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DESCRIPTION (provided by applicant): Recent advances in photoacoustic tomography (PAT) have demonstrated its potential for 3D noninvasive high resolution imaging of soft tissues at penetration depths of many centimeters. Further, and perhaps even more importantly, imaging of tissue structure can be achieved while also providing crucial information regarding tissue composition and functionality. These results represent a dramatic breakthrough in soft tissue imaging technology. While there are a host of applications for this technology, breast imaging for the purpose of cancer screening and diagnosis is one of considerable import, affecting both cost and quality of healthcare nationally and globally.17 PAT makes use of intense, short-duration (nanosecond) laser pulses at specific wavelengths. The selective absorption of these wavelengths by targeted tissues gives rise to a primary acoustic signal. High resolution acoustic imaging is achieved by means of an advanced array of acoustic detectors and associated signal processing electronics and software. Tissue discrimination is obtained from differential images at multiple (deep red and near infrared) wavelengths. For breast imaging, requiring deep tissue penetration and tumor localization, the key wavelengths ofinterest lie within the tuning range of alexandrite lasers (or of alexandrite and Nd:YAG lasers (700 - 1100 nm). Consequently, the development of alexandrite lasers that meet the specific requirements for photoacoustic imaging of the breast is critical forthe development of tumor diagnostic and imaging systems. These specific laser requirements relate primarily to the wavelengths used, pulse sequence in time, the pulse duration, the pulse energy, and the spatial uniformity of the beam produced by the lasersystem. Light Age Inc., is the inventor, designer, and principal developer of alexandrite and other solid-state laser systems. Over the past decade it has developed and delivered laser systems to researchers that meet certain key requirements for PAT These laser systems have been successfully developed for a variety of applications, including soft tissue imaging of the breast, and have recently provided some dramatic results (see Research Strategy section). The effort proposed here is to develop a prototype PAT system specifically for this application and to perform initial testing on animals and human subjects. Because the laser wavelengths are known to be non-mutagenic and the fluence levels used here are well-below those now routinely used to treat pigmented and vascular lesions in well-established and FDA-approved alexandrite laser-based medical devices, there is no conceivable risk to study subjects. The goal of this Phase I and follow-on Phase II program is to develop a laser-based PAT system suitablefor use by a clinical imaging technician. The prototype clinical system will meet all of the basic requirements for breast imaging with respect to performance, system packaging, and ease of use. Additionally, it can provide advanced breast tumor discrimination capabilities beyond the present-day state-of-the-art. In the Phase I program, we will develop and demonstrate an improved laser source for PAT. Among other improvements in its performance properties it will provide a novel laser operating mode having rapid (pulse-to-pulse) wavelength switching. This may enable improvements in the tissue discrimination that can be achieved by means of differential imaging of vascular tissues due to oxy- and deoxy- hemoglobin concentrations. We will also conduct studies to determine how operating factors such as greater repetition rate and higher pulse energy will affect system size and cost. These studies will help guide the specifications for future clinical laser systems. In the Phase II program we will deliver a laser system that incorporates the rapid wavelength switching feature, to Optosonics, Inc. (a PAT system developer based in N. Carolina) for testing and clinical qualification. In Phase II we will also develop refinements to the laser and PAT control systemsthat are additionally desirable for clinical operation. To ensure that our technical work remains focused on the key areas of performance for PAT, throughout the Phase I program we will consult with collaborators at Optosonics. PUBLIC HEALTH RELEVANCE PUBLIC HEALTH RELEVANCE: The purpose of this program is to develop a photoacoustic tomography (PAT) imaging system that can serve as a routine diagnostic tool for soft tissue evaluation in a clinical environment. Initial emphasis is placed on mammographic assay and breast tumor discrimination where high resolution imaging along with selective contrast enhancement of vascular functionality can provide improved tumor screening, promising earlier stage tumor detection and reduction of unnecessary biopsyand associated costs. Key to this are the development of specific laser performance characteristics and refinements that provide enhanced resolution and tumor contrast at depth; and which reduce system size. The advanced imaging devices that result can bereadily introduced into most hospitals and specialty clinics at rea