Benjamin Tsui

Realistic CT simulation using the 4D XCAT phantom.

The authors develop a unique CT simulation tool based on the 4D extended cardiac-torso (XCAT) phantom, a whole-body computer model of the human anatomy and physiology based on NURBS surfaces. Unlike current phantoms in CT based on simple mathematical primitives, the 4D XCAT provides an accurate representation of the complex human anatomy and has the advantage, due to its design, that its organ shapes can be changed to realistically model anatomical variations and patient motion. A disadvantage to the NURBS basis of the XCAT, however, is that the mathematical complexity of the surfaces makes the calculation of line integrals through the phantom difficult. They have to be calculated using iterative procedures; therefore, the calculation of CT projections is much slower than for simpler mathematical phantoms. To overcome this limitation, the authors used efficient ray tracing techniques from computer graphics, to develop a fast analytic projection algorithm to accurately calculate CT projections directly from the surface definition of the XCAT phantom given parameters defining the CT scanner and geometry. Using this tool, realistic high-resolution 3D and 4D projection images can be simulated and reconstructed from the XCAT within a reasonable amount of time. In comparison with other simulators with geometrically defined organs, the XCAT-based algorithm was found to be only three times slower in generating a projection data set of the same anatomical structures using a single 3.2 GHz processor. To overcome this decrease in speed would, therefore, only require running the projection algorithm in parallel over three processors. With the ever decreasing cost of computers and the rise of faster processors and multi-processor systems and clusters, this slowdown is basically inconsequential, especially given the vast improvement the XCAT offers in terms of realism and the ability to generate 3D and 4D data from anatomically diverse patients. As such, the authors conclude that the efficient XCAT-based CT simulator developed in this work will have applications in a broad range of CT imaging research.

Ectopic Expression of the Sodium-Iodide Symporter Enables Imaging of Transplanted Cardiac Stem Cells In Vivo by Single-Photon Emission Computed Tomography or Positron Emission Tomography

OBJECTIVES We examined the sodium-iodide symporter (NIS), which promotes in vivo cellular uptake of technetium 99m ((99m)Tc) or iodine 124 ((124)I), as a reporter gene for cell tracking by single-photon emission computed tomography (SPECT) or positron emission tomography (PET) imaging. BACKGROUND Stem cells offer the promise of cardiac repair. Stem cell labeling is a prerequisite to tracking cell fate in vivo. METHODS The human NIS complementary deoxyribonucleic acid was transduced into rat cardiac-derived stem cells (rCDCs) using lentiviral vectors. Rats were injected intramyocardially with up to 4 million NIS(+)-rCDCs immediately after left anterior descending coronary artery ligation. Dual isotope SPECT (or PET) imaging was performed, using (99m)Tc (or (124)I) for cell detection and thallium 201 (or ammonia 13) for myocardial delineation. In a subset of animals, high resolution ex vivo SPECT scans of explanted hearts were obtained to confirm that in vivo signals were derived from the cell injection site. RESULTS NIS expression in rCDCs did not affect cell viability and proliferation. NIS activity was verified in isolated transduced cells by measuring (99m)Tc uptake. NIS(+) rCDCs were visualized in vivo as regions of (99m)Tc or (124)I uptake within a perfusion deficit in the SPECT and PET images, respectively. Cells could be visualized by SPECT up to 6 days post-injection. Ex vivo SPECT confirmed that in vivo (99m)Tc signals were localized to the cell injection sites. CONCLUSIONS Ectopic NIS expression allows noninvasive in vivo stem cell tracking in the myocardium, using either SPECT or PET. The general approach shows significant promise in tracking the fate of transplanted cells participating in cardiac regeneration, given its ability to observe living cells using clinically applicable imaging modalities.

Analytic system matrix resolution modeling in PET: an application to Rb-82 cardiac imaging

An area of growing interest in PET imaging has been that of incorporating increasingly more accurate system matrix elements into the reconstruction task, thus arriving at images of higher quality. This work explores application of an analytic approach which individually models and combines the various resolution degrading phenomenon in PET (inter-crystal scattering, inter-crystal penetration, photon non-collinearity and positron range), and does not require extensive experimental measurements and/or simulations. The approach is able to produce considerable enhancements in image quality. The reconstructed resolution is seen to improve from 5.1mm-7.7mm across the field-of-view (FoV) to ap3.5mm nearly uniformly across the FoV. Furthermore, phantom studies indicate clearly improved images, while similar significant improvements are seen for the particular task of Rb-82 cardiac imaging.

Fast modelling of the collimator–detector response in Monte Carlo simulation of SPECT imaging using the angular response function

Interactions of incident photons with the collimator and detector, including septal penetration, scatter and x-ray fluorescence, are significant sources of image degradation in applications of SPECT including dual isotope imaging and imaging using radioisotopes that emit high- or medium-energy photons. Modelling these interactions using full Monte Carlo (MC) simulations is computationally very demanding. We present a new method based on the use of angular response functions (ARFs). The ARF is a function of the incident photons direction and energy and represents the probability that a photon will either interact with or pass through the collimator, and be detected at the intersection of the photons direction vector and the detection plane in an energy window of interest. The ARFs were pre-computed using full MC simulations of point sources that include propagation through the collimator-detector system. We have implemented the ARF method for use in conjunction with the SimSET/PHG MC code to provide fast modelling of both interactions in the patient and in the collimator-detector system. Validation results in the three cases studied show that there was good agreement between the projections generated using the ARF method and those from previously validated full MC simulations, but with hundred to thousand fold reductions in simulation time.

MicroCT with energy-resolved photon-counting detectors.

The goal of this paper was to investigate the benefits that could be realistically achieved on a microCT imaging system with an energy-resolved photon-counting x-ray detector. To this end, we built and evaluated a prototype microCT system based on such a detector. The detector is based on cadmium telluride (CdTe) radiation sensors and application-specific integrated circuit (ASIC) readouts. Each detector pixel can simultaneously count x-ray photons above six energy thresholds, providing the capability for energy-selective x-ray imaging. We tested the spectroscopic performance of the system using polychromatic x-ray radiation and various filtering materials with K-absorption edges. Tomographic images were then acquired of a cylindrical PMMA phantom containing holes filled with various materials. Results were also compared with those acquired using an intensity-integrating x-ray detector and single-energy (i.e. non-energy-selective) CT. This paper describes the functionality and performance of the system, and presents preliminary spectroscopic and tomographic results. The spectroscopic experiments showed that the energy-resolved photon-counting detector was capable of measuring energy spectra from polychromatic sources like a standard x-ray tube, and resolving absorption edges present in the energy range used for imaging. However, the spectral quality was degraded by spectral distortions resulting from degrading factors, including finite energy resolution and charge sharing. We developed a simple charge-sharing model to reproduce these distortions. The tomographic experiments showed that the availability of multiple energy thresholds in the photon-counting detector allowed us to simultaneously measure target-to-background contrasts in different energy ranges. Compared with single-energy CT with an integrating detector, this feature was especially useful to improve differentiation of materials with different attenuation coefficient energy dependences.

Development of a dynamic model for the lung lobes and airway tree in the NCAT phantom

The 4D NCAT phantom was developed to realistically model human anatomy based on the Visible Human data and cardiac and respiratory motions based on 4D tagged MRI and respiratory-gated CT data from normal human subjects. Currently, the 4D NCAT phantom does not include the airway tree or its motion within the lungs. Also, each lung is defined with a single surface; the individual lobes are not distinguished. We further the development of the phantom by creating dynamic models for the individual lung lobes and for the airway tree in each lobe. NURBS surfaces for the lobes and an initial airway tree model (/spl sim/4 generations) were created through manual segmentation of the Visible Human data. A mathematical algorithm with physiological constraints will be used to extend the original airway model to fill each lobe. For each parent airway branch inside a lobe, the algorithm extends the airway tree by creating two daughter branches modeled with cylindrical tubes. Parameters for the cylindrical tubes such as diameter, length, and angle are constrained based on flow parameters and available lung space. The bifurcating branches are propagated within a lung lobe until it is filled. Once each lobe is filled, the cylindrical tubes are converted into NURBS surfaces and blended with the original airway tree obtained through segmentation. The respiratory model previously developed using the respiratory-gated CT data is then applied to the surfaces of the lobes and airway tree to create the new 4D respiratory model. This improved model will provide a useful tool in future studies researching the effects of respiratory motion on lung tumor imaging. It is also an important step in advancing the 4D NCAT for applications in more high-resolution imaging modalities such as X-ray CT.

Investigation of the use of photon counting x-ray detectors with energy discrimination capability for material decomposition in micro-computed tomography

Recently developed solid-state detectors combined with high-speed ASICs that allow individual pixel pulse processing may prove useful as detectors for small animal micro-computed tomography. One appealing feature of these photon-counting x-ray detectors (PCXDs) is their ability to discriminate between photons with different energies and count them in a small number (2-5) of energy windows. The data in these energy windows may be thought of as arising from multiple simultaneous x-ray beams with individual energy spectra, and could thus potentially be used to perform material composition analysis. The goal of this paper was to investigate the potential advantages of PCXDs with multiple energy window counting capability as compared to traditional integrating detectors combined with acquisition of images using x-ray beams with 2 different kVps. For the PCXDs, we investigated 3 potential sources of crosstalk: scatter in the object and detector, limited energy resolution, and pulse piluep. Using Monte Carlo simulations, we showed that scatter in the object and detector results in relatively little crosstalk between the data in the energy windows. To study the effects of energy resolution and pulse-pileup, we performed simulations evaluating the accuracy and precision of basis decomposition using a detector with 2 or 5 energy windows and a single kVp compared to an dual kVp acquisitions with an integrating detector. We found that, for noisy data, the precision of estimating the thickness of two basis materials for a range of material compositions was better for the single kVp multiple energy window acquisitions compared to the dual kVp acquisitions with an integrating detector. The advantage of the multi-window acquisition was somewhat reduced when the energy resolution was reduced to 10 keV and when pulse pileup was included, but standard deviations of the estimated thicknesses remained better by more than a factor of 2.

Extension of the 4D NCAT phantom to dynamic X-ray CT simulation

The 4D NCAT phantom, developed to provide a realistic model of the human anatomy and physiology, is widely used in SPECT imaging research, but lacks anatomical details for application to high-resolution imaging such as X-ray CT and MRI. At the same time, current phantoms used in these areas lack the sufficient realism and flexibility to depict the complex shapes of real human organs and the deformations of those shapes due to anatomical variation and normal physiologic motion. We seek to fill that void by building upon the existing 4D NCAT phantom. Tissues distinguishable in X-ray CT imaging, including small details such as the pulmonary artery tree in the lungs and vasculature in the organs and body, were modeled based on segmented visible human CT data and high-resolution multi-slice spiral CT (MSCT) data. The models were created using a combination of NURBS and subdivision (SD) surfaces. The anatomy was extended to include structures in the head and abdomen for brain and prostate imaging applications. To efficiently simulate high-resolution X-ray CT images, we developed a new analytic projection algorithm to accurately calculate the projections (parallel, fan, or cone-beam geometries) directly from the surface definition of the phantom without using voxelization. The projection data were reconstructed using algorithms developed in our laboratory for fan- and cone-beam reconstruction of X-ray CT projection images. We conclude that the new 4D NCAT with its enhanced anatomy and physiology will provide an important tool in high-resolution imaging research.

Detection of Dose Response in Chronic Doxorubicin- Mediated Cell Death with Cardiac Technetium 99m Annexin V Single-Photon Emission Computed Tomography

The aim of this study was to evaluate whether technetium 99m hydrazinonicotinamide (99mTc-HYNIC)-annexin V single-photon emission computed tomography (SPECT) would detect dose-dependent doxorubicin (DOX)-mediated cell death in the heart compared with functional echocardiography. Adult female Sprague-Dawley rats were treated with DOX (cumulative dose of 15 or 7.5 mg/kg) or saline (n = 7) and monitored by echocardiography. Rats were injected with 7 to 8 mCi 99mTc-HYNIC-annexin V and imaged 1 hour postinjection using a small animal dual-head SPECT/computed tomography (CT) system with multipinhole technology. Two regions of interest were drawn in the myocardium and soft tissue regions to calculate the cardiac uptake ratio (CUR) of reconstructed images. Myocardium and blood were harvested for radioactivity measurements or TUNEL assay. Biodistribution of 99mTc-HYNIC-annexin V uptake, CUR from SPECT/CT fused cardiac images, and TUNEL of myocardium demonstrated a dose-dependent toxicity response, with the cumulative 15 mg/kg DOX treatment showing the greatest degree of cell death. In contrast, echocardiography detected functional deficits only at the highest DOX dose. In vivo molecular imaging of DOX-induced cardiac toxicity with 99mTc-HYNIC-annexin V detects dose-dependent cell death before ventricular deficits are observed with echocardiography. 99mTc-HYNIC-annexin V SPECT-based molecular imaging may provide an attractive new technique for assessing early changes in myocardial function in patients undergoing DOX therapy.

Validation and evaluation of model-based cross-talk compensation method in simultaneous /sup 99m/Tc stress and /sup 201/Tl rest myocardial perfusion SPECT

Simultaneous acquisition of /sup 99m/Tc stress and /sup 201/Tl rest myocardial perfusion SPECT has several potential advantages, but the image quality is degraded by crosstalk between the Tc and Tl data. We have previously developed a crosstalk model that includes estimates of the downscatter and Pb X-ray for use in crosstalk compensation. In this work, we validated the model by comparing the crosstalk from /sup 99m/Tc to the Tl window calculated using a combination of the SimSET-MCNP Monte Carlo simulation codes. We also evaluated the model-based crosstalk compensation method using both simulated data from the 3-D MCAT phantom and experimental data from a physical phantom with a myocardial defect. In these studies, the Tl distributions were reconstructed from crosstalk contaminated data without crosstalk compensation, with compensation using the model-based crosstalk estimate, and with compensation using the known true crosstalk, and were compared with the Tl distribution reconstructed from uncontaminated Tl data. Results show that the model gave good estimates of both the downscatter photons and Pb X-rays in the simultaneous dual-isotopes myocardial perfusion SPECT. The model-based compensation method provided image quality that was significantly improved as compared to no compensation and was very close to that from the separate acquisition.