Thrombus Imaging Research Articles

Activated Platelet-Homing Nanoplatform for Targeting Magnetic Resonance Imaging of Aneurysm-Related Thrombus in Rabbits.

Thrombosis is closely related to the instability of intracranial aneurysm (IA), whose rupture is associated with high morbidity and mortality. It is difficult to detect an IA-related thrombus because traditional magnetic resonance imaging (MRI) and even contrast-enhanced MRI cannot clearly distinguish a thrombus from the surrounding tissues. Herein, a nanoplatform [(MFe2O4-ZnDPA nanoparticles (NPs)], consisting of Zn0.4Co0.6Fe2O4@Zn0.4Mn0.6Fe2O4 NPs for imaging and Zn(II)-bis(dipicolylamine) (ZnDPA) for thrombus targeting, is constructed to target an experimental aneurysm-related thrombus in rabbits via MRI. In vitro experiments including platelet safety evaluation primarily prove that MFe2O4-ZnDPA NPs with a high MRI transverse relaxation time (T2) have good biocompatibility. MFe2O4-ZnDPA NPs could target a thrombus via the special interaction between ZnDPA and phosphatidylserine of activated platelets in the thrombus through MRI and Fe quantification assays. Moreover, after MFe2O4-ZnDPA NPs are injected into the ear vein of common carotid artery aneurysm model rabbits, MRI shows that MFe2O4-ZnDPA NPs could accumulate in the aneurysm-related thrombus from 0 to 15 min after injection and decrease in the next 45 min. Meanwhile, MFe2O4-ZnDPA NPs could decrease the MRI T2 signal of the aneurysm-related thrombus to enhance the outline of the aneurysm. This study demonstrates that a nanoplatform can enhance the detection of an aneurysm-related thrombus as well as aneurysm itself to assist further treatment of IA.

Incidence and predictors of left atrial appendage thrombus on transoesophageal echocardiography before elective cardioversion

Abstract Introduction Guidelines recommend transoesophageal echocardiography (TOE) before cardioversion in thrombogenic arrhythmias when the requirement of ≥3 weeks of anticoagulation is not met. Current data to support this approach, especially with direct oral anticoagulants (DOAC), are scarce. Methods We analysed consecutive elective pre-cardioversion TOE in a high-volume electrophysiology centre for the occurrence of LAA thrombi or reduced LAA flow velocity. Possible predictors were recorded and compared in a multivariate logistic regression analysis. Results Consecutive pre-cardioversion TOE in 512 patients (148 female, median age 69 years) were included. In all patients, indication for TOE was either intake of anticoagulation <3 weeks before cardioversion or uncertain adherence to the prescribed anticoagulation regimen. Of the 512 TOE, 19 (3.7%) depicted a LAA thrombus. An additional 41 patients (8.0%) showed either a reduced LAA flow velocity (≤20cm/s), LAA sludge, or both (see figure). In a multivariate logistic regression analysis, QRS width on admission 12-lead ECG emerged as a possible predictor of LAA thrombus and reduced LAA flow (p=0.008). Noteworthy, a high CHA2DS2-VaSc-Score was not associated with an increased risk of reduced LAA emptying velocity and LAA thrombi were even found in patients with a CHA2DS2-VaSc-Score of 0 (n=1) and 1 (n=1). Conclusion The presence of LAA thrombus before an elective cardioversion is a rare event in the age of direct oral anticoagulants. However, LAA thrombi occurred even in supposed low-risk individuals according to the CHA2DS2-VaSc score. QRS width may aid in identifying patients at a high risk of a reduced LAA flow velocity. Funding Acknowledgement Type of funding sources: None. Figure 1. Representative images of a solid LAA thrombus (panel A), LAA sludge (panel B, not containing a solid thrombus on i.v. contrast imaging), and a LAA free of thrombus or sludge (panel C). Panel D shows the PW Doppler signal in a patient with LAA emptying velocity reduced ≤20cm/s while panel E shows a LAA with normal flow characteristics.

In vivo coronary artery thrombus imaging with 18F-GP1 PET-CT

Abstract Background Coronary artery thrombus is typically present in type 1 myocardial infarction, but small volumes in the setting of an uncertain culprit lesion may be beyond the detection limit of current imaging modalities. Purpose Using a novel glycoprotein IIb/IIIa-receptor radiotracer, 18F-GP1, we investigated whether positron emission tomography-computed tomography (PET-CT) could detect thrombus formation in coronary arteries. Methods In a single centre cross-sectional study, patients over 40 years of age with myocardial infarction were recruited after myocardial infarction and underwent underwent CT angiography and 18F-GP1 PET-CT. Stable patients with and without coronary artery disease formed a control cohort. Coronary artery 18F-GP1 uptake was visually assessed and quantified using maximum target-to-background ratios (TBRmax). Results Ninety-four (44 post-myocardial infarction and 50 control patients) were included in the cross-sectional analysis. The mean age of the post-myocardial infarction group was 61±9 years, three-quarters were male and two thirds had presented with ST elevation on electrocardiography. 34 (80%) patients post-myocardial infarction, but none of the control patients, demonstrated focal 18F-GP1 uptake in the coronary arteries. Of 42 vessels with an angiographic culprit lesion, 35 (83%) had 18F-GP1 uptake which was significantly higher than non-culprit vessels (p<0.0001) as well as control vessels (p<0.0001), while non-culprit vessel uptake was similar to control vessel uptake (p=0.567): culprit vessel median TBRmax 1.2 [interquartile range 0.96–1.44], non-culprit vessel TBRmax 0.96 [0.84–1.03] and control vessel TBRmax 0.9 [0.76 to 0.94]. Linear regression models demonstrated univariable associations between coronary 18F-GP1 TBRmax and time from myocardial infarction, male sex and presence of culprit vessel. On multivariable analysis, only culprit vessel status was associated with TBRmax (adjusted R2= 0.22, P<0.001). Based on the Youden's index of the ROC curves, the optimal cut-off of predicting the presence of a culprit vessel was 1.20 with a specificity of 97%, accuracy of 83%, sensitivity (60%) and c-statictic of 0.74. A patient with ectatic vessel and visual thrombus demonstrated the most intense 18F-GP1 uptake (TBRmax 2.0, highest in the cohort) in the region of heaviest thrombus burden (Figure 2). Extra-coronary uptake was seen in regions of left ventricular thrombus, left atrial appendage thrombus, pulmonary thromboembolism and intramyocardial microvascular obstruction. Conclusions 18F-GP1 PET-CT is able to detect coronary artery thrombus in culprit lesions following myocardial infarction, as well as extra-coronary thrombotic pathologies that may be important in guiding patient management. 18F-GP1 is highly specific in recognising a culprit lesion from a non-culprit lesion both visually as well as quantitatively. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): British Heart Foundation Figure 1Figure 2

A Nano-Based P1Cminimum Probe to Monitor Thrombosis in Grafts and Improve Cardiac Function After Coronary Artery Bypass Grafting Surgery.

Magnetic resonance imaging is widely used to identify and monitor thrombi in grafted vessels following coronary artery bypass grafting surgery (CABG). We produced a biosensor, P1Cm-SPIO-Cy5.5, composed of P1Cm peptide, superparamagnetic iron oxide nanoparticles (SPIO), and polyethylene glycol (PEG), for use in MRI thrombus imaging. Activated platelets induced by adenosine diphosphate were used for combination tests in vitro. A rat model of common carotid artery thrombosis was used for anti-thrombus experiments in vivo. P1Cm-SPIO-Cy5.5 remains stable in vitro and has good anticoagulation capacity. It can bind specifically to activated platelets and thrombi. In rats that underwent bypass surgery, P1Cm-SPIO-Cy5.5 could detect and label thrombi over a long period, and prevent thrombosis in grafted vessels. P1Cm-SPIO-Cy5.5 improved cardiac function in rats following CABG surgery. P1Cm-SPIO-Cy5.5 is a potential sensor for use in MRI for the early diagnosis and prevention of thrombosis after CABG surgery.

Diagnostic performance of MR black-blood thrombus imaging for cerebral venous thrombosis in real-world clinical practice.

MR black-blood thrombus imaging (BTI) has been developed for the detection of cerebral venous thrombosis (CVT). Yet, there is a lack of real-world data to verifying its clinical performance. This study aims to evaluate the performance of BTI in diagnosing and staging CVT in a 5-year period. Patients suspected of CVT were enrolled between 2014 and 2019. Patients with or without BTI scans were classified into group A and group B, respectively. The prevalence of correct diagnosis of CVT and patients with evaluable clot age were compared. The diagnostic performance of BTI including sensitivity, specificity, and specific staging information was further analyzed. Two hundred and twenty-one of the 308 patients suspected of CVT were eligible in the current study (114 in group A and 97 in group B), with 125 diagnosed by multidisciplinary teams to have CVTs (56 in group A, 69 in group B). The rate of correct diagnosis of CVT was higher in group A than that in group B (94.7% vs 60.8%, p < 0.001, x2 = 36.517) after adding BTI images. The percent of patients with evaluable staged segments between the two groups were 96.4% and 33.9%, respectively (x2 = 48.191, p < 0.001). BTI showed a sensitivity of 96.4% and 87.9% in the detection of CVT on per-patient and per-segment level, respectively. Up to 98.1% of all thrombosed segments could be staged by BTI and 59.6% of them were matched with clinical staging. In the actual clinical practice, BTI improves diagnostic confidence and has an excellent performance in confirming and staging CVT. • Black-blood thrombus imaging has good diagnostic performance in detecting cerebral venous thrombosis compared to traditional imaging methods with strong evidence in the actual clinical setting. • BTI helps clinicians to diagnose CVT with more accuracy and confidence, which can be served as a promising imaging examination. • BTI can also provide additional information of different thrombus ages objectively, the valuable reference for clinical strategy.

Thrombus-specific theranostic nanocomposite for codelivery of thrombolytic drug, algae-derived anticoagulant and NIR fluorescent contrast agent

Thrombolysis is a standard treatment for rapidly restoring blood flow. However, the application of urokinase-type plasminogen activator (Uk) in clinical therapy is limited due to its nonspecific distribution and inadequate therapeutic accumulation. Precise thrombus imaging and site-specific drug delivery can enhance the diagnostic and therapeutic efficacy for thrombosis. Accordingly, we developed a P-selectin-specific, photothermal theranostic nanocomposite for thrombus-targeted codelivery of Uk and indocyanine green (ICG, a contrast agent for near-infrared (NIR) fluorescence imaging). We evaluated its capabilities for thrombus imaging and enzyme/hyperthermia combined thrombolytic therapy. Mesoporous silica-coated gold nanorods (Si-AuNRs) were functionalized with an arginine-rich peptide to create an organic template for the adsorption of ICG and fucoidan (Fu), an algae-derived anticoagulant. Uk was loaded into the SiO2 pores of the Si-AuNRs through the formation of a Fu-Uk-ICG complex on the peptide-functionalized template. The Fu-Uk/ICG@SiAu NRs nanocomposite increased the photostability of ICG and improved its targeting/accumulation at blood clot sites with a strong NIR fluorescence intensity for precise thrombus imaging. Furthermore, ICG incorporated into the nanocomposite enhanced the photothermal effect of Si-AuNRs. Fu, as a P-selectin-targeting ligand, enabled the nanocomposite to target a thrombus site where platelets were activated. The nanocomposite enabled a faster release of Uk for rapid clearing of blood clots and a slower release of Fu for longer lasting prevention of thrombosis regeneration. The nanocomposite with multiple functions, including thrombus-targeting drug delivery, photothermal thrombolysis, and NIR fluorescence imaging, is thus an advanced theranostic platform for thrombolytic therapy with reduced hemorrhaging risk and enhanced imaging/thrombolysis efficiency. Statement of significanceHerein, for the first time, a P-selectin specific, photothermal theranostic nanocomposite for thrombus-targeted co-delivery of urokinase and NIR fluorescence contrast agent indocyanine green (ICG) was developed. We evaluated the potential of this theranostic nanocomposite for thrombus imaging and enzyme/hyperthermia combined thrombolytic therapy. The nanocomposite showed multiple functions including thrombus targeting and imaging, and photothermal thrombolysis. Besides, it allowed faster release of the thrombolytic urokinase for rapidly clearing blood clots and slower release of a brown algae-derived anticoagulant fucoidan (also acting as a P-selectin ligand) for prevention of thrombosis regeneration. The nanocomposite is thus a new and advanced theranostic platform for targeted thrombolytic therapy.

Detection of upper extremity deep vein thrombosis by magnetic resonance non‐contrast thrombus imaging

BackgroundCompression ultrasonography (CUS) is the first‐line imaging test for diagnosing upper extremity deep vein thrombosis (UEDVT), but often yields inconclusive test results. Contrast venography is still considered the diagnostic standard but is an invasive technique. ObjectivesWe aimed to determine the diagnostic accuracy of magnetic resonance noncontrast thrombus imaging (MR‐NCTI) for the diagnosis of UEDVT. MethodsIn this international multicenter diagnostic study, we prospectively included patients with clinically suspected UEDVT who were managed according to a diagnostic algorithm that included a clinical decision rule (CDR), D‐dimer test, and diagnostic imaging. UEDVT was confirmed by CUS or (computed tomography [CT]) venography. UEDVT was excluded by (1) an unlikely CDR and normal D‐dimer, (2) a normal serial CUS or (3) a normal (CT) venography. Within 48 h after the final diagnosis was established, patients underwent MR‐NCTI. MR‐NCTI images were assessed post hoc by two independent radiologists unaware of the presence or absence of UEDVT. The sensitivity, specificity, and interobserver agreement of MR‐NCTI for UEDVT were determined. ResultsMagnetic resonance noncontrast thrombus imaging demonstrated UEDVT in 28 of 30 patients with UEDVT and was normal in all 30 patients where UEDVT was ruled out, yielding a sensitivity of 93% (95% CI 78–99) and specificity of 100% (95% CI 88–100). The interobserver agreement of MR‐NCTI had a kappa value of 0.83 (95% CI 0.69–0.97). ConclusionsMagnetic resonance noncontrast thrombus imaging is an accurate and reproducible method for diagnosing UEDVT. Clinical outcome studies should determine whether MR‐NCTI can replace venography as the second‐line imaging test in case of inconclusive CUS.

Radiology-Pathology Correlations of Intracranial Clots: Current Theories, Clinical Applications, and Future Directions.

In recent years, there has been substantial progression in the field of stroke clot/thrombus imaging. Thrombus imaging aims to deduce the histologic composition of the clot through evaluation of various imaging characteristics. If the histology of a thrombus can be reliably determined by noninvasive imaging methods, critical information may be extrapolated about its expected response to treatment and about the patient's clinical outcome. Crucially, as we move into an era of stroke therapy individualization, determination of the histologic composition of a clot may be able to guide precise and targeted therapeutic effort. Most radiologists, however, remain largely unfamiliar with the topic of clot imaging. This article will review the current literature regarding clot imaging, including its histologic backdrop, the correlation of images with cellular components and treatment responsiveness, and future expectations.

Incidence of Left Atrial Thrombus Development and Imaging Approach in Patients Scheduled for Repeat Catheter Ablation for Atrial Fibrillation

The risk for developing left atrial (LA) thrombi after initial catheter ablation for atrial fibrillation (AF) and requirements for imaging evaluation for thrombi screening at repeat ablation is unclear. This study aimed to assess the occurrence of thrombus development and frequency of any imaging study evaluating thrombus formation during repeat ablation for AF. Of 2,066 patients undergoing initial catheter ablation for AF with uninterrupted oral anticoagulation, 615 patients underwent repeat ablation after 258.0 (105.0-882.0) days. We investigated the factors associated with safety outcomes and requirements for thrombus screening. All patients underwent at least one imaging examination to screen for thrombi in the initial session; however, the examination rate decreased to 476 patients (77%) before the repeat session. The frequency of imaging evaluations was 5.0%, 11%, 21%, 84%, and 91% for transesophageal echocardiography and 18%, 33%, 49%, 98%, and 99% for any imaging modality at repeat ablation performed ≤60 days, ≤90 days, ≤180 days, >180 days, and >1 year after the initial session, respectively. Three patients (0.5%) developed LA thrombi at repeat ablation due to identifiable causes, and no patients experienced thromboembolic events when no imaging evaluation was performed. Multivariate analysis revealed that repeat ablation performed after >180 days, non-paroxysmal atrial arrhythmias, and lower left ventricular ejection fraction were predictors of thrombus development and severe spontaneous echocardiography contrast. In conclusion, the risk for thrombus development at repeat ablation for AF was low. There needs to be a risk stratification of the imaging screening for thrombi at repeat ablation.

Acute pulmonary embolism with high-intensity signals on magnetic resonance direct thrombus imaging.

Acute pulmonary embolism with high-intensity signals on magnetic resonance direct thrombus imaging.

High-Resolution Magnetic Resonance Black Blood Thrombus Imaging and Serum D-Dimer in the Confirmation of Acute Cortical Vein Thrombosis.

Cerebral cortical vein thrombosis (CCVT) is often misdiagnosed because of its non-specific diagnostic symptoms. Here, we analyzed a cohort of patients with CCVT in hopes of improving understandings and treatments of the disease. A total of 23 patients with CCVT (confirmed with high-resolution imaging), who had been diagnosed between 2017 and 2019, were enrolled in this cohort study. Baseline demographics, clinical manifestations, laboratory data, radiological findings, treatment, and outcomes were collected and analyzed. Fourteen females and nine males were enrolled (mean age: 32.7 ± 11.9 years), presenting in the acute (within 7 days, n = 9), subacute (8–30 days, n = 7), and chronic (over 1 month, n = 7) stages. Headaches (65.2%) and seizures (39.1%) were the most common symptoms. Abnormally elevated plasma D-dimers were observed in the majority of acute stage patients (87.5%). The diagnostic accuracy of contrast-enhanced magnetic resonance venography (CE-MRV) and high-resolution magnetic resonance black-blood thrombus imaging (HR-MRBTI) in detecting CCVT were 57.1 and 100.0%, respectively. All patients had good functional outcomes after 6-month of standard anticoagulation (mRS 0–1) treatment. However, four CCVT patients that had cases involving multiple veins showed symptom relief after batroxobin therapy (p = 0.030). HR-MRBTI may be a fast and accurate tool for non-invasive CCVT diagnosis. HR-MRBTI combined with D-dimer can also precisely identify the pathological stage of CCVT. Batroxobin may safely accelerate cortical venous recanalization in combination with anticoagulation. Follow-up studies with larger sample sizes are suggested to evaluate the safety and efficacy of batroxobin for treating CCVT.

Early recanalization in large-vessel occlusion stroke patients transferred for endovascular treatment

BackgroundWe performed an exploratory analysis to identify patient and thrombus characteristics associated with early recanalization in large-vessel occlusion (LVO) stroke patients transferred for endovascular treatment (EVT) from a primary (PSC)...

Left Ventricular Thrombi: Insights from Cardiac Magnetic Resonance Imaging.

Objective: Cardiovascular magnetic resonance imaging (CMR) late gadolinium enhancement technique (LGE) detects thrombus rather than anatomical presence based on tissue properties and is theoretically highly accurate. The present study’s goal was to compare the diagnostic accuracy obtained with various CMR techniques and transthoracic echocardiography to diagnose left ventricular thrombus and evaluate the prevalence and perspectives of left ventricular (LV) thrombus among patients with impaired systolic left ventricular function. Methods: In a single academic referral center, a retrospective database review of all CMR assessments of the established left ventricular thrombus was carried out in 206 consecutive patients with reduced systolic function for five years. To assess thrombus risk factors, clinical and imaging parameters were analyzed. Sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), echocardiography, and cine-CMR sequence accuracy have been identified. LV structural parameters were quantified to detect markers for thrombus and predictors of the additive usefulness of contrast-enhanced thrombus imaging. Comparisons against LGE-CMR were made, which was used as the standard. Results: A 7.8 percent prevalence of left ventricular thrombus was identified by LGE-CMR. Cine-CMR increased the diagnostic efficiency for echocardiographic thrombus identification in this group, with sensitivity increasing from 50 percent by echocardiography to 75 percent by cine-CMR (p = 0.008). Dark blood CMR (DB-CMR) has better sensitivity and accuracy than echocardiography (p < 0.001), comparable to cine-CMR. The transmural infarct size was an independent marker for thrombus after correction for the LVEF and LV volume while considering only CMR parameters. There were significantly higher embolic events (HR = 71.33; CI 8.31–616.06, p < 0.0001) in LV thrombus patients detected by LGE-CMR. Conclusion: CMR imaging was more sensitive to left ventricular thrombi identification compared with transthoracic echocardiography. An additional parameter available from LGE-CMR and shown as an independent risk factor for left ventricular thrombus is the myocardial scar.

MRI- and CT-venography in the diagnosis of hemodynamic disorders in patients suffering from lower extremities chronic venous disorders. Part II. Possibilities of MRI in diagnostics of the deep vein thrombosis

In this literature review, the analysis of the studies of venous blood flow pathology in the inferior Vena cava system using magnetic resonance imaging (MRI) is carried out. Special attention is paid to the attempts made to use this method in the diagnosis of chronic lower limb vein disorders (CVD) through magnetic resonance venography (MRV). Historically and methodically, the gradual introduction of MRV methods in the diagnosis of lower limb vein thrombosis (LEDVT) and venous thromboembolism (VTE) has been shown.Methods of non-contrast MRV based on the effect of blood flow, as in the case of MR-Angiography, are divided into two principal groups: methods based on the amplitude effects of Time-of-Flight (TOF) and methods based on Phase Contrast effects (PC). Techniques for conducting contrast-free MRV are described in detail. Attention is paid to pulse sequences used in the world for visualization of veins in contrast-free MRV in TOF and PC mode (FR-FBI, SPADE, SSFP) and post-processing methods: 2D-TOF MRV FLASH, 2D-TOF MRV CRASS, FIPS, VED, VENS.Contrast-enhanced MRV (CE MRV) is based on the use of “blood pool” contrast agents, which feature the ability to form stable compounds with blood plasma proteins. Worldwidesubstances with magnetic and supermagnetic properties based on gadolinium or iron oxide are used as contrast agents for CE MRV. The result of using these contrast agents is an increase in the quality of visualization due to a better signal to noise ratio (SNR) using 3D image processing (3D CE MRV) using fast sequences: GRE, TFLAS, VESPA, CAT, in conditions of direct and indirect CE MRV.It is noted that in recent years, certain restrictions have been imposed on certain linear contrast agents containing gadolinium in their further use. Therefore, for the purpose of CE MRV, it is efficientl to use only cyclic contrast agents to avoid unnecessary risks.Contrast-free MRV has again received intensive development in recent years, due to the restrictions imposed, one of these methods is direct thrombus imaging (Direct Thrombus Imaging – DTI or Magnetic Resonance Direct Thrombus Imaging - MRDTI) using fast pulse sequences: bSSFP, BBTI, DANTE. The latest research on this LEDVT diagnostic method was published in 2019 and has shown high diagnostic value.For all the most commonly used methods of MRV, specificity and sensitivity are shown.Further MRV in patients with CVD and DVT is a promising diagnostic task in modern phlebology. MRV should be introduced into clinical practice more actively than it is today.

Cost-effectiveness of magnetic resonance imaging for diagnosing recurrent ipsilateral deep vein thrombosis

The diagnostic workup of recurrent ipsilateral deep vein thrombosis (DVT) using compression ultrasonography (CUS) can be complicated by persistent intravascular abnormalities after a previous DVT. We showed that magnetic resonance direct thrombus imaging (MRDTI) can exclude recurrent ipsilateral DVT. However, it is unknown whether the application of MRDTI in daily clinical practice is cost effective. The aim of this study was to evaluate the cost effectiveness of MRDTI-based diagnosis for suspected recurrent ipsilateral DVT during first year of treatment and follow-up in the Dutch health care setting. Patient-level data of the Theia study (NCT02262052) were analyzed in 10 diagnostic scenarios, including a clinical decision rule and D-dimer test and imaging with CUS and/or MRDTI. The total costs of diagnostic tests and treatment during 1-year follow-up, including costs of false-positive and false-negative diagnoses, were compared and related to the associated mortality. The 1-year health care costs with MRDTI (range, €1219-1296) were generally lower than strategies without MRDTI (range, €1278-1529). This was because of superior specificity, despite higher initial diagnostic costs. Diagnostic strategies including CUS alone and CUS followed by MRDTI in case of an inconclusive CUS were potential optimal cost-effective strategies, with estimated average costs of €1529 and €1263 per patient and predicted mortality of 1 per 737 patients and 1 per 609 patients, respectively. Our model shows that diagnostic strategies with MRDTI for suspected recurrent ipsilateral DVT have generally lower 1-year health care costs than strategies without MRDTI. Therefore, compared with CUS alone, applying MRDTI did not increase health care costs.

Asymmetric pathological pachymeningeal enhancement: A new imaging feature for cerebral venous thrombosis

PurposeCerebral venous thrombosis (CVT) has various clinical presentations and has a median onset delay of 7 days. So it is important to find more identifiable early imaging manifestations for CVT. MethodThis was a retrospective study. Patients with CVT (CVT group, n = 26) diagnosed by conventional imaging techniques (magnetic resonance imaging and/or digital subtraction angiogram) and patients with symptomatic intracranial atherosclerosis (control group, n = 30) were included. Magnetic resonance black-blood thrombus imaging (MRBTI) technique had been performed in both groups. The CVT group was divided into 3 groups based on the duration of clinical onset: ≤7 days (group 1), between 7 and 30 days (group 2), and >30 days (group 3). Pathological pachymeningeal enhancement and its characteristics were analyzed between the CVT group and the control group. ResultsPathological pachymeningeal enhancement was found in 14 CVT patients (54 %) and none in control group (P value = 0.000). The bilateral pathological pachymeningeal enhancement was involved in 10 CVT patients, 6 patients were asymmetric, and 4 patients had ipsilateral enhancement. Asymmetric pathological pachymeningeal enhancement was 71 % and predominantly located on the thrombosed sinus side. Strong enhancement was found in the venous sinus wall beside the thrombus. Pathological pachymeningeal enhancement percentages of three subgroups were 75 % in group 1, 55 % in group 2, and 29 % in group 3 and had no statistical differences (p value = 0.198). ConclusionsCurrent findings suggest asymmetrical pathological pachymeningeal enhancement was associated was CVT and may be a new imaging feature for CVT.

Time-efficient and contrast-free magnetic resonance imaging approach to the diagnosis of deep vein thrombosis on black-blood gradient-echo sequence: a pilot study.

Black-blood thrombus imaging (BTI) has shown to be advantageous for the diagnosis of deep vein thrombosis (DVT). However, previous techniques using fast spin echo have a high specific absorption rate. As DANTE (delay alternating with nutation for tailored excitation) black-blood preparation can suppress blood flows over a broad range of velocities, we hypothesized that a DANTE black-blood preparation combined with a fast low-angle shot (FLASH) gradient-echo readout-DANTE-FLASH could be used to diagnose DVT. Eleven healthy volunteers and 30 suspected DVT patients were recruited to undergo DANTE-FLASH and magnetic resonance direct thrombus imaging (MRDTI). The suspected DVT patients were also examined by ultrasound (US). For the segment level, a total of 1,066 venous vessel segments were analyzed. Using US and MRDTI as the references, the sensitivity (SE), specificity (SP), positive and negative predictive values (PPV and NPV), and accuracy (ACC) of DANTE-FLASH were calculated. To quantitatively compare image quality between DANTE-FLASH and MRDTI, image signal-to-noise ratio (SNR), apparent contrast-to-noise ratio (CNR) between muscle and the venous lumen, and the apparent CNR between the thrombus and venous lumen were measured. Additionally, diagnostic confidence, image quality, and clot burden were also evaluated. Using the consensus results of US and MRDTI as a standard reference, the diagnostic SE, SP, PPV, NPV, and ACC of DANTE-FLASH for the 2 readers were 97.0% and 93.2%, 99.0% and 98.2%, 93.4% and 87.9%, 99.6% and 99.0%, and 98.8% and 97.6%, respectively. According to the image quantitative analysis results, DANTE-FLASH demonstrated higher image SNR and CNR than MRDTI. The image quality and diagnostic confidence scores of DANTE-FLASH were higher than MRDTI (3.66±0.44 vs. 3.52±0.52, P<0.001, and 3.84±0.36 vs. 3.76±0.41, P<0.001). There was excellent agreement between DANTE-FLASH and MRDTI on clot burden evaluation. DANTE-FLASH provided better image quality than MRDTI and accurately detected thrombi. It may, therefore, serve as a safe and convenient alternative for the diagnosis of DVT.

Short‐Term Cessation of Dabigatran Causes a Paradoxical Prothrombotic State

It is unclear if stopping treatment with dabigatran, a new oral anticoagulant (NOAC), induces a paradoxical rebound prothrombotic state. We investigated if short-term (1-3 days) dabigatran cessation is associated with a higher thrombus volume than expected from a simple reversal of the anticoagulant effect. Ten-week-old C57Bl/6 mice (n = 338) received one of the following oral treatments: phosphate-buffered saline (PBS), dabigatran for 7 days with or without 1 to 4 day cessation, and aspirin in either a single dose or daily for 7 days. Some of the animals that ceased dabigatran for 1 to 3 days received single-dose aspirin. Thereafter, we induced FeCl3 -mediated carotid thrombosis in 130 mice, after which we performed micro computed tomography thrombus imaging. The other 208 mice underwent coagulation assays or platelet function tests. As an explorative pilot study, we reviewed the medical records of 18 consecutive patients with NOAC cessation-related cerebral infarction in a large acute stroke cohort. We observed a ~ 40% higher volume of carotid thrombus after dabigatran cessation at 1 to 3 days than after vehicle treatment and showed that this effect could be prevented by single-dose aspirin pretreatment. Dabigatran cessation unduly increased platelet aggregability for 2 days after drug cessation, an effect mediated through thrombin or arachidonic acid, which effect was significantly attenuated by single-dose aspirin pretreatment. In patients, short-term (≤ 3 days) cessation of NOAC therapy, compared with longer-term (≥ 5 days) cessation, tended to be associated with relatively high stroke severity. We provide the first preclinical evidence that a rebound prothrombotic state follows short-term cessation of dabigatran therapy. ANN NEUROL 2021;89:444-458.

Functionalized polymeric hybrid micelles as an efficient nanotheranostic agent for thrombus imaging and thrombolysis

Pathological thrombosis within a vessel hampers blood flow and is the mainspring of numerous fatal cardiovascular complications. In order to specifically image and dissolve a thrombus, we rationally designed a functionalized polymeric hybrid micelle (PHM) system self-assembled from amphiphilic polycaprolactone-polyethylenimine (PCL-PEI) and polycaprolactone-polyethylene glycol (PCL-PEG). Based on a biological component of thrombi, activated coagulation factor XIII (FXIIIa), which is responsible for fibrin crosslinking, we further developed FXIIIa-targeted near infrared imaging and thrombolytic nanoparticles, termed IR780/FPHM/LK NPs, through chemical conjugation of peptides to the system. In a ferric chloride (FeCl3)-induced mouse carotid thrombosis model, IR780/FPHM/LK NPs specifically targeted the thrombus and significantly enhanced the photoacoustic signal for an accurate diagnosis. When loaded with the fibrinolytic drug lumbrokinase (LK), FPHM remarkably dissociated the thrombus accompanied by an increase in the d-dimer level, a fibrin degradation product, and alleviation of fatal nonspecific hemorrhagic risk. Given its thrombus-specific imaging along with potent therapeutic activities, IR780/FPHM/LK NPs hold promise for developing nanotheranostic agents in preclinical thrombotic vascular disease models.

Thrombus Imaging Using 3D Printed Middle Cerebral Artery Model and Preclinical Imaging Techniques: Application to Thrombus Targeting and Thrombolytic Studies.

Diseases with the highest burden for society such as stroke, myocardial infarction, pulmonary embolism, and others are due to blood clots. Preclinical and clinical techniques to study blood clots are important tools for translational research of new diagnostic and therapeutic modalities that target blood clots. In this study, we employed a three-dimensional (3D) printed middle cerebral artery model to image clots under flow conditions using preclinical imaging techniques including fluorescent whole-body imaging, magnetic resonance imaging (MRI), and computed X-ray microtomography (microCT). Both liposome-based, fibrin-targeted, and non-targeted contrast agents were proven to provide a sufficient signal for clot imaging within the model under flow conditions. The application of the model for clot targeting studies and thrombolytic studies using preclinical imaging techniques is shown here. For the first time, a novel method of thrombus labeling utilizing barium sulphate (Micropaque®) is presented here as an example of successfully employed contrast agents for in vitro experiments evaluating the time-course of thrombolysis and thus the efficacy of a thrombolytic drug, recombinant tissue plasminogen activator (rtPA). Finally, the proof-of-concept of in vivo clot imaging in a middle cerebral artery occlusion (MCAO) rat model using barium sulphate-labelled clots is presented, confirming the great potential of such an approach to make experiments comparable between in vitro and in vivo models, finally leading to a reduction in animals needed.