Benjamin M. W. Tsui

Dynamic Imaging of Allogeneic Mesenchymal Stem Cells Trafficking to Myocardial Infarction

Background—Recent results from animal studies suggest that stem cells may be able to home to sites of myocardial injury to assist in tissue regeneration. However, the histological interpretation of postmortem tissue, on which many of these studies are based, has recently been widely debated. Methods and Results—With the use of the high sensitivity of a combined single-photon emission CT (SPECT)/CT scanner, the in vivo trafficking of allogeneic mesenchymal stem cells (MSCs) colabeled with a radiotracer and MR contrast agent to acute myocardial infarction was dynamically determined. Redistribution of the labeled MSCs after intravenous injection from initial localization in the lungs to nontarget organs such as the liver, kidney, and spleen was observed within 24 to 48 hours after injection. Focal and diffuse uptake of MSCs in the infarcted myocardium was already visible in SPECT/CT images in the first 24 hours after injection and persisted until 7 days after injection and was validated by tissue counts of radioactivity. In contrast, MRI was unable to demonstrate targeted cardiac localization of MSCs in part because of the lower sensitivity of MRI. Conclusions—Noninvasive radionuclide imaging is well suited to dynamically track the biodistribution and trafficking of mesenchymal stem cells to both target and nontarget organs.

Three-dimensional iterative reconstruction algorithms with attenuation and geometric point response correction

A three-dimensional iterative reconstruction algorithm which incorporates models of the geometric point response in the projector-backprojector is presented for parallel, fan, and cone beam geometries. The algorithms have been tested on an IBM 3090-600S supercomputer. The iterative EM reconstruction algorithm is 50 times longer with geometric response and photon attenuation models than without modeling these physical effects. An improvement in image quality in the reconstruction of projection data collected from a single-photon-emission computed tomography (SPECT) imaging system has been observed. Significant improvements in image quality are obtained when the geometric point response and attenuation are appropriately compensated. It is observed that resolution is significantly improved with attenuation correction alone. Using phantom experiments, it is observed that the modeling of the spatial system response imposes a smoothing without loss of resolution. >

A realistic spline-based dynamic heart phantom

We develop a realistic computerized heart phantom for use in medical imaging research. This phantom is a hybrid of realistic patient-based phantoms and flexible geometry-based phantoms. The surfaces of heart structures are defined using non-uniform rational B-splines (NURBS), as used in 3D computer graphics. The NURBS primitives define continuous surfaces allowing the phantom to be defined at any resolution. Also, by fitting NURBS to patient data, the phantom is more realistic than those based on solid geometry. An important innovation is the extension of NURBS to the fourth dimension, time, to model heart motion. Points on the surfaces of heart structures were selected from a gated MRI study of a normal patient. Polygon surfaces were fit to the points for each time frame, and smoothed. 3D NURBS surfaces were fit to the smooth polygon surfaces and then a 4D NURBS surface was fit through these surfaces. Each of the principal 4D surfaces (atria, ventricles, inner and outer walls) contains approximately 200 control points, We conclude that 4D NURBS are an efficient and flexible way to describe the heart and other anatomical objects for a realistic phantom.

Modeling respiratory mechanics in the MCAT and spline-based MCAT phantoms

Respiratory motion can cause artifacts in myocardial SPECT and computed tomography (CT). The authors incorporate models of respiratory mechanics into the current 4D MCAT and into the next generation spline-based MCAT phantoms. In order to simulate respiratory motion in the current MCAT phantom, the geometric solids for the diaphragm, heart, ribs, and lungs were altered through manipulation of parameters defining them. Affine transformations were applied to the control points defining the same respiratory structures in the spline-based MCAT phantom to simulate respiratory motion. The Non-Uniform Rational B-Spline (NURBS) surfaces for the lungs and body outline were constructed in such a way as to be linked to the surrounding ribs. Expansion and contraction of the thoracic cage then coincided with expansion and contraction of the lungs and body. The changes both phantoms underwent were spline-interpolated over time to create time continuous 4D respiratory models. The authors then used the geometry-based and spline-based MCAT phantoms in an initial simulation study of the effects of respiratory motion on myocardial SPECT. The simulated reconstructed images demonstrated distinct artifacts in the inferior region of the myocardium. It is concluded that both respiratory models can be effective tools for researching effects of respiratory motion.

Implementation of simultaneous attenuation and detector response correction in SPECT

Simultaneous correction of nonuniform attenuation and detector response was implemented in single-photon-emission computed tomography (SPECT) image reconstruction. A ray-driven projector-backprojector that exactly models attenuation in the reconstructed image slice and the spatially variant detector response was developed and used in the iterative maximum-likelihood algorithm for the correction. A computer-generated heart-lung phantom was used in simulation studies to compare the simultaneous correction method with an intrinsic attenuation correction method using a smoothing filter, and intrinsic attenuation correction method using a deconvolution filter, and a modified Chang attenuation correction method using a nonuniform attenuation distribution. The results demonstrate that the present method provides more-accurate quantitation and superior image quality. >

A new method for modeling the spatially-variant, object-dependent scatter response function in SPECT

Scatter compensation using iterative reconstruction results in improved image quality and quantitative accuracy compared to subtraction-based methods, However, this requires knowledge of the spatially-varying, object-dependent scatter response function (SRF), We have previously developed a method, slab derived scatter estimation (SDSE) for estimating the SRF. However, this method has reduced accuracy for nonuniform attenuators and Tl-201 imaging. In this paper we present a new method which provides better modeling of the SRF for Tl-201 SPECT, and should provide improved accuracy for nonuniform attenuators. The method requires 3 image space convolutions and an attenuated projection for each viewing angle. Implementation in a projector-backprojector pair for use with an iterative reconstruction algorithm would require 2 image space Fourier transforms and 6 image space inverse Fourier transforms per iteration. We observed good agreement between SRFs and projection data estimated using this new model compared to those obtained using Monte Carlo simulations.

Quantitative cardiac SPECT reconstruction with reduced image degradation due to patient anatomy

Patient anatomy has complicated effects on cardiac SPECT images. The authors investigated reconstruction methods which substantially reduced these effects for improved image quality. A 3D mathematical cardiac-torso (MCAT) phantom which models the anatomical structures in the thorax region were used in the study. The phantom was modified to simulate variations in patient anatomy including regions of natural thinning along the myocardium, body size, diaphragmatic shape, gender, and size and shape of breasts for female patients. Distributions of attenuation coefficients and Tl-201 uptake in different organs in a normal patient were also simulated. Emission projection data were generated from the phantoms including effects of attenuation and detector response. The authors have observed the attenuation-induced artifacts caused by patient anatomy in the conventional FBP reconstructed images. Accurate attenuation compensation using iterative reconstruction algorithms and attenuation maps substantially reduced the image artifacts and improved quantitative accuracy. The authors conclude that reconstruction methods which accurately compensate for nonuniform attenuation can substantially reduce image degradation caused by variations in patient anatomy in cardiac SPECT. >

Noise properties of the EM algorithm. II. Monte Carlo simulations

In an earlier paper we derived a theoretical formulation for estimating the statistical properties of images reconstructed using the iterative ML-EM algorithm. To gain insight into this complex problem, two levels of approximation were considered in the theory. These techniques revealed the dependence of the variance and covariance of the reconstructed image noise on the source distribution, imaging system transfer function, and iteration number. In this paper a Monte Carlo approach was taken to study the noise properties of the ML-EM algorithm and to test the predictions of the theory. The study also served to evaluate the approximations used in the theory. Simulated data from phantoms were used in the Monte Carlo experiments. The ML-EM statistical properties were calculated from sample averages of a large number of images with different noise realizations. The agreement between the more exact form of the theoretical formulation and the Monte Carlo formulation was better than 10% in most cases examined, and for many situations the agreement was within the expected error of the Monte Carlo experiments. Results from the studies provide valuable information about the noise characteristics of ML-EM reconstructed images. Furthermore, the studies demonstrate the power of the theoretical and Monte Carlo approaches for investigating noise properties of statistical reconstruction algorithms.

Performance evaluation of A-SPECT: a high resolution desktop pinhole SPECT system for imaging small animals

Pinhole collimation of gamma rays to image distributions of radiolabeled tracers is considered promising for use in small animal imaging. The recent availability of transgenic mice, coupled with the development of /sup 125/I and /sup 99m/Tc labeled tracers, has allowed the study of a range of human disease models while creating demand for ultrahigh resolution imaging devices. We have developed a compact gamma camera that, in combination with pinhole collimation, allows for accessible, ultrahigh resolution in vivo single photon emission computed tomography (SPECT) imaging of small animals. The system is based on a pixilated array of NaI(Tl) crystals coupled to an array of position sensitive photomultiplier tubes. Interchangeable tungsten pinholes with diameters ranging from 0.5 to 3 mm are available, allowing the camera to be optimized for a variety of imaging situations. We use a three dimensional maximum likelihood expectation maximization algorithm to reconstruct the images. Our evaluation indicates that high quality, submillimeter spatial resolution images can be achieved in living mice. Reconstructed axial spatial resolution was measured to be 0.53, 0.74, and 0.96 mm full width at half maximum (FWHM) for rotation radii of 1, 2, and 3 cm, respectively, using the 0.5-mm pinhole. In this configuration, sensitivity is comparable to that of a high-resolution parallel hole collimator. SPECT images of hot- and cold-rod phantoms and a highly structured monkey brain phantom illustrate that high quality images can be obtained with the system. Images of living mice demonstrate the ability of the system to obtain high-resolution images in vivo. The effect of object size on the quantitative assessment of isotope distributions in an image was also studied.

Attenuation compensation for cardiac single-photon emission computed tomographic imaging: Part 1. Impact of attenuation and methods of estimating attenuation maps

Attenuation is believed to be one of the major causes of false-positive cardiac single-photon emission computed tomographic (SPECT) perfusion images. This article reviews the physics of attenuation, the artifacts produced by attenuation, and the need for scatter correction in combination with attenuation correction. The review continues with a comparison of the various configurations for transmission imaging that could be used to estimate patient specific attenuation maps, and an overview of how these are being developed for use on multiheaded SPECT systems, including discussions of truncation, noise, and spatial resolution of the estimated attenuation maps. Ways of estimating patient specific attenuation maps besides transmission imaging are also discussed.