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.

Assessment of multi-energy inter-pixel coincidence counters for photon-counting detectors at the presence of charge sharing and pulse pileup: A simulation study.

PURPOSE: Spectral distortion due to charge sharing (CS) and pulse pileup (PP) in photon-counting detectors (PCDs) degrades the quality of PCD data. We recently proposed multi-energy inter-pixel coincidence counters (MEICC) that provided spectral cross-talk information related to CS. When PP was absent, the normalized Cramér-Rao lower bounds (nCRLBs) of 225-µm pixel PCDs with MEICC was comparable to those of 450-µm pixel PCD without MEICC. The aim of this study was to assess the performance of PCDs with MEICC in the presence of both CS and PP using computer simulations. METHODS: An in-house Monte Carlo program was modified to incorporate the following four temporal elements: (1) A pulse shape with a pulse duration of 20 ns, (2) delays of up to 10 ns in anode arrival times when photons were incident on pixel boundaries, (3) offsets proportional to a vertical separation between the primary and secondary charge clouds at the rate of ±4 ns per ±100 µm, and (4) a stochastic fluctuation of anode arrival times for all of the charge clouds with a standard deviation of 2 ns. We assessed the performance of five PCDs, (a)-(f), for three spectral tasks, (A)-(C): (a) The conventional PCD, (b) a PCD with MEICC, (c) a PCD with one coincidence counter (1CC), (d) a PCD with a 3 × 3 analog charge summing scheme (ACS), and (e) a PCD with a 3 × 3 digital count summing scheme (DCS); (A) conventional CT imaging with water (i.e., linear attenuation coefficient maps), (B) water-bone material decomposition, and (C) K-edge imaging with tungsten. The tube current was changed from 1 mA to 1000 mA and the nCRLB was assessed. RESULTS: The recorded count rate curves were fitted by the non-paralyzable detection model with the effective deadtime parameter. The best fit was achieved by 25.8 ns for the conventional PCD, 18.6 ns for MEICC and 1CC, 140.5 ns for ACS, and 209.0 ns for DCS. The nCRLBs were strongly dependent on count rates. MEICC provided the best nCRLBs for all of the imaging tasks over the count rate range investigated except for a few conditions such as K-edge imaging at 1 mA. PP decreased the merit of MEICC over the conventional PCD in addressing CS. Nonetheless, MEICC consistently provided better nCRLBs than the conventional PCD did. The nCRLBs of MEICC were in the range of 49-58% of those of the conventional PCD for K-edge imaging, 45-76% for water-bone material decomposition, and 81-88% for the conventional CT imaging (i.e., linear attenuation coefficient maps). ACS provided better nCRLBs than the conventional PCD did only when the effect of PP was minor (e.g., when the counting efficiency of the conventional PCD was higher than 0.95 with the tube current of up to 100 mA). CONCLUSION: Besides a few cases, MEICC provides the best nCRLBs for all of the tasks at all of the count rates. ACS and DCS provide better nCRLBs than the conventional PCD does only when count rates are very low.

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.

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.

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.

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.

Intraoperative gamma imaging of axillary sentinel lymph nodes in breast cancer patients.

Sentinel lymph node (SLN) biopsy is now standard practice in the management of many breast cancer patients. Localization protocols vary in complexity and rates of success. The least complex involve only intraoperative gamma counting of radiotracer uptake or intraoperative visualization of blue-dye uptake; the most complex involve preoperative gamma imaging, intraoperative counting and intraoperative dye visualization. Intraoperative gamma imaging may improve some protocols. This study was conducted to obtain preliminary experience and information regarding intraoperative imaging. Sixteen patients were enrolled: 8 in a protocol that included intraoperative counting and dye visualization (probe/dye), 8 in a protocol that involved intraoperative imaging, counting and dye visualization (camera/probe/dye). Preoperative imaging of all 16 patients was performed using a GE 500 gamma camera with a LEAP collimator (300 cpm/muCi). The results of this imaging were not, however, given to the surgeon until the surgeon had completed the procedures required for the study. A Care Wise C-Trak probe was used for intraoperative counting. A Gamma Medica Inc. GammaCAM/OR (12.5 x 12.5 cm FOV) with a LEHR collimator (135 cpm/muCi) was used for intraoperative imaging. Times from start of surgery to external detection of a radioactive focus and to completion of excision of SLNs were recorded. Foci were detected preoperatively via imaging in 16/16 patients. Intraoperative external detection using the probe was accomplished in less than 4 min (mean = 1.5 min) in 15/16 patients, and via intraoperative imaging in 6/8 patients. The average time for completion of excision of nodes was 19 min for probe/dye and 28 min for camera/probe/dye. In one probe/dye case, review of the preoperative images prompted the surgeon to resume axillary dissection and remove one additional SLN.

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.

Intravascular probe for detection of vulnerable plaque.

PURPOSE: Coronary angiography defines geometry of lumen of artery. However, perhaps 70% of heart attacks occur when minimally obstructive thin capped fibroatheroma rupture, causing thrombus and arterial occlusion. We have developed an intravascular imaging detector to identify vulnerable coronary artery plaque. PROCEDURE: Detector measures beta or conversion electron emissions from plaque-binding radiotracers. Detector assembly fits into a 2-mm diameter catheter and overcomes technical constraints of size, sensitivity, and conformance to intravascular environment. RESULTS: Device was tested by stepping test point sources past detector to verify function. System resolution is 6.7 mm and sensitivity is 400 cps/microCi one mm from detector. CONCLUSION: This prototype is a first step in imaging of labeled vulnerable plaque in coronary arteries. This type of system may assist in development of targeted and cost effective therapies to lower incidence of acute coronary artery diseases (CAD) such as unstable angina, acute myocardial infarction, and sudden cardiac death.

A novel silicon array designed for intraoperative charged particle imaging.

A novel Si-PIN imaging array is under investigation for a charged particle (beta, positron, or alpha) sensitive intraoperative camera to be used for (residual) tumor identification during surgery. This class of collimator-less nuclear imaging device has a higher signal response for direct interactions than its scintillator-optical detector-based counterparts. Monte Carlo simulations with 635 keV betas were performed, yielding maximum and projected ranges of 1.64 and 0.55 mm in Si. Up to 90% of these betas were completely absorbed in the first 0.30 mm. Based on these results, 300 microm thick prototype Si detector arrays were designed in a 16 x 16 crossed-grid arrangement with 0.8 mm wide orthogonal strips on 1.0 mm pitch. A NIM- and CAMAC-based high-density data acquisition and processing system was used to collect the list mode data. The system was calibrated by comparisons of measured spectra to energy deposition simulations or by direct measurement of various >100 keV conversion electron or beta emitters. Mean electronic noise per strip was <3.6 keV FWHM at room temperature. When detecting positrons, which have an accompanying 511 keV annihilation background, the flood irradiated beta/gamma ratio was approximately 40, indicating that beta images could be made without the use of background rejection techniques. The intrinsic spatial resolution corresponds to the 1 x 1 mm2 pixel size, and measurements of beta emitting point and line sources yielded FWHM resolutions of 1.5 (lateral) and 2.5 mm (diagonal), respectively, with the larger widths due to particle range blurting effects. Deconvolution of the finite source size yielded intrinsic resolutions that corresponded to the image pixel size. Transmission images of circle and line phantoms with various hole sizes and pitch were resolved with either pure beta or positron irradiation without a background correction. This novel semiconductor imaging device facilitates high charged particle and low gamma sensitivity, high signal/noise ratio, and allows for compact design to potentially aid surgical guidance by providing in situ images of clinical relevance.

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.

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.

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.

Vision 20/20: Single photon counting x-ray detectors in medical imaging.

Photon counting detectors (PCDs) with energy discrimination capabilities have been developed for medical x-ray computed tomography (CT) and x-ray (XR) imaging. Using detection mechanisms that are completely different from the current energy integrating detectors and measuring the material information of the object to be imaged, these PCDs have the potential not only to improve the current CT and XR images, such as dose reduction, but also to open revolutionary novel applications such as molecular CT and XR imaging. The performance of PCDs is not flawless, however, and it seems extremely challenging to develop PCDs with close to ideal characteristics. In this paper, the authors offer our vision for the future of PCD-CT and PCD-XR with the review of the current status and the prediction of (1) detector technologies, (2) imaging technologies, (3) system technologies, and (4) potential clinical benefits with PCDs.

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.