Thrombus Volume Research Articles

Thrombus attenuation predicts natural history of hypo-attenuating leaflet thickening after transcatheter aortic valve replacement

Abstract Background Hypo-attenuating leaflet thickening (HALT) after transcatheter aortic valve replacement (TAVR) occurs in up to 25% of patients and is characterized by diverse temporal dynamics. Several studies investigated the natural history of HALT in transcatheter and surgical cohorts, but little is known about the imaging features of persistent thrombus. Purpose To examine the association of quantitative HALT volume and attenuation from computed tomography angiography (CTA) with its natural history. Methods We prospectively examined patients with HALT present on CTA at 30 days after TAVR and who underwent a follow-up CTA at one year. Hypoattenuation affecting motion (HAM) was defined as the presence of HALT with at least moderately reduced (>50%) leaflet motion. HALT was quantified by segmenting the inner volume of the bioprosthetic frame at the level of the leaflets and extracting voxels between a threshold of -200 to 200 HU. Thrombus volume, mean thrombus attenuation and thrombus heterogeneity measured with standard deviation of attenuation were automatically calculated (Figure 1). Results A total of 37 patients (70% men, 71±7 years old) undergoing TAVR with balloon-expandable SAPIEN3 (86%) and self-expanding EVOLUT (14%) valves were evaluated. Hypoattenuation affecting motion (HAM) at 30 days after TAVR was present in 29 (74%) patients. Patients with HAM had higher thrombus volume than patients without reduced leaflet motion (0.40cm3 [IQR 0.16 – 0.61cm3] vs 0.14 [IQR 0.06 – 0.19 cm3], p=0.009) but comparable mean attenuation values (145HU [IQR 141-151HU] vs 123 [IQR 114 – 141HU], p=0.079). Only 3 patients were switched to oral anticoagulation following HALT detection. At one year, HALT resolution was observed in 18/37 (48%) and HAM resolution in 19/29 (65%). No difference in quantitative thrombus features was noted between patients with persistent and resolved HALT. Notably, patients with persistent HAM had higher mean thrombus attenuation (141HU [IQR 123-156HU] vs 123HU [IQR 110 – 138 HU), p=0.045; Figure 2) and thrombus heterogeneity (58HU [IQR 51-63HU] vs 48HU [IQR 41- 54HU], p=0.021) than resolved HAM. Mean thrombus attenuation (area under the curve of 0.732, p=0.044) and thrombus heterogeneity (area under the curve of 0.763, p=0.022) were predictive of HAM resolution at one year. The optimal cutoff values as determined by Youden index was 140HU for mean attenuation and 52HU for heterogeneity. There was an increase in the mean transvalvular gradients between measurements at 30 days and one year in patients with persistent HAM as compared to patients with HAM resolution (Δ3mmHg [IQR -3 – 11mmHg] vs Δ-1mmHg [IQR -4 – 0mmHg], p=0.049). The volume of thrombus at one year was associated with the magnitude of change in transvalvular gradients (β = 10.3, 95% CI 1.6- 19.0, p=0.025). Conclusion Quantitative evaluation of HALT by CTA may aid the identification of patients at risk of persistent thrombus.

Mapping 18F-FDG PET uptake in the aortic wall and thrombus

Abstract Background Positron Emission Tomography (PET) uptake allows for the assessment of molecular activity, being 18F-FDG uptake indicative of glucose metabolism. PET uptake is commonly quantified manually by drawing regions of interest, which is subjective, poorly-reproducible and may miss relevant information. Purpose To develop and test an image analysis method to quantify and map 18F-FDG uptake on the whole aortic wall and thrombus. Methods PET-MRI was acquired in patients with thoracic or abdominal aortic aneurysms. The aorta was semi-automatically segmented in the MR angiography using 3DSlicer, generating a surface mesh that was expanded by 3 mm inward and outward. PET uptake was interpolated over this volume with a uniform spatial resolution of 1 mm. By means of 9 reference points, the aortic wall was discretized into 52 (thoracic) or 80 (thoraco-abdominal) standardized regions (i.e. wall patches). For each aortic patch and for the whole thrombus volume, the target to background Ratio (TBR) was calculated by dividing the uptake by a reference uptake in the left atrium. Two observers segmented the aorta and thrombus, located the anatomical reference points and quantified TBR. Inter-observer agreement for segmentation and aortic wall discretization was evaluated in terms of the 95% Hausdorff Distance (HD) and Dice Score Coefficient (DSC), while both median and 95% TBR in each region were tested via intra-class correlation coefficient (absolute value, single measure). Results Data from 20 patients with thoracic or abdominal aneurysms were analysed, 10 of them presented thrombus. The reproducibility of the segmentation of the aorta (median HD 3.16 IQR [2.42 - 3.94] mm, DSC 0.90 [0.89 - 0.92]) and of the thrombus (HD 4.87 [3.51 - 8.45] mm, DSC 0.85 [0.80 - 0.87]) were excellent. The inter-observer agreement in the localization of reference points was good (HD 5.10 [3.29 - 8.73] mm), resulting in excellent overlapping of the standardized aortic wall patches (HD 3.80 [2.44 - 5.08] mm). Inter-observer agreement of median and 95% TBR in each aortic patch were excellent (ICC of 0.90 and 0.93, respectively, Figure 1), with minimal bias (Figure 2). Similarly, excellent interobserver reproducibility was observed for median and 95% TBR in the thrombus (ICC of 0.97 and 0.96, respectively, Figure 2). Conclusions A robust and reproducible image analysis method to map PET uptake along the aortic wall was developed, extending the possibilities to study aortic diseases molecular activity and its association with local aortic characteristics.

Reduction of thrombus burden by cangrelor in ticagrelor-loaded st-elevation myocardial infarction patients with high residual platelet reactivity: the imaging sub-study of the ERMIT randomized trial

Abstract Background Residual high platelet reactivity (HPR) at the time of primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI) is associated with higher residual thrombus burden and the subsequent suboptimal reperfusion. Purpose We sought to determine the impact of intravenous Cangrelor on the residual post-PCI thrombus burden in patients with HPR admitted for primary PCI in a prespecified intracoronary optical coherence tomography (OCT) sub-study of the ERMIT randomized trial. Methods In the ERMIT trial patients pre-treated with ticagrelor and aspirin with residual HPR (baseline platelet reactivity unit >208) were randomly assigned in a 1:1 ratio to receive cangrelor on top of standard therapy or standard therapy alone prior to PCI. The primary endpoint of the sub-study was the relative thrombus volume quantified on OCT. Other OCT quantified parameters were predefined as secondary endpoints. Results After screening of 128 patients, a total of 60 patients with HPR were enrolled and randomized. The OCT sub-study included 53 patients, 29 in the cangrelor and 24 in the control group. As reported in the table, baseline characteristics were similar between the groups. The post-PCI PRU was dramatically lower in the cangrelor as compared to the standard group (p<0.001). The primary endpoint was 4.5% [3.4;7.2] versus 6.9% [5.2;8.5], (p=0.03) in the cangrelor and control groups respectively. All other imaging parameters confirmed the significantly lower thrombus burden in patients receiving cangrelor (Table). Conclusion The imaging sub-study of the randomized ERMIT trial shows that cangrelor use is associated with a more effective platelet inhibition and lower post-PCI residual thrombus burden in ticagrelor-loaded STEMI patients with residual HPR. The clinical implications of such finding warrant larger size trials.Table

Evolution of Left Ventricular Thrombus on Serial Cardiovascular Magnetic Resonance Imaging.

Current management of left ventricular (LV) thrombus relies on limited, non-contemporary, echocardiography-based studies. Data on LV thrombus evolution and the associated embolic risk are scarce. We aimed to describe the evolution of LV thrombus on serial cardiovascular magnetic resonance imaging (CMR) - the current reference standard for the detection of LV thrombus, and identify correlates of no resolution and the embolic risk associated with resolution status. We conducted a retrospective cohort study of 107 consecutive patients with LV thrombus who had 213 serial CMRs at a median of 255 days after the index CMR. Of these, 97.2% were anticoagulated. At 3 months after detection by CMR, 75% (47/63) had no resolution of LV thrombus; at 6 months, 53% (35/66) had no resolution; and at 12 months, 37% (23/63) had no resolution. Correlates of no resolution at 6 months included a history of myocardial infarction, LV aneurysm, ischemic etiology of cardiomyopathy, and larger thrombus volume. Recurrence of LV thrombus was rare at 5.3%. On survival analysis using the landmark analysis method, embolic events often occurred beyond 6 months, more frequently in patients with unresolved LV thrombus. Our findings challenge previous literature by demonstrating a lower rate of resolution of LV thrombus and substantial embolic risk beyond 6 months associated with unresolved LV thrombus on serial CMR. Our findings advocate for extended anticoagulation, particularly in patients with markers associated with no resolution. These findings have important implications for clinical practice and research into managing patients with LV thrombus.

Imaging of experimental venous thrombus by means of Doppler and CEUS techniques in dogs.

Venous thrombosis has been widely studied in humans, but not in dogs. This study was designed to evaluate a venous thrombus in dogs, from creation to solution, by means of various ultrasonographic techniques. Nine healthy Beagle dogs were included in the study. The venous thrombus was formatted by puncturing the lumen of the external jugular veins and then, the veins were examined with B-mode, color Doppler, pulsed-wave Doppler, and contrast-enhanced ultrasound (CEUS) techniques, at regular intervals, within 210-270min after venipuncture. Haemodynamic parameters were calculated at two different locations, before and after the site of the thrombus formation. The existence of a thrombus was confirmed by CEUS technique. Thrombus volume and echogenicity were evaluated. The results showed that the visualization of the venous thrombus by color Doppler modality was not feasible in some veins. The blood volume was the parameter that could more precisely indicate the presence or absence of a thrombus. In cases where thrombus volume was less than 0.001 cm3, it was impossible to detect its presence using haemodynamic parameters. The CEUS imaging depicted accurately the size and shape of an anechoic venous thrombus, even when its volume was 0.001cm3.

Novel use of a stent retriever as a distal filler protection device for prevention of secondary embolization.

Distal embolus due to mechanical thrombectomy is a frequent complication and directly results in a poor prognosis. Therefore, it is important to decrease distal embolus as much as possible in mechanical thrombectomy. EmboTrap III may be useful as a filter to prevent distal embolus in patients with a large volume of thrombus. Here, we report the results of one suggestive case and we also provide experimental data from a vessel model. The patient was a 78-year-old female who was admitted to hospital as an emergency case with chief complaints including dysarthria and left hemiplegia, including facial paralysis. She was diagnosed as large vessel occlusion-acute ischemic stroke with right tandem lesions by workup and underwent mechanical thrombectomy. A large volume of secondary thrombus due to flow stasis was assumed based around the occlusion site, and worsening of neurological symptoms was a concern due to distal embolus caused by recanalization of the cervical internal carotid artery. The SEIMLESS technique was performed under distal protection using EmboTrap III. There was no distal embolus or deterioration of neurological symptoms, and a good prognosis was achieved. This outcome suggests that PTA under distal protection using EmboTrap III may be useful for prevention of distal embolus.

Abdominal aneurysm sac thrombus CT density and volume after EVAR: which association with underlying endoleak?

BackgroundOur aim was to analyse abdominal aneurysm sac thrombus density and volume on computed tomography (CT) after endovascular aneurysm repair (EVAR).MethodsPatients who underwent EVAR between January 2005 and December 2010 and had at least four follow-up CT exams available over the first five years of follow-up were included in this retrospective single-centre study. Thrombus density and aneurysm sac volume were calculated on unenhanced CT scans. Linear mixed models were used for data analysis.ResultsOut of 82 patients, 44 (54%) had an endoleak on post-EVAR contrast-enhanced CT. Thrombus density significantly increased over time in both the endoleak and non-endoleak groups, with a slope of 0.159 UH/month (95% confidence interval [CI] 0.115–0.202), p < 0.0001) and 0.052 UH/month (95% CI 0.002–0.102, p = 0.041). In patients without endoleak, a significant decrease in aneurysm sac volume was identified over time (slope -0.891 cc/month, 95% CI -1.200 to -0.581); p < 0.001) compared to patients with endoleak (slope 0.284 cc/month, 95% CI -0.031 to 0.523, p = 0.082). The association between thrombus density and aneurysm sac volume was positive in the endoleak group (slope 1.543 UH/cc, 95% CI 0.948–2.138, p < 0.001) and negative in the non-endoleak group (slope -1.450 UH/cc, 95% CI -2.326 to -0.574, p = 0.001).ConclusionWe observed a progressive increase in thrombus density of the aneurysm sac after EVAR in patients with and without endoleak, more pronounced in patients with endoleak. The association between aneurysm volume and thrombus density was positive in patients with and negative in those without endoleak.Relevance statementA progressive increase in thrombus density and volume of abdominal aortic aneurysm sac on unenhanced CT might suggest underlying endoleak lately after EVAR.Key PointsThrombus density of the aneurysm sac after EVAR increased over time.Progressive increase in thrombus density was significantly associated to the underlying endoleak.The association between aneurysm volume and thrombus density was positive in patients with and negative in those without endoleak.Graphical

The impact of aneurysm volume on midterm Post-EVAR outcomes

Aim: We examined the impact of preoperative three-dimensional aortic volume on outcomes following Endovascular Aortic Repair (EVAR). Material and Methods: A total of 146 patients who underwent elective EVAR at our hospital between January 2018 and January 2023, and who had preoperative and postoperative multislice Computed Tomographic Angiography (CTA), were included in the study. The effects of aneurysm sac volumetric measurements on post-EVAR endoleak, reintervention, and late mortality were evaluated. Since there is no definite cut-off value for aneurysm volume and EVAR results in the literature, we compared patients with aneurysm volumes above and below 231.7 cm³ obtained by roc analysis. Results: During the follow-up period, the rate of secondary intervention was higher if the preoperative aneurysm volume was greater than 231.7 cm³ (p=0.001) or if the preoperative thrombus volume was greater than 206.1 cm³ (p=0.002). There was no notable difference in terms of endoleak (p=0.5) and during follow-up mortality rate (p=0.8) between patients with sac volumes above and below 231.7 cm³. After EVAR, when morphological changes were examined, it was noted that there was a dilatation of the neck (preoperative 23±4 mm and postoperative 26±4 mm) (p&lt;0.001) and a decrease in neck (infrarenal) angulation (preoperative 39 degrees and postoperative 31.5 degrees) (p&lt;0.001). Conclusion: This study demonstrates that aneurysms with high volume are prone to secondary intervention. However, it is not correlated with early or midterm mortality and outcomes. Volumetric analysis of the aneurysms preoperatively may be an indicator of surveillance protocols and treatment choices. Lifetime follow-up and volumetric analysis of aneurysms seem crucial for effective and reliable surveillance.

The Role of Platelets and Aneurysm Thrombus in the EVAR Post Implantation Syndrome

ObjectivePost implantation syndrome (PIS) is a well-defined entity with unclear etiology, complicating a number of patients with AAAs treated with EVAR. The aim of this study was to assess the platelets’ role and the influence of aneurysmal sac thrombus volumes in the development of PIS. DesignA retrospective analysis of prospectively collected data was performed and 76 patients that were treated by EVAR (2011-2013) were studied. Aneurysms with endoleak were not included in the study. Based on the criteria for SIRS (Systemic Inflammatory Response Syndrome), 17 patients (22%) developed PIS (which is considered a SIRS analogue), while 59 (78%) did not. MethodsThe two groups were compared in relation to the following parameters: baseline platelet count (PLT), decrease of platelet count (PLT drop), volume of the arterial flow before the procedure (V Flow), volume of thrombus of the aneurysm (V thromb), ratio of thrombus volume to aneurysm sac volume (V ratio) and the volume of new formed thrombus (V new). Volume flow measurements were calculated by Osirix ™ software preoperatively and in the 1st month postoperatively. Parametric and non-parametric techniques (unpaired t-test, Mann-Whitney U test) were used accordingly. ResultsBaseline platelets absolute count was greater in the PIS group (239000 ± 17000) vs. the non-PIS group (194000 ± 6900, p=0.004), and the PLT drop was larger in the PIS group (74000 ± 15600 vs. 45000 ± 5300, p=0.019). No difference was found regarding the aneurysm volumes (Vflow, Vthromb, Vratio, Vnew) between the two groups. ConclusionPlatelets, in terms of their absolute baseline count and their decrease after the procedure, seem to be an important factor in developing PIS after EVAR. Further, more tailored studies are needed to elucidate the role of platelets and flow/thrombus volumes in the development of PIS.

Ferumoxytol-enhanced MRI assessment of venous Thrombus resolution and macrophage content in a murine deep vein thrombosis model

BackgroundImaging evaluation of acute deep vein thrombosis (DVT) or post-thrombotic syndrome (PTS) in animal or clinical models is limited to anatomical assessment of the location and extent of thrombi. We hypothesize that Fe-MRI, used to evaluate macrophage content in other inflammatory diseases, can be useful to evaluate the thromboinflammatory features after DVT over time. MethodsNineteen wild-type CD-1 mice underwent surgical IVC ligation to induce DVT. Mice received either saline or 5 mg/kg of 14E11, a Factor XI inhibitor, before the procedure. Fe-MRI was performed on days 6–7 after ligation to evaluate thrombus volume, perfusion, and macrophage content via T2-weighted images. Mice were euthanized at days 3–15 after surgery. The thrombi and adjacent vein walls were excised, weighed, formalin-fixed, and paraffin-embedded for immunohistological analysis. Specimens were stained with specific antibodies to evaluate macrophage content, collagen deposition, neovascularization, and recanalization. Significance was determined using the Mann-Whitney U or Student's t-test. ResultsAfter IVC-ligation in control mice, thrombus weights decreased by 59 % from day 3 to 15. Thrombus volumes peaked on day 5 before decreasing by 85 % by day 13. FXI inhibition led to reduced macrophage content in both thrombi (p = .008) and vein walls (p = .01), decreased thrombus volume (p = .03), and decreased thrombus mass (p = .01) compared to control mice. CCR2+ staining corroborated these findings, showing significantly reduced macrophage presence in the thrombi (p = .002) and vein wall (p = .002). ConclusionsFe-MRI T2 relaxation times can be used to characterize and quantify post-thrombotic changes of perfusion, macrophage content, and thrombus volume over time in a surgical mouse model of venous thrombosis. This approach could lead to better quantification of in vivo inflammation correlating monocyte and macrophage content within resolving thrombi and veins and may serve as a useful tool for research and clinically in the evaluation of the post-thrombotic environment.

Evaluation of acute thrombus regression effect of edoxaban for deep vein thrombosis in patients with cancer: a single-center prospective observational study.

Although there are reports on the recurrence prevention in the chronic phase using direct oral anticoagulants (DOACs) for deep vein thrombosis (DVT) in patients with cancer, acute thrombus regression effect using DOACs has not been assessed. This study aimed to assess the thrombus regression effect of initial treatment using edoxaban for acute lower-extremity DVT in patients with active cancer. In this observational study, among the inpatients with cancer and lower-extremity DVT who underwent initial treatment with edoxaban at our hospital from November 2019 to December 2021, 34 consenting patients were recruited in this study. The quantitative ultrasound thrombus (QUT) score of thrombus volume was calculated at baseline (before administration) and 7-14 days after the start of edoxaban administration, using lower-extremity venous ultrasound to evaluate changes in thrombus volume. The primary and secondary endpoints were the acute thrombus regression effect of edoxaban and the impact of patients' clinical frailty on the thrombus regression effect, respectively. Anticoagulant therapy with edoxaban significantly reduced QUT score (p < 0.001). In addition, regardless of the Clinical Frailty Scale scores, QUT score decreased significantly. Initial treatment with edoxaban was effective for lower-extremity DVT in patients with cancer. In addition, the effect was the same independent of the degree of frailty.

The Value of Aortic Volume and Intraluminal Thrombus Quantification for Predicting Aortic Events after Endovascular Thoracic Aneurysm Repair.

Objectives: To assess the ability of the aortic aneurysm volume (AAV), aneurysmal lumen volume (ALV), and aneurysmal thrombus volume (ATV) to predict the need for aortic reintervention when using the maximal aortic diameter as a reference. Methods: This monocentric retrospective study included 31 consecutive patients who underwent successful thoracic endovascular aortic repair (TEVAR) to treat an atheromatous thoracic aortic aneurysm. All patients underwent clinical and computed tomography angiography (CTA) for 3 years after TEVAR. The patients were categorized into group 0 if no aortic reintervention was required during the follow-up period and categorized into group 1 if they experienced a type I or III endoleak or aneurysm diameter increase requiring intervention. The maximum aneurysm sac diameter and the AAV, ALV, and ATV were calculated using CTA images obtained preoperatively (T0) and at 6-12 months (T1), 24 months (T2), and 36 months (T3) postoperatively, and their changes over time were analyzed. Correlations between diameter and changes in AAV, ALV, and ATV were assessed, and the association between diameter and volume changes and reintervetion was examined. The cutoff values for predicting the need for reintervention was determined using a receiver operating characteristic (ROC) curve. The accuracy of volume change versus diameter change for predicting the need for reintervention was analyzed. Results: There were no significant differences in terms of the mean aneurysm diameter or AAV, ALV or ATV between the groups at preoperative CTA or after one year of follow-up imaging. The mean ATV was higher in group 1 than in group 0 at 2 years (187.6 ± 86.3 mL vs. 114.7 ± 64.7 mL; p = 0.057) and after 3 years (195.0 ± 86.7 mL vs. 82.1 ± 39.9 mL; p = 0.013). The maximal diameter was greater in group 1 than in group 0 at 3 years (67.3 ± 9.5 mm vs. 55.3 ± 12.6 mm; p = 0.044). The rate of AAV change between T0 and T1 was significantly higher in group 1 (7 ± 4.5%) than in group 0 (-6 ± 6.8%; p < 0.001). The rate of ATV change between T1-T3 was significantly higher in group 1 than in group 0 (34 ± 40.9% vs. -13 ± 14.4% (p = 0.041)); similar results were observed for the rate of ATV change between T2 and T3 (27 ± 50.1% for group 1 vs. -8 ± 49.5% in group 0 (p < 0.001)). According to our multivariate analysis, the annual growth rate for AAV between T0 and T1 was the only independent factor that was significantly associated with aortic reintervention (area under the curve (AUC) = 0.84, OR = 1.57, p = 0.025; optimal cutoff +0.4%). An increase in the annual growth rate of the ATV between T0 and T3 was independently associated with the need for aortic reintervention (area under the curve (AUC) = 0.90, OR = 1.11, p = 0.0347; optimal cutoff +10.1%). Conclusions: Aortic volume analysis can predict the need for aortic reintervention more accurately and earlier than maximal aortic diameter.

Use of Artificial Intelligence With Deep Learning Approaches for the Follow-up of Infrarenal Endovascular Aortic Repair.

Endoleaks represent one of the main complications after endovascular aortic repair (EVAR) and can lead to increased re-intervention rates and secondary rupture. Serial lifelong surveillance is required and traditionally involves cross-sectional imaging with manual axial measurements. Artificial intelligence (AI)-based imaging analysis has been developed and may provide a more precise and faster assessment. This study aims to evaluate the ability of an AI-based software to assess post-EVAR morphological changes over time, detect endoleaks, and associate them with EVAR-related adverse events. Patients who underwent EVAR at a tertiary hospital from January 2017 to March 2020 with at least 2 follow-up computed tomography angiography (CTA) were analyzed using PRAEVAorta 2 (Nurea). The software was compared to the ground truth provided by human experts using Sensitivity (Se), Specificity (Sp), Negative Predictive Value (NPV), and Positive Predictive Value (PPV). Endovascular aortic repair-related adverse events were defined as aneurysm-related death, rupture, endoleak, limb occlusion, and EVAR-related re-interventions. Fifty-six patients were included with a median imaging follow-up of 27 months (interquartile range [IQR]: 20-40). There were no significant differences overtime in the evolution of maximum aneurysm diameters (55.62 mm [IQR: 52.33-59.25] vs 54.34 mm [IQR: 46.13-59.47]; p=0.2162) or volumes (130.4 cm3 [IQR: 113.8-171.7] vs 125.4 cm3 [IQR: 96.3-169.1]; p=0.1131) despite a -13.47% decrease in the volume of thrombus (p=0.0216). PRAEVAorta achieved a Se of 89.47% (95% confidence interval [CI]: 80.58 to 94.57), a Sp of 91.25% (95% CI: 83.02 to 95.70), a PPV of 90.67% (95% CI: 81.97 to 95.41), and an NPV of 90.12% (95% CI: 81.70 to 94.91) in detecting endoleaks. Endovascular aortic repair-related adverse events were associated with global volume modifications with an area under the curve (AUC) of 0.7806 vs 0.7277 for maximum diameter. The same trend was observed for endoleaks (AUC of 0.7086 vs 0.6711). The AI-based software PRAEVAorta enabled a detailed anatomic characterization of aortic remodeling post-EVAR and showed its potential interest for automatic detection of endoleaks during follow-up. The association of aortic aneurysmal volume with EVAR-related adverse events and endoleaks was more robust compared with maximum diameter. The integration of PRAEVAorta AI software into clinical practice promises a transformative shift in post-EVAR surveillance. By offering precise and rapid detection of endoleaks and comprehensive anatomic assessments, clinicians can expect enhanced diagnostic accuracy and streamlined patient management. This innovation reduces reliance on manual measurements, potentially reducing interpretation errors and shortening evaluation times. Ultimately, PRAEVAorta's capabilities hold the potential to optimize patient care, leading to more timely interventions and improved outcomes in endovascular aortic repair.

Abstract 2093: Quantitative Assessment Of Venous Thrombus Resolution And Macrophage Content In Mice Using Ferumoxytol-enhanced Magnetic Resonance Imaging

Objective: The objective of this study is to explore the feasibility of ferumoxytol-enhanced magnetic resonance imaging (Fe-MRI) for noninvasive assessment of deep venous thrombus (DVT) resolution and macrophage content in resolving thrombi in a surgical murine model of inferior vena cava (IVC) ligation. Background: Imaging evaluation of acute DVT or post-thrombotic syndrome (PTS) in animal or clinical models is limited to assessment of anatomy. We hypothesize that Fe-MRI, used to evaluate macrophage content in other inflammatory diseases, can be useful to evaluate thromboinflammatory features after DVT. Methods: Nineteen wild-type CD-1 mice underwent surgical IVC ligation to induce DVT. Mice received either saline or administered 5 mg/kg of 14E11, a Factor XI inhibitor, before the procedure. Fe-MRI was performed from days 6-7 after ligation to evaluate thrombus volume, perfusion and macrophage content via T2, and T2 *-weighted images. Mice were euthanized at days 3-15 after surgery. The thrombi and adjacent vein walls were excised, weighed, formalin fixed, and paraffin embedded for histological analysis. Specimens were stained with specific antibodies to evaluate macrophage activity, collagen deposition, neovascularization, and recanalization. Significance was determined using the Mann-Whitney U or Student’s t-test. Results: After IVC-ligation in control mice, thrombus weights decreased by 59% from day 3 to day 15. FXI inhibition led to reduced macrophage content in both thrombus (p = .008) and vein wall (p = .01), decreased thrombus volume (p = .03), decreased thrombus mass (p = .01) and impaired thrombus perfusion (p = .01) compared to control mice. Iba1 staining supported these findings, showing significantly reduced macrophage presence in thrombi (p = .02). Conclusions: Fe-MRI T2 and T2 * relaxation times can be used to characterize and quantify post-thrombotic changes of perfusion, macrophage activity, and volume over time in a surgical mouse model of venous thrombosis. This approach could lead to better quantification of in vivo inflammation correlating monocyte and macrophage activity within resolving thrombi and veins and may serve as a useful tool in research and clinically in the evaluation of DVT or PTS.

The clinical characteristics of neutrophil extracellular trap in patients with severe cerebral venous sinus thrombosis and its prognostic value in acute and subacute patients

Objective: To explore the clinical characteristics of neutrophil extracellular trap (NET) in patients with severe cerebral venous sinus thrombosis (CVST) and to study their prognostic value in the acute and subacute phases. Methods: This study is a retrospective case series analysis. Clinical and pathological data of 52 patients with severe cerebral venous sinus thrombosis who underwent endovascular treatment in the Department of Neurosurgery, Tianjin Huanhu Hospital from June 2019 to June 2022 were retrospectively analyzed. There were 20 males and 32 females, with an age of (40.1±13.6) years(range:18 to 66 years). Forty-five healthy physical examinees were included in the control group. High-resolution MRI was used to stage the thrombus, with 11 cases in the acute group, 28 cases in the subacute group, and 13 cases in the chronic group. Thrombus specimens were obtained through endovascular treatment, and the fluorescence intensity of NET in peripheral blood at different time points was analyzed by immunofluorescence contrast,including the double-stranded DNA structure and adhesion protein components (citrolinated histone H3 (CitH3), myeloperoxidase-DNA complex(MPO-DNA), neutrophil elastase (NE)). The NET markers were determined by ELISA. Spearman rank correlation analysis was used to analyze the correlation between the NET markers in peripheral blood of patients with severe cerebral venous sinus thrombosis in the acute and subacute phases and the volume of venous sinus thrombus, the degree of venous sinus recanalization after treatment, and the discharge modified Rankin scale(mRS)score. The accuracy of NET markers in predicting the prognosis of patients with severe cerebral venous sinus thrombosis was analyzed by drawing receiver operating characteristic (ROC) curve and calculating the area under the curve (AUC). Results: The results of immunofluorescence staining and ELISA showed that no NET structure was formed in the peripheral blood of the control group, while CitH3, MPO-DNA and NE levels in the peripheral blood of CVST patients were increased, among which the acute stage group was the highest, followed by the subacute group, and the chronic group was the lowest. Spearman correlation analysis showed that CitH3, MPO-DNA and NE levels in peripheral blood of patients in acute group and subacute group were positively correlated with thrombus volume and mRS score at discharge (P<0.05). The levels of CitH3 and MPO-DNA in peripheral blood of patients with complete venous sinus recanalization were lower than those of patients with partial venous sinus recanalization (P<0.01). ROC curve analysis results showed that MPO-DNA and NE had no predictive ability for the prognosis of CVST patients (P values were 0.614 and 0.324, respectively), and the AUC of CitH3 was 0.800 (95%CI: 0.638~0.962, P=0.032), the best cut-off value was 13.5 μg/L, the sensitivity was 100%, and the specificity was 58.8%. Conclusions: A large number of NET are formed in patients with severe cerebral venous sinus thrombosis in acute stage. Patients with severe cerebral venous sinus thrombosis in acute stage and subacute stage with high peripheral blood NET content has a low rate of complete sinus revascularization and poor neurological function recovery after treatment.

Dynamic Perviousness Predicts Revascularization Success in Acute Ischemic Stroke.

The predictive value of thrombus perviousness in acute ischemic stroke (AIS), as measured by computed tomography (CT), has been intensively studied with conflicting results. In this study, we investigate the predictive potential of the novel concept of dynamic perviousness using three-dimensional (3D) volumetric evaluation of occlusive thrombi. The full thrombus volume in 65 patients with a hyperdense artery sign on non-contrast CT (NCCT), who underwent mechanical thrombectomy (MT), was segmented. Perviousness maps were computed voxel-wise for the entire thrombus volume as thrombus attenuation increase (TAI) between NCCT and CT angiography (CTA) as well as between CTA and late venous phase CT (CTV). Perviousness was analyzed for its association with NIHSS at admission, Thrombolysis In Cerebral Infarction (TICI) score, and number of MT passes. The mean late-uptake TAI of thrombi with NIHSS scores greater than 21 at admission was approximately 100% higher than for lower scored NIHSS (p between 0.05 and 0.005). Concerning revascularization results, thrombi requiring less than four MT passes had ca. 80% higher group mean late-uptake TAI than clots requiring four or more passes (p = 0.03), and thrombi with TICI score III had ca. 95% higher group mean late-uptake TAI than thrombi with TICI II (p = 0.03). Standard perviousness showed no significant correlation with MT results. Standard thrombus perviousness of 3D clot volume is not associated with revascularization results in AIS. In contrast, dynamic perviousness assessed with a voxel-wise characterization of 3D thrombi volume may be a better predictor of MT outcomes than standard perviousness.

Value of Automatically Derived Full Thrombus Characteristics: An Explorative Study of Their Associations with Outcomes in Ischemic Stroke Patients.

(1) Background: For acute ischemic strokes caused by large vessel occlusion, manually assessed thrombus volume and perviousness have been associated with treatment outcomes. However, the manual assessment of these characteristics is time-consuming and subject to inter-observer bias. Alternatively, a recently introduced fully automated deep learning-based algorithm can be used to consistently estimate full thrombus characteristics. Here, we exploratively assess the value of these novel biomarkers in terms of their association with stroke outcomes. (2) Methods: We studied two applications of automated full thrombus characterization as follows: one in a randomized trial, MR CLEAN-NO IV (n = 314), and another in a Dutch nationwide registry, MR CLEAN Registry (n = 1839). We used an automatic pipeline to determine the thrombus volume, perviousness, density, and heterogeneity. We assessed their relationship with the functional outcome defined as the modified Rankin Scale (mRS) at 90 days and two technical success measures as follows: successful final reperfusion, which is defined as an eTICI score of 2b-3, and successful first-pass reperfusion (FPS). (3) Results: Higher perviousness was significantly related to a better mRS in both MR CLEAN-NO IV and the MR CLEAN Registry. A lower thrombus volume and lower heterogeneity were only significantly related to better mRS scores in the MR CLEAN Registry. Only lower thrombus heterogeneity was significantly related to technical success; it was significantly related to a higher chance of FPS in the MR CLEAN-NO IV trial (OR = 0.55, 95% CI: 0.31-0.98) and successful reperfusion in the MR CLEAN Registry (OR = 0.88, 95% CI: 0.78-0.99). (4) Conclusions: Thrombus characteristics derived from automatic entire thrombus segmentations are significantly related to stroke outcomes.

Reduced Monocyte and Neutrophil Infiltration and Activation by P-Selectin/CD62P Inhibition Enhances Thrombus Resolution in Mice.

Venous thromboembolism is a major health problem. After thrombus formation, its resolution is essential to re-establish blood flow, which is crucially mediated by infiltrating neutrophils and monocytes in concert with activated platelets and endothelial cells. Thus, we aimed to modulate leukocyte function during thrombus resolution post-thrombus formation by blocking P-selectin/CD62P-mediated cell interactions. Thrombosis was induced by inferior vena cava stenosis through ligation in mice. After 1 day, a P-selectin-blocking antibody or isotype control was administered and thrombus composition and resolution were analyzed. Localizing neutrophils and macrophages in thrombotic lesions of wild-type mice revealed that these cells enter the thrombus and vessel wall from the caudal end. Neutrophils were predominantly present 1 day and monocytes/macrophages 3 days after vessel ligation. Blocking P-selectin reduced circulating platelet-neutrophil and platelet-Ly6Chigh monocyte aggregates near the thrombus, and diminished neutrophils and Ly6Chigh macrophages in the cranial thrombus part compared with isotype-treated controls. Depletion of neutrophils 1 day after thrombus initiation did not phenocopy P-selectin inhibition but led to larger thrombi compared with untreated controls. In vitro, P-selectin enhanced human leukocyte function as P-selectin-coated beads increased reactive oxygen species production by neutrophils and tissue factor expression of classical monocytes. Accordingly, P-selectin inhibition reduced oxidative burst in the thrombus and tissue factor expression in the adjacent vessel wall. Moreover, blocking P-selectin reduced thrombus density determined by scanning electron microscopy and increased urokinase-type plasminogen activator levels in the thrombus, which accelerated caudal fibrin degradation from day 3 to day 14. This accelerated thrombus resolution as thrombus volume declined more rapidly after blocking P-selectin. Inhibition of P-selectin-dependent activation of monocytes and neutrophils accelerates venous thrombosis resolution due to reduced infiltration and activation of innate immune cells at the site of thrombus formation, which prevents early thrombus stabilization and facilitates fibrinolysis.

Impact of preoperative transcatheter arterial chemoembolization (TACE) on postoperative long-term survival in patients with nonsmall hepatocellular carcinoma: a propensity score matching analysis

BackgroundThe purpose of this propensity score matching (PSM) analysis was to compare the effects of preoperative transcatheter arterial chemoembolization (TACE) and non-TACE on the long-term survival of patients who undergo radical hepatectomy.MethodsPSM analysis was performed for 387 patients with hepatocellular carcinoma (HCC) (single > 3 cm or multiple) who underwent radical resection of HCC at our centre from January 2011 to June 2018. The patients were allocated to a preoperative TACE group (n = 77) and a non-TACE group (n = 310). The main outcome measures were progression-free survival (PFS) and overall survival (OS) since the treatment date.ResultsAfter PSM, 67 patients were included in each of the TACE and non-TACE groups. The median PFS times in the preoperative TACE and non-TACE groups were 24.0 and 11.3 months, respectively (p = 0.0117). The median OS times in the preoperative TACE and non-TACE groups were 41.5 and 29.0 months, respectively (p = 0.0114). Multivariate Cox proportional hazard regression analysis revealed that preoperative TACE (hazard ratio, 1.733; 95% CI, 1.168–2.570) and tumour thrombosis (hazard ratio, 0.323; 95% CI, 0.141–0.742) were independent risk factors significantly associated with OS.ConclusionsPreoperative TACE is related to improving PFS and OS after resection of HCC. Preoperative TACE and tumour thrombus volume were also found to be independent risk factors associated with OS.

Curcumin alleviates myocardial inflammation, apoptosis, and oxidative stress induced by acute pulmonary embolism by regulating microRNA-145-5P/insulin receptor substrate 1 axis.

The treatment of patients with acute pulmonary embolism (APE) is extremely challenging due to the complex clinical presentation and prognosis of APE related to the patient's hemodynamic status and insufficient arterial blood flow and right ventricular overload. Protective efficacy against cardiovascular diseases of curcumin, a common natural polyphenolic compound, which has antithrombotic properties and reduces platelet accumulation in the circulation by inhibiting thromboxane synthesis has been demonstrated. However, the direct effect of curcumin on APE has rarely been studied. Therefore, the present study aimed to investigate the therapeutic potential of curcumin in APE and associated myocardial injury to provide new insights into curcumin as a promising competitive new target for the treatment of APE. A suspension of 12 mg/kg microspheres was injected intravenously into rats. An APE rat model was built. Before modeling, intragastric 100 mg/kg curcumin was given, and/or lentiviral plasmid vector targeting microRNA-145-5p or insulin receptor substrate 1 (IRS1) was injected. Pulmonary artery pressure was measured to assess right ventricular systolic pressure (RVSP). Hematoxylin and eosin (H&E) staining was performed on liver tissues and myocardial tissues of APE rats. TUNEL (terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling) staining and immunohistochemical (IHC) staining were conducted to measure apoptosis and CyPA-CD147 expression in the myocardium, respectively. Inflammatory indices interleukin-1beta (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) were measured by ELISA in cardiac tissues. RT-qPCR and Western blot were performed to determine the expression levels of related genes. In addition, by dual luciferase reporter assay and RIP assay, the relationship between microRNA-145-5p and insulin receptor substrate 1 (IRS1) was confirmed. In results: curcumin improved APE-induced myocardial injury, reduced myocardial tissue edema, and thrombus volume. It attenuated APE-induced myocardial inflammation and apoptosis, as well as reduced lung injury and pulmonary artery pressure. Curcumin promoted microRNA-145-5p expression in APE rat myocardium. MicroRNA-145-5p overexpression protected against APE-induced myocardial injury, and microRNA-145-5p silencing abolished the beneficial effects of curcumin in APE-induced myocardial injury. IRS1 was targeted by microRNA-145-5p. IRS1 silencing attenuated APE-induced myocardial injury, and enhanced therapeutic effect of curcumin on myocardial injury in APE rats. In conclusion, curcumin alleviates myocardial inflammation, apoptosis, and oxidative stress induced by APE by regulating microRNA-145-5p/IRS1 axis.