Novel imaging strategies in venous thromboembolism

Venous thromboembolism (VTE) encompasses pulmonary embolism (PE) and deep vein thrombosis (DVT). DVT most commonly occurs in the deep veins of the lower extremity but can also occur in the veins of upper extremity, abdomen and cerebrum. As symptoms of VTE are nonspecific, the diagnosis of VTE is based on diagnostic tests, including clinical decision rules (CDR), D-dimer tests and imaging. Although the diagnostic management of VTE has greatly advanced in recent years with the introduction of novel CDRs and high-sensitive D-dimer tests, the diagnosis may still be challenging in certain settings. The latter is mainly caused by the indirect way of thrombus visualisation by current imaging tests, such as by showing incompressibility with compression ultrasonography (CUS) or a filling defect on contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI).This thesis focuses on challenging settings for diagnosing VTE, including suspected recurrent ipsilateral DVT, upper extremity DVT, cerebral vein thrombosis and portal vein thrombosis. We studied a novel imaging technique called Magnetic Resonance Non-Contrast Thrombus Imaging (MR-NCTI) and its application in these different VTE settings. Dutch Heart Foundation, LEO Pharma B.V., Bayer Healthcare B.V., Federatie van Nederlandse Trombosediensten, STAGO B.V., Boehringer-Ingelheim B.V., Chipsoft anf, Nederlandse Vereniging voor Spoedeisende Hulp Artsen (NVSHA)LUMC / Geneeskund

Current Imaging Modalities for Diagnosing Cerebral Vein Thrombosis - A Critical Review

Cerebral vein thrombosis (CVT) is a rare presentation of venous thromboembolism. Prompt and accurate diagnosis is essential as delayed recognition and treatment may lead to permanent disability or even death. Since no validated diagnostic algorithms exist, the diagnosis of CVT mainly relies on neuroimaging. Digital subtraction angiography (DSA) is the historical diagnostic standard for CVT, but is rarely used nowadays and replaced by computed tomography (CT) and magnetic resonance imaging (MRI). High quality studies to evaluate the diagnostic test characteristics of state of the art imaging modalities are however unavailable to date. This review provides an overview of the best available evidence regarding the diagnostic performance of CT and MRI for the diagnosis of CVT. Notably, available studies are observational, mostly small, outdated, and with a high risk of bias. Therefore, direct comparison between studies is difficult due to large diversity in study design, imaging method, reference standard, patient selection and sample size. In general, contrast-enhanced techniques are more accurate for the diagnosis of CVT then non-contrast-enhanced techniques. CT venography and MRI have been both reported to be adequate for establishing a final diagnosis of CVT, but choice of modality as used in clinical practice depends on availability, local preference and experience, as well as patient characteristics. Our review underlines the need for high-quality diagnostic studies comparing CT venography and MRI in specific settings, to improve clinical care and standardize clinical trials.Perioperative Medicine: Efficacy, Safety and Outcome (Anesthesiology/Intensive Care

More on clinical and computed tomography characteristics of COVID-19 associated acute pulmonary embolism

Perioperative Medicine: Efficacy, Safety and Outcome (Anesthesiology/Intensive Care

⁸⁹Zr-Trastuzumab PET/CT Imaging of HER2-Positive Breast Cancer for Predicting Pathological Complete Response after Neoadjuvant Systemic Therapy:A Feasibility Study

Background: Approximately 20% of invasive ductal breast malignancies are human epidermal growth factor receptor 2 (HER2)-positive. These patients receive neoadjuvant systemic therapy (NAT) including HER2-targeting therapies. Up to 65% of patients achieve a pathological complete response (pCR). These patients might not have needed surgery. However, accurate preoperative identification of a pCR remains challenging. A radiologic complete response (rCR) on MRI corresponds to a pCR in only 73% of patients. The current feasibility study investigates if HER2-targeted PET/CT-imaging using Zirconium-89 (89Zr)-radiolabeled trastuzumab can be used for more accurate NAT response evaluation. Methods: HER2-positive breast cancer patients scheduled to undergo NAT and subsequent surgery received a 89Zr-trastuzumab PET/CT both before (PET/CT-1) and after (PET/CT-2) NAT. Qualitative and quantitative response evaluation was performed. Results: Six patients were enrolled. All primary tumors could be identified on PET/CT-1. Four patients had a pCR and two a pathological partial response (pPR) in the primary tumor. Qualitative assessment of PET/CT resulted in an accuracy of 66.7%, compared to 83.3% of the standard-of-care MRI. Quantitative assessment showed a difference between the SUVR on PET/CT-1 and PET/CT-2 (ΔSUVR) in patients with a pPR and pCR of −48% and −90% (p = 0.133), respectively. The difference in tumor-to-blood ratio on PET/CT-1 and PET/CT-2 (ΔTBR) in patients with pPR and pCR was −79% and −94% (p = 0.133), respectively. Three patients had metastatic lymph nodes at diagnosis that were all identified on PET/CT-1. All three patients achieved a nodal pCR. Qualitative assessment of the lymph nodes with PET/CT resulted in an accuracy of 66.7%, compared to 50% of the MRI. Conclusions: NAT response evaluation using 89Zr-trastuzumab PET/CT is feasible. In the current study, qualitative assessment of the PET/CT images is not superior to standard-of-care MRI. Our results suggest that quantitative assessment of 89Zr-trastuzumab PET/CT has potential for a more accurate response evaluation of the primary tumor after NAT in HER2-positive breast cancer.</p

Early effects of unfractionated heparin on clinical and radiological signs and D-dimer levels in patients with COVID-19 associated pulmonary embolism: an observational cohort study

Perioperative Medicine: Efficacy, Safety and Outcome (Anesthesiology/Intensive Care

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

Background Compression 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.Objectives We aimed to determine the diagnostic accuracy of magnetic resonance noncontrast thrombus imaging (MR-NCTI) for the diagnosis of UEDVT.Methods In 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.Results Magnetic 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).Conclusions Magnetic 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.Cardiovascular Aspects of Radiolog

[F-18]FDG-PET/CT to prevent futile surgery in indeterminate thyroid nodules: a blinded, randomised controlled multicentre trial

Purpose To assess the impact of an [F-18]FDG-PET/CT-driven diagnostic workup to rule out malignancy, avoid futile diagnostic surgeries, and improve patient outcomes in thyroid nodules with indeterminate cytology.Methods In this double-blinded, randomised controlled multicentre trial, 132 adult euthyroid patients with scheduled diagnostic surgery for a Bethesda III or IV thyroid nodule underwent [F-18]FDG-PET/CT and were randomised to an [F-18] FDG-PET/CT-driven or diagnostic surgery group. In the [F-18]FDG-PET/CT-driven group, management was based on the [F-18]FDG-PET/CT result: when the index nodule was visually [F-18]FDG-positive, diagnostic surgery was advised; when [F-18]FDG-negative, active surveillance was recommended. The nodule was presumed benign when it remained unchanged on ultrasound surveillance. In the diagnostic surgery group, all patients were advised to proceed to the scheduled surgery, according to current guidelines. The primary outcome was the fraction of unbeneficial patient management in one year, i.e., diagnostic surgery for benign nodules and active surveillance for malignant/borderline nodules. Intention-to-treat analysis was performed. Subgroup analyses were performed for non-Hurthle cell and Hurthle cell nodules.Results Patient management was unbeneficial in 42% (38/91 [95% confidence interval [CI], 32-53%]) of patients in the [F-18] FDG-PET/CT-driven group, as compared to 83% (34/41 [95% CI, 68-93%]) in the diagnostic surgery group (p < 0.001). [F-18]FDG-PET/CT-driven management avoided 40% (25/63 [95% CI, 28-53%]) diagnostic surgeries for benign nodules: 48% (23/48 [95% CI, 33-63%]) in non-Hurthle cell and 13% (2/15 [95% CI, 2-40%]) in I-Liable cell nodules (p = 0.02). No malignant or borderline tumours were observed in patients under surveillance. Sensitivity, specificity, negative and positive predictive value, and benign call rate (95% CI) of [F-18]FDG-PET/CT were 94.1% (80.3-99.3%), 39.8% (30.0-50.2%), 95.1% (83.5-99.4%), 35.2% (25.4-45.9%), and 31.1% (23.3-39.7%), respectively.Conclusion An [F-18]FDG-PET/CT-driven diagnostic workup of indeterminate thyroid nodules leads to practice changing management, accurately and oncologically safely reducing futile surgeries by 40%. For optimal therapeutic yield, application should be limited to non-Hurthle cell nodules.Imaging- and therapeutic targets in neoplastic and musculoskeletal inflammatory diseas

Overview and future perspectives on tumor-targeted positron emission tomography and fluorescence imaging of pancreatic cancer in the era of neoadjuvant therapy

Simple Summary Patients diagnosed with pancreatic cancer have a poor prognosis at time of diagnosis, with a 5-year survival rate of merely 10%. The only treatment with curative intent is surgical resection of the tumor and adjacent tumor-containing lymph nodes. To improve surgical outcome and survival, additional (imaging) tools are needed that support complete surgical tumor resection. Firstly, more accurate monitoring of tumor response to neoadjuvant treatment and subsequent determination of resectability is needed. Secondly, an imaging tool is needed for intraoperative guidance allowing accurate identification, delineation, and complete resection of the tumor and suspected lymph nodes. Therefore, both tumor-targeted PET/CT before surgery and real time fluorescence-guidance during surgery could be helpful to improve patient outcome. This review focusses on literature considering tumor-targeted PET/CT and near-infrared fluorescence (NIRF) imaging. Several tumor-targeted agents are under clinical evaluation, and several other promising agents are currently tested preclinically, both with promising results. Their additional diagnostic value and feasibility for future implementation in standard clinical care of PDAC has yet to be established in phase III clinical trials. Background: Despite recent advances in the multimodal treatment of pancreatic ductal adenocarcinoma (PDAC), overall survival remains poor with a 5-year cumulative survival of approximately 10%. Neoadjuvant (chemo- and/or radio-) therapy is increasingly incorporated in treatment strategies for patients with (borderline) resectable and locally advanced disease. Neoadjuvant therapy aims to improve radical resection rates by reducing tumor mass and (partial) encasement of important vascular structures, as well as eradicating occult micrometastases. Results from recent multicenter clinical trials evaluating this approach demonstrate prolonged survival and increased complete surgical resection rates (R0). Currently, tumor response to neoadjuvant therapy is monitored using computed tomography (CT) following the RECIST 1.1 criteria. Accurate assessment of neoadjuvant treatment response and tumor resectability is considered a major challenge, as current conventional imaging modalities provide limited accuracy and specificity for discrimination between necrosis, fibrosis, and remaining vital tumor tissue. As a consequence, resections with tumor-positive margins and subsequent early locoregional tumor recurrences are observed in a substantial number of patients following surgical resection with curative intent. Of these patients, up to 80% are diagnosed with recurrent disease after a median disease-free interval of merely 8 months. These numbers underline the urgent need to improve imaging modalities for more accurate assessment of therapy response and subsequent re-staging of disease, thereby aiming to optimize individual patient's treatment strategy. In cases of curative intent resection, additional intra-operative real-time guidance could aid surgeons during complex procedures and potentially reduce the rate of incomplete resections and early (locoregional) tumor recurrences. In recent years intraoperative imaging in cancer has made a shift towards tumor-specific molecular targeting. Several important molecular targets have been identified that show overexpression in PDAC, for example: CA19.9, CEA, EGFR, VEGFR/VEGF-A, uPA/uPAR, and various integrins.Tumor-targeted PET/CT combined with intraoperative fluorescence imaging, could provide valuable information for tumor detection and staging, therapy response evaluation with re-staging of disease and intraoperative guidance during surgical resection of PDAC. Methods: A literature search in the PubMed database and (inter)national trial registers was conducted, focusing on studies published over the last 15 years. Data and information of eligible articles regarding PET/CT as well as fluorescence imaging in PDAC were reviewed. Areas covered: This review covers the current strategies, obstacles, challenges, and developments in targeted tumor imaging, focusing on the feasibility and value of PET/CT and fluorescence imaging for integration in the work-up and treatment of PDAC. An overview is given of identified targets and their characteristics, as well as the available literature of conducted and ongoing clinical and preclinical trials evaluating PDAC-targeted nuclear and fluorescent tracers.Imaging- and therapeutic targets in neoplastic and musculoskeletal inflammatory diseas

Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in √s = 7 TeV pp collisions with the ATLAS detector

A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fb−1 of proton–proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results

Jet size dependence of single jet suppression in lead-lead collisions at sqrt(s(NN)) = 2.76 TeV with the ATLAS detector at the LHC

Measurements of inclusive jet suppression in heavy ion collisions at the LHC provide direct sensitivity to the physics of jet quenching. In a sample of lead-lead collisions at sqrt(s) = 2.76 TeV corresponding to an integrated luminosity of approximately 7 inverse microbarns, ATLAS has measured jets with a calorimeter over the pseudorapidity interval |eta| < 2.1 and over the transverse momentum range 38 < pT < 210 GeV. Jets were reconstructed using the anti-kt algorithm with values for the distance parameter that determines the nominal jet radius of R = 0.2, 0.3, 0.4 and 0.5. The centrality dependence of the jet yield is characterized by the jet "central-to-peripheral ratio," Rcp. Jet production is found to be suppressed by approximately a factor of two in the 10% most central collisions relative to peripheral collisions. Rcp varies smoothly with centrality as characterized by the number of participating nucleons. The observed suppression is only weakly dependent on jet radius and transverse momentum. These results provide the first direct measurement of inclusive jet suppression in heavy ion collisions and complement previous measurements of dijet transverse energy imbalance at the LHC.Comment: 15 pages plus author list (30 pages total), 8 figures, 2 tables, submitted to Physics Letters B. All figures including auxiliary figures are available at http://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/HION-2011-02