Intraoperative detection of blood vessels with an imaging needle during neurosurgery in humans

Intracranial hemorrhage can be a devastating complication associated with needle biopsies of the brain. Hemorrhage can occur to vessels located adjacent to the biopsy needle as tissue is aspirated into the needle and removed. No intraoperative technology exists to reliably identify blood vessels that are at risk of damage. To address this problem, we developed an “imaging needle” that can visualize nearby blood vessels in real time. The imaging needle contains a miniaturized optical coherence tomography probe that allows differentiation of blood flow and tissue. In 11 patients, we were able to intraoperatively detect blood vessels (diameter, \u3e500 μm) with a sensitivity of 91.2% and a specificity of 97.7%. This is the first reported use of an optical coherence tomography needle probe in human brain in vivo. These results suggest that imaging needles may serve as a valuable tool in a range of neurosurgical needle interventions

An optically-guided cochlear implant sheath for real-time monitoring of electrode insertion into the human cochlea

In cochlear implant surgery, insertion of perimodiolar electrode arrays into the scala tympani can be complicated by trauma or even accidental translocation of the electrode array within the cochlea. In patients with partial hearing loss, cochlear trauma can not only negatively affect implant performance, but also reduce residual hearing function. These events have been related to suboptimal positioning of the cochlear implant electrode array with respect to critical cochlear walls of the scala tympani (modiolar wall, osseous spiral lamina and basilar membrane). Currently, the position of the electrode array in relation to these walls cannot be assessed during the insertion and the surgeon depends on tactile feedback, which is unreliable and often comes too late. This study presents an image-guided cochlear implant device with an integrated, fiber-optic imaging probe that provides real-time feedback using optical coherence tomography during insertion into the human cochlea. This novel device enables the surgeon to accurately detect and identify the cochlear walls ahead and to adjust the insertion trajectory, avoiding collision and trauma. The functionality of this prototype has been demonstrated in a series of insertion experiments, conducted by experienced cochlear implant surgeons on fresh-frozen human cadaveric cochleae

Developing Tamoxifen-Based Chemical Probes for Use with a Dual-Modality Fluorescence and Optical Coherence Tomography Imaging Needle

Fluorescent small molecules based on the chemotherapeutic tamoxifen have been synthesised for use with an imaging needle capable of acquiring simultaneous fluorescence and optical coherence tomography (OCT) images. The chemical probes are based on the active metabolite of the drug, 4-hydroxytamoxifen that is coupled with a diamine linker to commercially available Alexa Fluor or 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) dyes. The tamoxifen derivatives were then added to cultures of live oestrogen receptor positive MCF-7 human breast cancer cells and imaged using the miniaturised fibre-optic device enclosed within a 23-gauge needle (outer diameter 640 μm). The OCT images showed the micro-architecture of the cell culture, while the fluorescence identified oestrogen receptor positive cells. Both dyes were found to have suitable excitation and emission properties and are good candidates to further develop as probes for fluorescence-guided surgery

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

Media 1: High-sensitivity anastigmatic imaging needle for optical coherence tomography

Originally published in Optics Letters on 15 December 2012 (ol-37-24-5247

Two-photon polymerisation 3D printed freeform micro-optics for optical coherence tomography fibre probes

Miniaturised optical coherence tomography (OCT) fibre-optic probes have enabled high-resolution cross-sectional imaging deep within the body. However, existing OCT fibre-optic probe fabrication methods cannot generate miniaturised freeform optics, which limits our ability to fabricate probes with both complex optical function and dimensions comparable to the optical fibre diameter. Recently, major advances in two-photon direct laser writing have enabled 3D printing of arbitrary three-dimensional micro/nanostructures with a surface roughness acceptable for optical applications. Here, we demonstrate the feasibility of 3D printing of OCT probes. We evaluate the capability of this method based on a series of characterisation experiments. We report fabrication of a micro-optic containing an off-axis paraboloidal total internal reflecting surface, its integration as part of a common-path OCT probe, and demonstrate proof-of-principle imaging of biological samples

Media 2: Optofluidic needle probe integrating targeted delivery of fluid with optical coherence tomography imaging

Originally published in Optics Letters on 15 May 2014 (ol-39-10-2888