Distinguishing Iron and Calcium using MARS Spectral CT Searle, Emily K; Butler, Anthony P H; Raja, Aamir Y ...
2018 IEEE Nuclear Science Symposium and Medical Imaging Conference Proceedings (NSS/MIC),
2018-Nov.
Conference Proceeding
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 400mg/ml ferric nitrate and 100mg/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.
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 CO2 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.
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