The attenuation-contrast mechanism underlying clinical and pre-clinical x-ray imaging has remained essentially the same since Roentgen’s revolutionary discovery. As a consequence, improvements in image contrast resolution are limited by the required increase in radiation dose. Alternatively, the phase-contrast mechanism, using the wave nature of the x-ray beam, is sensitive to the refractive index of the tissue rather than the attenuation coefficient. Since many soft tissues have quite different refractive indices but very similar attenuation coefficients, phase contrast imaging provides a thousand-fold improvement in contrast resolution with lower radiation dose. This has numerous major biomedical applications, such as x-ray phase-contrast in vitro characterization, small animal imaging, and mammography.
X-ray phase imaging with a synchrotron radiation source provides outstanding soft tissue contrast and information on a par with histological staining methods. Phase imaging is usually conducted with a synchrotron radiation source or a micro-focus tube. Synchrotron sources, of which there are fewer than 30 worldwide, require multi-million-dollar facilities. Micro-focus sources, while significantly less expensive, are severely limited by anode heating and have long imaging times, yet are unable to compete with synchrotron sources in terms of image quality. In 2006, Pfeiffer et al. reported groundbreaking results that x-ray phase-contrast imaging can be done using a hospital-grade x-ray tube instead of a synchrotron facility or micro-focus tube. The design, as a novel application of the Talbot effect, uses three gratings to produce coherent wavelets from a hospital-grade x-ray tube, construct interference patterns at an appropriate distance, extract the differential phase of wave-fronts distorted by an object irradiated by these wavelets, and finally form phase-contrast images in terms of the refractive index.
Recognizing the great potential of their work as the foundation of a less expensive and smaller in vitro and preclinical imaging system, supported by internal funding from Dr. Wang’s institution and in a newly established collaboration with NIST’s neutron phase imaging group (see Dr. Arif’s Letter), we are close to completing a 1D grating-based x-ray imaging platform as described in C.1. This revised proposal is to upgrade the current 1D-grating-based system with 2D-gratings to provide imaging performance similar to that obtained with a synchrotron source, but in an exceedingly cost-effective manner. The general hypothesis is that 2D grating-based phase-contrast imaging techniques can be developed to produce more accurate and robust phase-contrast images of biomedical interest than the competing 1D techniques. The overall goal is to develop the 2D-grating-based x-ray phase-contrast technology into a preclinical imaging tool. The specific aims are as follows.
Specific Aim 1 – Theory & Methods: Develop novel theory and methods for 2D grating-based x-ray phase-contrast imaging. Task 1.1 – Forward Modeling: The forward model for 2D grating-based x-ray phase-contrast imaging will be formulated. Initially, only a weakly absorbing object is considered. Then, the model will be refined to take absorption and scattering into account. Task 1.2 – Inversion Schemes: Based on the forward model, phase retrieval and tomographic reconstruction algorithms will be developed. Practical factors will be taken into account such as system calibration, data preprocessing and computational efficiency.
Specific Aim 2 – System Prototyping: Prototype a 2D-grating-based imaging platform for projective and tomographic imaging. Task 2.1 – 1D-grating-based Configuration: Initially, we will complete the development of our current 1D grating-based phase-contrast imaging system to produce a flexible imaging platform for further R&D. Task 2.2 – 2D-grating-based Configuration: The current 1D-gratings will be replaced by chessboard-like 2D-gratings for extraction of phase information more accurately and robustly than the 1D grating-based system. The entire system will be calibrated and optimized for the highest signal-to-noise ratio and best image quality. Testing, operation and quality assurance procedures will be developed and documented.
Specific Aim 3 – Validation & Application: Evaluate and validate the proposed technology, and demonstrate its utility for in vitro imaging. Task 3.1 – Simulation Studies: The proposed techniques will be evaluated in numerical simulation and validated in phantom experiments with respect to phantom specifications and imaging parameters. Key image quality measures will be determined. Task 3.2 – In vitro Studies: The proposed technology will be applied to in vitro studies with an emphasis on spatial and contrast resolution for visualization of atherosclerotic plaques in vessels from an existing mouse model of differential diet. The imaging results will be compared to their counterparts acquired using state of the art histology, micro-CT and micro-MRI. The data will be systematically analyzed for statistical significance.