University of Western Australia

Pilot study of optical coherence tomography angiography-derived microvascular metrics in hands and feet of healthy and diabetic people

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Optical coherence tomography angiography (OCTA) is a non-invasive, high-resolution imaging modality with growing application in dermatology and microvascular assessment. Accepted reference values for OCTA-derived microvascular parameters in skin do not yet exist but need to be established to drive OCTA into the clinic. In this pilot study, we assess a range of OCTA microvascular metrics at rest and after post-occlusive reactive hyperaemia (PORH) in the hands and feet of 52 healthy people and 11 people with well-controlled type 2 diabetes mellitus (T2DM). We calculate each metric, measure test–retest repeatability, and evaluate correlation with demographic risk factors. Our study delivers extremity-specific, age-dependent reference values and coefficients of repeatability of nine microvascular metrics at baseline and at the maximum of PORH. Significant differences are not seen for age-dependent microvascular metrics in hand, but they are present for several metrics in the foot. Signi...

Pilot study of optical coherence tomography angiography-derived microvascular metrics in hands and feet of healthy and diabetic peopl

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Optical coherence tomography angiography (OCTA) is a non-invasive, high-resolution imaging modality with growing application in dermatology and microvascular assessment. Accepted reference values for OCTA-derived microvascular parameters in skin do not yet exist but need to be established to drive OCTA into the clinic. In this pilot study, we assess a range of OCTA microvascular metrics at rest and after post-occlusive reactive hyperaemia (PORH) in the hands and feet of 52 healthy people and 11 people with well-controlled type 2 diabetes mellitus (T2DM). We calculate each metric, measure test–retest repeatability, and evaluate correlation with demographic risk factors. Our study delivers extremity-specific, age-dependent reference values and coefficients of repeatability of nine microvascular metrics at baseline and at the maximum of PORH. Significant differences are not seen for age-dependent microvascular metrics in hand, but they are present for several metrics in the foot. Signi...

Novel Optical Measurement and Imaging Technologies using Broadband Light Sources – Special Issue in Frontiers in Physics Journal

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Optical measurement and imaging have been key fields in scientific and technological advancements. Historically, from the development of theories of quantum mechanics and relativity, to the discovery of DNA structure and astronomical events, optical measurement and imaging technologies, such as Michelson interferometer, large-scale space telescopes, high-resolution microscopy and crystallography, played critical roles in identifying key signals, structures, and interactions between light field and various types of materials. Recently, broadband light sources, such as ultrafast lasers, wavelength-swept lasers, super-luminescent LEDs, and super-continuum sources, have enabled versatile optical innovations, which opens up new possibilities to achieve fast-speed, large-volume, high-resolution, and high-dimensional optical measurements with unique capabilities. Herein, the main scope of this Research Topic is to bring together interesting novel optical measurement and imaging t...

Novel Optical Measurement and Imaging Technologies using Broadband Light Sources – Special Issue in Frontiers in Physics Journal

Optical measurement and imaging have been key fields in scientific and technological advancements. Historically, from the development of theories of quantum mechanics and relativity, to the discovery of DNA structure and astronomical events, optical measurement and imaging technologies, such as Michelson interferometer, large-scale space telescopes, high-resolution microscopy and crystallography, played critical roles in identifying key signals, structures, and interactions between light field and various types of materials.  Recently, broadband light sources, such as ultrafast lasers, wavelength-swept lasers, super-luminescent LEDs, and super-continuum sources, have enabled versatile optical innovations, which opens up new possibilities to achieve fast-speed, large-volume, high-resolution, and high-dimensional optical measurements with unique capabilities.  Herein, the main scope of this Research Topic is to bring together interesting novel optical measurement a...

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

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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 nov...

Novel microendoscope design improves bio-imaging

Microendoscopes using fiber optics are becoming increasingly important imaging tools, but they have physical limitations. They are essential for applications that require a long working distance, high resolution, and a minimum probe diameter. A paper in IEEE Photonics Journal by Karol Karnowski of Poland’s International Centre for Translational Eye Research , Gavrielle Untracht of Technical University of Denmark , Michael Hackmann of University of Western Australia , Onur Cetinkaya of ICTER and David Sampson of the University of Surrey, UK, sheds new light on modern microendoscopes. The researchers show that endoscopic imaging probes, particularly those for so-called side viewing, combining fiber-optic (GRIN) and spherical lenses, “offer excellent performance over the entire range of numerical apertures and open the way to a broader range of imaging applications”. The performance of endoscopic imaging probes is comparable to commonly used single focusing element pr...

Quantitative Micro-Elastography Enables In Vivo Detection of Residual Cancer in the Surgical Cavity during Breast-Conserving Surgery

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Breast-conserving surgery (BCS) is commonly used for the treatment of early-stage breast cancer. Following BCS, approximately 20% to 30% of patients require reexcision because postoperative histopathology identifies cancer in the surgical margins of the excised specimen. Quantitative micro-elastography (QME) is an imaging technique that maps microscale tissue stiffness and has demonstrated a high diagnostic accuracy (96%) in detecting cancer in specimens excised during surgery. However, current QME methods, in common with most proposed intraoperative solutions, cannot image cancer directly in the patient, making their translation to clinical use challenging. In this proof-of-concept study, we aimed to determine whether a handheld QME probe, designed to interrogate the surgical cavity, can detect residual cancer directly in the breast cavity in vivo during BCS. In a first-in-human study, 21 BCS patients were scanned in vivo with the QME probe by five surgeons. For validation, protoco...

How to improve microendoscopes? New probe design brings promises to improve biomedical imaging

Microendoscopes are the cornerstone of modern medical diagnostics—they allow us to see what we could not even describe two decades ago. The technology is constantly improving, with ICTER scientists contributing to the development of the probes. Microendoscopes using fiber optics are becoming increasingly important imaging tools, but they have physical limitations. They are essential for applications that require a long working distance, high resolution, and a minimum probe diameter. A new research paper by Dr. Karol Karnowski of ICTER, Dr. Gavrielle Untracht of the Technical University of Denmark (DTU), Dr. Michael Hackmann of the University of Western Australia (UWA), Onur Cetinkaya of ICTER and Prof. David Sampson of the University of Surrey, sheds new light on modern microendoscopes. The research work started while the authors worked in the same research group at UWA. ( Read Full Article )

Superior Imaging Performance of All-Fiber, Two-Focusing-Element Microendoscopes

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All-fiber-optic imaging microendoscopes are emerging as an important tool in bioimaging studies, including those conducted with optical coherence tomography, but physical limitations constrain the achievable beam characteristics of designs using a single focusing element. These constraints are especially relevant for applications that require a long working distance, high resolution, and/or minimal probe diameter. Through detailed analysis based on ABCD matrix modelling, we show that side-viewing probes combining a graded-index (GRIN) fiber with a ball lens – GRIN-ball-lens probes (GBLPs) – offer superior performance over a range of numerical apertures and pave the way for a broader range of imaging applications. The performance of side-viewing GBLPs designed for 1300-nm optical coherence tomography imaging is compared against commonly used single-focusing-element all-fiber side-viewing probe designs, namely, ball-lens probes (BLPs) and GRIN-fiber probes (GFPs). All poss...

Cocoa flavanol consumption improves lower extremity endothelial function in healthy individuals and people with type 2 diabetes

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Background : diabetes and age are major risk factors for the development of lower extremity peripheral artery disease (PAD). Cocoa flavanol (CF) consumption is associated with lower risk for PAD and improves brachial artery (BA) endothelial function. Objectives : to assess if femoral artery (FA) endothelial function and dermal microcirculation are impaired in individuals with type 2 diabetes mellitus (T2DM) and evaluate the acute effect of CF consumption on FA endothelial function. Methods : in a randomised, controlled, double-blind, cross-over study, 22 individuals ( n = 11 healthy, n = 11 T2DM) without cardiovascular disease were recruited. Participants received either 1350 mg CF or placebo capsules on 2 separate days in random order. Endothelial function was measured as flow-mediated dilation (FMD) using ultrasound of the common FA and the BA before and 2 hours after interventions. The cutaneous microvasculature was assessed using optical coherence tomography angiography. Results...

Correcting magnification error in foveal avascular zone area measurements of optical coherence tomography angiography images with estimated axial length

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Background: To generate and validate a method to estimate axial length estimated (AL est ) from spherical equivalent (SE) and corneal curvature [keratometry (K)], and to determine if this AL est can replace actual axial length (AL act ) for correcting transverse magnification error in optical coherence tomography angiography (OCTA) images using the Littmann-Bennett formula. Methods: Data from 1301 participants of the Raine Study Gen2-20 year follow-up were divided into two datasets to generate (n = 650) and validate (n = 651) a relationship between AL, SE, and K. The developed formula was then applied to a separate dataset of 46 participants with AL, SE, and K measurements and OCTA images to estimate and compare the performance of AL est against AL act in correcting transverse magnification error in OCTA images when measuring the foveal avascular zone area (FAZA). Results: The formula for AL est yielded the equation: AL est = 2.102K - 0.4125SE + 7.268, R 2 = 0.794. There was good ag...

Visualising and quantifying microvascular structure and function in patients with heart failure using optical coherence tomography

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Heart failure (HF) is characterised by abnormal conduit and resistance artery function in humans. Microvascular function in HF is less well characterised, due in part to the lack of tools to image these vessels in vivo . The skin microvasculature is a surrogate for systemic microvascular function and health and plays a key role in thermoregulation, which is dysfunctional in HF. We deployed a novel optical coherence tomography (OCT) technique to visualise and quantify microvascular structure and function in ten subjects with HF and ten age- and sex-matched controls. OCT images were obtained from the ventral aspect of the forearm, at baseline (33⁰C) and after 30 minutes of localised skin heating. At rest, OCT-derived microvascular density (20.3 ± 8.7%, P = 0.004), diameter (35.1 ± 6.0μm, P = 0.006), and blood flow (82.9 ± 41.1 pL/s, P = 0.021) were significantly lower in HF than CON (27.2 ± 8.0%, 40.4 ± 5.8 μm, 110.8 ± 41.9 pL/s), whilst...

Multimodal imaging needle combining optical coherence tomography and fluorescence for imaging of live breast cancer cells labeled with a fluorescent analog of tamoxifen

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Significance: Imaging needles consist of highly miniaturized focusing optics encased within a hypodermic needle. The needles may be inserted tens of millimeters into tissue and have the potential to visualize diseased cells well beyond the penetration depth of optical techniques applied externally. Multimodal imaging needles acquire multiple types of optical signals to differentiate cell types. However, their use has not previously been demonstrated with live cells. Aim: We demonstrate the ability of a multimodal imaging needle to differentiate cell types through simultaneous optical coherence tomography (OCT) and fluorescence imaging. Approach: We characterize the performance of a multimodal imaging needle. This is paired with a fluorescent analog of the therapeutic drug, tamoxifen, which enables cell-specific fluorescent labeling of estrogen receptor-positive (ER+) breast cancer cells. We perform simultaneous OCT and fluorescence in situ imaging on MCF-7 ER+ breast cancer cells an...

Macular Vascular Imaging and Connectivity Analysis Using High-Resolution Optical Coherence Tomography

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Purpose: To characterize macular blood flow connectivity in vivo using high-resolution optical coherence tomography (HighRes OCT). Methods: Cross-sectional, observational study. Dense (6-µm interscan distance) perifoveal HighRes OCT raster scans were performed on healthy participants. To mitigate the limitations of projection-resolved OCT-angiography, flow and structural data were used to observe the vascular structures of the superficial vascular complex (SVC) and the deep vascular complex. Vascular segmentation and rendering were performed using Imaris 9.5 software. Inflow and outflow patterns were classified according to vascular diameter and branching order from superficial arteries and veins, respectively. Results: Eight eyes from eight participants were included in this analysis, from which 422 inflow and 459 outflow connections were characterized. Arteries had direct arteriolar connections to the SVC (78%) and to the intermediate capillary plexus (ICP, 22%). Deep capill...

Multi-class classification of breast tissue using optical coherence tomography and attenuation imaging combined via deep learning

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We demonstrate a convolutional neural network (CNN) for multi-class breast tissue classification as adipose tissue, benign dense tissue, or malignant tissue, using multi-channel optical coherence tomography (OCT) and attenuation images, and a novel Matthews correlation coefficient (MCC)-based loss function that correlates more strongly with performance metrics than the commonly used cross-entropy loss. We hypothesized that using multi-channel images would increase tumor detection performance compared to using OCT alone. 5,804 images from 29 patients were used to fine-tune a pre-trained ResNet-18 network. Adding attenuation images to OCT images yields statistically significant improvements in several performance metrics, including benign dense tissue sensitivity (68.0% versus 59.6%), malignant tissue positive predictive value (PPV) (79.4% versus 75.5%), and total accuracy (85.4% versus 83.3%), indicating that the additional contrast from attenuation imaging is most beneficial for dis...

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