Peter D. Olcott

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.

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.

Analog signal multiplexing for PSAPD-based PET detectors: simulation and experimental validation.

A 1 mm(3) resolution clinical positron emission tomography (PET) system employing 4608 position-sensitive avalanche photodiodes (PSAPDs) is under development. This paper describes a detector multiplexing technique that simplifies the readout electronics and reduces the density of the circuit board design. The multiplexing scheme was validated using a simulation framework that models the PSAPDs and front-end multiplexing circuits to predict the signal-to-noise ratio and flood histogram performance. Two independent experimental setups measured the energy resolution, time resolution, crystal identification ability and count rate both with and without multiplexing. With multiplexing, there was no significant degradation in energy resolution, time resolution and count rate. There was a relative 6.9 ± 1.0% and 9.4 ± 1.0% degradation in the figure of merit that characterizes the crystal identification ability observed in the measured and simulated ceramic-mounted PSAPD module flood histograms, respectively.

Radioluminescence microscopy: measuring the heterogeneous uptake of radiotracers in single living cells.

Radiotracers play an important role in interrogating molecular processes both in vitro and in vivo. However, current methods are limited to measuring average radiotracer uptake in large cell populations and, as a result, lack the ability to quantify cell-to-cell variations. Here we apply a new technique, termed radioluminescence microscopy, to visualize radiotracer uptake in single living cells, in a standard fluorescence microscopy environment. In this technique, live cells are cultured sparsely on a thin scintillator plate and incubated with a radiotracer. Light produced following beta decay is measured using a highly sensitive microscope. Radioluminescence microscopy revealed strong heterogeneity in the uptake of [18F]fluoro-deoxyglucose (FDG) in single cells, which was found consistent with fluorescence imaging of a glucose analog. We also verified that dynamic uptake of FDG in single cells followed the standard two-tissue compartmental model. Last, we transfected cells with a fusion PET/fluorescence reporter gene and found that uptake of FHBG (a PET radiotracer for transgene expression) coincided with expression of the fluorescent protein. Together, these results indicate that radioluminescence microscopy can visualize radiotracer uptake with single-cell resolution, which may find a use in the precise characterization of radiotracers.

Novel Electro-Optical Coupling Technique for Magnetic Resonance-Compatible Positron Emission Tomography Detectors:

A new magnetic resonance imaging (MRI)-compatible positron emission tomography (PET) detector design is being developed that uses electro-optical coupling to bring the amplitude and arrival time information of high-speed PET detector scintillation pulses out of an MRI system. The electro-optical coupling technology consists of a magnetically insensitive photodetector output signal connected to a nonmagnetic vertical cavity surface emitting laser (VCSEL) diode that is coupled to a multimode optical fiber. This scheme essentially acts as an optical wire with no influence on the MRI system. To test the feasibility of this approach, a lutetium-yttrium oxyorthosilicate crystal coupled to a single pixel of a solid-state photomultiplier array was placed in coincidence with a lutetium oxyorthosilicate crystal coupled to a fast photomultiplier tube with both the new nonmagnetic VCSEL coupling and the standard coaxial cable signal transmission scheme. No significant change was observed in 511 keV photopeak energy resolution and coincidence time resolution. This electro-optical coupling technology enables an MRI-compatible PET block detector to have a reduced electromagnetic footprint compared with the signal transmission schemes deployed in the current MRI/PET designs.

Convex Optimization of Coincidence Time Resolution for a High-Resolution PET System

We are developing a dual panel breast-dedicated positron emission tomography (PET) system using LSO scintillators coupled to position sensitive avalanche photodiodes (PSAPD). The charge output is amplified and read using NOVA RENA-3 ASICs. This paper shows that the coincidence timing resolution of the RENA-3 ASIC can be improved using certain list-mode calibrations. We treat the calibration problem as a convex optimization problem and use the RENA-3s analog-based timing system to correct the measured data for time dispersion effects from correlated noise, PSAPD signal delays and varying signal amplitudes. The direct solution to the optimization problem involves a matrix inversion that grows order (n3) with the number of parameters. An iterative method using single-coordinate descent to approximate the inversion grows order (n). The inversion does not need to run to convergence, since any gains at high iteration number will be low compared to noise amplification. The system calibration method is demonstrated with measured pulser data as well as with two LSO-PSAPD detectors in electronic coincidence. After applying the algorithm, the 511 keV photopeak paired coincidence time resolution from the LSO-PSAPD detectors under study improved by 57%, from the raw value of 16.3 ± 0.07 ns full-width at half-maximum (FWHM) to 6.92 ±0.02 ns FWHM (11.52 ±0.05 ns to 4.89 ± 0.02 ns for unpaired photons).

Clinical evaluation of a novel intraoperative handheld gamma camera for sentinel lymph node biopsy

OBJECTIVE Preoperative lymphoscintigraphy (PLS) combined with intraoperative gamma probe (GP) localization is standard procedure for localizing the sentinel lymph nodes (SLN) in melanoma and breast cancer. In this study, we evaluated the ability of a novel intraoperative handheld gamma camera (IHGC) to image SLNs during surgery. METHODS The IHGC is a small-field-of-view camera optimized for real-time imaging of lymphatic drainage patterns. Unlike conventional cameras, the IHGC can acquire useful images in a few seconds in a free-running fashion and be moved manually around the patient to find a suitable view of the node. Thirty-nine melanoma and eleven breast cancer patients underwent a modified SLN biopsy protocol in which nodes localized with the GP were imaged with the IHGC. The IHGC was also used to localize additional nodes that could not be found with the GP. RESULTS The removal of 104 radioactive SLNs was confirmed ex vivo by GP counting. In vivo, the relative node detection sensitivity was 88.5 (82.3, 94.6)% for the IHGC (used in conjunction with the GP) and 94.2 (89.7, 98.7)% for the GP alone, a difference not found to be statistically significant (McNemar test, p = 0.24). CONCLUSION Small radioactive SLNs can be visualized intraoperatively using the IHGC with exposure time of 20 s or less, with no significant difference in node detection sensitivity compared to a GP. The IHGC is a useful complement to the GP, especially for SLNs that are difficult to locate with the GP alone.

Pulse width modulation: A novel readout scheme for high energy photon detection

In standard PET scintillation detection, the energy, timing, and location of the incoming photon are recovered using analog signal processing techniques. The energy and location information are processed using an analog-to-digital (ADC) converter that samples an analog value that is proportional to the integral of the charge created by the scintillation event. We propose to change the paradigm and modulate the width (rather than amplitude) of a digital pulse to be proportional to the integral of the charge created. The analog value of the outgoing digital pulses is recovered by using a time-to-digital converter (TDC) in the back-end electronics, without the need for an ADC. Note that in this new scenario the same TDC used to record the time of the event is used to recover the amplitude. The main performance parameter that must be optimized is the dynamic range versus the dead-time of the front-end detector. The goal is an 8-bit dynamic range for this pulse-width modulation (PWM) scheme, which is adequate for high resolution PET systems based on semiconductor detectors such as avalanche photodiodes (APD) or cadmium zinc telluride (CZT). A novel circuit has been designed, fabricated, and tested for the proposed PWM readout scheme. This circuit is different than previously developed time over threshold pulse width modulation circuits used in high energy physics. PWM techniques simplify the routing to the back end electronics without degrading the performance of the system. A readout architecture based on PWM processes digital rather than analog pulses, which can be easily multiplexed, enabling one to achieve very high channel density required for ultra-high resolution, 3-D positioning PET detector systems.

Prototype positron emission tomography insert with electro-optical signal transmission for simultaneous operation with MRI

The simultaneous acquisition of PET and MRI data shows promise to provide powerful capabilities to study disease processes in human subjects, guide the development of novel treatments, and monitor therapy response and disease progression. A brain-size PET detector ring insert for an MRI system is being developed that, if successful, can be inserted into any existing MRI system to enable simultaneous PET and MRI images of the brain to be acquired without mutual interference. The PET insert uses electro-optical coupling to relay all the signals from the PET detectors out of the MRI system using analog modulated lasers coupled to fiber optics. Because the fibers use light instead of electrical signals, the PET detector can be electrically decoupled from the MRI making it partially transmissive to the RF field of the MRI. The SiPM devices and low power lasers were powered using non-magnetic MRI compatible batteries. Also, the number of laser-fiber channels in the system was reduced using techniques adapted from the field of compressed sensing. Using the fact that incoming PET data is sparse in time and space, electronic circuits implementing constant weight codes uniquely encode the detector signals in order to reduce the number of electro-optical readout channels by 8-fold. Two out of a total of sixteen electro-optical detector modules have been built and tested with the entire RF-shielded detector gantry for the PET ring insert. The two detectors have been tested outside and inside of a 3T MRI system to study mutual interference effects and simultaneous performance with MRI. Preliminary results show that the PET insert is feasible for high resolution simultaneous PET/MRI imaging for applications in the brain.

A New Positioning Algorithm for Position-Sensitive Avalanche Photodiodes

We are using a novel position sensitive avalanche photodiode (PSAPD) for the construction of a high resolution positron emission tomography (PET) camera. Up to now most researchers working with PSAPDs have been using an Anger-like positioning algorithm involving the four corner readout signals of the PSAPD. This algorithm yields a significant non-linear spatial ldquopin-cushionrdquo distortion in raw crystal positioning histograms. In this paper, we report an improved positioning algorithm, which combines two diagonal corner signals of the PSAPD followed by a 45degC rotation to determine the X or Y position of the interaction. We present flood positioning histogram data generated with the old and new positioning algorithms using a 3times4 array of 2times2times3mm and a 3times8 array of 1times1times3 mm3 of LSO crystals coupled to 8times8 mm2 PSAPDs. This new algorithm significantly reduces the pin-cushion distortion in raw flood histogram image.