Phase-locked Fourier domain optical coherence tomography

Fourier or spectral domain optical coherence tomography (FDOCT) is a multi-dimensional interferometric imaging modality that has attracted increasing interest during the last few years. The reason is its outstanding sensitivity allowing high speed 2D and 3D imaging of weakly backscattering biological tissues in vivo and with high axial resolution. FDOCT has today largely replaced the preceding time domain OCT due to its marked advantage in sensitivity and acquisition speed. In particular, for fast in vivo retinal imaging with high resolution in 3D, FDOCT has become the method of choice. Recent developments enhance the clinical and biomedical potential of FDOCT by aiming from purely structural to functional tissue imaging, revealing tissue dynamics and physiology. The imaging parameter space is becoming highly multi-dimensional by including polarization, Doppler flow and spectroscopy. Two operating modes of FDOCT exist: spectrometer-based and swept-source. The latter captivates with its unprecedented depth-scan speed of several 100kHz whereas the spectrometer-based FDOCT offers ultra-high axial resolution capabilities of 2µm or even better. However, there are drawbacks to both FDOCT modalities including the depth-dependent sensitivity decay as well as the complex ambiguity of the FDOCT signal which leads to disturbing mirror structures as well as a restricted maximum depth range. Phase shifting techniques allow reconstruction of the complex sample signal, resolving the complex ambiguities, therefore reducing these drawbacks considerably. In addition, in the spectrometer-based FDOCT, any sample movement during camera integration causes a blurring of the interference fringes and thus reduces the sensitivity for flow detection. However, information on flow is especially interesting in ophthalmology since several studies of retinal blood flow – using laser Doppler flowmetry – have already outlined that vessel flow properties are early indicators of retinal pathologies like glaucoma, diabetic retinopathy or age related macula degeneration. This thesis proposes two new spectrometer-based FDOCT modalities, both based on the phase-sensitive nature of OCT. Appropriate locking of acquisition speed, exposure time and triggering onto artificially provoked signal phase changes allows the technique to benefit from additional degrees of freedom in the signal detection. The various established models were experimentally verified on biological and technical samples. First, spectrometer-based heterodyne FDOCT, without chromatic phase-shifting errors, was presented and discussed. The achromatic phase-shifting is achieved by using acousto-optic frequency shifters (AOFS). In vivo measurements showed experimentally the suppression of FDOCT-inherent artifacts like complex mirror terms due to the full complex signal reconstruction by quadrature detection of a stable beating frequency at 20'000 depth-scans per second using integrating buckets. In the search for ultra-high axial resolution, the currently available AOFS used were found to be a limiting factor and so further AOFS were developed to provide truly broadband devices. A dual beam extension allowed phase sensitive measurements even through long probing fibers. Phase stability issues with respect to the complex signal reconstruction algorithms used were discussed and it was shown theoretically, and verified experimentally, that amplitude errors are equally disturbing as phase errors. Second, a novel FDOCT modality called resonant Doppler FDOCT was introduced preventing interference fringe blurring caused by moving structures such as flow. The proposed method overcomes this problem by phase-matching the interferometer reference signal to the sample motion by means of an electro-optic phase modulator. Extraction of in vivo blood flow in 3D on a purely intensity basis with an improved velocity range as compared to currently performed color Doppler FDOCT was shown. In addition, for this proposed method, the detectable velocity range is independent of the detector speed. Quantitative flow detection was demonstrated with the same method.