Biology subjects

Hacker, L.

Publications and source records attributed to Hacker, L..

6 recordsLinked to original sources

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

Segmentation of 3D blood vessel networks using unsupervised deep learning

Mesoscopic photoacoustic imaging (PAI) enables label-free visualisation of vascular networks in tissue at high contrast and resolution. The segmentation of vascular networks from 3D PAI data and interpretation of their meaning in the context of physiological and pathological processes is a crucial but time consuming and error-prone task. Deep learning holds potential to solve these problems, but current supervised analysis frameworks require human-annotated ground-truth labels. Here, we overcome the need for ground-truth labels by introducing an unsupervised image-to-image translation deep learning model called the vessel segmentation generative adversarial network (VAN-GAN). VAN-GAN integrates synthetic blood vessel networks that closely resemble real-life anatomy into its training process and learns to replicate the underlying physics of the PAI system in order to learn how to segment vasculature from 3D biomedical images. With a variety of in silico, in vitro and in vivo data, including patient-derived breast cancer xenograft models, we show that VAN-GAN facilitates accurate and unbiased segmentation of 3D vascular networks from PAI data volumes. By leveraging synthetic data to reduce the reliance on manual labelling, VAN-GAN lowers the barrier to entry for high-quality blood vessel segmentation to benefit users in the life sciences applying PAI to studies of vascular structure and function.

biophysics↗

bioRxiv2022

Performance evaluation of mesoscopic photoacoustic imaging

Photoacoustic mesoscopy visualises vascular architecture and associated tissue structures at high resolution at up to 3 mm depth. The technique has shown promise in both preclinical and clinical imaging studies, with possible applications in oncology and dermatology, however, the accuracy and precision of photoacoustic mesoscopy has not been well established. Here, we present a performance evaluation of a commercial photoacoustic mesoscopy system for imaging vascular structures. Typical artefact types are first highlighted and limitations due to non-isotropic illumination and detection are evaluated with respect to rotation, angularity, and depth of the target. Then, using tailored phantoms and mouse models we demonstrate high system precision, with acceptable coefficients of variation (COV) between repeated scans (short term (1h): COV=1.2%; long term (25 days): COV=9.6%), from target repositioning (without: COV=1.2%, with: COV=4.1%), or from varying in vivo user experience (experienced: COV=15.9%, unexperienced: COV=20.2%). While our findings support the robustness of the technique, they also underscore the general challenges of limited field-of-view photoacoustic systems in accurately imaging vessel-like structures, thereby guiding users to correctly interpret biologically-relevant information.

bioengineering↗

bioRxiv2021

Quantification of vascular networks in photoacoustic mesoscopy

Mesoscopic photoacoustic imaging (PAI) enables non-invasive visualisation of tumour vasculature and has the potential to assess prognosis and therapeutic response. Currently, evaluating vasculature using mesoscopic PAI involves visual or semi-quantitative 2D measurements, which fail to capture 3D vessel network complexity, and lack robust ground truths for assessment of segmentation accuracy. Here, we developed an in silico, phantom, in vivo, and ex vivo-validated end-to-end framework to quantify 3D vascular networks captured using mesoscopic PAI. We applied our framework to evaluate the capacity of rule-based and machine learning-based segmentation methods, with or without vesselness image filtering, to preserve blood volume and network structure by employing topological data analysis. We first assessed segmentation performance against ground truth data of in silico synthetic vasculatures and a photoacoustic string phantom. Our results indicate that learning-based segmentation best preserves vessel diameter and blood volume at depth, while rule-based segmentation with vesselness image filtering accurately preserved network structure in superficial vessels. Next, we applied our framework to breast cancer patient-derived xenografts (PDXs), with corresponding ex vivo immunohistochemistry. We demonstrated that the above segmentation methods can reliably delineate the vasculature of 2 breast PDX models from mesoscopic PA images. Our results underscore the importance of evaluating the choice of segmentation method when applying mesoscopic PAI as a tool to evaluate vascular networks in vivo.

bioengineering↗

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↗