Yibao Wu

Simultaneous in vivo positron emission tomography and magnetic resonance imaging

Positron emission tomography (PET) and magnetic resonance imaging (MRI) are widely used in vivo imaging technologies with both clinical and biomedical research applications. The strengths of MRI include high-resolution, high-contrast morphologic imaging of soft tissues; the ability to image physiologic parameters such as diffusion and changes in oxygenation level resulting from neuronal stimulation; and the measurement of metabolites using chemical shift imaging. PET images the distribution of biologically targeted radiotracers with high sensitivity, but images generally lack anatomic context and are of lower spatial resolution. Integration of these technologies permits the acquisition of temporally correlated data showing the distribution of PET radiotracers and MRI contrast agents or MR-detectable metabolites, with registration to the underlying anatomy. An MRI-compatible PET scanner has been built for biomedical research applications that allows data from both modalities to be acquired simultaneously. Experiments demonstrate no effect of the MRI system on the spatial resolution of the PET system and <10% reduction in the fraction of radioactive decay events detected by the PET scanner inside the MRI. The signal-to-noise ratio and uniformity of the MR images, with the exception of one particular pulse sequence, were little affected by the presence of the PET scanner. In vivo simultaneous PET and MRI studies were performed in mice. Proof-of-principle in vivo MR spectroscopy and functional MRI experiments were also demonstrated with the combined scanner.

Initial Characterization of a Dedicated Breast PET/CT Scanner During Human Imaging

We have constructed a dedicated breast PET/CT scanner capable of high-resolution functional and anatomic imaging. Here, we present an initial characterization of scanner performance during patient imaging. Methods: The system consisted of a lutetium oxyorthosilicate–based dual–planar head PET camera (crystal size, 3 × 3 × 20 mm) and 768-slice cone-beam CT. The position of the PET heads (separation and height) could be adjusted for varying breast dimensions. For scanning, the patient lay prone on a specialized bed and inserted a single pendent breast through an aperture in the table top. Compression of the breast as used in mammography is not required. PET and CT systems rotate in the coronal plane underneath the patient sequentially to collect fully tomographic datasets. PET images were reconstructed with the fully 3-dimensional maximum a posteriori method, and CT images were reconstructed with the Feldkamp algorithm, then spatially registered and fused for display. Phantom scans were obtained to assess the registration accuracy between PET and CT images and the influence of PET electronics and activity on CT image quality. We imaged 4 women with mammographic findings highly suggestive of breast cancer (breast imaging reporting and data system, category 5) in an ongoing clinical trial. Patients were injected with 18F-FDG and imaged for 12.5 min per breast. From patient data, noise-equivalent counting rates and the singles-to-trues ratio (a surrogate for the randoms fraction) were calculated. Results: The average registration error between PET and CT images was 0.18 mm. PET electronics and activity did not significantly affect CT image quality. For the patient trial, biopsy-confirmed cancers were visualized on dedicated breast PET/CT on all patient scans, including the detection of ductal carcinoma in situ in 1 case. The singles-to-trues ratio was found to be inversely correlated with breast volume in the field of view, suggesting that larger breasts trend toward increased noise-equivalent counting rates for all other things equal. Conclusion: Scanning of the uncompressed breast with dedicated breast PET/CT can accurately visualize suspected lesions in 3 dimensions.

A Prototype PET Scanner with DOI-Encoding Detectors

Detectors with depth-encoding allow a PET scanner to simultaneously achieve high sensitivity and high spatial resolution. Methods: A prototype PET scanner, consisting of depth-encoding detectors constructed by dual-ended readout of lutetium oxyorthosilicate (LSO) arrays with 2 position-sensitive avalanche photodiodes (PSAPDs), was developed. The scanner comprised 2 detector plates, each with 4 detector modules, and the LSO arrays consisted of 7 × 7 elements, with a crystal size of 0.9225 × 0.9225 × 20 mm and a pitch of 1.0 mm. The active area of the PSAPDs was 8 × 8 mm. The performance of individual detector modules was characterized. A line-source phantom and a hot-rod phantom were imaged on the prototype scanner in 2 different scanner configurations. The images were reconstructed using 20, 10, 5, 2, and 1 depth-of-interaction (DOI) bins to demonstrate the effects of DOI resolution on reconstructed image resolution and visual image quality. Results: The flood histograms measured from the sum of both PSAPD signals were only weakly depth-dependent, and excellent crystal identification was obtained at all depths. The flood histograms improved as the detector temperature decreased. DOI resolution and energy resolution improved significantly as the temperature decreased from 20°C to 10°C but improved only slightly with a subsequent temperature decrease to 0°C. A full width at half maximum (FWHM) DOI resolution of 2 mm and an FWHM energy resolution of 15% were obtained at a temperature of 10°C. Phantom studies showed that DOI measurements significantly improved the reconstructed image resolution. In the first scanner configuration (parallel detector planes), the image resolution at the center of the field of view was 0.9-mm FWHM with 20 DOI bins and 1.6-mm FWHM with 1 DOI bin. In the second scanner configuration (detector planes at a 40° angle), the image resolution at the center of the field of view was 1.0-mm FWHM with 20 DOI bins and was not measurable when using only 1 bin. Conclusion: PET scanners based on this detector design offer the prospect of high and uniform spatial resolution (crystal size, ∼1 mm; DOI resolution, ∼2 mm), high sensitivity (20-mm-thick detectors), and compact size (DOI encoding permits detectors to be tightly packed around the subject and minimizes number of detectors needed).

Experimental characterization and system simulations of depth of interaction PET detectors using 0.5 mm and 0.7 mm LSO arrays

Small animal PET scanners may be improved by increasing the sensitivity, improving the spatial resolution and improving the uniformity of the spatial resolution across the field of view. This may be achieved by using PET detectors based on crystal elements that are thin in the axial and transaxial directions and long in the radial direction, and by employing depth of interaction (DOI) encoding to minimize the parallax error. With DOI detectors, the diameter of the ring of the PET scanner may also be decreased. This minimizes the number of detectors required to achieve the same solid angle coverage as a scanner with a larger ring diameter and minimizes errors due to non-collinearity of the annihilation photons. In this study, we characterize prototype PET detectors that are finely pixelated with individual LSO crystal element sizes of 0.5 mm x 0.5 mm x 20 mm and 0.7 mm x 0.7 mm x 20 mm, read out at both ends by position sensitive avalanche photodiodes (PSAPDs). Both a specular reflector and a diffuse reflector were evaluated. The detectors were characterized based on the ability to clearly resolve the individual crystal elements, the DOI resolution and the energy resolution. Our results indicate that a scanner based on any of the four detector designs would offer improved spatial resolution and more uniform spatial resolution compared to present day small animal PET scanners. The greatest improvements to spatial resolution will be achieved when the detectors employing the 0.5 mm x 0.5 mm x 20 mm crystals are used. Monte Carlo simulations were performed to demonstrate that 2 mm DOI resolution is adequate to ensure uniform spatial resolution for a small animal PET scanner geometry using these detectors. The sensitivity of such a scanner was also simulated using Monte Carlo simulations and was shown to be greater than 10% for a four ring scanner with an inner diameter of 6 cm, employing 20 detectors per scanner ring.

Depth of interaction calibration for PET detectors with dual-ended readout by PSAPDs

Many laboratories develop depth-encoding detectors to improve the trade-off between spatial resolution and sensitivity in positron emission tomography (PET) scanners. One challenge in implementing these detectors is the need to calibrate the depth of interaction (DOI) response for the large numbers of detector elements in a scanner. In this work, we evaluate two different methods, a linear detector calibration and a linear crystal calibration, for determining DOI calibration parameters. Both methods can use measurements from any source distribution and location, or even the intrinsic lutetium oxyorthosilicate (LSO) background activity, and are therefore well suited for use in a depth-encoding PET scanner. The methods were evaluated by measuring detector and crystal DOI responses for all eight detectors in a prototype depth-encoding PET scanner. The detectors utilize dual-ended readout of LSO scintillator arrays with position-sensitive avalanche photodiodes (PSAPDs). The LSO arrays have 7 x 7 elements, with a crystal size of 0.92 x 0.92 x 20 mm(3) and pitch of 1.0 mm. The arrays are read out by two 8 x 8 mm(2) area PSAPDs placed at opposite ends of the arrays. DOI is measured by the ratio of the amplitude of the total energy signals measured by the two PSAPDs. Small variations were observed in the DOI responses of different crystals within an array as well as DOI responses for different arrays. A slightly nonlinear dependence of the DOI ratio on depth was observed and the nonlinearity was larger for the corner and edge crystals. The DOI calibration parameters were obtained from the DOI responses measured in a singles mode. The average error between the calibrated DOI and the known DOI was 0.8 mm if a linear detector DOI calibration was used and 0.5 mm if a linear crystal DOI calibration was used. A line source phantom and a hot rod phantom were scanned on the prototype PET scanner. DOI measurement significantly improved the image spatial resolution no matter which DOI calibration method was used. A linear crystal DOI calibration provided slightly better image spatial resolution compared with a linear detector DOI calibration.

A microPET/CT system for in vivo small animal imaging

A microCT scanner was designed, fabricated and integrated with a previously reported microPET II scanner (Tai et al 2003 Phys. Med. Biol. 48 1519, Yang et al 2004 Phys. Med. Biol. 49 2527), forming a dual modality system for in vivo anatomic and molecular imaging of the mouse. The system was designed to achieve high-spatial-resolution and high-sensitivity PET images with adequate CT image quality for anatomic localization and attenuation correction with low x-ray dose. The system also has relatively high throughput for screening, and a flexible gantry and user interface. X-rays were produced by a 50 kVp, 1.5 mA fixed tungsten anode tube, with a focal spot size of 70 microm. The detector was a 5 x 5 cm(2) photodiode detector incorporating 48 microm pixels on a CMOS array and a fast gadolinium oxysulfide (GOS) intensifying screen. The microCT system has a flexible C-arm gantry design with adjustable detector positioning, which acquires CT projection images around the common microPET/CT bed. The design and the initial characterization of the microCT system is described, and images of the first mouse scans with microPET/CT scanning protocols are shown.

PET characteristics of a dedicated breast PET/CT scanner prototype

A dedicated breast PET/CT system has been constructed at our institution, with the goal of having increased spatial resolution and sensitivity compared to whole-body systems. The purpose of this work is to describe the design and the performance characteristics of the PET component of this device. Average spatial resolution of a line source in warm background using maximum a posteriori (MAP) reconstruction was 2.5 mm, while the average spatial resolution of a phantom containing point sources using filtered back projection (FBP) was 3.27 mm. A sensitivity profile was computed with a point source translated across the axial field of view (FOV) and a peak sensitivity of 1.64% was measured at the center of the FOV. The average energy resolution determined on a per-crystal basis was 25%. The characteristic dead time for the front-end electronics and data acquisition (DAQ) was determined to be 145 ns and 3.6 micros, respectively. With no activity outside the FOV, a peak noise-equivalent count rate of 18.6 kcps was achieved at 318 microCi (11.766 MBq) in a cylindrical phantom of diameter 75 mm. After the effects of exposing PET detectors to x-ray flux were evaluated and ameliorated, a combined PET/CT scan was performed. The percentage standard deviations of uniformity along axial and transaxial directions were 3.7% and 2.8%, respectively. The impact of the increased reconstructed spatial resolution compared to typical whole-body PET scanners is currently being assessed in a clinical trial.

Continuous depth-of-interaction encoding using phosphor-coated scintillators.

We investigate a novel detector using a lutetium oxyorthosilicate (LSO) scintillator and YGG (yttrium-aluminum-gallium oxide:cerium, Y(3)(Al,Ga)(5)O(12):Ce) phosphor to construct a detector with continuous depth-of-interaction (DOI) information. The far end of the LSO scintillator is coated with a thin layer of YGG phosphor powder which absorbs some fraction of the LSO scintillation light and emits wavelength-shifted photons with a characteristic decay time of approximately 50 ns. The near end of the LSO scintillator is directly coupled to a photodetector. The photodetector detects a mixture of the LSO light and the light emitted by YGG. With appropriate placement of the coating, the ratio of the light converted from the YGG coating with respect to the unconverted LSO light can be made to depend on the interaction depth. DOI information can then be estimated by inspecting the overall light pulse decay time. Experiments were conducted to optimize the coating method. 19 ns decay time differences across the length of the detector were achieved experimentally when reading out a 1.5 x 1.5 x 20 mm(3) LSO crystal with unpolished surfaces and half-coated with YGG phosphor. The same coating scheme was applied to a 4 x 4 LSO array. Pulse shape discrimination (PSD) methods were studied to extract DOI information from the pulse shape changes. The DOI full-width-half-maximum (FWHM) resolution was found to be approximately 8 mm for this 2 cm thick array.

PET Performance Evaluation of an MR-Compatible PET Insert

A magnetic resonance (MR) compatible positron emission tomography (PET) insert has been developed in our laboratory for simultaneous small animal PET/MR imaging. This system is based on lutetium oxyorthosilicate (LSO) scintillator arrays with position-sensitive avalanche photodiode (PSAPD) photodetectors. The PET performance of this insert has been measured. The average reconstructed image spatial resolution was 1.51 mm. The sensitivity at the center of the field of view (CFOV) was 0.35%, which is comparable to the simulation predictions of 0.40%. The average photopeak energy resolution was 25%. The scatter fraction inside the MRI scanner with a line source was 12% (with a mouse-sized phantom and standard 35 mm Bruker 1 H RF coil), 7% (with RF coil only) and 5% (without phantom or RF coil) for an energy window of 350-650 keV. The front-end electronics had a dead time of 390 ns, and a trigger extension dead time of 7.32 mus that degraded counting rate performance for injected doses above ~0.75 mCi (28 MBq). The peak noise-equivalent count rate (NECR) of 1.27 kcps was achieved at 290 muCi (10.7 MBq). The system showed good imaging performance inside a 7-T animal MRI system; however improvements in data acquisition electronics and reduction of the coincidence timing window are needed to realize improved NECR performance.

Tapered LSO Arrays for Small Animal PET

By using detectors with good depth encoding accuracy (∼2 mm), an animal PET scanner can be built with a small ring diameter and thick crystals to simultaneously obtain high spatial resolution and high sensitivity. However, there will be large wedge-shaped gaps between detector modules in such a scanner if traditional cuboid crystal arrays are used in a polygonal arrangement. The gaps can be minimized by using tapered scintillator arrays enabling the sensitivity of the scanner to be further improved. In this work, tapered lutetium oxyorthosilicate (LSO) arrays with different crystal dimensions and different combinations of inter-crystal reflector and crystal surface treatments were manufactured and their performance was evaluated. Arrays were read out from both ends by position-sensitive avalanche photodiodes (PSAPDs). In the optimal configuration, arrays consisting of 0.5 mm LSO elements could be clearly resolved and a depth of interaction resolution of 2.6 mm was obtained for a 20 mm thick array. For this tapered array, the intrinsic spatial is degraded from 0.67 to 0.75 mm compared to a standard cuboidal array with similar dimensions, while the increase in efficiency is 41%. Tapered scintillator arrays offer the prospect of improvements in sensitivity and sampling for small-bore scanners, without large increases in manufacturing complexity.