Ingrid Leguerney | Gustave Roussy - Paris Sud University (original) (raw)

Papers by Ingrid Leguerney

International Journal of Molecular Sciences

Standard imaging cannot reliably predict the nature of renal tumors. Among malignant renal tumors... more Standard imaging cannot reliably predict the nature of renal tumors. Among malignant renal tumors, clear cell renal cell carcinoma (ccRCC) is the most common histological subtype, in which the vascular endothelial growth factor 2 (VEGFR-2) is highly expressed in the vascular endothelium. BR55, a contrast agent for ultrasound imaging, consists of gas-core lipid microbubbles that specifically target and bind to the extracellular portion of the VEGFR-2. The specific information provided by ultrasound molecular imaging (USMI) using BR55 was compared with the vascular tumor expression of the VEGFR-2 by immunohistochemical (IHC) staining in a preclinical model of ccRCC. Patients’ ccRCCs were orthotopically grafted onto Nod-Scid-Gamma (NSG) mice to generate patient-derived xenografts (PdX). Mice were divided into four groups to receive either vehicle or axitinib an amount of 2, 7.5 or 15 mg/kg twice daily. Perfusion parameters and the BR55 ultrasound contrast signal on PdX renal tumors wer...

Journal of Biophotonics, Jul 19, 2020

Proceedings of SPIE, Mar 5, 2015

In vivo high-resolution imaging of tumor development is possible through dorsal skinfold chamber ... more In vivo high-resolution imaging of tumor development is possible through dorsal skinfold chamber implantable on mice model. However, current intravital imaging systems are weakly tolerated along time by mice and do not allow multimodality imaging. Our project aims to develop a new chamber for: 1-long-term micro/macroscopic visualization of tumor (vascular and cellular compartments) and tissue microenvironment; and 2-multimodality imaging (photonic, MRI and sonography). Our new experimental device was patented in March 2014 and was primarily assessed on 75 mouse engrafted with 4T1-Luc tumor cell line, and validated in confocal and multiphoton imaging after staining the mice vasculature using Dextran 155KDa-TRITC or Dextran 2000kDa-FITC. Simultaneously, a universal stage was designed for optimal removal of respiratory and cardiac artifacts during microscopy assays. Experimental results from optical, ultrasound (Bmode and pulse subtraction mode) and MRI imaging (anatomic sequences) showed that our patented design, unlike commercial devices, improves longitudinal monitoring over several weeks (35 days on average against 12 for the commercial chamber) and allows for a better characterization of the early and late tissue alterations due to tumour development. We also demonstrated the compatibility for multimodality imaging and the increase of mice survival was by a factor of 2.9, with our new skinfold chamber. Current developments include: 1-defining new procedures for multi-labelling of cells and tissue (screening of fluorescent molecules and imaging protocols); 2-developing ultrasound and MRI imaging procedures with specific probes; 3-correlating optical/ultrasound/MRI data for a complete mapping of tumour development and microenvironment.

Ultrasound in Medicine and Biology, Apr 1, 2015

Medical Physics

BackgroundThe DCE‐US (Dynamic Contrast‐Enhanced Ultrasonography) imaging protocol predicts the va... more BackgroundThe DCE‐US (Dynamic Contrast‐Enhanced Ultrasonography) imaging protocol predicts the vascular modifications compared with Response Evaluation Criteria in Solid Tumors (RECIST) based mainly on morphological changes. A quantitative biomarker has been validated through the DCE‐US multi‐centric study for early monitoring of the efficiency of anti‐angiogenic cancer treatments. In this context, the question of transposing the use of this biomarker to other types of ultrasound scanners, probes and settings has arisen to maintain the follow‐up of patients under anti‐angiogenic treatments. As a consequence, radiologists encounter standardization issues between the different generations of ultrasound scanners to perform quantitative imaging protocols.PurposeThe aim of this study was to develop a new calibration setup to transpose the DCE‐US imaging protocol to the new generation of ultrasound scanners using both abdominal and linear probes.MethodsThis calibration method has been des...

International Journal of Molecular Sciences, 2020

Carbonic Anhydrase IX (CAIX) is a well-described enzyme in renal cell carcinoma, with its express... more Carbonic Anhydrase IX (CAIX) is a well-described enzyme in renal cell carcinoma, with its expression being regulated by the hypoxia-inducible factor 1 alpha, it is known for interfering with hypoxia processes. Renal carcinoma encompasses a broad spectrum of histological entities and is also described as a heterogeneous malignant tumor. Recently, various combinations of checkpoint inhibitors and targeted therapies have been validated to manage this disease. Reliable markers to confirm the diagnosis, estimate the prognosis, predict or monitor the treatment response are required. Molecular imaging developments allow a comprehensive analysis of the tumor, overcoming the spatial heterogeneity issue. CAIX, being highly expressed at the tumor cell surfaces of clear cell renal carcinoma, also represents a potential treatment target. In this manuscript we reviewed the current knowledge from the literature on the pathophysiological interactions between renal cell carcinoma and CAIX, the role ...

Journal of Biophotonics, 2020

International Journal of Radiology and Imaging Technology, Dec 31, 2017

Scientific Reports, 2020

Recent treatment developments for metastatic renal cell carcinoma offer combinations of immunothe... more Recent treatment developments for metastatic renal cell carcinoma offer combinations of immunotherapies or immunotherapy associated with tyrosine kinase inhibitors (TKI). There is currently no argument to choose one solution or another. Easy-to-use markers to assess longitudinal responses to TKI are necessary to determine when to switch to immunotherapies. These new markers will enable an earlier adaptation of therapeutic strategy in order to prevent tumor development, unnecessary toxicity and financial costs. This study evaluates the potential of ultrasound molecular imaging to track the response to sunitinib in a clear cell renal carcinoma model (ccRCC). We used a patient-derived xenograft model for this imaging study. Mice harboring human ccRCC were randomized for sunitinib treatment vs. control. The tumors were imaged at days 0, 7, 14 and 28 with ultrasound molecular imaging. Signal enhancement was quantified and compared between the two groups after injections of non-targeted m...

Journal of Biophotonics, 2019

Optical imaging of living animals is a unique method of studying the dynamics of physiological an... more Optical imaging of living animals is a unique method of studying the dynamics of physiological and pathological processes at a subcellular level. One‐shot acquisitions at high resolution can be achieved on exteriorized organs before animal euthanasia. For longitudinal follow‐up, intravital imaging can be used and involves imaging windows implanted in cranial, thoracic or dorsal regions. Several imaging window models exist, but none have proven to be applicable for long‐term monitoring and most biological processes take place over several weeks. Moreover, none are compatible with multiple imaging modalities, meaning that different biological parameters cannot be assessed in an individual animal. We developed a new dorsal chamber that was well tolerated by mice (over several months) and allowed individual and collective cell tracking and behaviour analysis by optical imaging, ultrasound and magnetic resonance tomography. This new model broadens potential applications to areas requirin...

Physics in Medicine & Biology, 2018

Dynamic contrast-enhanced ultrasonography is a recent functional dynamic imaging technique that a... more Dynamic contrast-enhanced ultrasonography is a recent functional dynamic imaging technique that allows evaluation of the efficacy of anti-angiogenic treatments by quantifying changes in specific parameters of the tumor vasculature. Preclinical and clinical experimental studies now reveal the existence of sources of variability in the quantitative methods. In order to study the reliability of quantification methods (both semi-quantitative and quantitative), we have developed the first numerical model of blood flow and contrast agents in vascular networks with computational fluid dynamics Fluent software version 15.0 (ANSYS, France). We studied four vascular networks (1.84 × 10-3, 2.28 × 10-3, 2.4 × 10-3 and 2.54 × 10-3 ml) and four blood velocities (0.01, 0.02, 0.03 and 0.05 m s-1). For variations in tumor vascular volume the quantitative method is more sensitive, with variations of parameter perfusion of 25.7%, in contrast to variations of the semi-quantitative parameters between 14.9 and 19.5%. For changes in blood velocity the semi-quantitative method is more sensitive, with variation of the area under the enhancement curve (64%), the maximum of the enhancement curve (60%), and the slope of the enhancement curve (73%). The transit time parameters from the two quantitative methods were weakly sensitive to both blood volume and blood flow variations. This study is hopeful and may be extended to the treatment of more complex vascular networks, to approach clinical conditions, and to the evaluation of quantification methods in contrast imaging.

European Urology Supplements, 2019

Ultrasonic imaging, Sep 1, 2018

Tumor microvascularization is a biomarker of response to antiangiogenic treatments and is accurat... more Tumor microvascularization is a biomarker of response to antiangiogenic treatments and is accurately assessed by ultrasound imaging. Imaging modes used to visualize slow flows include Power Doppler imaging, dynamic contrast-enhanced ultrasonography, and more recently, microvascular Doppler. Flow phantoms are used to evaluate the performance of Doppler imaging techniques, but they do not have a steady flow and sufficiently small channels. We report a novel device for robust and stable microflow measurements and the study of the microvascularization. Based on microfluidics technology, the prototype features wall-less cylindrical channels of diameters ranging from as small as 147 up to 436 µm, cast in a soft silicone polymer and perfused via a microfluidic flow pressure controller. The device was assessed using flow rates from 49 to 146 µL/min, with less than 1% coefficient of variation over three minutes, corresponding to velocities of 6 to 142 mm/s. This enabled us to evaluate and co...

Contrast Media & Molecular Imaging, 2017

Molecular magnetic resonance imaging targeted to an endothelial integrin involved in neoangiogene... more Molecular magnetic resonance imaging targeted to an endothelial integrin involved in neoangiogenesis was compared to DCE-US and immunochemistry to assess the early response of three different therapeutic agents in renal cell carcinoma. Human A498 renal cells carcinoma was subcutaneously inoculated into 24 nude mice. Mice received either phosphate-buffered saline solution, sunitinib, everolimus, or bevacizumab during 4 days. DCE-US and molecular MRI targeting αvβ3 were performed at baseline and 4 days after treatment initiation. PI, AUC, relaxation rate variations ΔR2⁎, and percentage of vessels area quantified on CD31-stained microvessels were compared. Significant decreases were observed for PI and AUC parameters measured by DCE-US for bevacizumab group as early as 4 days, whereas molecular αvβ3-targeted MRI was able to detect significant changes in both bevacizumab and everolimus groups. Percentage of CD31-stained microvessels was significantly correlated with DCE-US parameters, P...

2015 International Conference on Image Processing Theory, Tools and Applications (IPTA), 2015

Http Www Theses Fr, 2005

PARIS-BIUSJ-Thèses (751052125) / SudocSudocFranceF

Acoustical Imaging, 2004

Bone mechanical properties are determined by an ensemble of complex characteristics, such as micr... more Bone mechanical properties are determined by an ensemble of complex characteristics, such as microstructure (organization of collagen fibers and hydroxyapatite crystals, integrity of collagen-mineral interface), degree of mineralization, micro-architecture, and tissue elasticity. These characteristics strongly contribute by varying degrees to bone strength and resistance to fracture.

2007 IEEE Ultrasonics Symposium Proceedings, 2007

A 50-MHz quantitative scanning acoustic microscope (23 mum lateral resolution) has been used to a... more A 50-MHz quantitative scanning acoustic microscope (23 mum lateral resolution) has been used to assess spatial distribution of tissue acoustic impedance Z and microstructure features of cortical bone of human radii with the aim to determine, if these parameters vary in the different regions of the cortex. Ten fresh bone specimens taken from diaphyses of 10 human radii were explored.