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.
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.
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.
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.
Computed Tomography (CT) is the gold standard for image evaluation of lung disease, including lung cancer and cystic fibrosis. It provides detailed information of the lung anatomy and lesions, but at a relatively high cost and high dose of radiation. Chest radiography is a low dose imaging modality but it has low sensitivity. Digital chest tomosynthesis (DCT) is an imaging modality that produces 3D images by collecting x-ray projection images over a limited angle. DCT is less expensive than CT and requires about 1/10 th the dose of radiation. Commercial DCT systems acquire the projection images by mechanically scanning an x-ray tube. The movement of the tube head limits acquisition speed.We recently demonstrated the feasibility of stationary digital chest tomosynthesis (s-DCT) using a carbon nanotube (CNT) x-ray source array in benchtop phantom studies. The stationary x-ray source allows for fast image acquisition. The objective of this study is to demonstrate the feasibility of s-DCT for patient imaging. We have successfully imaged 31 patients. Preliminary evaluation by board certified radiologists suggests good depiction of thoracic anatomy and pathology.
Objectives: Intraoral dental tomosynthesis and closely related tuned-aperture CT (TACT) are low-dose three-dimensional (3D) imaging modalities that have shown improved detection of multiple dental diseases. Clinical interest in implementing these technologies waned owing to their time-consuming nature. Recently developed carbon nanotube (CNT) X-ray sources allow rapid multi-image acquisition without mechanical motion, making tomosynthesis a clinically viable technique. The objective of this investigation was to evaluate the feasibility of and produce high-quality images from a digital tomosynthesis system employing CNT X-ray technology. Methods: A test-bed stationary intraoral tomosynthesis unit was constructed using a CNT X-ray source array and a digital intraoral sensor. The source-to-image distance was modified to make the system comparable in image resolution to current two-dimensional intraoral radiography imaging systems. Anthropomorphic phantoms containing teeth with simulated and real caries lesions were imaged using a dose comparable to D-speed film dose with a rectangular collimation. Images were reconstructed and analysed. Results: Tomosynthesis images of the phantom and teeth specimen demonstrated perceived image quality equivalent or superior to standard digital images with the added benefit of 3D information. The ability to "scroll" through slices in a buccal-lingual direction significantly improved visualization of anatomical details. In addition, the subjective visibility of dental caries was increased. Conclusions: Feasibility of the stationary intraoral tomosynthesis is demonstrated. The results show clinical promise and suitability for more robust observer and clinical studies.
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