Ultrasensitive and multiplexed tracking of single cells using whole-body PET/CT.

In vivo molecular imaging tools are crucially important for elucidating how cells move through complex biological systems; however, achieving single-cell sensitivity over the entire body remains challenging. Here, we report a highly sensitive and multiplexed approach for tracking upward of 20 single cells simultaneously in the same subject using positron emission tomography (PET). The method relies on a statistical tracking algorithm (PEPT-EM) to achieve a sensitivity of 4 becquerel per cell and a streamlined workflow to reliably label single cells with over 50 becquerel per cell of 18F-fluorodeoxyglucose (FDG). To demonstrate the potential of the method, we tracked the fate of more than 70 melanoma cells after intracardiac injection and found they primarily arrested in the small capillaries of the pulmonary, musculoskeletal, and digestive organ systems. This study bolsters the evolving potential of PET in offering unmatched insights into the earliest phases of cell trafficking in physiological and pathological processes and in cell-based therapies.

Efficient and multiplexed tracking of single cells using whole-body PET/CT.

In vivo molecular imaging tools are crucially important for elucidating how cells move through complex biological systems, however, achieving single-cell sensitivity over the entire body remains challenging. Here, we report a highly sensitive and multiplexed approach for tracking upwards of 20 single cells simultaneously in the same subject using positron emission tomography (PET). The method relies on a new tracking algorithm (PEPT-EM) to push the cellular detection threshold to below 4 Bq/cell, and a streamlined workflow to reliably label single cells with over 50 Bq/cell of 18F-fluorodeoxyglucose (FDG). To demonstrate the potential of method, we tracked the fate of over 70 melanoma cells after intracardiac injection and found they primarily arrested in the small capillaries of the pulmonary, musculoskeletal, and digestive organ systems. This study bolsters the evolving potential of PET in offering unmatched insights into the earliest phases of cell trafficking in physiological and pathological processes and in cell-based therapies.

Advanced Monte Carlo simulations of emission tomography imaging systems with GATE.

Built on top of the Geant4 toolkit, GATE is collaboratively developed for more than 15 years to design Monte Carlo simulations of nuclear-based imaging systems. It is, in particular, used by researchers and industrials to design, optimize, understand and create innovative emission tomography systems. In this paper, we reviewed the recent developments that have been proposed to simulate modern detectors and provide a comprehensive report on imaging systems that have been simulated and evaluated in GATE. Additionally, some methodological developments that are not specific for imaging but that can improve detector modeling and provide computation time gains, such as Variance Reduction Techniques and Artificial Intelligence integration, are described and discussed.

A novel approach for computing 3D mice distal femur properties using high-resolution micro-computed tomography scanning.

One of the most-scanned joints in preclinical animal models dealing with musculoskeletal pathologies is the mouse knee. While three-dimensional (3D) characterization of bone tissue porosity have previously been performed on cortical bone, it has not yet been comprehensively performed for the subchondral bone (SB) and the calcified cartilage (CC), which compose the subchondral mineralized zone (SMZ). Thus, it remains challenging to assess changes that occur in the SMZ of the mouse knee during pathologies such as osteoarthritis. One of the keys to addressing this challenge is to segment each layer to measure their morphologies, material properties, and porosity. Our study presents a novel approach for computing Tissue Mineral Density, 3D porosity, and the thickness of SB and CC in a mouse distal femur using High-Resolution Micro-Computed Tomography (HR-µCT). We have segmented the Vascular Porosity network, the osteocytes' lacunae of the SB, and the chondrocytes of the CC by using multi-thresholding and the percentage of chondrocytes porosity. Our results show a low intra- and inter-observer coefficient of variability. Regarding porosity and geometrical properties of both CC and SB, our results are within the range of the literature. Our approach opens new avenues for assessing porosity and vascular changes in the distal femur of preclinical animal models dealing with musculoskeletal pathologies such as osteoarthritis.