Biology subjects

Bohndiek, S.

Publications and source records attributed to Bohndiek, S..

4 recordsLinked to original sources

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

Raman micro-spectroscopy reveals the spatial distribution of fumarate in cells and tissues.

Aberrantly accumulated metabolites such as fumarate elicit intra- and inter-cellular pro-oncogenic cascades, yet current methods to measure them require sample perturbation or disruption and lack spatio-temporal resolution, limiting our ability to fully characterize their function and distribution in cells and within a tissue. Raman spectroscopy (RS) is a powerful bio-analytical tool that directly characterizes the chemical composition of a sample based solely on the optical fingerprint of vibrational modes. Here, we show for the first time that RS can directly detect fumarate in living cells in vivo and animal tissues ex vivo. Using the observed linear relationship between Raman scattered intensity and fumarate concentration, we demonstrate that RS can distinguish between Fumarate hydratase (Fh1)-deficient and Fh1-proficient cells based on their fumarate concentration. Moreover, RS reveals the spatial compartmentalization of fumarate within cellular organelles: consistent with disruptive methods, in Fh1-deficient cells we observe the highest fumarate concentration (37 {+/-} 19 mM) in the mitochondria, where the TCA cycle operates, followed by the cytoplasm (24 {+/-} 13 mM) and then the nucleus (9 {+/-} 6 mM). Finally, we apply RS to tissues from an inducible mouse model of FH loss in the kidney, demonstrating that RS can accurately classify FH status in these tissues. These results suggest that RS could be adopted as a valuable tool for small molecule metabolic imaging, enabling in situ dynamic evaluation of fumarate compartmentalization.

cell biology↗

bioRxiv2020

Photoacoustics resolves species-specific differences in haemoglobin concentration and oxygenation

Introduction Photoacoustic imaging (PAI) enables the detection of blood haemoglobin (HB) concentration and oxygenation (SO2) with high contrast and resolution. To date, the relationship between photoacoustically determined total Haemoglobin (THbMSOT) and oxygen saturation (SO2) biomarkers and the underlying biochemical blood parameters has yet to be established. We sought to explore these relationships in a species-specific manner.Methods Experiments were performed in vitro using tissue-mimicking agar phantoms. Blood was extracted from mouse, rat, human and naked mole-rat (Heterocephalus glaber), anticoagulated in EDTA and measured within 48 hours. THbMSOT and SO2MSOT were measured using a commercial photoacoustic tomography system (InVision 128, iThera Medical GmBH). Biochemical blood parameters such as haemoglobin concentration (HB, g/dL), haematocrit (HCT, %) and red blood cell count (RBC, μL-1) were assessed using a haematology analyser (Mythic 18 Vet, Woodley Equipment).Results A significant correlation was observed between THbMSOT and biochemical HB, HCT and RBC in mouse and rat blood. Moreover, PAI accurately recapitulated inter-species variations in HB and HCT between mouse and rat blood and resolved differences in the oxygen dissociation curves between human, mouse and rat. With these validation data in hand, we applied PAI to studies of blood obtained from naked mole-rats and could confirm the high oxygen affinity of this species in comparison to other rodents of similar size.Conclusion In summary, our results demonstrate the high sensitivity of photoacoustically determined biomarkers towards species-specific variations in vitro.Competing Interest StatementJB, IQG and SEB have previously received research support from iThera Medical GmbH and Cyberdyne Inc.View Full Text

bioengineering↗

bioRxiv2019

Co-Registration of Optoacoustic Tomography and Magnetic Resonance Imaging Data from Murine Tumour Models

As optoacoustic tomography emerges as a mainstream preclinical imaging modality, understanding the relationship between optoacoustic and other imaging biomarkers in the context of the underlying tissue biology becomes vitally important. For example, assessment of blood haemoglobin concentration and oxygenation can be achieved using OT, and also by several magnetic resonance imaging (MRI)-based techniques. To evaluate the relationship between these metrics and the relative performance of the two modalities in assessment of haemoglobin physiology, co-registration of their output imaging data is required. Unfortunately, this poses a significant challenge due to differences in the data acquisition geometries. Here, we present an integrated framework for registration of OT and MR image data in small animals. Our framework combines a novel MR animal holder, to improve animal positioning for deformable tissues, and a landmark-based software co-registration algorithm. We demonstrate that our protocol significantly improves registration of both body and tumour contours between these modalities.

bioengineering↗