Comparison of hemodynamic features and thrombosis risk of membrane oxygenators with different structures: A numerical study.

PURPOSE: The geometric structure of the membrane oxygenator can exert an impact on its hemodynamic features, which contribute to the development of thrombosis, thereby affecting the clinical efficacy of ECMO treatment. The purpose of this study is to investigate the impact of varying geometric structures on hemodynamic features and thrombosis risk of membrane oxygenators with different designs. METHODS: Five oxygenator models with different structures, including different number and location of blood inlet and outlet, as well as variations in blood flow path, were established for investigation. These models are referred to as Model 1 (Quadrox-i Adult Oxygenator), Model 2 (HLS Module Advanced 7.0 Oxygenator), Model 3 (Nautilus ECMO Oxygenator), Model 4 (OxiaACF Oxygenator) and Model 5 (New design oxygenator). The hemodynamic features of these models were numerically analyzed using the Euler method combined with computational fluid dynamics (CFD). The accumulated residence time (ART) and coagulation factor concentrations (C[i], where i represents different coagulation factors) were calculated by solving the convection diffusion equation. The resulting relationships between these factors and the development of thrombosis in the oxygenator were then investigated. RESULTS: Our results show that the geometric structure of the membrane oxygenator, including the location of the blood inlet and outlet as well as the design of the flow path, has a significant impact on the hemodynamic surroundings within the oxygenator. In comparison to Model 4, which had the inlet and outlet located in the center position, Model 1 and Model 3, which had the inlet and outlet at the edge of the blood flow field, exhibited a more uneven distribution of blood flow within the oxygenator, particularly in areas distant from the inlet and outlet, which was accompanied with lower flow velocity and higher values of ART and C[i], leading to the formation of flow dead zones and an elevated risk of thrombosis. The oxygenator of Model 5 is designed with a structure that features multiple inlets and outlets, which greatly improves the hemodynamic environment inside the oxygenator. This results in a more even distribution of blood flow within the oxygenator, reducing areas with high values of ART and C[i], and ultimately lowering the risk of thrombosis. The oxygenator of Model 3 with circular flow path section shows better hemodynamic performance compared to the oxygenator of Model 1 with square circular flow path. The overall ranking of hemodynamic performance for all five oxygenators is as follows: Model 5 > Model 4 > Model 2 > Model 3 > Model 1, indicating that Model 1 has the highest thrombosis risk while Model 5 has the lowest. CONCLUSION: The study reveals that the different structures can affect the hemodynamic characteristics inside membrane oxygenators. The design of multiple inlets and outlets can improve the hemodynamic performance and reduce the thrombosis risk in membrane oxygenators. These findings of this study can be used to guide the optimization design of membrane oxygenators for improving hemodynamic surroundings and reducing thrombosis risk.

Optimal Delay Time of CT Perfusion for Predicting Cerebral Parenchymal Hematoma After Intra-Arterial tPA Treatment.

Background and Purpose: Cerebral hemorrhage is a serious potential complication of stroke revascularization, especially in patients receiving intra-arterial tissue-type plasminogen activator (tPA) therapy. We investigated the optimal pre-intervention delay time (DT) of computed tomography perfusion (CTP) measurement to predict cerebral parenchymal hematoma (PH) in acute ischemic stroke (AIS) patients after intra-arterial tissue plasminogen activator (tPA) treatment. Methods: The study population consisted of a series of patients with AIS who received intra-arterial tPA treatment and had CTP and follow-up computed tomography/magnetic resonance imaging (CT/MRI) to identify hemorrhagic transformation. The association of increasing DT thresholds (>2, >4, >6, >8, and >10 s) with PH was examined using receiver operating characteristic (ROC) analysis and logistic regression. Results: Of 94 patients, 23 developed PH on follow-up imaging. Receiver operating characteristic analysis revealed that the greatest area under the curve for predicting PH occurred at DT > 4 s (area under the curve, 0.66). At this threshold of > 4 s, DT lesion volume ≥ 30.85 mL optimally predicted PH with 70% sensitivity and 59% specificity. DT > 4 s volume was independently predictive of PH in a multivariate logistic regression model (P < 0.05). Conclusions: DT > 4 s was the parameter most strongly associated with PH. The volume of moderate, not severe, hypo-perfusion on DT is more strongly associated and may allow better prediction of PH after intra-arterial tPA thrombolysis.

Dynamic Contrast-enhanced MRI in Renal Tumors: Common Subtype Differentiation using Pharmacokinetics.

Preoperative renal tumor subtype differentiation is important for radiology and urology in clinical practice. Pharmacokinetic data (K trans & V e, etc.) derived from dynamic contrast-enhanced MRI (DCE-MRI) have been used to investigate tumor vessel permeability. In this prospective study on DCE-MRI pharmacokinetic studies, we enrolled patients with five common renal tumor subtypes: clear cell renal cell carcinoma (ccRCC; n = 65), papillary renal cell carcinoma (pRCC; n = 12), chromophobic renal cell carcinoma (cRCC; n = 9), uroepithelial carcinoma (UEC; n = 14), and fat-poor angiomyolipoma (fpAML; n = 10). The results show that K trans of ccRCC, pRCC, cRCC, UEC and fpAML (0.459 ± 0.190 min-1, 0.206 ± 0.127 min-1, 0.311 ± 0.111 min-1, 0.235 ± 0.116 min-1, 0.511 ± 0.159 min-1, respectively) were different, but V e was not. K trans could distinguish ccRCC from non-ccRCC (pRCC & cRCC) with a sensitivity of 76.9% and a specificity of 71.4%, respectively, as well as to differentiate fpAML from non-ccRCC with a sensitivity of 100% and a specificity of 76.2%, respectively. Our findings suggest that DCE-MRI pharmacokinetics are promising for differential diagnosis of renal tumors, especially for RCC subtype characterization and differentiation between fpAML and non-ccRCC, which may facilitate the treatment of renal tumors.

CT Permeability Imaging Predicts Clinical Outcomes in Acute Ischemic Stroke Patients Treated with Intra-arterial Thrombolytic Therapy.

In this study, we determined whether a prediction of final infarct volume (FIV) and clinical outcomes in patients with an acute stroke is improved by using a contrast transfer coefficient (K trans) as a biomarker for blood-brain barrier (BBB) dysfunction. Here, consecutive patients admitted with signs and symptoms suggesting acute hemispheric stroke were included in this study. Ninety-eight participants with intra-arterial therapy were assessed (46 female). Definition of predicted FIV was performed using conventional perfusion CT (PCT-PIV) parameters alone and in combination with K trans (K trans-PIV). Multiple logistic regression analyses and linear regression modeling were conducted to determine independent predictors of the 90-day modified Rankin score (mRS) and FIV, respectively. We found that patients with favorable outcomes were younger and had lower National Institutes of Health Stroke Scale (NIHSS) score, smaller PCT-PIV, K trans-PIV, and smaller FIV (P < 0.001). K trans-PIV showed good correlation with FIV (P < 00.001, R 2 = 0.6997). In the regression analyses, K trans-PIV was the best predictor of clinical outcomes (P = 0.009, odds ratio (OR) = 1.960) and also the best predictor for FIV (F = 75.590, P < 0.0001). In conclusion, combining PCT and K trans maps derived from first-pass PCT can identify at-risk cerebral ischemic tissue more precisely than perfusion parameters alone. This provides improved accuracy in predicting FIV and clinical outcomes.

The Role of Dynamic Contrast-Enhanced MR in Evaluating Level III Collateral Circulation in a Rat Model of Acute Ischemic Stroke.

The study aimed to investigate the correlations between parameters of permeability magnetic resonance (MR) and the intensity of vasculature in the focal ischemic cortex of a rat model of middle cerebral artery occlusion. In the present study, sham operation or ischemic-reperfusion with tissue plasminogen activator (tPA) thrombolysis were performed in rats. Cranial MR scans and brain tissue samples were obtained from all animals. Brain slices were stained for immunohistological analyses with confocal fluorescence microscopy, and the intensities of microvessels and capillaries were calculated. Consistency between collateral circulation imaging classification and pathological vascular density was analyzed. We found that the K trans value and capillary intensity have the similar trends of declining and increasing, according to different time points, if compared with the sham operation group (P < 0.05). Permeability parameters have better correlations with capillary intensity, and K trans value had the best correlation at 4.5 h (kappa = 0.764, P < 0.001), while injection area under curve (IAUC) at 7 days (kappa = 0.725, P < 0.001). Susceptibility-weighted imaging (SWI) exhibited better correlation with microvessel intensity at both 3 days (kappa = 0.715, P < 0.001) and 7 days (kappa = 0.719, P < 0.001). In conclusion, the permeability parameters, such as IAUC and K trans map, can quantitatively assess capillary intensity, which may indicate angiogenesis categorized as level III collateral circulation after ischemic stroke.

DCE-MRI Perfusion and Permeability Parameters as predictors of tumor response to CCRT in Patients with locally advanced NSCLC.

In this prospective study, 36 patients with stage III non-small cell lung cancers (NSCLC), who underwent dynamic contrast-enhanced MRI (DCE-MRI) before concurrent chemo-radiotherapy (CCRT) were enrolled. Pharmacokinetic analysis was carried out after non-rigid motion registration. The perfusion parameters [including Blood Flow (BF), Blood Volume (BV), Mean Transit Time (MTT)] and permeability parameters [including endothelial transfer constant (Ktrans), reflux rate (Kep), fractional extravascular extracellular space volume (Ve), fractional plasma volume (Vp)] were calculated, and their relationship with tumor regression was evaluated. The value of these parameters on predicting responders were calculated by receiver operating characteristic (ROC) curve. Multivariate logistic regression analysis was conducted to find the independent variables. Tumor regression rate is negatively correlated with Ve and its standard variation Ve_SD and positively correlated with Ktrans and Kep. Significant differences between responders and non-responders existed in Ktrans, Kep, Ve, Ve_SD, MTT, BV_SD and MTT_SD (P < 0.05). ROC indicated that Ve < 0.24 gave the largest area under curve of 0.865 to predict responders. Multivariate logistic regression analysis also showed Ve was a significant predictor. Baseline perfusion and permeability parameters calculated from DCE-MRI were seen to be a viable tool for predicting the early treatment response after CCRT of NSCLC.

Dynamic Contrast-enhanced MR Imaging in Renal Cell Carcinoma: Reproducibility of Histogram Analysis on Pharmacokinetic Parameters.

Pharmacokinetic parameters derived from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) have been increasingly used to evaluate the permeability of tumor vessel. Histogram metrics are a recognized promising method of quantitative MR imaging that has been recently introduced in analysis of DCE-MRI pharmacokinetic parameters in oncology due to tumor heterogeneity. In this study, 21 patients with renal cell carcinoma (RCC) underwent paired DCE-MRI studies on a 3.0 T MR system. Extended Tofts model and population-based arterial input function were used to calculate kinetic parameters of RCC tumors. Mean value and histogram metrics (Mode, Skewness and Kurtosis) of each pharmacokinetic parameter were generated automatically using ImageJ software. Intra- and inter-observer reproducibility and scan-rescan reproducibility were evaluated using intra-class correlation coefficients (ICCs) and coefficient of variation (CoV). Our results demonstrated that the histogram method (Mode, Skewness and Kurtosis) was not superior to the conventional Mean value method in reproducibility evaluation on DCE-MRI pharmacokinetic parameters (K( trans) &Ve) in renal cell carcinoma, especially for Skewness and Kurtosis which showed lower intra-, inter-observer and scan-rescan reproducibility than Mean value. Our findings suggest that additional studies are necessary before wide incorporation of histogram metrics in quantitative analysis of DCE-MRI pharmacokinetic parameters.

Mismatch of Low Perfusion and High Permeability Predicts Hemorrhagic Transformation Region in Acute Ischemic Stroke Patients Treated with Intra-arterial Thrombolysis.

This study sought to determine whether the permeability related parameter K(trans), derived from computed tomography perfusion (CTP) imaging, can predict hemorrhagic transformation (HT) in patients with acute ischemic stroke who receive intra-arterial thrombolysis. Data from patients meeting the criterion were examined. CTP was performed and K(trans) maps were used to assess the permeability values in HT and non-HT regions. A receiver operating characteristic (ROC) curve was calculated, showing the sensitivity and specificity of K(trans) for predicting HT risk. Composite images were produced to illustrate the spatial correlations among perfusion, permeability changes and HT. This study examined 41 patients. Twenty-six patients had hemorrhagic infarction and 15 had parenchymal hemorrhage. The mean K(trans) value in HT regions was significantly lower than that in the non-HT regions (0.26 ± 0.21/min vs. 0.78 ± 0.64/min; P < 0.001). The ROC curve analysis identified an optimal cutoff value of 0.334/min for K(trans) to predict HT risk. Composite images suggested ischemic regions with low permeability, or the mismatch area of low perfusion and high permeability, more likely have HT. HT regions after intra-arterial thrombolysis had lower permeability values on K(trans) maps. The mismatch area of lower perfusion and higher permeability are more likely to develop HT.

Reproducibility of Dynamic Contrast-Enhanced MRI in Renal Cell Carcinoma: A Prospective Analysis on Intra- and Interobserver and Scan-Rescan Performance of Pharmacokinetic Parameters.

The objective of this study was to investigate the intra- and interobserver as well as scan-rescan reproducibility of quantitative parameters of renal cell carcinomas (RCCs) with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). A total of 21 patients with clear cell RCCs (17 men, 4 woman; age 37-69 years, mean age 54.6 years, mean size, 5.0 ±â€Š2.2 cm) were prospectively recruited from September 2012 to November 2012. Patients underwent paired DCE-MRI studies on a 3.0 T MR system with an interval of 48 to 72 hours. The extended-Tofts model and population-based arterial input function were used to calculate kinetic parameters. Three observers defined the 2-dimensional whole-tumor region of interest at the slice with the maximum diameter of the RCC. Intraobserver and scan-rescan differences were assessed using paired t tests, whereas interobserver differences using two-way analysis of variance. Intra- and interobserver reproducibility and scan-rescan reproducibility were evaluated using within-subject coefficient of variation (wCoV) and intraclass correlation coefficient (ICC). There were no significant intra-, interobserver, or scan-rescan differences in parameters (all P > 0.05). All ICCs for intra- and interobserver agreements were >0.75 (P < 0.05), whereas the scan-rescan agreement was moderate to good; V(e) (0.764, 95% confidence interval [CI]: 0.378-0.925) and K(ep) (0.906, 95% CI: 0.710-0.972) had higher ICC than K(trans) (0.686; 95% CI: 0.212-0.898) and V(p) (0.657; 95% CI: 0.164-0.888). In intra- and interobserver variability analyses, all parameters except V(p) had low wCoV values. K(trans) and V(e) had slightly lower intraobserver wCoV (1.2% and 0.9%) compared with K(ep) (3.7%), whereas all 3 of these parameters had similar interobserver wCoV values (2.5%, 3.1%, and 2.9%, respectively). Regarding scan-rescan variability, K(trans) and K(ep) showed slightly higher variation (15.6% and 15.4%) than V(e) (10.1%). V(p) had the largest wCoV in all variability analyses (all >30%). DCE-MRI demonstrated good intra- and interobserver reproducibility and moderate to good scan-rescan performance in the assessment of RCC using K(trans), K(ep), and V(e) as parameters under noncontinuous scanning mode. V(p) showed poor reproducibility, and thus may not be suitable for this scanning protocol.

Comparison of contrast-enhanced isotropic 3D-GRE-T1WI sequence versus conventional non-isotropic sequence on preoperative staging of cervical cancer.

PURPOSE: To compare contrast-enhanced isotropic 3D-GRE-T1WI sequence vs. conventional non-isotropic sequence in terms of image quality, estimated signal-to-noise ratio (eSNR), relative tumor contrast and performance of cervical cancer staging. METHODS: This retrospective study was approved by the institutional review board, and informed consent was waived. Seventy-one patients (47 ± 9.4 years), with pathologically-confirmed cervical cancer underwent axial contrast-enhanced 1 mm3 isotropic 3D-GRE-T1WI sequence (herein referred to Isotropy), and 3-mm-thick non-isotropic sagittal and coronal sequences. Image quality score, eSNR and relative contrast between tumor to myometrium, gluteal muscle, and fat respectively, were compared between 3-mm-thick reconstructed images from Isotropy and directly scanned non-isotropic images by paired t-test. Difference in tumor staging obtained from Isotropy and combined Three-planes including reconstructed axial images, directly scanned sagittal and coronal sequence were compared by McNemar test. RESULTS: Both sequences showed similar image quality. Reconstructed images demonstrated higher eSNR, equal or lower relative tumor contrast compared with non-isotropic images. Compared with performing diagnosis on Three-planes, both reviewers showed higher accuracy when diagnosing vaginal invasion on Isotropy (p = 0.039 and 0.003, respectively). CONCLUSION: Compared with non-isotropic sequence, 3.0T MR isotropic 3D-GRE-T1WI sequence exhibited better eSNR, providing more reliable clinical information for preoperative staging of cervical cancer.

Using standard first-pass perfusion computed tomographic data to evaluate collateral flow in acute ischemic stroke.

BACKGROUND AND PURPOSE: The study aims to determine whether volume transfer constant (K(trans)) maps calculated from first-pass perfusion computed tomographic data are a biomarker of cerebral collateral circulation and predict the clinical outcome in acute ischemic stroke caused by proximal arterial occlusion. METHODS: Consecutive patients with acute occlusion of the middle cerebral artery who received endovascular treatment were enrolled. Digital subtraction angiography, computed tomographic angiography with maximum intensity projection, and K(trans) maps were used to assess their collateral circulation. Agreement between different methods was evaluated using the χ(2) tests. The correlations of various radiological and clinical outcomes with the collateral flow score, as determined from K(trans) maps, were calculated. RESULTS: Seventy-five patients were included, comprising 39 women and 36 men, with a mean age of 65.3±14.6 years. Collateral flow score on K(trans) maps had the highest correlation with digital subtraction angiography (κ=0.8101; P=0.9796). Twenty-five patients had poor collateral circulation on K(trans) maps, 25 had intermediate collateral flow, 20 had good collateral flow, and 5 had excellent collateral flow. Better collateral circulation was associated with better clinical outcome (P<0.0001). CONCLUSIONS: K(trans) maps extracted from standard first-pass perfusion computed tomography are correlated with collateral circulation status after acute proximal arterial occlusion and predictive of outcome.

Assessment of esophageal carcinoma undergoing concurrent chemoradiotherapy with quantitative dynamic contrast-enhanced magnetic resonance imaging.

The aim of the present study was to investigate whether quantitative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can predict an early response in primary esophageal carcinoma patients undergoing concurrent chemoradiotherapy. A total of 25 patients with who were pathologically confirmed stage II-III esophageal carcinoma underwent quantitative DCE-MRI prior to chemoradiotherapy, and at 3 weeks post-treatment, the quantitative parameters [Ktrans (volume transfer constant; the rate at which contrast agent distributes from the plasma to the EES), Kep (rate contrast; the rate at which the contrast agent that has diffused to the EES returns to the plasma) and Ve (the contrast agent percentage in the space of the extracellular fluid)] were analyzed respectively. The 25 cases were categorized as a complete response (CR) or a partial response (PR). An independent samples Mann-Whitney U test was used to compare the quantitative parameters between CR and PR. A receiver operating characteristic curve (ROC) was used to determine the best predictor. In total, 17 patients were in the CR group and 8 patients were in the PR group. Pretreatment Ktrans, Kep and Ve values were 0.54±0.17/min, 1.12±0.46/min and 0.37±0.14, respectively, in the CR group, and 0.40±0.21/min, 1.07±0.37/min and 0.40±0.22, respectively, in the PR group. There was a significant difference between the two groups for Ktrans, but there were no significant differences between the two groups for Kep and Ve. The Ktrans, Kep and Ve values at 3 weeks post-treatment were 0.33±0.11/min, 0.86±0.31/min and 0.66±0.05, respectively, in the CR group, and 0.62±0.22/min, 1.19±0.39/min and 0.45±0.19, respectively, in the PR group. The corresponding U values were -3.319, -1.719 and -2.628, respectively, and the P-values were 0.006, 0.119 and 0.021, respectively. The areas under the ROC curve of Ktrans prior to chemoradiotherapy, and of Ktrans and Kep at 3 weeks post-treatment were 0.648, 0.741 and 0.796, respectively. In conclusion, DCE-MRI can predict an early response in primary esophageal carcinoma following 3 weeks of concurrent chemoradiotherapy. Ktrans prior to chemoradiotherapy, and Ktrans and Kep at 3 weeks post-treatment are sensitive prediction parameters.

Permeability Imaging as a Biomarker of Leptomeningeal Collateral Flow in Patients with Intracranial Arterial Stenosis.

Different methods of angiography are of great clinical utility; however, it still remains unstandardized as which method would be suitable to determine cerebral collateral circulation. Here we compared digital subtraction angiography (DSA), computer tomography angiography (CTA) and dynamic contrast-enhanced T1-weighted imaging magnetic resonance imaging (MRI) findings in seven patients with severe intracranial arterial stenosis, and determine whether volume transfer constant (K(trans)) maps of permeability imaging could be used as the biomarkers of cerebral collateral circulation. We retrospectively reviewed seven adult patients with severe intracranial arterial stenosis or occlusion with a complete parenchymal and vascular imaging work-up. DSA, CTA source imaging (CTA-SI), arterial spin labeling (ASL), and K(trans) maps were used to assess their collateral flow. Cohen's Kappa coefficient was calculated to test the consistency of their collateral scores. A reasonable agreement was found between DSA and K(trans) maps (Kappa = 0.502, P < 0.001) when all 15 regional vascular sites were included, and a better agreement found after exclusion of perforating artery territories (N = 10 sites, Kappa = 0.766, P < 0.001). The agreement between CTA-SI and DSA was moderate on all 15 sites (Kappa = 0.413, P < 0.001) and 10 sites (Kappa = 0.329, P < 0.001). The agreement between ASL and DSA was least favorable, no matter for all 15 sites (Kappa = 0.270, P < 0.001) or 10 sites (Kappa = 0.205, P = 0.002). K(trans) maps are useful and promising for leptomeningeal collateral assessment, when compared to CTA-SI or ASL. Further studies are requited for verify its validity in a large registry of patients.