Technical validation studies of a dual-wavelength LED-based photoacoustic and ultrasound imaging system.

Recent advances in high power, pulsed, light emitting diodes (LEDs) have shown potential as fast, robust and relatively inexpensive excitation sources for photoacoustic imaging (PAI), yet systematic characterization of performance for biomedical imaging is still lacking. We report here technical and biological validation studies of a commercial dual-wavelength LED-based PAI and ultrasound system. Phantoms and small animals were used to assess temporal precision. In phantom studies, we found high temporal stability of the LED-based PAI system, with no significant drift in performance observed during 6 h of operation or over 30 days of repeated measurements. In vivo dual-wavelength imaging was able to map the dynamics of changes in blood oxygenation during oxygen-enhanced imaging and reveal the kinetics of indocyanine green contrast agent inflow after intravenous administration (Tmax∼6 min). Taken together, these studies indicate that LED-based excitation could be promising for future application in functional and molecular PAI

Multispectral Optoacoustic Tomography of Matrix Metalloproteinase Activity in Vulnerable Human Carotid Plaques

Elevated expression of cathepsins, integrins and matrix metalloproteinases (MMPs) is typically associated with atherosclerotic plaque instability. While fluorescent tagging of such molecules has been amply demonstrated, no imaging method was so far shown capable of resolving these inflammation-associated tags with high fidelity and resolution beyond microscopic depths. This study is aimed at demonstrating a new method with high potential for noninvasive clinical cardiovascular diagnostics of vulnerable plaques using high-resolution deep-tissue multispectral optoacoustic tomography (MSOT) technology. MMP-sensitive activatable fluorescent probe (MMPSense (TM) 680) was applied to human carotid plaques from symptomatic patients. Atherosclerotic activity was detected by tuning MSOT wavelengths to activation-dependent absorption changes of the molecules, structurally modified in the presence of enzymes. MSOT analysis simultaneously provided morphology along with heterogeneous MMP activity with better than 200 micron resolution throughout the intact plaque tissue. The results corresponded well with epi-fluorescence images made from thin cryosections. Elevated MMP activity was further confirmed by zymography, accompanied by increased macrophage influx. We demonstrated, for the first time to our knowledge, the ability of MSOT to provide volumetric images of activatable molecular probe distribution deep within optically diffuse tissues. High-resolution mapping of MMP activity was achieved deep in the vulnerable plaque of intact human carotid specimens. This performance directly relates to pre-clinical screening applications in animal models and to clinical decision potential as it might eventually allow for highly specific visualization and staging of plaque vulnerability thus impacting therapeutic clinical decision making

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

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

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

Crowdfunding: A Chance to Fund Student Films the Easy Way?

This thesis focuses on crowdfunding for no- and low-budget film projects of students in Germany. The research examines how student film projects in Germany successfully can be crowdfunded on the online platform startnext. Further motivations of initiators and supporters to join crowdfunding campaigns are getting illuminated. Factors of success for crowdfunding campaigns get identified. After literature research three example projects get analysed and discussed regarding the factors of success. Crowdfunding was found to be a chance to finance student films with low budgets. For the future cooperations of traditional fundraising with crowdfunding can create new possibilities to fund films

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