2015 — 2016 |
Prasad, Paras N. [⬀] Xia, Jun |
R21Activity Code Description: To encourage the development of new research activities in categorical program areas. (Support generally is restricted in level of support and in time.) |
Potentiometric Photoacoustic Imaging of Brain Activity Enabled by Near Infrared to Visible Light Converting Nanoparticles @ State University of New York At Buffalo
? DESCRIPTION (provided by applicant): This application is in response to the President's Brain Research through Advancing Innovative Neurotechnologies (BRAIN) initiative. A central goal of the BRAIN Initiative is to understand how electrical and chemical signals code information in neural circuits and give rise to sensations, thoughts, emotions and actions. Existing technologies are not sufficient to accomplish this goal and have to be significantly improved or novel tools should be introduced to analyze circuit-specific processes in the brain, leading to transformative advances in our understanding of the brain function and behavior. RFA-EY-15-001 seeks technology at the very earliest stage of development, which can assist recording and/or manipulating neural circuit activity in human and animal experiments. The specific goal of the proposed work is to introduce and validate a new voltage-sensitive upconverting photoacoustic imaging (VSUPAI) technique. It is based on voltage-sensitive dye (VSD) imaging, which exploits change of optical properties of dye associated with a cell membrane with variation of a membrane potential, allowing for real-time probing of the neuronal activity via non-invasive optical methods. VSDs have limited use in deep brain imaging, because they require excitation in the visible range. This proposal addresses the current limitation of VSD imaging through the convergence of photoacoustic tomography (PAT), biocompatible upconversion (UC) nanoparticles, and VSDs. In the proposed method, we exploit the voltage-sensitive change in dye absorbance to produce a change in the photoacoustic signal, as opposed to fluorescence-based probing with conventional VSDs. In our proposal, the PAT technique will involve NIR excitation and ultrasound detection, while UCNPs will serve as nanotransformers that convert skull penetrating NIR light to VIS light, which will be absorbed by the locally administered VSDs, allowing us to monitor changes in their absorption, induced by changes in action potentials, and, correspondingly, map the deeper brain neuronal activity.
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0.934 |
2020 — 2021 |
Xia, Jun |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Multiparametric Photoacoustic and Ultrasonic Imaging of the Breast in Cranial-Caudal View @ State University of New York At Buffalo
ABSTRACT The ultimate goal of this project is to address the unmet clinical need in breast cancer screening for women with high breast density. This population (BI-RADS density grades C and D) accounts for nearly half of women. The high breast density reduces mammography sensitivity to as low as 62%, and it is also associated with a two-fold higher risk of breast cancer (American College of Obstetricians and Gynecologists, Management of Women With Dense Breasts Diagnosed by Mammography, 2016). While 30 states have now passed breast density notification laws, there is no promising modality for large-scale screening of patients with dense breasts. For instance, the breast ultrasound (US) is operator-dependent, and has limited sensitivity and a high false positive rate; while dynamic contrast-enhanced (DCE) breast magnetic resonance imaging (MRI) is limited by its high cost, required injection of gadolinium contrast, and limited availability. To address this issue, this project will develop a three- dimensional (3D) breast screening system with both photoacoustic (PA) and US imaging capabilities. The proposal is capitalized on the team?s recent advances in the double-scan PA technology, which utilized two linear transducer arrays and two linear optical fiber bundles to image a slightly compressed breast from both the cranial and caudal (CC) sides. With a novel co-planar optical illumination and acoustic detection design, the prototype system successfully imaged through a 7-cm-thick compressed breast. This depth has never been achieved by any other PA breast imaging systems. The CC-view detection also presents images in a form that is familiar to radiologists. In addition, the system is portable and images the patient in a standing pose, both of these features will significantly facilitate clinical workflow. This R01 project will further advance the dual-scan system to achieve better breast coverage, higher spatial resolution, better US capability, and multi-parametric quantification of breast tissue. To ensure successful implementation of the project, the team possesses multidisciplinary expertise in photoacoustics, ultrasound, computational informatics, biostatistics, as well as breast oncology and radiology. The project has also secured support from the Buffalo?s two busiest breast imaging centers ? Roswell Park Cancer Institute and Windsong Radiology Group. The specific aims of the project are as follows: Aim 1. Develop a compact double-scan photoacoustic and ultrasonic breast imaging system. Aim 2. Develop photoacoustic and ultrasound image acquisition and processing algorithms. Aim 3. Investigate photoacoustic and ultrasonic features of breast malignancy.
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0.934 |
2021 |
Xia, Jun |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Development of Photoacoustic Tomography For Non-Invasive, Label-Free Imaging of Tissue Perfusion in Chronic Wounds @ State University of New York At Buffalo
Project summary Chronic leg ulcers are affecting approximately 6.5 million Americans and the disease includes venous stasis ulcers, arterial ulcers, pressure ulcers, and diabetic (neuropathic) ulcers. They are associated with significant mortality (28% over two years), reduced quality of life (nonambulatory), and high treatment costs (>$25 billion/yr in the U.S.). Since many chronic ulcers have underlying vascular insufficiency, accurate assessment of blood perfusion to the wound is critical to treatment planning and monitoring. However, existing clinical tests fail to meet this need in practice. Without timely information on circulation, a patient may need to wait months after the revascularization surgery before any additional intervention can be planned. An accurate, noninvasive tool for circulation assessment would greatly improve post-surgical decision making and clinical outcomes of wound patients. This project aims to develop a three-dimensional (3D) wound assessment system using photoacoustic tomography (PAT), a hybrid modality that detects optical absorption in tissue through the photoacoustic effect. The conversion of optical absorption into acoustic waves breaks through the optical diffusion limit, allowing for high-resolution imaging in three dimensions. Since hemoglobin serves as the major endogenous contrast at near-infrared wavelengths, PAT provides label-free, three-dimensional imaging of hemoglobin distribution, which is closely related to circulation. While PAT has shown promising results in vascular imaging, various hurdles have prevented its application in wound evaluation. Capitalizing on the recent innovations in photoacoustic system development and image processing, the team will address these hurdles and develop a PAT-based wound imaging system with unique advantages in terms of spatial resolution, penetration depth, and portability. To ensure successful implementation of the project, the PI has gathered a multidisciplinary team with expertise in photoacoustic imaging, wound healing, vascular surgery, biostatistics, and computer science. The project has also secured support from the region?s busiest vascular clinic located at Buffalo Generation Hospital and Erie County Medical Center and their outpatient clinics. More importantly, the team has already worked together and acquired preliminary data through support from the University at Buffalo?s NIH Clinical and Translational Science Awards (CTSA) Program. Through the four-year project, the team will achieve the following aims: Aim 1: Develop a versatile, high-resolution 3D photoacoustic imaging system that can be easily rotated and positioned to image any regions on the foot; Aim 2: Validate the system at vascular clinics and identify photoacoustic features of tissue perfusion; and Aim 3: Test the feasibility of using PAT to monitor tissue perfusion and guide post-surgical assessment and treatment planning.
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0.934 |
2021 |
Xia, Jun |
K99Activity Code Description: To support the initial phase of a Career/Research Transition award program that provides 1-2 years of mentored support for highly motivated, advanced postdoctoral research scientists. |
The Role of Aquaporin 3 in Arsenic-Induced Dna Damage and Mutagenesis @ Baylor College of Medicine
PROJECT SUMMARY Arsenic is a widespread toxin in drinking water that affects millions of people, increasing the risks of neurodegenerative and cardiovascular diseases and cancers. High doses of arsenic cause DNA damage and genome instability. However, the health effects associated with low-dose arsenic are controversial. Recently, we discovered that large networks of DNA damageome proteins (DDPs) promote DNA damage and genome instability (Xia et al. Cell 2019). We also found that Aquaporin 3 (AQP3) is a new lung cancer-associated DDP. This application describes the mechanism by which AQP3 interacts with low-dose arsenic to promote DNA damage, an approach to map AQP3, arsenic-induced double-strand break (DSB) hotspots, and associated mutation signatures in human cells and populations. Specifically, it will (1) provide mechanistic insights into how AQP3 potentiates arsenic-induced DNA Damage, (2) map DSBs caused by AQP3 and low-dose arsenic interactions, and (3) identify AQP3 and arsenic-induced genome instability and mutational signatures. The proposed studies will bring function to endogenous DNA damage and the DNA damageome proteins when interacting with environmental toxicants. Mechanistic insights into how low-dose arsenic interacts with risk genes are critical knowledge for the prevention, diagnosis, and treatment of arsenic-associated diseases. This project will identify early biomarkers to predict the long-term health impacts of arsenic, and uncover mutational signatures to infer cancer etiology and reveal past arsenic exposure. Lastly, the platform developed in this proposal will be useful for uncovering the effects of environmental toxicants and/or carcinogens with host genes. In addition to its scientific proposal, this application also lays out a comprehensive training plan that will help the candidate achieve his career goal of becoming an independent investigator who will apply his unique background in endogenous DNA damage to better understand genes-exogenous environmental agents (e.g. arsenic) interactions. Further interdisciplinary knowledge in environmental health, formal bioinformatics, and quantitative genomics training, as well as CRISPR and organoid training will put him in a unique position to tackle challenging environmental health research problems. Dr. Chris Amos, Director of the Institute for Clinical and Translational Research at the Baylor College of Medicine will lead a group of co-mentors and advisory committee members to provide advice on research and career development with advancement to a tenure track position.
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0.909 |