The aim is to perform qualitative and quantitative assessment of metal induced artefacts of small titanium biomaterials using photon counting spectral CT. The energy binning feature of some photon counting detectors enables the measured spectrum to be segmented into low, mid and high energy bins in a single exposure. In this study, solid and porous titanium implants submerged in different concentrations of calcium solution were scanned using the small animal MARS photon counting spectral scanner equipped with a polyenergetic X-ray source operated at 118 kVp. Five narrow energy bins (7-45 keV, 45-55 keV, 55-65 keV, 65-75 keV and 75-118 keV) in charge summing mode were utilised. Images were evaluated in the energy domain (spectroscopic images) as well as material domain (material segmentation and quantification). Results show that calcium solution outside titanium implants can be accurately quantified. However, there was an overestimation of calcium within the pores of the scaffold. This information is critical as it can severely limit the assessment of bone ingrowth within metal structures. The energy binning feature of the spectral scanner was exploited and a correction factor, based on calcium concentrations adjacent to and within metal structures, was used to minimise the variation. Qualitative and quantitative evaluation of bone density and morphology with and without titanium screw shows that photon counting spectral CT can assess bone-metal interface with less pronounced artefacts. Quantification of bone growth in and around the implants would help in orthopaedic applications to determine the effectiveness of implant treatment and assessment of fracture healing.

This study demonstrates the translation of small-bore MARS photon-counting CT technology to live human spectral imaging within a clinical radiation dose level. We used the same spectral CT technology platform (hardware and software) for the acquisition of spectral CT data, image reconstruction, material decomposition and visualisation as used in small-bore MARS photon-counting CT. Small-bore MARS photon-counting CT has been used to produce promising results in the fields of cancer, bone and cartilage health, and cardio-vascular diseases. With the development of large-bore MARS photon-counting CT, small-animal studies can now be translated to humans, sheep, or pigs. Spectral CT data at eight energy-channels were acquired simultaneously to scan body-parts of a human volunteer. Two scans were performed, the first a part of the lower-leg, and the second of the wrist. After reconstructing the spectral CT images with voxel dimensions of 90 × 90 × 90 μm 3 , a constrained leastsquare based material decomposition was applied to estimate the density of soft-tissue components (water and fat) and bone (calcium) in each voxel. The computed tomography dose index was measured to assess the radiation dose delivered in scanning the lower-leg of a live human. The previous studies conducted on small-bore MARS photon-counting CT have indicated that spectral information is beneficial for the assessment of cancer, bone and cartilage health, and cardio-vascular diseases. This study also demonstrates that spectral information obtained with the large-bore MARS photon-counting CT provides a similar level of material information to that obtained with small-bore MARS photon-counting CT. The measured weighted computed tomography dose index for scanning the two body-parts in this study was below 5 mGy in each scan. Obtaining diagnostic quality spectral CT images of a human within a clinical radiation dose level demonstrates the potential for using large-bore MARS photon-counting CT in human clinical trials.

The aim of the present study is to show that non-invasive MARS imaging can differentiate between infected and healthy pulmonary tissue using an iodine-based contrast agent at high resolution. One C57BL/6J mouse with chronic tuberculosis (TB) was euthanized with CO 2 and the pulmonary tissue excised. The TB lungs were incubated in 3% iodine solution. Mouse pulmonary tissue free of TB was also excised and incubated in the iodine solution for control purposes. Calibration of the MARS scanner involved scanning a phantom containing four concentrations of iodine along with water (soft tissue) and lipid (fat). The calibration phantom, control, and TB infected tissue were imaged at four threshold energy levels (20, 27, 34, 45 keV) at a constant 60 kVp tube voltage and 90 μA tube current. Following analysis of the calibration phantom, material decomposition (MD) was applied to the pulmonary tissue samples and iodine to obtain material images. MARS Vision software was used to visualize the materials to produce 3D material images. TB granulomas are visible within the lung lobes due to the iodine uptake. The amount of iodine uptake can be measured in mg by analysis of the material images using MARS Vision. MARS imaging was able to better differentiate between infected and healthy tissue. The present study demonstrated non-invasive, photon-counting CT is capable of differentiating between infected and healthy tissue. Future studies will consider development of TB markers, or drug markers labelled with gold nanoparticles, to enhance the understanding of the basic biology and mechanisms underpinning TB, and its relevance to the phenomenon of persistence in the infected host during therapy.

This study aims to demonstrate that spectral CT imaging can identify and quantify inflammatory components of unstable plaque such as iron, calcium and lipid in phantoms and excised human atherosclerotic plaques. Spectral CT acquisition protocol was optimised using the MARS spectral scanner. A phantom with multiple concentrations of ferric nitrate (25, 50, 100, 200 and 400 mg/ml), hydroxyapatite (104.3, 402.3, and 603.3 mg/cm 3 ), iodine (9 and 18 mg/ml), lipid and water was scanned followed by blood clots and excised human plaques using energy thresholds 20, 28, 36 and 44 keV at 80 kVp, 55 μA tube current and 100 ms exposure time. CT images were reconstructed in narrow energy bins. Differences in linear attenuation coefficients between different concentrations of ferric nitrate and hydroxyapatite were compared using the receiver operating characteristic (ROC) curve and considered successful if AUC≥0.8. Differentiation between iron and calcium was successful at 400 mg/ml ferric nitrate and 100 mg/ml hydroxyapatite (AUC≥0.9; 99% correct material identification). The optimised calibrations were implemented in blood clots and plaque scans, which successfully identified iron signal within the clots, and areas of intraplaque haemorrhage and calcification in the carotid plaque specimens.

Treatment failure in cancer is often due to variation in tumour characteristics within the same tumour, or across tumour sites, or over time. At present, most cancers are staged with imaging; treatment is selected, then the patient is re-imaged to see if the treatment is working. We intend to transform that approach by using a novel non-invasive spectral imaging technology together with targeted and non-targeted gold nanoparticles to measure tumour burden as well as drug delivery. In this study, we report spectral CT imaging of four different cancer cell types (ovarian, breast, Raji cancer cells and Lewis lung carcinoma) using gold nanoparticles. We also report that drug labelled targeted gold nanoparticles can specifically target HER2+ breast cancer cells and can be quantified by a spectral scanner. MARS CT incorporated with Medipix3RX detector was used. For image acquisition, four energy thresholds were set between 18 to 118keV to detect the K-edge of gold nanoparticles. Reconstructed images in narrow energy bins were used for material decomposition. In the first study, two ovarian cancer cell lines (OVCAR5 and SKOV3) were incubated in four sizes of gold nanoparticles (18, 40, 60 and 80nm). Results indicated a high uptake of 18 and 80nm of the gold nanoparticle by SKOV3; OVCAR5 show less uptake for all four nanoparticle sizes. In the second study, Lewis lung carcinoma was implanted in C57BL mice, and 15nm non-functionalized gold nanoparticles were injected via tail vein. Gold nanoparticles were visualized and quantified (0.497mg) in the peripheral region of a tumour whilst showing tumour necrosis in the middle. The third study showed the successful cross-over experiment of gold nanoparticles labelled to two drugs, Rituximab, and Herceptin to target Raji, and breast cancer cells respectively. The findings demonstrated spectral CT has the potential to enable the imaging and quantification of nanoparticles to monitor biological or disease processes and drug delivery to specific cell types.