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

Published online: 01 July 2016Identifying 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.Martin Villiger, Dirk Lorenser, Robert A. McLaughlin, Bryden C. Quirk, Rodney W. Kirk, Brett E. Bouma and David D. Sampso

Optical fibre-enabled photoswitching for localised activation of an anti-cancer therapeutic drug

Local activation of an anti-cancer drug when and where needed can improve selectivity and reduce undesirable side effects. Photoswitchable drugs can be selectively switched between active and inactive states by illumination with light; however, the clinical development of these drugs has been restricted by the difficulty in delivering light deep into tissue where needed. Optical fibres have great potential for light delivery in vivo, but their use in facilitating photoswitching in anti-cancer compounds has not yet been explored. In this paper, a photoswitchable chemotherapeutic is switched using an optical fibre, and the cytotoxicity of each state is measured against HCT-116 colorectal cancer cells. The performance of optical-fibre-enabled photoswitching is characterised through its dose response. The UV–Vis spectra confirm light delivered by an optical fibre effectively enables photoswitching. The activated drug is shown to be twice as effective as the inactive drug in causing cancer cell death, characterised using an MTT assay and fluorescent microscopy. This is the first study in which a photoswitchable anti-cancer compound is switched using an optical fibre and demonstrates the feasibility of using optical fibres to activate photoswitchable drugs for potential future clinical applications.Kathryn A. Palasis, Noor A. Lokman, Bryden C. Quirk, Alaknanda Adwal, Loretta Scolaro, Weikun Huang, Carmela Ricciardelli, Martin K. Oehler, Robert A. McLaughlin and Andrew D. Abel

3D-printed micro lens-in-lens for in vivo multimodal microendoscopy

Published online: March 1, 2022Multimodal microendoscopes enable co-located structural and molecular measurements in vivo, thus providing useful insights into the pathological changes associated with disease. However, different optical imaging modalities often have conflicting optical requirements for optimal lens design. For example, a high numerical aperture (NA) lens is needed to realize high-sensitivity fluorescence measurements. In contrast, optical coherence tomography (OCT) demands a low NA to achieve a large depth of focus. These competing requirements present a significant challenge in the design and fabrication of miniaturized imaging probes that are capable of supporting high-quality multiple modalities simultaneously. An optical design is demonstrated which uses two-photon 3D printing to create a miniaturized lens that is simultaneously optimized for these conflicting imaging modalities. The lens-in-lens design contains distinct but connected optical surfaces that separately address the needs of both fluorescence and OCT imaging within a lens of 330 µm diameter. This design shows an improvement in fluorescence sensitivity of >10x in contrast to more conventional fiber-optic design approaches. This lens-in-lens is then integrated into an intravascular catheter probe with a diameter of 520 µm. The first simultaneous intravascular OCT and fluorescence imaging of a mouse artery in vivo is reported.Jiawen Li, Simon Thiele, Rodney W. Kirk, Bryden C. Quirk, Ayla Hoogendoorn, Yung Chih Chen, Karlheinz Peter, Stephen J. Nicholls, Johan W. Verjans, Peter J. Psaltis, Christina Bursill, Alois M. Herkommer, Harald Giessen, and Robert A. McLaughli

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

3D visualization of tissue microstructures using optical coherence tomography needle probes

Optical coherence tomography (OCT) needle probes use miniaturized focusing optics encased in a hypodermic needle. Needle probes can scan areas of the body that are too deep to be imaged by other OCT systems. This paper presents an OCT needle probe-based system that is capable of acquiring three-dimensional scans of tissue structures. The needle can be guided to a target area and scans acquired by rotating and pulling-back the probe. The system is demonstrated using ex vivo human lymph node and sheep lung samples. Multiplanar reconstructions are shown of both samples, as well as the first published 3D volume rendering of lung tissue acquired with an OCT needle probe

3D visualization of tissue microstructures using optical coherence tomography needle probes

Optical coherence tomography (OCT) needle probes use miniaturized focusing optics encased in a hypodermic needle. Needle probes can scan areas of the body that are too deep to be imaged by other OCT systems. This paper presents an OCT needle probe-based system that is capable of acquiring three-dimensional scans of tissue structures. The needle can be guided to a target area and scans acquired by rotating and pulling-back the probe. The system is demonstrated using ex vivo human lymph node and sheep lung samples. Multiplanar reconstructions are shown of both samples, as well as the first published 3D volume rendering of lung tissue acquired with an OCT needle probe

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

High-sensitivity anastigmatic imaging needle for optical coherence tomography

We present a high-optical-quality imaging needle for optical coherence tomography (OCT) that achieves sensitivity and resolution comparable to conventional free-space OCT sample arms. The side-viewing needle design utilizes total internal reflection from an angle-polished fiber tip, encased in a glass microcapillary. Fusion of the capillary to the fiber provides a robust, optical-quality output window. The needle's focusing optics are based on an astigmatism-free design, which exploits the "focal shift" phenomenon for focused Gaussian beams to achieve equal working distances (WDs) for both axes. We present a fabricated needle with a WD ratio of 0.98 for imaging in an aqueous environment. Our needle achieves the highest sensitivity of currently reported OCT imaging needles (112 dB), and we demonstrate its performance by superficial imaging of human skin and 3D volumetric imaging within a biological sample

Optofluidic needle probe integrating targeted delivery of fluid with optical coherence tomography imaging

We present an optofluidic optical coherence tomography (OCT) needle probe capable of modifying the local optical properties of tissue to improve needle-probe imaging performance. The side-viewing probe comprises an all-fiberoptic design encased in a hypodermic needle (outer diameter 720 μm) and integrates a coaxial fluid-filled channel, terminated by an outlet adjacent to the imaging window, allowing focal injection of fluid to a target tissue. This is the first fully integrated OCT needle probe design to incorporate fluid injection into the imaging mechanism. The utility of this probe is demonstrated in air-filled sheep lungs, where injection of small quantities of saline is shown, by local refractive index matching, to greatly improve image penetration through multiple layers of alveoli. 3D OCT images are correlated against histology, showing improvement in the capability to image lung structures such as bronchioles and blood vessels

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 0.31mm) needle probe are demonstrated. Extreme miniaturization is achieved by using a simple all-fiber probe design incorporating an anglepolished and reflection-coated fiber-tip beam deflector. When inserted into biological tissue, aqueous interstitial fluids reduce the probe's 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 840nm 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