Subcellular optical coherence tomography with a Kerr lens mode-locked Ti:Al₂O₃ laser

The longitudinal resolution of optical coherence tomography (OCT) is currently limited by the optical bandwidth of the light source, typically a superluminescent diodes, to approximately 10-15 μm. This resolution is insufficient to identify individual cells or to assess subcellular structures such as nuclei or mitotic figures. The ability to perform subcellular imaging with OCT could greatly enhance the detection of early neoplastic changes and improve early cancer diagnosis or the imaging of developing biological morphology. Higher resolution OCT would also improve specificity of diagnosis for several ocular diseases, such as glaucoma, which require precise, detailed imaging and measurement of retinal nerve fiber layer thickness. State of the art Kerr-lens mode-locked (KLM) Ti:A₂O₃ lasers using double chirped dispersion compensating mirrors can generate pulse durations of <7 fs and bandwidths of 200 nm or more at 800 nm center wavelength. These pulse durations and bandwidths can be used for OCT, resulting in longitudinal resolutions of less than 2 μm. The use of such broad bandwidths also enables the extraction of localized, wavelength dependent absorption and scattering tissue characteristic by detecting the full interferometric fringe signal and using Fourier signal processing. In this paper we demonstrate an ultra-high, subcellular level resolution, spectroscopic OCT system based on a mode-locked Ti:Al₂O₃ laser. In vivo imaging of developmental biology specimens as well as preliminary in vivo spectroscopic OCT results are demonstrated.