Most of the fundamental pathological processes in living tissues exhibit changes at the nanoscale. Noninvasive, label-free detection of structural changes in biological samples pose a significant challenge to both researchers and healthcare professionals. It is highly desirable to be able to resolve these structural changes, during physiological processes, both spatially and temporally. Modern nanoscopy largely requires labeling, is limited to superficial 2D imaging, and is generally not suitable for in vivo applications. Furthermore, it is becoming increasingly evident that 2D biology often does not translate into the real 3D situation. Here, we present a method, spatial frequency domain correlation mapping optical coherence tomography (sf-cmOCT), for detection of depth resolved nanoscale structural changes noninvasively. Our approach is based on detection and correlation of the depth resolved spectra of axial spatial frequencies of the object which are extremely sensitive to structural alterations. The presented work describes the principles of this approach and demonstrates its feasibility by monitoring internal structural changes within objects, including human skin in vivo. Structural changes can be visualized at each point in the sample in space from a single image or over time using two or more images. These experimental results demonstrate possibilities for the study of nanoscale structural changes, without the need for biomarkers or labels. Thus, sf-cmOCT offers exciting and far-reaching opportunities for early disease diagnosis and treatment response monitoring, as well as a myriad of applications for researchers.

An all-acousto-optically switched picosecond Nd:YAG regenerative amplifier has been developed for operation at pulse repetition rates in the 20-100-kHz range. The amplifier produces stable 50-ps pulses at 1064 nm in a TEMOO transverse mode with pulse energies of the order of 20-100 AJ. Generation of the second harmonic at 532 nm in KTP crystal results in conversion efficiencies greater than 40%. Using the frequency-doubled TEMoo output of the regenerative amplifier to pump a two-pass dye amplifier, we have amplified the 50-fs output pulses from an antiresonant ring dye laser to the 200-nJ level and have successfully produced a stable whitelight continuum at a 100-kHz repetition rate. This preliminary demonstration of synchronous dye-laser amplification and continuum generation attests to the overall quality of the regenerative amplifier output and the general utility of this approach for high-repetition-rate amplification. Limitations of the current regenerative amplifier design and scaling to higher pulse energies are briefly discussed.

Optical coherence tomography (OCT) is emerging as a powerful noncontact imaging technique, allowing high-quality cross-sectional imaging of scattering specimens nondestructively. However, the complexity and cost of current embodiments of an OCT system limit its use in various nondestructive testing (NDT) applications at resource-limited settings. In this paper, we demonstrate the feasibility of a novel low-cost OCT system for a range of nondestructive testing (NDT) applications. The proposed imaging system is based on an enhanced time-domain OCT system with a low cost and small form factor reference arm optical delay, called multiple reference OCT (MR-OCT), which uses a miniature voice coil actuator and a partial mirror for extending the axial scan range. The proposed approach is potentially a low-cost, compact, and unique optical imaging modality for a range of NDT applications in a low-resource setting. Using this method, we demonstrated the capability of MR-OCT to perform cross-sectional and volumetric imaging at 1200 A-scans per second.

Abstract:In this paper, we report the feasibility of integrating a novel low cost optical coherence tomography (OCT) system with a dermascope for point-of-care applications. The proposed OCT system is based on an enhanced time-domain optical coherence tomographic system, called multiple reference OCT (MR-OCT), which uses a single miniature voice coil actuator and a partial mirror for extending the axial scan range. The system can simultaneously register both the superficial dermascope image and the depth-resolved OCT sub-surface information by an interactive beam steering method. A practitioner is able to obtain the depth resolved information of the point of interest by simply using the mouse cursor. The proposed approach of combining a dermascope with a low cost OCT provides a unique powerful optical imaging modality for a range of dermatological applications. Hand-held dermascopic OCT devices would also enable point of care and remote health monitoring.

Multiple reference optical coherence tomography (MR-OCT) is a technology ideally suited to low-cost, compact OCT imaging. This modality is an extension of time-domain OCT with the addition of a partial mirror in front of the reference mirror. This enables extended, simultaneous depth scanning with the relatively short scan range of a miniature voice coil motor on which the scanning mirror is mounted. This work details early stage development of the first iteration of a miniature MR-OCT device. This iteration utilizes a fiber-coupled input from an off-board superluminescent diode. The dimensions of the module are 40 × 57 ?? mm . Off-the-shelf miniature optical components, voice coil motors, and photodetectors are used, with the complexity of design depending on the specific application. The photonic module can be configured as either polarized or nonpolarized and can include balanced detection. The results shown in this work are from the nonpolarized device. The system was characterized through measurement of the input spectrum, axial resolution, and signal-to-noise ratio. Typical B-scans of static and in vivo samples are shown, which illustrate the potential applications for such a technology.

For both fundamental study of biological processes and early diagnosis of diseases, information about nanoscale changes in tissue and cell structure is crucial. Nowadays, almost all currently known nanoscopy methods rely upon the contrast created by fluorescent stains attached to the object or molecule of interest. This causes limitations due to the impact of the label on the object and its environment, as well as its applicability in vivo, particularly in humans. In this paper, a new label-free approach to visualize small structure with nano-sensitivity to structural alterations is introduced. Numerically synthesized profiles of the axial spatial frequencies are used to probe the structure within areas whose size can be beyond the diffraction resolution limit. Thereafter, nanoscale structural alterations within such areas can be visualized and objects, including biological ones, can be investigated with sub-wavelength resolution, in vivo, in their natural environment. Some preliminary results, including numerical simulations and experiments, which demonstrate the nano-sensitivity and super-resolution ability of our approach, are presented.

These results show that MR-OCT has the potential to measure the curing time and monitor the curing process as a function of depth. Moreover, MR-OCT as a product has potential to be compact, low-cost and to fit into a smartphone. Using such a device for monitoring the curing of the resin will be suitable for dentists in stationary and mobile clinical settings.

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