Optical coherence tomography (OCT) is a recently developed optical imaging technique that performs high resolution, cross-sectional tomographic imaging of microstructure in biological systems. OCT is analogous to ultrasound B mode imaging except that it uses light instead of sound. OCT performs imaging by using low coherence interferometry to measure the optical backscattering of tissue as a function of echo delay and transverse position . The resulting two-dimensional data set can be displayed as a gray scale or false color image. OCT functions as a type of "optical biopsy" to provide cross sectional images of tissue structure on the micron scale. OCT is a powerful imaging technology because, unlike conventional histopathology, which requires removal of a tissue specimen and processing for microscopic examination, OCT can provide images of tissue in situ and in real time, without the need for excision. OCT has originally been developed and applied by our group for tomographic diagnostics in ophthalmology [2,3]. OCT can provide images of the retina with resolutions of 10 p,m, one order of magnitude higher than conventional ultrasound. Working in collaboration with the New England Eye Center and MIT Lincoln Laboratory, we have developed a clinical prototype OCT instrument and examined over 5000 patients. The technology has been transferred to industry, and a commercial product was introduced into the ophthalmic market in 1996. Studies in ophthalmology show that OCT is especially promising for the diagnosis and monitoring of diseases such as glaucoma or macular edema associated with diabetic retinopathy where it provides quantitative information on disease progression. In many cases OCT has the ability to detect and diagnose early stages of disease before physical symptoms and loss of vision occur. Recent research on OCT has focused on developing technology to perform optical biopsy in internal medicine [4-6]. OCT at optical wavelengths in the near infrared where tissue scattering is minimized allows imaging to be performed to depths of 2-3 mm. Using solid state modelocked laser sources which can provide both short coherence lengths and high powers, high resolution and high speed imaging may be achieved. Image resolutions of 5-10 im and high speed acquisition of 250 x 250 pixel images at rates of 8 frames per second have been achieved. OCT imaging has been integrated with microscopy to perform imaging of specimens in vitro. A prototype single mode fiber optic catheter/endoscope with a diameter of 1 mm has been developed which can transluminally image internal tissue structures such as the respiratory tract, gastrointestinal tract, or arteries. In recent studies, catheter/endoscope based OCT imaging of internal organs in an animal model has been demonstrated . Endoscopic OCT imaging in patients has also been demonstrated . Ultrahigh resolution OCT has recently been developed and demonstrated. Kerr lens modelocked Ti:sapphire lasers have achieved sub-two cycle duration optical pulses with a corresponding bandwidth from 650 nm to 1000 nm . Since the axial resolution of OCT is inversely proportional to the bandwidth of the light source, axial resolutions of 1 -2 im can be achieved. A novel C-scan focus tracking and image fusion technique has also been demonstrated to overcome depth of field limitations and permit 3 im transverse resolutions. This system can achieve subcellular level resolution and promises to be a powerful research tool in developmental biology and future clinical studies . OCT is a promising and powerful medical imaging technique because it can permit the in situ visualization of tissue microstructure without the need to remove a specimen excisionally as in conventional biopsy and histopathology. The concept of nonexcisional "optical biopsy" provided by OCT and the ability to visualize tissue architectural morphology in real time under operator guidance can have many applications in several scenarios: 1) For situations where conventional biopsy is either hazardous or impossible, 2) Where biopsy has an unacceptably high false negative rate due to sampling errors, and 3) For guiding surgical intervention. This presentation will discuss technology and applications of this new imaging modality.