Bryden C. Quirk

In vivo three-dimensional optical coherence elastography

Abstract: We present the first three-dimensional (3D) data sets recorded using optical coherence elastography (OCE). Uni-axial strain rate was measured on human skin in vivo using a spectral-domain optical coherence tomography (OCT) system providing >450 times higher line rate than previously reported for in vivo OCE imaging. Mechanical excitation was applied at a frequency of 125 Hz using a ring actuator sample arm with, for the first time in OCE measurements, a controlled static preload. We performed 3D-OCE, processed in 2D and displayed in 3D, on normal and hydrated skin and observed a more elastic response of the stratum corneum in the hydrated case.

In vivo dynamic optical coherence elastography using a ring actuator

We present a novel sample arm arrangement for dynamic optical coherence elastography based on excitation by a ring actuator. The actuator enables coincident excitation and imaging to be performed on a sample, facilitating in vivo operation. Sub-micrometer vibrations in the audio frequency range were coupled to samples that were imaged using optical coherence tomography. The resulting vibration amplitude and microstrain maps are presented for bilayer silicone phantoms and multiple skin sites on a human subject. Contrast based on the differing elastic properties is shown, notably between the epidermis and dermis. The results constitute the first demonstration of a practical means of performing in vivo dynamic optical coherence elastography on a human subject.

Ultrathin side-viewing needle probe for optical coherence tomography

We present the smallest reported side-viewing needle probe for optical coherence tomography (OCT). Design, fabrication, optical characterization, and initial application of a 30-gauge (outer diameter 0.31 mm) needle probe are demonstrated. Extreme miniaturization is achieved by using a simple all-fiber probe design incorporating an angle-polished and reflection-coated fiber-tip beam deflector. When inserted into biological tissue, aqueous interstitial fluids reduce the probes inherent astigmatism ratio to 1.8, resulting in a working distance of 300 μm and a depth-of-field of 550 μm with beam diameters below 30 μm. The needle probe was interfaced with an 840 nm spectral-domain OCT system and the measured sensitivity was shown to be only 7 dB lower than that of a comparable galvo-scanning sample arm configuration. 3D OCT images of lamb lungs were acquired over a depth range of ~600 μm, showing individual alveoli and bronchioles.

Imaging of Breast Cancer With Optical Coherence Tomography Needle Probes: Feasibility and Initial Results

Optical coherence tomography (OCT) is a high-resolution imaging modality with the potential to provide in situ assessment to distinguish normal from cancerous tissue. However, limited image penetration depth has restricted its utility. This paper demonstrates the feasibility of an OCT needle probe to perform interstitial imaging deep below the tissue surface. The side-facing needle probe comprises miniaturized focusing optics consisting of no-core and GRIN fiber encased within either a 22- or 23-gauge needle. 3-D OCT volumetric data sets were acquired by rotating and retracting the probe during imaging. We present the first published image of a human breast cancer tumor margin, and of human axillary lymph nodes acquired with an OCT needle probe. Through accurate correlation with the histological gold standard, OCT is shown to enable a clear delineation of tumor boundary from surrounding adipose tissue, and identification of microarchitectural features.

In situ imaging of lung alveoli with an optical coherence tomography needle probe

In situ imaging of alveoli and the smaller airways with optical coherence tomography (OCT) has significant potential in the assessment of lung disease. We present a minimally invasive imaging technique utilizing an OCT needle probe. The side-facing needle probe comprises miniaturized focusing optics consisting of no-core and GRIN fiber encased within a 23-gauge needle. 3D-OCT volumetric data sets were acquired by rotating and retracting the probe during imaging. The probe was used to image an intact, fresh (not fixed) sheep lung filled with normal saline, and the results validated against a histological gold standard. We present the first published images of alveoli acquired with an OCT needle probe and demonstrate the potential of this technique to visualize other anatomical features such as bifurcations of the bronchioles.

Dual-modality needle probe for combined fluorescence imaging and three-dimensional optical coherence tomography

To the best of our knowledge, we present the first needle probe for combined optical coherence tomography (OCT), and fluorescence imaging. The probe uses double-clad fiber (DCF) that guides the OCT signal and fluorescence excitation light in the core and collects and guides the returning fluorescence in the large-diameter multimode inner cladding. It is interfaced to a 1310 nm swept-source OCT system that has been modified to enable simultaneous 488 nm fluorescence excitation and >500 nm emission detection by using a DCF coupler to extract the returning fluorescence signal in the inner cladding with high efficiency. We present imaging results from an excised sheep lung with fluorescein solution infused through the vasculature. We were able to identify alveoli, bronchioles, and blood vessels. The results demonstrate that the combined OCT plus fluorescence needle images provide improved tissue differentiation over OCT alone.

Static and dynamic imaging of alveoli using optical coherence tomography needle probes

Imaging of alveoli in situ has for the most part been infeasible due to the high resolution required to discern individual alveoli and limited access to alveoli beneath the lung surface. In this study, we present a novel technique to image alveoli using optical coherence tomography (OCT). We propose the use of OCT needle probes, where the distal imaging probe has been miniaturized and encased within a hypodermic needle (as small as 30-gauge, outer diameter 310 μm), allowing insertion deep within the lung tissue with minimal tissue distortion. Such probes enable imaging at a resolution of ∼12 μm within a three-dimensional cylindrical field of view with diameter ∼1.5 mm centered on the needle tip. The imaging technique is demonstrated on excised lungs from three different species: adult rats, fetal sheep, and adult pigs. OCT needle probes were used to image alveoli, small bronchioles, and blood vessels, and results were matched to histological sections. We also present the first dynamic OCT images acquired with an OCT needle probe, allowing tracking of individual alveoli during simulated cyclical lung inflation and deflation.

Deep tissue volume imaging of birefringence through fibre-optic needle probes for the delineation of breast tumour

Identifying tumour margins during breast-conserving surgeries is a persistent challenge. We have previously developed miniature needle probes that could enable intraoperative volume imaging with optical coherence tomography. In many situations, however, scattering contrast alone is insufficient to clearly identify and delineate malignant regions. Additional polarization-sensitive measurements provide the means to assess birefringence, which is elevated in oriented collagen fibres and may offer an intrinsic biomarker to differentiate tumour from benign tissue. Here, we performed polarization-sensitive optical coherence tomography through miniature imaging needles and developed an algorithm to efficiently reconstruct images of the depth-resolved tissue birefringence free of artefacts. First ex vivo imaging of breast tumour samples revealed excellent contrast between lowly birefringent malignant regions, and stromal tissue, which is rich in oriented collagen and exhibits higher birefringence, as confirmed with co-located histology. The ability to clearly differentiate between tumour and uninvolved stroma based on intrinsic contrast could prove decisive for the intraoperative assessment of tumour margins.

Ultrasound-Guided Optical Coherence Tomography Needle Probe for the Assessment of Breast Cancer Tumor Margins

OBJECTIVE The purpose of this study was to evaluate a new imaging technique for the assessment of breast cancer tumor margins. The technique entails deployment of a high-resolution optical imaging needle under ultrasound guidance. Assessment was performed on fresh ex vivo tissue samples. CONCLUSION Use of the ultrasound-guided optical needle probe allowed in situ assessment of fresh tissue margins. The imaging findings corresponded to the histologic findings.

Miniaturized single-fiber-based needle probe for combined imaging and sensing in deep tissue

The ability to visualize structure while simultaneously measuring chemical or physical properties of a biological tissue has the potential to improve our understanding of complex biological processes. We report the first miniaturized single-fiber-based imaging+sensing probe capable of simultaneous optical coherence tomography (OCT) imaging and temperature sensing. An OCT lens is fabricated at the distal end of a double-clad fiber, including a thin layer of rare-earth-doped tellurite glass to enable temperature measurements. The high refractive index of the tellurite glass enables a common-path interferometer configuration for OCT, allowing easy exchange of probes for biomedical applications. The simultaneous imaging+sensing capability is demonstrated on rat brains.