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Simulation involves computer generated phantoms, models of the imaging process, and fast computational methods, Fig. 1. Computer phantoms provide a model of the subjectís anatomy and physiology. Given a model of the physics of the imaging process, acquired data of a computer phantom can be generated using the computational methods. A major advantage to using computer-generated phantoms in simulation studies is that the exact anatomy and physiological functions of the phantom are known, thus providing a gold standard from which to evaluate and improve medical imaging devices and image processing and reconstruction techniques. Other advantages are that computer phantoms are always willing participants and can be altered easily to model different anatomies and medical situations providing a large population of subjects from which to perform research. It is frequently difficult both ethically and practically to test every combination of parameters on patients under clinical conditions.
A vital aspect of simulation is to have a realistic phantom or model of the subject's anatomy. Without this, the results of the simulation may not be indicative of what would occur in actual patients or animal subjects and would, therefore, have limited practical value. We develop two digital human phantoms in our laboratory for use in medical imaging research, the 4D MCAT and XCAT* phantoms. In addition, we develop a digital mouse phantom, the 4D MOBY phantom, for molecular imaging research.
The Mathematical Cardiac Torso (MCAT) phantom, Fig. 2, is a digital anthropomorphic phantom developed for use in nuclear medicine imaging research, specifically single-photon emission computed tomography (SPECT) and positron emission tomography (PET). The anatomy of the 4D MCAT phantom is based on simple geometric primitives but uses overlap, cut planes, and intersection to form the complex biological shapes. Using mathematical formulae, the size, shape and configurations of the major thoracic structures and organs- such as the heart, liver, breasts, and rib cage- are modeled for imaging purposes. Though anatomically less realistic than phantoms derived from CT or MRI images of patients, the MCAT phantom has the advantage that it can be easily modified to simulate a wide variety of patient anatomies and to simulate patient motion. Anatomical variations and patient motions are simulated by varying the parameters that define the different geometric primitives and cut planes describing the internal organs (cardiac, liver, breast etc). The 4D MCAT phantom includes an ellipsoid-based model for the beating heart based on gated MRI patient data and a respiratory model based on known respiratory mechanics. The phantom is capable of simulating two physical models: a 3D distribution of attenuation coefficients for a given photon energy and a 3D distribution of emission radionuclide activity for the various organs. To simulate emission imaging data, the organs are assigned their individual uptake ratios for the desired radiopharmaceutical. To simulate transmission imaging data, the various organs are assigned their individual attenuation coefficients for a given photon energy.
Fig. 2. (Left) Anterior view of the 4D MCAT phantom. (Right) Emission and transmission simulations performed using the phantom.
The 4D NURBS-based Cardiac-Torso (XCAT*) phantom (Fig. 3) was originally developed to provide a realistic and flexible model of the human anatomy and physiology for use in nuclear medicine research, specifically single-photon emission computed tomography (SPECT) and positron emission tomography (PET). Non-uniform rational b-splines, or NURBS surfaces were used to construct the organ shapes in the XCAT* phantom using the three-dimensional Visible Human CT dataset as their basis. NURBS surfaces can be altered easily to model anatomical variations and patient motion. The XCAT* phantom was extended to four dimensions to model common patient motions such as the cardiac and respiratory motions using 4D tagged magnetic resonance imaging (MRI) data and 4D high-resolution respiratory-gated CT data respectively. Both datasets were acquired from normal patient volunteers. With its basis upon human data and the inherent flexibility of the NURBS primitives, the result is a computer-generated phantom that closely resembles the anatomical structures and cardiac and respiratory motions of a normal human subject. Combined with accurate models of the imaging process, the 4D XCAT* is capable of simulating imaging data close to that of actual patients. The 4D XCAT* phantom has provided an excellent tool with which to study the effects of anatomy and patient motions on SPECT and PET images. It is widely used in nuclear medicine imaging research.
Fig. 3. (Left) Anterior view of the original 4D XCAT* phantom. (Middle) Cardiac and respiratory motion models of the XCAT* phantom. (Right) Emission and transmission simulations performed using the phantom.
Although capable of being far more realistic, the 4D XCAT* phantom was originally designed for low-resolution nuclear medicine imaging research, and lacks the anatomical detail required for use in higher-resolution imaging modalities such as x-ray CT. At the same time, there is a lack of realistic and flexible computer-based phantoms for use in this area. We plan to fill that void by building upon the existing 4D XCAT* phantom and other simulation tools developed in our laboratory. Unlike current computer phantoms used in x-ray CT, the XCAT* has the advantage, due to its design, that its organ shapes can be changed to realistically model different anatomical variations and patient motion. The anatomy and physiology of the XCAT* phantom is currently being updated to include the level of detail needed for use in high-resolution x-ray CT imaging research, Fig. 4. In addition, sophisticated models of the x-ray CT imaging process are being developed to generate CT images from the phantom that accurately mimic that obtained from actual patients.
As x-ray CT evolves towards 4D dynamic functional imaging, the simulation tools developed in this work will have applications in a broad range of imaging research in developing image acquisition strategies, image processing and reconstruction methods, and image visualization and interpretation techniques. Also, the tools provide the necessary foundation to achieve our longer range goal to optimize clinical CT applications so as to obtain the highest possible image quality with the minimum possible radiation dose to the patient. Such a task can only be practically and efficiently performed using accurate and realistic computer simulation methods which we are developing.
Fig. 4. (Left) Initial extension of the 4D XCAT* anatomy. (Right) Simulated chest x-ray CT images from the extended 4D XCAT*. Coronal (top row) and transaxial (bottom 2 rows) reconstructed slices are shown. Images are more realistic than those shown in Fig. 3.
The rapid growth in genetics and molecular biology combined with the development of techniques for genetically engineering small animals has led to increased interest in in vivo small animal imaging. With the rise of small animal imaging, new instrumentation, data acquisition strategies, and image processing and reconstruction techniques are being developed and researched. A major challenge is how to evaluate the results of these new developments. Simulation techniques can provide a vital tool to evaluate and improve molecular imaging devices and techniques. Currently, there is a lack of realistic computer-generated phantoms modeling the mouse anatomy and physiological functions for use in molecular imaging research.
The same methods and techniques used to develop the 4D XCAT* phantom were used in the creation of a new 4D mouse whole body (MOBY) phantom, Fig. 5. The organ shapes are modeled with NURBS surfaces. High-resolution 3D magnetic resonance microscopy (MRM) data obtained from the Duke Center for In Vivo Microscopy was used as the basis for the formation of the surfaces. Cardiac and respiratory motions were modeled using a gated black-blood magnetic resonance imaging (bb-MRI) dataset of a normal mouse as the basis for the cardiac model and respiratory-gated MRI and known respiratory mechanics as the basis for the respiratory model. The gated MR images were obtained from the University of Virginia. In each case, the time-changing 3D surfaces are defined by a set of time curves to create time continuous dynamic or 4D NURBS surface models. The MOBY phantom provides a unique and useful tool in molecular imaging research, especially in the development of new imaging instrumentation, image acquisition strategies, and image processing and reconstruction methods.
Fig. 5. (Left) Anterior view of the 4D MOBY phantom. (Middle) Cardiac and respiratory motions of the MOBY phantom. (Right) MicroCT and MicroSPECT images simulated using the phantom.