Enter Your Search:
Results 1-2 (2)
Go to page number:
Select a Filter Below
Molecular Imaging and Biology (1)
PLoS ONE (1)
Ntziachristos, Vasilis (2)
Razansky, Daniel (2)
Taruttis, Adrian (2)
Burton, Neal C. (1)
Harlaar, Niels J. (1)
Herzog, Eva (1)
Hillebrands, Jan Luuk (1)
Morscher, Stefan (1)
Prow, Tarl Wayne (1)
Zeebregts, Clark J. (1)
van Dam, Gooitzen M. (1)
Year of Publication
Fast Multispectral Optoacoustic Tomography (MSOT) for Dynamic Imaging of Pharmacokinetics and Biodistribution in Multiple Organs
Burton, Neal C.
Prow, Tarl Wayne
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.
Multispectral Optoacoustic Tomography of Matrix Metalloproteinase Activity in Vulnerable Human Carotid Plaques
Harlaar, Niels J.
Hillebrands, Jan Luuk
Zeebregts, Clark J.
van Dam, Gooitzen M.
Molecular Imaging and Biology
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.
Methods and results
MMP-sensitive activatable fluorescent probe (MMPSense™ 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 in situ 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.
Atherosclerosis; Optoacoustic imaging; Carotid arteries; Plaque; Contrast media; Inflammation; Medicine & Public Health; Imaging / Radiology
Results 1-2 (2)
Go to page number:
Remove citation from clipboard
Add citation to clipboard
This will clear all selections from your clipboard. Do you wish proceed?
Clipboard is full! Please remove an item and try again.
PubMed Central Canada is a service of the
Canadian Institutes of Health Research
(CIHR) working in partnership with the National Research Council's
Canada Institute for Scientific and Technical Information
in cooperation with the
National Center for Biotechnology Information
U.S. National Library of Medicine
(NCBI/NLM). It includes content provided to the
PubMed Central International archive
by participating publishers.