Thrombus Imaging Research Articles

Imaging and implications of tumor thrombus in abdominal malignancies: reviewing the basics.

Extension of tumor tissue within a vein is a recognized prognostic factor in abdominal malignancy because of its influence on tumor staging and selection of therapeutic management. With the advent of newer surgical techniques, and variable treatment strategies, imaging plays a crucial role in categorizing patients according to the tumor resectability and vascular reconstruction techniques during surgery. Understanding the clinical impact of tumor thrombus increases the awareness of the radiologist about the key findings in tumor staging and decision-making of surgical approach. Ultrasound (US), computed tomography (CT), and magnetic resonance imaging (MRI) can be used individually and in combination to accurately assess the tumor thrombus. In our pictorial review, we will discuss the imaging findings and clinical consequences of tumor thrombosis in abdominal malignancies, including hepatocellular carcinoma, pancreatic neuroendocrine tumor, renal cancer, and adrenal cortical carcinoma.

Cerebral Venous Thrombosis: MR Black-Blood Thrombus Imaging with Enhanced Blood Signal Suppression.

The residual blood flow artifact is a critical confounder for MR black-blood thrombus imaging of cerebral venous sinus thrombosis. This study aimed to conduct a validation of a new MR black-blood thrombus imaging technique with enhanced blood signal suppression. Twenty-six participants (13 volunteers and 13 patients) underwent conventional imaging methods followed by 2 randomized black-blood thrombus imaging scans, with a preoptimized delay alternating with nutation for tailored excitation (DANTE) preparation switched on and off, respectively. The signal intensity of residual blood, thrombus, brain parenchyma, normal lumen, and noise on black-blood thrombus images were measured. The thrombus volume, SNR of residual blood, and contrast-to-noise ratio for residual blood versus normal lumen, thrombus versus residual blood, and brain parenchyma versus normal lumen were compared between the 2 black-blood thrombus imaging techniques. Segmental diagnosis of venous sinus thrombosis was evaluated for each black-blood thrombus imaging technique using a combination of conventional imaging techniques as a reference. In the volunteer group, the SNR of residual blood (11.3 ± 2.9 versus 54.0 ± 23.4, P < .001) and residual blood-to-normal lumen contrast-to-noise ratio (7.5 ± 3.4 versus 49.2 ± 23.3, P < .001) were significantly reduced using the DANTE preparation. In the patient group, the SNR of residual blood (16.4 ± 8.0 versus 75.0 ± 35.1, P = .002) and residual blood-to-normal lumen contrast-to-noise ratio (12.4 ± 7.8 versus 68.8 ± 35.4, P = .002) were also significantly lower on DANTE-prepared black-blood thrombus imaging. The new black-blood thrombus imaging technique provided higher thrombus-to-residual blood contrast-to-noise ratio, significantly lower thrombus volume, and substantially improved diagnostic specificity and agreement with conventional imaging methods. DANTE-prepared black-blood thrombus imaging is a reliable MR imaging technique for diagnosing cerebral venous sinus thrombosis.

Polydopamine-modified dual-ligand nanoparticles as highly effective and targeted magnetic resonance/photoacoustic dual-modality thrombus imaging agents.

BackgroundPlatelet activation and subsequent aggregation are the initial stages of thrombosis. A molecular probe that specifically targets activated platelets and remains retained under high shear stress in vivo can enhance the imaging effect to achieve early and accurate diagnosis.Methods and materialsIn this study, we constructed nanoparticles (NPs) using polydopamine to carry two peptides that simultaneously bind integrin αIIbβ3 and P-selectin on activated platelets to enhance the targeting of NPs to thrombus.ResultsThe targeting specificity and binding stability of the NPs on red and white thrombi were demonstrated in vitro using a simulated circulatory device and the targeting effect of the NPs on mixed thrombus was studied by magnetic resonance (MR)/photoacoustic (PA) dual-modality imaging in vivo. NPs that were surface modified with both peptides have higher selectivity and retention to red and white thrombi in vitro than NPs with a single or no peptide, and the targeting effect was closely related to the number and distribution of activated platelets as well as the structure and type of thrombus. The NPs also have MR/PA dual-modality imaging functionality, significantly enhancing the imaging of mixed thrombus in vivo.ConclusionThese dual-targeted NPs have improved targeting specificity and binding stability to different thrombi under high shear stress and are beneficial for the early diagnosis of thrombosis.

Trombo séptico localizado na topografia de átrio direito em um recém-nascido pré-termo: Relato de caso

Detalhamento do caso: Recém-nascido do sexo feminino, idade gestacional de 33 semanas, internada na unidade de terapia intensiva neonatal devido a síndrome da membrana hialina. Evoluiu com quadro de sepse, necessitando de antibioticoterapia e instalação de cateter venoso central em membro superior direito. Após persistência da sepse, foi solicitado ecocardiograma que visualizou imagem de trombo em átrio direito de provável etiologia séptica, pedunculado, móvel, aderido ao septo atrial. Paciente foi submetida a trombólise e evoluiu com melhora clínica e seguimento ambulatorial após alta hospitalar. Discussão: A persistência de quadro sépticos em recém-nascidos leva a suspeita de trombos sépticos, principalmente quando há instalação de cateter venoso central, que é considerado o maior fator de risco. O diagnóstico é feito preferencialmente através do ecocardiograma ou arteriografia contrastada e o tratamento consiste na retirada dos cateteres e terapia com trombolíticos.

Thrombus Imaging Characteristics and Outcomes in Acute Ischemic Stroke Patients Undergoing Endovascular Treatment.

Background and Purpose- Thrombus imaging characteristics have been reported to be useful to predict functional outcome and reperfusion in acute ischemic stroke. However, conflicting data about this subject exist in patients undergoing endovascular treatment. Therefore, we aimed to evaluate whether thrombus imaging characteristics assessed on computed tomography are associated with outcomes in patients with acute ischemic stroke treated by endovascular treatment. Methods- The MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) Registry is an ongoing, prospective, and observational study in all centers performing endovascular treatment in the Netherlands. We evaluated associations of thrombus imaging characteristics with the functional outcome (modified Rankin Scale at 90 days), mortality, reperfusion, duration of endovascular treatment, and symptomatic intracranial hemorrhage using univariable and multivariable regression models. Thrombus characteristics included location, clot burden score (CBS), length, relative and absolute attenuation, perviousness, and distance from the internal carotid artery terminus to the thrombus. All characteristics were assessed on thin-slice (≤2.5 mm) noncontrast computed tomography and computed tomography angiography, acquired within 30 minutes from each other. Results- In total, 408 patients were analyzed. Thrombus with distal location, higher CBS, and shorter length were associated with better functional outcome (adjusted common odds ratio, 3.3; 95% CI, 2.0-5.3 for distal M1 occlusion compared with internal carotid artery occlusion; adjusted common odds ratio, 1.15; 95% CI, 1.07-1.24 per CBS point; and adjusted common odds ratio, 0.96; 95% CI, 0.94-0.99 per mm, respectively) and reduced duration of endovascular procedure (adjusted coefficient B, -14.7; 95% CI, -24.2 to -5.1 for distal M1 occlusion compared with internal carotid artery occlusion; adjusted coefficient B, -8.5; 95% CI, -14.5 to -2.4 per CBS point; and adjusted coefficient B, 7.3; 95% CI, 2.9-11.8 per mm, respectively). Thrombus perviousness was associated with better functional outcome (adjusted common odds ratio, 1.01; 95% CI, 1.00-1.02 per Hounsfield units increase). Distal thrombi were associated with successful reperfusion (adjusted odds ratio, 2.6; 95% CI, 1.4-4.9 for proximal M1 occlusion compared with internal carotid artery occlusion). Conclusions- Distal location, higher CBS, and shorter length are associated with better functional outcome and faster endovascular procedure. Distal thrombus is strongly associated with successful reperfusion, and a pervious thrombus is associated with better functional outcome.

An unmet clinical need: The history of thrombus imaging

Robust thrombus imaging is an unresolved clinical unmet need dating back to the mid 1970s. While early molecular imaging approaches began with nuclear SPECT imaging, contrast agents for virtually all biomedical imaging modalities have been demonstrated in vivo with unique strengths and common weaknesses. Two primary molecular imaging targets have been pursued for thrombus imaging: platelets and fibrin. Some common issues noted over 40 years ago persist today. Acute thrombus is readily imaged with all probes and modalities, but aged thrombus remains a challenge. Similarly, anti-coagulation continues to interfere with and often negate thrombus imaging efficacy, but heparin is clinically required in patients suspected of pulmonary embolism, deep venous thrombosis or coronary ruptured plaque prior to confirmatory diagnostic studies have been executed and interpreted. These fundamental issues can be overcome, but an innovative departure from the prior approaches will be needed.

Semiconducting Perylene Diimide Nanostructure: Multifunctional Phototheranostic Nanoplatform.

Precision medicine requires noninvasive and accurate early diagnosis and individually appropriate treatments. Phototheranostics has been considered a frontier precision medical technology to provide rapid and safe disease localization and efficient cure. Harnessing the power of advanced nanomedicine with photonics, phototheranostics is rapidly developing and progressively becoming irreplaceable in modern medicine. Nanoscale semiconducting materials, such as inorganic semiconductors, organic conjugated polymers, and small molecules with photonic properties, have been extensively explored in medical imaging (fluorescence imaging, optical coherence tomography, and photoacoustic [PA] imaging) and phototherapy (photothermal, photodynamic, and photocontrolled combination therapies). In practical clinical applications, organic semiconducting materials, because of their biocompatibility and natural metabolism, are preferred over inorganic materials for phototheranostics. Supramolecular self-assembly is considered a significant method for preparing organic detachable and multifunctional phototheranostics, as supramolecular interactions, such as π-π interactions, hydrogen bonding, hydrophobic effects, and electrostatic interactions, are non-covalent and dynamic. Developing new and effective organic supramolecular phototheranostics requires exploration of well-designed basic building blocks with optical properties, understanding of the assembly at the nanoscale, and optimization of the phototheranostics with unique and distinctive multifunctional efficacy. In this Account, we summarize our recent work on the development of small molecular semiconducting perylene diimide (SPDI) for advanced phototheranostics. SPDI is modified to have strong near-infrared absorption beyond 700 nm by the push-pull electronic effect and owns the merits of remarkable photostability, large extinction coefficient, and high photothermal conversion efficiency. By hydrophilic modification, the amphiphile can self-assemble into a nanomicellar structure that allows PA imaging and can serve as a photothermal conversion agent. After theranostics delivery is achieved, this SPDI can be further functionalized for multimodality imaging and photothermally triggered multimodal synergistic therapy. Several well-designed asymmetric structures of SPDI can be obtained by stepwise modification of imides. It is noteworthy that the self-assembly of SPDI is controllable, allowing the preparation of different-sized spherical nanoparticles and rodlike nanoparticles and nanodroplets. For biomedical applications of SPDI phototheranostics (SPDIPTs), the size effect of SPDIPTs has been highlighted in lymph node mapping and cancer imaging. The PA properties and targeting peptide modification of SPDIPTs have brought about the ultrasensitive imaging of early thrombus. The supramolecular nanoconstructs of SPDIPTs further permit multimodality-imaging-guided cancer therapy. In brief, the design of SPDIPTs considers synthetic chemistry, supramolecular self-assembly, nanotechnology, and photonics. Furthermore, SPDIPTs have diverse biomedical applications and offer many opportunities for advancing nanomedicine.

Bimodal Fucoidan-Coated Zinc Oxide/Iron Oxide-Based Nanoparticles for the Imaging of Atherothrombosis.

A polyol method was used to obtain ultrasmall ZnO nanoparticles (NPs) doped with iron ions and coated with a low molecular weight fucoidan in order to perform in vivo MR and ex vivo fluorescence imaging of athrothrombosis. During the synthesis, the early elimination of water by azeotropic distillation with toluene allowed us to produce NPs which size, determined by XRD and TEM, decreased from 7 nm to 4 nm with the increase of iron/zinc ratios from 0.05 to 0.50 respectively. For the highest iron content (NP-0.50) NPs were evidenced as a mixture of nanocrystals made of wurtzite and cubic phase with a molar ratio of 2.57:1, although it was not possible to distinguish one from the other by TEM. NP-0.50 were superparamagnetic and exhibited a large emission spectrum at 470 nm when excited at 370 nm. After surface functionalization of NP-0.50 with fucoidan (fuco-0.50), the hydrodynamic size in the physiological medium was 162.0 ± 0.4 nm, with a corresponding negative zeta potential of −48.7 ± 0.4 mV, respectively. The coating was evidenced by FT-IR spectra and thermogravimetric analysis. Aqueous suspensions of fuco-0.50 revealed high transverse proton relaxivities (T2) with an r2 value of 173.5 mM−1 s−1 (300 K, 7.0 T) and remained stable for more than 3 months in water or in phosphate buffer saline without evolution of the hydrodynamic size and size distribution. No cytotoxic effect was observed on human endothelial cells up to 48 h with these NPs at a dose of 0.1 mg/mL. After injection into a rat model of atherothrombosis, MR imaging allowed the localization of diseased areas and the subsequent fluorescence imaging of thrombus on tissue slices.

Predictors of successful endovascular treatment in severe cerebral venous sinus thrombosis.

ObjectiveThe objective of this study was to evaluate the thrombus characteristics affecting the extent of recanalization to identify patients with severe cerebral venous sinus thrombus (CVT) more likely to benefit from endovascular therapy.MethodsSevere CVT patients scheduled for endovascular treatment were prospectively recruited into the study. Each thrombosed venous segment was evaluated regarding complete or partial recanalization based on digital subtraction angiography (DSA) after treatment. Magnetic resonance black‐blood thrombus imaging (MRBTI) was performed 1 day before endovascular treatment. The signal‐to‐noise ratio (SNR) of the clot, age of the clot, and baseline volume of the clot were compared between the complete and partial recanalization groups. A logistic regression analysis was performed to identify the association between these clot characteristics and recanalization status.ResultsTwenty‐one CVT patients undergoing endovascular therapy were prospectively included. There were 110 thrombosed segments, 54 of these segments were completely recanalized after endovascular treatment. An acute clot sign (ACS) was found in 39 segments and a subacute clot sign (SCS) was found in 71 segments. There was no significant difference on baseline volume of the clot (1638.8 ± 1432.2 mm3 vs. 1957.5 ± 2056.1 mm3, P > 0.05) between the complete and partial recanalization groups. Logistic regression analysis showed that ACS on MRBTI was associated with complete recanalization (P < 0.001, odds ratio = 3.937, 95% confidence interval, 1.6–9.5).Interpretation ACS can be used to predict complete recanalization in patients undergoing endovascular treatment. MRBTI provides a robust method to define clot composition and is potentially useful in selecting the most appropriate CVT patients for endovascular treatment.

Thrombus perviousness is not associated with first-pass revascularization using stent retrievers.

Recent studies suggest that thrombus imaging characteristics such as Hounsfield unit (HU) and perviousness assessed on noncontrast computed tomography (NCCT) and CT angiography (CTA) can predict successful recanalization. We assessed whether these thrombus imaging characteristics could predict successful first-pass recanalization. We retrospectively reviewed cases of mechanical thrombectomy over a three-year period in which patients received a multiphase CTA and were treated with a stent retriever on first pass. Thrombus attenuation, thrombus enhancement on arterial- and delayed-phase CTA and percentage washout were calculated and their association with first-pass recanalization, successful recanalization and distal embolic complications was studied. Fifty-two mechanical thrombectomy patients were included. First-pass recanalization was achieved in 59.6% and complete revascularization (Thrombolysis in Cerebral Infarction scale 2b/3) was achieved in 84.6%. There was no correlation between first-pass recanalization with thrombus density on NCCT ( p = 0.94), percentage enhancement on arterial ( p = 0.61) and delayed-phase CTA ( p = 0.23) or thrombus length ( p = 0.16). There was no correlation between number of passes and either thrombus density on NCCT ( p = 0.91) or percentage enhancement on arterial- ( p = 0.79) and delayed-phase ( p = 0.14) CTA or thrombus length ( p = 0.34). Clot length was significantly higher in patients with distal embolic complications than in those without (18.5 ± 7.9 vs 11.4 ± 6.6 mm, p = 0.005). Our data suggest that thrombus imaging characteristics on multiphase CTA cannot predict first-pass recanalization or successful revascularization in acute ischemic stroke patients treated with stent retrievers. Longer clot length was associated with higher risk of distal embolic complications.

Abstract TP237: Characterization of Retrieved Thrombus Composition by Morphological, Histopathological and Imaging Analysis in Acute Ischemic Stroke

Introduction: The aim of this study was to assess whether we could distinguish stroke subtype by analyzing the size, weight, shape, color and imaging characteristics of the retrieved thrombus. Methods: From October 2013 to January 2016, 28 thrombi were classified as cardioembolism (CE) and 16 were large artery atherosclerosis (LAD). The size, shape, and color characteristics of the thrombus were analyzed. The weight of total thrombi of each case was measured. The weight, length, and sectional area of the largest thrombus of each case was measured again. We compared the degree of circularity, roundness, aspect ratio, and solidity of the largest thrombus. The color image of the largest thrombus was analyzed by using RGB histograms. Retrieved thrombus was subjected to post-MRI under ex vivo conditions. Results: The probability of stroke due to CE increases as the RBC composition of thrombus increases, and the probability of stroke due to LAD increases as the fibrin composition of thrombus increases (p=0.018). The size of the cross-sectional area of the largest thrombus (22.38 ±21.48mm2 vs. 12.15±10.86mm2, p=0.043) is larger in the CE group. Also, the weight of total thrombi (140.00±231.39mg vs. 37.50± 30.31mg, p=0.049) and the weight of the largest thrombus (46.14±47.34mg vs. 17.94±16.89mg, p=0.013) is heavier in the CE group. Higher RGB values in the LAD group mean that the thrombus of the LAD group is brighter than the thrombus of the CE group. In multivariate logistic regression analysis, the mean Green value of RGB (OR 1.488, 95% CI 1.032-2.146; p= 0.033) was independently associated with LAD. Blooming artifacts of the post-MRI under ex vivo conditions well correlate with that of the pre-MRI (p=0.016), and blooming artifacts of the post-MRI under ex vivo conditions was associated with red blood cell composition of thrombus (p=0.005). Conclusions: The shape of the thrombus did not help to determine the stroke subtype. The weight, cross-sectional area, and color difference of the thrombus helped to distinguish CE and LAD, and the mean Green value of RGB was found to be the most significant predictor. And blooming artifacts of the post-MRI under ex vivo conditions was well correlated with that of the pre-MRI and red blood cell composition of thrombus.

Batroxobin in combination with anticoagulation may promote venous sinus recanalization in cerebral venous thrombosis: A real-world experience.

SummaryAimsThe objective of this study was to evaluate cerebral venous recanalization with magnetic resonance black‐blood thrombus imaging (MRBTI) in patients with cerebral venous thrombosis (CVT) who underwent batroxobin treatment in combination with anticoagulation.MethodsA total of 31 CVT patients were enrolled in this real‐world registry study. The patients were divided into batroxobin (n = 21) and control groups (n = 10). In addition to the same standard anticoagulation as in the control group, patients in the batroxobin group underwent intravenous batroxobin for a total of three times.ResultsIn the batroxobin group compared with the control group, we found better odds of recanalization degree [adjusted OR (95%CI) of 8.10 (1.61‐40.7)] and segment‐stenosis attenuation [adjusted OR (95%CI) of 4.48 (1.69‐11.9)] with batroxobin treatment. We further noted a higher ratio of patients with the attenuation of stenosis [adjusted OR (95%CI) of 26.4 (1.10‐635)]; as well as a higher ratio of segments with stenosis reversion [adjusted OR (95%CI) of 4.52 (1.48‐13.8)]. However, neurological deficits between the two groups showed no statistical difference at 90‐day follow‐up (P > 0.05).ConclusionsBatroxobin may promote venous sinus recanalization and attenuate CVT‐induced stenosis. Further randomized study of this promising drug may be warranted to better delineate the amount of benefit.

Diagnosing Recurrent DVT of the Leg by Two Different Non-Contrast-Enhanced Magnetic Resonance Direct Thrombus Imaging Techniques: A Pilot Study.

Introduction Magnetic resonance direct thrombus imaging (MRDTI) is a promising technique to improve the diagnostic management of patients with a suspected ipsilateral recurrent deep vein thrombosis (DVT) by direct visualization of a thrombus. Another magnetic resonance imaging (MRI) technique, T1-weighted turbo spin-echo spectral attenuated inversion recovery (TSE-SPAIR), has the potential to image a thrombus directly with a high spatial resolution as well. The main aim of this pilot study was to investigate if adding the TSE-SPAIR sequence to an MRDTI sequence performed in patients with suspected recurrent DVT may increase the diagnostic confidence of expert MRDTI readers. Methods Fifteen patients with suspected acute recurrent DVT were included in this study. The TSE-SPAIR sequence was scanned directly after the MRDTI scan but not used to guide clinical decision making, and both scans were adjudicated post hoc two times separately by three independent expert MRDTI readers. Diagnostic confidence was scored on a 4-point Likert scale: (1) poor (definite diagnosis impossible), (2) fair (evaluation of major findings possible), (3) good (definite diagnosis possible), and (4) excellent (exact diagnosis possible). Results The diagnostic confidence of expert readers increased when adding the TSE-SPAIR sequence on top of the MRDTI sequence from “good” (median, 3.0; interquartile range [IQR], 2.66–3.0) to “excellent” (median, 3.67; IQR 3.33–3.67; p = 0.001). Evaluation of the scans in the reversed order 5 months after initial reading showed similar results. Diagnostic accuracy for proximal DVT of both scan techniques was good. Conclusion The extra TSE-SPAIR sequence may help increase diagnostic confidence of radiologists in cases of uncertain diagnosis in patients with suspected ipsilateral recurrent DVT.

Radiomics-Based Intracranial Thrombus Features on CT and CTA Predict Recanalization with Intravenous Alteplase in Patients with Acute Ischemic Stroke.

Thrombus characteristics identified on non-contrast CT (NCCT) are potentially associated with recanalization with intravenous (IV) alteplase in patients with acute ischemic stroke (AIS). Our aim was to determine the best radiomics-based features of thrombus on NCCT and CT angiography associated with recanalization with IV alteplase in AIS patients and proximal intracranial thrombi. With a nested case-control design, 67 patients with ICA/M1 MCA segment thrombus treated with IV alteplase were included in this analysis. Three hundred twenty-six radiomics features were extracted from each thrombus on both NCCT and CTA images. Linear discriminative analysis was applied to select features most strongly associated with early recanalization with IV alteplase. These features were then used to train a linear support vector machine classifier. Ten times 5-fold cross-validation was used to evaluate the accuracy of the trained classifier and the stability of the selected features. Receiver operating characteristic curves showed that thrombus radiomics features are predictive of early recanalization with IV alteplase. The combination of radiomics features from NCCT, CTA, and radiomics changes is best associated with early recanalization with IV alteplase (area under the curve = 0.85) and was significantly better than any single feature such as thrombus length (P < .001), volume (P < .001), and permeability as measured by mean attenuation increase (P < .001), maximum attenuation in CTA (P < .001), maximum attenuation increase (P < .001), and assessment of residual flow grade (P < .001). Thrombus radiomics features derived from NCCT and CTA are more predictive of recanalization with IV alteplase in patients with acute ischemic stroke with proximal occlusion than previously known thrombus imaging features such as length, volume, and permeability.

Stroke Risk Period After Acute Myocardial Infarction Revised

Stroke Risk Period After Acute Myocardial Infarction Revised

Glycoprotein IIb/IIIa receptor imaging with 18F-GP1 positron emission tomography for acute venous thromboembolism: an open-label, non-randomized, first-in-human phase 1 study.

18F-GP1 is a derivative of elarofiban with a high affinity to activated platelet glycoprotein IIb/IIIa (GPIIb/IIIa) and favorable in vivo characteristics for thrombus imaging in preclinical models. We aimed to explore the detection rate of thromboembolic foci with 18F-GP1 positron emission tomography/computed tomography (PET/CT) in patients with acute venous thromboembolism (VTE), and to evaluate the safety, biodistribution, pharmacokinetics, and metabolism of 18F-GP1. Methods: We studied patients who had signs or symptoms of acute deep vein thrombosis (DVT) of the leg or acute pulmonary embolism (PE) within 14 days prior to 18F-GP1 PET/CT, and had thromboembolic foci confirmed by conventional imaging (n = 10 for DVT and n = 10 for PE). Dynamic whole-body PET/CT images were acquired for up to 140 minutes after injection of 250 MBq of 18F-GP1. Results:18F-GP1 PET/CT was well tolerated without any drug-related adverse events, and showed high initial uptake in spleen, kidney, and blood pool, followed by rapid clearance. The overall image quality was excellent and allowed interpretation in all patients. 18F-GP1 PET/CT identified thromboembolic foci in all 20 patients with either DVT or PE. Vessel-level analysis revealed that 18F-GP1 PET/CT detected 89% (68/76) of vessels with DVT, and 60% (146/245) for PE. Importantly, 18F-GP1 PET/CT showed increased uptake in 32 vessels that were not detected by conventional imaging, of which 25 were located in distal veins of the lower extremity in 12 patients. A positive correlation was found between 18F-GP1 uptake and P-selectin-positive circulating platelets (r = 0.656, P = 0.002). Conclusion:18F-GP1 is a promising PET tracer for imaging acute VTE in patients. 18F-GP1 PET/CT may identify thrombi in distal veins of the leg, where conventional imaging has limitations.

Low-Fouling and Biodegradable Protein-Based Particles for Thrombus Imaging.

Nanomedicine holds great promise for vascular disease diagnosis and specific therapy, yet rapid sequestration by the mononuclear phagocytic system limits the efficacy of particle-based agents. The use of low-fouling polymers, such as poly(ethylene glycol), efficiently reduces this immune recognition, but these nondegradable polymers can accumulate in the human body and may cause adverse effects after prolonged use. Thus, new particle formulations combining stealth, low immunogenicity and biocompatible features are required to enable clinical use. Here, a low-fouling particle platform is described using exclusively protein material. A recombinant protein with superior hydrophilic characteristics provided by the amino acid repeat proline, alanine, and serine (PAS) is designed and cross-linked into particles with lysine (K) and polyglutamic acid (E) using mesoporous silica templating. The obtained PASKE particles have low-fouling behavior, have a prolonged circulation time compared to albumin-based particles, and are rapidly degraded in the cell's lysosomal compartment. When labeled with near-infrared fluorescent molecules and functionalized with an anti-glycoprotein IIb/IIIa single-chain antibody targeting activated platelets, the particles show potential as a noninvasive molecular imaging tool in a mouse model of carotid artery thrombosis. The PASKE particles constitute a promising biodegradable and versatile platform for molecular imaging of vascular diseases.

Assessing venous thrombus in renal cell carcinoma: preliminary results for unenhanced 3D-SSFP MRI

To test the potential of unenhanced cardiac- and respiratory-motion-corrected three-dimensional steady-state free precession (3D-SSFP) magnetic resonance imaging (MRI) for the assessment of inferior vena cava (IVC) thrombus in patients with clear-cell renal cell carcinoma (cRCC), compared to standard contrast-enhanced (CE)-MRI and CE-computed tomography (CT). Eighteen patients with cRCC and IVC thrombus, who received CE-MRI and 3D-SSFP at 1.5 T between June 2015 and December 2017, were included. The diagnostic performance of 3D-SSFP in determining the level of thrombus extension, contrast-to-noise ratio (CNR), and image quality were compared with standard MRI/CT and validated against intraoperative and histopathology results. There was 100% agreement between 3D-SSFP, 83.3% agreement between CE-MRI, and 71.4% agreement between CE-CT and surgical findings regarding the level of IVC thrombus. In addition, 3D-SSFP showed a slightly superior estimate of pathological IVC volume. 3D-SSFP reached a significantly higher CNR in the supra- and infrarenal IVC compared to the morphological sequence T2-weighted half-Fourier axial single-shot fast spin-echo (T2-HASTE) and all phases of CE-MRI. More specifically, 3D-SSFP showed a significantly higher CNR in the infrarenal IVC (mean CNR of 10.09±5.74 versus 4.21±2.33 in the delayed phase, p≤0.001) and in the suprarenal IVC (mean CNR of 9.22±4.11 versus 4.84±5.74 in the late arterial phase, p=0.015). CE-CT also was significantly inferior to 3D-SSFP (p≤0.01) and slightly inferior to CE-MRI (p>0.05). The thrombus delineation score for 3D-SSFP (4.38±0.67) was higher compared to CE-MRI (3.76±0.56, p=0.005). This preliminary study indicates that 3D-SSFP can achieve an accurate assessment of IVC thrombus in cRCC patients without the need for contrast medium administration, being superior to standard MRI and CT.

Cardiovascular magnetic resonance black-blood thrombus imaging for the diagnosis of acute deep vein thrombosis at 1.5 Tesla

BackgroundThe aim was to investigate the feasibility of a cardiovascular magnetic resonance (CMR) black-blood thrombus imaging (BBTI) technique, based on delay alternating with nutation for tailored excitation black-blood preparation and a variable flip angle turbo-spin-echo readout, for the diagnosis of acute deep vein thrombosis (DVT) at 1.5 T.MethodsBBTI was conducted in 15 healthy subjects and 30 acute DVT patients. Contrast-enhanced CMR venography (CE-CMRV) was conducted for comparison and only performed in the patients. Apparent contrast-to-noise ratios between the thrombus and the muscle/lumen were calculated to determine whether BBTI could provide an adequate thrombus signal for diagnosis. Two blinded readers assessed the randomized BBTI images from all participants and made independent decisions on the presence or absence of thrombus at the segment level. Images obtained by CE-CMRV were also randomized and assessed by the two readers. Using the consensus CE-CMRV as a reference, the sensitivity, specificity, positive and negative predictive values, and accuracy of BBTI, as well as its diagnostic agreement with CE-CMRV, were calculated. Additionally, diagnostic confidence and interobserver diagnostic agreement were evaluated.ResultsThe thrombi in the acute phase exhibited iso- or hyperintense signals on the BBTI images. All the healthy subjects were correctly identified from the participants based on the segment level. The diagnostic confidence of BBTI was comparable to that of CE-CMRV (3.69 ± 0.52 vs. 3.70 ± 0.47). High overall sensitivity (95.2%), SP (98.6%), positive predictive value (96.0%), negative predictive value (98.3%), and accuracy (97.7%), as well as excellent diagnostic and interobserver agreements, were achieved using BBTI.ConclusionBBTI is a reliable, contrast-free technique for the diagnosis of acute DVT at 1.5 T.

Diagnosing upper extremity deep vein thrombosis with non-contrast-enhanced Magnetic Resonance Direct Thrombus Imaging: A pilot study

Diagnosing upper extremity deep vein thrombosis (UEDVT) can be challenging. Compression ultrasonography is often inconclusive because of overlying anatomic structures that hamper compressing veins. Contrast venography is invasive and has a risk of contrast allergy. Magnetic Resonance Direct Thrombus Imaging (MRDTI) and Three Dimensional Turbo Spin-echo Spectral Attenuated Inversion Recovery (3D TSE-SPAIR) are both non-contrast-enhanced Magnetic Resonance Imaging (MRI) sequences that can visualize a thrombus directly by the visualization of methemoglobin, which is formed in a fresh blood clot. MRDTI has been proven to be accurate in diagnosing deep venous thrombosis (DVT) of the leg. The primary aim of this pilot study was to test the feasibility of diagnosing UEDVT with these MRI techniques. MRDTI and 3D TSE-SPAIR were performed in 3 pilot patients who were already diagnosed with UEDVT by ultrasonography or contrast venography. In all patients, UEDVT diagnosis could be confirmed by MRDTI and 3D TSE-SPAIR in all vein segments. In conclusion, this study showed that non-contrast MRDTI and 3D TSE-SPAIR sequences may be feasible tests to diagnose UEDVT. However diagnostic accuracy and management studies have to be performed before these techniques can be routinely used in clinical practice.