Significance: Using a full-field optical coherence tomography system, we measured changes in the time that light requires to pass through photoreceptor outer segments, when the retina is stimulated by a light pulse. This effect can be used to monitor the activity of single cones in the living human eye. Objective monitoring of photoreceptor activity using such intrinsic optical signals could have important diagnostic applications in ophthalmology and neurology and might provide insight to facilitate basic research.

Certain topics in research and advancements in medical diagnostics may benefit from improved temporal and spatial resolution during non-invasive optical imaging of living tissue. However, so far no imaging technique can generate entirely diffraction-limited tomographic volumes with a single data acquisition, if the target moves or changes rapidly, such as the human retina. Additionally, the presence of aberrations may represent further difficulties. We show that a simple interferometric setup–based on parallelized optical coherence tomography–acquires volumetric data with 10 billion voxels per second, exceeding previous imaging speeds by an order of magnitude. This allows us to computationally obtain and correct defocus and aberrations resulting in entirely diffraction-limited volumes. As demonstration, we imaged living human retina with clearly visible nerve fiber layer, small capillary networks, and photoreceptor cells. Furthermore, the technique can also obtain phase-sensitive volumes of other scattering structures at unprecedented acquisition speeds.

Descemet membrane endothelial keratoplasty (DMEK) has recently been introduced as an innovative surgical technique to selectively replace diseased endothelium in patients with Fuchs endothelial dystrophy and pseudophakic bullous endothelial keratopathy.¹ This technique has superseded perforating keratoplasty, in many cases sparing unaffected stromal tissue. Advantages of this tissue-selective approach include better visual outcome owing to maintenance of the corneal structural configuration,^2,3 faster visual recovery after initial surgery,^4-6 and fewer intraoperative complications, in particular, expulsive hemorrhage.⁷ In terms of graft rejection, DMEK demonstrates a 15-times lower rejection rate, which is thought to result from the limited amount of tissue and therefore potential antigen that is transplanted.^8-10 Despite all the advantages described, the overall procedure is challenging for the surgeon. Crucial yet difficult steps include preparation of the intact donor lamella, transfer of the graft into the anterior chamber (AC), unfolding and orientation of the graft, and final successful attachment after air filling. One important limiting factor in these difficulties is a deficient visibility of the delicate tissue due to the natural en face view through the operating microscope. This view hinders an estimation of the depth ratio, orientation of the transplanted graft, and drainage of the interface fluid. In this context, a cross-sectional view would greatly enhance the intraoperative overview and enable the surgeon to better control the procedure.

Introduction Intraoperative 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. Methods We 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. Results Optical 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. Conclusion This 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.