Cerebral Blood Volume ASPECTS Is the Best Predictor of Clinical Outcome in Acute Ischemic Stroke: A Retrospective,Combined Semi-Quantitative and Quantitative Assessment

Introduction

The capability of CT perfusion (CTP) Alberta Stroke Program Early CT Score (ASPECTS) to predict outcome and identify ischemia severity in acute ischemic stroke (AIS) patients is still questioned.

Methods

62 patients with AIS were imaged within 8 hours of symptom onset by non-contrast CT, CT angiography and CTP scans at admission and 24 hours. CTP ASPECTS was calculated on the affected hemisphere using cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) maps by subtracting 1 point for any abnormalities visually detected or measured within multiple cortical circular regions of interest according to previously established thresholds. MTT-CBV ASPECTS was considered as CTP ASPECTS mismatch. Hemorrhagic transformation (HT), recanalization status and reperfusion grade at 24 hours, final infarct volume at 7 days and modified Rankin scale (mRS) at 3 months after onset were recorded.

Results

Semi-quantitative and quantitative CTP ASPECTS were highly correlated (p<0.00001). CBF, CBV and MTT ASPECTS were higher in patients with no HT and mRS≤2 and inversely associated with final infarct volume and mRS (p values: from p<0.05 to p<0.00001). CTP ASPECTS mismatch was slightly associated with radiological and clinical outcomes (p values: from p<0.05 to p<0.02) only if evaluated quantitatively. A CBV ASPECTS of 9 was the optimal semi-quantitative value for predicting outcome.

Conclusions

Our findings suggest that visual inspection of CTP ASPECTS recognizes infarct and ischemic absolute values. Semi-quantitative CBV ASPECTS, but not CTP ASPECTS mismatch, represents a strong prognostic indicator, implying that core extent is the main determinant of outcome, irrespective of penumbra size.     

Effect of Extended CT Perfusion Acquisition Time on Ischemic Core and Penumbra Volume Estimation in Patients with Acute Ischemic Stroke due to a Large Vessel Occlusion

Background and Purpose

It has been suggested that CT Perfusion acquisition times <60 seconds are too short to capture the complete in and out-wash of contrast in the tissue, resulting in incomplete time attenuation curves. Yet, these short acquisitions times are not uncommon in clinical practice. The purpose of this study was to investigate the occurrence of time attenuation curve truncation in 48 seconds CT Perfusion acquisition and to quantify its effect on ischemic core and penumbra estimation in patients with acute ischemic stroke due to a proximal intracranial arterial occlusion of the anterior circulation.

Materials and Methods

We analyzed CT Perfusion data with 48 seconds and extended acquisition times, assuring full time attenuation curves, of 36 patients. Time attenuation curves were classified as complete or truncated. Ischemic core and penumbra volumes resulting from both data sets were compared by median paired differences and interquartile ranges. Controlled experiments were performed using a digital CT Perfusion phantom to investigate the effect of time attenuation curve truncation on ischemic core and penumbra estimation.

Results

In 48 seconds acquisition data, truncation was observed in 24 (67%) cases for the time attenuation curves in the ischemic core, in 2 cases for the arterial input function and in 5 cases for the venous output function. Analysis of extended data resulted in smaller ischemic cores and larger penumbras with a median difference of 13.2 (IQR: 4.3–26.0)ml (P<0.001) and; 12.4 (IQR: 4.1–25.7)ml (P<0.001), respectively. The phantom data showed increasing ischemic core overestimation with increasing tissue time attenuation curve truncation.

Conclusions

Truncation is common in patients with large vessel occlusion and results in repartitioning of the area of hypoperfusion into larger ischemic core and smaller penumbra estimations. Phantom experiments confirmed that truncation results in overestimation of the ischemic core.     

Reliability of Two Diameters Method in Determining Acute Infarct Size. Validation as New Imaging Biomarker

Background

In order to select patients most likely to benefit for thrombolysis and to predict patient outcome in acute ischemic stroke, the volumetric assessment of the infarcted tissue is used. However, infarct volume estimation on Diffusion weighted imaging (DWI) has moderate interrater variability despite the excellent contrast between ischemic lesion and healthy tissue. In this study, we compared volumetric measurements of DWI hyperintensity to a simple maximum orthogonal diameter approach to identify thresholds indicating infarct size >70 ml and >100 ml.

Methods

Patients presenting with ischemic stroke with an NIHSS of ≥ 8 were examined with stroke MRI within 24 h after symptom onset. For assessment of the orthogonal DWI lesion diameters (od-values) the image with the largest lesion appearance was chosen. The maximal diameter of the lesion was determined and a second diameter was measured perpendicular. Both diameters were multiplied. Od-values were compared to volumetric measurement and od-value thresholds identifying a lesion size of > 70 ml and > 100 ml were determined. In a selected dataset with an even distribution of lesion sizes we compared the results of the od value thresholds with results of the ABC/2 and estimations of lesion volumes made by two resident physicians.

Results

For 108 included patients (53 female, mean age 71.36 years) with a median infarct volume of 13.4 ml we found an excellent correlation between volumetric measures and od-values (r2 = 0.951). Infarct volume >100 ml corresponds to an od-value cut off of 42; > 70 ml corresponds to an od-value of 32. In the compiled dataset (n = 50) od-value thresholds identified infarcts > 100 ml / > 70 ml with a sensitivity of 90%/ 93% and with a specificity of 98%/ 89%. The od-value offered a higher accuracy in identifying large infarctions compared to both visual estimations and the ABC/2 method.

Conclusion

The simple od-value enables identification of large DWI lesions in acute stroke. The cutoff of 42 is useful to identify large infarctions with volume larger than 100 ml. Further studies can analyze the therapeutic utility of this new method.

Trail Registration

ClinicalTrials.org NCT00715533     

Comparison of Arterial Spin Labeling and Dynamic Susceptibility Contrast Perfusion MRI in Patients with Acute Stroke

Background

The aim of this study was to evaluate whether arterial spin labeling (ASL) perfusion magnetic resonance imaging (MRI) can reliably quantify perfusion deficit as compared to dynamic susceptibility contrast (DSC) perfusion MRI.

Methods

Thirty-nine patients with acute ischemic stroke in the anterior circulation territory were recruited. All underwent ASL and DSC MRI perfusion scans within 30 hours after stroke onset and 31 patients underwent follow-up MRI scans. ASL cerebral blood flow (CBF) and DSC time to maximum (T_max) maps were used to calculate the perfusion defects. The ASL CBF lesion volume was compared to the DSC T_max lesion volume by Pearson''s correlation coefficient and likewise the ASL CBF and DSC T_max lesion volumes were compared to the final infarct sizes respectively. A repeated measures analysis of variance and least significant difference post hoc test was used to compare the mean lesion volumes among ASL CBF, DSC T_max >4–6 s and final infarct.

Results

Mean patient age was 72.6 years. The average time from stroke onset to MRI was 13.9 hours. The ASL lesion volume showed significant correlation with the DSC lesion volume for T_max >4, 5 and 6 s (r = 0.81, 0.82 and 0.80; p<0.001). However, the mean lesion volume of ASL (50.1 ml) was significantly larger than those for T_max >5 s (29.2 ml, p<0.01) and T_max >6 s (21.8 ml, p<0.001), while the mean lesion volumes for T_max >5 or 6 s were close to mean final infarct size.

Conclusion

Quantitative measurement of ASL perfusion is well correlated with DSC perfusion. However, ASL perfusion may overestimate the perfusion defects and therefore further refinement of the true penumbra threshold and improved ASL technique are necessary before applying ASL in therapeutic trials.     

Effects of Body Mass Index on Risks for Ischemic Stroke,Thromboembolism, and Mortality in Chinese Atrial Fibrillation Patients: A Single-Center Experience

Background

Obesity is considered to be related to recurrence of atrial fibrillation (AF), left atrial thrombus formation, and atrial remodeling. However, whether obesity is an independent risk factor for stroke and other thromboembolic events is still controversial.

Objective

This study aimed to investigate the effects of body mass index (BMI) on the risks of stroke, thromboembolism, and mortality in AF patients.

Methods

Patients who were diagnosed with nonvalvular AF were included in this observational, retrospective study. The study population was stratified by BMI at baseline. The Cox proportional hazard model was adopted to calculate adjusted hazard ratios of risk factors for adverse clinical events (stroke, thromboembolism, and mortality).

Results

A total of 1286 AF patients (males, 78.30%; mean age, 74.50 years; 94.48% paroxysmal AF) were followed up for a median of 2.1 years (IQR: 1.5–2.9 years). Overall, 159 patients died. A total of 84 strokes and 35 thromboembolic events occurred. Multivariate analysis showed that overweight (25.0≤BMI<30.0 kg/m²) and age ≥75 years were independent risk factors for ischemic stroke (both P<0.01). Obesity (BMI ≥30.0 kg/m²), age ≥75 years, persistent/permanent AF, and prior thromboembolism were independent risk factors for thromboembolism (all P<0.05). Underweight (BMI <18.5 kg/m²), age ≥75 years, prior ischemic stroke/transient ischemic attack, renal dysfunction, and heart failure were independent risk factors for all-cause deaths (all P<0.05).

Conclusions

Overweight or obesity may be a risk factor of ischemic stroke and thromboembolism in AF patients. Excessive low weight is significantly associated with increased all-cause mortality.     

Intra-Arterial Transplantation of Allogeneic Mesenchymal Stem Cells Mounts Neuroprotective Effects in a Transient Ischemic Stroke Model in Rats: Analyses of Therapeutic Time Window and Its Mechanisms

Objective

Intra-arterial stem cell transplantation exerts neuroprotective effects for ischemic stroke. However, the optimal therapeutic time window and mechanisms have not been completely understood. In this study, we investigated the relationship between the timing of intra-arterial transplantation of allogeneic mesenchymal stem cells (MSCs) in ischemic stroke model in rats and its efficacy in acute phase.

Methods

Adult male Wistar rats weighing 200 to 250g received right middle cerebral artery occlusion (MCAO) for 90 minutes. MSCs (1×10⁶cells/ 1ml PBS) were intra-arterially injected at either 1, 6, 24, or 48 hours (1, 6, 24, 48h group) after MCAO. PBS (1ml) was intra-arterially injected to control rats at 1 hour after MCAO. Behavioral test was performed immediately after reperfusion, and at 3, 7 days after MCAO using the Modified Neurological Severity Score (mNSS). Rats were euthanized at 7 days after MCAO for evaluation of infarct volumes and the migration of MSCs. In order to explore potential mechanisms of action, the upregulation of neurotrophic factor and chemotactic cytokine (bFGF, SDF-1α) induced by cell transplantation was examined in another cohort of rats that received intra-arterial transplantation at 24 hours after recanalization then euthanized at 7 days after MCAO for protein assays.

Results

Behavioral test at 3 and 7 days after transplantation revealed that stroke rats in 24h group displayed the most robust significant improvements in mNSS compared to stroke rats in all other groups (p’s<0.05). Similarly, the infarct volumes of stroke rats in 24h group were much significantly decreased compared to those in all other groups (p’s<0.05). These observed behavioral and histological effects were accompanied by MSC survival and migration, with the highest number of integrated MSCs detected in the 24h group. Moreover, bFGF and SDF-1α levels of the infarcted cortex were highly elevated in the 24h group compared to control group (p’s<0.05).

Conclusions

These results suggest that intra-arterial allogeneic transplantation of MSCs provides post-stroke functional recovery and reduction of infarct volumes in ischemic stroke model of rats. The upregulation of bFGF and SDF-1α likely played a key mechanistic role in enabling MSC to afford functional effects in stroke. MSC transplantation at 24 hours after recanalization appears to be the optimal timing for ischemic stroke model, which should guide the design of clinical trials of cell transplantation for stroke patients.     

The Effect of Pre-Condition Cerebella Fastigial Nucleus Electrical Stimulation within and beyond the Time Window of Thrombolytic on Ischemic Stroke in the Rats

Objective

To investigate the effect of neurogenic neuroprotection conferred by cerebellar fastigial nucleus stimulation (FNS) and the role of PPARγ- mediated inflammation in a rat model of cerebral ischemia reperfusion.

Methods

After a continuous 1 hour fastigial nucleus electric stimulation, the male Sprague Dawley (SD) rats were given middle cerebral artery occlusion (MCAO) for 1, 3, 6, 9, 12 and 15 hours undergoing reperfusion with intravenous recombinant tissue plasminogen activator (rt-PA), while the control group received without FNS. After 72h of reperfusion, the neurological deficits, infarct volume and brain edema were evaluated. The brain tissue in ischemic penumbra was determined the myeloperoxidase (MPO) activity by a spectrophotometer and expression of PPARγ was measured by Rt-PCR and Western blotting.

Results

Our findings showed that FNS group had significantly reduced infarct volume and brain edema, and improved neurological deficits compared with the control group, especially in 6h and 9h reperfusion subgroups(p<0.05). The expression levels of PPARγ increased gradually and the peak may be before and after 9h reperfusion, the 3h, 6h, 9h, 12h and 15h reperfusion subgroups were higher than each control group(p<0.05). The MPO activity of 6h, 12h and 15h reperfusion subgroups were higher than each control group(p<0.05).

Conclusions

The neuroprotective effects of FNS have been shown to prolong the therapeutic window in cerebral ischemia/reperfusion, which might be related to the PPARγ mediated-inflammation in penumbral region.     

Reliability of Visual Assessment of Non-Contrast CT,CT Angiography Source Images and CT Perfusion in Patients with Suspected Ischemic Stroke

Background and Purpose

Good reliability of methods to assess the extent of ischemia in acute stroke is important for implementation in clinical practice, especially between observers with varying experience. Our aim was to determine inter- and intra-observer reliability of the 1/3 middle cerebral artery (MCA) rule and the Alberta Stroke Program Early CT Score (ASPECTS) for different CT modalities in patients suspected of acute ischemic stroke.

Methods

We prospectively included 105 patients with acute neurological deficit due to suspected acute ischemic stroke within 9 hours after symptom onset. All patients underwent non-contrast CT, CT perfusion and CT angiography on admission. All images were evaluated twice for presence of ischemia, ischemia with >1/3 MCA involvement, and ASPECTS. Four observers evaluated twenty scans twice for intra-observer agreement. We used kappa statistics and intraclass correlation coefficient to calculate agreement.

Results

Inter-observer agreement for the 1/3 MCA rule and ASPECTS was fair to good for non-contrast CT, poor to good for CT angiography source images, but excellent for all CT perfusion maps (cerebral blood volume, mean transit time, and predicted penumbra and infarct maps). Intra-observer agreement for the 1/3 MCA rule and ASPECTS was poor to good for non-contrast CT, fair to moderate for CT angiography source images, and good to excellent for all CT perfusion maps.

Conclusion

Between observers with a different level of experience, agreement on the radiological diagnosis of cerebral ischemia is much better for CT perfusion than for non-contrast CT and CT angiography source images, and therefore CT perfusion is a very reliable addition to standard stroke imaging.     

Comparison of Conventional versus Steerable-Catheter Guided Coronary Sinus Lead Positioning in Patients Undergoing Cardiac Resynchronization Device Implantation

Objectives

The aim of this study was to compare conventional versus steerable catheter guided coronary sinus (CS) cannulation in patients with advanced heart failure undergoing cardiac resynchronization therapy (CRT).

Background

Steerable catheter guided coronary sinus cannulation could reduce fluoroscopy time and contrast medium use during CRT implantation.

Methods

176 consecutive patients with ischemic and non-ischemic heart failure undergoing CRT implantation from January 2008 to December 2012 at the University Hospital of Cologne were identified. During the study period two concurrent CS cannulation techniques were used: standard CS cannulation technique (standard-group, n = 113) and CS cannulation using a steerable electrophysiology (EP) catheter (EPCath-group, n = 63). Propensity-score matched pairs of conventional and EP-catheter guided CS cannulation made up the study population (n = 59 pairs). Primary endpoints were total fluoroscopy time and contrast medium amount used during procedure.

Results

The total fluoroscopy time was 30.9 min (interquartile range (IQR), 19.9–44.0 min) in the standard-group and 23.4 min (IQR, 14.2-34-2 min) in the EPCath-group (p = 0.011). More contrast medium was used in the standard-group (60.0 ml, IQR, 30.0–100 ml) compared to 25.0 ml (IQR, 20.0–50.0 ml) in the EPCath-group (P<0.001).

Conclusions

Use of steerable EP catheter was associated with significant reduction of fluoroscopy time and contrast medium use in patients undergoing CRT implantation.     

Hyperglycaemia,Insulin Therapy and Critical Penumbral Regions for Prognosis in Acute Stroke: Further Insights from the INSULINFARCT Trial

Background

Recently, the concept of ‘clinically relevant penumbra’ was defined as an area saved by arterial recanalization and correlated with stroke outcome. This clinically relevant penumbra was located in the subcortical structures, especially the periventricular white matter. Our aims were to confirm this hypothesis, to investigate the impact of admission hyperglycemia and of insulin treatment on the severity of ischemic damages in this area and to study the respective contributions of infarct volume and ischemic damage severity of the clinically relevant penumbra on 3-month outcome.

Methods

We included 99 patients from the INSULINFARCT trial. Voxel-Based Analysis was carried on the Apparent Diffusion Coefficient (ADC) maps obtained at day one to localize the regions, which were more damaged in patients i) with poor clinical outcomes at three months and ii) without arterial recanalization. We determined the intersection of the detected areas, which represents the clinically relevant penumbra and investigated whether hyperglycemic status and insulin regimen affected the severity of ischemic damages in this area. We performed logistic regression to examine the contribution of infarct volume or early ADC decrease in this strategic area on 3-month outcome.

Findings

Lower ADC values were found in the corona radiata in patients with poor prognosis (p< 0.0001) and in those without arterial recanalization (p< 0.0001). The tracking analysis showed that lesions in this area interrupted many important pathways. ADC values in this area were lower in hyperglycemic than in normoglycemic patients (average decrease of 41.6 ± 20.8 x10⁻⁶mm²/s) and unaffected by the insulin regimen (p: 0.10). ADC values in the clinically relevant penumbra, but not infarct volumes, were significant predictors of 3-month outcome.

Conclusion

These results confirm that the deep hemispheric white matter is part of the clinically relevant penumbra and show that hyperglycaemia exacerbates the apparition of irreversible ischemic damage within 24 hours in this area. However, early intensive insulin therapy fails to protect this area from infarction.

Trial Registration

ClinicalTrials.gov NCT00472381     

Evaluating Variations of Bladder Volume Using an Ultrasound Scanner in Rectal Cancer Patients during Chemoradiation: Is Protocol-Based Full Bladder Maintenance Using a Bladder Scanner Useful to Maintain the Bladder Volume?

Purpose

The maintenance of full bladder is important to reduce radiation-induced toxicities and maintain the therapeutic consistency in locally advanced rectal cancer patients who underwent radiotherapy (RT). So, the aim of this study was to evaluate the effectiveness of protocol-based full bladder maintenance by assessing bladder volume variation using an ultrasound bladder scanner to maintain bladder volume.

Materials and Methods

From March 2011 to May 2011, twenty consecutive rectal cancer patients receiving external beam RT participated in this prospective study. Protocol-based full bladder maintenance consisted of education, training and continuous biofeedback by measuring bladder volume. Bladder volume was measured by bladder scan immediately before simulation CT scan and before each treatment three times weekly during the RT period. The relative bladder volume change was calculated. Intra-patient bladder volume variations were quantified using interquartile range (IQR) of relative bladder volume change in each patient. We compared intra-patient bladder volume variations obtained (n=20) with data from our previous study patients (n=20) performing self-controlled maintenance without protocol.

Results

Bladder volumes measured by bladder scan highly correlated with those on simulation CT scan (R=0.87, p<0.001). Patients from this study showed lower median IQR of relative bladder volume change compared to patients of self-controlled maintenance from our previous study, although it was not statistically significant (median 32.56% vs. 42.19%, p=0.058). Upon logistic regression, the IQR of relative bladder volume change was significantly related to protocol-based maintenance [relative risk 1.045, 95% confidence intervals (CI) 1.004-1.087, p=0.033]. Protocol-based maintenance included significantly more patients with an IQR of relative bladder volume change less than 37% than self-controlled maintenance (p=0.025).

Conclusion

Our findings show that bladder volume could be maintained more consistently during RT by protocol-based management using a bladder scan.     

Automated Entire Thrombus Density Measurements for Robust and Comprehensive Thrombus Characterization in Patients with Acute Ischemic Stroke

Background and Purpose

In acute ischemic stroke (AIS) management, CT-based thrombus density has been associated with treatment success. However, currently used thrombus measurements are prone to inter-observer variability and oversimplify the heterogeneous thrombus composition. Our aim was first to introduce an automated method to assess the entire thrombus density and then to compare the measured entire thrombus density with respect to current standard manual measurements.

Materials and Method

In 135 AIS patients, the density distribution of the entire thrombus was determined. Density distributions were described using medians, interquartile ranges (IQR), kurtosis, and skewedness. Differences between the median of entire thrombus measurements and commonly applied manual measurements using 3 regions of interest were determined using linear regression.

Results

Density distributions varied considerably with medians ranging from 20.0 to 62.8 HU and IQRs ranging from 9.3 to 55.8 HU. The average median of the thrombus density distributions (43.5 ± 10.2 HU) was lower than the manual assessment (49.6 ± 8.0 HU) (p<0.05). The difference between manual measurements and median density of entire thrombus decreased with increasing density (r = 0.64; p<0.05), revealing relatively higher manual measurements for low density thrombi such that manual density measurement tend overestimates the real thrombus density.

Conclusions

Automatic measurements of the full thrombus expose a wide variety of thrombi density distribution, which is not grasped with currently used manual measurement. Furthermore, discrimination of low and high density thrombi is improved with the automated method.     

Determinants of the Efficacy of Cardiac Ischemic Preconditioning: A Systematic Review and Meta-Analysis of Animal Studies

Background

Ischemic preconditioning (IPC) of the heart is a protective strategy in which a brief ischemic stimulus immediately before a lethal ischemic episode potently limits infarct size. Although very promising in animal models of myocardial infarction, IPC has not yet been successfully translated to benefit for patients.

Objective

To appraise all preclinical evidence on IPC for myocardial infarction and identify factors hampering translation.

Methods and results

Using systematic review and meta-analysis, we identified 503 animal studies reporting infarct size data from 785 comparisons between IPC-treated and control animals. Overall, IPC reduced myocardial infarction by 24.6% [95%CI 23.5, 25.6]. Subgroup analysis showed that IPC efficacy was reduced in comorbid animals and non-rodents. Efficacy was highest in studies using 2–3 IPC cycles applied <45 minutes before myocardial infarction. Local and remote IPC were equally effective. Reporting of study quality indicators was low: randomization, blinding and a sample size calculation were reported in 49%, 11% and 2% of publications, respectively.

Conclusions

Translation of IPC to the clinical setting may be hampered by the observed differences between the animals used in preclinical IPC studies and the patient population, regarding comorbidity, sex and age. Furthermore, the IPC protocols currently used in clinical trials could be optimized in terms of timing and the number of ischemic cycles applied. In order to inform future clinical trials successfully, future preclinical studies on IPC should aim to maximize both internal and external validity, since poor methodological quality may limit the value of the preclinical evidence.     

Venom Concentrations and Clotting Factor Levels in a Prospective Cohort of Russell’s Viper Bites with Coagulopathy

Background

Russell’s viper envenoming is a major problem in South Asia and causes venom induced consumption coagulopathy. This study aimed to investigate the kinetics and dynamics of venom and clotting function in Russell’s viper envenoming.

Methodology/Principal Findings

In a prospective cohort of 146 patients with Russell’s viper envenoming, we measured venom concentrations, international normalised ratio [INR], prothrombin time (PT), activated partial thromboplastin time (aPTT), coagulation factors I, II, V, VII, VIII, IX and X, and von Willebrand factor antigen. The median age was 39y (16–82y) and 111 were male. The median peak INR was 6.8 (interquartile range[IQR]:3.7 to >13), associated with low fibrinogen [median,<0.01g/L;IQR:<0.01–0.9g/L), low factor V levels [median,<5%;IQR:<5–4%], low factor VIII levels [median,40%;IQR:12–79%] and low factor X levels [median,48%;IQR:29–67%]. There were smaller reductions in factors II, IX and VII over time. All factors recovered over 48h post-antivenom. The median INR remained >3 at 6h post-antivenom but had reduced to <2, by 24h. The aPTT had also returned to close to normal (<50sec) at 24h. Factor VII, VIII and IX levels were unusually high pre-antivenom, median peak concentrations of 393%, 307% and 468% respectively. Pre-antivenom venom concentrations and the INR (r = 0.20, p = 0.02) and aPTT (r = 0.19, p = 0.03) were correlated (non-parametric Spearman analysis).

Conclusions

Russell’s viper coagulopathy results in prolonged aPTT, INR, low fibrinogen, factors V, VIII and X which recover over 48h. Severity of clotting abnormalities was associated with venom concentrations.     

Acceptance of Combined Coronary CT Angiography and Myocardial CT Perfusion versus Conventional Coronary Angiography in Patients with Coronary Stents—Intraindividual Comparison

Objectives

To evaluate how well patients with coronary stents accept combined coronary computed tomography angiography (CTA) and myocardial CT perfusion (CTP) compared with conventional coronary angiography (CCA).

Background

While combined CTA and CTP may improve diagnostic accuracy compared with CTA alone, patient acceptance of CTA/CTP remains to be defined.

Methods

A total of 90 patients with coronary stents prospectively underwent CTA/CTP (both with contrast agent, CTP with adenosine) and CCA as part of the CARS-320 study. In this group, an intraindividual comparison of patient acceptance of CTA, CTP, and CCA was performed.

Results

CTP was experienced to be significantly more painful than CTA (p<0.001) and was associated with a higher frequency of dyspnea (p<0.001). Comparison of CTA/CTP with CCA revealed no significant differences in terms of pain (p = 0.141) and comfort (p = 0.377). Concern before CTA/CTP and CCA and overall satisfaction were likewise not significantly different (p = 0.097 and p = 0.123, respectively). Nevertheless, about two thirds (n = 60, 68%) preferred CTA/CTP to CCA (p<0.001). Moreover, patients felt less helpless during CTA/CTP than during CCA (p = 0.026). Lack of invasiveness and absence of pain were the most frequently mentioned advantages of CTA/CTP over CCA in our patient population.

Conclusions

CCA and combined CTA/CTP are equally well accepted by patients; however, more patients prefer CTA/CTP. CTP was associated with more intense pain than CTA and more frequently caused dyspnea than CTA alone.

Trial Registration

ClinicalTrials.gov NCT00967876     

Fully Automated Pulmonary Lobar Segmentation: Influence of Different Prototype Software Programs onto Quantitative Evaluation of Chronic Obstructive Lung Disease

Objectives

Surgical or bronchoscopic lung volume reduction (BLVR) techniques can be beneficial for heterogeneous emphysema. Post-processing software tools for lobar emphysema quantification are useful for patient and target lobe selection, treatment planning and post-interventional follow-up. We aimed to evaluate the inter-software variability of emphysema quantification using fully automated lobar segmentation prototypes.

Material and Methods

66 patients with moderate to severe COPD who underwent CT for planning of BLVR were included. Emphysema quantification was performed using 2 modified versions of in-house software (without and with prototype advanced lung vessel segmentation; programs 1 [YACTA v.2.3.0.2] and 2 [YACTA v.2.4.3.1]), as well as 1 commercial program 3 [Pulmo3D VA30A_HF2] and 1 pre-commercial prototype 4 [CT COPD ISP ver7.0]). The following parameters were computed for each segmented anatomical lung lobe and the whole lung: lobar volume (LV), mean lobar density (MLD), 15^th percentile of lobar density (15^th), emphysema volume (EV) and emphysema index (EI). Bland-Altman analysis (limits of agreement, LoA) and linear random effects models were used for comparison between the software.

Results

Segmentation using programs 1, 3 and 4 was unsuccessful in 1 (1%), 7 (10%) and 5 (7%) patients, respectively. Program 2 could analyze all datasets. The 53 patients with successful segmentation by all 4 programs were included for further analysis. For LV, program 1 and 4 showed the largest mean difference of 72 ml and the widest LoA of [-356, 499 ml] (p<0.05). Program 3 and 4 showed the largest mean difference of 4% and the widest LoA of [-7, 14%] for EI (p<0.001).

Conclusions

Only a single software program was able to successfully analyze all scheduled data-sets. Although mean bias of LV and EV were relatively low in lobar quantification, ranges of disagreement were substantial in both of them. For longitudinal emphysema monitoring, not only scanning protocol but also quantification software needs to be kept constant.     

Classifiers for Ischemic Stroke Lesion Segmentation: A Comparison Study

Motivation

Ischemic stroke, triggered by an obstruction in the cerebral blood supply, leads to infarction of the affected brain tissue. An accurate and reproducible automatic segmentation is of high interest, since the lesion volume is an important end-point for clinical trials. However, various factors, such as the high variance in lesion shape, location and appearance, render it a difficult task.

Methods

In this article, nine classification methods (e.g. Generalized Linear Models, Random Decision Forests and Convolutional Neural Networks) are evaluated and compared with each other using 37 multiparametric MRI datasets of ischemic stroke patients in the sub-acute phase in terms of their accuracy and reliability for ischemic stroke lesion segmentation. Within this context, a multi-spectral classification approach is compared against mono-spectral classification performance using only FLAIR MRI datasets and two sets of expert segmentations are used for inter-observer agreement evaluation.

Results and Conclusion

The results of this study reveal that high-level machine learning methods lead to significantly better segmentation results compared to the rather simple classification methods, pointing towards a difficult non-linear problem. The overall best segmentation results were achieved by a Random Decision Forest and a Convolutional Neural Networks classification approach, even outperforming all previously published results. However, none of the methods tested in this work are capable of achieving results in the range of the human observer agreement and the automatic ischemic stroke lesion segmentation remains a complicated problem that needs to be explored in more detail to improve the segmentation results.     

Aspirin Resistance in the Acute Stages of Acute Ischemic Stroke Is Associated with the Development of New Ischemic Lesions

Background

Aspirin is a primary antiplatelet agent for the secondary prevention of ischemic stroke. However, if aspirin fails to inhibit platelet function, as is expected in acute ischemic stroke (AIS), it may increase the rate of early clinical events. Therefore, we sought to determine whether aspirin resistance in the acute stage was associated with early radiological events, including new ischemic lesions (NILs).

Methods

This study was a single-center, prospective, observational study conducted between April 2012 and May 2013. Aspirin 300 mg was initially administered followed by maintenance doses of 100 mg daily. The acute aspirin reaction unit (aARU) was consistently measured after 3 hours of aspirin loading. An aARU value ≥550 IU was defined as biological aspirin resistance (BAR). NILs on follow-up diffusion-weighted imaging (DWI) were defined as lesions separate from index lesions, which were not detected on the initial DWI.

Results

A total of 367 patients were analyzed in this study. BAR in aARU was detected in 60 patients (16.3%). On follow-up DWI, 81 patients (22.1%) had NILs, which were frequently in the same territory as the index lesions (79%), pial infarcts (61.7%), and located within the cortex (59.3%). BAR was independently associated with NILs on follow-up DWI (adjusted OR 2.00, 95% CIs 1.01–3.96; p = 0.047).

Conclusion

In conclusion, BAR in aARU could be associated with NILs on follow-up DWI in AIS. Therefore, a further prospective study with a longer follow-up period is necessary to evaluate the clinical implications of aARU in AIS.     

Temporal Evolution of Ischemic Lesions in Nonhuman Primates: A Diffusion and Perfusion MRI Study

MethodsPermanent MCA occlusion was induced with silk sutures through an interventional approach via the femoral artery in adult rhesus monkeys (n = 8, 10–21 years old). The stroke lesions were examined with high-resolution DWI and perfusion MRI, and T2-weighted imaging (T2W) on a clinical 3T scanner at 1–6, 48, and 96 hours post occlusion and validated with H&E staining.ResultsThe stroke infarct evolved via a natural logarithmic pattern with the mean infarct growth rate = 1.38 ± 1.32 ml per logarithmic time scale (hours) (n = 7) in the hyperacute phase (1–6 hours). The mean infarct volume after 6 hours post occlusion was 3.6±2.8 ml (n = 7, by DWI) and increased to 3.9±2.9 ml (n = 5, by T2W) after 48 hours, and to 4.7±2.2ml (n = 3, by T2W) after 96 hours post occlusion. The infarct volumes predicted by the natural logarithmic function were correlated significantly with the T2W-derived lesion volumes (n = 5, r = 0.92, p = 0.01) at 48 hours post occlusion. The final infarct volumes derived from T2W were correlated significantly with those from H&E staining (r = 0.999, p < 0.0001, n = 4). In addition, the diffusion-perfusion mismatch was visible generally at 6 hours but nearly diminished at 48 hours post occlusion.ConclusionThe infarct evolution follows a natural logarithmic pattern in the hyperacute phase of stroke. The logarithmic pattern of evolution could last up to 48 hours after stroke onset and may be used to predict the infarct volume growth during the acute phase of ischemic stroke. The nonhuman primate model, MRI protocols, and post data processing strategy may provide an excellent platform for characterizing the evolution of acute stroke lesion in mechanistic studies and therapeutic interventions of stroke disease.     

Accuracy of [18F]FDG PET/MRI for the Detection of Liver Metastases

Background

The aim of this study was to compare the diagnostic accuracy of [¹⁸F]FDG-PET/MRI with PET/CT for the detection of liver metastases.

Methods

32 patients with solid malignancies underwent [¹⁸F]FDG-PET/CT and subsequent PET/MRI of the liver. Two readers assessed both datasets regarding lesion characterization (benign, indeterminate, malignant), conspicuity and diagnostic confidence. An imaging follow-up (mean interval: 185±92 days) and/-or histopathological specimen served as standards of reference. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated for both modalities. Accuracy was determined by calculating the area under the receiver operating characteristic (ROC) curve. Values of conspicuity and diagnostic confidence were compared using Wilcoxon-signed-rank test.

Results

The standard of reference revealed 113 liver lesions in 26 patients (malignant: n = 45; benign: n = 68). For PET/MRI a higher accuracy (PET/CT: 82.4%; PET/MRI: 96.1%; p<0.001) as well as sensitivity (67.8% vs. 92.2%, p<0.01) and NPV (82.0% vs. 95.1%, p<0.05) were observed. PET/MRI offered higher lesion conspicuity (PET/CT: 2.0±1.1 [median: 2; range 0–3]; PET/MRI: 2.8±0.5 [median: 3; range 0–3]; p<0.001) and diagnostic confidence (PET/CT: 2.0±0.8 [median: 2; range: 1–3]; PET/MRI 2.6±0.6 [median: 3; range: 1–3]; p<0.001). Furthermore, PET/MRI enabled the detection of additional PET-negative metastases (reader 1: 10; reader 2: 12).

Conclusions

PET/MRI offers higher diagnostic accuracy compared to PET/CT for the detection of liver metastases.