Ali Douraghy

Source Reconstruction for Spectrally-resolved Bioluminescence Tomography with Sparse A priori Information

Through restoration of the light source information in small animals in vivo, optical molecular imaging, such as fluorescence molecular tomography (FMT) and bioluminescence tomography (BLT), can depict biological and physiological changes observed using molecular probes. A priori information plays an indispensable role in tomographic reconstruction. As a type of a priori information, the sparsity characteristic of the light source has not been sufficiently considered to date. In this paper, we introduce a compressed sensing method to develop a new tomographic algorithm for spectrally-resolved bioluminescence tomography. This method uses the nature of the source sparsity to improve the reconstruction quality with a regularization implementation. Based on verification of the inverse crime, the proposed algorithm is validated with Monte Carlo-based synthetic data and the popular Tikhonov regularization method. Testing with different noise levels and single/multiple source settings at different depths demonstrates the improved performance of this algorithm. Experimental reconstruction with a mouse-shaped phantom further shows the potential of the proposed algorithm.

Spectrally resolved bioluminescence tomography with the third-order simplified spherical harmonics approximation

Bioluminescence imaging has been extensively applied to in vivo small animal imaging. Quantitative three-dimensional bioluminescent source information obtained by using bioluminescence tomography can directly and much more accurately reflect biological changes as opposed to planar bioluminescence imaging. Preliminary simulated and experimental reconstruction results demonstrate the feasibility and promise of bioluminescence tomography. However, the use of multiple approximations, particularly the diffusion approximation theory, affects the quality of in vivo small animal-based image reconstructions. In the development of new reconstruction algorithms, high-order approximation models of the radiative transfer equation and spectrally resolved data introduce new challenges to the reconstruction algorithm and speed. In this paper, an SP(3)-based (the third-order simplified spherical harmonics approximation) spectrally resolved reconstruction algorithm is proposed. The simple linear relationship between the unknown source distribution and the spectrally resolved data is established in this algorithm. A parallel version of this algorithm is realized, making BLT reconstruction feasible for the whole body of small animals especially for fine spatial domain discretization. In simulation validations, the proposed algorithm shows improved reconstruction quality compared with diffusion approximation-based methods when high absorption, superficial sources and detection modes are considered. In addition, comparisons between fine and coarse mesh-based BLT reconstructions show the effects of numerical errors in reconstruction image quality. Finally, BLT reconstructions using in vivo mouse experiments further demonstrate the potential and effectiveness of the SP(3)-based reconstruction algorithm.

Experimental Bioluminescence Tomography with Fully Parallel Radiative-transfer-based Reconstruction Framework

Bioluminescence imaging is a very sensitive imaging modality, used in preclinical molecular imaging. However, in its planar projection form, it is non-quantitative and has poor spatial resolution. In contrast, bioluminescence tomography (BLT) promises to provide three dimensional quantitative source information. Currently, nearly all BLT reconstruction algorithms in use employ the diffusion approximation theory to determine light propagation in tissues. In this process, several approximations and assumptions that are made severely affect the reconstruction quality of BLT. It is therefore necessary to develop novel reconstruction methods using high-order approximation models to the radiative transfer equation (RTE) as well as more complex geometries for the whole-body of small animals. However, these methodologies introduce significant challenges not only in terms of reconstruction speed but also for the overall reconstruction strategy. In this paper, a novel fully-parallel reconstruction framework is proposed which uses a simplified spherical harmonics approximation (SPN). Using this framework, a simple linear relationship between the unknown source distribution and the surface measured photon density can be established. The distributed storage and parallel operations of the finite element-based matrix make SPN-based spectrally resolved reconstruction feasible at the small animal whole body level. Performance optimization of the major steps of the framework remarkably improves reconstruction speed. Experimental reconstructions with mouse-shaped phantoms and real mice show the effectiveness and potential of this framework. This work constitutes an important advance towards developing more precise BLT reconstruction algorithms that utilize high-order approximations, particularly second-order self-adjoint forms to the RTE for in vivo small animal experiments.

FPGA electronics for OPET: A dual-modality optical and positron emission tomograph

The development of a prototype dual-modality optical and PET (OPET) small animal imaging tomograph is underway in the Crump Institute for Molecular Imaging at the University of California Los Angeles. OPET consists of a single ring of six detector modules with a diameter of 3.5 cm. Each detector has an 8 times 8 array of optically isolated BGO scintillators which are coupled to multichannel photomultiplier tubes and open on the front end. The system operates in either PET or optical mode and reconstructs the data sets as 3D tomograms. The detectors are capable of detecting both annihilation events (511 keV) from PET tracers as well as single photon events (SPEs) (2-3 eV) from bioluminescence. Detector channels are readout using a custom multiplex readout scheme and then filtered in analog circuitry using either a gamma-ray or SPE specific filter. Shaped pulses are sent to a digital signal processing (DSP) unit for event processing. The DSP unit has 100 MHz analog-to-digital converters on the front-end which send digitized samples to field programmable gate arrays which are programmed via user configurable algorithms to process PET coincidence events or bioluminescence SPEs. Information determined using DSP includes: event timing, energy determination-discrimination, position determination-lookup, and coincidence processing. Coincidence or SPE events are recorded to an external disk and minimal post processing is required prior to image reconstruction. Initial results from a two-detector version of OPET are shown for a PET phantom image reconstruction as well as for an optical mode acquisition. Projection images of an optical pattern placed on the front end of the detector module in the vicinity of a SPE source and positron emitting source are shown. Current work includes assembly of the full ring system and tomographic reconstruction of an optical source.

FPGA Electronics for OPET: A Dual-Modality Optical and Positron Emission Tomograph

The development of a prototype dual-modality optical and PET (OPET) small animal imaging tomograph is underway in the Crump Institute for Molecular Imaging at the University of California Los Angeles. OPET consists of a single ring of six detector modules with a diameter of 3.5 cm. Each detector has an 8times8 array of optically isolated BGO scintillators which are coupled to multichannel photomultiplier tubes and open on the front end. The system operates in either PET or optical mode and reconstructs the data sets as 3D tomograms. The detectors are capable of detecting both annihilation events (511 keV) from PET tracers as well as single photon events (SPEs) (2-3 eV) from bioluminescence. Detector channels are readout using a custom multiplex readout scheme and then filtered in analog circuitry using either a gamma-ray or SPE specific filter. Shaped pulses are sent to a digital signal processing (DSP) unit for event processing. The DSP unit has 100 MHz analog-to-digital converters on the front-end which send digitized samples to field programmable gate arrays which are programmed via user configurable algorithms to process PET coincidence events or bioluminescence SPEs. Information determined using DSP includes: event timing, energy determination-discrimination, position determination-lookup, and coincidence processing. Coincidence or SPE events are recorded to an external disk and minimal post processing is required prior to image reconstruction. Initial imaging results from a phantom filled with 18FDG solution and an optical pattern placed on the front end of a detector module in the vicinity of a SPE source are shown.

Performance Characteristics of BGO Detectors for a Low Cost Preclinical PET Scanner

PETbox is a low-cost benchtop PET scanner dedicated to high throughput preclinical imaging that is currently under development at our institute. This paper presents the design and characterization of the detectors that are used in the PETbox system. In this work, bismuth germanate scintillator was used for the detector, taking advantage of its high stopping power, high photoelectric event fraction, lack of intrinsic background radiation and low cost. The detector block was segmented into a pixelated array consisting of 20 × 44 elements, with a crystal pitch of 2.2 mm and a crystal cross section of 2 mm × 2 mm. The effective area of the array was 44 mm × 96.8 mm. The array was coupled to two Hamamatsu H8500 position sensitive photomultiplier tubes, forming a flat-panel type detector head with a sensitive area large enough to cover the whole body of a typical laboratory mouse. Two such detector heads were constructed and their performance was characterized. For one detector head, the energy resolution ranged from 16.1% to 38.5% full width at half maximum (FWHM), with a mean of 20.1%; for the other detector head, the energy resolution ranged from 15.5% to 42.7% FWHM, with a mean of 19.6 %. The intrinsic spatial resolution was measured to range from 1.55 mm to 2.39 mm FWHM along the detector short axis and from 1.48 mm to 2.33 mm FWHM along the detector long axis, with an average of 1.78 mm. Coincidence timing resolution for the detector pair was measured to be 4.1 ns FWHM. These measurement results show that the detectors are suitable for our specific application.

A facile route to bulk high-Z polymer composites for gamma ray scintillation

Two classes of bulk high-Z polymer composites were prepared, which exhibit scintillation properties for gamma-radiation detection.

Performance evaluation of PETbox: A low cost bench top PET scanner dedicated to high throughput preclinical imaging

PETbox is designed to be a low cost and easy to use bench top small animal PET scanner dedicated for high throughput quantitative pharmacokinetic and pharmacodynamic studies. To achieve this goal, the scanner is integrated with a complete animal management system that provides life support including reproducible positioning, temperature control, anesthesia, real-time monitoring of animal respiration and a pathogen barrier. This approach minimizes the overall cost and complexity of preclinical PET imaging and should enable non-imaging scientists to embrace the technology. The system uses two opposing detector heads, each one consisting of a pixilated BGO array coupled to two H8500 multi-channel photomultiplier tubes. The BGO crystals were segmented into 20 ? 44 arrays with a pixel pitch of 2.2 mm and a total active area of 44 mm ? 96.8 mm. Position and timing signals from the photomultiplier tube readout circuitry were connected to a field programmable gate array (FPGA) board with eight ADC channels, each running at 100 MHz. Signal processing algorithms were developed for the FPGA to process received PET events and raw list-mode data were generated by the FPGA board and transferred to a host PC for storage. Basic system performance parameters were measured. The system has an average intrinsic spatial resolution of 1.72 mm FWHM along detector long axis and 1.84 mm FWHM along detector short axis. The coincidence timing resolution was measured to be 4.1 ns FWHM. The average energy resolution of the crystals was 19.8% and the absolute sensitivity of the system was measured to be 3.8% at the center of the gantry. Initial imaging studies were also performed with live mice. A mouse tumor xenograft was imaged 1 hour after a 32uCi [18F]FDG injection for 20 minutes. 3D images were generated using a ML-EM method. Results demonstrate the capability and potential of the PETbox system for dedicated high throughput mouse studies such as biodistribution and organ uptake quantification.

System Performance of OPET: A Combined Optical and PET Imaging System

OPET is an imaging system that detects both highenergy γ-rays and optical wavelength photons. This system is capable of non-invasively and repeatedly imaging small animal models in-vivo for the presence of γ-rays from PET tracers and optical signals from bioluminescence. OPET consists of six detector modules arranged to form a ring with a bore diameter of 3.5cm, where each module is made up of a 64-channel multichannel photomultiplier tube (PMT) coupled to an 8×8 BGO crystal array. The crystal lengths and widths are 2.15mm x 2.15mm respectively. The crystal heights vary along the face of the PMT such that the array presents a smooth curving profile. The front surface of the crystals is left open to allow optical wavelength photons to enter the detector module. A charge-division readout circuit is implemented to decode the signals from the 64 outputs of each PMT into four signals from which position information is obtained. These signals are amplified, shaped, and digitized, and finally processed using a field programmable gate array (FPGA). Flood images are used to obtain position look-up tables as well as pulse height spectra for each crystal in both PET and Optical mode operation. Basic system performance parameters have been measured for both operation modes of OPET including: sensitivity and count-rate performance. In PET mode the system has a sensitivity of 3.5% at the center of the field of view and an energy resolution around 36%. The sensitivity for optical wavelength photons was measured for each detector using a calibrated light source and varied from 0.6% to 2.0%. The maximum count rate in Optical mode is 106 cps per detector. The first dual-mode data acquisition of OPET was performed using a two chamber phantom. In one chamber was a set of six 0.8mm diameter rods filled with FDG, while the other chamber was filled with an enzyme and substrate used in bioluminescence studies of small animals. Images from both modes of operation are be presented.

Čerenkov radiation imaging as a method for quantitative measurements of beta particles in a microfluidic chip

This work proposes a novel method for quantitative imaging of radioactivity on microfluidic chips by using visible light emission from Cerenkov radiation. Cerenkov radiation is generated when charged particles travel through an optically transparent material with a velocity greater than that of light in that material. It has been observed at UCLA that microfluidic chips used for 18F-related radio-synthesis studies have shown unidentified visible light emissions. In this study, the origin of the light was investigated and its feasibility as a quantitative imaging source was tested.