First Report of Two Cases of Acute Gastric Ischemia after Robot-Assisted Radical Cystectomy.

Gastrointestinal ischemia is rare after small pelvis surgery. Minimal invasive robotic surgery requires adaptation of the surgical approach for cystectomy and derivation construction such as the use of pneumoperitoneum and Trendelenburg positioning of the patient. Two cases with gastric ischemic complications after robot-assisted radical cystectomy are described. The first case was a 68-year-old female who had prolonged gastroparalysis and blood in a replaced gastric tube at day 10 after robotic cystectomy and Bricker urinary derivation. Gastroscopy revealed ischemia of gastric and proximal duodenal mucosa while computed tomography showed multiple calcifications and thrombi in the coeliac trunk branches and splenic infarcts. The stenosis of the origin of the mesenteric superior artery was stented via an endovascular procedure, and the patient recovered with normal gastroscopy 1 month postoperatively. The second case was a 73-year-old male who developed abdominal pain and fever 5 days after robotic cystectomy and Bricker. On abdominal computed tomography imaging, subcutaneous emphysema, intra-abdominal air, and calcification at the origin of the coeliac trunk were found. At laparotomy 5 days after the cystectomy, a 3 cm hole in the fundus of the stomach was found which was removed with the major stomach curvature. Gastroscopy 5 days after hemigastrectomy revealed no remnant ischemia. The prolonged pneumoperitoneum during robotic cystectomy, the deep Trendelenburg position, and the preoperatively impaired vascular system can be the reasons of our first two cases of gastric ischemia. This rare complication should be kept in mind in patients with symptoms of gastric ischemia since it can result in gastric perforation.

Xanthogranulomatous pyelonephritis caused by fusobacterium nucleatum. Case report and review of literature.

Xanthogranulomatous pyelonephritisis (XGP) is a rare and aggressive form of chronic urinary tract infection. The most common microorganism is Proteus but other microorganisms have been described in the literature. In this article, we describe a sixty-year-old male who presented with urosepsis and sever thrombocytopenia secondary to Fusobacterium nucleatum urinary tract infection which led to poorly functioning XGP. The rarity of the microorganism and the devastating clinical course encourages us to report it as anaerobes don't usually cause UTI but unusual microorganism should be suspected if the clinical course is atypical or if urinary tract abnormalities are present.

Intracranial Cerebrospinal Fluid Volume as a Predictor of Malignant Middle Cerebral Artery Infarction.

Background and Purpose- Predicting malignant middle cerebral artery (MCA) infarction can help to identify patients who may benefit from preventive decompressive surgery. We aimed to investigate the association between the ratio of intracranial cerebrospinal fluid (CSF) volume to intracranial volume (ICV) and malignant MCA infarction. Methods- Patients with an occlusion proximal to the M3 segment of the MCA were selected from the DUST (Dutch Acute Stroke Study). Admission imaging included noncontrast computed tomography (CT), CT perfusion, and CT angiography. Patient characteristics and CT findings were collected. The ratio of intracranial CSF volume to ICV (CSF/ICV) was quantified on admission thin-slice noncontrast CT. Malignant MCA infarction was defined as a midline shift of >5 mm on follow-up noncontrast CT, which was performed 3 days after the stroke or in case of clinical deterioration. To test the association between CSF/ICV and malignant MCA infarction, odds ratios and 95% CIs were calculated for 3 multivariable models by using binary logistic regression. Model performances were compared by using the likelihood ratio test. Results- Of the 286 included patients, 35 (12%) developed malignant MCA infarction. CSF/ICV was independently associated with malignant MCA infarction in 3 multivariable models: (1) with age and admission National Institutes of Health Stroke Scale (odds ratio, 3.3; 95% CI, 1.1-11.1), (2) with admission National Institutes of Health Stroke Scale and poor collateral score (odds ratio, 7.0; 95% CI, 2.6-21.3), and (3) with terminal internal carotid artery or proximal M1 occlusion and poor collateral score (odds ratio, 7.7; 95% CI, 2.8-23.9). The performance of model 1 (areas under the receiver operating characteristic curves, 0.795 versus 0.824; P=0.033), model 2 (areas under the receiver operating characteristic curves, 0.813 versus 0.850; P<0.001), and model 3 (areas under the receiver operating characteristic curves, 0.811 versus 0.856; P<0.001) improved significantly after adding CSF/ICV. Conclusions- The CSF/ICV ratio is associated with malignant MCA infarction and has added value to clinical and imaging prediction models in limited numbers of patients.

Stroke progression and clinical outcome in ischemic stroke patients with a history of migraine.

BACKGROUND: Patients with migraine might be more susceptible of spreading depolarizations, which are known to affect vascular and neuronal function and penumbra recovery after stroke. We investigated whether these patients have more severe stroke progression and less favorable outcomes after recanalization therapy. METHODS: We included patients from a prospective multicenter ischemic stroke cohort. Lifetime migraine history was based on the International Classification of Headache Disorders II criteria. Patients without confirmed migraine diagnosis were excluded. Patients underwent CT angiography and CT perfusion <9 h of onset and follow-up CT after three days. On admission, presence of a perfusion deficit, infarct core and penumbra volume, and blood brain barrier permeability (BBBP) were assessed. At follow-up we assessed malignant edema, hemorrhagic transformation, and final infarct volume. Outcome at three months was evaluated with the modified Rankin Scale (mRS). We calculated adjusted relative risks (aRR) or difference of means (aB) with regression analyses. RESULTS: We included 600 patients of whom 43 had migraine. There were no differences between patients with or without migraine in presence of a perfusion deficit on admission (aRR: 0.98, 95%CI: 0.77-1.25), infarct core volume (aB: -10.8, 95%CI: -27.04-5.51), penumbra volume (aB: -11.6, 95%CI: -26.52-3.38), mean blood brain barrier permeability (aB: 0.08, 95%CI: -3.11-2.96), malignant edema (0% vs. 5%), hemorrhagic transformation (aRR: 0.26, 95%CI: 0.04-1.73), final infarct volume (aB: -14.8, 95%CI: 29.9-0.2) or outcome after recanalization therapy (mRS > 2, aRR: 0.50, 95%CI: 0.21-1.22). CONCLUSION: Elderly patients with a history of migraine do not seem to have more severe stroke progression and have similar treatment outcomes compared with patients without migraine.

Wake-Up Stroke versus Stroke with Known Onset Time: Clinical and Multimodality CT Imaging Characteristics.

BACKGROUND: Current guidelines for the treatment of acute ischemic stroke are mainly based on the time between symptom onset and initiation of treatment. This time is unknown in patients with wake-up stroke (WUS). We investigated clinical and multimodality CT imaging characteristics on admission in patients with WUS and in patients with a stroke with a known onset time. METHODS: All patients were selected from a large prospective cohort study (Dutch acute stroke study). WUS patients last seen well > 4.5 and ≤4.5 h were separately compared to patients with a known onset time ≤4.5 h. In addition, WUS patients with a proximal occlusion of the anterior circulation last seen well > 6 and ≤6 h were separately compared to patients with a known onset time ≤6 h and a proximal occlusion. National Institute of Health Stroke Score, age, gender, history of atrial fibrillation, non-contrast CT (NCCT) Alberta Stroke Program Early CT Score (ASPECTS), CT-perfusion abnormalities, proximal occlusions, and collateral filling on CT angiography were compared between groups using the Mann-Whitney U test and Fisher's exact test. RESULTS: WUS occurred in 149/1,393 (10.7%) patients. Admission clinical and imaging characteristics of WUS patients last seen well > 4.5 h (n = 81) were not different from WUS patients last seen well ≤4.5 h (n = 68). Although WUS patients last seen well > 4.5 h had a significantly lower NCCT ASPECTS than patients with a known time of stroke symptom onset of ≤4.5 h (n = 1,026), 85.2% had an NCCT ASPECTS > 7 and 75% had a combination of favorable ASPECTS > 7 and good collateral filling. There were no statistically significant differences between the admission clinical and imaging characteristics of WUS patients with proximal occlusions last seen well > 6 h (n = 23), last seen well ≤6 h (n = 40), and patients with a known time to stroke symptom onset ≤6 h (n = 399). Of all WUS patients with proximal occlusions last seen well > 6 h, only 4.3% had severe ischemia (ASPECTS < 5), 13 (56.5%) had ASPECTS > 7 and good collateral filling. CONCLUSIONS: There are only minor differences between clinical and imaging characteristics of WUS patients and patients who arrive in the hospital within the time criteria for intravenous or endovascular treatment. Therefore, CT imaging may help to identify WUS patients who would benefit from treatment and rule out those patients with severe ischemia and poor collaterals.

Computed Tomography Perfusion Derived Blood-Brain Barrier Permeability Does Not Yet Improve Prediction of Hemorrhagic Transformation.

INTRODUCTION: Hemorrhagic transformation (HT) in acute ischemic stroke can occur as a result of reperfusion treatment. While withholding treatment may be warranted in patients with increased risk of HT, prediction of HT remains difficult. Nonlinear regression analysis can be used to estimate blood-brain barrier permeability (BBBP). The aim of this study was to identify a combination of clinical and imaging variables, including BBBP estimations, that can predict HT. MATERIALS AND METHODS: From the Dutch acute stroke study, 545 patients treated with intravenous recombinant tissue plasminogen activator and/or intra-arterial treatment were selected, with available admission extended computed tomography (CT) perfusion and follow-up imaging. Patient admission treatment characteristics and CT imaging parameters regarding occlusion site, stroke severity, and BBBP were recorded. HT was assessed on day 3 follow-up imaging. The association between potential predictors and HT was analyzed using univariate and multivariate logistic regression. To compare the added value of BBBP, areas under the curve (AUCs) were created from 2 models, with and without BBBP. RESULTS: HT occurred in 57 patients (10%). In univariate analysis, older age (OR 1.03, 95% CI 1.006-1.05), higher admission National Institutes of Health Stroke Scale (NIHSS; OR 1.13, 95% CI 1.08-1.18), higher clot burden (OR 1.28, 95% CI 1.16-1.41), poor collateral score (OR 3.49, 95% CI 1.85-6.58), larger Alberta Stroke Program Early CT Score cerebral blood volume deficit size (OR 1.26, 95% CI 1.14-1.38), and increased BBBP (OR 2.22, 95% CI 1.46-3.37) were associated with HT. In multivariate analysis with age and admission NIHSS, the addition of BBBP did not improve the AUC compared to both independent predictors alone (AUC 0.77, 95% CI 0.71-0.83). CONCLUSION: BBBP predicts HT but does not improve prediction with age and admission NIHSS.

Internal Carotid Artery Stenosis and Collateral Recruitment in Stroke Patients.

PURPOSE: Leptomeningeal collaterals improve outcome in stroke patients. There is great individual variability in their extent. Internal carotid artery (ICA) stenosis may lead to more extensive recruitment of leptomeningeal collaterals. The purpose of this study was to evaluate the association of pre-existing ICA stenosis with leptomeningeal collateral filling visualized with computed tomography perfusion (CTP). METHODS: From a prospective acute ischemic stroke cohort, patients were included with an M1 middle cerebral artery (MCA) occlusion and absent ipsilateral, extracranial ICA occlusion. ICA stenosis was determined on admission CT angiography (CTA). Leptomeningeal collaterals were graded as good (>50%) or poor (≤50%) collateral filling in the affected MCA territory on CTP-derived vessel images of the admission scan. The association between ipsilateral ICA stenosis ≥70% and extent of collateral filling was analyzed using logistic regression. In a multivariable analysis the odds ratio (OR) of ICA stenosis ≥70% was adjusted for complete circle of Willis, gender and age. RESULTS: We included 188 patients in our analyses, 50 (26.6%) patients were classified as having poor collateral filling and 138 (73.4%) as good. Of the patients 4 with poor collateral filling had an ICA stenosis ≥70% and 14 with good collateral filling. Unadjusted and adjusted ORs of ICA stenosis ≥70% for good collateral filling were 1.30 (0.41-4.15) and 2.67 (0.81-8.77), respectively. Patients with poor collateral filling had a significantly worse outcome (90-day modified Rankin scale 3-6; 80% versus 52%, p = 0.001). CONCLUSION: No association was found between pre-existing ICA stenosis and extent of CTP derived collateral filling in patients with an M1 occlusion.

Prediction of Clinical Outcome After Acute Ischemic Stroke: The Value of Repeated Noncontrast Computed Tomography, Computed Tomographic Angiography, and Computed Tomographic Perfusion.

BACKGROUND AND PURPOSE: Early prediction of outcome in acute ischemic stroke is important for clinical management. This study aimed to compare the relationship between early follow-up multimodality computed tomographic (CT) imaging and clinical outcome at 90 days in a large multicenter stroke study. METHODS: From the DUST study (Dutch Acute Stroke Study), patients were selected with (1) anterior circulation occlusion on CT angiography (CTA) and ischemic deficit on CT perfusion (CTP) on admission, and (2) day 3 follow-up noncontrast CT, CTP, and CTA. Follow-up infarct volume on noncontrast CT, poor recanalization on CTA, and poor reperfusion on CTP (mean transit time index ≤75%) were related to unfavorable outcome after 90 days defined as modified Rankin Scale 3 to 6. Four multivariable models were constructed: (1) only baseline variables (model 1), (2) model 1 with addition of infarct volume, (3) model 1 with addition of recanalization, and (4) model 1 with addition of reperfusion. Area under the curves of the receiver operating characteristic curves of the models were compared using the DeLong test. RESULTS: A total of 242 patients were included. Poor recanalization was found in 21%, poor reperfusion in 37%, and unfavorable outcome in 44%. The area under the curve of the receiver operating characteristic curve without follow-up imaging was 0.81, with follow-up noncontrast CT 0.85 (P=0.02), CTA 0.86 (P=0.01), and CTP 0.86 (P=0.01). All 3 follow-up imaging modalities improved outcome prediction compared with no imaging. There was no difference between the imaging models. CONCLUSIONS: Follow-up imaging after 3 days improves outcome prediction compared with prediction based on baseline variables alone. CTA recanalization and CTP reperfusion do not outperform noncontrast CT at this time point. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00880113.

Permeable Thrombi Are Associated With Higher Intravenous Recombinant Tissue-Type Plasminogen Activator Treatment Success in Patients With Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Preclinical studies showed that thrombus permeability improves recombinant tissue-type plasminogen activator (r-tPA) efficacy. We hypothesize that thrombus permeability estimated from radiological imaging is associated with improved recanalization after treatment with intravenously administered r-tPA (r-tPA) and with better functional outcome. METHODS: We assessed thrombus attenuation increase (TAI) in patients from the Dutch Acute Stroke Study with an occlusion of an intracranial artery on computed tomographic angiography. Patients were included within 9 hours after the stroke onset. After dichotomization of TAI as pervious or impervious, logistic regressions analyses were performed to estimate associations of intravenous r-tPA therapy with complete recanalization and with favorable functional outcome (modified Rankin Scale score of ≤2). RESULTS: Three hundred eight patients matched the inclusion criteria. The median TAI was 20.1 (interquartile range, 8.5-37.8) Hounsfield unit (HU). We found a significant increase in the odds of complete recanalization with increasing TAI for patients treated with intravenous r-tPA (P=0.030). One hundred thirty-one (42%) thrombi were classified as pervious with TAI of ≥23 HU. In patients with a pervious thrombus, complete recanalization was more frequent after treatment with intravenous r-tPA than after conservative treatment (odds ratio, 6.26; 95% confidence interval, 2.4-16.8; P<0.001). In patients with an impervious thrombus, the effect of intravenous r-tPA was not significant (odds ratio, 1.4; 95% confidence interval, 0.5-4.1; P=0.47). Favorable outcome was more common in patients with a pervious thrombi than without (odds ratio, 2.1; 95% confidence interval, 1.3-3.4; P=0.001). CONCLUSIONS: Thrombus perviousness, as measured on computed tomography in the acute stage of ischemic stroke, is strongly associated with recanalization after intravenous r-tPA treatment and with favorable functional outcome.

CT angiography and CT perfusion improve prediction of infarct volume in patients with anterior circulation stroke.

INTRODUCTION: We investigated whether baseline CT angiography (CTA) and CT perfusion (CTP) in acute ischemic stroke could improve prediction of infarct presence and infarct volume on follow-up imaging. METHODS: We analyzed 906 patients with suspected anterior circulation stroke from the prospective multicenter Dutch acute stroke study (DUST). All patients underwent baseline non-contrast CT, CTA, and CTP and follow-up non-contrast CT/MRI after 3 days. Multivariable regression models were developed including patient characteristics and non-contrast CT, and subsequently, CTA and CTP measures were added. The increase in area under the curve (AUC) and R (2) was assessed to determine the additional value of CTA and CTP. RESULTS: At follow-up, 612 patients (67.5%) had a detectable infarct on CT/MRI; median infarct volume was 14.8 mL (interquartile range (IQR) 2.8-69.6). Regarding infarct presence, the AUC of 0.82 (95% confidence interval (CI) 0.79-0.85) for patient characteristics and non-contrast CT was improved with addition of CTA measures (AUC 0.85 (95% CI 0.82-0.87); p < 0.001) and was even higher after addition of CTP measures (AUC 0.89 (95% CI 0.87-0.91); p < 0.001) and combined CTA/CTP measures (AUC 0.89 (95% CI 0.87-0.91); p < 0.001). For infarct volume, adding combined CTA/CTP measures (R (2) = 0.58) was superior to patient characteristics and non-contrast CT alone (R (2) = 0.44) and to addition of CTA alone (R (2) = 0.55) or CTP alone (R (2) = 0.54; all p < 0.001). CONCLUSION: In the acute stage, CTA and CTP have additional value over patient characteristics and non-contrast CT for predicting infarct presence and infarct volume on follow-up imaging. These findings could be applied for patient selection in future trials on ischemic stroke treatment.

Relation between stroke severity, patient characteristics and CT-perfusion derived blood-brain barrier permeability measurements in acute ischemic stroke.

PURPOSE: Increased blood-brain barrier permeability (BBBP) can result from ischemia. In this study the relation between stroke severity, patient characteristics and admission BBBP values measured with CT-perfusion (CTP) was investigated in acute ischemic stroke patients. METHODS: From prospective data of the Dutch Acute Stroke Study 149 patients with a middle cerebral artery stroke and extended CTP were selected. BBBP values were measured in the penumbra and infarct core as defined by CTP thresholds, and in the contra-lateral hemisphere. The relation between stroke (severity) variables and patient characteristics, including early CT signs, dense vessel sign (DVS), time to scan and National Institute of Health Stroke Score (NIHSS), and BBBP parameters in penumbra and infarct core was quantified with regression analysis. RESULTS: Early CT signs were related to higher BBBP values in the infarct core (B = 0.710), higher ipsi- to contra-lateral BBBP ratios (B = 0.326) and higher extraction ratios in the infarct core (B = 16.938). Females were found to have lower BBBP values in penumbra and infarct core (B = - 0.446 and - 0.776 respectively) and lower extraction ratios in the infarct core (B = - 10.463). If a DVS was present the ipsi- to contra-lateral BBBP ratios were lower (B = - 0.304). There was no relation between NIHSS or time to scan and BBBP values. CONCLUSION: Early CT signs are related to higher BBBP values in the infarct core, suggesting that only severe ischemic damage alters BBBP within the first hours after symptom onset.

No Relation between Body Temperature and Arterial Recanalization at Three Days in Patients with Acute Ischaemic Stroke.

BACKGROUND: Recanalization of an occluded intracranial artery is influenced by temperature-dependent enzymes, including alteplase. We assessed the relation between body temperature on admission and recanalization. METHODS: We included 278 patients with acute ischaemic stroke within nine hours after symptom onset, who had an intracranial arterial occlusion on admission CT angiography, in 13 participating centres. We calculated the relation per every 0.1°Celsius increase in admission body temperature and recanalization at three days. RESULTS: Recanalization occurred in 80% of occluded arteries. There was no relation between body temperature and recanalization at three days after adjustments for age, NIHSS score on admission and treatment with alteplase (adjusted odds ratio per 0.1°Celsius, 0.99; 95% confidence interval, 0.94-1.05; p = 0.70). Results for patients treated or not treated with alteplase were essentially the same. CONCLUSIONS: Our findings suggest that in patients with acute ischaemic stroke there is no relation between body temperature on admission and recanalization of an occluded intracranial artery three days later, irrespective of treatment with alteplase.

The Prognostic Value of CT Angiography and CT Perfusion in Acute Ischemic Stroke.

BACKGROUND: CT angiography (CTA) and CT perfusion (CTP) are important diagnostic tools in acute ischemic stroke. We investigated the prognostic value of CTA and CTP for clinical outcome and determined whether they have additional prognostic value over patient characteristics and non-contrast CT (NCCT). METHODS: We included 1,374 patients with suspected acute ischemic stroke in the prospective multicenter Dutch acute stroke study. Sixty percent of the cohort was used for deriving the predictors and the remaining 40% for validating them. We calculated the predictive values of CTA and CTP predictors for poor clinical outcome (modified Rankin Scale score 3-6). Associations between CTA and CTP predictors and poor clinical outcome were assessed with odds ratios (OR). Multivariable logistic regression models were developed based on patient characteristics and NCCT predictors, and subsequently CTA and CTP predictors were added. The increase in area under the curve (AUC) value was determined to assess the additional prognostic value of CTA and CTP. Model validation was performed by assessing discrimination and calibration. RESULTS: Poor outcome occurred in 501 patients (36.5%). Each of the evaluated CTA measures strongly predicted outcome in univariable analyses: the positive predictive value (PPV) was 59% for Alberta Stroke Program Early CT Score (ASPECTS) ≤7 on CTA source images (OR 3.3; 95% CI 2.3-4.8), 63% for presence of a proximal intracranial occlusion (OR 5.1; 95% CI 3.7-7.1), 66% for poor leptomeningeal collaterals (OR 4.3; 95% CI 2.8-6.6), and 58% for a >70% carotid or vertebrobasilar stenosis/occlusion (OR 3.2; 95% CI 2.2-4.6). The same applied to the CTP measures, as the PPVs were 65% for ASPECTS ≤7 on cerebral blood volume maps (OR 5.1; 95% CI 3.7-7.2) and 53% for ASPECTS ≤7 on mean transit time maps (OR 3.9; 95% CI 2.9-5.3). The prognostic model based on patient characteristics and NCCT measures was highly predictive for poor clinical outcome (AUC 0.84; 95% CI 0.81-0.86). Adding CTA and CTP predictors to this model did not improve the predictive value (AUC 0.85; 95% CI 0.83-0.88). In the validation cohort, the AUC values were 0.78 (95% CI 0.73-0.82) and 0.79 (95% CI 0.75-0.83), respectively. Calibration of the models was satisfactory. CONCLUSIONS: In patients with suspected acute ischemic stroke, admission CTA and CTP parameters are strong predictors of poor outcome and can be used to predict long-term clinical outcome. In multivariable prediction models, however, their additional prognostic value over patient characteristics and NCCT is limited in an unselected stroke population.

Influence of Thin Slice Reconstruction on CT Brain Perfusion Analysis.

OBJECTIVES: Although CT scanners generally allow dynamic acquisition of thin slices (1 mm), thick slice (≥5 mm) reconstruction is commonly used for stroke imaging to reduce data, processing time, and noise level. Thin slice CT perfusion (CTP) reconstruction may suffer less from partial volume effects, and thus yield more accurate quantitative results with increased resolution. Before thin slice protocols are to be introduced clinically, it needs to be ensured that this does not affect overall CTP constancy. We studied the influence of thin slice reconstruction on average perfusion values by comparing it with standard thick slice reconstruction. MATERIALS AND METHODS: From 50 patient studies, absolute and relative hemisphere averaged estimates of cerebral blood volume (CBV), cerebral blood flow (CBF), mean transit time (MTT), and permeability-surface area product (PS) were analyzed using 0.8, 2.4, 4.8, and 9.6 mm slice reconstructions. Specifically, the influence of Gaussian and bilateral filtering, the arterial input function (AIF), and motion correction on the perfusion values was investigated. RESULTS: Bilateral filtering gave noise levels comparable to isotropic Gaussian filtering, with less partial volume effects. Absolute CBF, CBV and PS were 22%, 14% and 46% lower with 0.8 mm than with 4.8 mm slices. If the AIF and motion correction were based on thin slices prior to reconstruction of thicker slices, these differences reduced to 3%, 4% and 3%. The effect of slice thickness on relative values was very small. CONCLUSIONS: This study shows that thin slice reconstruction for CTP with unaltered acquisition protocol gives relative perfusion values without clinically relevant bias. It does however affect absolute perfusion values, of which CBF and CBV are most sensitive. Partial volume effects in large arteries and veins lead to overestimation of these values. The effects of reconstruction slice thickness should be taken into account when absolute perfusion values are used for clinical decision making.

Relation between reperfusion and hemorrhagic transformation in acute ischemic stroke.

INTRODUCTION: Intravenous recombinant tissue plasminogen activator (IV-rtPA) is given in acute ischemic stroke patients to achieve reperfusion. Hemorrhagic transformation (HT) is a serious complication of IV-rtPA treatment and related to blood-brain barrier (BBB) injury. It is unclear whether HT occurs secondary to reperfusion in combination with ischemic BBB injury or is caused by the negative effect of IV-rtPA on BBB integrity. The aim of this study was to establish the association between reperfusion and the occurrence of HT. METHODS: From the DUST study, patients were selected with admission and follow-up non-contrast CT (NCCT) and CT perfusion (CTP) imaging, and a perfusion deficit in the middle cerebral artery territory on admission. Reperfusion was categorized qualitatively as reperfusion or no-reperfusion by visual comparison of admission and follow-up CTP. Occurrence of HT was assessed on follow-up NCCT. The association between reperfusion and occurrence of HT on follow-up was estimated by calculating odds ratios (ORs) and 95 % confidence intervals (CIs) with additional stratification for IV-rtPA treatment. RESULTS: Inclusion criteria were met in 299 patients. There was no significant association between reperfusion and HT (OR 1.2 95%CI 0.5-3.1). In patients treated with IV-rtPA (n = 203), the OR was 1.3 (95%CI 0.4-4.0), and in patients not treated with IV-rtPA (n = 96), the OR was 0.8 (95%CI 0.1-4.5). HT occurred in 14 % of the IV-rtPA patients and in 7 % of patients without IV-rtPA (95%CI of difference -1 to 14 %). CONCLUSION: Our results suggest that the increased risk of HT after acute ischemic stroke treatment is not dependent on the reperfusion status.

CT perfusion analysis by nonlinear regression for predicting hemorrhagic transformation in ischemic stroke.

PURPOSE: Intravenous thrombolysis can improve clinical outcome in acute ischemic stroke patients but increases the risk of hemorrhagic transformation (HT). Blood-brain barrier damage, which can be quantified by the vascular permeability for contrast agents, is a potential predictor for HT. This study aimed to assess whether this prediction can be improved by measuring vascular permeability using a novel fast nonlinear regression (NLR) method instead of Patlak analysis. METHODS: From a prospective ischemic stroke multicenter cohort study, 20 patients with HT on follow-up imaging and 40 patients without HT were selected. The permeability transfer constant K(trans) was measured in three ways; using standard Patlak analysis, Patlak analysis with a fixed offset, and the NLR method. In addition, the permeability-surface (PS) area product and the conventional perfusion parameters (blood volume, flow, and mean transit time) were measured using the NLR method. Relative values were calculated in two ways, i.e., by dividing the average in the infarct core by the average in the contralateral hemisphere, and by dividing the average in the ipsilateral hemisphere by the average in the contralateral hemisphere. Mann-Whitney U tests and receiver operating characteristic (ROC) analyses were performed to assess the discriminative power of each of the relative parameters. RESULTS: Both the infarct-core and whole-hemisphere averaged relative K(trans) (rK(trans)) values, measured with the NLR method, were significantly higher in the patients who developed HT as compared with those who did not. The rK(trans) measured with standard Patlak analysis was not significantly different. The relative PS (rPS), measured with NLR, had the highest discriminative power (P = 0.002). ROC analysis of rPS showed an area under the curve (AUC) of 0.75 (95% confidence interval: 0.62-0.89) and a sensitivity of 0.75 at a specificity of 0.75. The AUCs of the Patlak rK(trans), the Patlak rK(trans) with fixed offset, and the NLR rK(trans) were 0.58, 0.66, and 0.67, respectively. CONCLUSIONS: CT perfusion analysis may aid in predicting HT, but standard Patlak analysis did not provide estimates for rK(trans) that were significantly higher in the HT group. The rPS, measured in the infarct core with NLR, had superior discriminative power compared with K(trans) measured with either Patlak analysis with a fixed offset or NLR, and conventional perfusion parameters.

Prediction of outcome in patients with suspected acute ischaemic stroke with CT perfusion and CT angiography: the Dutch acute stroke trial (DUST) study protocol.

BACKGROUND: Prediction of clinical outcome in the acute stage of ischaemic stroke can be difficult when based on patient characteristics, clinical findings and on non-contrast CT. CT perfusion and CT angiography may provide additional prognostic information and guide treatment in the early stage. We present the study protocol of the Dutch acute Stroke Trial (DUST). The DUST aims to assess the prognostic value of CT perfusion and CT angiography in predicting stroke outcome, in addition to patient characteristics and non-contrast CT. For this purpose, individualised prediction models for clinical outcome after stroke based on the best predictors from patient characteristics and CT imaging will be developed and validated. METHODS/DESIGN: The DUST is a prospective multi-centre cohort study in 1500 patients with suspected acute ischaemic stroke. All patients undergo non-contrast CT, CT perfusion and CT angiography within 9 hours after onset of the neurological deficits, and, if possible, follow-up imaging after 3 days. The primary outcome is a dichotomised score on the modified Rankin Scale, assessed at 90 days. A score of 0-2 represents good outcome, and a score of 3-6 represents poor outcome. Three logistic regression models will be developed, including patient characteristics and non-contrast CT (model A), with addition of CT angiography (model B), and CT perfusion parameters (model C). Model derivation will be performed in 60% of the study population, and model validation in the remaining 40% of the patients. Additional prognostic value of the models will be determined with the area under the curve (AUC) from the receiver operating characteristic (ROC) curve, calibration plots, assessment of goodness-of-fit, and likelihood ratio tests. DISCUSSION: This study will provide insight in the added prognostic value of CTP and CTA parameters in outcome prediction of acute stroke patients. The prediction models that will be developed in this study may help guide future treatment decisions in the acute stage of ischaemic stroke.

Radiation dose reduction in cerebral CT perfusion imaging using iterative reconstruction.

OBJECTIVES: To investigate whether iterative reconstruction (IR) in cerebral CT perfusion (CTP) allows for 50% dose reduction while maintaining image quality (IQ). METHODS: A total of 48 CTP examinations were reconstructed into a standard dose (150 mAs) with filtered back projection (FBP) and half-dose (75 mAs) with two strengths of IR (middle and high). Objective IQ (quantitative perfusion values, contrast-to-noise ratio (CNR), penumbra, infarct area and penumbra/infarct (P/I) index) and subjective IQ (diagnostic IQ on a four-point Likert scale and overall IQ binomial) were compared among the reconstructions. RESULTS: Half-dose CTP with high IR level had, compared with standard dose with FBP, similar objective (grey matter cerebral blood volume (CBV) 4.4 versus 4.3 mL/100 g, CNR 1.59 versus 1.64 and P/I index 0.74 versus 0.73, respectively) and subjective diagnostic IQ (mean Likert scale 1.42 versus 1.49, respectively). The overall IQ in half-dose with high IR level was scored lower in 26-31%. Half-dose with FBP and with the middle IR level were inferior to standard dose with FBP. CONCLUSION: With the use of IR in CTP imaging it is possible to examine patients with a half dose without significantly altering the objective and diagnostic IQ. The standard dose with FBP is still preferable in terms of subjective overall IQ in about one quarter of patients. KEY POINTS: • Computed tomography perfusion (CTP) is increasingly important in ischaemia imaging. • Radiation exposure of CTP is a drawback. • Iterative reconstruction (IR) allows reduction of radiation dose in unenhanced head CT. • CTP IR enables 50% dose reduction without altering objective and diagnostic quality.