SummaryComputed tomography is a powerful medical imaging modality for longitudinal studies in cancer to follow neoplasia progression and evaluate anticancer therapies. Here, we report the generation of a photon-counting micro-computed tomography (PC-CT) method based on hybrid pixel detectors with enhanced sensitivity and precision of tumor imaging. We then applied PC-CT for longitudinal imaging in a clinically relevant liver cancer model, the Alb-R26Met mice, and found a remarkable heterogeneity in the dynamics for tumors at the initiation phases. Instead, the growth curve of evolving tumors exhibited a comparable exponential growth, with a constant doubling time. Furthermore, longitudinal PC-CT imaging in mice treated with a combination of MEK and BCL-XL inhibitors revealed a drastic tumor regression accompanied by a striking remodeling of macrophages in the tumor microenvironment. Thus, PC-CT is a powerful system to detect cancer initiation and progression, and to monitor its evolution during treatment.

We characterize the imaging performance of the micro computed tomography (micro-CT) prototype PIXSCAN equipped with an x-ray photon counting camera based on XPAD3/Si hybrid pixel detectors. The camera, which is composed of eight distinctive horizontal modules, permits the performance of whole-body mouse scans. Photon counting supplied by hybrid pixels guarantees acquisitions at a Poisson noise level exclusively determined by the detected photon statistics. First, we characterize the performance of the imaging system while assessing its linearity, noise, spatial resolution and low contrast detectability estimated from scans of appropriate phantoms. Then, we show CT images of mice data acquired either in vivo or post mortem, without or with an injection of iodine as a contrast agent. Although hybrid pixels guarantee a minimal noise to the images, the limited detection efficiency of Si sensors impairs detected photon statistics and therefore the improvement in contrast-to-noise ratio for standard tomographic imaging. Indeed, the most innovative potential of the PIXSCAN prototype is its capacity to perform spectral tomographic imaging and fast dynamic imaging. The first is thanks to the possibility of setting an energy threshold on the detected photons, and the second is thanks to its fast acquisition rate (till 500 images/s). We present some examples of these imaging methods applied to mice and discuss their main limiting factors.

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We investigate the improvement from the use of high-Z CdTe sensors for pre-clinical K-edge imaging with the hybrid pixel detectors XPAD3. We compare XPAD3 chips bump bonded to Si or CdTe sensors in identical experimental conditions. Image performance for narrow energy bin acquisitions and contrast-to-noise ratios of K-edge images are presented and compared. CdTe sensors achieve signal-to-noise ratios at least three times higher than Si sensors within narrow energy bins, thanks to their much higher detection efficiency. Nevertheless Si sensors provide better contrast-to-noise ratios in K-edge imaging when working at equivalent counting statistics, due to their better estimation of the attenuation coefficient of the contrast agent. Results are compared to simulated data in the case of the XPAD3/Si detector. Good agreement is observed when including charge sharing between pixels, which have a strong impact on contrast-to-noise ratios in K-edge images.