Romain Lacoste

The average baboon brain: MRI templates and tissue probability maps from 89 individuals

The baboon (Papio) brain is a remarkable model for investigating the brain. The current work aimed at creating a population-average baboon (Papio anubis) brain template and its left/right hemisphere symmetric version from a large sample of T1-weighted magnetic resonance images collected from 89 individuals. Averaging the prior probability maps output during the segmentation of each individual also produced the first baboon brain tissue probability maps for gray matter, white matter and cerebrospinal fluid. The templates and the tissue probability maps were created using state-of-the-art, freely available software tools and are being made freely and publicly available: http://www.nitrc.org/projects/haiko89/ or http://lpc.univ-amu.fr/spip.php?article589. It is hoped that these images will aid neuroimaging research of the baboon by, for example, providing a modern, high quality normalization target and accompanying standardized coordinate system as well as probabilistic priors that can be used during tissue segmentation.

Feasibility and reproducibility of ShearWaveTM elastography of fetal baboon organs

The purpose of this study was to assess the feasibility and reproducibility of transabdominal ShearWaveTM elastography of fetal organs in pregnant baboons.

Detection and quantification of STLV-1 and SFV proviral load in blood and saliva of naturally infected non-human primates

Simian T Lymphotropic Virus type 1 (STLV-1) and Simian Foamy Virus (SFV) retroviruses infect Old World non-human primates (NHP) and humans. Inter-human transmission has been described for HTLV-1 but not for SFV. SFV infection is asymptomatic in its hosts, while STLV-1 and its human counterpart HTLV-1 are the etiologic agents of Adult T-cell Leukemia/Lymphoma. Both STLV-1 and SFV can be zoonotically transmitted from NHP to humans through severe bites, thus involving contact between virus-containing saliva in the donor and blood in the recipient. Surprisingly, while the presence of both SFV RNA and DNA has been characterized into the saliva of NHP, neither STLV-1 DNA, nor STLV-1 RNA was quantified. Thus, the goal of our study was to search for STLV-1 provirus in the cells present in the saliva of NHP and then to quantify the proviral load of both viruses. We took advantages of a cohort of 45 papio anubis, naturally infected by STLV-1. We first assessed SFV infection and then potential SFV/STLV-1 co-infections. To this end, we designed semi-nested PCR and qPCR protocols (1) to diagnose infection and (2) to quantify STLV-1 and/or SFV proviral load in peripheral blood cells and in saliva. First, STLV-1 provirus was detected by semi-nested PCR in 8/10 blood samples tested, but only in the saliva of 1/10 NHP who had a high STLV-1 proviral load in peripheral blood cells. SFV DNA was detected by nested-PCR in blood samples from 10/10 baboons and in the saliva of 8/10 animals. A second study performed with 20 animals will be presented. We will show whether a correlation exists between blood and saliva STLV-1/SFV proviral load and whether infection with one retrovirus impacts proviral load of the other. Altogether, our current results suggest that SFV is more frequently present in saliva than STLV-1. This should impact the ability of both viruses to be zoonotically transmitted through bites.

Whole body clonality analysis in an aggressive STLV-1 associated leukemia (ATLL) reveals an unexpected clonal complexity

HTLV-1 causes Adult T cell Leukemia/Lymphoma (ATLL) in humans. We describe an ATL-like disease in a 9 year-old female baboon naturally infected with STLV-1 (the simian counterpart of HTLV-1), with a lymphocyte count over 1010/L, lymphocytes with abnormal nuclear morphology, and pulmonary and skin lesions. The animal was treated with a combination of AZT and alpha interferon. Proviral load (PVL) was measured every week. Because the disease continued to progress, the animal was euthanized. Abnormal infiltrates of CD3+CD25+ lymphocytes and Tax-positive cells were found by histological analyses in both lymphoid and non-lymphoid organs. PVL was measured and clonal diversity was assessed by LM-PCR (Ligation-Mediated Polymerase Chain Reaction) and high throughput sequencing, in blood during treatment and in 14 different organs. The highest PVL was found in lymph nodes, spleen and lungs. One major clone and a number of intermediate abundance clones were present in blood throughout the course of treatment, and in organs. These results represent the first multi-organ clonality study in ATLL. We demonstrate a previously undescribed clonal complexity in ATLL. Our data reinforce the usefulness of natural STLV-1 infection as a model of ATLL.

Élastographie par ondes de cisaillement (shear waves) du placenta chez la babouine gestante

OBJECTIVES To evaluate tissue characteristics of the placenta by transabdominal ShearWave Elastography in pregnant baboon. MATERIALS AND METHOD For 9 months (03/2013-12/2013) two operators (EQ, GG) performed ultrasound of the placenta during pregnancy pregnant baboons station partner primatology project. The identification of the placenta was performed previously in 2D ultrasound. The elastography method was then activated. Three measurements were carried out by operator for each placenta. The intraclass correlation coefficients within and between observers were calculated for the objective assessment (elastography) of placental maturity. RESULTS During the study period, 21 pregnant baboons were included and ultrasounds were performed between 1 and 3 times each. The measurements have been carried out by two operators in 100% of cases. The intra- and inter-observer ICC for single values are respectively 0.657 - 95% CI (0.548 to 0.752) and 0.458 - 95% CI (0.167 to 0.675). The intra- and inter-observer ICC for average values are respectively 0.852 - 95% CI (0.784 to 0.901) and 0.628 - 95% CI (0.286 to 0.806). CONCLUSION The study by transabdominal ShearWave Elastography of placentas pregnant baboons is possible. The intra- and inter-operator reproducibility of this method is good using the average of three measurements. The objective study via elastography ShearWave of the degree of placental maturity seems not yet be used in clinical practice. Studies of larger cohorts are needed.

Left Brain Asymmetry of the Planum Temporale in a Nonhominid Primate: Redefining the Origin of Brain Specialization for Language

The planum temporale (PT) is a critical region of the language functional network in the human brain showing a striking size asymmetry toward the left hemisphere. Historically considered as a structural landmark of the left-brain specialization for language, a similar anatomical bias has been described in great apes but never in monkeys-indicating that this brain landmark might be unique to Hominidae evolution. In the present in vivo magnetic resonance imaging study, we show clearly for the first time in a nonhominid primate species, an Old World monkey, a left size predominance of the PT among 96 olive baboons (Papio anubis), using manual delineation of this region in each individual hemisphere. This asymmetric distribution was quasi-identical to that found originally in humans. Such a finding questions the relationship between PT asymmetry and the emergence of language, indicating that the origin of this cerebral specialization could be much older than previously thought, dating back, not to the Hominidae, but rather to the Catarrhini evolution at the common ancestor of humans, great apes and Old World monkeys, 30-40 million years ago.

Transoesophageal HIFU for cardiac ablation: In-vivo experiments in non-human primates

Transesophageal HIFU was proposed as an alternative to the current atrial fibrillation treatments. The present work described a feasibility study of transesophageal thermal ablation in the heart of non-human primates. An endoscope integrating a 5MHz 64-element commercial transesophageal echocardiography probe and a 8-element HIFU transducer was built. The transducer was cooled at 5°C and ultrasonic beam could be steered over a 15 to 55 mm range. The probe was tested in-vivo on three 30kg-baboons. Left atrium and ventricles were exposed to repeated continuous sonications (4-15 times during 16s) at a focal intensity of 3000 W/cm². B-mode, shear-wave and passive elastographies were performed before and after treatments in an attempt to monitor thermal lesions. T1 mapping and contrast MR imaging were realized the day after treatment. Clinical states of the subjects during and after the treatment were positive. One lesion in the left ventricle could be evidenced by elastography and confirmed by MRI. Experiment...

Myocardial Thermal Ablation with a Transesophageal High-Intensity Focused Ultrasound Probe: Experiments on Beating Heart Models

Described here is a study of transesophageal thermal ablation of isolated and perfused beating hearts and non-human primates. An endoscope integrating a transesophageal echocardiography probe and a high-intensity focused ultrasound transducer was built and tested on five Langendorff-isolated hearts and three 30-kg baboons. B-Mode ultrasound, passive elastography and magnetic resonance imaging were performed to monitor thermal lesions. In isolated hearts, continuous and gated sonication parameters were evaluated with acoustic intensities of 9-12 W/cm2. Sonication parameters of gated exposures with 12 W/cm2 acoustic intensity for 5 min consistently produced visible lesions in the ventricles of isolated hearts. In animals, left atria and ventricles were exposed to repeated continuous sonications (4-15 times for 16 s) at an acoustic intensity at the surface of the transducer of 9 W/cm2. Clinical states of the baboons during and after the treatment were good. One suspected lesion in the left ventricle could be evidenced by elastography, but was not confirmed by magnetic resonance imaging. The transesophageal procedure therefore has the potential to create thermal lesions in beating hearts and its safety in clinical practice seems promising. However, further technical exploration of the energy deposition in the target would be necessary before the next pre-clinical experiments.

STLV-1 co-infection is correlated with an increased SFV proviral load in the peripheral blood of SFV/STLV-1 naturally infected non-human primates

Simian T-Leukemia Virus type 1 and Simian Foamy Virus infect non-human primates. While STLV-1, as HTLV-1, causes Adult T-cell Leukemia/lymphoma, SFV infection is asymptomatic. Both retroviruses can be transmitted from NHPs to humans through bites that allow contact between infected saliva and recipient blood. Because both viruses infect CD4+ T-cells, they might interfere with each other replication, and this might impact viral transmission. Impact of STLV-1 co-infection on SFV replication was analyzed in 18 SFV-positive/STLV-1-negative and 18 naturally SFV/STLV-1 co-infected Papio anubis. Even if 9 animals were found STLV-1-positive in saliva, STLV-1 PVL was much higher in the blood. SFV proviruses were detected in the saliva of all animals. Interestingly, SFV proviral load was much higher in the blood of STLV-1/SFV co-infected animals, compared to STLV-1-negative animals. Given that soluble Tax protein can enter uninfected cells, we tested its effect on foamy virus promoter and we show that Tax protein can transactivate the foamy LTR. This demonstrates that true STLV-1 co-infection or Tax only has an impact on SFV replication and may influence the ability of the virus to be zoonotically transmitted as well as its ability to promote hematological abnormalities.

Transoesophageal HIFU for cardiac ablation : Experiments on beating hearts

Atrial fibrillation and ventricular tachycardia are currently treated with catheter ablation using radiofrequency or cryoenergy. These endocardiac approaches are invasive and not fully satisfactory as the treatments are often incomplete and can be associated with side effects. HIFU were proposed as an alternative strategy, by using the excellent acoustic window between heart and esophagus. The present work described feasibility of trans-oesophageal thermal ablation on ex-vivo beating heart and non-human primates.