High-resolution optoacoustic imaging of tissue responses to vascular-targeted therapies

Nat Biomed Eng. 2020 Mar;4(3):286-297. doi: 10.1038/s41551-020-0527-8. Epub 2020 Mar 12.

Abstract

The monitoring of vascular-targeted therapies using magnetic resonance imaging, computed tomography or ultrasound is limited by their insufficient spatial resolution. Here, by taking advantage of the intrinsic optical properties of haemoglobin, we show that raster-scanning optoacoustic mesoscopy (RSOM) provides high-resolution images of the tumour vasculature and of the surrounding tissue, and that the detection of a wide range of ultrasound bandwidths enables the distinction of vessels of differing size, providing detailed insights into the vascular responses to vascular-targeted therapy. Using RSOM to examine the responses to vascular-targeted photodynamic therapy in mice with subcutaneous xenografts, we observed a substantial and immediate occlusion of the tumour vessels followed by haemorrhage within the tissue and the eventual collapse of the entire vasculature. Using dual-wavelength RSOM, which distinguishes oxyhaemoglobin from deoxyhaemoglobin, we observed an increase in oxygenation of the entire tumour volume immediately after the application of the therapy, and a second wave of oxygen reperfusion approximately 24 h thereafter. We also show that RSOM enables the quantification of differences in neoangiogenesis that predict treatment efficacy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / diagnostic imaging
  • Cerebral Ventricle Neoplasms / diagnostic imaging
  • Colonic Neoplasms / diagnostic imaging
  • Colonic Neoplasms / pathology
  • Craniotomy
  • Diagnostic Imaging / methods*
  • Disease Models, Animal
  • Endothelin-1
  • Epinephrine
  • Female
  • Heterografts
  • Image Processing, Computer-Assisted / methods
  • Imaging, Three-Dimensional
  • Lasers
  • Mice
  • Mice, Inbred BALB C
  • Neovascularization, Pathologic / diagnosis*
  • Oxygen
  • Photoacoustic Techniques / methods*
  • Ultrasonography / methods*
  • Urinary Bladder Neoplasms / diagnostic imaging
  • Urinary Bladder Neoplasms / pathology
  • Vascular Neoplasms / diagnostic imaging*
  • Vascular Neoplasms / pathology
  • Vasoconstriction

Substances

  • Endothelin-1
  • Oxygen
  • Epinephrine