Yiping Shao

Simultaneous PET and MR imaging

We have developed a prototype PET detector which is compatible with a clinical MRI system to provide simultaneous PET and MR imaging. This single-slice PET system consists of 48 2 x 2 x 10 mm3 LSO crystals in a 38 mm diameter ring configuration that can be placed inside the receiver coil of the MRI system, coupled to three multi-channel photomultipliers housed outside the main magnetic field via 4 m long and 2 mm diameter optical fibres. The PET system exhibits 2 mm spatial resolution, 41% energy resolution at 511 keV and 20 ns timing resolution. Simultaneous PET and MR phantom images were successfully acquired.

Simple charge division readouts for imaging scintillator arrays using a multi-channel PMT

Three simple charge division circuits were assembled and tested as 2-D position encoding readouts for multi-channel photomultiplier tubes (MC-PMT). They were evaluated with an 8/spl times/8 array of individual scintillators (2/spl times/2/spl times/10 mm BGO) coupled to a 64 channel MC-PMT (Philips XP1722) via 25 cm long, 2 mm diameter, double clad, optical fibers (Kuraray). This type of gamma-ray imaging detector has many potential applications in medical and industrial imaging. Though independent channel readout would allow for the discrimination of scatter within the array, and higher count rates, it would also require an excessive amount of supporting electronics. This is especially true for systems comprised of many MC-PMTs. In this study, the number of channels being read out was reduced from 64 to 4 using three different simple resistor networks. These circuits take advantage of the discretized nature of the scintillator array, the low interchannel crosstalk of the MC-PMT and low input impedance current-sensitive preamplifiers. For each circuit, the scintillator identification accuracy was compared. The identification accuracy as a function of deposited energy was also determined by exposure to various gamma-ray emitters. It was found that the preamplifier circuit noise contributed the most to the degradation of the detectors spatial response so several low noise op amps were evaluated. It was also determined that keeping the preamplifier input impedance small was necessary for accurate positioning. The coincidence timing resolution of the detector (15 ns) is only slightly degraded by the readout circuit.

Development of a PET detector system compatible with MRI/NMR systems

We report the development of a prototype positron emission tomography (PET) scanner compatible with clinical magnetic resonance imaging (MRI) scanners and nuclear magnetic resonance (NMR) spectrometers. This single slice PET system consists of 72 2/spl times/2/spl times/5 mm lutetium oxyorthosilicate (LSO) crystals coupled by 2 mm diameter, 4 meter long double clad optical fibers to three multi-channel photomultiplier tubes (MC-PMTs) shielded inside an aluminum closure. The ring diameter is 54 mm and the slice thickness is /spl sim/1 mm FWHM. Measurements with a point source demonstrate that this PET system has a reconstructed resolution of 2.1 mm, a coincidence time resolution of 26 ns and a typical energy resolution of 45%. Simultaneously acquired PET and MR phantom images, show no significant artifacts or distortions. We also obtained simultaneous NMR spectra and PET images from an isolated, perfused rat heart, demonstrating the power of obtaining temporally correlated PET and NMR information in biological systems. Again, no artifacts in the PET or NMR data were apparent, despite the high field strength of 9.4 T. The challenge for the future is to scale up the design to develop a high resolution, high sensitivity device that can be used in simultaneous PET and MR studies of in vivo systems.

The Skp2-SCF E3 ligase regulates Akt ubiquitination, glycolysis, herceptin sensitivity, and tumorigenesis.

Akt kinase plays a central role in cell growth, metabolism, and tumorigenesis. The TRAF6 E3 ligase orchestrates IGF-1-mediated Akt ubiquitination and activation. Here, we show that Akt ubiquitination is also induced by activation of ErbB receptors; unexpectedly, and in contrast to IGF-1 induced activation, the Skp2 SCF complex, not TRAF6, is a critical E3 ligase for ErbB-receptor-mediated Akt ubiquitination and membrane recruitment in response to EGF. Skp2 deficiency impairs Akt activation, Glut1 expression, glucose uptake and glycolysis, and breast cancer progression in various tumor models. Moreover, Skp2 overexpression correlates with Akt activation and breast cancer metastasis and serves as a marker for poor prognosis in Her2-positive patients. Finally, Skp2 silencing sensitizes Her2-overexpressing tumors to Herceptin treatment. Our study suggests that distinct E3 ligases are utilized by diverse growth factors for Akt activation and that targeting glycolysis sensitizes Her2-positive tumors to Herceptin treatment.

Design and evaluation of an LSO PET detector for breast cancer imaging

Functional imaging with positron emission tomography (PET) may be a promising technique in conjunction with x-ray mammography for breast cancer patient management. Conventional whole body PET scanners provide metabolic images of breast cancer patients with several shortcomings related to the general-purpose nature of these systems. In whole body scanners, the detectors are typically 20-30 cm away from the breast or axilla, reducing sensitivity, and these scanners have relatively large detector elements (> 4 mm), limiting spatial resolution. Dedicated PET systems for breast imaging aim to overcome these limitations and improve the overall diagnostic quality of the images by bringing the detectors closer to the area to be imaged, thereby improving sensitivity, and by using smaller detector elements to improve the spatial resolution. We have designed and developed a modular PET detector that is composed of a 9x9 array of 3x3x20 mm3 lutetium oxyorthosilicate (LSO) scintillator crystals coupled to an optical fiber taper, which in turn is coupled to a Hamamatsu R5900-C8 position-sensitive photomultiplier tube. These detectors can be tiled together without gaps to construct large area detector arrays to form a dedicated PET breast cancer imaging system. Two complete detector modules have been built and tested. All detector elements are clearly visualized upon flood irradiation of the module. The intrinsic spatial resolution (full-width at half-maximum) was measured to be 2.26 mm (range 1.8-2.6 mm). The average energy resolution was 19.5% (range 17%-24%) at 511 keV. The coincidence time resolution was measured to be 2.4 ns. The detector efficiency for 511 keV gamma rays was 53% using a 350 keV energy threshold. These promising results support the feasibility of developing a high resolution, high sensitivity dedicated PET scanner for breast cancer applications.

A study of artefacts in simultaneous PET and MR imaging using a prototype MR compatible PET scanner

We have assessed the possibility of artefacts that can arise in attempting to perform simultaneous positron emission tomography (PET) and magnetic resonance imaging (MRI) using a small prototype MR compatible PET scanner (McPET). In these experiments, we examine MR images for any major artefacts or loss in image quality due to inhomogeneities in the magnetic field, radiofrequency interference or susceptibility effects caused by operation of the PET system inside the MR scanner. In addition, possible artefacts in the PET images caused by the static and time-varying magnetic fields or radiofrequency interference from the MR system were investigated. Biological tissue and a T2-weighted spin echo sequence were used to examine susceptibility artefacts due to components of the McPET scanner (scintillator, optical fibres) situated in the MR field of view. A range of commonly used MR pulse sequences was studied while acquiring PET data to look for possible artefacts in either the PET or MR images. Other than a small loss in signal-to-noise using gradient echo sequences, there was no significant interaction between the two imaging systems. Simultaneous PET and MR imaging of simple phantoms was also carried out in different MR systems with field strengths ranging from 0.2 to 4.7 T. The results of these studies demonstrate that it is possible to acquire PET and MR images simultaneously, without any significant artefacts or loss in image quality, using our prototype MR compatible PET scanner.

Optical fiber readout of scintillator arrays using a multi-channel PMT: a high resolution PET detector for animal imaging

The authors report the results from a new high resolution gamma ray imaging detector designed for use in a positron emission tomography (PET) system dedicated to small animal imaging. The detectors consist of an 8/spl times/8 array of 2/spl times/2/spl times/10 mm bismuth germanate (BGO) crystals coupled by 2 mm diameter double clad optical fibers to a 64 pixel multi-channel photomultiplier tube (MC-PMT). A charge division readout board is used to convert the 64 output channels into four position sensitive signals which determine the crystal of interaction. Measurements with a pair of these detectors demonstrate an intrinsic spatial resolution of 1.4 mm, a coincidence timing resolution of 15 ns and an energy resolution ranging between 35 and 60%. Based on these encouraging results, the design for a dedicated animal PET tomograph is proposed and simulations of this system project a reconstructed resolution of less than 2 mm within a 5 cm diameter transaxial field of view.

A study of inter-crystal scatter in small scintillator arrays designed for high resolution PET imaging

Inter-crystal scatter causes mispositioning of scintillation events, which is of particular concern in imaging detectors based on small discrete scintillator elements. Because it is difficult to measure the scatter and its effects on detector intrinsic spatial resolution, a Monte Carlo simulation has been used to study inter-crystal scatter effects for evaluating and optimizing the design of a high resolution animal PET detector based on an array of small scintillator crystals. In this simulation, the authors quantitatively assess the mispositioning of events due to inter-crystal scatter as a function of parameters such as different scintillator materials, crystal geometry, /spl gamma/-ray incident angle and applied energy threshold. In analyzing the tradeoff between the detector efficiency and the position detection accuracy, the authors found that the mispositioning is not sensitive to the energy threshold, however it does change rapidly with the crystal length and the gap between crystals. The authors also compared four different crystal positioning algorithms to provide a theoretical estimate of positioning accuracy and to determine the best algorithm to use. To study how inter-crystal scatter affects detector spatial resolution, the authors analyzed the coincidence line spread function with and without inter-crystal scatter and found that the inter-crystal scatter had very little effect on the FWHM and FWTM of the coincidence line spread function.

Design studies of a high resolution PET detector using APD arrays

The authors evaluated a compact, high resolution PET detector module using avalanche photodiode (APD) arrays to replace bulky position sensitive PMTs. The newly developed APD array is a planar processed 4/spl times/4 array which has a 2/spl times/2 mm/sup 2/ pixel size with 0.4 mm gaps between pixels, about 60% quantum efficiency at 420 nm wavelength, and uniform high gain (>1000) across all channels. A 4/spl times/4 array of 2/spl times/2/spl times/10 mm/sup 3/ LSO crystals was coupled to an APD array. Different readout electronics and signal multiplexing schemes were explored. All crystals in the detector array were clearly identified in the flood source histogram, with average peak-to-valley ratios of about 12:1 using a charge sharing resistor network. The energy resolution was measured to be /spl sim/14% at 511 keV in the detector array. The measured timing resolution was 2.6 ns in coincidence with a LSO/PMT detector. By optimizing the readout electronics currently being used, it is likely that detector performance can be further improved. The authors have also determined depth-of-interaction (DOI) by reading out two APD arrays connected to the ends of a 2/spl times/2/spl times/22 mm/sup 3/ LSO crystal. Preliminary measurements show good DOI measurement capability with DOI positioning uncertainty between 4 and 6.5 mm.

Design of a small animal MR compatible PET scanner

Using a combination of Monte Carlo simulations and experimental measurements we have designed a small-animal MRI-compatible PET (McPET) scanner for simultaneous PET imaging and MRI of mice and rats in vivo. The scanner consists of one ring of 480 LSO (Lu/sub 2/SiO/sub 5/) crystals arranged in three layers, with 160 crystals per layer. The crystal dimensions are 2/spl times/3/spl times/7.5 mm/sup 3/. This was based on a target resolution of 215 mm and simulations showing that a depth of 7.5 mm avoided significant depth-of-interaction effects across the desired field of view. The system diameter of 11.2 cm is large enough to accommodate the animal positioned inside a stereotactic frame. Each crystal is coupled through 2-mm diameter optical fibers to multi-channel photomultiplier tubes which reside outside the main magnetic field. Through 50 cm of optical fiber, a photopeak is clearly seen and the measured energy resolution is 25%. Prototype optical fiber connectors have been tested to increase the flexibility of the system and result in a light loss of only 6%. The proposed system has adequate resolution and sensitivity for a number of applications with small animals and is the first practical device for simultaneous in-vivo imaging with PET and MRI.