Presentation

Van BeersV2Bernard Van Beers

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Laboratory of biomarkers in imaging – LBI

The main focus of our team is translational research in medical imaging for the development and validation of novel imaging biomarkers in inflammation, fibrosis and cancer. Our efforts range from fundamental research in imaging methods to applied preclinical and clinical research in hepatic and abdominal diseases.

Our developments are mainly devoted to improve rapid, functional and quantitative methods of magnetic resonance imaging (MRI) (diffusion MRI, perfusion, elastography, susceptibility and relaxometry), as well as assess novel tracers for cellular imaging. These developments are first validated on thin tissue sections and in small animal disease models. Once the proofs of concept are obtained, the methods are transferred to clinical imaging for increasing disease understanding and improving the detection, characterization and treatment response monitoring of inflammation, fibrosis and cancer.

Our LBI laboratory participates in the imaging research network “France Life Imaging”, with Bernard Van Beers acting as coordinator of the Paris Centre node. Our laboratory is also active within the Université de Paris “Imageries du Vivant” network. In addition, the LBI laboratory is one of the two imaging research teams in charge of the preclinical imaging platform “FRIM”.

Main research projects

Imaging of hepatic inflammation in metabolic diseases

The non-invasive evaluation of inflammation and hepatocyte injury is an important objective for the clinical diagnosis of non-alcoholic steatohepatitis or NASH. The ANR “QUID-NASH” project that we pursue with other academic and industrial partners aims to assess new non-invasive imaging methods of NASH in murine models of steatohepatitis and in a cohort of 600 diabetic patients with biopsy-proven hepatic steatosis. We develop a virtual hepatic biopsy approach, integrating multi-omic data, including quantitative parameters obtained with ultrafast ultrasound and multiparametric MRI, such as multifrequential viscoelastic properties, R1 and R2* relaxation rates, and lipid MRI composition.

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Steatosis (left) and hepatic stiffness (right) maps in a patient with cirrhosis on NASH (graded S2, A3, F4 at histopatholgy). The MRI-measured fat fraction within the liver is 23% which corresponds to S2 steatosis grade. The MR elastography-derived shear modulus is 10 kPa, compatible with the diagnosis of cirrhosis

 

Imaging of the forces in hepatic cancer 

To provide advanced characterization of tumor mechanical properties, the apparent elasticity at different levels of static load can be measured. We measure the tissue mechanical properties after preload at MR elastography to assess tumor interstitial pressure and solid stress, two parameters playing a role in the efficiency of targeted treatments (H2020 European project “FORCE”).

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Elasticity maps of patient-derived hepatocarcinoma xenografted in nude mouse, measured at different levels of static load, showing increase in elasticity under load (Pagé G et al. J Magn Reson Imaging 2019)

 

Functional contrast-enhanced MRI of the liver

Hepatospecific agents

Liver perfusion and hepatocyte transport are important determinants of hepatic function. Using MRI with hepatospecific contrast agents and developing a two-input, three-compartment hepatobiliary model, we study the pharmacokinetic parameter changes in chronic liver disease. The aim of this research is to use MRI pharmacokinetic parameters as biomarkers of liver function.

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Parametric maps of biliary efflux at hepatobiliary contrast-enhanced MRI, showing decreasing biliary efflux according to fibrosis severity at histopathology (Leporq B et al. Clin Sci 2018)

 

Macrophage-based contrast agents in fibrogenesis

The dynamics of fibrogenesis and fibrolysis has been seldom studied with biomedical imaging. Using dedicated MRI acquisition sequences with administration of ultrasmall iron oxide particles (USPIO), we observe the different macrophage populations involved in this dynamic process, according to their endocytic capacity.

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Assessment of R2 (a), R2* (b), R2’ (c) relaxation rates and magnetic susceptibility (d) show that pro-inflammatory M1 macrophages exhibit higher MRI parameters than M0 and M2 macrophages, because of higher USPIO concentration within the former. This increased uptake in M1 macrophages is confirmed at immunofluorescence (right panels) (Khaled W et al. J Magn Reson Imaging 2019)

 

MRI of liver cirrhosis and portal hypertension

Classically, the assessment of cirrhosis and portal hypertension severity relies on hepatic venous pressure gradient measurements. We have shown that MR elastography provides a non-invasive method for assessing portal hypertension severity (Ronot M et al. Eur Radiol 2014). We aim to improve this approach will be by integrating MR elastography data with radiomic information and biological data extracted from microcirculating vesicles (IFB project “Integrative bioinformatics”).

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Parametric maps showing increase in hepatic (top) and splenic (bottom) shear modulus according to portal hypertension severity (A and D: hepatic venous pressure gradient below 10 mmHg; B and E: pressure gradient between 10 and 11 mmHg; C and F: pressure gradient above 11 mmHg) (Van Beers B et al. Semin Liv Dis 2017)

Pancreatic quantitative MRI in obesity

We observed that pancreatic tissue in obesity could be characterized before and after bariatric surgery with quantitative MRI, including the measurements of the mechanical properties, fat fraction and R2* relaxation rate. We are currently developing a similar approach in the ANR project “PAIR-pancréas” to detect the pre-tumoral pancreatic lesions associated with the metabolic syndrome.

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Elasticity (left), fat fraction (middle) and R2* relaxation rate (right) in the pancreas of control rats, obese rats and obese rats after bariatric surgery. Obesity induces increase in MRI parameters, which is partially reversed after bariatric surgery. Histological analysis of pancreatic tissue confirms these observations (Rebours V, Garteiser P et al. Sci Rep 2018)

 

Quantitative MRI of intestinal inflammation and fibrosis

In a rat model of radiation-induced colitis, we observe that combining MRI parameters of signal intensity, perfusion, diffusion and magnetization transfer is useful for assessing inflammation and fibrosis, which has potential therapeutic implications (Zappa M et al. NMR Biomed 2018).

 

You want to join our team as Post-doc, PhD or Master student, please contact us: [mailto:Bernard.van-beers@inserm.fr]

Selected publications

Selected publications

 

  • Khaled W, Piraquive J, Leporq B, Wan JH, Lambert SA, Mignet N, Doan BT, Lotersztajn S, Garteiser P, Van Beers BE. In vitro distinction between proinflammatory and antiinflammatory macrophages with gadolinium-liposomes and ultrasmall superparamagnetic iron oxide particles at 3.0T. J Magn Reson Imaging. 2019 Apr;49(4):1166-1173. doi: 10.1002/jmri.26331
  • Pagé G, Tardieu M, Besret L, Blot L, Lopes J, Sinkus R, Van Beers BE, Garteiser P. Assessing Tumor Mechanics by MR Elastography at Different Strain Levels. J Magn Reson Imaging. 2019 May 14. doi: 10.1002/jmri.26787.
  • Leporq B, Daire JL, Pastor CM, Deltenre P, Sempoux C, Schmidt S, Van Beers BE. Quantification of hepatic perfusion and hepatocyte function with dynamic gadoxetic acid-enhanced MRI in patients with chronic liver disease. Clin Sci (Lond). 2018 Apr 16;132(7):813-824. doi: 10.1042/CS20171131
  • Rebours V, Garteiser P, Ribeiro-Parenti L, Cavin JB, Doblas S, Pagé G, Bado A, Couvineau A, Ruszniewski P, Paradis V, Le Gall M, Van Beers BE, Couvelard A. Obesity-induced pancreatopathy in rats is reversible after bariatric surgery. Sci Rep. 2018 Nov 2;8(1):16295. doi: 10.1038/s41598-018-34515-3
  • Giraudeau C, Leporq B, Doblas S, Lagadec M, Pastor CM, Daire JL, Van Beers BE. Gadoxetate-enhanced MR imaging and compartmental modelling to assess hepatocyte bidirectional transport function in rats with advanced liver fibrosis. Eur Radiol. 2017 May;27(5):1804-1811. doi: 10.1007/s00330-016-4536-7
  • Leitão HS, Doblas S, Garteiser P, d’Assignies G, Paradis V, Mouri F, Geraldes CF, Ronot M, Van Beers BE. Hepatic Fibrosis, Inflammation, and Steatosis: Influence on the MR Viscoelastic and Diffusion Parameters in Patients with Chronic Liver Disease. Radiology. 2017 Apr;283(1):98-107. doi: 10.1148/radiol.2016151570
  • Van Beers BE, Garteiser P, Leporq B, Rautou PE, Valla D. Quantitative Imaging in Diffuse Liver Diseases. Semin Liver Dis. 2017 Aug;37(3):243-258. doi: 10.1055/s-0037-1603651.
  • Leporq B, Lambert SA, Ronot M, Boucenna I, Colinart P, Cauchy F, Vilgrain V, Paradis V, Van Beers BE. Hepatic fat fraction and visceral adipose tissue fatty acid composition in mice: Quantification with 7.0T MRI. Magn Reson Med. 2016 Aug;76(2):510-8. doi: 10.1002/mrm.25895
  • Lagadec M, Doblas S, Giraudeau C, Ronot M, Lambert SA, Fasseu M, Paradis V, Moreau R, Pastor CM, Vilgrain V, Daire JL, Van Beers BE. Advanced fibrosis: correlation between pharmacokinetic parameters at dynamic gadoxetate-enhanced MR imaging and hepatocyte organic anion transporter expression in rat liver. Radiology. 2015 Feb;274(2):379-86. doi: 10.1148/radiol.14140313
  • Van Beers BE, Daire JL, Garteiser P. New imaging techniques for liver diseases. J Hepatol. 2015 Mar;62(3):690-700. doi: 10.1016/j.jhep.2014.10.014
Team members
Equipe Bernard Van Beers, PUPH
Chercheurs Philippe Garteiser, CR
Catherine Pastor, PU
  Maxime Ronot, PUPH
  Bernard Van Beers, PUPH
  Valérie Vilgrain, PUPH
  Magaly Zappa, PH
Doctorants Marco Dioguardi-Burgio
Post-doctorants Anton Abyzov
Afef Bouchouicha
Felicia Julea
Gwenael Page
Ingénieurs et techniciens Kahina Abbas, FLI Project manager
  Jean-Luc Daire, medical Physicist
Sabrina Doblas, IR