Craig S. Levin

Calculation of positron range and its effect on the fundamental limit of positron emission tomography system spatial resolution.

Developments in positron emission tomography (PET) technology have resulted in systems with finer detector elements designed to further improve spatial resolution. However, there is a limit to what extent reducing detector element size will improve spatial resolution in PET. The spatial resolution of PET imaging is limited by several other factors, such as annihilation photon non-collinearity, positron range, off-axis detector penetration, detector Compton scatter, undersampling of the signal in the linear or angular directions for the image reconstruction process, and patient motion. The overall spatial resolution of the systems is a convolution of these components. Of these other factors that contribute to resolution broadening, perhaps the most uncertain, poorly understood, and, for certain isotopes, the most dominant effect is from positron range. To study this latter effect we have developed a Monte Carlo simulation code that models positron trajectories and calculates the distribution of the end point coordinates in water for the most common PET isotopes used: 18F, 13N, 11C and 15O. In this work we present some results from these positron trajectory studies and calculate what effect positron range has on the overall PET system spatial resolution, and how this influences the choice of PET system design parameters such as detector element size and system diameter. We found that the fundamental PET system spatial resolution limit set from detector size, photon non-collinearity and positron range alone varied from nearly 1 mm FWHM (2 mm FWTM) for a 10-20 cm diameter system typical for animal studies with 18F to roughly 4 mm FWHM (7 mm FWTM) for an 80 cm diameter system typical for human imaging using 15O.

Primer on molecular imaging technology

A wide range of technologies is available for in vivo, ex vivo, and in vitro molecular and cellular imaging. This article focuses on three key in vivo imaging system instrumentation technologies used in the molecular imaging research described in this special issue of Eur J Nucl Med Mol Imaging: positron emission tomography, single-photon emission computed tomography, and bioluminescence imaging. For each modality, the basics of how it works, important performance parameters, and the state-of-the-art instrumentation are described. Comparisons and integration of multiple modalities are also discussed. The principles discussed in this article apply to both human and small animal imaging.

Fast, Accurate and Shift-Varying Line Projections for Iterative Reconstruction Using the GPU

List-mode processing provides an efficient way to deal with sparse projections in iterative image reconstruction for emission tomography. An issue often reported is the tremendous amount of computation required by such algorithm. Each recorded event requires several back- and forward line projections. We investigated the use of the programmable graphics processing unit (GPU) to accelerate the line-projection operations and implement fully-3D list-mode ordered-subsets expectation-maximization for positron emission tomography (PET). We designed a reconstruction approach that incorporates resolution kernels, which model the spatially-varying physical processes associated with photon emission, transport and detection. Our development is particularly suitable for applications where the projection data is sparse, such as high-resolution, dynamic, and time-of-flight PET reconstruction. The GPU approach runs more than 50 times faster than an equivalent CPU implementation while image quality and accuracy are virtually identical. This paper describes in details how the GPU can be used to accelerate the line projection operations, even when the lines-of-response have arbitrary endpoint locations and shift-varying resolution kernels are used. A quantitative evaluation is included to validate the correctness of this new approach.

Design of a high-resolution and high-sensitivity scintillation crystal array for PET with nearly complete light collection

Spatial resolution improvements in positron emission tomography (PET) can be achieved by developing detector arrays with finer resolution elements. To maintain high sensitivity and image quality, the challenge is to develop a finely pixellated scintillation crystal array with both high detection efficiency and high light collection. High detection efficiency means the crystals must be relatively long and tightly packed. Extracting a high fraction of the available scintillation light from the ends of long and skinny crystals proves to be very difficult and there is a strong variation with light source depth. The result is inadequate energy resolution. To facilitate light collection, the crystals must be highly polished, which significantly increases costs and complexity. In this paper, we examine this poor light collection phenomenon in more detail. We also describe a novel solution we are developing for readout of an array of 1 mm crystals using avalanche photodiodes (APD). We demonstrate through optical photon tracking simulations that the crystal light collection for this new design is nearly perfect (/spl ges/ 95 %) and is independent of the crystal length, width, and surface treatment and origin of the light created.

A Monte Carlo correction for the effect of Compton scattering in 3-D PET brain imaging

A Monte Carlo simulation has been developed to simulate and correct for the effect of Compton scatter in 3-D acquired PET brain scans. The method utilizes the 3-D reconstructed image volume as the source intensity distribution for a photon-tracking Monte Carlo simulation. It is assumed that the number of events in each pixel of the image represents the isotope concentration at that location in the brain. The history of each annihilation photons interactions in the scattering medium is followed, and the sinograms for the scattered and unscattered photon pairs are generated in a simulated 3-D PET acquisition. The calculated scatter contribution is used to correct the original data set. The method is general and can be applied to any scanner configuration or geometry. In its current form the simulation requires 25 hours on a single Sparc10 CPU when every pixel in a 15-plane, 128/spl times/128 pixel image volume is sampled, and less than 2 hours when 16 pixels (4/spl times/4) are grouped as a single pixel. Results of the correction applied to 3-D human and phantom studies are presented. >

A comparison of PET detector modules employing rectangular and round photomultiplier tubes

We have compared the high resolution BGO detector blocks from the EXACT HR PET system which use two dual-cathode rectangular photomultiplier (PM) tubes with a new block design, the EXACT HR PLUS, which uses four round PM tubes. Despite the lower coupling area between photocathode and scintillator, the HR PLUS block compares favorably with the HR block. The energy resolution averages 20% for the HR PLUS block and 23% for the HR block, with efficiency variations of 17% in both blocks. Additional measurements were carried out on the HR PLUS block to characterize depth of interaction effects and cross-talk between elements. Coincidence line spread function measurements had a FWHM of 3.0 mm in the axial direction and 2.9 mm in the transaxial direction. In light of these results, limitations of the BGO block design are discussed and some solutions proposed. >

Investigation of position sensitive avalanche photodiodes for a new high-resolution PET detector design

We are developing a high-resolution PET detector design with a goal of nearly complete scintillation light collection in /spl les/1 mm width, /spl ges/20 mm effective thickness LSO crystals. The design uses position sensitive avalanche photodiodes in novel layered configurations that significantly improve the light collection aspect ratio. To reduce design complexity and dead area we are investigating the use of 1 mm thick sheets of LSO in addition to discrete crystal rods, and the use of PSAPDs which require only four readout channels per device. The raw spatial response of a 1 mm thick crystal sheet coupled to a PSAPD exhibits a compressed dynamic range compared to that observed with discrete crystals. Measurements with the proposed configurations using /sup 22/Na irradiation achieved 10%-13% FWHM energy resolution at 511 keV and 2 ns coincidence time resolution. 1 mm width crystals with a saw cut surface finish an no inter-crystal reflector were well resolved in flood images.

Optimizing timing performance of silicon photomultiplier-based scintillation detectors

Precise timing resolution is crucial for applications requiring time-of-flight (ToF) information such as ToF positron emission tomography (PET). Silicon photomulipliers (SiPM) for PET, with their high output capacitance, are known to require custom preamplifiers to maximize timing performance. In this paper, we prove that simple alternative front-end electronics based on a commercial low-noise RF preamplifier can achieve excellent timing resolution. Two radiation detectors with L(Y)SO:Ce scintillators coupled to Hamamatsu SiPMs (MPPC S10362-33-050C) and front-end electronics based on an RF amplifier (MAR-3SM+), have been fabricated. These detectors were used to detect annihilation gamma photons from a Ge-68 source and the output signals were subsequently digitized by a high speed oscilloscope for offline processing. A coincident resolving time (CRT) of 125 ± 2 ps, 147 ± 3 ps and 186 ± 3 ps FWHM with 2 × 2 × 3 mm3 3 × 3 × 5 mm3 and 3 × 3 × 20 mm3 sized L(Y)SO crystals were measured respectively.

New Imaging Technologies to Enhance the Molecular Sensitivity of Positron Emission Tomography

Positron emission tomography (PET) is used in the clinic and in vivo small animal research to study certain molecular processes associated with diseases such as cancer, heart disease, and neurological disorders and guide the discovery and development of new treatments. New PET molecular probes and associated small animal imaging assays are under development to target, visualize, and quantify subtle molecular and cellular processes such as protein-protein interactions in signal transduction pathways, cancer cell trafficking, therapeutic stem cells and their progeny, interaction of the immune system and tumor cells, and gene delivery and expression in living animals. These next-generation PET molecular imaging assays require an order of magnitude increase in PETs ability to detect, visualize, and quantify low concentrations of probe interacting with its target, which we will refer to as molecular sensitivity , in order to study the subtle signatures associated with these molecular processes. The molecular sensitivity is determined by a combination of the probe and biological/physiological properties of the subject that determine its specificity for the target, and the performance capabilities of the imaging system that determine how well the resulting signal can be measured. This paper focuses on the second aspect: the challenges of advancing PET technology and some of the new imaging system technologies under investigation to substantially enhance PETs molecular sensitivity. If successful, these novel imaging system technology advances, together with new probe molecules that target specific molecular processes associated with disease, will substantially enhance the molecular sensitivity of PET and thus increase its role in preclinical and clinical research as well as evaluating and managing disease in the clinic.

First Performance Results of Ce:GAGG Scintillation Crystals With Silicon Photomultipliers

A new single-crystal Cerium doped Gd₃Al₂Ga₃ O₁₂₃Al₂Ga₃ O₁₂ (GAGG) scintillation crystal with high luminosity, high density and relatively fast decay time has successfully been grown. We report on the first performance results of the new GAGG scintillation crystal read out with silicon photomultipliers (SiPM) from Hamamatsu (MPPC) and FBK. The best energy resolution (511 keV peak of Ge-68) of 7.9% was attained with GAGG coupled to MPPC and 9.0% with the FBK SiPM after correcting for non-linearity. On the other hand, the best coincidence resolving time (FWHM) of polished 3 × 3 × 5 mm³ and 3 × 3 × 20mm³crystals were 464 ±12 ps and 577 ±22 ps for GAGG crystals compared to 179 ±8 ps and 214 ±6 ps for LYSO crystals respectively with MPPCs. The rise time of GAGG was measured to be 200 ps (75%) and 6 ns (25%) while the decay time was 140 ns (92%), 500 ns (7.7%) 6000 ns (0.3%).