Cellulose Nanoparticles are a Biodegradable Photoacoustic Contrast Agent for Use in Living Mice.

Molecular imaging with photoacoustic ultrasound is an emerging field that combines the spatial and temporal resolution of ultrasound with the contrast of optical imaging. However, there are few imaging agents that offer both high signal intensity and biodegradation into small molecules. Here we describe a cellulose-based nanoparticle with peak photoacoustic signal at 700 nm and an in vitro limit of detection of 6 pM (0.02 mg/mL). Doses down to 0.35 nM (1.2 mg/mL) were used to image mouse models of ovarian cancer. Most importantly, the nanoparticles were shown to biodegrade in the presence of cellulase both through a glucose assay and electron microscopy

Development of a blood oxygenation phantom for photoacoustic tomography combined with online pO2 detection and flow spectrometry

Photoacoustic tomography (PAT) is intrinsically sensitive to blood oxygen saturation (sO2) in vivo. However, making accurate sO2 measurements without knowledge of tissue- and instrumentation-related correction factors is extremely challenging. We have developed a low-cost flow phantom to facilitate validation of PAT systems. The phantom is composed of a flow circuit of tubing partially embedded within a tissue-mimicking material, with independent sensors providing online monitoring of the optical absorption spectrum and partial pressure of oxygen in the tube. We first test the flow phantom using two small molecule dyes that are frequently used for photoacoustic imaging: methylene blue and indocyanine green. We then demonstrate the potential of the phantom for evaluating sO2 using chemical oxygenation and deoxygenation of blood in the circuit. Using this dynamic assessment of the photoacoustic sO2 measurement in phantoms in relation to a ground truth, we explore the influence of multispectral processing and spectral coloring on accurate assessment of sO2. Future studies could exploit this low-cost dynamic flow phantom to validate fluence correction algorithms and explore additional blood parameters such as pH and also absorptive and other properties of different fluids

Listening to reporter proteins: how loud does the message need to be?

Optical imaging as non-invasive modality has tremendous research applications in the area of biomedical sciences such as characterization of cancerous cells. However, this imaging modality is limited by depth of light penetration of around 1 mm in living tissues obscuring visualization in vivo. Optoacoustic imaging is a potential solution of this problem based on detection of ultrasound produced by light-absorbing molecules exposed to laser radiation resulting in a tissue contrast. The image contrast relies on absorption of laser emission, however providing ultrasound resolution in living tissues. This study characterized properties of colorectal adenocarcinoma cells expressing Near-infrared Fluorescent proteins (iRFPs) for detection and visualization in Multispectral Optoacoustic Tomography (MSOT) settings in both tissue-mimicking phantoms and mice. We estimated variables affecting MSOT imaging of 3D multicellular tissue spheroids such as size, expression of iRFP in vitro. We tested MSOT for detection of subcutaneously implanted tumours expressing iRFPs in BALB/C nude mice in vivo

Hyperspectral imaging in biomedical applications

No abstract available

Listening to reporter proteins: how loud does the message need to be?

Optical imaging as non-invasive modality has tremendous research applications in the area of biomedical sciences such as characterization of cancerous cells. However, this imaging modality is limited by depth of light penetration of around 1 mm in living tissues obscuring visualization in vivo. Optoacoustic imaging is a potential solution of this problem based on detection of ultrasound produced by light-absorbing molecules exposed to laser radiation resulting in a tissue contrast. The image contrast relies on absorption of laser emission, however providing ultrasound resolution in living tissues. This study characterized properties of colorectal adenocarcinoma cells expressing Near-infrared Fluorescent proteins (iRFPs) for detection and visualization in Multispectral Optoacoustic Tomography (MSOT) settings in both tissue-mimicking phantoms and mice. We estimated variables affecting MSOT imaging of 3D multicellular tissue spheroids such as size, expression of iRFP in vitro. We tested MSOT for detection of subcutaneously implanted tumours expressing iRFPs in BALB/C nude mice in vivo

A background correction method to compensate illumination variation in hyperspectral imaging.

Hyperspectral imaging (HSI) can measure both spatial (morphological) and spectral (biochemical) information from biological tissues. While HSI appears promising for biomedical applications, interpretation of hyperspectral images can be challenging when data is acquired in complex biological environments. Variations in surface topology or optical power distribution at the sample, encountered for example during endoscopy, can lead to errors in post-processing of the HSI data, compromising disease diagnostic capabilities. Here, we propose a background correction method to compensate for such variations, which estimates the optical properties of illumination at the target based on the normalised spectral profile of the light source and the measured HSI intensity values at a fixed wavelength where the absorption characteristics of the sample are relatively low (in this case, 800 nm). We demonstrate the feasibility of the proposed method by imaging blood samples, tissue-mimicking phantoms, and ex vivo chicken tissue. Moreover, using synthetic HSI data composed from experimentally measured spectra, we show the proposed method would improve statistical analysis of HSI data. The proposed method could help the implementation of HSI techniques in practical clinical applications, where controlling the illumination pattern and power is difficult

Coherent Imaging through Multicore Fibres with Applications in Endoscopy

Imaging through optical fibres has recently emerged as a promising method of micro-scale optical imaging within a hair-thin form factor. This has significant applications in endoscopy and may enable minimally invasive imaging deep within live tissue for improved diagnosis of disease. Multi-mode fibres (MMF) are the most common choice because of their high resolution but multicore fibres (MCF) offer a number of advantages such as widespread clinical use, ability to form approximate images without correction and an inherently sparse transmission matrix (TM) enabling simple and fast characterisation. We present a novel experimental investigation into properties of MCF important for imaging, specifically: a new method to upsample and downsample measured TMs with minimal information loss, the first experimental measurement of MCF spatial eigenmodes, a novel statistical treatment of behaviour under bending based on a wireless fading model, and an experimental observation of TM drift due to self-heating effects and discussion of how to compensate this. We next present practical techniques for imaging through MCFs, including alignment, how to parallelise TM characterisation measurements to improve speed and how to use non-interferometric phase and polarisation recovery for improved stability. Finally, we present two recent applications of MCF imaging: polarimetric imaging using a robust Bayesian inference approach, and entropic imaging for imaging early-stage tumours

Contrast agents for molecular photoacoustic imaging.

Photoacoustic imaging (PAI) is an emerging tool that bridges the traditional depth limits of ballistic optical imaging and the resolution limits of diffuse optical imaging. Using the acoustic waves generated in response to the absorption of pulsed laser light, it provides noninvasive images of absorbed optical energy density at depths of several centimeters with a resolution of ∼100 μm. This versatile and scalable imaging modality has now shown potential for molecular imaging, which enables visualization of biological processes with systemically introduced contrast agents. Understanding the relative merits of the vast range of contrast agents available, from small-molecule dyes to gold and carbon nanostructures to liposome encapsulations, is a considerable challenge. Here we critically review the physical, chemical and biochemical characteristics of the existing photoacoustic contrast agents, highlighting key applications and present challenges for molecular PAI.This work was supported by CRUK (Career Establishment Award no. C47594/A16267 to J.W. and S.E.B., Core Funding C14303/A17197 to J.W. and S.E.B.), the European Commission (CIG FP7-PEOPLE- 2013-CIG-630729 to J.W. and S.E.B.), the EPSRC-CRUK Cancer Imaging Centre in Cambridge and Manchester (C197/A16465 to J.W. and S.E.B.), King’s College London and University College London Comprehensive Cancer Imaging Centre Cancer Research UK & Engineering and Physical Sciences Research Council, in association with the Medical Research Council and the Department of Health, UK (P.B.), and the European Union (project FAMOS FP7 ICT, contract 317744 to P.B.).This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/nmeth.392