Reduced acquisition time for L-shell x-ray fluorescence computed tomography using polycapillary x-ray optics.

PURPOSE: X-ray fluorescence computed tomography (XFCT) is an emerging molecular imaging modality for preclinical and clinical applications with high atomic number contrast agents. XFCT allows detection of molecular biomarkers at tissue depths of 4-9 mm at L-shell energies and several centimeters for K-shell energies, while maintaining high spatial resolution. This is typically not possible for other molecular imaging modalities. The purpose of this study is to demonstrate XFCT imaging with reduced acquisition times. To accomplish this, x-ray focusing polycapillary optics are utilized to simultaneously increase x-ray fluence rate and spatial resolution in L-shell XFCT imaging. MATERIALS AND METHODS: A prototype imaging system using a polycapillary focusing optic was demonstrated. The optic, which was custom-designed for this prototype, provided a high fluence rate with a focal spot size of 2.6 mm at a source to isocenter distance of 3 cm with a ten times higher fluence rate compared to standard collimation. The study evaluates three different phantoms to explore different trade-offs and limitations of L-shell XFCT imaging. A low-contrast gold phantom and a high-contrast gold phantom, each with three target regions with gold concentrations of 60, 80, and 100 µg ml - 1 for low contrast and 200, 600, and 1000 µg ml - 1 for high contrast, and a mouse-sized water phantom with gold concentrations between 300 and 500 µg ml - 1 were imaged. X-ray fluorescence photons were measured using a silicon drift detector (SDD) with an energy resolution of 180 eV FWHM at an x-ray energy of 11 keV. Images were reconstructed with an iterative image reconstruction algorithm and analyzed for contrast to noise ratio (CNR) and signal to noise ratio (SNR). RESULTS: The XFCT data acquisition could be reduced from 17 h to under 1 h. The polycapillary x-ray optic increases the x-ray fluence rate and lowers the amount of background scatter which leads to reduced imaging time and improved sensitivity. The quantitative analysis of the reconstructed images validates that concentrations of 60 µg ml - 1 of gold can be visualized with L-shell XFCT imaging. For a mouse-sized phantom, a concentration of 300 µg ml - 1 gold was detected within a 66 min measurement. CONCLUSIONS: With a high fluence rate pencil beam from a polycapillary x-ray source, a reduction in signal integration time is achieved. It is presented that subtle amounts of contrast agents can be detected with L-shell XFCT within biologically relevant time frames. Our basic measurements show that the polycapillary x-ray source technology is appropriate to realize preclinical L-shell XFCT imaging. The integration of more SDDs into the system will lower the dose and increase the sensitivity.

Coded-Aperture Compressed Sensing X-Ray Luminescence Tomography.

OBJECTIVE: The purpose of this work is to introduce and study a novel imaging geometry for X-ray luminescence computed tomography (XLCT), termed coded aperture compressive X-ray luminescence tomography (CAC-XLCT). METHODS: CAC-XLCT is studied through simulations of X-ray and diffuse light propagation and the implementation of a compressed sensing image reconstruction algorithm. RESULTS: CAC-XLCT is compared against cone beam XLCT considering simulated targets with varying complexity, and it is found to offer a remarkable enhancement in spatial resolution and image quality with only a small overhead in image acquisition time. CONCLUSIONS AND SIGNIFICANCE: XLCT has been mainly investigated so far in pencil beam and cone beam excitation geometries which suffer from either very long image acquisition time or low spatial resolution and accuracy. CAC-XLCT presents a very promising alternative, which can offer simultaneously high spatial resolution, high image quality, and fast image acquisition, appropriate for in vivo imaging.

Polarized x-ray excitation for scatter reduction in x-ray fluorescence computed tomography.

PURPOSE: X-ray fluorescence computer tomography (XFCT) is a new molecular imaging modality which uses x-ray excitation to stimulate the emission of fluorescent photons in high atomic number contrast agents. Scatter contamination is one of the main challenges in XFCT imaging which limits the molecular sensitivity. When polarized x rays are used, it is possible to reduce the scatter contamination significantly by placing detectors perpendicular to the polarization direction. This study quantifies scatter contamination for polarized and unpolarized x-ray excitation and determines the advantages of scatter reduction. METHODS: The amount of scatter in preclinical XFCT is quantified in Monte Carlo simulations. The fluorescent x rays are emitted isotropically, while scattered x rays propagate in polarization direction. The magnitude of scatter contamination is studied in XFCT simulations of a mouse phantom. In this study, the contrast agent gold is examined as an example, but a scatter reduction from polarized excitation is also expected for other elements. The scatter reduction capability is examined for different polarization intensities with a monoenergetic x-ray excitation energy of 82 keV. The study evaluates two different geometrical shapes of CZT detectors which are modeled with an energy resolution of 1 keV FWHM at an x-ray energy of 80 keV. Benefits of a detector placement perpendicular to the polarization direction are shown in iterative and analytic image reconstruction including scatter correction. The contrast to noise ratio (CNR) and the normalized mean square error (NMSE) are analyzed and compared for the reconstructed images. RESULTS: A substantial scatter reduction for common detector sizes was achieved for 100% and 80% linear polarization while lower polarization intensities provide a decreased scatter reduction. By placing the detector perpendicular to the polarization direction, a scatter reduction by factor up to 5.5 can be achieved for common detector sizes. The image reconstruction showed that for a scatter magnitude decrease by a factor of 2.4, the molecular sensitivity could almost be doubled. CONCLUSION: Scatter reduction lowers the amount of noise in the projection datasets and reconstructed images which enhance molecular sensitivity at equal dose. The results support the use of linear polarized x rays to reduce scatter in XFCT imaging.

A unified material decomposition framework for quantitative dual- and triple-energy CT imaging.

PURPOSE: Many clinical applications depend critically on the accurate differentiation and classification of different types of materials in patient anatomy. This work introduces a unified framework for accurate nonlinear material decomposition and applies it, for the first time, in the concept of triple-energy CT (TECT) for enhanced material differentiation and classification as well as dual-energy CT (DECT). METHODS: We express polychromatic projection into a linear combination of line integrals of material-selective images. The material decomposition is then turned into a problem of minimizing the least-squares difference between measured and estimated CT projections. The optimization problem is solved iteratively by updating the line integrals. The proposed technique is evaluated by using several numerical phantom measurements under different scanning protocols. The triple-energy data acquisition is implemented at the scales of micro-CT and clinical CT imaging with commercial "TwinBeam" dual-source DECT configuration and a fast kV switching DECT configuration. Material decomposition and quantitative comparison with a photon counting detector and with the presence of a bow-tie filter are also performed. RESULTS: The proposed method provides quantitative material- and energy-selective images examining realistic configurations for both DECT and TECT measurements. Compared to the polychromatic kV CT images, virtual monochromatic images show superior image quality. For the mouse phantom, quantitative measurements show that the differences between gadodiamide and iodine concentrations obtained using TECT and idealized photon counting CT (PCCT) are smaller than 8 and 1 mg/mL, respectively. TECT outperforms DECT for multicontrast CT imaging and is robust with respect to spectrum estimation. For the thorax phantom, the differences between the concentrations of the contrast map and the corresponding true reference values are smaller than 7 mg/mL for all of the realistic configurations. CONCLUSIONS: A unified framework for both DECT and TECT imaging has been established for the accurate extraction of material compositions using currently available commercial DECT configurations. The novel technique is promising to provide an urgently needed solution for several CT-based diagnostic and therapy applications, especially for the diagnosis of cardiovascular and abdominal diseases where multicontrast imaging is involved.

Synergistically Enhancing the Therapeutic Effect of Radiation Therapy with Radiation Activatable and Reactive Oxygen Species-Releasing Nanostructures.

Nanoparticle-based radio-sensitizers can amplify the effects of radiation therapy on tumor tissue even at relatively low concentrations while reducing the potential side effects to healthy surrounding tissues. In this study, we investigated a hybrid anisotropic nanostructure, composed of gold (Au) and titanium dioxide (TiO2), as a radio-sensitizer for radiation therapy of triple-negative breast cancer (TNBC). In contrast to other gold-based radio sensitizers, dumbbell-like Au-TiO2 nanoparticles (DATs) show a synergistic therapeutic effect on radiation therapy, mainly because of strong asymmetric electric coupling between the high atomic number metals and dielectric oxides at their interfaces. The generation of secondary electrons and reactive oxygen species (ROS) from DATs triggered by X-ray irradiation can significantly enhance the radiation effect. After endocytosed by cancer cells, DATs can generate a large amount of ROS under X-ray irradiation, eventually inducing cancer cell apoptosis. Significant tumor growth suppression and overall improvement in survival rate in a TNBC tumor model have been successfully demonstrated under DAT uptake for a radio-sensitized radiation therapy.

Feasibility study of Compton cameras for x-ray fluorescence computed tomography with humans.

X-ray fluorescence imaging is a promising imaging technique able to depict the spatial distributions of low amounts of molecular agents in vivo. Currently, the translation of the technique to preclinical and clinical applications is hindered by long scanning times as objects are scanned with flux-limited narrow pencil beams. The study presents a novel imaging approach combining x-ray fluorescence imaging with Compton imaging. Compton cameras leverage the imaging performance of XFCT and abolish the need for pencil beam excitation. The study examines the potential of this new imaging approach on the base of Monte-Carlo simulations. In the work, it is first presented that the particular option of slice/fan-beam x-ray excitation has advantages in image reconstruction in regard of processing time and image quality compared to traditional volumetric Compton imaging. In a second experiment, the feasibility of the approach for clinical applications with tracer agents made from gold nano-particles is examined in a simulated lung scan scenario. The high energy of characteristic x-ray photons from gold is advantageous for deep tissue penetration and has lower angular blurring in the Compton camera. It is found that Doppler broadening in the first detector stage of the Compton camera adds the largest contribution on the angular blurring; physically limiting the spatial resolution. Following the analysis of the results from the spatial resolution test, resolutions in the order of one centimeter are achievable with the approach in the center of the lung. The concept of Compton imaging allows one to distinguish to some extent between scattered photons and x-ray fluorescent photons based on their difference in emission position. The results predict that molecular sensitivities down to 240 pM l-1 for 5 mm diameter lesions at 15 mGy for 50 nm diameter gold nano-particles are achievable. A 45-fold speed up time for data acquisition compared to traditional pencil beam XFCT could be achieved for lung imaging at the cost of a small sensitivity decrease.

A model-based scatter artifacts correction for cone beam CT.

PURPOSE: Due to the increased axial coverage of multislice computed tomography (CT) and the introduction of flat detectors, the size of x-ray illumination fields has grown dramatically, causing an increase in scatter radiation. For CT imaging, scatter is a significant issue that introduces shading artifact, streaks, as well as reduced contrast and Hounsfield Units (HU) accuracy. The purpose of this work is to provide a fast and accurate scatter artifacts correction algorithm for cone beam CT (CBCT) imaging. METHODS: The method starts with an estimation of coarse scatter profiles for a set of CBCT data in either image domain or projection domain. A denoising algorithm designed specifically for Poisson signals is then applied to derive the final scatter distribution. Qualitative and quantitative evaluations using thorax and abdomen phantoms with Monte Carlo (MC) simulations, experimental Catphan phantom data, and in vivo human data acquired for a clinical image guided radiation therapy were performed. Scatter correction in both projection domain and image domain was conducted and the influences of segmentation method, mismatched attenuation coefficients, and spectrum model as well as parameter selection were also investigated. RESULTS: Results show that the proposed algorithm can significantly reduce scatter artifacts and recover the correct HU in either projection domain or image domain. For the MC thorax phantom study, four-components segmentation yields the best results, while the results of three-components segmentation are still acceptable. The parameters (iteration number K and weight ß) affect the accuracy of the scatter correction and the results get improved as K and ß increase. It was found that variations in attenuation coefficient accuracies only slightly impact the performance of the proposed processing. For the Catphan phantom data, the mean value over all pixels in the residual image is reduced from -21.8 to -0.2 HU and 0.7 HU for projection domain and image domain, respectively. The contrast of the in vivo human images is greatly improved after correction. CONCLUSIONS: The software-based technique has a number of advantages, such as high computational efficiency and accuracy, and the capability of performing scatter correction without modifying the clinical workflow (i.e., no extra scan/measurement data are needed) or modifying the imaging hardware. When implemented practically, this should improve the accuracy of CBCT image quantitation and significantly impact CBCT-based interventional procedures and adaptive radiation therapy.