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a SPECIFIC AIMS The overarching goal for the proposed Network for Translations! Research (NTR) Center is to translate anovel real-time noninvasive multimodal clinical imaging tool into clinical practice for sentinel lymph node (SLN)mapping. The proposed imaging tool is a hybrid technology, referred to as photoacoustic tomography (PAT), tobe used in combination with conventional ultrasound imaging (ultrasonography). Ultrasound imaging will beused to image lymph nodes which are hypoechoic, whereas PAT will be used to identify whether a node issentinel (the first draining node) by detecting the accumulated methylene blue dye. Ultrasound imaging cannotdetect methylene blue dye because the dye has little mechanical contrast. In comparison, PAT hasdemonstrated high sensitivity in detecting methylene blue dye because the dye has high optical contrast. Inother words, while ultrasound imaging provides structural information, PAT provides functional informationabout the lymphatics. In addition, the task-specific projects will enhance functional PAT in several aspects,especially, in molecular imaging of metastases.Sentinel lymph node biopsy (SLNB) has become the standard method of axillary staging for patients withbreast cancer and clinically negative axillae. Even though SLNB using both methylene blue dye andradioactive tracers (Tc-99 colloids) has a high identification rate, it still relies on an invasive surgical procedurewith associated morbidity. Axillary ultrasound has emerged as a diagnostic tool to evaluate the axilla, but it canonly assess morphology and cannot specifically identify the SLN. The ability to identify the SLN noninvasivelyin vivo would be a highly useful clinical tool for breast cancer patients, as it would enable the clinician toidentify the SLN in vivo so that non-invasive diagnostic methods (e.g., fine needle aspiration biopsy andreverse transcription polymerase chain reaction) could be utilized to stage the axilla without the morbidity of anoperative procedure. The proposed multimodal technology can potentially map SLN noninvasively with highspatial resolution in real time yet without the use of radioactive tracers; consequently, invasive surgicalprocedures are avoided. Furthermore, photoacoustic molecular imaging can potentially identify metastases insitu without even needle biopsy and monitor therapy as well. Therefore, the proposed multi-modalphotoacoustic/ultrasound imaging technology has high potential impact on breast axillary staging andmanagement.We hypothesize that PAT can reliably map SLNs, which accumulate methylene blue dye. Methylene bluedye is in routine clinical use and is an excellent optical contrast agent for PAT. Its peak absorption wavelengthis 690 nm, which lies near the optimal optical penetration window. Therefore, imaging SLNs is a perfect clinicalapplication of PAT.PAT is based on the generation of photoacoustic waves by safely depositing short-pulsed optical energyinto tissue. Each laser pulse causes a rapid temperature rise usually on the order of 10 millidegrees. Theultrasonic emission due to thermoelastic expansion is detected with an array of ultrasonic transducers andthen used to reconstruct an image. The PAT technology is designed to overcome the poor spatial resolution ofpure optical imaging yet to retain the high optical contrasts. In terms of spatial resolution, pure optical imagingsuffers from strong optical scattering in tissue. By contrast, ultrasonic waves can propagate in tissue withrelatively low scattering and can therefore provide good spatial resolution. The applicants have demonstratedspeckle-free photoacoustic images at high spatial resolution. Therefore, PAT integrates high optical contrastwith high ultrasonic resolution in a single hybrid imaging modality.
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