ObjectivePatients with clinically suspect arthralgia (CSA) are at risk for developing rheumatoid arthritis (RA). These patients often report joint swelling while this is not objectified by physical... Show moreObjectivePatients with clinically suspect arthralgia (CSA) are at risk for developing rheumatoid arthritis (RA). These patients often report joint swelling while this is not objectified by physical examination. To explore the value of patient-reported swelling in CSA, we aimed to determine its association with subclinical joint inflammation on imaging and RA development.MethodsIn two independent, similarly designed CSA cohorts from the Netherlands, symptomatic patients at risk for RA were studied. At baseline, patients indicated whether they had experienced swelling in hand joints. Subclinical joint inflammation was assessed with MRI or US. Patients were followed for inflammatory arthritis development.ResultsIn total, 534 CSA patients from two independent cohorts were studied, and patient-reported swelling was present in 57% in cohort 1 and in 43% in cohort 2. In both cohorts patient-reported swelling was associated with subclinical joint inflammation. Using MRI, it associated specifically with tenosynovitis (odds ratio [OR] 3.7 [95% CI: 2.0, 6.9]) and when using US with synovitis (OR 2.3 [95% CI: 1.04, 5.3]). CSA patients with self-reported swelling at baseline developed arthritis more often, with hazard ratios of 3.7 (95% CI: 2.0, 6.9) and 3.4 (95% CI: 1.4, 8.4) in cohort 1 and 2, respectively. This was independent of clinical predictors (e.g. morning stiffness), autoantibody positivity and US-detected subclinical joint inflammation. However, when corrected for MRI-detected subclinical joint inflammation, self-reported swelling was no longer an independent predictor.ConclusionPatient-reported joint swelling in CSA relates to subclinical joint inflammation and is an independent risk factor for RA development, but it is less predictive than the presence of MRI-detected subclinical joint inflammation. Show less
Genderen, O.S. van; Wissen, R.C. van; Hamming, J.F.; Schaik, J. van; Vorst, J.R. van der 2023
Purpose: To describe the concept of aortic elastic deformation (ED) measurement using duplex ultrasonography (DUS) as a tool for detection of high aneurysm sac pressure following endovascular... Show morePurpose: To describe the concept of aortic elastic deformation (ED) measurement using duplex ultrasonography (DUS) as a tool for detection of high aneurysm sac pressure following endovascular aortic repair (EVAR). Technique: High aneurysm sac pressure, with or without proven endoleak, will result in a less compressible aneurysm. Using the dual image function in B-mode of the DUS device and a standardized amount of applied probe pressure, ED can be measured. It is defined as the percentage of deformation of the aneurysm sac on probe pressure application. We hypothesize that less ED of the aneurysm sac can be related with high aneurysm sac pressure and possibly the presence of clinically relevant endoleak. In this note, we describe the technical details of the procedure and report on the applicability and results of ED measurements in the framework of aortic aneurysm and EVAR follow-up in a cohort of 109 patients. Conclusion: ED measurement is the first noninvasive pressure-based method in the quest to find a practical and reliable diagnostic tool to exclude high aneurysm sac pressure. In our patient cohort, patients with proven endoleak showed a smaller ED (less compressible), implying the presence of high aneurysm sac pressure. Further research should confirm whether ED measurement using DUS could reliably exclude endoleak after EVAR and further explore its potential for clinical application in EVAR follow-up. Clinical Impact For the first time, a simple, fast, and inexpensive diagnostic tool is presented in this study for detecting high sac pressure following EVAR. High sac pressure is typically caused by clinically significant endoleaks, which can have significant consequences. Currently, computed tomography scanning is the most common method used to identify and characterize endoleaks. However, measuring elastic deformation may potentially replace more invasive and expensive modalities, such as the computed tomography in the future. Show less
Labriji, W.; Clauzel, J.; Mestas, J.L.; Lafond, M.; Lafon, C.; Salabert, A.S.; ... ; Desmoulin, F. 2023
PurposeThis work aims to explore the effect of Blood Brain Barrier (BBB) opening using ultrasound combined with microbubbles injection on cerebral blood flow in rats. MethodsTwo groups of n = 5... Show morePurposeThis work aims to explore the effect of Blood Brain Barrier (BBB) opening using ultrasound combined with microbubbles injection on cerebral blood flow in rats. MethodsTwo groups of n = 5 rats were included in this study. The first group was used to investigate the impact of BBB opening on the Arterial Spin Labeling (ASL) signal, in particular on the arterial transit time (ATT). The second group was used to analyze the spatiotemporal evolution of the change in cerebral blood flow (CBF) over time following BBB opening and validate these results using DSC-MRI. ResultsUsing pCASL, a decrease in CBF of up to 29.6 +/- 15.1%$$ 29.6\pm 15.1\% $$ was observed in the target hemisphere, associated with an increase in arterial transit time. The latter was estimated to be 533 +/- 121ms$$ 533\pm 12\mathrm{1ms} $$ in the BBB opening impacted regions against 409 +/- 93ms$$ 409\pm 93\mathrm{ms} $$ in the contralateral hemisphere. The spatio-temporal analysis of CBF maps indicated a nonlocal hypoperfusion. DSC-MRI measurements were consistent with the obtained results. ConclusionThis study provided strong evidence that BBB opening using microbubble intravenous injection induces a transient hypoperfusion. A spatiotemporal analysis of the hypoperfusion changes allows to establish some points of similarity with the cortical spreading depression phenomenon. Show less
Zijlker, L.P.; Bakker, M.; Hiel, B. van der; Bruining, A.; Klop, W.M.C.; Zuur, C.L.; ... ; Akkooi, A.C.J. van 2022
Background: Merkel cell carcinoma (MCC) is a cutaneous tumor with a high tendency to metastasize, and a significant proportion of patients have metastases at first presentation. This study aims to... Show moreBackground: Merkel cell carcinoma (MCC) is a cutaneous tumor with a high tendency to metastasize, and a significant proportion of patients have metastases at first presentation. This study aims to determine the value of baseline ultrasound (US) and (18)fluorodeoxyglucose-positron emission tomography/computed tomography ((18)FDG-PET/CT) imaging in both patients with clinically localized MCC (Stage I/II) and patients who present with palpable lymph nodes (Stage III). Methods: This retrospective cohort included 135 MCC patients who underwent baseline US (with fine needle aspiration cytology (FNAC)) and/or FDG-PET/CT imaging between 2015 and 2021. Results: Of the 104 patients with clinically localized disease, 48% were upstaged to Stage III and 3% to Stage IV by imaging or sentinel lymph node biopsy (SLNB). FDG-PET/CT imaging identified regional metastases in 23%, while US with FNAC identified regional metastases in 19%. SLNB was performed in 56 patients, of whom 57% were upstaged to Stage III. Of the 31 patients who presented with palpable lymph nodes, 16% were upstaged to Stage IV by FDG-PET/CT imaging. Conclusion: Baseline imaging frequently upstages Stage I/II MCC patients to Stage III, both by US and FDG-PET/CT, Stage IV disease is rarely identified. Patients who present with palpable nodes are frequently upstaged to Stage IV by FDG-PET/CT imaging. Show less
Jong, A. de; Sier, V.Q.; Peters, H.A.B.; Schilder, N.K.M.; Jukema, J.W.; Goumans, M.J.T.H.; ... ; Vries, M.R. de 2022
Aims: Vein grafts are frequently used to bypass coronary artery occlusions. Unfortunately, vein graft disease (VGD) causes impaired patency rates. ALK1 mediates signaling by TGF-beta via TGF beta... Show moreAims: Vein grafts are frequently used to bypass coronary artery occlusions. Unfortunately, vein graft disease (VGD) causes impaired patency rates. ALK1 mediates signaling by TGF-beta via TGF beta R2 or BMP9/10 via BMPR2, which is an important pathway in fibrotic, inflammatory, and angiogenic processes in vascular diseases. The role of the TGF-beta pathway in VGD is previously reported, however, the contribution of ALK1 signaling is not known. Therefore, we investigated ALK1 signaling in VGD in a mouse model for vein graft disease using either genetic or pharmacological inhibition of the Alk1 signaling. Methods and Results: Male ALK1 heterozygous (ALK1(+/-)), control C57BL/6, as well as hypercholesterolemic ApoE3*Leiden mice, underwent vein graft surgery. Histologic analyses of ALK1(+/-) vein grafts demonstrated increased outward remodeling and macrophage accumulation after 28 days. In hypercholesterolemic ApoE3*Leiden mice receiving weekly ALK1-Fc injections, ultrasound imaging showed 3-fold increased outward remodeling compared to controls treated with control-Fc, which was confirmed histologically. Moreover, ALK1-Fc treatment reduced collagen and smooth muscle cell accumulation, increased macrophages by 1.5-fold, and resulted in more plaque dissections. No difference was observed in intraplaque neovessel density. Flow cytometric analysis showed increased systemic levels of Ly6C(High) monocytes in ALK1-Fc treated mice, supported by in vitro increased MCP-1 and IL-6 production of LPS-stimulated and ALK1-Fc-treated murine monocytes and macrophages. Conclusion: Reduced ALK1 signaling in VGD promotes outward remodeling, increases macrophage influx, and promotes an unstable plaque phenotype. Translational Perspective: Vein graft disease (VGD) severely hampers patency rates of vein grafts, necessitating research of key disease-driving pathways like TGF-beta. The three-dimensional nature of VGD together with the multitude of disease driving factors ask for a comprehensive approach. Here, we combined in vivo ultrasound imaging, histological analyses, and conventional in vitro analyses, identifying the ambiguous role of reduced ALK1 signaling in vein graft disease. Reduced ALK1 signaling promotes outward remodeling, increases macrophage influx, and promotes an unstable plaque phenotype in murine vein grafts. Characterization of in vivo vascular remodeling over time is imperative to monitor VGD development and identify new therapies. Show less
This article is part of the point-of-care ultrasound (POCUS) series. During cardiopulmonary resuscitation, bedside ultrasound has important clinical value for confirming a diagnosis, establishing a... Show moreThis article is part of the point-of-care ultrasound (POCUS) series. During cardiopulmonary resuscitation, bedside ultrasound has important clinical value for confirming a diagnosis, establishing a prognosis and in therapeutic decision-making. In this article we provide a practical review on how to implement and apply POCUS during cardiopulmonary resuscitation and discuss its merits and pitfalls. Show less
Steenis, A. van; Fumagalli, M.; Kruit, M.C.; Peeters-Scholte, C.M.P.C.D.; Vries, L.S. de; Steggerda, S.J. 2020
Timely detection of severe infratentorial hemorrhage in neonates is crucial, especially in case of life-threatening brain stem compression and/or acute obstructive hydrocephalus, which need... Show moreTimely detection of severe infratentorial hemorrhage in neonates is crucial, especially in case of life-threatening brain stem compression and/or acute obstructive hydrocephalus, which need lifesaving neurosurgical intervention. Although the detection of infratentorial hemorrhage by ultrasound scanning is often considered as difficult, the use of additional acoustic windows and recognition of characteristic ultrasound features facilitate early diagnosis. In this case series, we report on newborns with severe, symptomatic infratentorial hemorrhage detected primarily by cranial ultrasound. We demonstrate the characteristic ultrasound features present in all cases and discuss how ultrasound diagnosis contributed to early diagnosis and treatment. Show less
Steenis, A. van; Fumagalli, M.; Kruit, M.C.; Peeters-Scholte, C.M.P.C.D.; Vries, L.S. de; Steggerda, S.J. 2020
Timely detection of severe infratentorial hemorrhage in neonates is crucial, especially in case of life-threatening brain stem compression and/or acute obstructive hydrocephalus, which need... Show moreTimely detection of severe infratentorial hemorrhage in neonates is crucial, especially in case of life-threatening brain stem compression and/or acute obstructive hydrocephalus, which need lifesaving neurosurgical intervention. Although the detection of infratentorial hemorrhage by ultrasound scanning is often considered as difficult, the use of additional acoustic windows and recognition of characteristic ultrasound features facilitate early diagnosis. In this case series, we report on newborns with severe, symptomatic infratentorial hemorrhage detected primarily by cranial ultrasound. We demonstrate the characteristic ultrasound features present in all cases and discuss how ultrasound diagnosis contributed to early diagnosis and treatment. Show less
In the last docade ultrasound has found its place in the intensive care unit. Initially, ultrasound was used primarily to increase safety and efficacy of line insertions but now many intensivists... Show moreIn the last docade ultrasound has found its place in the intensive care unit. Initially, ultrasound was used primarily to increase safety and efficacy of line insertions but now many intensivists use point-of-care ultrasound (POCUS) to aid in diagnosis, assessment of therapy and to guide therapeutic interventions. In this series we aim to highlight one specific POCUS technique at a time, which we believe will prove to be useful in clinical practice. Our aim is to provide the reader with a short and practical description of the technique as well as its merits and pitfalls. In this issue we describe the use of the rapid ultrasound in shock (RUSH) protocol to quickly investigate shock in the ICU. Show less
Background: Using ultrasound as a guidance tool during central venous catheter placement has repeatedly been shown to improve procedural safety. More recent evidence has shown its potential as a... Show moreBackground: Using ultrasound as a guidance tool during central venous catheter placement has repeatedly been shown to improve procedural safety. More recent evidence has shown its potential as a diagnostic modality to detect placement-associated complications. A protocol combining these modalities is lacking. This article uses the Indication, Acquisition, Interpretation and Medical decision-making (I-AIM) model, common to other ultrasound protocols, to provide a systematic ultrasound approach to guide central venous catheter placement and assess potential related complications. It is part of a larger series published in this journal.Methods: Relevant articles were found in a thorough search in PubMed using the MeSH terms: "diagnostic imaging" or "ultrasonography" or "sonography" and "central venous catheter" or "central venous cannulation" and "complications" or "placement procedure". Studies conducted on patients younger than 18 years and studies conducted in animals were excluded. Two independent researchers evaluated the articles for relevance and quality. The results of the various studies were used to create the following structured ultrasound approach.Recommended approach: Following the I-AIM model, acquiring the most valuable images is subdivided into patient, probe, picture and protocol considerations. Ultrasound guidance during central venous catheter placement should be conducted in four steps: pre-cannulation, confirming patency, dynamic guidance during insertion, and confirmation of intravenous central venous catheter position. After these steps, ultrasound should be used in the diagnostic evaluation of malposition and iatrogenic pneumothorax.Conclusions: This model provides a comprehensive and ready to use ultrasound approach to guide central venous catheter placement and assess potential placement associated complications. Show less
Objective Congenital heart defects (CHD) are still missed frequently in prenatal screening programs, which can result in severe morbidity or even death. The aim of this study was to evaluate the... Show moreObjective Congenital heart defects (CHD) are still missed frequently in prenatal screening programs, which can result in severe morbidity or even death. The aim of this study was to evaluate the quality of fetal heart images, obtained during the second-trimester standard anomaly scan (SAS) in cases of CHD, to explore factors associated with a missed prenatal diagnosis. Methods In this case-control study, all cases of a fetus born with isolated severe CHD in the Northwestern region of The Netherlands, between 2015 and 2016, were extracted from the PRECOR registry. Severe CHD was defined as need for surgical repair in the first year postpartum. Each cardiac view (four-chamber view (4CV), three-vessel (3V) view and left and right ventricular outflow tract (LVOT, RVOT) views) obtained during the SAS was scored for technical correctness on a scale of 0 to 5 by two fetal echocardiography experts, blinded to the diagnosis of CHD and whether it was detected prenatally. Quality parameters of the cardiac examination were compared between cases in which CHD was detected and those in which it was missed on the SAS. Regression analysis was used to assess the association of sonographer experience and of screening-center experience with the cardiac examination quality score.Results A total of 114 cases of isolated severe CHD at birth were analyzed, of which 58 (50.9%) were missed and 56 (49.1%) were detected on the SAS. The defects comprised transposition of the great arteries (17%), aortic coarctation (16%), tetralogy of Fallot (10%), atrioventricular septal defect (6%), aortic valve stenosis (5%), ventricular septal defect (18%) and other defects (28%). No differences were found in fetal position, obstetric history, maternal age or body mass index (BMI) or gestational age at examination between missed and detected cases. Ninety-two cases had available cardiac images from the SAS. Compared with the detected group, the missed group had significantly lower cardiac examination quality scores (adequate score (>= 12) in 32% vs 64%; P=0.002), rate of proper use of magnification (58% vs 84%; P=0.01) and quality scores for each individual cardiac plane (4CV (2.7 vs 3.9; P<0.001), 3V view (3.0 vs 3.8; P=0.02), LVOT view (1.9 vs 3.3; P<0.001) and RVOT view (1.9 vs 3.3; P<0.001)). In 49% of missed cases, the lack of detection was due to poor adaptational skills resulting in inadequate images in which the CHD was not clearly visible; in 31%, the images showed an abnormality (mainly septal defects and aortic arch anomalies) which had not been recognized at the time of the scan; and, in 20%, the cardiac planes had been obtained properly but showed normal anatomy. Multivariate regression analysis showed that the volume of SAS performed per year by each sonographer was associated significantly with quality score of the cardiac examination.Conclusions A lack of adaptational skills when performing the SAS, as opposed to circumstantial factors such as BMI or fetal position, appears to play an important role in failure to detect CHD prenatally. The quality of the cardiac views was inadequate significantly more often in undetected compared with detected cases. Despite adequate quality of the images, CHD was not recognized in 31% of cases. A high volume of SAS performed by each sonographer in a large ultrasound center contributes significantly to prenatal detection. In 20% of undetected cases, CHD was not visible even though the quality of the images was good. (c) 2019 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology. Show less
In the last decade ultrasound has found its place in the intensive care unit. Initially ultrasound was used primarily to increase safety and efficacy of line insertion but now many intensivists use... Show moreIn the last decade ultrasound has found its place in the intensive care unit. Initially ultrasound was used primarily to increase safety and efficacy of line insertion but now many intensivists use point-of-care ultrasound (POCUS) to aid in diagnosis, assessment of therapy and therapeutic interventions. In this series we aim to highlight one specific POCUS technique at a time, which we believe will prove to be useful in your clinical practice. In this issue our aim is to provide you with a short and practical description of the measurement of E-point septal separation to identify a severely reduced left ventricular ejection fraction. Show less
Emery, P.; Horton, S.; Dumitru, R.B.; Naraghi, K.; Heijde, D. van der; Wakefield, R.J.; ... ; Buch, M.H. 2020
ObjectivesWe sought to confirm in very early rheumatoid arthritis (ERA) a much greater superiority (30%) of first-line etanercept+methotrexate (ETN+MTX) over treat-to-target MTX (MTX-TT) than... Show moreObjectivesWe sought to confirm in very early rheumatoid arthritis (ERA) a much greater superiority (30%) of first-line etanercept+methotrexate (ETN+MTX) over treat-to-target MTX (MTX-TT) than previously reported in ERA (14%); and explore whether ETN following initial MTX secures a comparable response to first-line ETN+MTX.MethodsPragmatic, open-label, randomised controlled trial of treatment-naive ERA (<= 12 months symptom), Disease Activity Score 28 joint (DAS28)-erythrocyte sedimentation rate (ESR) >= 3.2, rheumatoid factor (RF)+/-anticitrullinated peptide antibody (ACPA) positive or ultrasound power Doppler (PD) if RF and ACPA negative. Subjects were randomised 1:1 to ETN+MTX; or MTX-TT, escalated to ETN if week 24 DAS28-ESR >= 2.6 and intramuscular corticosteroid at protocolised time points. Primary endpoint of week 48 DAS28ESR remission with clinical and imaging secondary endpoints.ResultsWe randomised 120 patients, 60 to each arm (71% female, 73% RF/84% ACPA positive, median (IQR) symptom duration 20.3 (13.1, 30.8) weeks; mean (SD) DAS28 5.1 (1.1)). Remission rates with ETN+MTX and MTX-TT, respectively, were 38% vs 33% at week 24; 52% vs 38% at week 48 (ORs 1.6, 95% CI 0.8 to 3.5, p=0.211). Greater, sustained DAS28-ESR remission observed with ETN+MTX versus MTX-TT (42% and 27%, respectively; p=0.035). PD was fully suppressed by week 48 in over 90% in each arm. Planned exploratory analysis revealed OR 2.84, 95% CI 0.8 to 9.6) of achieving remission after 24 weeks of ETN administered first line compared with administered post-MTX.ConclusionsCompared with remission rates typically reported with first-line tumour necrosis factor inhabitor+MTX versus MTX-TT, we did not demonstrate a larger effect in very ERA. Neither strategy conferred remission in the majority of patients although ultrasound confirmed local inflammation suppression. Poorer ETN response following failure of MTX-TT is also suggested. Show less
Objective: Uveal melanoma (UM) is the most common primary intra-ocular tumour. Treatment is determined by tumour size and location. Generally, smaller tumours are eligible for brachytherapy unless... Show moreObjective: Uveal melanoma (UM) is the most common primary intra-ocular tumour. Treatment is determined by tumour size and location. Generally, smaller tumours are eligible for brachytherapy unless they are located close to posterior pole. Larger tumours are enucleated or undergo proton beam therapy (PBT), which is more expensive than brachytherapy and less available. Accuracy of tumour size determination is critical for accurate planning and delivery of treatment, particularly to ensure tumour coverage, critical structure sparing, and for the choice of treatment modality. This is particularly the case for tumour dimensions that are close to the cut-off point for a specific type of treatment: in the case of the brachytherapy protocol at our institution, 6-8 mm. Ultrasound is conventionally used, but magnetic resonance imaging (MRI) has recently become an additional available tool. Although more expensive, it enables more accurate measurements and is particularly useful in combination with clinical fundus examination, fundus photography and ultrasound. Our aim in this paper was to determine the economic value of MRI for UM treatment.Methods: We retrospectively analysed 60 patients' MRI scans acquired as part of a study or for clinical care. For each patient, we assessed whether the extra cost of an MRI generated economic benefit or change in optimal treatment.Results: MRI indicated a smaller tumour prominence than US in 10% of patients with intermediate tumour size, resulting in a change from PBT to brachytherapy. The costs of MRI, (sic)200-(sic)1000, are significantly lower than the higher costs of PBT compared to brachytherapy, (sic)24,000 difference. In addition, the annual total economic burden of severe vision impairment associated with eye removal is (sic)10,000. Furthermore, for patients where ultrasound was impossible due to previous surgery, MRI enabled eye-preserving treatment.Conclusion: An additional MRI for specific patients with UM improves economic value as it enables less expensive treatment in a sufficient percentage of patients to compensate for the MRI costs. Value is increased in terms of quality of care as it enables for some a treatment option which spares more vision. Show less
Uveal melanoma (UM), the most common primary intraocular tumour, is often complicated by exudative retinal detachment (RD). Sometimes. this exudative RD is mistaken for a rhegmatogenous detachment... Show moreUveal melanoma (UM), the most common primary intraocular tumour, is often complicated by exudative retinal detachment (RD). Sometimes. this exudative RD is mistaken for a rhegmatogenous detachment and is subsequently treated with vitrectomy with silicone oil (SiOil) tamponade. As SiOil prevents ultrasound imaging, the diagnosis, treatment planning and/or follow-up of UM underlying the detachment are often severely hindered by the SiOil. We aim to develop and evaluate new MRI methods to image UM patients with a SiOil tamponade and evaluate this in vivo. A dedicated MRI protocol for 3 and 7 T was developed and subsequently evaluated in three patients. The MRI protocol developed was evaluated in three patients. In the first patient, SiOil hindered follow-up and therefore MRI was indicated. No tumour recurrence was found after two follow-up scans. The second and third patient underwent vitrectomy with SiOil for assumed rhegmatogenous RD in another hospital, during which a mass was found. In these cases, MRI was used to determine whether the lesion was UM and perform measurements to plan brachytherapy treatment. In general, the proposed workflow is more complicated on 7 T than on 3 T as the off-resonance effects scale linearly with field strength. For example, the shimming procedure needed modifications at 7 T, whereas at 3 T, the automatic shimming sufficed. However, at 7 T, higher resolution images were obtained compared with 3 T (0.6 vs. 0.8 mm(3)). A dedicated MRI protocol enables high-resolution imaging of vitrectomized eyes with SiOil tamponade, enabling treatment planning or follow-up in UM patients. Copyright (C) 2019 The Author(s). Published by Wolters Kluwer Health, Inc. Show less
Matta, J.E.L.; Kraemer, C.V.E.; Tuinman, P.R.; Westerloo, D.J. van 2019
