Image reconstruction and processing for stationary digital tomosynthesis systems

Digital tomosynthesis (DTS) is an emerging x-ray imaging technique for disease and cancer screening. DTS takes a small number of x-ray projections to generate pseudo-3D images, it has a lower radiation and a lower cost compared to the Computed Tomography (CT) and an improved diagnostic accuracy compared to the 2D radiography. Our research group has developed a carbon nanotube (CNT) based x-ray source. This technology enables packing multiple x-ray sources into one single x-ray source array. Based on this technology, our group built several stationary digital tomosynthesis (s-DTS) systems, which have a faster scanning time and no source motion blur. One critical step in both tomosynthesis and CT is image reconstruction, which generates a 3D image from the 2D measurement. For tomosynthesis, the conventional reconstruction method runs fast but fails in image quality. A better iterative method exists, however, it is too time-consuming to be used in clinics. The goal of this work is to develop fast iterative image reconstruction algorithm and other image processing techniques for the stationary digital tomosynthesis system, improving the image quality affected by the hardware limitation. Fast iterative reconstruction algorithm, named adapted fan volume reconstruction (AFVR), was developed for the s-DTS. AFVR is shown to be an order of magnitude faster than the current iterative reconstruction algorithms and produces better images over the classical filtered back projection (FBP) method. AFVR was implemented for the stationary digital breast tomosynthesis system (s-DBT), the stationary digital chest tomosynthesis system (s-DCT) and the stationary intraoral dental tomosynthesis system (s-IOT). Next, scatter correction technique for stationary digital tomosynthesis was investigated. A new algorithm for estimating scatter profile was developed, which has been shown to improve the image quality substantially. Finally, the quantitative imaging was investigated, where the s-DCT system was used to assess the coronary artery calcium score.Doctor of Philosoph

High Sensitivity Micro-Elastometry: Applications in Blood Coagulopathy

Highly sensitive methods for the assessment of clot structure can aid in our understanding of coagulation disorders and their risk factors. Rapid and simple clot diagnostic systems are also needed for directing treatment in a broad spectrum of cardiovascular diseases. Here we demonstrate a method for micro-elastometry, named Resonant Acoustic Spectroscopy with Optical Vibrometry (RASOV), which measures the clot elastic modulus (CEM) from the intrinsic resonant frequency of a clot inside a microwell. We observed a high correlation between the CEM of human blood measured by RASOV and a commercial Thromboelastograph (TEG), (R=0.966). Unlike TEG, RASOV requires only 150 μL of sample and offers improved repeatability. Since CEM is known to primarily depend upon fibrin content and network structure, we investigated the CEM of purified clots formed with varying amounts of fibrinogen and thrombin. We found that RASOV was sensitive to changes of fibrinogen content (0.5–6 mg/mL), as well as to the amount of fibrinogen converted to fibrin during clot formation. We then simulated plasma hypercoagulability via hyperfibrinogenemia by spiking whole blood to 150% and 200% of normal fibrinogen levels, and subsequently found that RASOV could detect hyperfibrinogenemia-induced changes in CEM and distinguish these conditions from normal blood

Imaging and Elastometry of Blood Clots Using Magnetomotive Optical Coherence Tomography and Labeled Platelets

Improved methods for imaging and assessment of vascular defects are needed for directing treatment of cardiovascular pathologies. In this paper, we employ magnetomotive optical coherence tomography (MMOCT) as a platform both to detect and to measure the elasticity of blood clots. Detection is enabled through the use of rehydrated, lyophilized platelets loaded with superparamagnetic iron oxides (SPIO-RL platelets) that are functional infusion agents that adhere to sites of vascular endothelial damage. Evidence suggests that the sensitivity for detection is improved over threefold by magnetic interactions between SPIOs inside RL platelets. Using the same MMOCT system, we show how elastometry of simulated clots, using resonant acoustic spectroscopy, is correlated with the fibrin content of the clot. Both methods are based upon magnetic actuation and phase-sensitive optical monitoring of nanoscale displacements using MMOCT, underscoring its utility as a broad-based platform to detect and measure the molecular structure and composition of blood clots

Contrast-enhanced imaging of SPIO-labeled platelets using magnetomotive ultrasound

The ability to image platelets in vivo can provide insight into blood clotting processes and coagulopathies, and aid in identifying sites of vascular endothelial damage related to trauma or cardiovascular disease. Toward this end, we have developed a magnetomotive ultrasound (MMUS) system that provides contrast-enhanced imaging of superparamagnetic iron oxide (SPIO) labeled platelets via magnetically-induced vibration. Platelets are a promising platform for functional imaging contrast because they readily take up SPIOs and are easily harvested from blood. Here we report a novel MMUS system that accommodates an arbitrarily thick sample while maintaining portability. We employed a frequency- and phase-locked motion detection algorithm based on bandpass filtering of the differential RF phase, which allows for the detection of sub-resolution vibration amplitudes on the order of several nanometers. We then demonstrated MMUS in homogenous tissue phantoms at SPIO concentrations as low as 0.09 mg/ml Fe (p < 0.0001, n = 6, t-test). Finally, we showed that our system is capable of 3-dimensional imaging of a 185 μL simulated clot containing SPIO-platelets. This highlights the potential utility for non-invasive imaging of platelet-rich clots, which would constitute a fundamental advance in technology for the study of hemostasis and detection of clinically relevant thrombi

Imaging and Elastometry of Blood Clots Using Magnetomotive Optical Coherence Tomography and Labeled Platelets

Improved methods for imaging and assessment of vascular defects are needed for directing treatment of cardiovascular pathologies. In this paper, we employ magnetomotive optical coherence tomography (MMOCT) as a platform both to detect and to measure the elasticity of blood clots. Detection is enabled through the use of rehydrated, lyophilized platelets loaded with superparamagnetic iron oxides (SPIO-RL platelets) that are functional infusion agents that adhere to sites of vascular endothelial damage. Evidence suggests that the sensitivity for detection is improved over threefold by magnetic interactions between SPIOs inside RL platelets. Using the same MMOCT system, we show how elastometry of simulated clots, using resonant acoustic spectroscopy, is correlated with the fibrin content of the clot. Both methods are based upon magnetic actuation and phase-sensitive optical monitoring of nanoscale displacements using MMOCT, underscoring its utility as a broad-based platform to detect and measure the molecular structure and composition of blood clots

Estimating scatter from sparsely measured primary signal

Scatter radiation severely degrades the image quality. Measurement-based scatter correction methods sample the scatter signal at sparsely distributed points, from which the scatter profile is estimated and deterministically removed from the projection image. The estimation of the scatter profile is generally done through a spline interpolation and the resulting scatter profile is quite smooth. Consequently, the noise is intact and the signal-to-noise ratio is reduced in the projection image after scatter correction, leading to image artifacts and increased noise in the reconstruction images. We propose a simple and effective method, referred to as filtered scatter-to-primary ratio ([Formula: see text]-SPR) estimation, to estimate the scatter profile using the sparsely sampled scatter signal. Using the primary sampling device and the stationary digital tomosynthesis systems previously developed in our lab, we evaluated and compared the [Formula: see text]-SPR method in comparison with existing methods in terms of contrast ratio, signal difference-to-noise ratio, and modulation transfer function. A significant improvement in image quality is observed in both the projection and the reconstruction images using the proposed method

High Sensitivity Micro-Elastometry: Applications in Blood Coagulopathy

Highly sensitive methods for the assessment of clot structure can aid in our understanding of coagulation disorders and their risk factors. Rapid and simple clot diagnostic systems are also needed for directing treatment in a broad spectrum of cardiovascular diseases. Here we demonstrate a method for micro-elastometry, named Resonant Acoustic Spectroscopy with Optical Vibrometry (RASOV), which measures the clot elastic modulus (CEM) from the intrinsic resonant frequency of a clot inside a microwell. We observed a high correlation between the CEM of human blood measured by RASOV and a commercial Thromboelastograph (TEG), (R=0.966). Unlike TEG, RASOV requires only 150 μL of sample and offers improved repeatability. Since CEM is known to primarily depend upon fibrin content and network structure, we investigated the CEM of purified clots formed with varying amounts of fibrinogen and thrombin. We found that RASOV was sensitive to changes of fibrinogen content (0.5–6 mg/mL), as well as to the amount of fibrinogen converted to fibrin during clot formation. We then simulated plasma hypercoagulability via hyperfibrinogenemia by spiking whole blood to 150% and 200% of normal fibrinogen levels, and subsequently found that RASOV could detect hyperfibrinogenemia-induced changes in CEM and distinguish these conditions from normal blood