We conduct research in medical imaging and image guidance. Our aim is to develop quantitative, functional imaging techniques to better understand the physiological processes underlying cardiovascular diseases and cancer, and to in turn utilize these techniques in guiding therapeutic and interventional procedures. In order to meet these goals, we develop novel ultrasound transducers, contrast agents, systems, and signal processing algorithms, which we then validate in laboratory experiments and in pre-clinical and clinical imaging studies.
Applications
The technologies developed in our lab target are applied in some of the following ways to enable diagnosis and to provide functional information for therapeutic planning at earlier stages in disease progression.
Endoscopic ultrasound in oncology
Pancreatic cancer is among the most lethal forms of cancer, with fewer than 10% of patients surviving beyond 5 years from initial diagnosis. However, if a suspicious lesion can be diagnosed while <1 cm in diameter, the survival rate increases to 75% . Currently, pancreatic adenocarcinoma is typically diagnosed by acquiring biopsy samples with a fine needle under endoscopic ultrasound guidance. The endoscopic ultrasound images used in biopsy guidance provide only basic anatomical information, causing many lesions to be missed entirely. In our lab, we develop novel endoscopic transducers to acquire the functional information necessary to improve biopsy guidance and diagnose small, early stage lesions while they are still treatable. In designing these devices, we must account for the interventional procedure in which they will be utilized, spatial limitations imposed by the vessel anatomy, and performance characteristics determined by the functional imaging needs of the disease.
(A) A contrast agent-specific endoscopic ultrasoud transducer and (B) a cross-sectional image acquired by this transducer in an ex vivo porcine artery showing the arterial structure in grayscale and the flow of microbubbles in red. This work was recently published in IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control.
Stroke, hemostasis and thrombosis
Georgia is one of 11 states considered to be in the “stroke belt” due to its abnormally high incidence of stroke and is also among the 5 leading states for sickle cell disease. Individuals with sickle cell disease are at increased risk for stroke and require regular monitoring.
Approximately 87% of all strokes are ischemic in nature, meaning that if hemorrhage can be ruled out within 4.5 hours of the onset of stroke symptoms, the patient can be given thrombolytic agents to re-open obstructed arteries and restore blood flow to the brain. Characterizing stroke requires rapid imaging, which can be provided safely, portably, and cost-effectively using transcranial ultrasound imaging.
The mechanisms underlying the formation of blood clots and clotting disorders are still in the process of being understood. While patients with sickle cell disease can be treated with transfusions to prevent arterial strokes, the clots that form due to the shape of the red blood cells by are primarily venous in nature. By developing technologies to image vascular structure and blood flow dynamics, we may be able to improve our understanding of the critical processes involved in clot formation and progression and to determine which individuals require immediate treatment.
(A) Scanning setup and (B) volume rendering of acquired 3D data set showing bilateral blood flow to the healthy adult brain through the intact skull. 3D Doppler data is shown in red, with the left and right middle cerebral arteries (MCA) and internal carotid arteries (ICA) visible. The falx cerebri can be seen in white from the grayscale data. This work was published in IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control and was the cover article.
Intravascular ultrasound in cardiovascular disease
Cardiovascular disease is the leading cause of death in the United States. Interventional procedures such as stent placements are currently effectively guided using a combination of techniques including X-ray fluoroscopy, intravascular ultrasound (IVUS), and optical coherence tomography (OCT). However, the pathophysiologies underlying many diseases of the coronary and peripheral vasculature are not fully understood, limiting the ability to arrive at correct diagnoses and to devise effective treatment plans at early stages in disease progression. In addition, complication rates can be high for some procedures.
In intravascular ultrasound, a small ultrasound transducer on the end of a catheter is used to acquire images of the vascular wall and lumen via an access point in the leg. In our lab, we design and fabricate novel minimally-invasive transducers to uniquely characterize the vascular environment, increasing the functional information available to physicians for planning treatment. Further details on intravascular imaging can be found in the following publications:
- Martin KH, Lindsey BD, Ma J, Nichols TC, Jiang X, and Dayton PA, “Ex Vivo Porcine Arterial and Chorioallantoic Membrane Acoustic Angiography Using Dual-Frequency Intravascular Ultrasound Probes,” Ultrasound in Medicine and Biology, 42, p. 2294-307, Sep 2016.
- Lindsey BD, Martin KH, Jiang X, and Dayton PA, “Adaptive windowing in contrast-enhanced intravascular ultrasound imaging,”Ultrasonics, vol. 70, 123-35, Aug. 2016.
Technologies
Ultrasound systems
Ultrasound is an imaging technique that uses non-ionizing radiation to form maps of acoustic scatterers within the body. A transducer transmits waves and receives echoes from acoustic scatterers within the body. We use ultrasound in all of our research. A diagram of a typical commercial ultrasound system that is used clinically is shown below. In our lab, we work with commercial systems and also with programmable research systems, the latter of which allows development of new processing algorithms. Our research system also allows us to exploit the properties of unique transducers and contrast agents.An ultrasound system or “scanner” drives the transducer and processes the acquired data into images for real-time display. In our lab, we are interested in 2D and 3D ultrasound imaging and in the development of new algorithms, signal processing, and image formation techniques for quantifying healthy or diseased tissues or which might provide new information about an individual patient. These may include measuring blood flow perfusion, quantifying vascular structure or spatially mapping and analyzing the expression of a biomarker.
Transducers
The transducer is the part of the ultrasound system responsible for transmitting sound into the human body and also converting backscattered acoustic energy into a voltage which can then be processed to form a digital image of structures within the body. In our lab, we utilize commercial array transducers in some of our work, while in other work we develop or own custom transducers to meet specific needs. These transducers are designed to meet the needs of specific clinical applications and to fit within existing procedures. Acoustic and electro-mechanical simulations form the basis for these designs, which are then fabricated using equipment in our lab and in the Marcus Nanotechnology Building on the Georgia Tech campus. Several of our custom transducers are shown below.
(A) Photograph of 25.3 mm matrix array transducer and with (B) 0.725 mm inter-element separation under fabrication. The completed array has 256 elements operating at 1.2 MHz. This transducer was designed for 3D cerebrovascular imaging and was successful in imaging individuals with highly attenuating skulls.
2.7 mm-diameter forward-looking intravascular thrombolysis transducers developed for minimally invasive treatment of severe thrombosis (scale bar = 5 mm). This work is described in detail in this publication and by a recent press release.
Microbubbles
Ultrasound waves are scattered whenever there is variation in acoustic impedance within a medium. Acoustic impedance (the product of density and speed of sound) is a property of materials that gives us information about the mechanical properties of the medium. Blood is a particularly poor scatter of sound (scattering from red blood cells is many times lower than scattering from liver tissue), making blood difficult to image with ultrasound, especially in small blood vessels. To address this challenge, contrast agents have been developed for ultrasound imaging. Ultrasound contrast agents are gas-filled bubbles 1-10 μm in diameter (“microbubbles”). The gas core gives them a markedly different acoustic impedance than their surrounding environment, providing a strong acoustic scatterer which can be safely administered intravenously and fills all vascular spaces. Gases in commercially-available and FDA-approved microbubbles typically are removed from the system through natural respiration in <30 minutes. Microbubbles enable new opportunities for imaging blood flow dynamics and can also be designed to target to specific markers expressed on the membranes of the endothelial cells lining the walls of blood vessels.
Microscope images of a single 4 μm-diameter microbubble contrast agent losing core gas to form a daughter bubble under repeated ultrasound pulsation.
High resolution ultrasound imaging of mouse microvascular anatomy in 3D (grayscale) and perfusion rate in 2D (orange). These images were formed using microbubbles and were recently published in Annals of Biomedical Engineering.