A novel score to estimate thrombus burden and predict intracranial hypertension in cerebral venous sinus thrombosis.

BACKGROUND: Current methods to evaluate the severity of cerebral venous sinus thrombosis (CVST) lack patient-specific indexes. Herein, a novel scoring method was investigated to estimate the thrombus burden and the intracranial pressure (ICP) of CVST. METHODS: In this retrospective study from January 2019 through December 2021, we consecutively enrolled patients with a first-time confirmed diagnosis of CVST by contrast-enhanced magnetic resonance venography (CE-MRV) or computed tomography venography (CTV). In these patients, a comprehensive CVST-Score was established using magnetic resonance black-blood thrombus imaging (MRBTI) to estimate the thrombus burden semi-quantitatively. The relationship between CVST-Score and ICP was explored to assess the potential of using the CVST-score to evaluate ICP noninvasively and dynamically. RESULTS: A total of 87 patients were included in the final analysis. The CVST-Scores in different ICP subgroups were as follows: 4.29±2.87 in ICP<250mmH2O subgroup, 11.36±3.86 in ICP =250-330mmH2O subgroup and 14.99±3.15 in ICP>330mmH2O subgroup, respectively (p<0.001). For patients with ICP ≤330mmH2O, the CVST-Score was linearly and positively correlated with ICP (R2=0.53). The receiver operating characteristic (ROC) curves showed the optimal CVST-Score cut-off values to predict ICP ≥250mmH2O and >330mmH2O were 7.15 and 11.62, respectively (P<0.001). Multivariate analysis indicated CVST-Score as an independent predictor of ICP ≥250mmH2O (odds ratio, 2.15; 95% confidence interval, 1.49-3.10; p<0.001). CONCLUSIONS: A simple and noninvasive CVST-Score can rapidly estimate the thrombus burden and predict the severity of intracranial hypertension in patients with CVST. The CVST-Score can aid in evaluating therapeutic responses and avoiding unnecessary invasive procedures at long-term follow-up.

Does thrombus imaging characteristics predict the degree of recanalisation after endovascular thrombectomy in acute ischaemic stroke?

BACKGROUND: Identification of computed tomography (CT) thrombus imaging characteristics can predict the degree of recanalization and outcome after endovascular thrombectomy (EVT) in patients with acute ischaemic stroke and large vessel occlusion. AIM: We analyzed the thrombus imaging characteristics and procedural factors and correlated with the degree of recanalization and functional outcome after EVT. METHODS: We evaluated the thrombus imaging characteristics (hyperdense MCA sign, thrombus location, length and thrombus permeability) from thin slice CT and CT angiogram. In addition, groin to recanalization time, number of passes, and EVT technique were documented. The primary outcome was degree of recanalization (mTICI score) and secondary outcome was modified Rankin scale (mRS) at 3 months. RESULTS: The mean age of 102 patients was 60.5±11.8 years. Patients with hyperdense MCA sign (90 % vs 75%, p=0.07) and permeable thrombus (86 % vs 70 %, p=0.09) had good recanalization (mTICI grade 2b,2c or 3). The requirement of <3 passes (90 % vs 62 %, p= 0.001) was associated with good recanalization. Multiple logistic regression analysis showed thrombus permeability (OR 5.9; 95% CI 1.3-26.6, p=0.02), use of stent retreiver alone (without aspiration) (OR 5.4; 95% CI 1.3-22.5, p=0.02) and a puncture to recanalization ≤60 minutes (OR 7.9; 95% CI 1.7-36.8; p=0.008) were associated with good recanalization. The requirement of ≥3 passes was associated with poor functional outcome (OR 3.4;95% CI 1.2-9.8; p=0.02). CONCLUSIONS: Thrombus permeability was a predictor of successful recanalization after EVT. The requirement of three or more passes during EVT was associated with poor recanalization and poor functional outcome.

Efficient synthesis of NIR emitting bis[2-(2'-hydroxylphenyl)benzoxazole] derivative and its potential for imaging applications.

Unassymetric bis[2-(2'-hydroxyphenylbenzoxole)] bis(HBO) derivatives with a DPA functionality for zinc binding have been developed with an efficient synthetic route, using the retrosynthetic analysis. Comparison of bis(HBO) derivatives with different substitution patterns allows us to verify and optimize their unique fluorescence properties. Upon binding zinc cation, bis(HBO) derivatives give a large fluorescence turn-on in both visible (λem ≈ 536 nm) and near-infrared (NIR) window (λem ≈ 746 nm). The probes are readily excitable by a 488 nm laser, making this series of compounds a suitable imaging tool for in vitro and in vivo study on a confocal microscope. The application of zinc binding-induced fluorescence turn-on is successfully demonstrated in cellular environments and thrombus imaging.

Value of thrombus imaging in predicting the outcomes of patients with large-vessel occlusive strokes after endovascular therapy.

BACKGROUND: Acute ischemic stroke leads to serious long-term disability and high mortality, especially in patients with large-vessel occlusive strokes. Nowadays, endovascular therapy is considered as an alternative treatment for these patients. Several studies have used thrombus characteristics based on non-contrast computed tomography (NCCT) and computed tomography angiography (CTA) to predict prognosis in ischemic stroke. We conducted a systematic review to identify potential imaging predictive factors for successful recanalization and improved clinical outcome after endovascular therapy in patients with large-vessel occlusion (LVO) in anterior arterial circulation. METHODS: The PubMed databases were searched for related studies reported between September 18, 2009, and September 18, 2019. RESULTS: We selected 11 studies on revascularization and 12 studies on clinical outcome. Patients with thrombus of higher Hounsfield unit (HU), shorter length, higher clot burden score, and increased thrombus permeability may achieve higher recanalization and improved clinical outcome, but the matter is still under debate. CONCLUSION: Imaging of thrombus can be used as an aseessment tool to predict the outcomes and it needs further studies in the future.

Quantitative Imaging of Cerebral Thromboemboli In Vivo: The Effects of Tissue-Type Plasminogen Activator.

BACKGROUND AND PURPOSE: Quantitative imaging for the noninvasive assessment of thrombolysis is needed to advance basic and clinical thrombosis-related research and tailor tissue-type plasminogen activator (tPA) treatment for stroke patients. We quantified the evolution of cerebral thromboemboli using fibrin-targeted glycol chitosan-coated gold nanoparticles and microcomputed tomography, with/without tPA therapy. METHODS: We injected thrombi into the distal internal carotid artery in mice (n=50). Fifty-five minutes later, we injected fibrin-targeted glycol chitosan-coated gold nanoparticles, and 5 minutes after that, we treated animals with tPA or not (25 mg/kg). We acquired serial microcomputed tomography images for 24 hours posttreatment. RESULTS: Thrombus burden at baseline was 784×103±59×103 µm2 for the tPA group (n=42) and 655×103±103×103 µm2 for the saline group (n=8; P=0.37). Thrombus shrinkage began at 0.5 to 1 hour after tPA therapy, with a maximum initial rate of change at 4603±957 µm2/min. The rate of change lowered to ≈61% level of the initial in hours 1 to 2, followed by ≈29% and ≈1% in hours 2 to 3 and 3 to 24, respectively. Thus, 85% of total thrombolysis over 24 hours (≈500 µm2, equivalent to 64% of the baseline thrombus burden) occurred within the first 3 hours of treatment. Thrombus burden at 24 hours could be predicted at around 1.5 to 2 hours. Saline treatment was not associated with significant changes in the thrombus burden. Infarct size was smaller in the tPA group versus saline group (18.1±2.3 versus 45.8±3.3 mm2; P<0.01). Infarct size correlated to final thrombus burden (r=0.71; P<0.01). Time to thrombolysis, completeness of thrombolysis, and tPA therapy were independent predictors of infarct size. CONCLUSIONS: Thromboembolic burden and the efficacy of tPA therapy can be assessed serially, noninvasively, and quantitatively using high-resolution microcomputed tomography and a fibrin-binding nanoparticle imaging agent.

Black-blood thrombus imaging (BTI): a contrast-free cardiovascular magnetic resonance approach for the diagnosis of non-acute deep vein thrombosis.

BACKGROUND: Deep vein thrombosis (DVT) is a common but elusive illness that can result in long-term disability or death. Accurate detection of thrombosis and assessment of its size and distribution are critical for treatment decision-making. In the present study, we sought to develop and evaluate a cardiovascular magnetic resonance (CMR) black-blood thrombus imaging (BTI) technique, based on delay alternating with nutation for tailored excitation black-blood preparation and variable flip angle turbo-spin-echo readout, for the diagnosis of non-acute DVT. METHODS: This prospective study was approved by institutional review board and informed consent obtained from all subjects. BTI was first conducted in 11 healthy subjects for parameter optimization and then conducted in 18 non-acute DVT patients to evaluate its diagnostic performance. Two clinically used CMR techniques, contrast-enhanced CMR venography (CE-MRV) and three dimensional magnetization prepared rapid acquisition gradient echo (MPRAGE), were also conducted in all patients for comparison. All images obtained from patients were analyzed on a per-segment basis. Using the consensus diagnosis of CE-MRV as the reference, the sensitivity (SE), specificity (SP), positive and negative predictive values (PPV and NPV), and accuracy (ACC) of BTI and MPRAGE as well as their diagnostic agreement with CE-MRV were calculated. Besides, diagnostic confidence and interreader diagnostic agreement were evaluated for all three techniques. RESULTS: BTI with optimized parameters effectively nulled the venous blood flow signal and allowed directly visualizing the thrombus within the black-blood lumen. Higher SE (90.4% vs 67.6%), SP (99.0% vs. 97.4%), PPV (95.4% vs. 85.6%), NPV (97.8% vs 92.9%) and ACC (97.4% vs. 91.8%) were obtained by BTI in comparison with MPRAGE. Good diagnostic confidence and excellent diagnostic and interreader agreements were achieved by BTI, which were superior to MPRAGE on detecting the chronic thrombus. CONCLUSION: BTI allows direct visualization of non-acute DVT within the dark venous lumen and has the potential to be a reliable diagnostic tool without the use of contrast medium.

Absence of susceptibility vessel sign and hyperdense vessel sign in patients with cancer-related stroke.

Background and aim: Identification of paraneoplastic hypercoagulability in stroke patients helps to guide investigations and prevent stroke recurrence. A previous study demonstrated an association between the absence of the susceptibility vessel sign (SVS) on brain MRI and active cancer in patients treated with mechanical thrombectomy. The present study aimed to confirm this finding and assess an association between the absence of the hyperdense vessel sign (HVS) on head CT and active cancer in all stroke patients. Methods: SVS and HVS status on baseline imaging were retrospectively assessed in all consecutive stroke patients treated at a comprehensive stroke center between 2015 and 2020. Active cancer, known at the time of stroke or diagnosed within 1 year after stroke (occult cancer), was identified. Adjusted odds ratios (aOR) and their 95% confidence interval (CI) for the association between the thrombus imaging characteristics and cancer were calculated using multivariable logistic regression. Results: Of the 2,256 patients with thrombus imaging characteristics available at baseline, 161 had an active cancer (7.1%), of which 36 were occult at the time of index stroke (1.6% of the total). The absence of SVS was associated with active cancer (aOR 3.14, 95% CI 1.45-6.80). No significance was reached for the subgroup of occult cancer (aOR 3.20, 95% CI 0.73-13.94). No association was found between the absence of HVS and active cancer (aOR 1.07, 95% CI 0.54-2.11). Conclusion: The absence of SVS but not HVS could help to identify paraneoplastic hypercoagulability in stroke patients with active cancer and guide patient care.

Deep learning prediction of stroke thrombus red blood cell content from multiparametric MRI.

BACKGROUND AND PURPOSE: Thrombus red blood cell (RBC) content has been shown to be a significant factor influencing the efficacy of acute ischemic stroke treatment. In this study, our objective was to evaluate the ability of convolutional neural networks (CNNs) to predict ischemic stroke thrombus RBC content using multiparametric MR images. MATERIALS AND METHODS: Retrieved stroke thrombi were scanned ex vivo using a three-dimensional multi-echo gradient echo sequence and histologically analyzed. 188 thrombus R2*, quantitative susceptibility mapping and late-echo GRE magnitude image slices were used to train and test a 3-layer CNN through cross-validation. Data augmentation techniques involving input equalization and random image transformation were employed to improve network performance. The network was assessed for its ability to quantitatively predict RBC content and to classify thrombi into RBC-rich and RBC-poor groups. RESULTS: The CNN predicted thrombus RBC content with an accuracy of 62% (95% CI 48-76%) when trained on the original dataset and improved to 72% (95% CI 60-84%) on the augmented dataset. The network classified thrombi as RBC-rich or poor with an accuracy of 71% (95% CI 58-84%) and an area under the curve of 0.72 (95% CI 0.57-0.87) when trained on the original dataset and improved to 80% (95% CI 69-91%) and 0.84 (95% CI 0.73-0.95), respectively, on the augmented dataset. CONCLUSIONS: The CNN was able to accurately predict thrombus RBC content using multiparametric MR images, and could provide a means to guide treatment strategy in acute ischemic stroke.

3D Turbo Spin-echo MRI-based Mechanical Thrombectomy at Middle Cerebral Artery Bifurcations.

We describe three cases with acute middle cerebral artery (MCA) occlusion. From the pre-operative MRI, including three-dimensional turbo spin-echo sequences using T1WI and T2WI, we assessed both thrombus configuration and arterial anatomy at the MCA bifurcations. For efficient endovascular thrombectomy, we identified the applied MCA segment 2 (M2) branch, in which the main thrombus was buried. Sufficient recanalization after a single pass was achieved and the patients made a marked recovery. Although mechanical thrombectomy for M2 occlusion has not been of proven benefit, the endovascular procedure based on three-dimensional turbo spin-echo imaging is useful for more complete thrombus removal at MCA bifurcations.

Magnetic resonance black-blood thrombus imaging can confirm chronic cerebral venous thrombosis: a case report and literature review.

BACKGROUND: Cerebral venous thrombosis (CVT) is easily missed or misdiagnosed in clinical settings because of its high variability in terms of symptoms and radiological findings. Herein, we aimed to explore a promising modality for confirming presumed CVT in the hope to uncover its superior diagnostic performance to conventional imaging modalities.Case presentation: The patient complained of intolerable pain in her forehead and left eye. Her lumbar puncture opening pressure was 140 mmH2O, and her cerebrospinal fluid composition was normal. No marked abnormalities were observed in routine brain images, including non-contrast computed tomography, magnetic resonance imaging, and contrast-enhanced magnetic resonance venography. However, chronic mural thrombi in the lumen of the left cortical veins, transverse/sigmoid sinus, and superior sagittal sinus were identified in magnetic resonance black-blood thrombus imaging (MRBTI) maps. CONCLUSIONS: MRBTI can be used to directly and non-invasively visualize thrombi, and may thus be a promising tool over alternative routine techniques for confirming the diagnosis of CVT.

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

PURPOSE: Cerebral 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. METHOD: This 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. RESULTS: Pathological 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). CONCLUSIONS: Current findings suggest asymmetrical pathological pachymeningeal enhancement was associated was CVT and may be a new imaging feature for CVT.

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.

Comparison Between the Diagnostic Performance of 1.5 T and 3.0 T field Strengths for Detecting Deep Vein Thrombosis Using Magnetic Resonance Black-Blood Thrombus Imaging.

BACKGROUND: Magnetic resonance (MR) black-blood thrombus imaging (BTI) is an accurate diagnostic technique for detecting deep vein thrombosis (DVT) but to date there have been no studies comparing the diagnostic performance and consistency of this technique at different field strengths. In this study, we evaluated and compared the diagnostic performance of BTI for detecting DVT at 1.5 T and 3.0 T field strengths. METHODS: A total of 40 patients with DVT were enrolled in this study from November 2015 up to October 2018. All patients underwent BTI, a contrast-free T1-weighted MR imaging technique for detecting DVT, and contrast-enhanced MR venography (CE-MRV) at 1.5 T or 3.0 T field strengths. The MR data analyses used 1160 segments from the venous lumen of the 40 patients. The signal-to-noise ratio and contrast-to-noise ratio between thrombus and muscle/lumen were calculated to compare BTI at 1.5 T or 3.0 T to determine the image performance for thrombus detection at 1.5 T or 3.0 T. Two physicians blinded to the study evaluated all BTI images and calculated the overall sensitivity (SE), specificity (SP), positive predictive value (PPV) and negative predictive value (NPV), accuracy, and diagnostic consistency at 1.5 T and 3.0 T. These images and values were compared to control CE-MRV images that had been obtained by 2 senior physicians and used as reference standards. In addition, the reliability and consistency of diagnoses between observers were also evaluated. RESULTS: Two study-blind physicians reviewed all BTI images to diagnose thrombus and to determine SE, SP, PPV, NPV, and accuracy. There were no statistical differences in SE, SP, PPV, NPV, or accuracy between the 1.5 T and 3.0 T groups. CONCLUSIONS: Black-blood thrombus imaging has high SE, SP, and accuracy for DVT diagnosis both at 1.5 T and 3.0 T field strengths. This noninvasive diagnostic technique, which does not require the use of contrast agents, can be widely used in the clinical screening of DVT and follow-up after treatment.

Magnetic Resonance Direct Thrombus Imaging (MRDTI) Can Distinguish Between Old and New Thrombosis in the Abdominal Aorta: a Case Report.

A 43-year-old man complaining of abdominal angina for several months showed a large suprarenal aneurysm of the abdominal aorta with extensive circumferential wall thrombosis, complete occlusion of the right renal artery and a critically stenosed left renal artery on CT angiography. He suffered from severe hypertension and renal failure. A percutaneous transluminal angioplasty (PTA) was planned. After the PTA procedure, which was complicated by the development of left renal artery occlusion, successful rescue revascularization surgery was performed. Since we were hesitant to start anticoagulant treatment because of a high bleeding risk, magnetic resonance direct thrombus imaging was performed to assess the age of the extensive arterial thrombosis. The aortic thrombus showed a low signal intensity, which is indicative of chronic rather than acute thrombosis. Therefore, oral anticoagulant treatment was not started. The patient recovered without major complications. LEARNING POINTS: Accurate diagnosis and treatment of aortic intraluminal thrombosis are of the utmost importance to prevent serious complications such as (peripheral) arterial embolic occlusion with resultant ischemia.Current imaging modalities do not allow for accurate distinction between acute and chronic thrombosis in the abdominal aorta. Hence, differentiating between stable and unstable thrombosis is challenging.The non-invasive magnetic resonance direct thrombus imaging technique may be a valuable additional imaging test to establish a definitive diagnosis and treatment plan in patients with abdominal aortic thrombosis.

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.

Spectroscopic Assessment of Gold Nanoparticle Biodistribution Using Surface Plasmon Resonance Phenomena.

Pharmacokinetic (PK) evaluation of nanomaterials are crucial for further clinical development of imaging nanomaterials. In spite of huge advances in nanoparticle-based biomedical research, PK assessment typically requires substantial resources. Here, we show a simple, inexpensive, and yet precise analytical method applicable to the PK interrogation of gold nanoparticles (AuNPs) in the body. We have developed a UV-vis spectroscopic technique that utilizes mechanochemical treatments to separate AuNPs from tissues and then employs surface plasmon of extracted AuNPs to quantify their distribution in the body. This method allows the detection of 10 µg/mL of AuNPs in solution, as was confirmed by using inductively coupled plasma mass spectrometry. We demonstrate biodistribution of fibrin-targeted AuNPs that enable microCT-based visualization of arterial thrombi in mice: blood and thrombi as well as various organs. We believe that our method is generally applicable to most PK studies utilizing AuNPs in medical applications.

Targeting Human Thrombus by Liposomes Modified with Anti-Fibrin Protein Binders.

Development of tools for direct thrombus imaging represents a key step for diagnosis and treatment of stroke. Nanoliposomal carriers of contrast agents and thrombolytics can be functionalized to target blood thrombi by small protein binders with selectivity for fibrin domains uniquely formed on insoluble fibrin. We employed a highly complex combinatorial library derived from scaffold of 46 amino acid albumin-binding domain (ABD) of streptococcal protein G, and ribosome display, to identify variants recognizing fibrin cloth in human thrombus. We constructed a recombinant target as a stretch of three identical fibrin fragments of 16 amino acid peptide of the Bß chain fused to TolA protein. Ribosome display selection followed by large-scale Enzyme-Linked ImmunoSorbent Assay (ELISA) screening provided four protein variants preferentially binding to insoluble form of human fibrin. The most specific binder variant D7 was further modified by C-terminal FLAG/His-Tag or double His-tag for the attachment onto the surface of nanoliposomes via metallochelating bond. D7-His-nanoliposomes were tested using in vitro flow model of coronary artery and their binding to fibrin fibers was demonstrated by confocal and electron microscopy. Thus, we present here the concept of fibrin-targeted binders as a platform for functionalization of nanoliposomes in the development of advanced imaging tools and future theranostics.

Thrombin-activatable fluorescent peptide incorporated gold nanoparticles for dual optical/computed tomography thrombus imaging.

Thrombosis is an important pathophysiologic phenomenon in various cardiovascular diseases, which can lead to oxygen deprivation and infarction of tissues by generation of a thrombus. Thus, direct thrombus imaging can provide beneficial in diagnosis and therapy of thrombosis. Herein, we developed thrombin-activatable fluorescent peptide (TAP) incorporated silica-coated gold nanoparticles (TAP-SiO2@AuNPs) for direct imaging of thrombus by dual near-infrared fluorescence (NIRF) and micro-computed tomography (micro-CT) imaging, wherein TAP molecules were used as targeted thrombin-activatable peptide probes for thrombin-specific NIRF imaging. The freshly prepared TAP-SiO2@AuNPs had an average diameter of 39.8 ± 2.55 nm and they showed the quenched NIRF signal in aqueous condition, due to the excellent quenching effect of TAP molecules on the silica-gold nanoparticle surface. However, 30.31-fold higher NIRF intensity was rapidly recovered in the presence of thrombin in vitro, due to the thrombin-specific cleavage of quenched TAP molecules on the gold particle surface. Furthermore, TAP-SiO2@AuNPs were successfully accumulated in thrombus by their particle size-dependent capturing property, and they presented a potential X-ray absorption property in a dose-dependent manner. Finally, thrombotic lesion was clearly distinguished from peripheral tissues by dual NIRF/micro-CT imaging after intravenous injection of TAP-SiO2@AuNPs in the in situ thrombotic mouse model, simultaneously. This study showed that thrombin-activatable fluorescent peptide incorporated silica-coated gold nanoparticles can be potentially used as a dual imaging probe for direct thrombus imaging and therapy in clinical applications.

Percutaneous endovascular biopsy in the diagnosis of venous sinus lesions: technical note.

Intracranial hypertension (IH) may be misdiagnosed owing to the lack of typical imaging features and pathological confirmation of the sinus lesions. The authors report the use of percutaneous endovascular biopsy (PEB) for the diagnosis of IH in patients with venous sinus lesions. A total of 9 patients (age 46 ± 9 years) underwent PEB between June 2016 and August 2017. All patients underwent lumbar puncture and contrast-enhanced MRI before the procedure. PEB was technically successful in 6 patients. No intra- or postprocedural complications occurred. The confirmed lesions were meningioma in 2 patients and fibrous thrombus in 4 patients. All patients received individualized treatment. PEB of venous sinus lesions is a safe and efficient method to establish an early diagnosis and appropriate treatment in patients with IH.

Direct Thrombus Imaging in Stroke.

There is an emergent need for imaging methods to better triage patients with acute stroke for tissue-plasminogen activator (tPA)-mediated thrombolysis or endovascular clot retrieval by directly visualizing the size and distribution of cerebral thromboemboli. Currently, magnetic resonance (MR) or computed tomography (CT) angiography visualizes the obstruction of blood flow within the vessel lumen rather than the thrombus itself. The present visualization method, which relies on observation of the dense artery sign (the appearance of cerebral thrombi on a non-enhanced CT), suffers from low sensitivity. When translated into the clinical setting, direct thrombus imaging is likely to enable individualized acute stroke therapy by allowing clinicians to detect the thrombus with high sensitivity, assess the size and nature of the thrombus more precisely, serially monitor the therapeutic effects of thrombolysis, and detect post-treatment recurrence. This review is intended to provide recent updates on stroke-related direct thrombus imaging using MR imaging, positron emission tomography, or CT.