Microcalcification detectability using a bench-top prototype photon-counting breast CT based on a Si strip detector.

PURPOSE: To investigate the feasibility of detecting breast microcalcification (µCa) with a dedicated breast computed tomography (CT) system based on energy-resolved photon-counting silicon (Si) strip detectors. METHODS: The proposed photon-counting breast CT system and a bench-top prototype photon-counting breast CT system were simulated using a simulation package written in matlab to determine the smallest detectable µCa. A 14 cm diameter cylindrical phantom made of breast tissue with 20% glandularity was used to simulate an average-sized breast. Five different size groups of calcium carbonate grains, from 100 to 180 µm in diameter, were simulated inside of the cylindrical phantom. The images were acquired with a mean glandular dose (MGD) in the range of 0.7-8 mGy. A total of 400 images was used to perform a reader study. Another simulation study was performed using a 1.6 cm diameter cylindrical phantom to validate the experimental results from a bench-top prototype breast CT system. In the experimental study, a bench-top prototype CT system was constructed using a tungsten anode x-ray source and a single line 256-pixels Si strip photon-counting detector with a pixel pitch of 100 µm. Calcium carbonate grains, with diameter in the range of 105-215 µm, were embedded in a cylindrical plastic resin phantom to simulate µCas. The physical phantoms were imaged at 65 kVp with an entrance exposure in the range of 0.6-8 mGy. A total of 500 images was used to perform another reader study. The images were displayed in random order to three blinded observers, who were asked to give a 4-point confidence rating on each image regarding the presence of µCa. The µCa detectability for each image was evaluated by using the average area under the receiver operating characteristic curve (AUC) across the readers. RESULTS: The simulation results using a 14 cm diameter breast phantom showed that the proposed photon-counting breast CT system can achieve high detection accuracy with an average AUC greater than 0.89 ± 0.07 for µCas larger than 120 µm in diameter at a MGD of 3 mGy. The experimental results using a 1.6 cm diameter breast phantom showed that the prototype system can achieve an average AUC greater than 0.98 ± 0.01 for µCas larger than 140 µm in diameter using an entrance exposure of 1.2 mGy. CONCLUSIONS: The proposed photon-counting breast CT system based on a Si strip detector can potentially offer superior image quality to detect µCa with a lower dose level than a standard two-view mammography.

Characterization of energy response for photon-counting detectors using x-ray fluorescence.

PURPOSE: To investigate the feasibility of characterizing a Si strip photon-counting detector using x-ray fluorescence. METHODS: X-ray fluorescence was generated by using a pencil beam from a tungsten anode x-ray tube with 2 mm Al filtration. Spectra were acquired at 90° from the primary beam direction with an energy-resolved photon-counting detector based on an edge illuminated Si strip detector. The distances from the source to target and the target to detector were approximately 19 and 11 cm, respectively. Four different materials, containing silver (Ag), iodine (I), barium (Ba), and gadolinium (Gd), were placed in small plastic containers with a diameter of approximately 0.7 cm for x-ray fluorescence measurements. Linear regression analysis was performed to derive the gain and offset values for the correlation between the measured fluorescence peak center and the known fluorescence energies. The energy resolutions and charge-sharing fractions were also obtained from analytical fittings of the recorded fluorescence spectra. An analytical model, which employed four parameters that can be determined from the fluorescence calibration, was used to estimate the detector response function. RESULTS: Strong fluorescence signals of all four target materials were recorded with the investigated geometry for the Si strip detector. The average gain and offset of all pixels for detector energy calibration were determined to be 6.95 mV/keV and -66.33 mV, respectively. The detector's energy resolution remained at approximately 2.7 keV for low energies, and increased slightly at 45 keV. The average charge-sharing fraction was estimated to be 36% within the investigated energy range of 20-45 keV. The simulated detector output based on the proposed response function agreed well with the experimental measurement. CONCLUSIONS: The performance of a spectral imaging system using energy-resolved photon-counting detectors is very dependent on the energy calibration of the detector. The proposed x-ray fluorescence technique offers an accurate and efficient way to calibrate the energy response of a photon-counting detector.

Characteristic performance evaluation of a photon counting Si strip detector for low dose spectral breast CT imaging.

PURPOSE: The possible clinical applications which can be performed using a newly developed detector depend on the detector's characteristic performance in a number of metrics including the dynamic range, resolution, uniformity, and stability. The authors have evaluated a prototype energy resolved fast photon counting x-ray detector based on a silicon (Si) strip sensor used in an edge-on geometry with an application specific integrated circuit to record the number of x-rays and their energies at high flux and fast frame rates. The investigated detector was integrated with a dedicated breast spectral computed tomography (CT) system to make use of the detector's high spatial and energy resolution and low noise performance under conditions suitable for clinical breast imaging. The aim of this article is to investigate the intrinsic characteristics of the detector, in terms of maximum output count rate, spatial and energy resolution, and noise performance of the imaging system. METHODS: The maximum output count rate was obtained with a 50 W x-ray tube with a maximum continuous output of 50 kVp at 1.0 mA. A109Cd source, with a characteristic x-ray peak at 22 keV from Ag, was used to measure the energy resolution of the detector. The axial plane modulation transfer function (MTF) was measured using a 67 µm diameter tungsten wire. The two-dimensional (2D) noise power spectrum (NPS) was measured using flat field images and noise equivalent quanta (NEQ) were calculated using the MTF and NPS results. The image quality parameters were studied as a function of various radiation doses and reconstruction filters. The one-dimensional (1D) NPS was used to investigate the effect of electronic noise elimination by varying the minimum energy threshold. RESULTS: A maximum output count rate of 100 million counts per second per square millimeter (cps/mm2) has been obtained (1 million cps per 100×100 µm pixel). The electrical noise floor was less than 4 keV. The energy resolution measured with the 22 keV photons from a 109Cd source was less than 9%. A reduction of image noise was shown in all the spatial frequencies in 1D NPS as a result of the elimination of the electronic noise. The spatial resolution was measured just above 5 line pairs per mm (lp/mm) where 10% of MTF corresponded to 5.4 mm(-1). The 2D NPS and NEQ shows a low noise floor and a linear dependence on dose. The reconstruction filter choice affected both of the MTF and NPS results, but had a weak effect on the NEQ. CONCLUSIONS: The prototype energy resolved photon counting Si strip detector can offer superior imaging performance for dedicated breast CT as compared to a conventional energy-integrating detector due to its high output count rate, high spatial and energy resolution, and low noise characteristics, which are essential characteristics for spectral breast CT imaging.

A cascaded model of spectral distortions due to spectral response effects and pulse pileup effects in a photon-counting x-ray detector for CT.

PURPOSE: Energy discriminating, photon-counting detectors (PCDs) are an emerging technology for computed tomography (CT) with various potential benefits for clinical CT. The photon energies measured by PCDs can be distorted due to the interactions of a photon with the detector and the interaction of multiple coincident photons. These effects result in distorted recorded x-ray spectra which may lead to artifacts in reconstructed CT images and inaccuracies in tissue identification. Model-based compensation techniques have the potential to account for the distortion effects. This approach requires only a small number of parameters and is applicable to a wide range of spectra and count rates, but it needs an accurate model of the spectral distortions occurring in PCDs. The purpose of this study was to develop a model of those spectral distortions and to evaluate the model using a PCD (model DXMCT-1; DxRay, Inc., Northridge, CA) and various x-ray spectra in a wide range of count rates. METHODS: The authors hypothesize that the complex phenomena of spectral distortions can be modeled by: (1) separating them into count-rate independent factors that we call the spectral response effects (SRE), and count-rate dependent factors that we call the pulse pileup effects (PPE), (2) developing separate models for SRE and PPE, and (3) cascading the SRE and PPE models into a combined SRE+PPE model that describes PCD distortions at both low and high count rates. The SRE model describes the probability distribution of the recorded spectrum, with a photo peak and a continuum tail, given the incident photon energy. Model parameters were obtained from calibration measurements with three radioisotopes and then interpolated linearly for other energies. The PPE model used was developed in the authors' previous work [K. Taguchi et al., "Modeling the performance of a photon counting x-ray detector for CT: Energy response and pulse pileup effects," Med. Phys. 38(2), 1089-1102 (2011)]. The agreement between the x-ray spectra calculated by the cascaded SRE+PPE model and the measured spectra was evaluated for various levels of deadtime loss ratios (DLR) and incident spectral shapes, realized using different attenuators, in terms of the weighted coefficient of variation (COVW), i.e., the root mean square difference weighted by the statistical errors of the data and divided by the mean. RESULTS: At low count rates, when DLR < 10%, the distorted spectra measured by the DXMCT-1 were in agreement with those calculated by SRE only, with COVW's less than 4%. At higher count rates, the measured spectra were also in agreement with the ones calculated by the cascaded SRE+PPE model; with PMMA as attenuator, COVW was 5.6% at a DLR of 22% and as small as 6.7% for a DLR as high as 55%. CONCLUSIONS: The x-ray spectra calculated by the proposed model agreed with the measured spectra over a wide range of count rates and spectral shapes. The SRE model predicted the distorted, recorded spectra with low count rates over various types and thicknesses of attenuators. The study also validated the hypothesis that the complex spectral distortions in a PCD can be adequately modeled by cascading the count-rate independent SRE and the count-rate dependent PPE.

A gantry-based tri-modality system for bioluminescence tomography.

A gantry-based tri-modality system that combines bioluminescence (BLT), diffuse optical (DOT), and x-ray computed tomography (XCT) into the same setting is presented here. The purpose of this system is to perform bioluminescence tomography using a multi-modality imaging approach. As parts of this hybrid system, XCT and DOT provide anatomical information and background optical property maps. This structural and functional a priori information is used to guide and restrain bioluminescence reconstruction algorithm and ultimately improve the BLT results. The performance of the combined system is evaluated using multi-modality phantoms. In particular, a cylindrical heterogeneous multi-modality phantom that contains regions with higher optical absorption and x-ray attenuation is constructed. We showed that a 1.5 mm diameter bioluminescence inclusion can be localized accurately with the functional a priori information while its source strength can be recovered more accurately using both structural and the functional a priori information.

Modeling the performance of a photon counting x-ray detector for CT: energy response and pulse pileup effects.

PURPOSE: Recently, photon counting x-ray detectors (PCXDs) with energy discrimination capabilities have been developed for potential use in clinical computed tomography (CT) scanners. These PCXDs have great potential to improve the quality of CT images due to the absence of electronic noise and weights applied to the counts and the additional spectral information. With high count rates encountered in clinical CT, however, coincident photons are recorded as one event with a higher or lower energy due to the finite speed of the PCXD. This phenomenon is called a "pulse pileup event" and results in both a loss of counts (called "deadtime losses") and distortion of the recorded energy spectrum. Even though the performance of PCXDs is being improved, it is essential to develop algorithmic methods based on accurate models of the properties of detectors to compensate for these effects. To date, only one PCXD (model DXMCT-1, DxRay, Inc., Northridge, CA) has been used for clinical CT studies. The aim of that study was to evaluate the agreement between data measured by DXMCT-1 and those predicted by analytical models for the energy response, the deadtime losses, and the distorted recorded spectrum caused by pulse pileup effects. METHODS: An energy calibration was performed using 99mTc (140 keV), 57Co (122 keV), and an x-ray beam obtained with four x-ray tube voltages (35, 50, 65, and 80 kVp). The DXMCT-1 was placed 150 mm from the x-ray focal spot; the count rates and the spectra were recorded at various tube current values from 10 to 500 microA for a tube voltage of 80 kVp. Using these measurements, for each pulse height comparator we estimated three parameters describing the photon energy-pulse height curve, the detector deadtime tau, a coefficient k that relates the x-ray tube current I to an incident count rate a by a = k x I, and the incident spectrum. The mean pulse shape of all comparators was acquired in a separate study and was used in the model to estimate the distorted recorded spectrum. The agreement between data measured by the DXMCT-1 and those predicted by the models was quantified by the coefficient of variation (COV), i.e., the root mean square difference divided by the mean of the measurement. RESULTS: Photon energy versus pulse height curves calculated with an analytical model and those measured using the DXMCT-1 were in agreement within 0.2% in terms of the COV. The COV between the output count rates measured and those predicted by analytical models was 2.5% for deadtime losses of up to 60%. The COVs between spectra measured and those predicted by the detector model were within 3.7%-7.2% with deadtime losses of 19%-46%. CONCLUSIONS: It has been demonstrated that the performance of the DXMCT-1 agreed exceptionally well with the analytical models regarding the energy response, the count rate, and the recorded spectrum with pulse pileup effects. These models will be useful in developing methods to compensate for these effects in PCXD-based clinical CT systems.

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.

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.

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.

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/mm(2)/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 16×16 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 (57)Co source. An output rate of 6×10(6) 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.

Polycrystalline Mercuric Iodide Films on CMOS Readout Arrays.

We have created high-resolution x-ray imaging devices using polycrystalline mercuric iodide (HgI(2)) films grown directly onto CMOS readout chips using a thermal vapor transport process. Images from prototype 400x400 pixel HgI(2)-coated CMOS readout chips are presented, where the pixel grid is 30 mum x 30 mum. The devices exhibited sensitivity of 6.2 muC/Rcm(2) with corresponding dark current of approximately 2.7 nA/cm(2), and a 80 mum FWHM planar image response to a 50 mum slit aperture. X-ray CT images demonstrate a point spread function sufficient to obtain a 50 mum spatial resolution in reconstructed CT images at a substantially reduced dose compared to phosphor-coated readouts. The use of CMOS technology allows for small pixels (30 mum), fast readout speeds (8 fps for a 3200x3200 pixel array), and future design flexibility due to the use of well-developed fabrication processes.

Gallstone detection at CT in vitro: effect of peak voltage setting.

This study was a retrospective single-institutional study approved by the Committee on Human Research and was HIPAA compliant. A waiver for informed consent was granted. The purpose of the study was to evaluate the effect of four peak voltage settings on the in vitro conspicuity of gallstones in an anthropomorphic phantom at computed tomography (CT). An anthropomorphic phantom was scanned with (n = 86) or without (n = 85) gallstones at CT by using 80, 100, 120, and 140 kVp. The sensitivity for gallstone detection was significantly higher at 140 kVp (86% [74 of 86] for reader 1 and 81% [70 of 86] for reader 2) than at lower voltage settings (up to 67% [58 of 86] for reader 1 and 63% [54 of 86] for reader 2, P < .05 for each reader), regardless of gallstone size (<1.0 cm vs > or =1.0 cm in diameter, P < .05 for each reader). CT attenuation measurements were not useful for determination of gallstone composition. Abdominal CT performed at 140 kVp may be useful when gallstone disease is of clinical concern.

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.

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 using (111)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 the 111In-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.