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Purpose: A major component of cells in tenosynovial giant cell tumor (TGCT) consists of bystander macrophages responding to CSF1 that is overproduced by a small number of neoplastic cells with a chromosomal translocation involving the CSF1 gene. An autocrine loop was postulated where the neoplastic cells would be stimulated through CSF1R expressed on their surface. Here, we use single-cell RNA sequencing (scRNA-seq) to investigate cellular interactions in TGCT. Experimental Design: A total of 18,788 single cells from three TGCT and two giant cell tumor of bone (GCTB) samples underwent scRNA-seq. The three TGCTs were additionally analyzed using long-read RNA sequencing. Immunofluorescence and IHC for a range of markers were used to validate and extend the scRNA-seq findings. Results: Two recurrent neoplastic cell populations were identified in TGCT that are highly similar to nonneoplastic synoviocytes. We identified GFPT2 as a marker that highlights the neoplastic cells in TCGT. We show that the neoplastic cells themselves do not express CSF1R. We identified overlapping MAB features between the giant cells in TGCT and GCTB. Conclusions: The neoplastic cells in TGCT are highly similar to nonneoplastic synoviocytes. The lack of CSF1R on the neoplastic cells indicates they may be unaffected by current therapies. High expression of GFPT2 in the neoplastic cells is associated with activation of the YAP1/TAZ pathway. In addition, we identified expression of the platelet-derived growth factor receptor in the neoplastic cells. These findings suggest two additional pathways to target in this tumor.

Age, location of the tumor, and detailed patient history can narrow the differential diagnosis of spinal bone lesions, including metastasis and primary benign and malignant bone tumors. Computed tomography and magnetic resonance imaging are both crucial in evaluating the characteristics of spinal bone tumors. Growth speed and Lodwick margin description can differentiate malignant from benign tumors to a certain degree. Positron emission tomography has a limited ability to differentiate malignant from benign tumors. A biopsy is often required for a definitive diagnosis. To select the optimal treatment for spinal metastasis, neurological status by epidural spinal cord compression grade (axial T2-weighted magnetic resonance image), radiosensitivity of tumor histology, mechanical instability by Spine Instability Neoplastic Score (sagittal and axial computed tomography image), and systemic disease should be evaluated by a multidisciplinary team. This review article summarizes the role of imaging for diagnosis and treatment of spinal bone tumors.

Giant cell tumour of bone (GCTB) typically occurs in young adults from 20-40 years old. Although the majority of lesions are located in the epi-metaphyses of the long bones, approximately one third of tumours are located in the axial skeleton, of which only 4% in the sacrum. Sacral tumours tend to be large at the time of presentation, and they present with aggressive features such as marked cortical destruction and an associated soft tissue component. The 2020 World Health Organisation classification of Soft Tissue and Bone Tumours describes GCTB as a neoplasm which is locally aggressive and rarely metastasizing. The tumour contains three different cell types: neoplastic mononuclear stromal cells, macrophages and osteoclast-like giant cells. Two tumour subtypes were defined: conventional GCTB and malignant GCTB. Only 1-4% of GCTB is malignant. In this review article, we will discuss imaging findings at the time of diagnosis to guide the musculoskeletal radiologist in reporting these tumours. In addition, imaging for response evaluation after various treatment options will be addressed, such as surgery, radiotherapy, embolization and denosumab. Specific findings will be presented per imaging modality and illustrated by cases from our tertiary sarcoma referral center. Common postoperative and post-radiotherapy findings in GCTB of the sacrum on MRI will be discussed.

Supplementary Figure from Interactions in CSF1-Driven Tenosynovial Giant Cell Tumors

Supplementary Table from Interactions in CSF1-Driven Tenosynovial Giant Cell Tumors

Purpose:A major component of cells in tenosynovial giant cell tumor (TGCT) consists of bystander macrophages responding to CSF1 that is overproduced by a small number of neoplastic cells with a chromosomal translocation involving the CSF1 gene. An autocrine loop was postulated where the neoplastic cells would be stimulated through CSF1R expressed on their surface. Here, we use single-cell RNA sequencing (scRNA-seq) to investigate cellular interactions in TGCT.Experimental Design:A total of 18,788 single cells from three TGCT and two giant cell tumor of bone (GCTB) samples underwent scRNA-seq. The three TGCTs were additionally analyzed using long-read RNA sequencing. Immunofluorescence and IHC for a range of markers were used to validate and extend the scRNA-seq findings.Results:Two recurrent neoplastic cell populations were identified in TGCT that are highly similar to nonneoplastic synoviocytes. We identified GFPT2 as a marker that highlights the neoplastic cells in TCGT. We show that the neoplastic cells themselves do not express CSF1R. We identified overlapping MAB features between the giant cells in TGCT and GCTB.Conclusions:The neoplastic cells in TGCT are highly similar to nonneoplastic synoviocytes. The lack of CSF1R on the neoplastic cells indicates they may be unaffected by current therapies. High expression of GFPT2 in the neoplastic cells is associated with activation of the YAP1/TAZ pathway. In addition, we identified expression of the platelet-derived growth factor receptor in the neoplastic cells. These findings suggest two additional pathways to target in this tumor.

Background and Objectives Surgery is the mainstay of treatment for tenosynovial giant cell tumors (TGCTs). However, achieving a cure through surgery alone remains challenging, especially for the diffuse-type (D-TGCT). Methods Our goal was to describe the surgical management of patients with D-TGCT related to large joints, treated between 2000 and 2020. We analyzed the effect of (in)complete resections and the presence of postoperative tumor (POT) on magnetic resonance imaging (MRI) on radiological and clinical outcomes. Results A total of 144 patients underwent open surgery for D-TGCT, of which 58 (40%) had treatment before. The median follow-up was 65 months. One hundred twenty-five patients underwent isolated open surgeries, in which 25 (20%) patients' D-TGCT was intentionally removed incompletely. POT presence on the first postoperative MRI was observed in 64%. Both incomplete resections and POT presence were associated with higher rates of radiological progression (73% vs. 44%; Kaplan-Meier [KM] analysis p = 0.021) and 59% versus 7%; KM analysis p < 0.001), respectively. Furthermore, patients with POT presence clinically worsened more often than patients without having POT (49% vs. 24%; KM analysis p = 0.003). Conclusions D-TGCT is often resected incompletely and tumor presence is commonly observed on the first postoperative MRI, resulting in worse radiological and clinical outcomes. Therefore, surgeons should try to remove D-TGCT in toto and consider other multimodal therapeutic strategies.

Introduction Tenosynovial giant cell tumor (TGCT) is a mono-articular, benign or locally aggressive and often debilitating neoplasm. Systemic therapies are becoming part of the multimodal armamentarium when surgery alone will not confer improvements. Since TGCT is characterized by colony-stimulating factor-1 (CSF1) rearrangements, the most studied molecular pathway is the CSF1 and CSF1 receptor (CSF1R) axis. Inhibiting CSF1-CSF1R interaction often yields considerable radiological and clinical responses; however, adverse events may cause treatment discontinuation because of an unfavorable risk-benefit ratio in benign disease. Only Pexidartinib is approved by the US FDA; however, the European Medicines Agency has not approved it due to a uncertain risk-benefit ratio. Thus, there is a need for safer and effective therapies. Areas covered Light is shed on disease mechanisms and potential drug targets. The safety and efficacy of different systemic therapies are evaluated. Expert opinion The CSF1-CSF1R axis is the principal drug target; however, the effect of CSF1R inhibition on angiogenesis and the role of macrophages, which are essential in the postoperative course, needs further elucidation. Systemic therapies have a promising role in treating mainly diffuse-type, TGCT patients who are not expected to clinically improve from surgery. Future drug development should focus on targeting neoplastic TGCT cells.

Hibernomas are rare lipomatous tumors composed of brown adipocytes. The relative paucity of reported cases involving the bones accounts for the poor understanding of this entity, which is known to affect almost exclusively the axial skeleton. We present a case of intraosseous hibernoma of the humerus, which was found incidentally in a 52-year-old woman and initially misinterpreted as a cartilaginous tumor on magnetic resonance imaging (MRI). The lesion was unchanged in size and morphology at short interval follow-up but increased in size during follow-up over 6 years with an 11 mm increase in the largest diameter. Given the patient’s concerns and lesion growth, curettage was performed. Pathology analysis revealed brown fat in keeping with the diagnosis of intraosseous hibernoma. Radiological and pathological findings and pitfalls are herein highlighted to enforce knowledge on this lesion rarely affecting the long bones. Radiologists should think of intraosseous hibernoma if they come across a sclerotic lesion on X-ray or computed tomography, which contains macroscopic fat and shows enhancement on contrast-enhanced MRI. In addition, an intraosseous hibernoma may be picked up incidentally on positron emission tomography-computed tomography due to high fluorodeoxyglucose avidity.

Weitere Nicht-UDE Autoren sind nicht mit aufgeführt. enosynovial giant cell tumour (TGCT) is a rare, locally aggressive, mesenchymal tumor arising from the joints, bursa and tendon sheaths. TGCT comprises a nodular- and a diffuse-type, with the former exhibiting mostly indolent course and the latter a locally aggressive behavior. Although usually not life-threatening, TGCT may cause chronic pain and adversely impact function and quality of life (QoL). CSFR1 inhibitors are effective with benefit on symptoms and QoL but are not available in most countries. The degree of uncertainty in selecting the most appropriate therapy and the lack of guidelines on the clinical management of TGCT make the adoption of new treatments inconsistent across the world, with suboptimal outcomes for patients. A global consensus meeting was organized in June 2022, involving experts from several disciplines and patient representatives from SPAGN to define the best evidence-based practice for the optimal approach to TGCT and generate the recommendations presented herein.

Hibernomas are rare lipomatous tumors composed of brown adipocytes. The relative paucity of reported cases involving the bones accounts for the poor understanding of this entity, which is known to affect almost exclusively the axial skeleton. We present a case of intraosseous hibernoma of the humerus, which was found incidentally in a 52-year-old woman and initially misinterpreted as a cartilaginous tumor on magnetic resonance imaging (MRI). The lesion was unchanged in size and morphology at short interval follow-up but increased in size during follow-up over 6 years with an 11 mm increase in the largest diameter. Given the patient's concerns and lesion growth, curettage was performed. Pathology analysis revealed brown fat in keeping with the diagnosis of intraosseous hibernoma. Radiological and pathological findings and pitfalls are herein highlighted to enforce knowledge on this lesion rarely affecting the long bones. Radiologists should think of intraosseous hibernoma if they come across a sclerotic lesion on X-ray or computed tomography, which contains macroscopic fat and shows enhancement on contrast-enhanced MRI. In addition, an intraosseous hibernoma may be picked up incidentally on positron emission tomography-computed tomography due to high fluorodeoxyglucose avidity.

Aims Clear cell chondrosarcomas are known to occasionally contain areas of low-grade conventional chondrosarcoma; however, the opposite phenomenon has not yet been described. We identified five cases of conventional chondrosarcoma alongside clear cell chondrosarcoma. Here, we report on their clinicopathological and molecular characteristics, and investigate whether these hybrid lesions should be considered to be a collision tumour, conventional chondrosarcoma with clear cell change, or clear cell chondrosarcoma with extensive areas of conventional chondrosarcoma, as this has clinical implications. Methods and results Clinicohistopathological features were characterised, immunohistochemistry was performed for H3 histone family member 3B (H3F3B), histone H3 trimethylated on lysine 27 (H3K27me3), and p53, and genetic alterations of IDH1 (encoding isocitrate dehydrogenase 1), IDH2 (encoding isocitrate dehydrogenase 2), TP53 and H3F3B were evaluated. All five chondrosarcomas consisted predominantly of areas with conventional chondrosarcoma. Different grades were found [grade I (n = 1), grade II (n = 2), and grade III (n = 2)]. Up to 20% of the tumour consisted of classic features of clear cell chondrosarcoma. Gradual merging between both components was observed. Molecular analysis of conventional chondrosarcoma components revealed an IDH1 c.395G>T, p.(Arg132Leu) mutation in two cases, and an IDH1 c.394C>T, p.(Arg132Cys) mutation in one case, with identical IDH mutations in the clear cell chondrosarcoma counterpart (100%). Two cases were IDH wild-type. In all cases, none of the components harboured H3F3B mutations. High-grade tumours had an aggressive course, as three patients died of the disease. Conclusion On the basis of clinicopathological characterisation and genetic alterations, it is suggested that these lesions should be considered to be conventional chondrosarcoma, with clear cell change. Pathologists should be aware of their existence to avoid confusion with clear cell chondrosarcoma, dedifferentiated chondrosarcoma, or chondroblastic osteosarcoma.

Introduction: Oligometastatic disease and/or oligoprogression in myxoid liposarcoma(oMLS) triggers discussions on local treatment options and delay of systemic treatments. We hypothesized that satisfactory local control and postponement of systemic therapy could be achieved with a modest radiotherapy(RT) dose in oMLS.Methods: The DOREMY trial is a multicenter, phase 2 trial evaluating efficacy and toxicity of a modest RT dose in both localized and oMLS; this report presents the data of the oMLS cohort treated with 36 Gy in 12-18 fractions with optional subsequent metastasectomy. The primary endpoint was local progression free survival(LPFS). Secondary endpoints included postponement of systemic therapy, symptom reduction, radiological objective response, and toxicity.Results: Nine patients with a total of 25 lesions were included, with a median follow-up of 23 months. The median number of lesions per patient was three and the trunk wall and bone were the most frequently affected sites. In lesions treated with definitive RT(n = 21), LPFS rates at 1, 2, and 3 years were respectively 73%, 61%, and 40%. Radiological objective response and clinical symptom reduction were achieved in 8/15(53%) and 9/10(90%) of the evaluable lesions, respectively. No local recurrences occurred in lesions treated with RT and metastasectomy(n = 4). For the entire study population, the median postponement of systemic therapy was 10 months. Grade >= 2 toxicity was observed in 2/9(22%) of patients.Conclusions: This trial suggests that 36 Gy could possibly be effective to achieve local control, postpone systemic therapy and reduce symptoms in oMLS. Given the minimal toxicity this treatment could be reasonably considered in oMLS.(c) 2021 Elsevier B.V. All rights reserved. Radiotherapy and Oncology 158 (2021) 33-39

Background Although curative surgery remains the cornerstone of the therapeutic strategy in patients with soft tissue sarcomas (STS), neoadjuvant radiotherapy and chemotherapy (NART and NACT, respectively) are increasingly used to improve operability, surgical margins and patient outcome. The best imaging modality for locoregional assessment of STS is MRI but these tumors are mostly evaluated in a qualitative manner. Objective After an overview of the current standard of care regarding treatment for patients with locally advanced STS, this review aims to summarize the principles and limitations of (i) the current methods used to evaluate response to neoadjuvant treatment in clinical practice and clinical trials in STS (RECIST 1.1 and modified Choi criteria), (ii) quantitative MRI sequences (i.e., diffusion weighted imaging and dynamic contrast enhanced MRI), and (iii) texture analyses and (delta-) radiomics.

Background: Histotype specific neoadjuvant therapy response data is scarce in soft tissue sarcomas. This study aimed to assess the impact of a moderate radiotherapy (RT) dose on resectability and to correlate MRI parameters to pathological treatment response in Myxoid Liposarcoma (MLS).Methods: This prospective, multicenter, single-arm, phase 2 trial assessed the radiological effects of 36 Gy of preoperative radiotherapy in primary non-metastatic MLS (n=34). Distance of the tumor to the neurovascular bundle, tumor dimensions, fat fraction, enhancing fraction were determined on MRI scans at baseline, after 8 and 16 fractions, and preoperatively. Pathological response was established by central pathology review.Results: Preoperative radiotherapy resulted in a median increase of 2 mm (IQR 0 to 6) of the distance of the tumor to the neurovascular bundle. As compared to baseline, the median change of the tumor volume, craniocaudal diameter and axial diameter at preoperative MRI were -60% (IQR -74 to -41), -19% (IQR -23 to -7) and -20% (IQR -29 to -12), respectively. The median fat fraction of 0.1 (IQR 0.0-0.1) and enhancing fraction of 0.8 (IQR 0.6 to 0.9) at baseline, changed to 0.2 (IQR 0.1 to 0.5) and to 0.5(IQR 0.4 to 0.9) preoperatively, respectively. Radiological signs of response in terms of volume, enhancing fraction and fat fraction were correlated with specific pathological signs of response like hyalinization, necrosis and fatty maturation.Conclusions: A moderate dose of preoperative radiotherapy may improve resectability in MLS and could facilitate achievement of clear margins and function preservation. MRI features which were predictive for expressions of pathological response, can play a role in further personalization of neoadjuvant treatment strategies in order to improve outcome in MLS. (C) 2021 Elsevier Ltd, BASO - The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

Giant cell tumours of bone (GCTB) are benign giant cell-rich tumours typically occurring in the epi-metaphysis of skeletally mature patients. Despite their benign classification, GCTB may be locally aggressive with local recurrence as a challenging issue. Denosumab is a human monoclonal antibody that inhibits osteolysis via the RANK-RANK ligand pathway. There is currently no consensus on optimal treatment duration or imaging modality for monitoring patients on denosumab therapy. This review illustrates the radiological findings of GCTB on denosumab treatment seen on plain radiographs, CT, MRI, PET-CT and DEXA, with reference to the current literature. Recognizing imaging features indicative of a positive response to denosumab is important for therapeutic decision-making. Imaging findings with respect to duration of denosumab treatment, tumour upregulation during treatment, tumour recurrence and malignant transformation are discussed. The development of a sclerotic neocortex and varying degrees of matrix osteosclerosis are seen on plain radiographs. Reconstitution of subarticular bone and articular surface irregularity are optimally evaluated on CT which can also quantify tumour density. MRI demonstrates heterogeneous low signal matrix and is useful to assess decrease in size of cystic and/or soft tissue components of GCTB. A fat-suppressed fluid-sensitive MR sequence is important to detect tumour reactivation. Reduction in 18F-FDG-PET avidity represents an early sensitive sign of response to denosumab treatment. Regardless of imaging modality, close follow-up in a specialist centre and careful evaluation of nonresponders is necessary as local recurrence after cessation of denosumab treatment and malignant transformation of GCTB have been described.

A 54-year-old man presented to the emergency department following a fall onto his outstretched right hand. Initial radiographs were considered negative for a fracture. A subsequently performed MRI of the wrist to exclude a radiographically occult scaphoid fracture demonstrated a linear high signal

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.

A 46-year-old woman was referred to our ultrasonography unit because of pain in the calves that initiated 8 days ago. At that time, she was wearing high heels and walking in a cramped manner. After 4 hours of walking on high heels she noticed severe pain in the calves bilaterally. The patient had

Risk factors for deep-vein thrombosis have been shown not to be always the same as for pulmonary embolism. A well-known example is the factor V Leiden (FVL) paradox: the FVL mutation poses a clearly higher risk for deep-vein thrombosis (DVT) than for pulmonary embolism. We aimed to expand this paradox and therefore present risk estimates for several established risk factors for DVT and pulmonary embolism separately. When such separate risk estimates could not be retrieved from the literature, we calculated these risks in our own data, a large population-based case-control study on venous thrombosis (the MEGA study). Our results showed that the FVL paradox can be broadened (ie, the risk factors oral contraceptive use, pregnancy, puerperium, minor leg injuries, and obesity have an effect comparable with FVL). Furthermore, we found that pulmonary conditions, such as chronic obstructive pulmonary disease, pneumonia, and sickle cell disease, were risk factors with an opposite effect: a higher risk of pulmonary embolism, but little or no effect on DVT. These findings suggest that pulmonary embolism and DVT may not always have the same etiology, and encourage unraveling this phenomenon in further studies.

Pulmonary embolism is considered to originate from embolization of a deep-vein thrombosis, resulting in two manifestations of one disease: venous thrombosis. However, in up to 50% of patients with pulmonary embolism no deep-vein thrombosis is found with ultrasonography. An explanation for this low proportion is currently lacking. Other imaging modalities may increase the yield of detection of deep-vein thrombosis in the calf or in the abdominal region. Alternatively, not all pulmonary emboli may originate from deep-vein thromboses in the extremities. We searched for the origin of pulmonary emboli, by performing total-body magnetic resonance imaging-scans to visualize thrombi. Ninety-nine patients with a first pulmonary embolism confirmed by computed tomography underwent a magnetic resonance direct thrombus imaging-scan, a validated technique using endogenous contrast. Additionally, acquired and genetic risk factors were assessed. No thrombus was found in 55 patients, whereas a thrombus was identified in 44 patients. The commonest thrombus location was the lower leg; 12 patients had isolated calf vein thrombosis and five had isolated superficial vein thrombosis. A peripheral thrombus was found by magnetic resonance imaging in less than half of patients with pulmonary embolism. We propose several hypotheses to explain the absence of thrombi, such as a cardiac thrombus origin or embolization of the whole deep-vein thrombus. The possibility that pulmonary embolism arises de novo in the lungs, due to local inflammation-driven coagulation, needs to be considered.

To evaluate the added value of CT pulmonary angiography (CTPA) in patients who have undergone this procedure for suspected pulmonary embolism (PE). We evaluated this added value by investigating both the rate of pulmonary embolism ascertained and the rate of CTPA without abnormal findings, each in relationship to various characteristics of the patient and referring individuals.Diagnostic cross sectional researchData on all patients 18 years and older who underwent CTPA from November 2008 to February 2011 at the Leiden University Medical Centre because of suspected pulmonary embolism were entered into a database. We collected information on the patient, referring individual, reason for referral and the outcome of the CTPA, and described the rate of positive CTPA for various subgroups. In addition, we described the rate of CTPA's within these groups in which no abnormalities were demonstrable.After exclusion of patients with a PE found by chance (n = 28), the total patient population was comprised of 1344 patients. In 19.1% of these patients, PE was confirmed by CTPA. This percentage was lower in the female population (16.9%; 95% CI: 14.4-19.6), and in outpatients (10.9%; 95% CI: 5.5-16.3). In 42% of CTPAs in the group of patients younger than 40 years, no abnormalities were foundThe CTPA yield could be improved in women and younger patients. This would increase cost-effectiveness and reduce unnecessary side effects. For this reason, further investigation into the motives of doctors referring young people, women and outpatients would be helpful in preventing the overuse of this diagnostic tool.

Superficial vein thrombosis (SVT) is regarded a self-limiting disorder, although the authors of recent studies showed that ultrasonographically diagnosed SVT is a precursor for venous thrombosis. We aimed to determine whether the same holds true for clinically diagnosed SVT and to what extent it is associated with thrombophilia in a population-based case-control study (ie, Multiple Environmental and Genetic Assessment of risk factors for venous thrombosis). We found that a history of clinical SVT was associated with a 6.3-fold (95% confidence interval [CI] 5.0-8.0) increased risk of deep-vein thrombosis and a 3.9-fold (95% CI 3.0-5.1) increased risk of pulmonary embolism. Blood group non-O and factor V Leiden showed a small increase in SVT risk in controls, with odds ratios of 1.3 (95% CI 0.9-2.0) and 1.5 (95% CI 0.7-3.3), respectively. In conclusion, clinically diagnosed SVT was a risk factor for venous thrombosis. Given that thrombophilia was only weakly associated with SVT, it is likely that other factors (varicosis, obesity, stasis) also play a role in its etiology.

Venous thromboembolism (VTE) is a disease that causes high morbidity and mortality in the population. At present the first-line imaging test for a suspected pulmonary embolism (PE) is computed tomography (CT) pulmonary angiography, and ultrasonography is widely used for the diagnosis of deep-vein thrombosis (DVT). Although these modalities are proven to be safe and accurate, unresolved issues remain, such as whether CT scanning in patients with a suspected PE should be extended to the legs. Another issue is the diagnosis of recurrent DVT. Magnetic resonance imaging (MRI) offers a number of advantages in the imaging of VTE. Recent developments of scanning protocols with shorter acquisition times, sometimes complemented by navigator gating or making use of endogenous contrast, offer new perspectives for the use of MRI. This review provides an overview of state of the art MRI techniques for the diagnosis of PE and DVT. Furthermore, the use of new contrast agents such as fibrin labeling to detect thrombi are addressed.

Objective— Age is the strongest risk factor for venous thrombosis. Vessel wall changes such as thickening of venous valves may be one of the contributing mechanisms. We determined thickness and function of venous valves in the popliteal vein with ultrasound in 77 healthy individuals. Methods and Results— The study included 6 age groups ranging from 20 to 80 years old. Thickness of the valves was compared between age groups. Valve closure time was assessed as an indicator for valve function. In 69 of 77 participants, valve parameters could be measured. We found an increasing thickness of the valves with age, with a mean thickness of 0.35 mm (range, 0.25 to 0.44 mm) in the group of 20 to 30 years and 0.59 mm (range, 0.30 to 1.21 mm) in the group of 71 to 80 years. The increase in valve thickness per year (linear regression coefficient) was 0.004 mm (95% CI, 0 to 0.009). Valve function was not directly associated with age. Valve thickness, however, was inversely associated with valve function. Conclusion— Our results show that deep venous valves change with age, with thicker valves in older individuals. The increase of valve thickness with age may be part of the explanation for the age gradient seen in the incidence of venous thrombosis.

Abstract 2297 Introduction Pulmonary embolism (PE) is thought to originate from embolisation of a deep-vein thrombosis (DVT), resulting in two clinical manifestations of one disease: venous thrombosis. However, in up to 50% of patients with PE, no DVT is found with ultrasound. A new technique in diagnosing DVT is ‘MR Direct Thrombus Imaging’ (MRDTI), using methaemoglobin in the thrombus as endogenous contrast. We performed total body MRIs to visualize thrombi from calf veins to subclavian veins, to assess the origin of PE. Methods Consecutive patients with a first PE diagnosed by Multi Detector CT scan are included. All patients undergo a 1.5 T MRDTI scan. In addition, blood is sampled for determination of genetic risk factors: the Factor V Leiden (FVL) and prothrombin G20210A (FII) mutations. Results 99 patients have been enrolled in the study. In 44/99 (44%) a thrombus was identified on MR images. Most thrombi originated from the left side of the body (27/44). The upper leg was involved most often (22/44), with thrombi extending into the calf in 16 of these patients. Other thrombi were present in the pelvic veins (4/44), and deep calf veins alone (12/44). 6 patients had merely thrombophlebitis. The FVL mutation was present in 14% (95% CI 6–27) of patients with a thrombus on MRI, and in 7% (95% CI 3–18) of patients without a thrombus. For FII, the prevalence in the group with a DVT on MRI was 2% (95% CI 0.4–12) and without a DVT 4% (95% CI 1–13). Conclusion In less than half of PE patients a thrombus can be found with total body MRI. When thrombi were present, they were mainly found in the upper leg, extending into the calf veins. Interestingly, 27% of PEs with a thrombus on MRI was related to isolated calf vein thrombosis and 14% to thrombophlebitis. In PE patients with no thrombus on MRI, a local origin of PE, a thrombus from cardiac origin or complete embolisation needs to be considered. Supported by Netherlands Heart Foundation grant number 2009B050 Disclosures: No relevant conflicts of interest to declare.