William C. Barber

Photon Counting Energy Dispersive Detector Arrays for X-ray Imaging

The development of an innovative detector technology for photon-counting in X-ray imaging is reported. This new generation of detectors, based on pixellated cadmium telluride (CdTe) and cadmium zinc telluride (CZT) detector arrays electrically connected to application specific integrated circuits (ASICs) for readout, will produce fast and highly efficient photon-counting and energy-dispersive X-ray imaging. There are a number of applications that can greatly benefit from these novel imagers including mammography, planar radiography, and computed tomography (CT). Systems based on this new detector technology can provide compositional analysis of tissue through spectroscopic X-ray imaging, significantly improve overall image quality, and may significantly reduce X-ray dose to the patient. A very high X-ray flux is utilized in many of these applications. For example, CT scanners can produce ~ 100 Mphotons/mm2 /s in the unattenuated beam. High flux is required in order to collect sufficient photon statistics in the measurement of the transmitted flux (attenuated beam) during the very short time frame of a CT scan. This high count rate combined with a need for high detection efficiency requires the development of detector structures that can provide a response signal much faster than the transit time of carriers over the whole detector thickness. We have developed CdTe and CZT detector array structures which are 3 mm thick with 16 times 16 pixels and a 1 mm pixel pitch. These structures, in the two different implementations presented here, utilize either a small pixel effect or a drift phenomenon. An energy resolution of 4.75% at 122 keV has been obtained with a 30 ns peaking time using discrete electronics and a 57Co source. An output rate of 6 times 106 counts per second per individual pixel has been obtained with our ASIC readout electronics and a clinical CT X-ray tube. Additionally, the first clinical CT images, taken with several of our prototype photon-counting and energy-dispersive detector modules, are shown.

An analytical model of the effects of pulse pileup on the energy spectrum recorded by energy resolved photon counting x-ray detectors.

Purpose: Recently, novel CdTe photon counting x-ray detectors (PCXDs) with energy discrimination capabilities have been developed. When such detectors are operated under a high x-ray flux, however, coincident pulses distort the recorded energy spectrum. These distortions are called pulse pileup effects. It is essential to compensate for these effects on the recorded energy spectrum in order to take full advantage of spectral information PCXDs provide. Such compensation can be achieved by incorporating a pileup model into the image reconstruction process for computed tomography, that is, as a part of the forward imaging process, and iteratively estimating either the imaged object or the line integrals using, e.g., a maximum likelihood approach. The aim of this study was to develop a new analytical pulse pileup model for both peak and tail pileup effects for nonparalyzable detectors. Methods: The model takes into account the following factors: The bipolar shape of the pulse, the distribution function of time intervals between random events, and the input probability density function of photon energies. The authors used Monte Carlo simulations to evaluate the model. Results: The recorded spectra estimated by the model were in an excellent agreement with those obtained by Monte Carlo simulations for various levels of pulse pileup effects. The coefficients of variation (i.e., the root mean square difference divided by the mean of measurements) were 5.3%–10.0% for deadtime losses of 1%–50% with a polychromatic incident x-ray spectrum. Conclusions: The proposed pulse pileup model can predict recorded spectrum with relatively good accuracy.

A multipinhole small animal SPECT system with submillimeter spatial resolution

Single photon emission computed tomography (SPECT) is an important technology for molecular imaging studies of small animals. In this arena, there is an increasing demand for high performance imaging systems that offer improved spatial resolution and detection efficiency. We have designed a multipinhole small animal imaging system based on position sensitive avalanche photodiode (PSAPD) detectors with the goal of submillimeter spatial resolution and high detection efficiency, which will allow us to minimize the radiation dose to the animal and to shorten the time needed for the imaging study. Our design will use 8 x 24 mm2 PSAPD detector modules coupled to thallium-doped cesium iodide [CsI(Tl)] scintillators, which can achieve an intrinsic spatial resolution of 0.5 mm at 140 keV. These detectors will be arranged in rings of 24 modules each; the animal is positioned in the center of the 9 stationary detector rings which capture projection data from the animal with a cylindrical tungsten multipinhole collimator. The animal is supported on a bed which can be rocked about the central axis to increase angular sampling of the object. In contrast to conventional SPECT pinhole systems, in our design each pinhole views only a portion of the object. However, the ensemble of projection data from all of the multipinhole detectors provide angular sampling that is sufficient to reconstruct tomographic data from the object. The performance of this multipinhole PSAPD imaging system was simulated using a ray tracing program that models the appropriate point spread functions and then was compared against the performance of a dual-headed pinhole SPECT system. The detection efficiency of both systems was simulated and projection data of a hot rod phantom were generated and reconstructed to assess spatial resolution. Appropriate Poisson noise was added to the data to simulate an acquisition time of 15 min and an activity of 18.5 MBq distributed in the phantom. Both sets of data were reconstructed with an ML-EM reconstruction algorithm. In addition, the imaging performance of both systems was evaluated with a uniformity phantom and a realistic digital mouse phantom. Simulations show that our proposed system produces a spatial resolution of 0.8 mm and an average detection efficiency of 630 cps/MBq. In contrast, simulations of the dual-headed pinhole SPECT system produce a spatial resolution of 1.1 mm and an average detection efficiency of 53 cps/MBq. These results suggest that our novel design will achieve high spatial resolution and will improve the detection efficiency by more than an order of magnitude compared to a dual-headed pinhole SPECT system. We expect that this system can perform SPECT with submillimeter spatial resolution, high throughput, and low radiation dose suitable for in vivo imaging of small animals.

Dual-modality imaging of function and physiology.

Dual-modality imaging is a technique in which computed tomography (CT) or magnetic resonance imaging is combined with positron emission tomography or single-photon emission CT to acquire structural and functional images with an integated system. The data are acquired in a single procedure; the patient remains on the scanner table while undergoing both x-ray and radionuclide studies to facilitate correlation between the structural and functional images. The resulting data can aid in localization, enabling more specific diagnosis than can be obtained with a conventional imaging study. In addition, the anatomic information can be used to compensate the correlated radionuclide data for physical perturbations such as photon attenuation, scatter radiation, and partial volume errors. Thus, dual-modality imaging provides a priori information that can improve both the visual quality and the quantitative accuracy of the radionuclide images. Dual-modality imaging systems are also being developed for biologic research involving small animals. Small-animal dual-modality systems offer advantages for measurements that currently are performed invasively with autoradiography and tissue sampling. By acquiring data noninvasively, dual-modality imaging permits serial studies in a single animal, enables measurements to be performed with fewer animals, and improves the statistical quality of the data.

Quantitative fluorescence tomography using a combined tri-modality FT/DOT/XCT system

In this work, a first-of-its-kind fully integrated tri-modality system that combines fluorescence, diffuse optical and x-ray tomography (FT/DOT/XCT) into the same setting is presented. The purpose of this system is to perform quantitative fluorescence tomography using multi-modality imaging approach. XCT anatomical information is used as structural priori while optical background heterogeneity information obtained by DOT measurements is used as functional priori. The performance of the hybrid system is evaluated using multi-modality phantoms. In particular, we show that a 2.4 mm diameter fluorescence inclusion located in a heterogeneous medium can be localized accurately with the functional a priori information, although the fluorophore concentration is recovered with 70% error. On the other hand, the fluorophore concentration can be accurately recovered within 8% error only when both DOT optical background functional and XCT structural a priori information are utilized to guide and constrain the FT reconstruction algorithm.

Characterization of a novel photon counting detector for clinical CT: count rate, energy resolution, and noise performance

We report on a characterization study of a multi-row direct-conversion x-ray detector used to generate the first photon counting clinical x-ray computed tomography (CT) patent images. In order to provide the photon counting detector with adequate performance for low-dose CT applications, we have designed and fabricated a fast application specific integrated circuit (ASIC) for data readout from the pixellated CdTe detectors that comprise the photon counting detector. The cadmium telluride (CdTe) detector has 512 pixels with a 1 mm pitch and is vertically integrated with the ASIC readout so it can be tiled in two dimensions similar to those that are tiled in an arc found in 32-row multi-slice CT systems. We have measured several important detector parameters including the maximum output count rate, energy resolution, and noise performance. Additionally the relationship between the output and input rate has been found to fit a non-paralyzable detector model with a dead time of 160 nsec. A maximum output rate of 6 × 106 counts per second per pixel has been obtained with a low output x-ray tube for CT operated between 0.01 mA and 6 mA at 140 keV and different source-to-detector distances. All detector noise counts are less that 20 keV which is sufficiently low for clinical CT. The energy resolution measured with the 60 keV photons from a 241Am source is ~12%. In conclusion, our results demonstrate the potential for the application of the CdTe based photon counting detector to clinical CT systems. Our future plans include further performance improvement by incorporating drift structures to each detector pixel.

Dual-Modality Imaging of Cancer with SPECT/CT

Dual-modality imaging is an in vivo diagnostic technique that obtains structural and functional information directly from patient studies in a way that cannot be achieved with separate imaging systems alone. Dual-modality imaging systems are configured by combining computed tomography (CT) with radionuclide imaging (using positron emission tomography (PET) or single-photon emission computed tomography (SPECT)) on a single gantry which allows both functional and structural imaging to be performed during a single imaging session without having the patient leave the imaging system. A SPECT/CT system developed at UCSF is being used in a study to determine if dual-modality imaging offers advantages for assessment of patients with prostate cancer using111 In-ProstaScint®, a radiolabeled antibody for the prostate-specific membrane antigen.111 In-ProstaScint® images are reconstructed using an iterative maximum-likelihood expectation-maximization (ML-EM) algorithm with correction for photon attenuation using a patient-specific map of attenuation coefficients derived from CT. The ML-EM algorithm accounts for the dual-photon nature of the111 In-labeled radionuclide, and incorporates correction for the geometric response of the radionuclide collimator. The radionuclide image then can be coregistered and overlaid in color on a grayscale CT image for improved localization of the functional information from SPECT. Radionuclide images obtained with SPECT/CT and reconstructed using ML-EM with correction for photon attenuation and collimator response improve image quality in comparison to conventional radionuclide images obtained with filtered backprojection reconstruction. These results illustrate the potential advantages of dual-modality imaging for improving the quality and the localization of radionuclide uptake for staging disease, planning treatment, and monitoring therapeutic response in patients with cancer.

Enabling photon counting clinical X-ray CT

Photon counting x-ray detectors (PCXDs) with energy discrimination capabilities offer various advantages over the current intensity integrating detectors, such as improved accuracy in material decomposition, reduced image noise, reduced radiation dose, etc. The major problem of PCXDs, however, is the limited speed. The required count rate for clinical x-ray CT scanners may be 109 counts-per-second-per-square-millimeters (cps), while the operational count rates (where a count rate loss is less than 5%) of available PCXDs are much lower, e.g., 5 × 105 cps. In this study, we propose to enable PCXD-based clinical CT imaging using these slower-than-desired detectors by a combination of four methods that reduce the count rate requirements and compensate for the effect of pileup.

A CCD-based detector for SPECT

We are investigating the use of a CCD for high-resolution radionuclide imaging. The use of a CCD has the potential to provide very high spatial resolution on the order of 200 to 400 /spl mu/m, while significantly simplifying the readout electronics. The detector is based on a special CCD with on-chip multiplication gain that allows high-speed operation while maintaining the read noise at a very low level of <1 electron. To achieve high detection efficiency and excellent spatial resolution for incident gamma flux, a specially fabricated thick microcolumnar CsI(Tl) scintillator was optically coupled to the CCD. A prototype SPECT imaging system was assembled by incorporating pinhole/parallel hole collimators in the design. The use of this system for radionuclide imaging has been demonstrated through tomographic imaging of a test phantom filled with /sup 99m/Tc.

Quantitative fluorescence tomography using a trimodality system: in vivo validation.

A fully integrated trimodality fluorescence, diffuse optical, and x-ray computed tomography (FT/DOT/XCT) system for small animal imaging is reported in this work. The main purpose of this system is to obtain quantitatively accurate fluorescence concentration images using a multimodality approach. XCT offers anatomical information, while DOT provides the necessary background optical property map to improve FT image accuracy. The quantitative accuracy of this trimodality system is demonstrated in vivo. In particular, we show that a 2-mm-diam fluorescence inclusion located 8 mm deep in a nude mouse can only be localized when functional a priori information from DOT is available. However, the error in the recovered fluorophore concentration is nearly 87%. On the other hand, the fluorophore concentration can be accurately recovered within 2% error when both DOT functional and XCT structural a priori information are utilized together to guide and constrain the FT reconstruction algorithm.