High-resolution optoacoustic imaging

High-resolution visualization of superficial microvasculature is critical for diagnosis and treatment monitoring of diseases like skin cancers, tumor angiogenesis and vascular disease. Conventional imaging modalities are able to assess microvasculature only with the help of contrast agents or invasive techniques. Raster-scanning optoacoustic mesoscopy (RSOM) utilizes laser excitation and high-frequency acoustic detection, thereby providing intrinsic optical tissue contrast, with up to 10 μm resolution, at several millimeters depth.

iThera Medical has developed RSOM imaging systems for explorative preclinical and clinical use. Clinically, RSOM can be utilized to detect diseases in which irregular accumulation of hemoglobin or melanin is involved, at mesoscopic scales. Preclinically, RSOM can additionally be used to resolve the presence of molecular probes.

Preclinical RSOM experiment workflow

iThera Medical's RSOM imaging systems facilitate a wide variety of imaging applications as well as extensive data analysis, and are yet easy to use. To get a first-hand impression of the RSOM experiment procedure for small animal studies, follow this link: play video

Preclinical imaging of tumor vasculature

(Top) System schematic of the preclinical RSOM system depicting general positioning of system components and the mouse.
(Bottom) Progression of tumor growth and angiogenesis was monitored with RSOM over 9 days. Maximum intensity projection images 900 μm below the skin surface at four time points (2, 4, 7 and 9 days after implantation) are shown; the insets in each image depict growth of microvasculature between two large vessels (arrows) over time. (Scale bar: 1 mm major images, 0.5 mm inset).

Clinical RSOM experiment workflow

Besides enabling small animal research, RSOM can now also be used for clinical research, particularly related to skin disease. To get a first-hand impression of scanning human skin using RSOM, follow this link: play video

Imaging of benign nevus using clinical prototype RSOM

(Left) System setup of the clinical RSOM prototype system. Depicted are the general positioning of all components and the human tissue of a healthy volunteer. (Right) (a) MIP image vertical to the skin surface of a scan region containing a ~1.5 mm benign nevus (b). The intense signal in the RSOM image is a result of high local levels of melanin in the nevus. (c,d) MIP images along the direction perpendicular to the skin surface within the limits marked in (a). In (d) the frequency filtered original image (white) is overlaid with an image filtered for vessels in green.

Schwarz M. et al., Implications of Ultrasound Frequency in Optoacoustic Mesoscopy of the Skin. IEEE Trans Med Imaging. 2015 Feb;34(2):672-7.

Technical information

  • Axial / lateral resolution: up to 10 / 40 µm
  • Penetration depth: up to 3 mm
  • 80 seconds acquisition time for 5 x 5 mm field of view
  • Pulsed laser illumination at 532 nm (multispectral planned for 2017)
  • 50 MHz single-element detector with ultra-wide bandwidth (>90 percent)
  • Image acquisition fully automated
  • Software for image reconstrution, visualization and analysis
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    Assessing hyperthermia-induced vasodilation in human skin in vivo using optoacoustic mesoscopy,
    J Biophotonics. 2018 Mar 23:e201700359. DOI: 10.1002/jbio.201700359.
  • Aguirre J et al.,
    Assessing nailfold microvascular structure with ultra-wideband raster-scan optoacoustic mesoscopy,
    Photoacoustics, 2018 Jun; 10:31-37. DOI: 10.1016/j.pacs.2018.02.002.
  • Knieling F et al.,
    Raster-Scanning Optoacoustic Mesoscopy for Gastrointestinal Imaging at High Resolution,
    Gastroenterology. 2018 Jan 5. DOI: 10.1053/j.gastro.2017.11.285.
  • Schwarz M et al.,
    Motion correction in optoacoustic mesoscopy
    Sci Rep. 2017 Sep 4;7(1):10386. DOI: 10.1038/s41598-017-11277-y.
  • Aguirre j et al.,
    Precision assessment of label-free psoriasis biomarkers with ultra-broadband optoacoustic mesoscopy,
    Nat. Biomed. Eng. 1, 0068 (2017). DOI:10.1038/s41551-017-0068.
  • Haedicke K et al.
    Sonophore labeled RGD: a targeted contrast agent for optoacoustic imaging,
    Photoacoustics. 2017;6:1-8. DOI:10.1016/j.pacs.2017.03.001.
  • Schwarz M et al.,
    Optoacoustic Dermoscopy of the Human Skin: Tuning Excitation Energy for Optimal Detection Bandwidth with Fast and Deep Imaging in vivo,
    IEEE Trans Med Imaging. 2017 Mar 1. DOI: 10.1109/TMI.2017.2664142.
  • Schwarz M et al.,
    Three-dimensional multispectral optoacoustic mesoscopy reveals melanin and blood oxygenation in human skin in vivo,
    J Biophotonics. 2016 Jan;9(1-2):55-60. DOI: 10.1002/jbio.201500247.
  • Schwarz M et al.,
    Implications of ultrasound frequency in optoacoustic mesoscopy of the skin,
    IEEE Trans Med Imaging. 2015 Feb;34(2):672-7. DOI: 10.1109/TMI.2014.2365239.
  • Omar M et al.,
    Pushing the optical imaging limits of cancer with multi-frequency-band raster-scan optoacoustic mesoscopy (RSOM),
    Neoplasia. 2015 Feb;17(2):208-14. DOI: 10.1016/j.neo.2014.12.010.
  • Aguirre J et al.,
    Broadband mesoscopic optoacoustic tomography reveals skin layers,
    Opt Lett. 2014 Nov 1;39(21):6297-300. DOI: 10.1364/OL.39.006297.
  • Omar M et al.,
    Ultrawideband reflection-mode optoacoustic mesoscopy,
    Opt Lett. 2014 Jul 1;39(13):3911-4. DOI: 10.1364/OL.39.003911.
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