Geng Fu

Experimental demonstration of novel imaging geometries for x‐ray fluorescence computed tomography

PURPOSE X-ray fluorescence computed tomography (XFCT) is an emerging imaging modality that maps the three-dimensional distribution of elements, generally metals, in ex vivo specimens and potentially in living animals and humans. At present, it is generally performed at synchrotrons, taking advantage of the high flux of monochromatic x rays, but recent work has demonstrated the feasibility of using laboratory-based x-ray tube sources. In this paper, the authors report the development and experimental implementation of two novel imaging geometries for mapping of trace metals in biological samples with ∼50-500 μm spatial resolution. METHODS One of the new imaging approaches involves illuminating and scanning a single slice of the object and imaging each slices x-ray fluorescent emissions using a position-sensitive detector and a pinhole collimator. The other involves illuminating a single line through the object and imaging the emissions using a position-sensitive detector and a slit collimator. They have implemented both of these using synchrotron radiation at the Advanced Photon Source. RESULTS The authors show that it is possible to achieve 250 eV energy resolution using an electron multiplying CCD operating in a quasiphoton-counting mode. Doing so allowed them to generate elemental images using both of the novel geometries for imaging of phantoms and, for the second geometry, an osmium-stained zebrafish. CONCLUSIONS The authors have demonstrated the feasibility of these two novel approaches to XFCT imaging. While they use synchrotron radiation in this demonstration, the geometries could readily be translated to laboratory systems based on tube sources.PURPOSE X-ray fluorescence computed tomography (XFCT) is an emerging imaging modality that maps the three-dimensional distribution of elements, generally metals, inex vivo specimens and potentially in living animals and humans. At present, it is generally performed at synchrotrons, taking advantage of the high flux of monochromatic x rays, but recent work has demonstrated the feasibility of using laboratory-based x-ray tube sources. In this paper, the authors report the development and experimental implementation of two novel imaging geometries for mapping of trace metals in biological samples with ∼50-500 μm spatial resolution. METHODS One of the new imaging approaches involves illuminating and scanning a single slice of the object and imaging each slices x-ray fluorescent emissions using a position-sensitive detector and a pinhole collimator. The other involves illuminating a single line through the object and imaging the emissions using a position-sensitive detector and a slit collimator. They have implemented both of these using synchrotron radiation at the Advanced Photon Source. RESULTS The authors show that it is possible to achieve 250 eV energy resolution using an electron multiplying CCD operating in a quasiphoton-counting mode. Doing so allowed them to generate elemental images using both of the novel geometries for imaging of phantoms and, for the second geometry, an osmium-stained zebrafish. CONCLUSIONS The authors have demonstrated the feasibility of these two novel approaches to XFCT imaging. While they use synchrotron radiation in this demonstration, the geometries could readily be translated to laboratory systems based on tube sources.

Investigation of the Intrinsic Spatial Resolution of an Intensified EMCCD Scintillation Camera

In this paper, we present an experimental and Monte Carlo investigation of the intrinsic spatial resolution that can be achieved with the intensified electron-multiplying charge-coupled device (I-EMCCD) gamma camera . This detector has a very low readout noise, an ultra-high spatial resolution and a large active area of ~ 80 mm diameter, which is well-suited for small animal imaging applications. The intrinsic detector resolutions achieved with different scintillators and under different experimental conditions were compared. In this study, the simple centroiding method was compared with two model-fitting approaches for finding the locations of gamma ray interactions. The results from Monte Carlo simulation have demonstrated that with an appropriate detector configuration, it is possible to achieve an intrinsic resolution of ~ 30 mum FWHM for detecting 27-35 keV gamma rays. The I-EMCCD scintillation camera offers a promising candidate for future ultra-high resolution SPECT imaging applications.

Design study of an MRI compatible ultra-high resolution SPECT for in vivo mice brain imaging

This paper presents the design study of an MRI compatible, ultra-high resolution SPECT system. This system consists of multiple ultra-high resolution energy-resolved photon counting (ERPC) CdTe detectors that are currently development. This detector is based on a novel readout ASIC that is roughly 1.1times2.2 cm2 in size and has a 32times64 array of 350times350 um2 pixels. A prototype detector was tested inside a 4.7 Tesla MRI scanner for simple pinhole imaging. The results obtained have demonstrated the feasibility of simultaneous acquisition of SPECT and MRI data. Extensive Monte Carlo simulation was performed to evaluate a number of system configurations.

X-ray fluorescence tomography using imaging detectors

This paper presents a feasibility study of using emission tomography (ET) systems for synchrotron X-ray fluorescence computer tomography (XFCT). The proposed detection system combines high-resolution semiconductor detectors with multiple-pinhole apertures. The key advantage of using an ET-based detection system is that 3D distributions of trace elements can be built up with much reduced scanning motion and potentially without need for tomographic reconstruction. In comparison to the conventional line-by-line scanning scheme, the ET-based imaging system allows a great reduction in imaging time, which has been one of the major hurdles for current XFCT studies. In order to compare different imaging schemes for XFCT studies, we developed an analytical performance index that is based on the fundamental tradeoffs between image noise and spatial resolution achievable with given detection configurations. To further demonstrate the feasibility of using SPECT apertures for XFCT, a prototype CCD-based multiple-pinhole imaging system was set up at the Advanced Photon Source (APS) for imaging phantoms that contain solutions of several trace metals. Simultaneously acquired 3D distributions of these elements are presented.

Aperture design for ultra-high resolution SPECT systems for small animal imaging

In this paper, we present the results from a design study for an ultra-high resolution SPECT system with various aperture designs. The system uses a recently developed ultrahigh resolution gamma camera based on an intensified Electron- multiplying Charge Coupled Device (EMCCD) sensor. It provides an intrinsic spatial resolution of < 60 mum and a high signal-to-noise ratio for imaging the 27-35 keV photons emitted by 1-125. The goal of present work is to optimize the multiple- pinhole aperture design for a stationary 4 headed SPECT system. The system is equipped with a variable aperture system that allows a large number of different aperture configurations to be used. In this study, we used the resolution-variance tradeoff as a performance index for selecting appropriate apertures for several imaging scenarios. A large number of apertures were compared with Monte Carlo simulations and experimental measurements.

A very-high resolution SPECT system based on the energy-resolved photon counting CdTe detectors

This paper presents preliminary experimental results obtained with a prototype SPECT system for small animal studies. This system is based on novel energy-resolved photon counting (ERPC) detectors we have recently developed for gamma ray imaging applications. The ERPC detector has basic modular configuration that offers an overall detection area of 4.5 cm × 4.5 cm, comprising of eight CdTe/CMOS detector hybrids. Each hybrid has a CdTe detector of 11 mm × 22 mm bump-bonded onto a dedicated readout ASIC that has 32 × 64 readout pixels with 350 μm pitch size. The 1mm and 2mm thickness CdTe detector have both been developed. This configuration offers a very-high spatial resolution of around 350 μm and an excellent energy resolution of around 3∼4 keV at 140 keV. The prototype SPECT system that consists of two or four ERPC detectors is mounted on a system gantry rotating around a horizontal axis. The detectors are coupled to apertures with differently sized pinholes. In order to utilize the imaging information provided by the ERPC detector, we have developed a comprehensive system modelling and calibration method that accounts for the irregular shapes and physical details in the collimation apertures. Detailed system design and experimental procedures will be described in this paper.

Accelerating X-ray fluorescence computed tomography

This paper presents new approaches to accelerating x-ray fluorescence tomography (XFCT) that are grounded in both novel image acquisition strategies that improve the quality of the data acquired and in image reconstruction strategies that reduce the amount of data acquired. First, we introduce an alternative imaging scheme that uses an emission tomography (ET) system to collect the fluorescence photons representing an entire 2D slice or volumetric projection of the object at one time. Preliminary results indicate that this could achieve a ten to hundredfold improvement in imaging speed. Secondly, novel image reconstruction algorithms are introduced that allow for improved quantitative accuracy as well as for imaging of regions of interest, which will lead to further reduction in data-acquisition time.

SPEM: a state-of-the-art instrument for high resolution molecular imaging of small animal organs

OBJECTIVE To describe the Single Photon Emission Microscope (SPEM), a state-of-the-art instrument for small animal SPECT imaging, and characterize its performance presenting typical images of different animal organs. METHODS SPEM consists of two independent imaging devices based on high resolution scintillators, high sensitivity and resolution Electron-Multiplying CCDs and multi-pinhole collimators. During image acquisition, the mouse is placed in a rotational vertical holder between the imaging devices. Subsequently, an appropriate software tool based on the Maximum Likelihood algorithm iteratively produces the volumetric image. Radiopharmaceuticals for imaging kidneys, heart, thyroid and brain were used. The mice were injected with 74 to 148 MBq/0,3mL and scanned for 40 to 80 minutes, 30 to 60 minutes afterwards. During this procedure, the animals remained under ketamine/xilazine anesthesia. RESULTS SPEM images of different mouse organs are presented, attesting the imaging capabilities of the instrument. CONCLUSION SPEM is an innovative technology for small animal SPECT imaging providing high resolution images with appropriate sensitivity for pre-clinical research. Its use with appropriate radiotracers will allow translational investigation of several animal models of human diseases, their pharmacological treatment and the development of potential new therapeutic agents.

Design and feasibility study of Gamma-Cube — a high resolution and high sensitivity SPECT system for in vivo mouse brain studies

In this paper, we report the design and feasibility study of a high resolution and high sensitivity SPECT (Gamma-Cube) system for mouse brain imaging. The system consists of six high resolution gamma ray detectors, arranged in cubic geometry, and a truncated spherical aperture with multiple pinholes, which offers a relatively uniform 4π angular coverage around the object. The proposed Gamma-Cube system is based on the so-called energy-resolved photon-counting (ERPC) detector that consists of multiple pixilated CdTe detectors bump-bonded to ERPC readout ASICs that are 1.1×2.2cm in size with a pixel pitch of 350μm×350μm. In this study, we used Monte Carlo simulation to optimize system geometry and multiple-pinhole patterns for detection of a tiny amount of radioactivity in mouse brain.

Least-square pinhole SPECT calibration using a forward projector modeling misalignment

Recent improvements in detector technology allow pinhole SPECT to approach spatial resolutions as low as 50 mum. Such high resolutions require a high accuracy of the imaging gantry for preclinical SPECT systems, and is not easily achieved in a laboratory setting. Analytical calibration methods are deemed to fail due to practical implications such as size and activity concentrations of the required point sources. Thus, we have developed a numerical calibration method based on least-square optimization that incorporates the modeling attributes of a forward projector frequently used in iterative reconstruction. The forward projector is currently capable of modeling detector misalignment such as detector rotation and pinhole translation, and will incorporate the pinhole point spread function as well as the size and shape of the point source. Currently, our calibration phantom consists of a single point source, positioned off-center in the object space. The optimization method involves a sequentially fitting of each individual parameter to the data, followed by fitting multiple parameters simultaneous in consecutive steps including all five parameters for the final fitting. The results of the optimization show an error of expected magnitude considering the relatively coarse sampling grid of our simulations. The relatively slow convergence of the y- and z-tilt require simulation of additional point sources. Further improvements of computational and memory efficiency need to be made, which enable the method to fit high resolution data as well as incorporation of the pinhole point spread function and the shape and size of the point sources.