LAMMP has played a leading role in the development of fiber-based microendoscopic OCT, MPM, CARS and translated these technologies for in vivo imaging [1-5]. Although each optical probing technique provides access to relevant diagnostic parameters, integration of several modalities will be necessary to advance the development of a reliable method for diagnosis and management of many complex diseases. An example is cardiovascular diseases such as atherosclerosis. Diagnosis of the latent vulnerability of a plaque lesion relies on tissue structure, chemical compositions, and tissue mechanical properties [6, 7]. Another example is cancer diagnosis. Tissue structure, angiogenesis, and extracellular matrix change are all important parameters for eariy cancer diagnosis. Although multimodal microscopy systems have been demonstrated by several groups [8-13], most reported systems are implemented in a bench top free space microscopy platform, which limits their potential applications for In vivo animal and human patient imaging. LAMMP has pioneered several important multimodal imaging modalities, such as fiber-based combined MPM/OCT system [14] and combined US/OCT endoscopy for intravascular imaging [15-17]. However, significant challenges remain that hinder the translation of this technology for in vivo imaging. The broad, long term objective of the proposed research is to develop integrated multimodality endoscopic technologies (MET) that can perform in vivo imaging of tissue structure, composition, and mechanical properties information with high imaging speed, contrast, sensitivity, and spatial resolution. We will focus on two technologies. The first is an integrated endoscopic/intravascular imaging system that combines intravascular optical coherence tomography (OCT), ultrasound (US), and phase-resolved acoustic radiation force optical coherence elastography (PR-ARF-OCE). The multimodal intravascular imaging system is unique in that it combines the advantages of high spatial resolution from OCT, broad imaging depth from US, and mechanical sensitivity from PR-ARF-OCE. Because the stiffness of arterial wails, soft tissues, atheroma, and calcifications vary widely, PR-ARF-OCE provides essential information to assess plaque vulnerability. The second is the development of a fiber-based micro-endoscopic/intravascular system that integrates OCT with coherent anti-Stokes Raman scattering (CARS) and multiphoton microscopy (MPM). MPM/CARS uses the nonlinear optical interaction of biological molecules with short laser pulses to provide high resolution imaging with molecular sensitivity. We will work closely TRD2 to integrate the advances in a compact fiber laser, photonic crystal fiber, and miniature probe to develop a fiber-based endoscopic OCT/MPM/CARS system with high spatial resolution and high molecular sensitivity. There are many driving biomedical problems that can benefit from these two platform technologies. We choose to focus on intravascular imaging as our flagship applications because the implementation of multimodality imaging for intravascular applications is most challenging. The integrated probe for intravascular imaging can be adapted for other endoscopic applications with minimum complications because the design parameters for intravascular application are most stringent. The two integrated imaging systems will allow imaging and evaluating intra-lesion lipid density and the cholesterol content in additional to the morphology of plaques obtained from OCT imaging. The proposed multimodality systems will provide biomedical researchers and physicians powerful tools for imaging, diagnosing, and managing vulnerable plaques.
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