Noninvasive functional imaging of molecular and cellular processes of vision may have immense impact on research and clinical diagnostics. Although suitable intrinsic optical signals (IOSs) have been observed ex vivo and in immobilized animals in vivo, detecting IOSs of photoreceptor activity in living humans was cumbersome and time consuming. Here, we observed clear spatially and temporally resolved changes in the optical path length of the photoreceptor outer segment as a response to an optical stimulus in the living human eye. To witness these changes, we evaluated phase data obtained with a parallelized and computationally aberration-corrected optical coherence tomography system. The noninvasive detection of optical path length changes shows neuronal photoreceptor activity of single cones in living human retina, and therefore, it may provide diagnostic options in ophthalmology and neurology and could provide insights into visual phototransduction in humans.functional optical coherence tomography | intrinsic optical signals | imaging | adaptive optics | phototransduction

IntroductionIntraoperative detection of residual tumor remains an important challenge in surgery to treat gliomas. New developments in optical techniques offer non-invasive high-resolution imaging that may integrate well into the workflow of neurosurgical operations. Using an intracranial glioma model, we have recently shown that time domain optical coherence tomography (OCT) allows discrimination of normal brain, diffusely invaded brain tissue, and solid tumor. OCT imaging allowed acquisition of 2D and 3D data arrays for multiplanar analysis of the tumor to brain interface. In this study we have analyzed biopsy specimens of human brain tumors and we present the first feasibility study of intraoperative OCT and post-image acquisition processing for non-invasive imaging of the brain and brain tumor.MethodsWe used a Sirius 713 Tomograph with a superluminescence diode emitting light at a near infrared central wavelength of 1,310 nm and a coherence length of 15 µm. The light is passed through an optical mono mode fiber to a modified OCT adapter containing a lens system with a working distance of 10 cm and an integrated pilot laser. Navigation-registered tumor biopsies were imaged ex vivo and the intraoperative site of optical tissue analysis was registered by marker acquisition using a neuronavigation system.ResultsOptical coherence tomography non-contact measurements of brain and brain tumor tissue produced B-scan images of 4 mm in width and 1.5–2.0 mm in depth at an axial and lateral optical resolution of 15 µm. OCT imaging demonstrated a different microstructure and characteristic signal attenuation profiles of tumor versus normal brain. Post-image acquisition processing and automated detection of the tissue to air interface was used to realign A-scans to compensate for image distortions caused by pulse- and respiration-induced movements of the target volume. Realigned images allowed monitoring of intensity changes within the scan line and facilitated selection of areas for the averaging of A-scans and the calculation of attenuation coefficients for specific regions of interest.ConclusionThis feasibility study has demonstrated that OCT analysis of the tissue microstructure and light attenuation characteristics discriminate normal brain, areas of tumor infiltrated brain, solid tumor, and necrosis. The working distance of the OCT adapter and the A-scan acquisition rate conceptually allows integration of the OCT applicator into the optical path of the operating microscopes. This would allow a continuous analysis of the resection plain, providing optical tomography, thereby adding a third dimension to the microscopic view and information on the light attenuation characteristics of the tissue.