A lack of accepted standards and standardized phantoms suitable for the technical validation of biophotonic instrumentation hinders the reliability and reproducibility of its experimental outputs. In this Perspective, we discuss general criteria for the design of tissue-mimicking biophotonic phantoms, and use these criteria and state-of-the-art developments to critically review the literature on phantom materials and on the fabrication of phantoms. By focusing on representative examples of standardization in diffuse optical imaging and spectroscopy, fluorescence-guided surgery and photoacoustic imaging, we identify unmet needs in the development of phantoms and a set of criteria (leveraging characterization, collaboration, communication and commitment) for the standardization of biophotonic instrumentation.
Photoacoustic imaging (PAI) standardisation demands a stable, highly reproducible physical phantom to enable routine quality control and robust performance evaluation. To address this need, we have optimised a low-cost copolymer-in-oil tissue-mimickingmaterial formulation. The base material consists of mineral oil, copolymer and stabiliser with defined Chemical Abstract Service numbers. Defined optical and acoustic properties were stable over almost a year and were minimally affected by recasting. The material showed high intra-laboratory reproducibility and good photo- and mechanical-stability in the relevant working range. The optimised copolymer-in-oil material represents an excellent candidate for widespread application in PAI phantoms, with properties suitable for broader use in biophotonics and ultrasound imaging standardisation efforts.
The results of this pilot first-in-human clinical trial demonstrate the potential of spectral endoscopy to reveal disease-associated vascular changes and to provide high-contrast delineation of neoplasia in the esophagus.
Multispectral imaging is an exciting technology that can be applied to extract morphological (spatial) and biochemical (spectral) information from tumours. Typically, each multispectral imaging application requires a specific spectral range and number of spectral bands, which is challenging for conventional manufacturing processes. We present here a versatile, wafer-scale framework for producing highly efficient, narrowband and customisable transmissive multispectral imaging filter arrays. We envisage that the process can be used to fabricate custom multispectral imaging cameras, paving the way in the future for widespread application of the technology in biomedicine, including for endoscopic and intraoperative imaging.
In this work, we demonstrate a hyperspectral endoscope (HySE) that simultaneously records intrinsically co-registered hyperspectral and standard-of-care white light images, which allows image distortions to be compensated computationally and an accurate hyperspectral data cube to be reconstructed as the endoscope moves in the lumen. Evaluation of HySE performance shows excellent spatial, spectral and temporal resolution and high colour fidelity. Application of HySE enables: quantification of blood oxygenation levels in tissue mimicking phantoms; differentiation of spectral profiles from normal and pathological ex vivo human tissues; and recording of hyperspectral data under freehand motion within an intact ex vivo pig oesophagus model. HySE therefore shows potential for enabling HSI in clinical endoscopy.
Oxygen Enhanced Optoacoustic Tomography (OE-OT) is a technique we developed and reported in 2017, exploiting gas challenge to provide high contrast insight into tumour vascular function. In this work, we show that OE-OT in combination with Dynamic Contrast Enhanced OT (DCE-OT), which relies on fluorescent contrast injection, can be used to accurately measure tumour oxygenation, maturity of the vascular network and the viability of the tumour tissue.
Nanodiamonds have demonstrated potential as powerful sensors in biomedicine. However, their translation into routine use requires a comprehensive understanding of their effect on the biological system being interrogated. In this paper we assessed the biological impact of graphitic and oxidized nanodiamond surfaces. We show for the first time that oxidized nanodiamonds possess improved biocompatibility compared to graphitic nanodiamonds in breast cancer cell lines, with graphitic nanodiamonds inducing higher levels of oxidative stress despite lower uptake.
In this work, researchers announce new advances in measuring blood flow velocity in deep tissue. Blood flow speed is a critical element in assessing tissue functionality as well as diagnosing diseases, and photoacoustic flowmetry (PAF) is already acknowledged as a promising technique for deep tissue measurement of blood flow velocity. The new work demonstrates successful use of a handheld ultrasound probe common in clinical settings, paving the way to explore the feasibility of measuring flow in a physiologically realistic situation.
Optoacoustic tomography (OT) is an emerging clinical imaging modality that provides static images of endogenous haemoglobin concentration and oxygenation. Here, we demonstrate oxygen enhanced (OE)-OT, exploiting an oxygen gas challenge to visualise the spatiotemporal heterogeneity of tumour vascular function.
Spectrally resolved detector arrays are an exciting new technology that allows spectral information to be recorded by conventional CMOS cameras (akin to those found in your smartphone). Here, we show that an SRDA can in fact be used to detect fluorescence signals for biomedical imaging applications.
In this work, we created a bimodal endoscope to reveal the binding of a near infrared fluorescent dye sprayed onto oesophageal tissue for detection of early malignancy.
The characterisation of modal propagation in fibre bundles is performed here to achieve lensless focusing of imaging data. This is a first step towards performing phase retrieval and lensless focusing during clinical endoscopy using a fibre bundle.
We were able to show here for the first time that optoacoustic imaging is able to detect both the vessel regression and normalisation that is commonly observed with anti-angiogenic therapy. This opens the possibility of using optoacoustic imaging to schedule combination therapy with cytotoxic drugs.
Recently, we developed a dedicated instrument for high throughput Raman spectroscopy, accelerating preclinical studies with this technique and hence improving the long-term prospects for clinical translation.
In this study, we demonstrated for the first time that vitamin C could be hyperpolarized and also used as a contrast agent to detect redox state noninvasively in living subjects.