Publications by authors named "Jean-Paul Vallée"

95 Publications

His-Optimized Cardiac Resynchronization Therapy With Ventricular Fusion Pacing for Electrical Resynchronization in Heart Failure.

JACC Clin Electrophysiol 2021 Feb 19. Epub 2021 Feb 19.

Department of Cardiology, University Hospital of Geneva, Geneva, Switzerland. Electronic address:

Objectives: This study sought to evaluate the effectiveness of His-optimized cardiac resynchronization therapy (HOT-CRT) for reducing left ventricular activation time (LVAT) compared to His bundle pacing (HBP) and biventricular (BiV) pacing (including multipoint pacing [MPP]), using electrocardiographic (ECG) imaging.

Background: HBP may correct bundle branch block (BBB) and has shown encouraging results for providing CRT. However, HBP does not correct BBB in all patients and may be combined with univentricular or BiV fusion pacing to deliver HOT-CRT to maximize resynchronization.

Methods: Nineteen patients with a standard indication for CRT, implanted with HBP without correction of BBB and BiV (n = 14) or right ventricular (n = 5) leads, were prospectively enrolled. Patients underwent ECG imaging while pacing in different configurations using different LV electrodes and at different HBP ventricular pacing (VP) delays. The primary endpoint was reduction in LVAT with HOT-CRT, and the secondary endpoints included various other dys-synchrony measurements including right ventricular activation time (RVAT).

Results: Compared to HBP, HOT-CRT reduced LVAT by 21% (-17 ms [95% confidence interval [CI]: -25 to -9 ms]; p < 0.001) and outperformed BiV by 24% (-22 ms [95% CI: -33 to -10 ms]; p = 0.002) and MPP by 13% (-11 ms [95% CI: -21 to -1 ms]; p = 0.035). Relative to HBP, HOT-CRT also reduced RVAT by 7% (-5 ms [95% CI: -9 to -1 ms; p = 0.035) in patients with right BBB, whereas RVAT was increased by BiV. The other electrical dyssynchrony measurements also improved with HOT-CRT.

Conclusions: HOT-CRT acutely improves ventricular electrical synchrony beyond BiV and MPP. The impact of this finding needs to be evaluated further in studies with clinical follow-up. (Electrical Resynchronization and Acute Hemodynamic Effects of Direct His Bundle Pacing Compared to Biventricular Pacing; NCT03452462).
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http://dx.doi.org/10.1016/j.jacep.2020.11.029DOI Listing
February 2021

A 13-Year-Old Male With Diagnosed Idiopathic Pulmonary Hypertension: Is it Really Idiopathic?

Chest 2020 Dec;158(6):e295-e298

Pediatric Cardiology Unit, University Hospitals of Geneva, Geneva, Switzerland; Centre Universitaire Romand de Cardiologie et Chirurgie Cardiaque Pédiatrique, University of Geneva and Lausanne, Switzerland.

Case Presentation: A 13-year-old male was referred after incidental finding of cardiomegaly on chest radiograph and signs of pulmonary hypertension on subsequent cardiology consult. He was diagnosed with idiopathic pulmonary hypertension, and came to our center for a second opinion. He was born from consanguineous parents. He reported to be asymptomatic in his daily life. He was not on medications. Family history was not contributive.
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http://dx.doi.org/10.1016/j.chest.2020.07.016DOI Listing
December 2020

Outcome of paediatric portopulmonary hypertension in the modern management era: A case report of 6 patients.

J Hepatol 2021 Mar 1;74(3):742-747. Epub 2020 Dec 1.

Pediatric Cardiology Unit, Children's University Hospital, Geneva, Switzerland; Centre Universitaire Romand de Cardiologie et Chirurgie Cardiaque Pédiatrique, Children's University Hospitals, Lausanne and Geneva, Switzerland; Pulmonary Hypertension Program, University Hospitals of Geneva, Geneva, Switzerland.

Portopulmonary hypertension is a rare but serious complication of portal hypertension or portosystemic shunting. Portopulmonary hypertension is an indication for liver transplantation or shunt closure. However, liver transplantation is contraindicated in patients with severe pulmonary arterial hypertension. Reported mortality rates are high in children with portopulmonary hypertension and there are scarce recommendations on its management. Our aim was to report on our real-world experience of managing portopulmonary hypertension in a specialised centre. We describe a series of 6 children with portopulmonary hypertension. Their median age at diagnosis was 13 years (range 10-15). The underlying liver conditions were cirrhosis of unknown origin (1), congenital portocaval shunts (3), biliary atresia (1), and portal vein cavernoma with surgical mesenterico-caval shunt (1). Median mean pulmonary arterial pressure was 47 mmHg (range 32-70), and median pulmonary vascular resistance was 6.6 Wood units (range 4.3-15.4). All patients except one were treated with a combination of pulmonary arterial hypertension-specific therapy (phosphodiesterase type 5 inhibitors and/or endothelin receptor antagonists and/or prostacyclin analogues). Three patients then benefited from shunt closure and the others underwent liver transplantation. Five patients showed improvement or stabilisation of pulmonary arterial hypertension with no deaths after a mean follow-up of 39 months. Based on our limited experience, early and aggressive treatment with a combination of pulmonary arterial hypertension-specific therapy significantly improves patients' haemodynamic profile and enables the performance of liver transplantation and shunt closure with satisfactory outcomes.
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http://dx.doi.org/10.1016/j.jhep.2020.11.039DOI Listing
March 2021

The effect of the elongation of the proximal aorta on the estimation of the aortic wall distensibility.

Biomech Model Mechanobiol 2021 Feb 31;20(1):107-119. Epub 2020 Jul 31.

Laboratory of Hemodynamics and Cardiovascular Technology (LHTC), IBI-STI, Ecole Polytechnique Fédérale de Lausanne (EPFL), MED 3 2226 (Batiment MED), Station 9, 1015, Lausanne, Switzerland.

The compliance of the proximal aortic wall is a major determinant of cardiac afterload. Aortic compliance is often estimated based on cross-sectional area changes over the pulse pressure, under the assumption of a negligible longitudinal stretch during the pulse. However, the proximal aorta is subjected to significant axial stretch during cardiac contraction. In the present study, we sought to evaluate the importance of axial stretch on compliance estimation by undertaking both an in silico and an in vivo approach. In the computational analysis, we developed a 3-D finite element model of the proximal aorta and investigated the discrepancy between the actual wall compliance to the value estimated after neglecting the longitudinal stretch of the aorta. A parameter sensitivity analysis was further conducted to show how increased material stiffness and increased aortic root motion might amplify the estimation errors (discrepancies between actual and estimated distensibility ranging from - 20 to - 62%). Axial and circumferential aortic deformation during ventricular contraction was also evaluated in vivo based on MR images of the aorta of 3 healthy young volunteers. The in vivo results were in good qualitative agreement with the computational analysis (underestimation errors ranging from - 26 to - 44%, with increased errors reflecting higher aortic root displacement). Both the in silico and in vivo findings suggest that neglecting the longitudinal strain during contraction might lead to severe underestimation of local aortic compliance, particularly in the case of women who tend to have higher aortic root motion or in subjects with stiff aortas.
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http://dx.doi.org/10.1007/s10237-020-01371-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7892736PMC
February 2021

Atlas Sampling for Prone Breast Automatic Segmentation of Organs at Risk: The Importance of Patients' Body Mass Index and Breast Cup Size for an Optimized Contouring of the Heart and the Coronary Vessels.

Technol Cancer Res Treat 2020 Jan-Dec;19:1533033820920624

Division of Radiation Oncology, Geneva University Hospital, Switzerland.

Objective: Delineation of organs at risk is a time-consuming task. This study evaluates the benefits of using single-subject atlas-based automatic segmentation of organs at risk in patients with breast cancer treated in prone position, with 2 different criteria for choosing the atlas subject. Together with laterality (left/right), the criteria used were either (1) breast volume or (2) body mass index and breast cup size.

Methods: An atlas supporting different selection criteria for automatic segmentation was generated from contours drawn by a senior radiation oncologist (RO_A). Atlas organs at risk included heart, left anterior descending artery, and right coronary artery. Manual contours drawn by RO_A and automatic segmentation contours of organs at risk and breast clinical target volume were created for 27 nonatlas patients. A second radiation oncologist (RO_B) manually contoured (M_B) the breast clinical target volume and the heart. Contouring times were recorded and the reliability of the automatic segmentation was assessed in the context of 3-D planning.

Results: Accounting for body mass index and breast cup size improved automatic segmentation results compared to breast volume-based sampling, especially for the heart (mean similarity indexes >0.9 for automatic segmentation organs at risk and clinical target volume after RO_A editing). Mean similarity indexes for the left anterior descending artery and the right coronary artery edited by RO_A expanded by 1 cm were ≥0.8. Using automatic segmentation reduced contouring time by 40%. For each parameter analyzed (eg, D), the difference in dose, averaged over all patients, between automatic segmentation structures edited by RO_A and the same structure manually drawn by RO_A was <1.5% of the prescribed dose. The mean heart dose was reliable for the unedited heart segmentation, and for right-sided treatments, automatic segmentation was adequate for treatment planning with 3-D conformal tangential fields.

Conclusions: Automatic segmentation for prone breast radiotherapy stratified by body mass index and breast cup size improved segmentation accuracy for the heart and coronary vessels compared to breast volume sampling. A significant reduction in contouring time can be achieved by using automatic segmentation.
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http://dx.doi.org/10.1177/1533033820920624DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7175049PMC
November 2020

Diffusion magnetic resonance imaging detects an increase in interstitial fibrosis earlier than the decline of renal function.

Nephrol Dial Transplant 2020 07;35(7):1274-1276

Service and Laboratory of Nephrology, Department of Internal Medicine Specialties and of Physiology and Metabolism, University and University Hospital of Geneva, Geneva, Switzerland.

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http://dx.doi.org/10.1093/ndt/gfaa007DOI Listing
July 2020

Ultrasound-driven cardiac MRI.

Phys Med 2020 Feb 4;70:161-168. Epub 2020 Feb 4.

Radiology Department, University Hospitals of Geneva, Geneva, Switzerland.

Purpose: One of the challenges of cardiac MR imaging is the compensation of respiratory motion, which causes the heart and the surrounding tissues to move. Commonly-used methods to overcome this effect, breath-holding and MR navigation, present shortcomings in terms of available acquisition time or need to periodically interrupt the acquisition, respectively. In this work, an implementation of respiratory motion compensation that obtains information from abdominal ultrasound and continuously adapts the imaged slice position in real time is presented.

Methods: A custom workflow was developed, comprising an MR-compatible ultrasound acquisition system, a feature-motion-tracking system with polynomial predictive capability, and a custom MR sequence that continuously adapts the position of the acquired slice according to the tracked position. The system was evaluated on a moving phantom by comparing sharpness and image blurring between static and moving conditions, and in vivo by tracking the motion of the blood vessels of the liver to estimate the cardiac motion. Cine images of the heart were acquired during free breathing.

Results: In vitro, the predictive motion correction yielded significantly better results than non-predictive or non-corrected acquisitions (p ≪ 0.01). In vivo, the predictive correction resulted in an image quality very similar to the breath-hold acquisition, whereas the uncorrected images show noticeable blurring artifacts.

Conclusion: In this work, the possibility of using ultrasound navigation with tracking for the real-time adaptation of MR imaging slices was demonstrated. The implemented technique enabled efficient imaging of the heart with resolutions that would not be feasible in a single breath-hold.
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http://dx.doi.org/10.1016/j.ejmp.2020.01.008DOI Listing
February 2020

Cardiomyocyte-Specific JunD Overexpression Increases Infarct Size following Ischemia/Reperfusion Cardiac Injury by Downregulating Sirt3.

Thromb Haemost 2020 Jan 13;120(1):168-180. Epub 2019 Dec 13.

Center for Molecular Cardiology, Schlieren Campus, University of Zurich, Zurich, Switzerland.

Ischemia/reperfusion (I/R) injury in acute myocardial infarction activates several deleterious molecular mechanisms. The transcription factor JunD regulates pathways involved in oxidative stress as well as in cellular proliferation, differentiation, and death. The present study investigated the potential role of JunD as a modulator of myocardial injury pathways in a mouse model of cardiac I/R injury. Infarct size, systemic and local inflammation, and production of reactive oxygen species, as well as cytosolic and mitochondrial apoptotic pathways were investigated in adult males after myocardial I/R. In wild-type (WT) mice, 30 minutes after ischemia and up to 24 hours following reperfusion, cardiac messenger ribonucleic acid expression was reduced while increased. Cardiac-specific JunD overexpressing mice ( ) displayed larger infarcts compared with WT. However, postischemic inflammatory or oxidative responses did not differ. JunD overexpression reduced Sirt3 transcription by binding to its promoter, thus leading to mitochondrial dysfunction, myocardial cell death, and increased infarct size. On the other hand, JunD silencing reduced, while Sirt3 silencing increased infarct size. In human myocardial autopsy specimens, JunD-positive areas within the infarcted left ventricle staining corresponded to undetectable Sirt3 areas in consecutive sections of the same heart. Cardiac-specific JunD overexpression increases myocardial infarct size following I/R. These effects are mediated via Sirt3 transcriptional repression, mitochondrial swelling, and increased apoptosis, suggesting that JunD is a key regulator of myocardial I/R injury. The present data set the stage for further investigation of the potential role of Sirt3 activation as a novel target for the treatment of acute myocardial infarction.
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http://dx.doi.org/10.1055/s-0039-3400299DOI Listing
January 2020

Consensus-based technical recommendations for clinical translation of renal diffusion-weighted MRI.

MAGMA 2020 Feb 1;33(1):177-195. Epub 2019 Nov 1.

Department of Radiology, Center for Biomedical Imaging (CBI), Center for Advanced Imaging Innovation and Research (CAI2R), NYU Langone Health, New York, NY, USA.

Objectives: Standardization is an important milestone in the validation of DWI-based parameters as imaging biomarkers for renal disease. Here, we propose technical recommendations on three variants of renal DWI, monoexponential DWI, IVIM and DTI, as well as associated MRI biomarkers (ADC, D, D*, f, FA and MD) to aid ongoing international efforts on methodological harmonization.

Materials And Methods: Reported DWI biomarkers from 194 prior renal DWI studies were extracted and Pearson correlations between diffusion biomarkers and protocol parameters were computed. Based on the literature review, surveys were designed for the consensus building. Survey data were collected via Delphi consensus process on renal DWI preparation, acquisition, analysis, and reporting. Consensus was defined as ≥ 75% agreement.

Results: Correlations were observed between reported diffusion biomarkers and protocol parameters. Out of 87 survey questions, 57 achieved consensus resolution, while many of the remaining questions were resolved by preference (65-74% agreement). Summary of the literature and survey data as well as recommendations for the preparation, acquisition, processing and reporting of renal DWI were provided.

Discussion: The consensus-based technical recommendations for renal DWI aim to facilitate inter-site harmonization and increase clinical impact of the technique on a larger scale by setting a framework for acquisition protocols for future renal DWI studies. We anticipate an iterative process with continuous updating of the recommendations according to progress in the field.
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http://dx.doi.org/10.1007/s10334-019-00790-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7021760PMC
February 2020

Epicardial fat mimicking left atrial appendage thrombus.

Cardiol J 2019 ;26(4):418-419

Cardiology Service, Geneva University Hospitals, Geneva, Switzerland.

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http://dx.doi.org/10.5603/CJ.2019.0080DOI Listing
July 2020

Impact of Liver Diseases on Heart and Lungs.

JACC Cardiovasc Imaging 2019 10 15;12(10):2071-2075. Epub 2019 May 15.

Department of Radiology, APHP, University Hospitals Paris Nord Val de Seine, Beaujon, Clichy, Hauts-de-Seine, France, and University Paris Diderot, Sorbonne Paris Cité, Paris, France; INSERM U1149, Centre de Recherche de L'inflammation, CRI, Paris, France.

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http://dx.doi.org/10.1016/j.jcmg.2019.03.020DOI Listing
October 2019

Validation of the corticomedullary difference in magnetic resonance imaging-derived apparent diffusion coefficient for kidney fibrosis detection: a cross-sectional study.

Nephrol Dial Transplant 2020 06;35(6):937-945

Service and Laboratory of Nephrology, Department for Statistics, Department of Internal Medicine Specialties and of Physiology and Metabolism, University Hospital and University of Geneva, Geneva, Switzerland.

Background: Kidney cortical interstitial fibrosis (IF) is highly predictive of renal prognosis and is currently assessed by the evaluation of a biopsy. Diffusion magnetic resonance imaging (MRI) is a promising tool to evaluate kidney fibrosis via the apparent diffusion coefficient (ADC), but suffers from inter-individual variability. We recently applied a novel MRI protocol to allow calculation of the corticomedullary ADC difference (ΔADC). We here present the validation of ΔADC for fibrosis assessment in a cohort of 164 patients undergoing biopsy and compare it with estimated glomerular filtration rate (eGFR) and other plasmatic parameters for the detection of fibrosis.

Methods: This monocentric cross-sectional study included 164 patients undergoing renal biopsy at the Nephrology Department of the University Hospital of Geneva between October 2014 and May 2018. Patients underwent diffusion-weighted imaging, and T1 and T2 mappings, within 1 week after biopsy. MRI results were compared with gold standard histology for fibrosis assessment.

Results: Absolute cortical ADC or cortical T1 values correlated poorly to IF assessed by the biopsy, whereas ΔADC was highly correlated to IF (r=-0.52, P < 0.001) and eGFR (r = 0.37, P < 0.01), in both native and allograft patients. ΔT1 displayed a lower, but significant, correlation to IF and eGFR, whereas T2 did not correlate to IF nor to eGFR. ΔADC, ΔT1 and eGFR were independently associated with kidney fibrosis, and their combination allowed detection of extensive fibrosis with good specificity.

Conclusion: ΔADC is better correlated to IF than absolute cortical or medullary ADC values. ΔADC, ΔT1 and eGFR are independently associated to IF and allow the identification of patients with extensive IF.
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http://dx.doi.org/10.1093/ndt/gfy389DOI Listing
June 2020

MRI micelles self-assembled from synthetic gadolinium-based nano building blocks.

Chem Commun (Camb) 2019 Jan;55(7):945-948

Pharmaceutical Technology, School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, 1211 Geneva 4, Switzerland.

A synthetic nano building block endowed with amphiphilic properties and chelated gadolinium is presented. Spontaneous self-assembly into small 12 nm corona-core stealth Gd-micelles with inherently high gadolinium loading occurs in water. Gd-Micelles are a new blood pool contrast agent with high relaxivity for magnetic resonance imaging.
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http://dx.doi.org/10.1039/c8cc08875fDOI Listing
January 2019

Image acquisition for intravoxel incoherent motion imaging of kidneys should be triggered at the instant of maximum blood velocity: evidence obtained with simulations and in vivo experiments.

Magn Reson Med 2019 01 26;81(1):583-593. Epub 2018 Aug 26.

Département de Medecine, Service de Néphrologie, Centre Hospitalier Universitaire Vaudois, Vaud, Switzerland.

Purpose: To demonstrate that diffusion-weighted images should be acquired at the instant of maximum blood velocity in kidneys to extract the perfusion fraction (PF) by the bi-exponential intravoxel incoherent motion model.

Methods: The PF values were measured in Monte-Carlo simulations corresponding to different blood velocities with a constant known PF. The distribution of the measured PF values (PF-distribution) was characterized quantitatively by 3 markers highlighting the deviation of the measurement from the true PF. Diffusion-weighted images of kidneys were acquired in 10 healthy volunteers at the instant of maximal respectively minimal blood velocity in the renal artery (V versus V acquisition). The PF-distributions measured from the V and V acquisitions were compared mutually and with simulated PF-distributions using the 3 markers. A radiologist evaluated the quality of the PF maps.

Results: The PF-distributions measured in the simulations were spread around the true PF value, and spreading was reduced as blood velocity increased. A comparison between simulated and in vivo PF-distributions suggests that a similar phenomenon is plausible in vivo. The quality of the PF maps of the V -acquisition was scored higher by the radiologist than those of the V -acquisition in 95% of cases (19 of 20).

Conclusions: The PF maps are of better quality when the V -acquisition is used. We show evidence supporting the hypothesis that the variation of PF along the cardiac cycle is due to oscillations between a poor estimation when the blood velocity is low, and a better estimation when blood velocity is higher.
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http://dx.doi.org/10.1002/mrm.27393DOI Listing
January 2019

Magnetic resonance imaging biomarkers for chronic kidney disease: a position paper from the European Cooperation in Science and Technology Action PARENCHIMA.

Nephrol Dial Transplant 2018 09;33(suppl_2):ii4-ii14

Leeds Imaging Biomarkers Group, Department of Biomedical Imaging Sciences, University of Leeds, Leeds, UK.

Functional renal magnetic resonance imaging (MRI) has seen a number of recent advances, and techniques are now available that can generate quantitative imaging biomarkers with the potential to improve the management of kidney disease. Such biomarkers are sensitive to changes in renal blood flow, tissue perfusion, oxygenation and microstructure (including inflammation and fibrosis), processes that are important in a range of renal diseases including chronic kidney disease. However, several challenges remain to move these techniques towards clinical adoption, from technical validation through biological and clinical validation, to demonstration of cost-effectiveness and regulatory qualification. To address these challenges, the European Cooperation in Science and Technology Action PARENCHIMA was initiated in early 2017. PARENCHIMA is a multidisciplinary pan-European network with an overarching aim of eliminating the main barriers to the broader evaluation, commercial exploitation and clinical use of renal MRI biomarkers. This position paper lays out PARENCHIMA's vision on key clinical questions that MRI must address to become more widely used in patients with kidney disease, first within research settings and ultimately in clinical practice. We then present a series of practical recommendations to accelerate the study and translation of these techniques.
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http://dx.doi.org/10.1093/ndt/gfy152DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6106645PMC
September 2018

Diffusion-weighted magnetic resonance imaging to assess diffuse renal pathology: a systematic review and statement paper.

Nephrol Dial Transplant 2018 09;33(suppl_2):ii29-ii40

Division of Radiology, Geneva University Hospitals, University of Geneva, Geneva, Switzerland.

Diffusion-weighted magnetic resonance imaging (DWI) is a non-invasive method sensitive to local water motion in the tissue. As a tool to probe the microstructure, including the presence and potentially the degree of renal fibrosis, DWI has the potential to become an effective imaging biomarker. The aim of this review is to discuss the current status of renal DWI in diffuse renal diseases. DWI biomarkers can be classified in the following three main categories: (i) the apparent diffusion coefficient-an overall measure of water diffusion and microcirculation in the tissue; (ii) true diffusion, pseudodiffusion and flowing fraction-providing separate information on diffusion and perfusion or tubular flow; and (iii) fractional anisotropy-measuring the microstructural orientation. An overview of human studies applying renal DWI in diffuse pathologies is given, demonstrating not only the feasibility and intra-study reproducibility of DWI but also highlighting the need for standardization of methods, additional validation and qualification. The current and future role of renal DWI in clinical practice is reviewed, emphasizing its potential as a surrogate and monitoring biomarker for interstitial fibrosis in chronic kidney disease, as well as a surrogate biomarker for the inflammation in acute kidney diseases that may impact patient selection for renal biopsy in acute graft rejection. As part of the international COST (European Cooperation in Science and Technology) action PARENCHIMA (Magnetic Resonance Imaging Biomarkers for Chronic Kidney Disease), aimed at eliminating the barriers to the clinical use of functional renal magnetic resonance imaging, this article provides practical recommendations for future design of clinical studies and the use of renal DWI in clinical practice.
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http://dx.doi.org/10.1093/ndt/gfy163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6106641PMC
September 2018

Low Iodine Contrast Injection for CT Acquisition Prior to Transcatheter Aortic Valve Replacement: Aorta Assessment and Screening for Coronary Artery Disease.

Acad Radiol 2019 07 1;26(7):e150-e160. Epub 2018 Aug 1.

Division of Radiology, University Hospitals of Geneva, Switzerland, Rue Gabrielle-Perret-Gentil 4, Geneva, Switzerland.

Rationale And Objectives: To assess both the complete aorta and coronary artery disease (CAD) using low iodine contrast computed-tomography angiography before transcatheter aortic valve replacement.

Materials And Methods: 84 patients underwent computed-tomography angiography before transcatheter aortic valve replacement: 42 with standard iodine injection protocol (P1:120 mL); 42 with a low dose iodine injection protocol (P2:60 mL). Mean attenuation and subjective image quality were rated at different levels of the aorta, iliac and coronary arteries. Sensitivity, specificity, negative and positive predictive values for depiction of CAD were calculated according to the coronary angiography.

Results: Mean attenuation was significantly higher in P1 for the ascending aorta (p < 0.001). No significant difference was observed regarding image quality of the aortic valve (p = 0.876), the ascending aorta (p = 0.306), or the abdominal aorta (p = 1.0). Diagnostic image quality of coronary arteries was excellent for P1 and P2 (94.6% vs 96.5%, p = 0.08). Sensitivity, specificity, negative and positive predictive values, and accuracy for depiction of CAD were excellent for P1 and P2 (100% vs 100%; 79% vs 86%, 70% vs 87%, 100% vs 100% and 86% vs 93%) without significant differences (p = 0.93; p = 0.58; p = 0.90; p = 1.0; p = 0.74), respectively.

Conclusion: Despite a difference in aortic mean attenuation, a reduced iodine injection protocol showed similar image quality and detection of CAD in comparison with a standard injection protocol.
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http://dx.doi.org/10.1016/j.acra.2018.06.016DOI Listing
July 2019

3D-printed heart model to guide LAA closure: useful in clinical practice?

Eur Radiol 2019 Jan 14;29(1):251-258. Epub 2018 Jun 14.

Division of Radiology, University Hospitals of Geneva, Rue Gabrielle-Perret-Gentil 4, 1291, Geneva, Switzerland.

Objectives: Correct device sizing for left atrial appendage (LAA) closure remains challenging due to complex LAA shapes. The aim of our study was to investigative the utility of personalized 3D-printed models (P3DPM) of the LAA to guide device size selection.

Methods: Fifteen patients (75.4 ±8.5years) scheduled for LAA closure using an Amulet device underwent cardiac computed tomography (CT). The LAA was segmented by semiautomatic algorithms using Vitrea® software. A 1.5-mm LAA thick shell was exported in stereolithography format and printed using TangoPlus flexible material. Different Amulet device sizes on the P3DPM were tested. New P3DPM-CT with the device was acquired in order to appreciate the proximal disc sealing the LAA ostium and the compression of the distal lobe within the LAA. We predicted the device size with P3DPM and compared this with the device sizes predicted by transesophageal echocardiography (TEE) and CT as well as the device size implanted in patients.

Results: The device size predicted by 3D-TEE and CT corresponded to the implanted device size in 8/15 (53%) and 10/15 (67%), respectively. The predicted device size from the P3DPM was accurate in all patients, obtaining perfect contact with the LAA wall, without device instability or excessive compression. P3DPM-CT with the deployed device showed device deformation and positioning of the disk in relation to the pulmonary veins, allowing us to determine the best device size in all 15 cases.

Conclusion: P3DPM allowed us to simulate the LAA closure procedure and thus helped to identify the best Amulet size and position within the LAA.

Key Points: • A 3D-printed heart model allows to simulate the LAA closure procedure. • A 3D-printed heart model allowed to identify the optimal Amulet size and position. • 3D-printed heart models may contribute to reduce the Amulet implantation learning curve.
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http://dx.doi.org/10.1007/s00330-018-5569-xDOI Listing
January 2019

The Effect of Neoadjuvant Androgen Deprivation Therapy on Tumor Hypoxia in High-Grade Prostate Cancer: An F-MISO PET-MRI Study.

Int J Radiat Oncol Biol Phys 2018 11 8;102(4):1210-1218. Epub 2018 Mar 8.

Radiation Oncology, Geneva University Hospitals, Geneva, Switzerland; Faculty of Medicine, Geneva University, Geneva, Switzerland.

Purpose: Tumor hypoxia is associated with radioresistance and poor prognosis after radiation therapy for prostate cancer (PCa). In this prospective pilot study, we assessed the ability of F-misonidazole (F-MISO) positron emission tomography (PET)-magnetic resonance imaging (MRI) to detect hypoxia in high-grade PCa patients who were candidates for curative radiation therapy, and we evaluated F-MISO PET-MRI modulation after 3 months of neoadjuvant androgen deprivation therapy (nADT).

Methods And Materials: Eleven PCa patients with a Gleason score (GS) ≥ 8 underwent F-fluorocholine (F-FCH) PET-computed tomography at diagnosis and an F-MISO hybrid PET-MRI examination before nADT; a second F-MISO PET-MRI examination was acquired after 3 months of nADT for all patients but one who dropped out because of noncompliance with nADT. Immunohistochemistry for tissue hypoxia- and proliferation-related biomarkers (glucose transporter 1, carbonic anhydrase IX, vascular endothelial growth factor A, Ki-67, hypoxia-inducible factor 1 alpha, and epidermal growth factor receptor) was performed in lesions bearing the highest GS. We used nonparametric tests to assess (1) the presence of F-MISO-positive regions (tumor-to-background ratio [TBR] ≥ 1.4) at baseline; (2) the correlation between imaging parameters (PET tracer uptake, Prostate Imaging Reporting and Data System [PIRADS] scores, and dynamic contrast enhancement perfusion markers) at baseline; (3) the difference in immunohistochemistry staining between F-MISO-positive and -negative lesions; and (4) the changes in F-MISO PET-MRI after nADT.

Results: Uptake of F-MISO was significant in 7 patients, being coincidental with the highest GS region in 5 of them. A significant correlation was found at baseline between GS and F-MISO TBR, between F-MISO TBR and MRI perfusion markers, between GS and F-FCH maximum standardized uptake value, between GS and PIRADS score, and between F-FCH maximum standardized uptake value and PIRADS score. No difference was found between F-MISO-positive and -negative biopsy specimens with respect to tissue biomarkers. The TBR of F-MISO diminished significantly after nADT only in high-grade lesions and in regions with a significant uptake at baseline.

Conclusions: PET imaging with F-MISO showed variable uptake in PCa, associated with a higher GS, lowering significantly after 3 months of nADT in high-grade lesions. These results suggest the existence of a hypoxic microenvironment in PCa and a reoxygenation effect of nADT.
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http://dx.doi.org/10.1016/j.ijrobp.2018.02.170DOI Listing
November 2018

Role of liver magnetic resonance imaging in hyperferritinaemia and the diagnosis of iron overload.

Swiss Med Wkly 2017 8;147:w14550. Epub 2017 Nov 8.

Department of Radiology, University Hospital Geneva, Switzerland.

Hyperferritinaemia is a frequent clinical problem. Elevated serum ferritin levels can be detected in different genetic and acquired diseases and can occur with or without anaemia. It is therefore important to determine whether hyperferritinaemia is due to iron overload or due to a secondary cause. The main causes of iron overload are intestinal iron hyperabsorption disorders and transfusion-dependent disorders. Iron homeostasis and iron overload are quantified by different diagnostic approaches. The evaluation of serum ferritin and transferrin saturation is the first diagnostic step to identify the cause of hyperferritinaemia. The assessment of liver iron concentration by liver biopsy or magnetic resonance imaging (MRI) may guide the further diagnostic and therapeutic workup. Liver biopsy is invasive and poorly accepted by patients and should only be carried out in selected patients with hereditary haemochromatosis. As a non-invasive approach, MRI is considered the standard method to diagnose and to monitor both hepatic iron overload and the effectiveness of iron chelation therapy in many clinical conditions such as thalassaemia and myelodysplastic syndromes. Accurate evaluation and monitoring of iron overload has major implications regarding adherence, quality of life and prognosis. There are different technical MRI approaches to measuring the liver iron content. Of these, T2 and T2* relaxometry are considered the standard of care. MRI with cardiac T2* mapping is also suitable for the assessment of cardiac iron. Currently there is no consensus which technique should be preferred. The choice depends on local availability and patient population. However, it is important to use the same MRI technique in subsequent visits in the same patient to get comparable results. Signal intensity ratio may be a good adjunct to R2 and R2* methods as it allows easy visual estimation of the liver iron concentration. In this review a group of Swiss haematologists and radiologists give an overview of different conditions leading to primary or secondary iron overload and on diagnostic methods to assess hyperferritinaemia with a focus on the role of liver MRI. They summarise the standard practice in Switzerland on the use of liver iron concentration MRI as well as disease-specific guideline recommendations.
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http://dx.doi.org/10.4414/smw.2017.14550DOI Listing
July 2018

Spatially Resolved MR-Compatible Doppler Ultrasound: Proof of Concept for Triggering of Diagnostic Quality Cardiovascular MRI for Function and Flow Quantification at 3T.

IEEE Trans Biomed Eng 2018 02 18;65(2):294-306. Epub 2017 Oct 18.

Objective: We demonstrate the use of a magnetic-resonance (MR)-compatible ultrasound (US) imaging probe using spatially resolved Doppler for diagnostic quality cardiovascular MR imaging (MRI) as an initial step toward hybrid US/MR fetal imaging.

Methods: A newly developed technology for a dedicated MR-compatible phased array ultrasound-imaging probe acquired pulsed color Doppler carotid images, which were converted in near-real time to a trigger signal for cardiac cine and flow quantification MRI. Ultrasound and MR data acquired simultaneously were interference free. Conventional electrocardiogram (ECG) and the proposed spatially resolved Doppler triggering were compared in 10 healthy volunteers. A synthetic "false-triggered" image was retrospectively processed using metric optimized gating (MOG). Images were scored by expert readers, and sharpness, cardiac function and aortic flow were quantified. Four-dimensional (4-D) flow (two volunteers) showed feasibility of Doppler triggering over a long acquisition time.

Results: Imaging modalities were compatible. US probe positioning was stable and comfortable. Image quality scores and quantified sharpness were statistically equal for Doppler- and ECG-triggering (p ). ECG-, Doppler-triggered, and MOG ejection fractions were equivalent (p ), with false-triggered values significantly lower (p < 0.0005). Aortic flow showed no difference between ECG- and Doppler-triggered and MOG (p > 0.05). 4-D flow quantification gave consistent results between ECG and Doppler triggering.

Conclusion: We report interference-free pulsed color Doppler ultrasound during MR data acquisition. Cardiovascular MRI of diagnostic quality was successfully obtained with pulsed color Doppler triggering.

Significance: The hardware platform could further enable advanced free-breathing cardiac imaging. Doppler ultrasound triggering is applicable where ECG is compromised due to pathology or interference at higher magnetic fields, and where direct ECG is impossible, i.e., fetal imaging.
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http://dx.doi.org/10.1109/TBME.2017.2764111DOI Listing
February 2018

4D cardiac imaging at clinical 3.0T provides accurate assessment of murine myocardial function and viability.

Magn Reson Imaging 2017 12 5;44:46-54. Epub 2017 Aug 5.

Division of Radiology, Department of Radiology and Medical Informatics, Geneva University Hospital and Faculty of Medicine, University of Geneva, 4 rue Gabrielle-Perret-Gentil, 1205 Geneva, Switzerland. Electronic address:

Objectives: We validate a 4D strategy tailored for 3T clinical systems to simultaneously quantify function and infarct size in wild type mice after ischemia/reperfusion, with improved spatial and temporal resolution by comparison to previous published protocols using clinical field MRI systems.

Methods: C57BL/6J mice underwent 60min ischemia/reperfusion (n=14) or were controls without surgery (n=6). Twenty-four hours after surgery mice were imaged with gadolinium injection and sacrificed for post-mortem MRI and histology with serum also taken for Troponin I levels. The double ECG- and respiratory-triggered 3D FLASH (Fast Low Angle Shot) gradient echo (GRE) cine sequence had an acquired isotropic resolution of 344μm, TR/TE of 7.8/2.9ms and acquisition time 25-35min. The conventional 2D FLASH cine sequence had the same in-plane resolution of 344μm, 1mm slice thickness and TR/TE 11/5.4ms for an acquisition time of 20-25min plus 5min for planning. Left ventricle (LV) and right ventricle (RV) volumes were measured and functional parameters compared 2D to 3D, left to right and for inter and intra observer reproducibility. MRI infarct volume was compared to histology.

Results: For the function evaluation, the 3D cine outperformed 2D cine for spatial and temporal resolution. Protocol time for the two methods was equivalent (25-35min). Flow artifacts were reduced (p=0.008) and epi/endo-cardial delineation showed good intra and interobserver reproducibility. Paired t-test comparing ejection volume left to right showed no significant difference for 3D (p=0.37), nor 2D (p=0.30) and correlation slopes of left to right EV were 1.17 (R=0.75) for 2D and 1.05 (R=0.50) for 3D. Quantifiable 'late gadolinium enhancement' infarct volume was seen only with the 3D cine and correlated to histology (R=0.89). Left ejection fraction and MRI-measured infarct volume correlated (R>0.3).

Conclusions: The 4D strategy, with contrast injection, was validated in mice for function and infarct quantification from a single scan with minimal slice planning.
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http://dx.doi.org/10.1016/j.mri.2017.07.024DOI Listing
December 2017

Diagnosis and assessment of renal fibrosis: the state of the art.

Swiss Med Wkly 2017 11;147:w14442. Epub 2017 May 11.

Service of Nephrology, Department of Internal Medicine Specialties, University Hospital of Geneva, Switzerland.

Chronic kidney disease (CKD) is defined as an alteration of kidney function and/or structure lasting for more than 3 months and is a major public health issue. Histologically, the severity of CKD correlates with the magnitude of kidney cortical interstitial fibrosis. Estimation of kidney fibrosis is crucial to assess prognosis and guide therapy in both native and allograft kidneys. Biopsy is currently the gold standard for assessing fibrosis with histological techniques. Although this procedure has become safer over recent years, complications and limitations remain. Given these restrictions, new, noninvasive techniques are necessary for the evaluation and follow-up of CKD patients. Radiological methods such as ultrasound and magnetic resonance imaging are emerging for assessment kidney fibrosis. These two techniques have advantages but also limitations. In addition to radiological assessment of fibrosis, urinary and plasma biomarkers are being developed and tested as predictive tools for histological lesions in the kidney. This article reviews the current evidence for these novel techniques in the evaluation of kidney interstitial fibrosis.
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http://dx.doi.org/10.4414/smw.2017.14442DOI Listing
May 2018

Posterior wall left ventricular aneurysm repair.

Multimed Man Cardiothorac Surg 2017 04 26;2017. Epub 2017 Apr 26.

Posterior wall aneurysms are a relatively rare form of left ventricular aneurysm that can sometimes involve the mitral valve. This tutorial illustrates the technical aspects of posterior wall left ventricular aneurysm repair.
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http://dx.doi.org/10.1510/mmcts.2017.007DOI Listing
April 2017

Comparison of readout-segmented and conventional single-shot for echo-planar diffusion-weighted imaging in the assessment of kidney interstitial fibrosis.

J Magn Reson Imaging 2017 12 10;46(6):1631-1640. Epub 2017 Mar 10.

Division of Radiology, Geneva University Hospitals, University of Geneva, Faculty of Medicine, Geneva, Switzerland.

Purpose: To compare readout-segmented echo-planar imaging (EPI) (RESOLVE) to single-shot EPI (ss-EPI) diffusion-weighted imaging (DWI) for the assessment of renal interstitial fibrosis.

Materials And Methods: A phantom, eight healthy volunteers (under 30 years to avoid age-fibrosis related) and 27 chronic kidney disease (CKD) patients (scheduled for kidney biopsy) were scanned (at 3T) with ss-EPI and 5-shot RESOLVE DWI (resolution: 2 × 2 × 5 mm , 10 b-values). The cortico-medullary difference for each DW parameter from a monoexponential fit (ΔADC) or, segmented biexponential fit (ΔD, ΔD*, ΔF ) were compared between both sequences. A fibrosis threshold of 40% was defined to separate all 35 subjects into low and high fibrosis groups. The linear relationship between DW parameters and percentage fibrosis (up to 80%) from Masson trichrome was assessed with the Pearson product-moment correlation coefficient. Fisher Z-transform was used for R correlation comparison.

Results: A coefficient of variation between ADCs of 3% was measured between both sequences in the phantom. In healthy volunteers, no significant difference was measured for all DW parameters. Both sequences separated low to high level of fibrosis with a significant decrease of ΔADC (RESOLVE P = 3.1 × 10 , ss-EPI P = 0.003) and ΔD (RESOLVE P = 8.2 × 10 , ss-EPI P = 0.02) in the high level of fibrosis. However, RESOLVE ΔADC had a stronger negative correlation (P = 0.04 for R comparison) with fibrosis than ss-EPI ΔADC (RESOLVE R  = 0.65, P = 5.9 × 10 , ss-EPI R  = 0.29, P = 8.9 × 10 ). ΔD (RESOLVE) was correlated (moderately) with fibrosis (R  = 0.29, P = 9.2 × 10 ); however, ΔD* and ΔF did not show, in our population, a significant correlation with interstitial fibrosis (0.01 < R < 0.08).

Conclusion: ΔADC derived from both sequences correlated with fibrosis. ΔADC from RESOLVE showed better correlation with fibrosis than ΔADC from ss-EPI and therefore has potential to monitor CKD.

Level Of Evidence: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017;46:1631-1640.
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http://dx.doi.org/10.1002/jmri.25687DOI Listing
December 2017

Yasui procedure.

Multimed Man Cardiothorac Surg 2016 12 9;2016. Epub 2016 Dec 9.

University Hospital of Lausanne.

There are rare situations in which the left ventricular outflow tract cannot be used for systemic output. The Yasui procedure allows leaving the left ventricle as the systemic ventricle, but uses the pulmonary valve as the systemic semilunar valve. These videos illustrate the technical aspects of the Yasui procedure.
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http://dx.doi.org/10.1510/mmcts.2016.005DOI Listing
December 2016

Dynamic Volume Assessment of Hepatocellular Carcinoma in Rat Livers Using a Clinical 3T MRI and Novel Segmentation.

J Invest Surg 2018 Feb 20;31(1):44-53. Epub 2017 Jan 20.

b Division of Radiology , University Hospitals of Geneva and Faculty of Medicine, University of Geneva , Geneva , Switzerland.

Purpose: In vivo liver cancer research commonly uses rodent models. One of the limitations of such models is the lack of accurate and reproducible endpoints for a dynamic assessment of growing tumor nodules. The aim of this study was to validate a noninvasive, true volume segmentation method using two rat hepatocellular carcinoma (HCC) models, correlating magnetic resonance imaging (MRI) with histological volume measurement, and with blood levels of α-fetoprotein.

Materials And Methods: We used 3T clinical MRI to quantify tumor volume with follow-up over time. Using two distinct rat HCC models, calculated MRI tumor volumes were correlated with volumes from histological sections, or with blood levels of α-fetoprotein. Eleven rats, comprising six Buffalo rats (n = 9 scans) and five Fischer rats (n = 14 tumors), were injected in the portal vein with 2.5 × 10 and 2.0 × 10 syngeneic HCC cells, respectively. Longitudinal (T1) relaxation time- and transverse (T2) relaxation time-weighted MR images were acquired.

Results: The three-dimensional (3D) T1-weighted gradient echo had 0.35-mm isotropic resolution allowing accurate semi-automatic volume segmentation. 2D T2-weighted imaging provided high tumor contrast. Segmentation of combined 3D gradient echo T1-weighted images and 2D turbo spin echo T2-weighted images provided excellent correlation with histology (y = 0.866x + 0.034, R² = 0.997 p < .0001) and with α-fetoprotein (y = 0.736x + 1.077, R² = 0.976, p < .0001). There was robust inter- and intra-observer reproducibility (intra-class correlation coefficient > 0.998, p < .0001).

Conclusions: We have developed a novel, noninvasive contrast imaging protocol which enables semi-automatic 3D volume quantification to analyze nonspherical tumor nodules and to follow up the growth of tumor nodules over time.
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http://dx.doi.org/10.1080/08941939.2016.1276987DOI Listing
February 2018

Phosphocalcic Markers and Calcification Propensity for Assessment of Interstitial Fibrosis and Vascular Lesions in Kidney Allograft Recipients.

PLoS One 2016 30;11(12):e0167929. Epub 2016 Dec 30.

Service of Nephrology, Department of Internal Medicine Specialities, University Hospital of Geneva, Geneva, Switzerland.

Renal interstitial fibrosis and arterial lesions predict loss of function in chronic kidney disease. Noninvasive estimation of interstitial fibrosis and vascular lesions is currently not available. The aim of the study was to determine whether phosphocalcic markers are associated with, and can predict, renal chronic histological changes. We included 129 kidney allograft recipients with an available transplant biopsy in a retrospective study. We analyzed the associations and predictive values of phosphocalcic markers and serum calcification propensity (T50) for chronic histological changes (interstitial fibrosis and vascular lesions). PTH, T50 and vitamin D levels were independently associated to interstitial fibrosis. PTH elevation was associated with increasing interstitial fibrosis severity (r = 0.29, p = 0.001), while T50 and vitamin D were protective (r = -0.20, p = 0.025 and r = -0.23, p = 0.009 respectively). On the contrary, fibroblast growth factor 23 (FGF23) and Klotho correlated only modestly with interstitial fibrosis (p = 0.045) whereas calcium and phosphate did not. PTH, vitamin D and T50 were predictors of extensive fibrosis (AUC: 0.73, 0.72 and 0.68 respectively), but did not add to renal function prediction. PTH, FGF23 and T50 were modestly predictive of low fibrosis (AUC: 0.63, 0.63 and 0.61) but did not add to renal function prediction. T50 decreased with increasing arterial lesions (r = -0.21, p = 0.038). The discriminative performance of T50 in predicting significant vascular lesions was modest (AUC 0.61). In summary, we demonstrated that PTH, vitamin D and T50 are associated to interstitial fibrosis and vascular lesions in kidney allograft recipients independently of renal function. Despite these associations, mineral metabolism indices do not show superiority or additive value to fibrosis prediction by eGFR and proteinuria in kidney allograft recipients, except for vascular lesions where T50 could be of relevance.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0167929PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5201285PMC
June 2017