Fast Multispectral Optoacoustic Tomography (MSOT) for Dynamic Imaging of Pharmacokinetics and Biodistribution in Multiple Organs

The characterization of pharmacokinetic and biodistribution profiles is an essential step in the development process of new candidate drugs or imaging agents. Simultaneously, the assessment of organ function related to the uptake and clearance of drugs is of great importance. To this end, we demonstrate an imaging platform capable of high-rate characterization of the dynamics of fluorescent agents in multiple organs using multispectral optoacoustic tomography (MSOT). A spatial resolution of approximately 150 µm through mouse cross-sections allowed us to image blood vessels, the kidneys, the liver and the gall bladder. In particular, MSOT was employed to characterize the removal of indocyanine green from the systemic circulation and its time-resolved uptake in the liver and gallbladder. Furthermore, it was possible to track the uptake of a carboxylate dye in separate regions of the kidneys. The results demonstrate the acquisition of agent concentration metrics at rates of 10 samples per second at a single wavelength and 17 s per multispectral sample with 10 signal averages at each of 5 wavelengths. Overall, such imaging performance introduces previously undocumented capabilities of fast, high resolution in vivo imaging of the fate of optical agents for drug discovery and basic biological research

Through-needle all-optical ultrasound imaging in vivo: a preclinical swine study

This work was funded through a Starting Grant from the European Research Council (ERC-2012-StG, Proposal 310970 MOPHIM), an Innovative Engineering for Health award from the Wellcome Trust (WT101957) and Engineering and Physical Sciences Research Council (EPSRC) (NS/A000027/1), and the EPSRC and European Union project FAMOS (FP7 ICT, Contract 317744). This work was partially funded by National Institute for Health Research University College London Hospitals Biomedical Research Centre and the National Institute for Health Research Barts and the London Biomedical Research Unit

Optical Drug Monitoring: Photoacoustic Imaging of Nanosensors to Monitor Therapeutic Lithium in Vivo

Personalized medicine could revolutionize how primary care physicians treat chronic disease and how researchers study fundamental biological questions. To realize this goal, we need to develop more robust, modular tools and imaging approaches for in vivo monitoring of analytes. In this report, we demonstrate that synthetic nanosensors can measure physiologic parameters with photoacoustic contrast, and we apply that platform to continuously track lithium levels in vivo. Photoacoustic imaging achieves imaging depths that are unattainable with fluorescence or multiphoton microscopy. We validated the photoacoustic results that illustrate the superior imaging depth and quality of photoacoustic imaging with optical measurements. This powerful combination of techniques will unlock the ability to measure analyte changes in deep tissue and will open up photoacoustic imaging as a diagnostic tool for continuous physiological tracking of a wide range of analytes

A practical guide to photoacoustic tomography in the life sciences

The life sciences can benefit greatly from imaging technologies that connect microscopic discoveries with macroscopic observations. One technology uniquely positioned to provide such benefits is photoacoustic tomography (PAT), a sensitive modality for imaging optical absorption contrast over a range of spatial scales at high speed. In PAT, endogenous contrast reveals a tissue's anatomical, functional, metabolic, and histologic properties, and exogenous contrast provides molecular and cellular specificity. The spatial scale of PAT covers organelles, cells, tissues, organs, and small animals. Consequently, PAT is complementary to other imaging modalities in contrast mechanism, penetration, spatial resolution, and temporal resolution. We review the fundamentals of PAT and provide practical guidelines for matching PAT systems with research needs. We also summarize the most promising biomedical applications of PAT, discuss related challenges, and envision PAT's potential to lead to further breakthroughs

Multispectral optoacoustic tomography for imaging of disease biomarkers.

Multispectral optoacoustic tomography (MSOT) is an emerging modality based on ultrasound detection of optical absorption via the photoacoustic effect. The technique allows the visualisation of intrinsic optical tissue contrast, as well as a multitude of exogenous contrast agents at the high resolution provided by ultrasound. This dissertation describes the critical methods developed and corresponding results obtained during a research effort aimed at evaluation of the technique in the context of in-vivo biomarker imaging. Studies were performed on mouse models of cancer and cardiovascular disease. In summary, MSOT was discovered to enable a number of applications, from the small animal imaging as described in this work, to future clinical translation

Translational optical imaging.

OBJECTIVE. Optical imaging is experiencing significant technologic advances. Simultaneously, an array of specific optical imaging agents has brought new capabilities to biomedical research and is edging toward clinical use. We review progress in the translation of macroscopic optical imaging-including fluorescence-guided surgery and endoscopy, intravascular fluorescence imaging, diffuse fluorescence and optical tomography, and multispectral optoacoustics (photoacoustics)-for applications ranging from tumor resection and assessment of atherosclerotic plaques to dermatologic and breast examinations. CONCLUSION. Optical imaging could play a major role in the move from imaging of structure and morphology to the visualization of the individual biologic processes underlying disease and could, therefore, contribute to more accurate diagnostics and improved treatment efficacy

Optical and optoacoustic imaging in the diffusive regime

Optical imaging is capable of providing valuable molecular contrast, cell tracking, genetic reporters, and a wide range of biomarkers that reveal the biological processes underlying a disease. For centuries, optical imaging has primarily been confined to superficial tissue layers, due to the high scattering of photons in tissue. Optical tomographic methods based on accurate models of diffusive deep-tissue light propagation have allowed fluorescence and endogenous contrast to be visualized and volumetrically quantified at depths of centimeters. Emerging optoacoustic methods allow optical absorption contrast to be pinpointed at high spatial resolutions by means of ultrasound waves, breaking through the resolution limitations imposed by diffusive light. This chapter introduces the principles of optical and optoacoustic methods for imaging biomedically relevant contrast in the diffusive regime

Fast deep-tissue multispectral optoacoustic tomography (MSOT) for preclinical imaging of cancer and cardiovascular disease.

Optoacoustic imaging has enabled the visualization of optical contrast at high resolutions in deep tissue. Our Multispectral optoacoustic tomography (MSOT) imaging results reveal internal tissue heterogeneity, where the underlying distribution of specific endogenous and exogenous sources of absorption can be resolved in detail. Technical advances in cardiac imaging allow motion-resolved multispectral measurements of the heart, opening the way for studies of cardiovascular disease. We further demonstrate the fast characterization of the pharmacokinetic profiles of lightabsorbing agents. Overall, our MSOT findings indicate new possibilities in high resolution imaging of functional and molecular parameters

Real-time handheld multispectral optoacoustic imaging.

Multispectral optoacoustic tomography (MSOT) of functional and molecular contrast has the potential to find broad deployment in clinical practice. We have developed the first handheld MSOT imaging device with fast wavelength tuning achieving a frame rate of 50 Hz. In this Letter, we demonstrate its clinical potential by dynamically resolving multiple disease-relevant tissue chromophores, including oxy-/deoxyhemoglobin, and melanin, in human volunteers