We implemented a wide field-of-view visible-light optical coherence microscope (OCM) for investigating ex-vivo brain tissue of patients diagnosed with Alzheimer’s disease (AD) and of a mouse model of AD. A submicrometer axial resolution in tissue was achieved using a broad visible light spectrum. The use of various objective lenses enabled reaching micrometer transversal resolution and the acquisition of images of microscopic brain features, such as cell structures, vessels, and white matter tracts. Amyloid-beta plaques in the range of 10 to 70 μm were visualized. Large field-of-view images of young and old mouse brain sections were imaged using an automated x − y − z stage. The plaque load was characterized, revealing an age-related increase. Human brain tissue affected by cerebral amyloid angiopathy was investigated and hyperscattering structures resembling amyloid beta accumulations in the vessel walls were identified. All results were in good agreement with histology. A comparison of plaque features in both human and mouse brain tissue was performed, revealing an increase in plaque load and a decrease in reflectivity for mouse as compared with human brain tissue. Based on the promising outcome of our experiments, visible light OCM might be a powerful tool for investigating microscopic features in ex-vivo brain tissue.
Polarization-sensitive optical coherence tomography (PS-OCT) provides intrinsic contrast related to tissue microstructure. In the past, PS-OCT has been successfully used for imaging the anterior eye of humans in a variety of pathologic conditions. Here, we present PS-OCT imaging of the anterior eye in mice. Spectral domain PS-OCT centered at a wavelength of 840 nm was performed in anaesthetized laboratory mice. Three dimensional data sets were acquired at a 70 kHz A-line rate. PS-OCT images displaying phase retardation, birefringent axis orientation and degree of polarization uniformity (DOPU) were computed. Similar to human anterior segments, depolarization was observed in the corneal stroma and in structures containing melanin pigments such as the iris and the ciliary body. Birefringence was detected in the sclera close to the limbus. Aside from depolarizing foci observed within structures affected by cataract, the lens appeared mostly polarization preserving. Increased birefringence was observed in a scarred cornea. Given the similarity of the polarization characteristics in the murine eye and the human eye, PS-OCT lends itself as an ideal candidate for non-invasive imaging in preclinical studies in mouse models of anterior segment pathology.
A few-mode fiber based detection for OCT systems is presented. The capability of few-mode fibers for delivering light through different fiber paths enables the application of these fibers for angular scattering tissue character- ization. Since the optical path lengths traveled in the fiber change between the fiber modes, the OCT image information will be reconstructed at different depth positions, separating the directly backscattered light from the light scattered at other angles. Using the proposed method, the relation between the angle of reflection from the sample and the respective modal intensity distribution was investigated. The system was demonstrated for imaging ex-vivo brain tissue samples of patients with Alzheimer’s disease.
A visible light spectral domain optical coherence microscopy system operating in the wavelength range of 450-680 nm was developed. The resulting large wavelength range of 230 nm enabled an ultrahigh axial resolution of 0.88μm in tissue. The setup consisted of a Michelson interferometer combined with a homemade spectrometer with a spectral resolution of 0.03 nm. Scanning of 1 x 1 mm2 and 0.5 x 0.5 mm2 areas was performed by an integrated microelectromechanical mirror. After scanning the light beam is focused onto the tissue by a commercial objective with a 10 x magnification, resulting in a transverse resolution of 2 μm . Specification measurements showed that a -89 dB sensitivity with a 24 dB/mm roll-off could be achieved with the system. First of all the capabilities of the system were tested by investigating millimeter paper, tape and the USAF (US Air Force) 1951 resolution test target. Finally cerebral tissues from non-pathological and Alzheimer's disease affected brains were investigated. The results showed that structures, such as white and gray matter, could be distinguished. Furthermore a first effort was made to differentiate Alzheimer's disease from healthy brain tissue.