Biology subjects

Else, T. R.

Publications and source records attributed to Else, T. R..

5 recordsLinked to original sources

bioRxiv2026

Spectral characterisation of short-wave infrared (SWIR) tissue chromophores and tissue-mimicking phantom optical properties

Significance Short-wave infrared (SWIR) sensors promise to expand the capabilities of optical sensing technologies, but the lack of robust data characterising tissue-constituent optical properties in the SWIR makes instrument design challenging. Aim We characterise and evaluate the optical properties of the dominant chromophores in tissue and tissue- mimicking phantoms, from visible to SWIR wavelengths. Approach Using single-integrating sphere systems, we measured the optical properties of single-component chromophores (H2O, haemoglobin, corn oil, synthetic melanin) and multi-component tissues (whole blood, lard), to decouple contributions from optical scattering, H2O absorption and other contributing chromophores; we also characterised commonly-used phantom materials and investigated their potential to mimic soft tissues in the SWIR range using simulations. Results We provide a consistent dataset of absorption and reduced scattering coefficients ({micro}a and {micro}'s) that characterise the dominant tissue chromophores from 450 nm out to 1600 nm. These results were shown to be consistent with literature data, where available. We integrate these data into an open-source Python toolkit, SIMPA, for optical modelling and demonstrate soft tissue simulations that can be probed continuously from visible to SWIR wavelengths. Our findings are compared with tissue-mimicking phantoms, highlighting a need for additives for polymer-based phantoms that mimic SWIR water absorption. Conclusions By providing this open-source dataset, we aim to enable future studies exploring SWIR light-tissue interactions that facilitate rapid assessment and prototyping of next-generation spectroscopy and imaging techniques.

bioengineering↗

bioRxiv2025

Unravelling the in vivo traits of vasculogenic mimicry

Vasculogenic mimicry (VM) describes the ability of cancer cells to acquire endothelial properties and form vessel-like channels that facilitate tumour blood supply. While the molecular drivers of VM have been well-explored in cell cultures and biopsies, an in vivo description remains elusive. Here, we used graph theory to define VM biomarkers and elucidate the spatiotemporal dynamics of VM using in vitro and in vivo breast cancer models with and without anti-angiogenic treatment. Optical microscopy was used to assess pseudo-vascular networks in vitro while photoacoustic imaging across scales was applied in vivo to identify and locate haemoglobin contrast-derived blood vessel morphology and functionality. VM was associated with greater oxygenation heterogeneity and poorer anti-angiogenic response, reflected as stable meshed networks in vitro and blood-containing circular structures in vivo. We demonstrate for the first time a multi-scale approach bridging the in vitro-in vivo translational gap to assess anti-vascular treatment resistance and the therapeutic potential in vasculogenic mimicry-rich tumours, exploring novel avenues in preclinical drug screening and systemic drug delivery.

cancer biology↗

bioRxiv2025

Early Radiation Therapy Response Assessment using Multi-scale Photoacoustic Imaging

There is a critical unmet clinical need to identify biomarkers that predict and detect radiotherapy response in cancer. Using the unique capabilities of multi-scale photoacoustic imaging (PAI) for depicting tumour oxygenation and vasculature in vivo, we identified surrogate biomarkers of radiation response in two human breast cancer models (MCF7 and MDA-MB-231), comparing hypofractionated delivery with an ablative single dose scheme. Ex vivo immunohistochemistry results underpinned findings from mesoscopic and multispectral tomographic PAI, performed 24h pre-RT, 24h post-RT, and at endpoint. A denser and more mature vasculature of the MCF7 xenografts afforded an improved response to both RT schemes compared to MDA-MB-231, in terms of overall tumour oxygenation, tumour volume and proliferation. Increased intratumoural blood oxygen saturation and oxygen diffusion pre-RT were associated with improved outcomes and decreased proliferation, expected given the oxygen-enhancement effect in RT. In vivo PAI revealed the differential effect between ablative courses of RT in both models, with the ablative scheme altering the tumour vasculature as early as 24h post-RT, and pruning the looping vessels and total blood volume at endpoint in the more radiosensitive MCF-7 xenografts. An increase in blood oxygen saturation at endpoint was observed only in the MCF7 xenografts treated with hypofractionated RT, confirming the reduced oxygen consumption of damaged tumour cells, indicative of response. Thus, we showed that PAI could capture early RT response and inform on radioresistance, thus demonstrating promise of PAI as an in vivo and future clinical tool to monitor the tumour vascular response to RT.

cancer biology↗

bioRxiv2023

The effects of skin tone on photoacoustic imaging and oximetry

SignificancePhotoacoustic imaging (PAI) provides contrast based on the concentration of optical absorbers in tissue, enabling the assessment of functional physiological parameters such as blood oxygen saturation (sO2). Recent evidence suggests that variation in melanin levels in the epidermis leads to measurement biases in optical technologies, which could potentially limit the application of these biomarkers in diverse populations. AimTo examine the effects of skin melanin pigmentation on photoacoustic imaging and oximetry. ApproachWe evaluated the effects of skin tone in PAI using a computational skin model, two-layer melanin-containing tissue-mimicking phantoms, and mice of a consistent genetic background with varying pigmentations. The computational skin model was validated by simulating the diffuse reflectance spectrum using the adding-doubling method, allowing us to assign our simulation parameters to approximate Fitzpatrick skin types. Monte Carlo simulations and acoustic simulations were run to obtain idealised photoacoustic images of our skin model. Photoacoustic images of the phantoms and mice were acquired using a commercial instrument. Reconstructed images were processed with linear spectral unmixing to estimate blood oxygenation. Linear unmixing results were compared with a learned unmixing approach based on gradient-boosted regression. ResultsOur computational skin model was consistent with representative literature for in vivo skin reflectance measurements. We observed consistent spectral colouring effects across all model systems, with an overestimation of sO2 and more image artefacts observed with increasing melanin concentration. The learned unmixing approach reduced the measurement bias, but predictions made at lower blood sO2 still suffered from a skin tone-dependent effect. ConclusionPAI demonstrates measurement bias, including an overestimation of blood sO2, in higher Fitzpatrick skin types. Future research should aim to characterise this effect in humans to ensure equitable application of the technology.

bioengineering↗

bioRxiv2023

In Vivo Monitoring of Cellular Senescence by Photoacoustic and Fluorescence Imaging Utilizing a Nanostructured Organic Probe

Senescent cells accumulate in multiple age-related disorders, including cancer, exacerbating the pathological manifestations, and the eradication of these cells has emerged as a promising therapeutic strategy. Despite the impact of senescence in diseases, the development of tools to monitor the senescent burden in vivo remains a challenge due to their suboptimal specificity, translatability, and tissue penetrance. Here, we have designed a nanostructured organic probe (NanoJaggs) based on biocompatible indocyanine green dye (ICG) building blocks forming J-aggregates, which possess distinct spectral properties allowing both fluorescence and photoacoustic tomography (PAT) detection. We show that NanoJaggs are taken up by an active process of endocytosis and exhibit selective accumulation at the lysosomal compartment in several in vitro models for senescence. Finally, NanoJagg probe is validated in two in vivo studies including live PAT imaging and shows remarkable specificity to tumours with chemotherapy-induced senescence compared to untreated proliferative tumors. In vitro, ex vivo and in vivo all indicate that NanoJaggs are a clinically translatable tool for detection of senescence and their robust PAT signal makes them suitable for longitudinal monitoring of the senescent burden in solid tumors after chemo or radiotherapy.

cancer biology↗