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PURPOSE: The aim of this study was to characterize a new generation stationary digital breast tomosynthesis system with higher tube flux and increased angular span over a first generation system. METHODS: The linear CNT x-ray source was designed, built, and evaluated to determine its performance parameters. The second generation system was then constructed using the CNT x-ray source and a Hologic gantry. Upon construction, test objects and phantoms were used to characterize system resolution as measured by the modulation transfer function (MTF), and artifact spread function (ASF). RESULTS: The results indicated that the linear CNT x-ray source was capable of stable operation at a tube potential of 49 kVp, and measured focal spot sizes showed source-to-source consistency with a nominal focal spot size of 1.1 mm. After construction, the second generation (Gen 2) system exhibited entrance surface air kerma rates two times greater the previous s-DBT system. System in-plane resolution as measured by the MTF is 7.7 cycles/mm, compared to 6.7 cycles/mm for the Gen 1 system. As expected, an increase in the z-axis depth resolution was observed, with a decrease in the ASF from 4.30 mm to 2.35 mm moving from the Gen 1 system to the Gen 2 system as result of an increased angular span. CONCLUSIONS: The results indicate that the Gen 2 stationary digital breast tomosynthesis system, which has a larger angular span, increased entrance surface air kerma, and faster image acquisition time over the Gen 1 s-DBT system, results in higher resolution images. With the detector operating at full resolution, the Gen 2 s-DBT system can achieve an in-plane resolution of 7.7 cycles per mm, which is better than the current commercial DBT systems today, and may potentially result in better patient diagnosis.

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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.

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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(-1) Fe (p < 0.0001, n = 6, t-test). Finally, we showed that our system is capable of three-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.

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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.

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Clot elastic modulus (CEM) has recently been shown to correlate with various hemostatic and thrombotic disorders and may be an important diagnostic parameter in cardiovascular diseases. Current methods of CEM measurement lack repeatability and require large sample volume. We present a novel method named resonant acoustic spectroscopy with optical vibrometry (RASOV) that has the potential to assess CEM with higher accuracy and speed, and lower sample volume. To validate RASOV, we measured the acoustic spectrum of agarose gel with varied concentrations in open-faced rectangular wells. Results showed a linear relationship between the natural resonant frequency and agarose content within a concentration range of 4 to 12 mg/mL. Furthermore, we observed that the resonant frequencies decrease with increasing transducer mass. As a highly accurate, resonance-based method, RASOV has great potential for biomechanical properties measurement, especially for human blood.

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Rehydratable, lyophilized platelets loaded with superparamagnetic iron oxides (SPIOs) has the potential to provide magnetomotive imaging contrast to sites of vascular damage, including thrombosis complicating atherosclerosis and hemorrhage. Magnetomotive optical coherence tomography (MMOCT) contrasts SPIO-platelets based on their nanoscale, magnetically-induced motion. We report improvements in MMOCT imaging contrast and sensitivity by optimizing the magnetic properties and SPIO loading of the platelets. SPIO-platelets have been shown to specifically adhere to sites of vascular damage in porcine arteries ex vivo. This may lead to new methods for detecting internal bleeding and monitoring the formation of blood clots using infused SPIO-platelets.

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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.