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

Socioeconomic inequalities in distance to and participation in a community-based running and walking activity : a longitudinal ecological study of parkrun 2010 to 2019

Objectives To conduct a longitudinal ecological analysis of the distance to and participation in free weekly outdoor physical activity events (parkrun) in England from 2010 to 2019, and related socioeconomic and ethnic inequalities, to inform policies to support participation in physically active community events. Methods We calculate distance to the nearest parkrun event for each English Lower Layer Super Output Area (LSOA) each month from January 2010 to December 2019. We then report the trends in distance to and participation in parkrun by Index of Multiple Deprivation quintile. We also report trends in the Relative Index of Inequality (RII) by deprivation for participation and distance to nearest event. We go on to investigate trends in LSOA level determinants (e.g. deprivation and ethnic density) of parkrun participation between 2010 and 2019, using multivariable Poisson regression models. Results Mean distance to the nearest parkrun event decreased from 34.1 km in 2010, to 4.6 km in 2019. Throughout the period, parkrun events tended to be situated closer to deprived areas compared to less deprived areas. Participation rates increased superlinearly (greater than linear increase) from 2010 to 2013 before slowing to linear growth. Participation over the period exhibits a clear socioeconomic gradient, with people from deprived areas having consistently lower participation rates over the period. parkrun participation rates became more equal between 2010 and 2013 (RII improved from 189 to 39), before stabilising at an RII between 32.9 and 39.6 from 2014 to 2019. The results of the Poisson regression model validate this finding; the coefficients on IMD score initially increased from −0.050 in 2010 to −0.038 in 2013, and then remained relatively stable to 2019 (−0.035). Conclusions Over the past 10 years, geodesic distance to the nearest parkrun decreased from a mean of 34 km to 5 km. In 2010, there was equality between the least and most deprived areas but by 2017 the distance of the most deprived areas was 29% that of the least deprived. Participation was shown to have increased over the past 10 years which can be split into two distinct phases: from 2010 to 2013 participation increased super-linearly and inequality in participation fell dramatically; from 2013 to 2019 participation increased linearly, and inequality in participation remained stable. Despite parkrun's ambitions of creating inclusive events and engaging with deprived communities, the socioeconomic gradient in participation rates remained high and stable since 2013. Gaining a better understanding of the reasons why parkrun grew so quickly may be useful for other physical activity movements, while further analysis of the relatively lower participation rates in areas with higher socioeconomic deprivation is important for developing initiatives to encourage physical activity in these communities

Multiple deprivation and geographic distance to community physical activity events — achieving equitable access to parkrun in England

© 2020 The Author(s) Objectives: To evaluate geographic access to free weekly outdoor physical activity events (‘parkrun’) in England, with a particular focus on deprived communities, and to identify optimal locations for future events to further maximise access. Study design: This study is a cross-sectional ecological analysis of the socio-economic disparities in geographic access to parkrun events in England in late 2018. Methods: We combined geolocation data on all English Lower Layer Super Output Areas and parkrun events to calculate geodesic distances to the nearest event for more than 32,000 communities in England. We use this measure of geographic access to summarise the relationship between access and socio-economic deprivation, measured using the index of multiple deprivation. We then used geographic coordinates of public green spaces in England to conduct a simple location-allocation analysis to identify 200 locations for future event locations that would maximise access. Results: In England, 69% of the population live within 5 km of one of the 465 parkrun events. There is a small negative correlation between distance and deprivation, indicating that access is slightly better in more socio-economically deprived areas. Setting up an additional 200 events in optimal locations would improve access: the average distance to the nearest parkrun event would improve by 1.22 km, from 4.65 km to 3.43 km, and approximately 82% of the English population would live within 5 km of a parkrun event. Conclusion: Over two-thirds of the English population live within 5 km of a parkrun event, and contrary to our expectation, we find that geographic access is slightly better for those living in more deprived communities. Creating additional events may improve geographic access, but effective strategies will still be needed to increase engagement in new and existing events by those living in socio-economically deprived areas

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