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Achievements and challenges of imaging in large animal models

Abstract : Biomedical imaging in non-rodent animals is important for several purposes. First, human size animals and/or smaller mammals with relevant anatomical similarities to humans are used to develop and validate new technologies before or concomitantly to being performed in humans. Second, some imaging techniques aim directly at visualizing or directly interfering (interventional imaging) with the model organism in order to monitor in vivo the development of marked cells or to induce a pathology. Third, techniques used in human medicine are directly employed in model animals to monitor model diseases or for therapeutic interventions to be performed as in humans. X-ray based imaging (scanner, absorbtiometry, angiography) and magnetic resonance (MRI, with high magnetic fields) equipment can accommodate a whole organism and provide fine information (down to the histological scale) on the whole body (such as fat layers, body composition), one organ or one area of the body. They are in general large and costly and often require that animals be anesthetized. Challenges include the coupling of scanner (bone) and MRI (soft tissues) and the removal of artefactual effects due to movements (heart beats, breathing). In order to provide contrast to visualize vascular beds, the injection of contrast agents in the right anatomical location is necessary through the use of minimally invasive image-guided procedures where catheters are inserted through the carotid or the femoral artery or directly in the location of interest. The same methods are also used for the delivery of therapeutic agents or drug coated beads directly at a location (for instance a tumor). Ultrasound and Doppler technologies are based on the propagation of ultrasounds through an organ. Equipments are smaller than the previous technologies (with many portable machines) and most examinations can be performed without the need of anesthesia, so that these techniques are very versatile. Volumic modes allow the analysis of a region of interest and, together with Doppler, to quantify blood flow in an organ. For small structures, ultrasound bio-microscopy can reach a resolution of less than 50µm with probe frequencies >50MHz. New developments include ultrafast Doppler which allows the visualization of very slow blood flow (such as the maternal blood in the intervillous chamber of the placenta) with up to 10000 images/second. Elastography can discriminate between tissues according to their stiffness, which cannot be achieved with regular ultrasound. These techniques can be also used as treatments (“theranostics”) with, for example, the removal of surgically unresectable tumors with very high frequency localized ultrasound or with the breaking-up of micro-bubbles (ultrasound contrast agents) containing drugs at the precise localization of the lesion. Finally, endoscopic techniques provide visual access to internal cavities in a non-invasive or mini- invasive manner. They can be coupled to ultrasound or microscopy. For example, fibered confocal endoscopy will enable the operator to study in vivo the location of GFP marked cells in an organ, to the depth of about 100µm. Amongst general challenges, the standardization of measured parameters is a major issue as soon as quantitative measurements are performed, first between experts using the same machines, but more, between different equipments using the same or different technological approaches. For example, for elastography, Acoustic Radiation Force Impulse (ARFI) and Supersonic Shear Wave (SSI) based systems do not provide the same results although they are meant to measure the same thing. Further challenges include shared concerns with the medical world about finding ways to go beyond imaging and obtain functional information from imaging techniques. Such approaches are giving promising results, especially in brain studies, but techniques that would allow easy, rapid and non-invasive access to blood parameters, blood pressure (for example in the fetus) and blood volume or whole tissue oxygenation still need to be to be developed. The cost of equipments and the expertise and skillfulness necessary to use them also plead for closer exchanges between medical specialists, veterinarians developing animal models and physicists.
Mots-clés : imagerie biomédicale
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Submitted on : Wednesday, June 3, 2020 - 1:49:25 AM
Last modification on : Thursday, August 5, 2021 - 3:51:16 AM

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  • HAL Id : hal-02741577, version 1
  • PRODINRA : 277574

Citation

Pascale Chavatte-Palmer, Eve Mourier, Christophe Richard, G. Renault, M. Muller, et al.. Achievements and challenges of imaging in large animal models. Opening Conference "COST Action BM1308. Sharing Advances on Large Animal Models", European Cooperation in Science and Technology (COST). BEL., Dec 2014, Munich, Germany. ⟨hal-02741577⟩

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