• The Inria's Research Teams produce an annual Activity Report presenting their activities and their results of the year. These reports include the team members, the scientific program, the software developed by the team and the new results of the year. The report also describes the grants, contracts and the activities of dissemination and teaching. Finally, the report gives the list of publications of the year.

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## Section: New Results

### Clinical Applications

#### Exploring kinetic energy as a new marker of cardiac function in the single ventricle circulation

Participants : Radomir Chabiniok [correspondant] , Tarique Hussain [ToFMOD] .

Ventricular volumetric ejection fraction (VV EF) is often normal in patients with single ventricle circulations despite them experiencing symptoms related to circulatory failure. We sought to determine if kinetic energy (KE) could be a better marker of ventricular performance. KE was prospectively quantified using four-dimensional flow MRI in 41 patients with a single ventricle circulation (aged 0.5-28 yr) and compared with 43 healthy volunteers (aged 1.5-62 yr) and 14 patients with left ventricular (LV) dysfunction (aged 28-79 yr). Intraventricular end-diastolic blood was tracked through systole and divided into ejected and residual blood components. Two ejection fraction (EF) metrics were devised based on the KE of the ejected component over the total of both the ejected and residual components using 1) instantaneous peak KE to assess KE EF or 2) summating individual peak particle energy (PE) to assess PE EF. KE metrics are markers of healthy cardiac function. PE EF may be useful in grading dysfunction. The work was published in Journal of Applied Physiology (J Appl Physiol 125: 889-900, 2018), [29]. The work represents a collaboration with King's College London (J. Wong, K. Pushparajah, R. Razavi) and with UT Southwestern Dallas (T. Hussain, the member of Inria Associate team ToFMOD).

#### Using a patient-specific biomechanical cardiovascular model to estimate continuously Left Ventricular Pressure Volume Loop: A proof of concept study

Participants : Arthur Le Gall, Fabrice Vallée, Philippe Moireau, Dominique Chapelle, Radomir Chabiniok [correspondant] .

Pressure Volume loops (PV loops) could contribute to optimise haemodynamic managements. While the invasiveness of PV loop acquisition prevents it from being routinely used during surgery, cardiovascular modelling could represent an alternative. Using continuous recording of aortic pressure and flow, we aimed at calibrating a patient-specific model and at interpreting the simulated PV loop during administration of noradrenaline (NOR). This study is the first to allow continuous PV loop monitoring during general anaesthesia. The work was pursued in the collaboration with Lariboisiere Hospital in Paris (A. Le Gall and F. Vallée, both dually affiliated at Inria and at AP-HP, “poste d'accueil”).

#### Augmenting the interpretation of cardiac MRI by biomechanical modeling: Application to Tetralogy of Fallot

Participants : Marija Gusseva, Philippe Moireau, Tarique Hussain [ToFMod] , Gerald Greil [ToFMod] , Animesh Tandon [ToFMOD] , Dominique Chapelle, Radomir Chabiniok [correspondant] .

The particularity of the mixed-valve disease – pulmonary regurgitation often combined with a stenosis – requested to extend our model-representation of the valve to allow the backflow during the heart relaxation. For each patient, biomechanical models of their left and right ventricles (LV, RV) were set up. These models then allowed to investigate the functional properties of dilated right ventricles (RV) with incompetent pulmonary valves and of the pulmonary circulation, properties not directly visible in the clinical data. In particular, immediately after deploying the new valve we could observe a decrease of RV contractility by 15%, while the output of RV into pulmonary circulation has increased. This suggests a positive immediate outcome, as the energy needs for function of RV will decrease. The higher cardiac output also suggests an increase of the filling of LV (preload), which could contribute to an improvement of LV function. The model also uncovered a decrease of resistance in the pulmonary circulation. This very preliminary result might suggest some pathophysiological changes, which are typically not thought of in clinics.

This work is pursued under the objectives of the Inria Associate Team ToFMod (T. Hussain, G. Greil, A. Tandon are members of ToFMOD and affiliated at UT Southwestern Medical Center Dallas, USA), the work was accepted for a conference of International Society of Magnetic Resonance in Medicine 2018 and is in preparation for publication.

#### Longitudinal study of ventricular remodeling and reverse-remodeling in tetralogy of Fallot patients using CMR coupled with biomechanical modelling

Participants : Marija Gusseva, Tarique Hussain [ToFMod] , Animesh Tandon [ToFMod] , Dominique Chapelle, Radomir Chabiniok [correspondant] .

A preliminary study was performed with the patient-specific models for RV and pulmonary circulations set up from three datasets including the 6-months post-PVR follow-up exams obtained in late 2018 from King's College London. Clinical data analyses show a positive result of pulmonary replacement therapy (PVR) and normalization of the RV size, i.e. the so-called reverse-remodeling of the pathologically dilated RV, in all three patients. The biomechanical modeling suggests a further reduction of the active stress needed to be developed by RV (contractility), i.e. a long-term unloading of the previously overloaded ventricle.

This work is pursued under the objectives of the Inria Associate Team ToFMOD (T. Hussain, A. Tandon are members of ToFMOD and affiliated at UT Southwestern Medical Center Dallas, USA). The main partner in this task is King's College London (“Other Participant” in the ToFMOD Associate team, K. Pushparajah, M. Jones, S. Qureshi) who provided unique clinical data of patients with a long-term follow-up after PVR. The work was submitted to the conference of International Society of Magnetic Resonance in Medicine 2019 – the world-wide major scientific & clinical event when MR data are involved.

#### Optical flow-based non-rigid registration of cardiac MR images

Participant : Radomir Chabiniok [correspondant] .

This work deals with non-rigid registration of cardiac MR images, particularly the MOLLI sequences. MOLLI sequence consists of 11 heart images acquired over 17 cardiac cycles. The images of MOLLI sequence are used for pixel-wise estimation of T1 relaxation time values. In this case the registration is necessary to correct the deformations that occur because of the patient's imperfect breath-holding during the acquisition. The main characteristics of the MOLLI sequence is the evolving intensity of the tissues and also large variations of the image contrast. This characteristics of the sequence make the registration process challenging and make the use of intensity-based registration method impossible. For this purpose, we propose a method based on optical flow, using information obtained by image segmentation. The first step of the registration process, is segmentation of the regions of interest, using the level set method. The segmented objects are represented by distance maps. The transformation between original images is determined by applying the optical flow method to the distance maps. The registration process is independent of the varying intensity and takes into account only the shape and position of the segmented areas, such as the myocardium or the ventricles. The implementation of the proposed method is described and the method is tested on several MOLLI sequences. The results are compared to the results of methods based on maximisation of mutual information, and the proposed method performs better for the images with significant changes in intensity.

The work represents a collaborative project with Institute for Clinical and Experimental Medicine (IKEM) Prague (J. Tintera) and with Czech Technical University in Prague (K. Solovska, T. Oberhuber).

#### Quantification of biventricular strains in heart failure with preserved ejection fraction using hyperelastic warping method[32]

Participant : Martin Genet.

Heart failure (HF) imposes a major global health care burden on society and suffering on the individual. About 50% of HF patients have preserved ejection fraction (HFpEF). More intricate and comprehensive measurement-focused imaging of multiple strain components may aid in the diagnosis and elucidation of this disease. Here, we describe the development of a semi-automated hyperelastic warping method for rapid comprehensive assessment of biventricular circumferential, longitudinal, and radial strains that is physiological meaningful and reproducible. We recruited and performed cardiac magnetic resonance (CMR) imaging on 30 subjects [10 HFpEF, 10 HF with reduced ejection fraction patients (HFrEF) and 10 healthy controls]. In each subject, a three-dimensional heart model including left ventricle (LV), right ventricle (RV), and septum was reconstructed from CMR images. The hyperelastic warping method was used to reference the segmented model with the target images and biventricular circumferential, longitudinal, and radial strain–time curves were obtained. The peak systolic strains are then measured and analyzed in this study. The ROC analysis indicated LV peak systolic circumferential strain to be the most sensitive marker for differentiating HFpEF from healthy controls. Our results suggest that the hyperelastic warping method with the CMR-derived strains may reveal subtle impairment in HF biventricular mechanics, in particular despite a “normal” ventricular ejection fraction in HFpEF.

#### Extra corporeal life support for cardiac arrest patients with post-cardiac arrest syndrome: the ECCAR study

Participant : Arthur Le Gall.

Purpose: Post-Cardiac Arrest Shock (PCAS) occurring after resuscitated cardiac arrest (CA), is a main cause of early death. Extra-Corporeal Life Support (ECLS) could be useful pending recovery of myocardial failure. We aimed to describe our PCAS population, and factors associated with ECLS initiation. Materials and Methods: This analysis included 924 patients admitted in two intensive care units (ICU) between 2005 and 2014 for CA and PCAS, and, of those patients, 43 patients for whom an ECLS was initiated. Neurological and ECLS-related outcomes were gathered retrospectively. Conclusions: ECLS, as a salvage therapy for PCAS, could represent an acceptable alternative for highly selected patients.

#### Evaluation of cardiac output variations with the peripheral pulse pressure to mean arterial pressure ratio.

Participant : Arthur Le Gall.

Cardiac output (CO) optimisation during surgery reduces post-operative morbidity. Various methods based on pulse pressure analysis have been developed to overcome difficulties to measure accurate CO variations in standard anaesthetic settings. Several of these methods include, among other parameters, the ratio of pulse pressure to mean arterial pressure (PP/MAP). The aim of this study was to evaluate whether the ratio of radial pulse pressure to mean arterial pressure ($\Delta$PPrad/MAP) could track CO variations ($\Delta$ CO) induced by various therapeutic interventions such as fluid infusions and vasopressors boluses [phenylephrine (PE), norepinephrine (NA) or ephedrine (EP)] in the operating room. Trans-oesophageal Doppler signal and pressure waveforms were recorded in patients undergoing neurosurgery. CO and PPrad/MAP were recorded before and after fluid challenges, PE, NA and EP bolus infusions as medically required during their anaesthesia. $\Delta$PPrad/MAP tracked $\Delta$CO variations during PE and NA vasopressor challenges. However, after positive fluid challenge or EP boluses, $\Delta$PPrad/MAP was not as performant to track $\Delta$CO which could make the use of this ratio difficult in current clinical practice.

#### Perioperative management of patients with coronary artery disease undergoing non-cardiac surgery: Summary from the French Society of Anaesthesia and Intensive Care Medicine 2017 convention

Participant : Arthur Le Gall.

This review summarises the specific stakes of preoperative, intraoperative, and postoperative periods of patients with coronary artery disease undergoing non-cardiac surgery. All practitioners involved in the perioperative management of such high cardiac risk patients should be aware of the modern concepts expected to decrease major adverse cardiac events and improve short- and long-term outcomes. A multidisciplinary approach via a functional heart team including anaesthesiologists, cardiologists and surgeons must be encouraged. Rational and algorithm-guided management of those patients should be known and implemented from preoperative to postoperative period.