Characterization of plaque vulnerability.

Heart disease is the leading cause of death in both men and women. Coronary heart disease is the most common type of heart disease, and is caused by the buildup of fatty plaques on the interior walls of the coronary arteries. This results in arterial narrowing, increased blood pressure, and in some cases occlusion of blood flow.

Early stages of heart disease – the time at which interventions would be most successful – are often asymptomatic. The need is therefore immense to develop strategies and technologies that can detect biomarkers of early heart disease. MSOT has the potential to non-invasively visualize blood vessels as well as molecular markers within them. For example, matrix metalloproteinases (MMP) have been implicated in vascular remodeling, and elevated expression of MMP-9 is considered a biomarker of atherosclerotic plaque instability.

With the combination of molecular probes that can detect MMP activity, MSOT can characterize at-risk plaques.

MSOT analysis of MMP activity in human carotid artery

Image left: Left column shows cross-sectional MSOT images of an excised human carotid artery. Right column represent the equivalent cross-sections of the two carotid slices as color photographs confirming the anatomical structures obtained by MSOT imaging.

Image middle: Multispectral MSOT image, with grayscale showing a single wavelength image for anatomical reference; the green color indicates the distribution of a activated MMPSense (PerkinElmer), a fluorescent probe activated by the matrix metalloproteinases present in the inflammatory cells surrounding atherosclerotic plaques.

Image right: In situ zymography of the ‘hot’ and ‘cold’ regions of interest accurately confirms the increased gelatinase activity in the ‘hot’ spot of the MSOT image.

Razansky D, Harlaar NJ, Hillebrands JL, Taruttis A, Herzog E, Zeebregts CJ, van Dam GM, Ntziachristos V, Multispectral Optoacoustic Tomography of Matrix Metalloproteinase Activity in Vulnerable Human Carotid Plaques, Mol Imaging Biol. 2011 Jul 1.

  • Dima A, Ntziachristos V,

    Non-invasive Carotid Imaging Using Optoacoustic Tomography,

    Optics Express, Vol. 20, Issue 22, pp. 25044-25057 (2012)
. DOI: 10.1364/OE.20.025044.
    Link
  • Razansky D et al.,
    
Multispectral Optoacoustic Tomography of Matrix Metalloproteinase Activity in Vulnerable Human Carotid Plaques,

    Mol Imaging Biol. 2011 Jul 1. DOI: 10.1007/s11307-011-0502-6.
    Link
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