title: Correlation of ultrasound contrast agent derived blood flow parameters with immunohistochemical angiogenesis markers in murine xenograft tumor models.
abstract: OBJECTIVE
  In this study we used temporal analysis of ultrasound contrast agent (UCA) estimate blood flow dynamics and demonstrate their improved correlation to angiogenesis markers relative to previously reported, non-temporal fractional vascularity estimates.
  
  
  METHODS
  Breast tumor (NMU) or glioma (C6) cells were implanted in either the abdomen or thigh of 144 rats. After 6, 8 or 10 days, rats received a bolus UCA injection of Optison (GE Healthcare, Princeton, NJ; 0.4 ml/kg) during power Doppler imaging (PDI), harmonic imaging (HI), and microflow imaging (MFI) using an Aplio ultrasound scanner with 7.5 MHz linear array (Toshiba America Medical Systems, Tustin, CA). Time-intensity curves of contrast wash-in were constructed on a pixel-by-pixel basis and averaged to calculate maximum intensity, time to peak, perfusion, and time integrated intensity (TII). Tumors were then stained for four immunohistochemical markers (bFGF, CD31, COX-2, and VEGF). Correlations between temporal parameters and the angiogenesis markers were investigated for each imaging mode. Effects of tumor model and implant location on these correlations were also investigated.
  
  
  RESULTS
  Significant correlation over the entire dataset was only observed between TII and VEGF for all three imaging modes (R=-0.35, -0.54, -0.32 for PDI, HI and MFI, respectively; p<0.0001). Tumor type and location affected these correlations, with the strongest correlation of TII to VEGF found to be with implanted C6 cells (R=-0.43, -0.54, -0.52 for PDI, HI and MFI, respectively; p<0.0002).
  
  
  CONCLUSIONS
  While UCA-derived temporal blood flow parameters were found to correlate strongly with VEGF expression, these correlations were also found to be influenced by both tumor type and implant location.
authors: Department of Radiology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
authors: John R
authors: JR
authors: Eisenbrey
authors: Christian C
authors: CC
authors: Wilson
authors: Raymond J
authors: RJ
authors: Ro
authors: Traci B
authors: TB
authors: Fox
authors: Ji-Bin
authors: JB
authors: Liu
authors: See-Ying
authors: SY
authors: Chiou
authors: Flemming
authors: F
authors: Forsberg
mesh_terms: D000418:Albumins / Q000493:pharmacokinetics*; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D001783:Blood Flow Velocity; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology; D003287:Contrast Media / Q000493:pharmacokinetics*; D004195:Disease Models, Animal; D005260:Female; D005466:Fluorocarbons / Q000493:pharmacokinetics*; D005910:Glioma / Q000000981:diagnostic imaging* / Q000473:pathology; D007150:Immunohistochemistry; D009389:Neovascularization, Pathologic / Q000000981:diagnostic imaging*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014183:Transplantation, Heterologous; D014463:Ultrasonography; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D000418:Albumins; D015415:Biomarkers; D003287:Contrast Media; C099458:FS 069; D005466:Fluorocarbons; D042461:Vascular Endothelial Growth Factor A
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