Ultrasound Measurement of Vascular Density to Evaluate Response to Anti-Angiogenic Therapy in Renal Cell Carcinoma

IEEE Trans Biomed Eng. 2019 Mar;66(3):873-880. doi: 10.1109/TBME.2018.2860932. Epub 2018 Jul 27.

Abstract

Background: Functional and molecular changes often precede gross anatomical changes, so early assessment of a tumor's functional and molecular response to therapy can help reduce a patient's exposure to the side effects of ineffective chemotherapeutics or other treatment strategies.

Objective: Our intent was to test the hypothesis that an ultrasound microvascular imaging approach might provide indications of response to therapy prior to assessment of tumor size.

Methods: Mice bearing clear-cell renal cell carcinoma xenograft tumors were treated with antiangiogenic and Notch inhibition therapies. An ultrasound measurement of microvascular density was used to serially track the tumor response to therapy.

Results: Data indicated that ultrasound-derived microvascular density can indicate response to therapy a week prior to changes in tumor volume and is strongly correlated with physiological characteristics of the tumors as measured by histology ([Formula: see text]). Furthermore, data demonstrated that ultrasound measurements of vascular density can determine response to therapy and classify between-treatment groups with high sensitivity and specificity.

Conclusion/significance: Results suggests that future applications utilizing ultrasound imaging to monitor tumor response to therapy may be able to provide earlier insight into tumor behavior from metrics of microvascular density rather than anatomical tumor size measurements.

Publication types

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

MeSH terms

  • Angiogenesis Inhibitors / pharmacology*
  • Angiography / methods
  • Animals
  • Carcinoma, Renal Cell* / blood supply
  • Carcinoma, Renal Cell* / diagnostic imaging
  • Drug Monitoring
  • Female
  • Heterografts
  • Kidney / blood supply
  • Kidney / diagnostic imaging
  • Kidney Neoplasms* / blood supply
  • Kidney Neoplasms* / diagnostic imaging
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Microvessels* / diagnostic imaging
  • Microvessels* / drug effects
  • Microvessels* / pathology
  • Ultrasonography / methods*

Substances

  • Angiogenesis Inhibitors