Regularized Image Reconstruction Algorithms for Dual-Isotope Myocardial Perfusion SPECT (MPS) Imaging Using a Cross-Tracer Prior

In simultaneous dual-isotope myocardial perfusion SPECT (MPS) imaging, data are simultaneously acquired to determine the distributions of two radioactive isotopes. The goal of this work was to develop penalized maximum likelihood (PML) algorithms for a novel cross-tracer prior that exploits the fact that the two images reconstructed from simultaneous dual-isotope MPS projection data are perfectly registered in space. We first formulated the simultaneous dual-isotope MPS reconstruction problem as a joint estimation problem. A cross-tracer prior that couples voxel values on both images was then proposed. We developed an iterative algorithm to reconstruct the MPS images that converges to the maximum a posteriori solution for this prior based on separable surrogate functions. To accelerate the convergence, we developed a fast algorithm for the cross-tracer prior based on the complete data OS-EM (COSEM) framework. The proposed algorithm was compared qualitatively and quantitatively to a single-tracer version of the prior that did not include the cross-tracer term. Quantitative evaluations included comparisons of mean and standard deviation images as well as assessment of image fidelity using the mean square error. We also evaluated the cross tracer prior using a three-class observer study with respect to the three-class MPS diagnostic task, i.e., classifying patients as having either no defect, reversible defect, or fixed defects. For this study, a comparison with conventional ordered subsets-expectation maximization (OS-EM) reconstruction with postfiltering was performed. The comparisons to the single-tracer prior demonstrated similar resolution for areas of the image with large intensity changes and reduced noise in uniform regions. The cross-tracer prior was also superior to the single-tracer version in terms of restoring image fidelity. Results of the three-class observer study showed that the proposed cross-tracer prior and the convergent algorithms improved the ima- - ge quality of dual-isotope MPS images compared to OS-EM.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/85873/1/Fessler3.pd

Device for lengthening of a musculotendinous unit by direct continuous traction in the sheep

Background Retraction, atrophy and fatty infiltration are signs subsequent to chronic rotator cuff tendon tears. They are associated with an increased pennation angle and a shortening of the muscle fibers in series. These deleterious changes of the muscular architecture are not reversible with current repair techniques and are the main factors for failed rotator cuff tendon repair. Whereas fast stretching of the retracted musculotendinous unit results in proliferation of non-contractile fibrous tissue, slow stretching may lead to muscle regeneration in terms of sarcomerogenesis. To slowly stretch the retracted musculotendinous unit in a sheep model, two here described tensioning devices have been developed and mounted on the scapular spine of the sheep using an expandable threaded rod, which has been interposed between the retracted tendon end and the original insertion site at the humeral head. Traction is transmitted in line with the musculotendinous unit by sutures knotted on the expandable threaded rod. The threaded rod of the tensioner is driven within the body through a rotating axis, which enters the body on the opposite side. The tendon end, which was previously released (16 weeks prior) from its insertion site with a bone chip, was elongated with a velocity of 1 mm/day. Results After several steps of technical improvements, the tensioner proved to be capable of actively stretching the retracted and degenerated muscle back to the original length and to withstand the external forces acting on it. Conclusion This technical report describes the experimental technique for continuous elongation of the musculotendinous unit and reversion of the length of chronically shortened muscle

Multiscale mechanobiology: mechanics at the molecular, cellular, and tissue levels

Mechanical force is present in all aspects of living systems. It affects the conformation of molecules, the shape of cells, and the morphology of tissues. All of these are crucial in architecture-dependent biological functions. Nanoscience of advanced materials has provided knowledge and techniques that can be used to understand how mechanical force is involved in biological systems, as well as to open new avenues to tailor-made bio-mimetic materials with desirable properties. In this article, we describe models and show examples of how force is involved in molecular functioning, cell shape patterning, and tissue morphology

Simultaneous technetium-99m/thallium-201 SPECT imaging with model-based compensation for cross-contaminating effects

Simultaneous acquisition of dual-isotope SPECT data offers a number of advantages over separately acquired data; however, simultaneous acquisition can result in cross-contamination between isotopes. In this work we propose and evaluate two frameworks for iterative model-based compensation of cross-contamination in dual-isotope SPECT. The methods were applied to cardiac imaging with Technetium-99m-sestamibi and Thallium-201, and they were compared to a subtraction-based compensation method using a cross-talk estimate obtained from an auxiliary energy window. Monte Carlo simulations were performed to carefully study aspects of bias and noise for the methods, and a torso phantom with cardiac insert was used to evaluate the performance of the methods for experimentally acquired data. The cross-talk compensation methods substantially improved lesion contrast and significantly reduced quantitative errors for simultaneously acquired data. Thallium image normalized mean square error (NMSE) was reduced from 0.522 without cross-talk compensation to as low as 0.052 with model-based cross-talk compensation. This is compared to a NMSE of 0.091 for the subtraction-based compensation method. The application of a preliminary model for crosstalk arising from lead fluorescence x-rays and collimator scatter gave promising results, and the future development of a more accurate model for collimator interactions would likely benefit simultaneous Tc/Tl imaging. Model-based compensation methods provide feasible cross-talk compensation in clinically acceptable times, and they may ultimately make simultaneous dual-isotope protocols an effective alternative for many imaging procedures

Analysis of the reconstructibility and noise properties of scattered photons in Tc SPECT

Since scattered photons carry degraded spatial information, scatter is typically considered a source of contamination in SPECT. However, with the advent of scatter modeling methods and reconstruction-based scatter compensation (RBSC), it may be possible to utilize scattered data in a productive manner. In this work we analyze the reconstructibility of scattered photon projection data and investigate the potential for using scattered photons to reduce the noise levels of SPECT images. We have simulated projection data for an elliptical phantom containing three cold rods in a uniform background of Tc-99m activity. A variety of photopeak and scatter energy windows were formed, as well as corresponding RBSC transfer matrices. Each statistically weighted matrix was decomposed using SVD and analyzed in terms of reconstructibility and noise properties. Results indicate that scattered photons contain sufficient information to reconstruct the source activity, but the scatter-only matrices are very poorly conditioned. We have also evaluated several methods of utilizing scattered events via RBSC, and compared them with other, idealized methods of handling scatter. It was found that scattered photons can be used productively when photopeak and non-photopeak data are separated through the use of multiple energy windows. The RBSC methods outperformed ideal scatter subtraction, but fell short of methods which assume perfect discrimination between scattered and primary events. The knowledge gained by this study may help guide future research and lead to better approaches to handling scatter in SPECT

Single molecule force measurements of perlecan/HSPG2: A key component of the osteocyte pericellular matrix

Perlecan/HSPG2, a large, monomeric heparan sulfate proteoglycan (HSPG), is a key component of the lacunar canalicular system (LCS) of cortical bone, where it is part of the mechanosensing pericellular matrix (PCM) surrounding the osteocytic processes and serves as a tethering element that connects the osteocyte cell body to the bone matrix. Within the pericellular space surrounding the osteocyte cell body, perlecan can experience physiological fluid flow drag force and in that capacity function as a sensor to relay external stimuli to the osteocyte cell membrane. We previously showed that a reduction in perlecan secretion alters the PCM fiber composition and interferes with bone's response to a mechanical loading in vivo. To test our hypothesis that perlecan core protein can sustain tensile forces without unfolding under physiological loading conditions, atomic force microscopy (AFM) was used to capture images of perlecan monomers at nanoscale resolution and to perform single molecule force measurement (SMFMs). We found that the core protein of purified full-length human perlecan is of suitable size to span the pericellular space of the LCS, with a measured end-to-end length of 170 ± 20 nm and a diameter of 2–4 nm. Force pulling revealed a strong protein core that can withstand over 100 pN of tension well over the drag forces that are estimated to be exerted on the individual osteocyte tethers. Data fitting with an extensible worm-like chain model showed that the perlecan protein core has a mean elastic constant of 890 pN and a corresponding Young's modulus of 71 MPa. We conclude that perlecan has physical properties that would allow it to act as a strong but elastic tether in the LCS