Assessment of Molecular Acoustic Angiography for Combined Microvascular and Molecular Imaging in Preclinical Tumor Models

Brooks D. Lindsey, Sarah E. Shelton, F. Stuart Foster, Paul A. Dayton

Research output: Research - peer-reviewArticle

  • 2 Citations

Abstract

Purpose: The purposes of the present study is to evaluate a new ultrasound molecular imaging approach in its ability to image a preclinical tumor model and to investigate the capacity to visualize and quantify co-registered microvascular and molecular imaging volumes. Procedures: Molecular imaging using the new technique was compared with a conventional ultrasound molecular imaging technique (multi-pulse imaging) by varying the injected microbubble dose and scanning each animal using both techniques. Each of the 14 animals was randomly assigned one of three doses; bolus dose was varied, and the animals were imaged for three consecutive days so that each animal received every dose. A microvascular scan was also acquired for each animal by administering an infusion of nontargeted microbubbles. These scans were paired with co-registered molecular images (VEGFR2-targeted microbubbles), the vessels were segmented, and the spatial relationships between vessels and VEGFR2 targeting locations were analyzed. In five animals, an additional scan was performed in which the animal received a bolus of microbubbles targeted to E- and P-selectins. Vessel tortuosity as a function of distance from VEGF and selectin targeting was analyzed in these animals. Results: Although resulting differences in image intensity due to varying microbubble dose were not significant between the two lowest doses, superharmonic imaging had significantly higher contrast-to-tissue ratio (CTR) than multi-pulse imaging (mean across all doses 13.98 dB for molecular acoustic angiography vs. 0.53 dB for multi-pulse imaging; p = 4.9 × 10−10). Analysis of registered microvascular and molecular imaging volumes indicated that vessel tortuosity decreases with increasing distance from both VEGFR2- and selectin-targeting sites. Conclusions: Molecular acoustic angiography (superharmonic molecular imaging) exhibited a significant increase in CTR at all doses tested due to superior rejection of tissue artifact signals. Due to the high resolution of acoustic angiography molecular imaging, it is possible to analyze spatial relationships in aligned microvascular and molecular superharmonic imaging volumes. Future studies are required to separate the effects of biomarker expression and blood flow kinetics in comparing local tortuosity differences between different endothelial markers such as VEGFR2, E-selectin, and P-selectin.

LanguageEnglish (US)
Pages194-202
Number of pages9
JournalMolecular Imaging and Biology
Volume19
Issue number2
DOIs
StatePublished - Apr 1 2017

Fingerprint

Molecular Imaging
Acoustics
Angiography
Neoplasms
Microbubbles
Pulse
Selectins
P-Selectin
E-Selectin
Ultrasonography
Spatial Analysis
Artifacts
Vascular Endothelial Growth Factor A
Biomarkers

Keywords

  • Angiogenesis
  • Contrast imaging
  • Microbubble
  • Microvasculature
  • Selectin
  • Superharmonic
  • Targeted imaging
  • Tortuosity
  • Ultrasound
  • VEGFR2

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

Cite this

Assessment of Molecular Acoustic Angiography for Combined Microvascular and Molecular Imaging in Preclinical Tumor Models. / Lindsey, Brooks D.; Shelton, Sarah E.; Foster, F. Stuart; Dayton, Paul A.

In: Molecular Imaging and Biology, Vol. 19, No. 2, 01.04.2017, p. 194-202.

Research output: Research - peer-reviewArticle

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N2 - Purpose: The purposes of the present study is to evaluate a new ultrasound molecular imaging approach in its ability to image a preclinical tumor model and to investigate the capacity to visualize and quantify co-registered microvascular and molecular imaging volumes. Procedures: Molecular imaging using the new technique was compared with a conventional ultrasound molecular imaging technique (multi-pulse imaging) by varying the injected microbubble dose and scanning each animal using both techniques. Each of the 14 animals was randomly assigned one of three doses; bolus dose was varied, and the animals were imaged for three consecutive days so that each animal received every dose. A microvascular scan was also acquired for each animal by administering an infusion of nontargeted microbubbles. These scans were paired with co-registered molecular images (VEGFR2-targeted microbubbles), the vessels were segmented, and the spatial relationships between vessels and VEGFR2 targeting locations were analyzed. In five animals, an additional scan was performed in which the animal received a bolus of microbubbles targeted to E- and P-selectins. Vessel tortuosity as a function of distance from VEGF and selectin targeting was analyzed in these animals. Results: Although resulting differences in image intensity due to varying microbubble dose were not significant between the two lowest doses, superharmonic imaging had significantly higher contrast-to-tissue ratio (CTR) than multi-pulse imaging (mean across all doses 13.98 dB for molecular acoustic angiography vs. 0.53 dB for multi-pulse imaging; p = 4.9 × 10−10). Analysis of registered microvascular and molecular imaging volumes indicated that vessel tortuosity decreases with increasing distance from both VEGFR2- and selectin-targeting sites. Conclusions: Molecular acoustic angiography (superharmonic molecular imaging) exhibited a significant increase in CTR at all doses tested due to superior rejection of tissue artifact signals. Due to the high resolution of acoustic angiography molecular imaging, it is possible to analyze spatial relationships in aligned microvascular and molecular superharmonic imaging volumes. Future studies are required to separate the effects of biomarker expression and blood flow kinetics in comparing local tortuosity differences between different endothelial markers such as VEGFR2, E-selectin, and P-selectin.

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