Al-Hafeez Dhalla

Doppler velocity detection limitations in spectrometer-based versus swept-source optical coherence tomography

Recent advances in Doppler techniques have enabled high sensitivity imaging of biological flow to measure blood velocities and vascular perfusion. Here we compare spectrometer-based and wavelength-swept Doppler OCT implementations theoretically and experimentally, characterizing the lower and upper observable velocity limits in each configuration. We specifically characterize the washout limit for Doppler OCT, the velocity at which signal degradation results in loss of flow information, which is valid for both quantitative and qualitative flow imaging techniques. We also clearly differentiate the washout effect from the separate phenomenon of phase wrapping. We demonstrate that the maximum detectable Doppler velocity is determined by the fringe washout limit and not phase wrapping. Both theory and experimental results from phantom flow data and retinal blood flow data demonstrate the superiority of the swept-source technique for imaging vessels with high flow rates.

Structured oblique illumination microscopy for enhanced resolution imaging of non-fluorescent, coherently scattering samples.

Many biological structures of interest are beyond the diffraction limit of conventional microscopes and their visualization requires application of super-resolution techniques. Such techniques have found remarkable success in surpassing the diffraction limit to achieve sub-diffraction limited resolution; however, they are predominantly limited to fluorescent samples. Here, we introduce a non-fluorescent analogue to structured illumination microscopy, termed structured oblique illumination microscopy (SOIM), where we use simultaneous oblique illuminations of the sample to multiplex high spatial-frequency content into the frequency support of the system. We introduce a theoretical framework describing how to demodulate this multiplexed information to reconstruct an image with a spatial-frequency support exceeding that of the system’s classical diffraction limit. This approach allows enhanced-resolution imaging of non-fluorescent samples. Experimental confirmation of the approach is obtained in a reflection test target with moderate numerical aperture.

Complex conjugate resolved heterodyne swept source optical coherence tomography using coherence revival

We describe a simple and low-cost technique for resolving the complex conjugate ambiguity in Fourier domain optical coherence tomography (OCT) that is applicable to many swept source OCT (SSOCT) systems. First, we review the principles of coherence revival, wherein an interferometer illuminated by an external cavity tunable laser (ECTL) exhibits interference fringes when the two arms of the interferometer are mismatched by an integer multiple of the laser cavity length. Second, we report observations that the spectral interferogram obtained from SSOCT systems employing certain ECTLs are automatically phase modulated when the arm lengths are mismatched this way. This phase modulation results in a frequency-shifted interferogram, effectively creating an extended-depth heterodyne SSOCT system without the use of acousto-optic or electro-optic modulators. We suggest that this phase modulation may be caused by the ECTL cavity optical pathlength varying slightly over the laser sweep, and support this hypothesis with numerical simulations. We also report on the successful implementation of this technique with two commercial swept source lasers operating at 840nm and 1040nm, with sweep rates of 8kHz and 100kHz respectively. The extended imaging depth afforded by this technique was demonstrated by measuring the sensitivity fall-off profiles of each laser with matched and mismatched interferometer arms. The feasibility of this technique for clinical systems is demonstrated by imaging the ocular anterior segments of healthy human volunteers.

Simultaneous swept source optical coherence tomography of the anterior segment and retina using coherence revival

We report on an implementation of coherence revival-based heterodyne swept source optical coherence tomography that is capable of simultaneously imaging the anterior and posterior eye. A polarization-encoded sample arm was used to efficiently focus orthogonal polarizations on the anterior segment and retina. Depth encoding was achieved using coherence revival, which allows for multiple depths within a sample to be simultaneously imaged and frequency encoded by carefully controlling the optical pathlength of each sample path. This design is a significant step toward whole-eye optical coherence tomography (OCT), which would enable customized ray-traced modeling of patient eyes to improve refractive surgical interventions and eliminate optical artifacts in retinal OCT diagnostics. We demonstrated the feasibility of this system for in vivo imaging by simultaneously acquiring images of the anterior segments and retinas in healthy human volunteers.

Crosstalk rejection in parallel optical coherence tomography using spatially incoherent illumination with partially coherent sources

The continuing improvement of high-speed area-scan cameras has made possible the construction of parallel optical coherence tomography (OCT) systems that are competitive with the fastest demonstrated swept-source OCT systems. Unfortunately, when imaging through turbid media using a partially coherent source, parallel OCT suffers resolution loss from coherent multiple scattering, a phenomenon known as crosstalk. We demonstrate the use of a full-field OCT system employing multimode fiber in the illumination arm to reduce the spatial coherence of a partially coherent source. By reducing the spatial coherence area below the systems lateral resolution, we create a spatial coherence gate that rejects these multiply scattered photons. We quantify the image quality and resolution improvement of this method by comparing images of a USAF test chart acquired beneath turbid phantoms using both coherent and incoherent illumination and computing the resulting modulation transfer functions. We demonstrate the feasibility of this method for imaging biological specimens by imaging a Drosophila melanogaster sample.

Coherence revival multiplexed, buffered swept source optical coherence tomography: 400 kHz imaging with a 100 kHz source

The effective speed of a swept source optical coherence tomography (SSOCT) imaging system was quadrupled using efficient sweep buffering along with coherence revival and spatial multiplexing. A polarizing beam splitter and fold mirror assembly were used to create a dual spot sample arm with a common objective designed for near-diffraction-limited retinal imaging. Using coherence revival, a variable optical delay line allowed for separate locations within a sample to be simultaneously imaged and frequency encoded by carefully controlling the optical path length of each sample path. This method can be used to efficiently quadruple the imaging speed of any SSOCT system employing a low duty-cycle laser that exhibits coherence revival. The system was used to image the retina of healthy human volunteers.

Efficient sweep buffering in swept source optical coherence tomography using a fast optical switch.

We describe a novel buffering technique for increasing the A-scan rate of swept source optical coherence tomography (SSOCT) systems employing low duty cycle swept source lasers. This technique differs from previously reported buffering techniques in that it employs a fast optical switch, capable of switching in 60 ns, instead of a fused fiber coupler at the end of the buffering stage, and is therefore appreciably more power efficient. The use of the switch also eliminates patient exposure to light that is not used for imaging that occurs at the end of the laser sweep, thereby increasing the system sensitivity. We also describe how careful management of polarization can remove undesirable artifacts due to polarization mode dispersion. In addition, we demonstrate how numerical compensation techniques can be used to modify the signal from a Mach-Zehnder interferometer (MZI) clock obtained from the original sweep to recalibrate the buffered sweep, thereby reducing the complexity of systems employing lasers with integrated MZI clocks. Combining these methods, we constructed an SSOCT system employing an Axsun technologies laser with a sweep rate of 100kHz and 6dB imaging range of 5.5mm. The sweep rate was doubled with sweep buffering to 200 kHz, and the imaging depth was extended to 9 mm using coherence revival. We demonstrated the feasibility of this system by acquiring images of the anterior segments and retinas of healthy human volunteers.

Optimization of confocal scanning laser ophthalmoscope design

Abstract. Confocal scanning laser ophthalmoscopy (cSLO) enables high-resolution and high-contrast imaging of the retina by employing spatial filtering for scattered light rejection. However, to obtain optimized image quality, one must design the cSLO around scanner technology limitations and minimize the effects of ocular aberrations and imaging artifacts. We describe a cSLO design methodology resulting in a simple, relatively inexpensive, and compact lens-based cSLO design optimized to balance resolution and throughput for a 20-deg field of view (FOV) with minimal imaging artifacts. We tested the imaging capabilities of our cSLO design with an experimental setup from which we obtained fast and high signal-to-noise ratio (SNR) retinal images. At lower FOVs, we were able to visualize parafoveal cone photoreceptors and nerve fiber bundles even without the use of adaptive optics. Through an experiment comparing our optimized cSLO design to a commercial cSLO system, we show that our design demonstrates a significant improvement in both image quality and resolution.

Complete complex conjugate resolved heterodyne swept-source optical coherence tomography using a dispersive optical delay line.

Swept-source optical coherence tomography (SSOCT) provides a substantial sensitivity advantage over its time-domain counterpart, but suffers from a reduced imaging depth range due to sensitivity falloff and complex conjugate ambiguity. Heterodyne complex conjugate-resolved SSOCT (HCCR-SSOCT) has been previously demonstrated as a technique to completely resolve the complex conjugate ambiguity, effectively doubling the falloff limited imaging depth, without the reduction in imaging speed associated with other CCR techniques. However, previous implementations of this technique have employed expensive and lossy optical modulators to provide the required differential phase modulation. In this paper, we demonstrate the use of a dispersive optical delay line (D-ODL) as the reference arm of an OCT system to realize HCCR-SSOCT. This technique maintains the existing advantages of HCCR-SSOCT in that it completely resolves the complex conjugate artifact and does not reduce imaging speed, while conferring the additional advantages of being low cost, maintaining system sensitivity and resolution, not requiring any additional signal processing, and working at all wavelengths and imaging speeds. The D-ODL also allows for hardware correction of unbalanced dispersion in the reference and sample arm, adding further flexibility to system design. We demonstrate the technique using an SSOCT system operating at 100kHz with a central wavelength of 1040nm. Falloff measurements performed using a standard OCT configuration and the proposed D-ODL demonstrate a doubling of the effective imaging range with no sensitivity or resolution penalty. Feasibility of the technique for in vivo imaging was demonstrated by imaging the ocular anterior segments of healthy human volunteers.

Feasibility of near-infrared diffuse optical spectroscopy on patients undergoing imageguided core-needle biopsy.

We describe a side-firing fiber optic sensor based on near-infrared spectroscopy for guiding core needle biopsy diagnosis of breast cancer. The sensor is composed of three side firing optical fibers (two source fibers and one detection fiber), providing two source-detector separations. The entire assembly is inserted into a core biopsy needle, allowing for sampling to occur at the biopsy site. A multi-wavelength frequency-domain near-infrared instrument is used to collect diffuse reflectance in the breast tissue through an aperture on the biopsy needle before the tissue is removed for histology. Preliminary in vivo measurements performed on 10 normal or benign breast tissues from 5 women undergoing stereo- or ultrasound-guided core needle biopsy show the ability of the system to determine tissue optical properties and constituent concentrations, which are correlated with breast tissue composition derived from histopathology.