A Pilot Clinical and Technical Validation of an Immersive Virtual Reality Platform for 3D Anatomical Modeling and Contouring in Support of Surgical and Radiation Oncology Treatment Planning.

The aim of this study was to validate a novel medical virtual reality (VR) platform used for medical image segmentation and contouring in radiation oncology and 3D anatomical modeling and simulation for planning medical interventions, including surgery. The first step of the validation was to verify quantitatively and qualitatively that the VR platform can produce substantially equivalent 3D anatomical models, image contours, and measurements to those generated with existing commercial platforms. To achieve this, a total of eight image sets and 18 structures were segmented using both VR and reference commercial platforms. The image sets were chosen to cover a broad range of scanner manufacturers, modalities, and voxel dimensions. The second step consisted of evaluating whether the VR platform could provide efficiency improvements for target delineation in radiation oncology planning. To assess this, the image sets for five pediatric patients with resected standard-risk medulloblastoma were used to contour target volumes in support of treatment planning of craniospinal irradiation, requiring complete inclusion of the entire cerebral-spinal volume. Structures generated in the VR and the commercial platforms were found to have a high degree of similarity, with dice similarity coefficient ranging from 0.963 to 0.985 for high-resolution images and 0.920 to 0.990 for lower resolution images. Volume, cross-sectional area, and length measurements were also found to be in agreement with reference values derived from a commercial system, with length measurements having a maximum difference of 0.22 mm, angle measurements having a maximum difference of 0.04°, and cross-sectional area measurements having a maximum difference of 0.16 mm2. The VR platform was also found to yield significant efficiency improvements, reducing the time required to delineate complex cranial and spinal target volumes by an average of 50% or 29 min.

Deep learning prediction of renal anomalies for prenatal ultrasound diagnosis.

Deep learning algorithms have demonstrated remarkable potential in clinical diagnostics, particularly in the field of medical imaging. In this study, we investigated the application of deep learning models in early detection of fetal kidney anomalies. To provide an enhanced interpretation of those models' predictions, we proposed an adapted two-class representation and developed a multi-class model interpretation approach for problems with more than two labels and variable hierarchical grouping of labels. Additionally, we employed the explainable AI (XAI) visualization tools Grad-CAM and HiResCAM, to gain insights into model predictions and identify reasons for misclassifications. The study dataset consisted of 969 ultrasound images from unique patients; 646 control images and 323 cases of kidney anomalies, including 259 cases of unilateral urinary tract dilation and 64 cases of unilateral multicystic dysplastic kidney. The best performing model achieved a cross-validated area under the ROC curve of 91.28% ± 0.52%, with an overall accuracy of 84.03% ± 0.76%, sensitivity of 77.39% ± 1.99%, and specificity of 87.35% ± 1.28%. Our findings emphasize the potential of deep learning models in predicting kidney anomalies from limited prenatal ultrasound imagery. The proposed adaptations in model representation and interpretation represent a novel solution to multi-class prediction problems.

HDAC1/2 inhibitor therapy improves multiple organ systems in aged mice.

Aging increases the risk of age-related diseases, imposing substantial healthcare and personal costs. Targeting fundamental aging mechanisms pharmacologically can promote healthy aging and reduce this disease susceptibility. In this work, we employed transcriptome-based drug screening to identify compounds emulating transcriptional signatures of long-lived genetic interventions. We discovered compound 60 (Cmpd60), a selective histone deacetylase 1 and 2 (HDAC1/2) inhibitor, mimicking diverse longevity interventions. In extensive molecular, phenotypic, and bioinformatic assessments using various cell and aged mouse models, we found Cmpd60 treatment to improve age-related phenotypes in multiple organs. Cmpd60 reduces renal epithelial-mesenchymal transition and fibrosis in kidney, diminishes dementia-related gene expression in brain, and enhances cardiac contractility and relaxation for the heart. In sum, our two-week HDAC1/2 inhibitor treatment in aged mice establishes a multi-tissue, healthy aging intervention in mammals, holding promise for therapeutic translation to promote healthy aging in humans.

Childhood Cerebral Vasculitis : A Multidisciplinary Approach.

Cerebral vasculitis is increasingly recognized as a common cause of pediatric arterial stroke. It can present with focal neurological deficits, psychiatric manifestations, seizures, and encephalopathy. The etiopathogenesis of childhood cerebral vasculitis (CCV) is multifactorial, making an inclusive classification challenging. In this review, we describe the common and uncommon CCV with a comprehensive discussion of etiopathogenesis, the role of various imaging modalities, and advanced techniques in diagnosing CCV. We also highlight the implications of relevant clinical, laboratory, and genetic findings to reach the final diagnosis. Based on the clinicoradiological findings, a stepwise diagnostic approach is proposed to facilitate CCV diagnosis and rule out potential mimics. Identification of key clinical manifestations, pertinent blood and cerebrospinal fluid results, and evaluation of central nervous system vessels for common and disease-specific findings will be emphasized. We discuss the role of magnetic resonance imaging, MR angiography, and vessel wall imaging as the imaging investigation of choice, and reservation of catheter angiography as a problem-solving tool. We emphasize the utility of brain and leptomeningeal biopsy for diagnosis and exclusion of imitators and masqueraders.

Using deep-learning in fetal ultrasound analysis for diagnosis of cystic hygroma in the first trimester.

OBJECTIVE: To develop and internally validate a deep-learning algorithm from fetal ultrasound images for the diagnosis of cystic hygromas in the first trimester. METHODS: All first trimester ultrasound scans with a diagnosis of a cystic hygroma between 11 and 14 weeks gestation at our tertiary care centre in Ontario, Canada were studied. Ultrasound scans with normal nuchal translucency were used as controls. The dataset was partitioned with 75% of images used for model training and 25% used for model validation. Images were analyzed using a DenseNet model and the accuracy of the trained model to correctly identify cases of cystic hygroma was assessed by calculating sensitivity, specificity, and the area under the receiver-operating characteristic (ROC) curve. Gradient class activation heat maps (Grad-CAM) were generated to assess model interpretability. RESULTS: The dataset included 289 sagittal fetal ultrasound images;129 cystic hygroma cases and 160 normal NT controls. Overall model accuracy was 93% (95% CI: 88-98%), sensitivity 92% (95% CI: 79-100%), specificity 94% (95% CI: 91-96%), and the area under the ROC curve 0.94 (95% CI: 0.89-1.0). Grad-CAM heat maps demonstrated that the model predictions were driven primarily by the fetal posterior cervical area. CONCLUSIONS: Our findings demonstrate that deep-learning algorithms can achieve high accuracy in diagnostic interpretation of cystic hygroma in the first trimester, validated against expert clinical assessment.

Tranexamic acid in patients with intracerebral haemorrhage (STOP-AUST): a multicentre, randomised, placebo-controlled, phase 2 trial.

BACKGROUND: Despite intracerebral haemorrhage causing 5% of deaths worldwide, few evidence-based therapeutic strategies other than stroke unit care exist. Tranexamic acid decreases haemorrhage in conditions such as acute trauma and menorrhoea. We aimed to assess whether tranexamic acid reduces intracerebral haemorrhage growth in patients with acute intracerebral haemorrhage. METHODS: We did a prospective, double-blind, randomised, placebo-controlled, investigator-led, phase 2 trial at 13 stroke centres in Australia, Finland, and Taiwan. Patients were eligible if they were aged 18 years or older, had an acute intracerebral haemorrhage fulfilling clinical criteria (eg, Glasgow Coma Scale score of >7, intracerebral haemorrhage volume <70 mL, no identified or suspected secondary cause of intracerebral haemorrhage, no thrombotic events within the previous 12 months, no planned surgery in the next 24 h, and no use of anticoagulation), had contrast extravasation on CT angiography (the so-called spot sign), and were treatable within 4·5 h of symptom onset and within 1 h of CT angiography. Patients were randomly assigned (1:1) to receive either 1 g of intravenous tranexamic acid over 10 min followed by 1 g over 8 h or matching placebo, started within 4·5 h of symptom onset. Randomisation was done using a centralised web-based procedure with randomly permuted blocks of varying size. All patients, investigators, and staff involved in patient management were masked to treatment. The primary outcome was intracerebral haemorrhage growth (>33% relative or >6 mL absolute) at 24 h. The primary and safety analyses were done in the intention-to-treat population. The trial is registered at ClinicalTrials.gov (NCT01702636). FINDINGS: Between March 1, 2013, and Aug 13, 2019, we enrolled and randomly assigned 100 participants to the tranexamic acid group (n=50) or the placebo group (n=50). Median age was 71 years (IQR 57-79) and median intracerebral haemorrhage volume was 14·6 mL (7·9-32·7) at baseline. The primary outcome was not different between the two groups: 26 (52%) patients in the placebo group and 22 (44%) in the tranexamic acid group had intracerebral haemorrhage growth (odds ratio [OR] 0·72 [95% CI 0·32-1·59], p=0·41). There was no evidence of a difference in the proportions of patients who died or had thromboembolic complications between the groups: eight (16%) in the placebo group vs 13 (26%) in the tranexamic acid group died and two (4%) vs one (2%) had thromboembolic complications. None of the deaths was considered related to study medication. INTERPRETATION: Our study does not provide evidence that tranexamic acid prevents intracerebral haemorrhage growth, although the treatment was safe with no increase in thromboembolic complications. Larger trials of tranexamic acid, with simpler recruitment methods and an earlier treatment window, are justified. FUNDING: National Health and Medical Research Council, Royal Melbourne Hospital Foundation.

Independent Validation of the Hematoma Expansion Prediction Score: A Non-contrast Score Equivalent in Accuracy to the Spot Sign.

BACKGROUND AND PURPOSE: The computed tomography angiography (CTA) spot sign is widely used to assess the risk of hematoma expansion following acute intracerebral hemorrhage (ICH). However, not all patients can receive intravenous contrast nor are all hospital systems equipped with this technology. We aimed to independently validate the Hematoma Expansion Prediction (HEP) Score, an 18-point non-contrast prediction scale, in an external cohort and compare its diagnostic capability to the CTA spot sign. METHODS: We performed a retrospective analysis of the predicting hematoma growth and outcome in intracerebral hemorrhage using contrast bolus CT (PREDICT) Cohort Study. Primary outcome was significant hematoma expansion (≥ 6 mL or ≥ 33%). We generated a receiver operating characteristic (ROC) curve comparing the HEP score to significant expansion. We calculated sensitivity, specificity, positive and negative predictive values (PPV/NPV) for each score point. We determined independent predictors of significant hematoma expansion via logistic regression. RESULTS: A total of 292 patients were included in primary analysis. Hematoma growth of ≥ 6 mL or ≥ 33% occurred in 94 patients (32%). The HEP score was associated with significant expansion (adjusted odds ratio [aOR] 1.14, 95% confidence interval [CI] 1.01-1.30). ROC curves comparing HEP score to significant expansion had an area under the curve of 0.64 (95% CI 0.57-0.71). Youden's method showed an optimum score of 4. HEP Scores ≥ 4 (n = 100, sensitivity 49%, specificity 73%, PPV 46%, NPV 75%, aOR 1.99, 95% CI 1.09-3.64) accurately predicted significant expansion. PPV increased with higher HEP scores, but at the cost of lower sensitivity. The diagnostic characteristics of the spot sign (n = 82, Sensitivity 49%, Specificity 81%, PPV 55%, NPV 76%, aOR 2.95, 95% CI 1.61-5.42) were similar to HEP scores ≥ 4. CONCLUSION: The HEP score is predictive of significant expansion (≥ 6 mL or ≥ 33%) and is comparable to the spot sign in diagnostic accuracy. Non-contrast prediction tools may have a potential role in the recruitment of patients in future intracerebral hemorrhage trials.

An Algorithm for Managing Intraosseous Vascular Anomalies of the Craniofacial Skeleton.

BACKGROUND: Intraosseous vascular anomalies (IOVA) are rare in the craniofacial skeleton and present a diagnostic and therapeutic challenge. This study aims to describe the clinical management based on a large case series. METHODS: A retrospective chart review was performed and 9 IOVA were identified over a 15-year period. Data on demographics, diagnostic features, clinical management, and outcomes were reviewed. RESULTS: Five frontal bone IOVA and 4 orbital IOVA were identified. The postoperative follow-up ranged from 4 months to 4 years. All 9 lesions were diagnosed with computed tomography (CT) imaging. Magnetic resonance imaging (MRI) was used to delineate soft tissue involvement in 2 patients presenting with oculo-orbital dystopia and ophthalmoplegia. En bloc excision was performed in all patients. Preoperative interventional embolization was critical in the successful resection of an orbital IOVA following 2 previously failed attempts that were aborted secondary to hemorrhage. Intraoperative 3-dimensional stereotactic navigation was used for the accurate en bloc excision of a frontal IOVA to prevent injury to the frontal sinus. Reconstruction of esthetic and functional deformities was successfully accomplished. CONCLUSION: The diagnosis of IOVA relies primarily on clinical assessment and CT imaging. Further interpretation of the involvement of periorbital, facial, and intracranial soft tissue is best defined by MRI. Multidisciplinary care with interventional radiology and neurosurgery must be considered for ensuring the safe and adequate en bloc excision of craniofacial IOVA.

Diffusion Tensor Imaging Tractography of the Facial Nerve in Patients With Cerebellopontine Angle Tumors.

OBJECTIVE: To demonstrate the utility of diffusion tensor imaging (DTI) fiber tractography of the facial nerve in patients with cerebellopontine angle (CPA) tumors. STUDY DESIGN: Prospective. SETTING: Tertiary referral center. PATIENTS: DTI technique was established in 113 patients without tumors and in 28 patients with CPA tumors. Subsequently, DTI results were compared with intraoperative findings in 21 patients with medium and large-sized tumors, treated surgically via a translabyrinthine approach. INTERVENTION: Three Tesla magnetic resonance (MR) was used for DTI tractography. For patients without CPA tumors, the scanning protocol was 32 directions with a 3 × 3 × 3 mm voxel size. For CPA tumor patients, scanning protocol was 32 directions with a 2 × 2 × 2 mm voxel size. DTI data were used to track the facial nerve. MAIN OUTCOME MEASURES: Facial nerve identification rate. RESULTS: Facial nerve identification rate in MR-DTI was 97% and 100% in patients without tumors and in patients with tumors of the CPA of the internal auditory canal that were not treated surgically, respectively. MR-DTI identification of the facial nerve was successful in 20 patients who were treated surgically (95%). Good agreement between surgical findings and MR-DTI results was found in 19 patients (90%). CONCLUSION: MR DTI tractography is an effective technique in positively identifying the position of the facial nerve in patients with CPA tumors.

Emergency Imaging of Intracerebral Haemorrhage.

Spontaneous intracerebral haemorrhage (ICH) is a devastating condition with high mortality and morbidity despite advances in neurocritical care. Early deterioration is common in the first few hours after ICH onset, secondary to rapid haematoma expansion and growth. Rapid diagnosis and aggressive early management of these patients are therefore crucial. Imaging plays a key role in establishing the diagnosis and the underlying aetiology of ICH, identifying complications and predicting patients who are at high risk for haematoma expansion. In this chapter, we present an evidence-based imaging framework for the management of spontaneous ICH in the acute setting. Non-enhanced computed tomography is long established as the gold standard for ICH diagnosis but has limitations in demonstrating the underlying aetiology in cases of secondary ICH. There is now growing evidence for the ability of non-invasive angiography to establish the underlying aetiology and to predict further haematoma expansion. The presence of small enhancing foci within the haematoma on computed tomography angiography (CTA), the CTA Spot Sign, has been prospectively validated as a predictor of haematoma expansion. Early identification of patients at risk of haematoma expansion allows for the appropriate escalation of care to a neurosurgical team, admission to a neurocritical care unit, appropriate supportive therapy and targeted novel medical and surgical interventions. Catheter angiography, which remains the gold standard for identifying underlying secondary vascular lesions, should be used in selected cases. However, non-invasive vascular imaging should be considered as an important step in the diagnosis and early management of secondary ICH patients. Previous concerns related to the radiation dose, contrast-induced nephropathy and cost are addressed in this chapter. Recently, animal models have enabled the qualitative assessment of haematoma expansion, and our increased understanding of ICH may inform future trials of targeted medical and surgical therapies.

Non Tumor Perfusion Changes Following Stereotactic Radiosurgery to Brain Metastases.

PURPOSE: To evaluate early perfusion changes in normal tissue following stereotactic radiosurgery (SRS). METHODS: Nineteen patients harboring twenty-two brain metastases treated with SRS were imaged with dynamic susceptibility magnetic resonance imaging (DSC MRI) at baseline, 1 week and 1 month post SRS. Relative cerebral blood volume and flow (rCBV and rCBF) ratios were evaluated outside of tumor within a combined region of interest (ROI) and separately within gray matter (GM) and white matter (WM) ROIs. Three-dimensional dose distribution from each SRS plan was divided into six regions: (1) <2 Gy; (2) 2-5 Gy; (3) 5-10 Gy; (4) 10-12 Gy; (5) 12-16 Gy; and (6) >16 Gy. rCBV and rCBF ratio differences between baseline, 1 week and 1 month were compared. Best linear fit plots quantified normal tissue dose-dependency. RESULTS: Significant rCBV ratio increases were present between baseline and 1 month for all ROIs and dose ranges except for WM ROI receiving <2 Gy. rCBV ratio for all ROIs was maximally increased from baseline to 1 month with the greatest changes occurring within the 5-10 Gy dose range (53.1%). rCBF ratio was maximally increased from baseline to 1 month for all ROIs within the 5-10 Gy dose range (33.9-45.0%). Both rCBV and rCBF ratios were most elevated within GM ROIs. A weak, positive but not significant association between dose, rCBV and rCBF ratio was demonstrated. Progressive rCBV and rCBF ratio increased with dose up to 10 Gy at 1 month. CONCLUSION: Normal tissue response following SRS can be characterized by dose, tissue, and time specific increases in rCBV and rCBF ratio.

The spot sign and tranexamic acid on preventing ICH growth--AUStralasia Trial (STOP-AUST): protocol of a phase II randomized, placebo-controlled, double-blind, multicenter trial.

RATIONALE: No evidence-based acute therapies exist for intracerebral hemorrhage. Intracerebral hemorrhage growth is an important determinant of patient outcome. Tranexamic acid is known to reduce hemorrhage in other conditions. AIM: The study aims to test the hypothesis that intracerebral hemorrhage patients selected with computed tomography angiography contrast extravasation 'spot sign' will have lower rates of hematoma growth when treated with intravenous tranexamic acid within 4.5-hours of stroke onset compared with placebo. DESIGN: The Spot sign and Tranexamic acid On Preventing ICH growth--AUStralasia Trial is a multicenter, prospective, 1:1 randomized, double-blind, placebo-controlled, investigator-initiated, academic Phase II trial. Intracerebral hemorrhage patients fulfilling clinical criteria (e.g. Glasgow Coma Scale >7, intracerebral hemorrhage volume <70 ml, no identified secondary cause of intracerebral hemorrhage, no thrombotic events within the previous 12 months, no planned surgery) and demonstrating contrast extravasation on computed tomography angiography will receive either intravenous tranexamic acid 1 g 10-min bolus followed by 1 g eight-hour infusion or placebo. A second computed tomography will be performed at 24 ± 3 hours to evaluate intracerebral hemorrhage growth and patients followed up for three-months. STUDY OUTCOMES: The primary outcome measure is presence of intracerebral hemorrhage growth by 24 ± 3 hours, defined as either >33% or >6 ml increase from baseline, and will be adjusted for baseline intracerebral hemorrhage volume. Secondary outcome measures include growth as a continuous measure, thromboembolic events, and the three-month modified Rankin Scale score. DISCUSSION: This is the first trial to evaluate the efficacy of tranexamic acid in intracerebral hemorrhage patients selected based on an imaging biomarker of high likelihood of hematoma growth. The trial is registered as NCT01702636.

Successful pregnancy, epidural anaesthesia, labour, and delivery in a woman with Sturge-Weber syndrome and previous hemispherectomy.

BACKGROUND: The outcomes of pregnancy and subsequent delivery of healthy neonates in women who have undergone previous near total hemispherectomy for Sturge-Weber syndrome (SWS) have rarely been reported. CASE: A woman with SWS had two successful and uncomplicated pregnancies and deliveries under epidural anaesthesia after undergoing a near total hemispherectomy with subsequent unilateral cerebral palsy. Non-contrast MRI of the brain revealed post hemispherectomy changes with no residual meningeal angiomatosis. CONCLUSION: As more women who undergo surgical resection for underlying SWS grow into the child-bearing years, additional reports of pregnancy and delivery outcomes in this patient population can be expected and will be valuable.

Contexte : Les issues de grossesse et l'accouchement subséquent d'enfants en santé chez des femmes ayant au préalable subi une hémisphérectomie presque totale en raison du syndrome de Sturge-Weber (SSW) n'ont que rarement fait l'objet de signalements. Cas : Une femme présentant le SSW a connu deux grossesses et accouchements réussis et sans complications sous anesthésie péridurale, après avoir subi une hémisphérectomie presque totale ayant subséquemment donné lieu à une infirmité motrice cérébrale unilatérale. Une IRM du cerveau menée sans produits de contraste a révélé la présence de modifications post-hémisphérectomie, sans angiomatose méningée résiduelle. Conclusion : Au fur et à mesure que nous verrons un nombre de plus en plus important de femmes, ayant subi une résection chirurgicale en raison d'un SSW sous-jacent, atteindre l'âge de procréation, nous pouvons nous attendre à d'autres signalements d'issues de grossesse et d'accouchement portant sur cette population de patientes; ces signalements prendront alors toute leur valeur.

Severe hypomagnesemia associated with reversible subacute ataxia and cerebellar hyperintensities on MRI.

INTRODUCTION: Hypomagnesemia has been associated with various neurological symptoms including ataxia. Reversible changes in cerebellar function have been described due to hypertensive changes, eclampsia, and immunosuppressive therapy in the context of posterior reversible encephalopathy syndrome. In this report we document isolated, reversible cerebellar findings with the corresponding neuroimaging correlates associated with critically low magnesium levels. CASE REPORT: A 72-year-old male with metastatic colorectal cancer and short gut syndrome presented with subacute ataxia and cerebellar T2 hyperintensities on magnetic resonance imaging. The patient showed rapid clinical and radiologic improvement in his cerebellar findings after receiving only magnesium supplementation. CONCLUSIONS: Our report suggests that low magnesium levels may mimic the vascular endothelial dysregulation that is seen in the context of rapid rises in blood pressure in both posterior reversible encephalopathy syndrome and eclampsia. This rare case suggests a potential role of magnesium in stabilizing the vascular endothelium and, when deficient, in contributing to cerebral edema of the posterior circulation territories.

Rare frontal lobe intraparenchymal epidermoid cyst with atypical imaging.

Epidermoid cysts are slow-growing benign tumors derived from ectodermal tissue that are hypothesized to have been inwardly displaced from the ectodermal surfaces during embryologic development. These cysts represent 1% to 2% of all intracranial tumors, and occur most commonly in the cerebellopontine angle, parasellar region, and subarachnoid spaces of the basal cisterns. Epidermoid cysts that are exclusively intraparenchymal are very rare, and can be difficult to diagnose as they often do not have classic radiologic findings, and share many similar radiologic features to other tumors such as astrocytomas, arachnoid cysts, dermoid cysts, and cavernomas. The authors present a patient with a rare intraparenchymal epidermoid cyst of the frontal lobe with atypical imaging features.

Prediction of haematoma growth and outcome in patients with intracerebral haemorrhage using the CT-angiography spot sign (PREDICT): a prospective observational study.

BACKGROUND: In patients with intracerebral haemorrhage (ICH), early haemorrhage expansion affects clinical outcome. Haemostatic treatment reduces haematoma expansion, but fails to improve clinical outcomes in many patients. Proper selection of patients at high risk for haematoma expansion seems crucial to improve outcomes. In this study, we aimed to prospectively validate the CT-angiography (CTA) spot sign for prediction of haematoma expansion. METHODS: PREDICT (predicting haematoma growth and outcome in intracerebral haemorrhage using contrast bolus CT) was a multicentre prospective observational cohort study. We recruited patients aged 18 years or older, with ICH smaller than 100 mL, and presenting at less than 6 h from symptom onset. Using two independent core laboratories, one neuroradiologist determined CTA spot-sign status, whereas another neurologist masked for clinical outcomes and imaging measured haematoma volumes by computerised planimetry. The primary outcome was haematoma expansion defined as absolute growth greater than 6 mL or a relative growth of more than 33% from initial CT to follow-up CT. We reported data using standard descriptive statistics stratified by the CTA spot sign. Mortality was assessed with Kaplan-Meier survival analysis. FINDINGS: We enrolled 268 patients. Median time from symptom onset to baseline CT was 135 min (range 22-470), and time from onset to CTA was 159 min (32-475). 81 (30%) patients were spot-sign positive. The primary analysis included 228 patients, who had a follow-up CT before surgery or death. Median baseline ICH volume was 19·9 mL (1·5-80·9) in spot-sign-positive patients versus 10·0 mL (0·1-102·7) in spot-sign negative patients (p<0·001). Median ICH expansion was 8·6 mL (-9·3 to 121·7) for spot-sign positive patients and 0·4 mL (-11·7 to 98·3) for spot-negative patients (p<0·001). In those with haematoma expansion, the positive predictive value for the spot sign was61% (95% CI 47­73) for the positive predictive value and 78% (71­84) for the negative predictive value, with 51% (39­63) sensitivity and 85% (78­90) specificity[corrected]. Median 3-month modified Rankin Scale (mRS) was 5 in CTA spot-sign-positive patients, and 3 in spot-sign-negative patients (p<0·001). Mortality at 3 months was 43·4% (23 of 53) in CTA spot-sign positive versus 19·6% (31 of 158) in CTA spot-sign-negative patients (HR 2·4, 95% CI 1·4-4·0, p=0·002). INTERPRETATION: These findings confirm previous single-centre studies showing that the CTA spot sign is a predictor of haematoma expansion. The spot sign is recommended as an entry criterion for future trials of haemostatic therapy in patients with acute ICH. FUNDING: Canadian Stroke Consortium and NovoNordisk Canada.

Reproducibility of semi-automated measurement of carotid stenosis on CTA.

PURPOSE: To compare the reproducibility of semi-automated vessel analysis software to manual measurement of carotid artery stenosis on computed tomography angiography (CTA). METHODS: Two observers separately analyzed 81 carotid artery CTAs using semi-automated vessel analysis software according to a blinded protocol. The software measured the narrowest stenosis in millimeters (mm), distal internal carotid artery (ICA) in mm, and calculated percent stenosis based on NASCET criteria. One observer performed this task twice on each carotid, the second analysis delayed two months in order to mitigate recall bias. Two other observers manually measured the narrowest stenosis in mm, distal ICA in mm, and calculated NASCET percent stenosis in a blinded fashion. Correlation coefficients were calculated for each group comparing the narrowest stenosis in mm, distal ICA in mm, and NASCET percent stenosis. RESULTS: The semi-automated vessel analysis software provided excellent intraobserver correlation for narrowest stenosis in mm, distal ICA in mm, and NACSET percent stenosis (Pearson correlation coefficients of 0.985, 0.954, and 0.977 respectively). The semi-automated vessel analysis software provided excellent interobserver correlation (0.925, 0.881, and 0.892 respectively). The interobserver correlation for manual measurement was good (0.595, 0.625, and 0.555 respectively). There was a statistically significant difference in the interobserver correlation between the semi-automated vessel analysis software observers and the manual measurement observers (P < 0.001). CONCLUSION: Semi-automated vessel analysis software is a highly reproducible method of quantifying carotid artery stenosis on CTA. In this study, semi-automated vessel analysis software determination of carotid stenosis was shown to be more reproducible than manual measurement.