sensitivity or false positive rate. CONCLUSION: The HIT and HINTS exams appear to be moderately good discriminators of central and PV. However, in most papers, the tests were administered by neurologists and were evaluated beyond 24 h, which may limit utility in the ED setting.

Convexity subarachnoid haemorrhage: a practical guide.

Atraumatic convexity subarachnoid haemorrhage describes spontaneous bleeding into the convexities of the brain sulci without parenchymal involvement. Its many causes include reversible cerebral vasoconstriction syndrome, cerebral sinus venous thrombosis, posterior reversible encephalopathy syndrome and (in older people) cerebral amyloid angiopathy. We describe the clinical and radiological features of non-traumatic convexity subarachnoid haemorrhage with its various presentations, causes, treatments and prognoses, and use clinical vignettes to highlight important clinical points and pitfalls.

Stroke in patients with cancer in the era of hyperacute stroke intervention.

BACKGROUND: The natural history of patients with stroke and cancer remains poorly understood in the modern era of hyperacute stroke therapies (recombinant tissue plasminogen activator and endovascular clot retrieval (ECR)). Prior to these advances in stroke treatment, a highly cited study reported median overall survival (mOS) 4.5 months after stroke in a cohort of patients with cancer (2004, n = 96). AIMS: Our hypothesis is that patients with stroke and cancer have better outcome than in earlier studies. METHODS: Retrospective analysis of admission to a tertiary Stroke Unit between January 2015 and September 2017 (n = 1910), evaluation of hospital records and cancer treatment records. Cancer was categorised as early stage (Stages I and II) and advanced stage (Stage III or IV) using the RD-Staging system. Survival analysis was performed in R. RESULTS: There were 143 stroke patients with cancer (62% male) with mean age 73.2 ± 12.5 years. Ischaemic stroke occurred in 74.1% and 45 of 106 (42.5%) patients received intravenous thrombolysis (34/45) and/or ECR (11/45). One patient who received ECR died within 30 days of stroke. Those with early stage disease had mOS of 19.6 months (interquartile range (IQR) 3.1-31.5 months) and in advanced stage cancer mOS was 2.5 months (IQR 0.4-6.3 months; P < 0.01). CONCLUSION: In the modern era of stroke therapy, our cohort of patients with advanced cancer has lower survival post-stroke compared to those with early stage cancer.

Googling Service Boundaries for Endovascular Clot Retrieval Hub Hospitals in a Metropolitan Setting: Proof-of-Concept Study.

BACKGROUND AND PURPOSE: There is great interest in how endovascular clot retrieval hubs provide services to a population. We applied a computational method to objectively generate service boundaries for such endovascular clot retrieval hubs, defined by traveling time to hub. METHODS: Stroke incidence data merged with population census to estimate numbers of stroke in metropolitan Melbourne, Australia. Traveling time from randomly generated addresses to 4 endovascular clot retrieval-capable hubs (Royal Melbourne Hospital [RMH], Monash Medical Center [MMC], Alfred Hospital [ALF], and Austin Hospital [AUS]) estimated using Google Map application program interface. Boundary maps generated based on traveling time at various times of day for combinations of hubs. RESULTS: In a 2-hub model, catchment was best distributed when RMH was paired with MMC (model 1a, RMH 1765 km2 and MMC 1164 km2) or with AUS (model 1c, RMH 1244 km2 and AUS 1685 km2), with no statistical difference between models (P=0.20). Catchment was poorly distributed when RMH was paired with ALF (model 1b, RMH 2252 km2 and ALF 676 km2), significantly different from both models 1a and 1c (both P<0.05). Model 1a had the greatest proportion of patients arriving within ideal time of 30 minutes followed by model 1c (P<0.001). In a 3-hub model, the combination of RMH, MMC, and AUS was superior to that of RMH, MMC, and ALF in catchment distribution and travel time. The method was also successfully applied to the city of Adelaide demonstrating wider applicability. CONCLUSIONS: We provide proof of concept for a novel computational method to objectively designate service boundaries for endovascular clot retrieval hubs.

Positron Emission Tomographic Imaging in Stroke: Cross-Sectional and Follow-Up Assessment of Amyloid in Ischemic Stroke.

BACKGROUND AND PURPOSE: Cardiovascular risk factors significantly increase the risk of developing Alzheimer disease. A possible mechanism may be via ischemic infarction-driving amyloid deposition. We conducted a study to determine the presence of ß-amyloid in infarct, peri-infarct, and hemispheric areas after stroke. We hypothesized that an infarct would trigger ß-amyloid deposition, with deposition over time. METHODS: Patients were recruited within 40 days of acute ischemic stroke and imaged with computed tomographic or magnetic resonance imaging and Pittsburgh compound B (11C-PiB) positron emission tomographic scans. Follow-up positron emission tomographic scanning was performed in a subgroup ≤18 months after the stroke event. Standardized uptake value ratios for regions of interest were analyzed after coregistration. RESULTS: Forty-seven patients were imaged with (11)C-PiB positron emission tomography. There was an increase in (11)C-PiB accumulation in the stroke area compared with a reference region in the contralesional hemisphere, which was not statistically significant (median difference in standardized uptake value ratio, 0.07 [95% confidence interval, -0.06 to 0.123]; P=0.452). There was no significant increase in the accumulation of (11)C-PiB in the peri-infarct region or in the ipsilesional hemisphere (median difference in standardized uptake value ratio, 0.04 [95% confidence interval, -0.02 to 0.10]; P=0.095). We repeated (11)C-PiB positron emission tomography in 21 patients and found a significant reduction in accumulation of (11)C-PiB between regions of interest (median difference in standardized uptake value ratio, -0.08 [95% confidence interval, -0.23 to -0.03]; P=0.04). CONCLUSIONS: There was no significant increase in (11)C-PiB accumulation in or around the infarct. There was no increase in ipsilesional hemispheric (11)C-PiB accumulation over time. We found no evidence that infarction leads to sustained or increased ß-amyloid deposition ≤18 months after stroke.

Facility-Based Delivery during the Ebola Virus Disease Epidemic in Rural Liberia: Analysis from a Cross-Sectional, Population-Based Household Survey.

BACKGROUND: The Ebola virus disease (EVD) epidemic has threatened access to basic health services through facility closures, resource diversion, and decreased demand due to community fear and distrust. While modeling studies have attempted to estimate the impact of these disruptions, no studies have yet utilized population-based survey data. METHODS AND FINDINGS: We conducted a two-stage, cluster-sample household survey in Rivercess County, Liberia, in March-April 2015, which included a maternal and reproductive health module. We constructed a retrospective cohort of births beginning 4 y before the first day of survey administration (beginning March 24, 2011). We then fit logistic regression models to estimate associations between our primary outcome, facility-based delivery (FBD), and time period, defined as the pre-EVD period (March 24, 2011-June 14, 2014) or EVD period (June 15, 2014-April 13, 2015). We fit both univariable and multivariable models, adjusted for known predictors of facility delivery, accounting for clustering using linearized standard errors. To strengthen causal inference, we also conducted stratified analyses to assess changes in FBD by whether respondents believed that health facility attendance was an EVD risk factor. A total of 1,298 women from 941 households completed the survey. Median age at the time of survey was 29 y, and over 80% had a primary education or less. There were 686 births reported in the pre-EVD period and 212 in the EVD period. The unadjusted odds ratio of facility-based delivery in the EVD period was 0.66 (95% confidence interval [CI] 0.48-0.90, p-value = 0.010). Adjustment for potential confounders did not change the observed association, either in the principal model (adjusted odds ratio [AOR] = 0.70, 95%CI 0.50-0.98, p = 0.037) or a fully adjusted model (AOR = 0.69, 95%CI 0.50-0.97, p = 0.033). The association was robust in sensitivity analyses. The reduction in FBD during the EVD period was observed among those reporting a belief that health facilities are or may be a source of Ebola transmission (AOR = 0.59, 95%CI 0.36-0.97, p = 0.038), but not those without such a belief (AOR = 0.90, 95%CI 0.59-1.37, p = 0.612). Limitations include the possibility of FBD secular trends coincident with the EVD period, recall errors, and social desirability bias. CONCLUSIONS: We detected a 30% decreased odds of FBD after the start of EVD in a rural Liberian county with relatively few cases. Because health facilities never closed in Rivercess County, this estimate may under-approximate the effect seen in the most heavily affected areas. These are the first population-based survey data to show collateral disruptions to facility-based delivery caused by the West African EVD epidemic, and they reinforce the need to consider the full spectrum of implications caused by public health emergencies.

Stroke Severity and Comorbidity Index for Prediction of Mortality after Ischemic Stroke from the Virtual International Stroke Trials Archive-Acute Collaboration.

BACKGROUND: There is increasing interest in the use of administrative data (incorporating comorbidity index) and stroke severity score to predict ischemic stroke mortality. The aim of this study was to determine the optimal timing for the collection of stroke severity data and the minimum clinical dataset to be included in models of stroke mortality. To address these issues, we chose the Virtual International Stroke Trials Archive (VISTA), which contains National Institutes of Health Stroke Scale (NIHSS) on admission and at 24 hours, as well as outcome at 90 days. METHODS: VISTA was searched for patients who had baseline and 24-hour NIHSS. Improvement in regression models was performed by the net reclassification improvement (NRI) method. RESULTS: The clinical data among 5206 patients were mean age, 69 ± 13; comorbidity index, 3.3 ± .9; median NIHSS at baseline, 12 (interquartile range [IQR] 8-17); NIHSS at 24 hours, 9 (IQR 8-15); and death at 90 days in 15%. The baseline model consists of age, gender, and comorbidity index. Adding the baseline NIHSS to model 1 improved the NRI by 0.671 (95% confidence interval [CI] 0.595-0.747) [or 67.1% correct reclassification between model 1 and model 2]. Adding the 24 hour NIHSS term to model 1 (model 3) improved the NRI by 0.929 (95% CI 0.857-1.000) for model 3 versus model 1. Adding the variable thrombolysis to model 3 (model 4) improve NRI by 0.1 (95% CI 0.023-0.178) [model 4 versus model 3]. CONCLUSION: The optimal model for the prediction of mortality was achieved by adding the 24-hour NIHSS and thrombolysis to the baseline model.

Comparison of Dual Antiplatelet Therapies for Minor, Nondisabling, Acute Ischemic Stroke: A Bayesian Network Meta-Analysis.

Importance: Dual antiplatelet therapy (DAPT) appears to be an effective treatment option for minor (nondisabling) acute ischemic stroke. This conclusion is based on trials that include both transient ischemic attack (TIA) and minor stroke; however, these 2 conditions may differ. Objective: To compare DAPT regimens specifically for minor stroke. Data Sources: PubMed was searched for randomized clinical trials published up to November 4, 2023. Search terms strategy included TIA, transient ischemic attack, minor stroke, or moderate stroke, with the filter randomized controlled trial. Unpublished data on minor stroke were sourced from authors and/or institutions. Study Selection: Trials testing DAPT within the first 24 hours of a minor stroke (defined as a National Institutes of Health Stroke Scale score ≤5) were included by consensus. Of 1508 studies screened, 6 (0.3%) initially met inclusion criteria and were reviewed. Data Extraction and Synthesis: The study was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines by multiple observers. Bayesian fixed-effect network meta-analysis was conducted. Secondary analysis performed for high-risk TIA alone. Main Outcomes and Measures: Treatments were ranked using a probability measure called surface under the cumulative rank curve (SUCRA). The primary outcome was subsequent ischemic stroke at 90 days. Secondary outcomes included major hemorrhage, mortality, and hemorrhagic stroke. The number needed to treat (NNT) and number needed to harm (NNH) were obtained. Results: Five trials were included that described 28 148 patients, of whom 22 203 (78.9%) had a minor stroke. Of these, 13 995 (63.0%) were in DAPT groups and 8208 (37.0%) in aspirin (acetylsalicylic acid) groups. Aspirin and ticagrelor had a 94% probability of being the superior treatment for minor stroke (SUCRA, 0.94) for the primary outcome. Both aspirin and ticagrelor (NNT, 40; 95% CI, 31-64) and aspirin and clopidogrel (NNT, 58; 95% CI, 39-136) were superior to aspirin alone in the prevention of recurrent ischemic stroke at 90 days. Both treatments had higher rates of major hemorrhage than aspirin alone (NNH for aspirin and ticagrelor, 284; 95% CI, 108-1715 vs NNH for aspirin and clopidogrel, 330; 95% CI, 118-3430), but neither had increased risk of hemorrhagic stroke or death. For high-risk TIA, ticagrelor and aspirin had a 60% probability (SUCRA, 0.60) and clopidogrel and aspirin had a 40% probability (SUCRA 0.40) of being a superior treatment; neither was optimum, but both were superior to aspirin alone for the primary outcome. Conclusions and Relevance: These findings suggest that DAPT with aspirin and ticagrelor has higher probability of being the superior treatment among patients with minor stroke when presence of CYP2C19 loss-of-function alleles has not been excluded. For patients with TIA, the superiority of aspirin and ticagrelor vs aspirin and clopidogrel was not demonstrated.

Dimensions of subcortical infarcts associated with first- to third-order branches of the basal ganglia arteries.

BACKGROUND: It has been described that lacunar infarct is characterized by its smallish size (15-20 mm) in the axial plane. However, the size of the basal ganglia artery responsible for this type of infarct is uncertain. Detection of small arterial occlusion is not possible with current angiography, hindering correlation of arterial occlusion with subcortical infarct size. Recently, investigators have published microangiographic templates of arteries supplying the basal ganglia. These templates display first-order (proximal) to third-order (distal) branching of these arteries and can help with estimating the likely site of arterial disease in subcortical infarcts. We correlated the dimensions of subcortical infarcts with the order of arterial branching described in a microangiographic template. Such data may provide further clues about the type of arteries associated with subcortical infarcts and assist in refining the concept of lacunar infarction. METHOD: Patients with subcortical infarcts on MR imaging (MRI) admitted to our institution between 2009 and 2011 were included in the study. Infarcts were manually segmented and registered to a standard brain template. These segmented infarcts were scaled and overlapped with published microangiographic templates, and used by 6 raters who independently estimated the branching order of arterial disease that might result in these infarcts. We used regression analysis to relate these ratings to infarct dimensions. RESULTS: Among 777 patients, there were 33 (58% male) patients with subcortical infarcts. The mean age was 63.1 ± 15.1 years. Infarct dimensions for the groups were as follows: group 1 (first-order branch): height 37.6 ± 7.4 mm, horizontal width 21.2 ± 11.6 mm, anterior-posterior length 36.8 ± 20.1 mm; group 2 (second-order branch): height 25.2 ± 7.9 mm, horizontal width 16.6 ± 22.8 mm, anterior-posterior length 16.1 ± 8.0 mm; group 3 (third-order branch): height 11.6 ± 5.7 mm, axial width 5.3 ± 3.1 mm, anterior-posterior length 5.5 ± 3.8 mm. Increasing vessel branching order (from large to small vessels) was linearly and negatively associated with infarct height (ß = -16.7 mm per change in branching order disease, 95% CI -20.3, -13.1 mm, p < 0.01) and anterior-posterior length (ß = -16.8 mm per change in branching order disease, 95% CI -23.2, -10.5 mm, p < 0.01). DISCUSSION: Based on MRI infarct dimensions and a microangiographic template, it may be possible to estimate the branching order of the artery involved in subcortical infarcts. Further, our small data set suggests that reliance on an axial dimension of 15-20 mm may not be the best approach to classifying lacunar infarct. This finding needs to be confirmed in a larger data set.

Effect of alteplase, benzodiazepines and beta-blocker on post-stroke pneumonia: Exploration of VISTA-Acute.

BACKGROUND: Post-stroke pneumonia is a frequent complication of stroke and is associated with high mortality. Investigators have described its associations with beta-blocker. However, there has been no evaluation of the role of recombinant tissue plasminogen activator (RTPA). We postulate that RTPA may modify the effect of stroke on pneumonia by reducing stroke disability. We explore this using data from neuroprotection trials in Virtual International Stroke Trials Archive (VISTA)-Acute. METHOD: We evaluated the impact of RTPA and other medications in random forest model. Random forest is a type of supervised ensemble tree-based machine learning method. We used the standard approach for performing random forest and partitioned the data into training (70%) and validation (30%) sets. This action enabled to the model developed on training data to be evaluated in the validation data. We borrowed idea from Coalition Game Theory on fair distribution of marginal profit (Shapley value) to determine proportional contribution of a covariate to the model. Consistent with other analysis using the VISTA-Acute data, the diagnosis of post-stroke pneumonia was based on reports of serious adverse events. RESULTS: The overall frequency of pneumonia was 10.9% (614/5652). It was present in 11.5% of the RTPA (270/2358) and 10.4% (344/3295) of the no RTPA groups. There was significant (p<0.05) imbalance in covariates (age, baseline National Institutes of Health Stroke Scale (NIHSS), diabetes, and sex). The AUC for training data was 0.70 (95% CI 0.65-0.76), validation data was 0.67 (95% CI 0.62-0.73). The Shapley value shows that baseline NIHSS (≥10) and age (≥80) made the largest contribution to the model of pneumonia while absence of benzodiazepine may protect against pneumonia. RTPA and beta-blocker had very low effect on frequency of pneumonia. CONCLUSION: In this cohort pneumonia was strongly associated with stroke severity and age whereas RTPA had a much lower effect. An intriguing finding is a possible association between benzodiazepine and pneumonia but this requires further evaluation.

Corrigendum: Phase I trial outcome of amnion cell therapy in patients with ischemic stroke (I-ACT).

[This corrects the article DOI: 10.3389/fnins.2023.1153231.].

Phase I trial outcome of amnion cell therapy in patients with ischemic stroke (I-ACT).

Background: We proposed a Phase I dose escalation trial to assess the safety of allogeneic human amniotic epithelial cells (hAECs) in stroke patients with a view to informing the design for a Phase II trial. Methods: The design is based on 3 + 3 dose escalation design with additional components for measuring MR signal of efficacy as well as the effect of hAECs (2-8 × 106/kg, i.v.) on preventing immunosuppression after stroke. Results: Eight patients (six males) were recruited within 24 h of ischemic stroke onset and were infused with hAECs. We were able to increase the dose of hAECs to 8 × 106 cells/kg (2 × 106/kg, n = 3; 4 × 106/kg, n = 3; 8 × 106/kg, n = 2). The mean age is 68.0 ± 10.9 (mean ± SD). The frequencies of hypertension and hyperlipidemia were 87.5%, diabetes was 37.5%, atrial fibrillation was 50%, ischemic heart disease was 37.5% and ever-smoker was 25%. Overall, baseline NIHSS was 7.5 ± 3.1, 7.8 ± 7.2 at 24 h, and 4.9 ± 5.4 at 1 week (n = 8). The modified Rankin scale at 90 days was 2.1 ± 1.2. Supplemental oxygen was given in five patients during hAEC infusion. Using pre-defined criteria, two serious adverse events occurred. One patient developed recurrent stroke and another developed pulmonary embolism whilst in rehabilitation. For the last four patients, infusion of hAECs was split across separate infusions on subsequent days to reduce the risk for fluid overload. Conclusion: Our Phase I trial demonstrates that a maximal dose of 2 × 106/kg hAECs given intravenously each day over 2 days (a total of 4 × 106/kg) is safe and optimal for use in a Phase II trial. Clinical trial registration: ClinicalTrials.gov, identifier ACTRN12618000076279P.

Silent infarcts and cerebral microbleeds modify the associations of white matter lesions with gait and postural stability: population-based study.

BACKGROUND AND PURPOSE: Although cerebral white matter lesions (WMLs), silent infarcts (SIs), and microbleeds (MBs) are individually associated with poorer gait and balance, it is unknown if they interact. We studied the interactions of WML volume with SI and MB on gait and postural stability. METHODS: Participants in a population-based study aged 60 to 86 years underwent brain MRI, computerized gait measurement, and a physiological profile assessment of postural stability. Segmentation procedures and standard rating methods were used to measure WML, SI, and MB. Linear regression was used to test interactions between lesions on gait and postural stability, adjusting for age, sex, and total intracranial volume. RESULTS: There were 395 participants (mean age, 72 years; SD, 7.0). SIs were predominantly located in subcortical frontal white matter and in deep gray structures, and MBs were largely lobar. Participants with SI or MB had higher WML volumes than those without (P<0.001 and P=0.05, respectively). The presence of SI (P for interaction=0.01) or MB (P for interaction <0.01) magnified the adverse association of WML volume with gait. SI (P for interaction=0.02), but not MB, magnified the adverse association of WML volume with postural stability. CONCLUSIONS: Subclinical cerebrovascular lesions are adversely associated with gait and postural stability in older people in a cumulative fashion.

Subacute ischemic stroke is associated with focal 11C PiB positron emission tomography retention but not with global neocortical Aß deposition.

BACKGROUND AND PURPOSE: Conflicting evidence exists as to whether focal cerebral ischemia contributes to cerebral amyloid deposition. We aimed to look at Aß deposits, detected by N-methyl-2-(4'-methylaminophenyl)-6-hydroxybenzothiazole (PiB) positron emission tomography, in patients with recent ischemic stroke. Specifically, we hypothesized that patients with recent ischemic stroke have higher local and neocortical PiB positron emission tomography retention and that this may be associated with major vascular risk factors. METHODS: Ischemic stroke patients were studied using PiB positron emission tomography within 30 days and compared to age-matched controls. Distribution volume ratio maps were created using Logan graphical analysis with the cerebellar cortex as a reference. RESULTS: Among the 21 ischemic stroke patients (median age, 76 years; interquartile range, 68-77), the ipsilateral peri-infarct region PiB retention was higher compared to the contralateral mirror region, with a PiB distribution volume ratio difference of 0.29 (95% CI, 0.2-0.44; P=0.001) at median 10 (interquartile range, 7-14) days after stroke. Two patients also had higher PiB retention within the infarct compared to the contralateral side. There was no difference in the neocortical PiB retention elsewhere in the brain among ischemic stroke patients compared with 22 age-matched normal controls (P=0.22). Among the risk factors in the ischemic stroke patients, diabetes was associated with a higher neocortical PiB retention (Spearman Rho=0.48; 95% CI, 0.28-0.72). CONCLUSIONS: PiB retention was higher in the peri-infarct region among patients with recent ischemic stroke. This did not translate into a higher global neocortical PiB retention except possibly in patients with diabetes. The cause of the focal PiB retention is uncertain and requires further investigation.

Application of principal component analysis to study topography of hypoxic-ischemic brain injury.

The regions at risk of ischemia following cardio-respiratory arrest have not been systematically analysed. This knowledge may be of use in determining the mechanism of ischemic injury at vulnerable sites. The aim of this study is to evaluate the use of principal component analysis to analyse the covariance patterns of hypoxic ischemic injury. The inclusion criteria were: age ≥ 17 years, cardio-respiratory arrest and coma on admission (2003-2011). Regions of ischemic injury were manually segmented on fluid attenuated inversion recovery (FLAIR) and diffusion weighted (DWI) sequences and linearly registered into common stereotaxic coordinate space. Topography of ischemic injury was assessed using principal component analysis (covariance data) and compared qualitatively against current method of topography analysis, the probabilistic method (frequency data). For the probabilistic data, subgroup analyses were performed using t-statistics while for the covariance data, subgroup analyses were performed by calculating the angle between the principle components. To account for bias due to a higher frequency of coma survivors in the studied group, we performed sensitivity analysis by sequentially removing coma survivors such that the final data set contained higher rate of death. Quantitative analysis between these methods could not be performed as they have different units of measurement. Forty one patients were included in this series (mean age ± SD=51.5 ± 18.9 years). In our probabilistic map, the highest frequency of ischemic injury on the DWI and FLAIR sequences was putamen (0.250), caudate (0.225), temporal lobes (0.175), occipital (0.150) and hippocampus (0.125). The first 6 principal components contained 77.7% of the variance of the data. The first component showed covariance between the deep grey matter nuclei and posterior cortical structures (contains 50.2% of the variance of the data). There was similarity in the findings of the subgroup analyses by the downtime whether it was assessed by t-statistics for probabilistic data or angle between the principal components for the covariance data. The sensitivity analysis showed that the pattern of ischemic injury did not change when the analysis was restricted to patients who died. In conclusion, PCA method has many advantages over probabilistic method. In the context of this dataset, PCA showed covariance between deep grey matter nuclei and the posterior cortical structures whereas the probabilistic map provided complementary information on the frequency of occurrence at these locations.

Semi-automatic analysis of standard uptake values in serial PET/CT studies in patients with lung cancer and lymphoma.

BACKGROUND: Changes in maximum standardised uptake values (SUVmax) between serial PET/CT studies are used to determine disease progression or regression in oncologic patients. To measure these changes manually can be time consuming in a clinical routine. A semi-automatic method for calculation of SUVmax in serial PET/CT studies was developed and compared to a conventional manual method. The semi-automatic method first aligns the serial PET/CT studies based on the CT images. Thereafter, the reader selects an abnormal lesion in one of the PET studies. After this manual step, the program automatically detects the corresponding lesion in the other PET study, segments the two lesions and calculates the SUVmax in both studies as well as the difference between the SUVmax values. The results of the semi-automatic analysis were compared to that of a manual SUVmax analysis using a Philips PET/CT workstation. Three readers did the SUVmax readings in both methods. Sixteen patients with lung cancer or lymphoma who had undergone two PET/CT studies were included. There were a total of 26 lesions. RESULTS: Linear regression analysis of changes in SUVmax show that intercepts and slopes are close to the line of identity for all readers (reader 1: intercept = 1.02, R2 = 0.96; reader 2: intercept = 0.97, R2 = 0.98; reader 3: intercept = 0.99, R2 = 0.98). Manual and semi-automatic method agreed in all cases whether SUVmax had increased or decreased between the serial studies. The average time to measure SUVmax changes in two serial PET/CT examinations was four to five times longer for the manual method compared to the semi-automatic method for all readers (reader 1: 53.7 vs. 10.5 s; reader 2: 27.3 vs. 6.9 s; reader 3: 47.5 vs. 9.5 s; p < 0.001 for all). CONCLUSIONS: Good agreement was shown in assessment of SUVmax changes between manual and semi-automatic method. The semi-automatic analysis was four to five times faster to perform than the manual analysis. These findings show the feasibility of using semi-automatic methods for calculation of SUVmax in clinical routine and encourage further development of programs using this type of methods.

Risk of intracranial haemorrhage and ischaemic stroke after convexity subarachnoid haemorrhage in cerebral amyloid angiopathy: international individual patient data pooled analysis.

OBJECTIVE: To investigate the frequency, time-course and predictors of intracerebral haemorrhage (ICH), recurrent convexity subarachnoid haemorrhage (cSAH), and ischemic stroke after cSAH associated with cerebral amyloid angiopathy (CAA). METHODS: We performed a systematic review and international individual patient-data pooled analysis in patients with cSAH associated with probable or possible CAA diagnosed on baseline MRI using the modified Boston criteria. We used Cox proportional hazards models with a frailty term to account for between-cohort differences. RESULTS: We included 190 patients (mean age 74.5 years; 45.3% female) from 13 centers with 385 patient-years of follow-up (median 1.4 years). The risks of each outcome (per patient-year) were: ICH 13.2% (95% CI 9.9-17.4); recurrent cSAH 11.1% (95% CI 7.9-15.2); combined ICH, cSAH, or both 21.4% (95% CI 16.7-26.9), ischemic stroke 5.1% (95% CI 3.1-8) and death 8.3% (95% CI 5.6-11.8). In multivariable models, there is evidence that patients with probable CAA (compared to possible CAA) had a higher risk of ICH (HR 8.45, 95% CI 1.13-75.5, p = 0.02) and cSAH (HR 3.66, 95% CI 0.84-15.9, p = 0.08) but not ischemic stroke (HR 0.56, 95% CI 0.17-1.82, p = 0.33) or mortality (HR 0.54, 95% CI 0.16-1.78, p = 0.31). CONCLUSIONS: Patients with cSAH associated with probable or possible CAA have high risk of future ICH and recurrent cSAH. Convexity SAH associated with probable (vs possible) CAA is associated with increased risk of ICH, and cSAH but not ischemic stroke. Our data provide precise risk estimates for key vascular events after cSAH associated with CAA which can inform management decisions.

The hidden mismatch: an explanation for infarct growth without perfusion-weighted imaging/diffusion-weighted imaging mismatch in patients with acute ischemic stroke.

BACKGROUND AND PURPOSE: In ischemic stroke, MR perfusion-weighted imaging (PWI) and diffusion-weighted imaging (DWI) mismatch represents tissue at risk for infarction. Infarct growth should only take place in the presence of mismatch, although there have been reports of this occurring. We hypothesized that this observation may be attributable to the presence of undetected "hidden mismatch," which may become obvious when coregistration techniques are used. METHODS: MR PWI/DWI was performed within 48 hours of stroke onset and a final T2-weighted image at ≈3 months. Volumetric-subtraction mismatch volume was defined as PWI minus DWI volume and infarct growth was defined as T2 minus DWI volume. Coregistration mismatch volume was PWI not overlapped by DWI. Mismatch salvage was the proportion of coregistered mismatch tissue that had not progressed to infarction. RESULTS: Thirty-four patients were studied with MR at a median of 4.9 hours (interquartile range, 2.9-21.1 hours). With the volumetric-subtraction technique, 5 patients (14.7%; 95% CI, 0.05%-0.31%) had infarct growth exceeding mismatch volume, 11 patients (32.0%) had no mismatch and, among these, 3 (27.3%) had infarct growth (median volume, 2.2 mL; interquartile range, 1.0-6.5 mL). All patients had mismatch volume identified by coregistration method that was greater than infarct growth volume. The proportion of this volume salvaged was 77.7% (interquartile range, 63.0%-98.9%). CONCLUSIONS: The illogical finding of infarct growth volume being greater than the presence of mismatch volume can be explained by the presence of "hidden mismatch," which may be detected by coregistration methods.

Cerebral ß-amyloid detected by Pittsburgh compound B positron emission topography predisposes to recombinant tissue plasminogen activator-related hemorrhage.

Cerebral amyloid angiopathy (CAA) may be an important predisposing factor for the hemorrhagic complications of recombinant tissue-type plasminogen activator (rt-PA) therapy. We studied patients treated within 3 hours of onset of ischemic stroke with rt-PA using positron emission tomography to compare Pittsburgh compound B (PiB) (a cerebral ß-amyloid ligand) retention in those with and without parenchymal hemorrhage (PH) and normal controls. Neocortical PiB retention was higher among patients with PH compared with patients without PH and normal controls, suggesting underlying CAA as a predisposing factor for rt-PA-related hemorrhage. This finding may provide an impetus for the development of a more practical rapid pretreatment screening technique.

Post-reconstruction enhancement of [18F]FDG PET images with a convolutional neural network.

BACKGROUND: The aim of the study was to develop and test an artificial intelligence (AI)-based method to improve the quality of [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) images. METHODS: A convolutional neural network (CNN) was trained by using pairs of excellent (acquisition time of 6 min/bed position) and standard (acquisition time of 1.5 min/bed position) or sub-standard (acquisition time of 1 min/bed position) images from 72 patients. A test group of 25 patients was used to validate the CNN qualitatively and quantitatively with 5 different image sets per patient: 4 min/bed position, 1.5 min/bed position with and without CNN, and 1 min/bed position with and without CNN. RESULTS: Difference in hotspot maximum or peak standardized uptake value between the standard 1.5 min and 1.5 min CNN images fell short of significance. Coefficient of variation, the noise level, was lower in the CNN-enhanced images compared with standard 1 min and 1.5 min images. Physicians ranked the 1.5 min CNN and the 4 min images highest regarding image quality (noise and contrast) and the standard 1 min images lowest. CONCLUSIONS: AI can enhance [18F]FDG-PET images to reduce noise and increase contrast compared with standard images whilst keeping SUVmax/peak stability. There were significant differences in scoring between the 1.5 min and 1.5 min CNN image sets in all comparisons, the latter had higher scores in noise and contrast. Furthermore, difference in SUVmax and SUVpeak fell short of significance for that pair. The improved image quality can potentially be used either to provide better images to the nuclear medicine physicians or to reduce acquisition time/administered activity.