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

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

Semi-analytic off-axis X-ray source model

Spectral computed tomography (CT) systems are employed with energy-resolving photon counting detectors. Incorporation of a spectrally accurate x-ray beam model in image reconstruction helps to improve material identification and quantification by these systems. Using an inaccurate x-ray model in spectral reconstruction can lead to severe image artifacts, one of the extreme cases of this is the well-known beam-hardening artifacts. An often overlooked spectral feature of x-ray beams in spectral reconstruction models is the angular dependence of the spectrum with reference to the central beam axis. To address these factors, we have developed a parameterized semi-analytical x-ray source model in the diagnostic imaging range (30-120 kVp) by applying regression techniques to data obtained from Monte Carlo simulations (EGSnrc). This x-ray beam model is generalized to describe the off-axis spectral information within ±17o along θ (vertical direction), ±5o along phgr (horizontal direction) of the central axis, and can be parameterized for specific x-ray tube models. Comparisons of our model with those generated by SpekCalc, TOPAS, and IPEM78 at central axis show good agreement (within 2 %). We have evaluated the model with experimental data collected with a small animal spectral scanner

Oblique fluorescence in a MARS scanner with a CdTe-Medipix3RX

The latest version of the MARS small bore scanner makes use of the Medipix3RX ASIC, bonded to a CdTe or CZT semi-conductor layer, to count x-ray photons and create a spectroscopic CT data set. The MARS imaging chain uses the energy-resolved 2D transmission images to construct quantitative 3D spectral and material images. To improve the spectral performance of the imaging system it is important that the energy response of the detector is well calibrated. A common methodology for energy calibration is to use x-ray fluorescence (XRF), due to its effective monochromatic nature. Oblique (off-axis) XRF can be measured in situ in the MARS small bore scanner. A monoatomic foil is placed in front of the x-ray source and off-axis XRF is measured. A key issue is identifying near optimal measurement positions that maximize the XRF signal while minimizing transmitted and scattered x-rays from the primary beam. This work shows the development of a theoretical model that is able to identify where in the detector plane XRF is maximum. We present: (1) a theoretical model that calculates the XRF photon distribution across the detector plane produced from illuminated foils attached to the scanner’s filter bar; (2) preliminary experimental measurements of the XRF distribution outside of the main beam taken with a CdTe-Medipix3RX detector; and (3) a comparison between the model and experiment. The main motivation behind creating this model is to identify the region in the detector plane outside of the main beam where XRF is at a maximum. This provides the optimum detector location for measuring a monochromatic XRF source with minimal polychromatic contamination for its use in per-pixel energy calibration of Medipix3RX detectors in MARS scanners

Per-pixel energy calibration of photon counting detectors

Energy resolving performance of spectral CT systems is influenced by the accuracy of the detector’s energy calibration. Global energy calibration maps a given threshold to the average energy response of all pixels of the detector. Variations arising from CMOS manufacturing processes and properties of the sensor cause different pixels to respond differently to photons of the same energy. Threshold dispersion adversely affects spectral imaging by degrading energy resolution, which contributes to blurring of the energy information. In this paper, we present a technique for per-pixel energy calibration of photon-counting x-ray detectors (PCXDs) that quantifies the energy response of individual pixels relative to the average response. This technique takes advantage of the measurements made by an equalized chip. It uses a known global energy map to quantify the effect of threshold dispersion on the energy response of the detector pixels across an energy range of interest.The proposed technique was assessed using a MARS scanner with an equalized Medipix3RX chip flip-bonded to 2mm thick CdTe semiconductor crystal at a pitch of 110ᵤm. Measurements were made of characteristic x-rays of a molybdenum foil. Results were compared between the case that the global calibration was used on its own and the case of using it in conjunction with our per-pixel calibration technique. The proposed technique quantified up to 1:87 keV error in energy response of 100 pixels of a selected region of interest (ROI). It made an improvement of 28:3% in average FWHM. The additional information provided by this per-pixel calibration technique can be used to improve spectral reconstruction

MARS-MD: rejection based image domain material decomposition

This paper outlines image domain material decomposition algorithms that have been routinely used in MARS spectral CT systems. These algorithms (known collectively as MARS-MD) are based on a pragmatic heuristic for solving the under-determined problem where there are more materials than energy bins. This heuristic contains three parts: (1) splitting the problem into a number of possible sub-problems, each containing fewer materials; (2) solving each sub-problem; and (3) applying rejection criteria to eliminate all but one sub-problem's solution. An advantage of this process is that different constraints can be applied to each sub-problem if necessary. In addition, the result of this process is that solutions will be sparse in the material domain, which reduces crossover of signal between material images. Two algorithms based on this process are presented: the Segmentation variant, which uses segmented material classes to define each sub-problem; and the Angular Rejection variant, which defines the rejection criteria using the angle between reconstructed attenuation vectors

Per-pixel energy calibration of photon counting detectors

Energy resolving performance of spectral CT systems is influenced by the accuracy of the detector's energy calibration. Global energy calibration maps a given threshold to the average energy response of all pixels of the detector. Variations arising from CMOS manufacturing processes and properties of the sensor cause different pixels to respond differently to photons of the same energy. Threshold dispersion adversely affects spectral imaging by degrading energy resolution, which contributes to blurring of the energy information. In this paper, we present a technique for per-pixel energy calibration of photon-counting x-ray detectors (PCXDs) that quantifies the energy response of individual pixels relative to the average response. This technique takes advantage of the measurements made by an equalized chip. It uses a known global energy map to quantify the effect of threshold dispersion on the energy response of the detector pixels across an energy range of interest. The proposed technique was assessed using a MARS scanner with an equalized Medipix3RX chip flip-bonded to 2 mm thick CdTe semiconductor crystal at a pitch of 110 μ m. Measurements were made of characteristic x-rays of a molybdenum foil. Results were compared between the case that the global calibration was used on its own and the case of using it in conjunction with our per-pixel calibration technique. The proposed technique quantified up to 1.87 keV error in energy response of 100 pixels of a selected region of interest (ROI). It made an improvement of 28.3% in average FWHM. The additional information provided by this per-pixel calibration technique can be used to improve spectral reconstruction

MARS-MD: Rejection based image domain material decomposition

This paper outlines image domain material decomposition algorithms that have been routinely used in MARS spectral CT systems. These algorithms (known collectively as MARS-MD) are based on a pragmatic heuristic for solving the under-determined problem where there are more materials than energy bins. This heuristic contains three parts: (1) splitting the problem into a number of possible sub-problems, each containing fewer materials; (2) solving each sub-problem; and (3) applying rejection criteria to eliminate all but one sub-problem's solution. An advantage of this process is that different constraints can be applied to each sub-problem if necessary. In addition, the result of this process is that solutions will be sparse in the material domain, which reduces crossover of signal between material images. Two algorithms based on this process are presented: the Segmentation variant, which uses segmented material classes to define each sub-problem; and the Angular Rejection variant, which defines the rejection criteria using the angle between reconstructed attenuation vectors

Oblique fluorescence in a MARS scanner with a CdTe-Medipix3RX

The latest version of the MARS small bore scanner makes use of the Medipix3RX ASIC, bonded to a CdTe or CZT semi-conductor layer, to count x-ray photons and create a spectroscopic CT data set. The MARS imaging chain uses the energy-resolved 2D transmission images to construct quantitative 3D spectral and material images. To improve the spectral performance of the imaging system it is important that the energy response of the detector is well calibrated. A common methodology for energy calibration is to use x-ray fluorescence (XRF), due to its effective monochromatic nature. Oblique (off-axis) XRF can be measured in situ in the MARS small bore scanner. A monoatomic foil is placed in front of the x-ray source and off-axis XRF is measured. A key issue is identifying near optimal measurement positions that maximize the XRF signal while minimizing transmitted and scattered x-rays from the primary beam. This work shows the development of a theoretical model that is able to identify where in the detector plane XRF is maximum. We present: (1) a theoretical model that calculates the XRF photon distribution across the detector plane produced from illuminated foils attached to the scanner's filter bar, (2) preliminary experimental measurements of the XRF distribution outside of the main beam taken with a CdTe-Medipix3RX detector, and (3) a comparison between the model and experiment. The main motivation behind creating this model is to identify the region in the detector plane outside of the main beam where XRF is at a maximum. This provides the optimum detector location for measuring a monochromatic XRF source with minimal polychromatic contamination for its use in per-pixel energy calibration of Medipix3RX detectors in MARS scanners