Molecular Imaging of Pulmonary Tuberculosis in an Ex-Vivo Mouse Model Using Spectral Photon-Counting Computed Tomography and Micro-CT

Assessment of disease burden and drug efficacy is achieved preclinically using high resolution micro computed tomography (CT). However, micro-CT is not applicable to clinical human imaging due to operating at high dose. In addition, the technology differences between micro-CT and standard clinical CT prevent direct translation of preclinical applications. The current proof-of-concept study presents spectral photon-counting CT as a clinically translatable, molecular imaging tool by assessing contrast uptake in an ex-vivo mouse model of pulmonary tuberculosis (TB). Iodine, a common contrast used in clinical CT imaging, was introduced into a murine model of TB. The excised mouse lungs were imaged using a standard micro-CT subsystem (SuperArgus) and the contrast enhanced TB lesions quantified. The same lungs were imaged using a spectral photoncounting CT system (MARS small-bore scanner). Iodine and soft tissues (water and lipid) were materially separated, and iodine uptake quantified. The volume of the TB infection quantified by spectral CT and micro-CT was found to be 2.96 mm(3) and 2.83 mm(3), respectively. This proof-of-concept study showed that spectral photon-counting CT could be used as a predictive preclinical imaging tool for the purpose of facilitating drug discovery and development. Also, as this imaging modality is available for human trials, all applications are translatable to human imaging. In conclusion, spectral photon-counting CT could accelerate a deeper understanding of infectious lung diseases using targeted pharmaceuticals and intrinsic markers, and ultimately improve the efficacy of therapies by measuring drug delivery and response to treatment in animal models and later in humans

Investigation of MARS Spectral CT: X-ray Source and Detector Characterization

This thesis describes a series of interrelated studies that I performed to characterize two key modules of MARS spectral CT scanner: the x-ray source and the x-ray detector. Characterizing and optimizing the outputs of these two modules are steps towards utilizing the full advantages of the multi-channel spectroscopic imaging from the MARS spectral CT to enhance material resolution. I contributed to developing a parameterized semi-analytic x-ray source model. The main body of this work and its utilization in other MARS projects have been disseminated through a submitted paper, a published paper, and three conference proceedings. I also developed a method for profile assessment and characterization. This work has given rise to a submitted paper and a conference proceeding. I contributed to characterizing the Medipix3RX performance at the pixel level through two distinct projects including characterization and calibration of per-pixel energy response, and pixel classification based on time analysis. The industrial importance of this research outcome resulted in the filing of two patents: an algorithm for generating a pixel mask, and a method for identification and correction of unstable pixel clusters. The parameterized semi-analytic x-ray source model provides on- and off-axis x-ray spectra in the diagnostic imaging energy range of 30-120 kVp, across the field of view of the MARS spectral CT. This development was in response to a need for accurately providing the energy and position of the incident photon to a future polychromatic-based material reconstruction technique in the MARS group. Considering the polychromatic structure of the beam in data processing will enable us to make better use of the spectroscopic information that is available in the Medipix3RX ASIC. The beam profile assessment and characterization method was motivated by the instabilities of the beam profile observed in a poorly-calibrated MARS spectral CT prototype. To monitor the beam profile, several beam profile properties were measured in the MARS spectral CT and compared with the profiles of the x-ray source model. This method is capable of identifying temporal or spatial fluctuations in the beam profile. The accurate offset parameters provided by this method are then used to calibrate the MARS source model for each scanner. This, therefore, enables us to accurately express the incident photons of the x-ray beam for the future spectral reconstruction techniques. Characterization and calibration of the individual pixel energy response addressed degradation of spectral fidelity of the images caused by inter-pixel variation of energy response. The significance of the proposed method is to measure and calibrate per-pixel energy response when the MARS spectral CT operates in a standard acquisition mode without using any additional equipment. A by-product of this system is the measurement of the unequal effective pixel area, which can be used in the study related to sensor layer manufacturing. A pilot study of pixel classification based on temporal pixel behavior was also conducted to an improved method. This method is capable of identifying malfunctioning and slow-drift pixels and masking them out from the data processing chain. Because of the precise threshold criteria were chosen in this method, it is unlikely to label a flickering pixel as a well-behaved pixel. This method significantly improved the signal-to-noise ratio of the reconstructed image. Furthermore, a group of malfunctioning pixels was identified as behaving correlatively. The overall response of all pixels can be treated as a well-behaved pixel, enabling reliable utilization of the low-grade sensors

Multi‐“Color” Delineation of Bone Microdamages Using Ligand‐Directed Sub‐5 nm Hafnia Nanodots and Photon Counting CT Imaging

The early detection of bone microdamages is crucial to make informed deci-sions about the therapy and taking precautionary treatments to avoid cata-strophic fractures. Conventional computed tomography (CT) imaging faces obstacles in detecting bone microdamages due to the strong self-attenuation of photons from bone and poor spatial resolution. Recent advances in CT tech-nology as well as novel imaging probes can address this problem effectively. Herein, the bone microdamage imaging is demonstrated using ligand-directed nanoparticles in conjunction with photon counting spectral CT. For the first time, Gram-scale synthesis of hafnia (HfO2) nanoparticles is reported with surface modification by a chelator moiety. The feasibility of delineating these nanoparticles from bone and soft tissue of muscle is demonstrated with photon counting spectral CT equipped with advanced detector technology. The ex vivo and in vivo studies point to the accumulation of hafnia nanoparticles at micro-damage site featuring distinct spectral signal. Due to their small sub-5 nm size, hafnia nanoparticles are excreted through reticuloendothelial system organs without noticeable aggregation while not triggering any adverse side effects based on histological and liver enzyme function assessments. These preclinical studies highlight the potential of HfO2-based nanoparticle contrast agents for skeletal system diseases due to their well-placed K-edge binding energy

Thermal impact of dykes on ignimbrite and implications for fluid flow compartmentalisation in calderas

International audienceIgnimbrites within calderas host intrusions with hazardous and/or economically significant hydrothermal systems. The Hvítserkur ignimbrite at Breiðuvík caldera, north-eastern Iceland, is intruded by basaltic dykes. Our data show that the ignimbrite immediately adjacent to the dyke is hard, dark-coloured, recrystallised quartz, plagioclase, and alkali feldspar with a low permeability and porosity and frequent macrofractures. At 1-2 m from the dyke, the ignimbrite is hard, dominantly glassy with pervasive perlitic microfractures, has high permeability, but low porosity and frequent macrofractures. A narrow zone of pervasive unlithified clay exists 2 m from the dyke. Beyond this, the ignimbrite is soft and zeolite-rich, has low permeability, high porosity and fewer macrofractures. The dyke intrusion promoted a narrow zone of welding, fracturing and perlitisation in the ignimbrite resulting in high permeability and focussed alteration. Our study shows how intrusions and their thermal aureoles create vertical pathways for, and horizontal barriers to, geothermal fluid flow

Thermal impact of dykes on ignimbrite and implications for fluid flow compartmentalisation in calderas

Ignimbrites within calderas host intrusions with hazardous and/or economically significant hydrothermal systems. The Hvítserkur ignimbrite at Breiðuvík caldera, north-eastern Iceland, is intruded by basaltic dykes. Our data show that the ignimbrite immediately adjacent to the dyke is hard, dark-coloured, recrystallised quartz, plagioclase, and alkali feldspar with a low permeability and porosity and frequent macrofractures. At 1-2 m from the dyke, the ignimbrite is hard, dominantly glassy with pervasive perlitic microfractures, has high permeability, but low porosity and frequent macrofractures. A narrow zone of pervasive unlithified clay exists 2 m from the dyke. Beyond this, the ignimbrite is soft and zeolite-rich, has low permeability, high porosity and fewer macrofractures. The dyke intrusion promoted a narrow zone of welding, fracturing and perlitisation in the ignimbrite resulting in high permeability and focussed alteration. Our study shows how intrusions and their thermal aureoles create vertical pathways for, and horizontal barriers to, geothermal fluid flow

Beam profile assessment in spectral CT scanners.

In this paper, we present a method that uses a combination of experimental and modeled data to assess properties of x-ray beam measured using a small-animal spectral scanner. The spatial properties of the beam profile are characterized by beam profile shape, the angular offset along the rotational axis, and the photon count difference between experimental and modeled data at the central beam axis. Temporal stability of the beam profile is assessed by measuring intra- and interscan count variations. The beam profile assessment method was evaluated on several spectral CT scanners equipped with Medipix3RX-based detectors. On a well-calibrated spectral CT scanner, we measured an integral count error of 0.5%, intrascan count variation of 0.1%, and an interscan count variation of less than 1%. The angular offset of the beam center ranged from 0.8° to 1.6° for the studied spectral CT scanners. We also demonstrate the capability of this method to identify poor performance of the system through analyzing the deviation of the experimental beam profile from the model. This technique can, therefore, aid in monitoring the system performance to obtain a robust spectral CT; providing the reliable quantitative images. Furthermore, the accurate offset parameters of a spectral scanner provided by this method allow us to incorporate a more realistic form of the photon distribution in the polychromatic-based image reconstruction models. Both improvements of the reliability of the system and accuracy of the volume reconstruction result in a better discrimination and quantification of the imaged materials

Assessment of metal implant induced artefacts using photon counting spectral CT

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