title: Comparison of photoacoustically derived hemoglobin and oxygenation measurements with contrast-enhanced ultrasound estimated vascularity and immunohistochemical staining in a breast cancer model.
abstract: In this preliminary study, we compared two noninvasive techniques for imaging intratumoral physiological conditions to immunohistochemical staining in a murine breast cancer model. MDA-MB-231 tumors were implanted in the mammary pad of 11 nude rats. Ultrasound and photoacoustic (PA) scanning were performed using a Vevo 2100 scanner (Visualsonics, Toronto, Canada). Contrast-enhanced ultrasound (CEUS) was used to create maximum intensity projections as a measure of tumor vascularity. PAs were used to determine total hemoglobin signal (HbT), oxygenation levels in detected blood (SO2 Avg), and oxygenation levels over the entire tumor area (SO2 Tot). Tumors were then stained for vascular endothelial growth factor (VEGF), cyclooxygenase-2 (Cox-2), and the platelet endothelial cell adhesion molecule CD31. Correlations between findings were analyzed using Pearson's coefficient. Significant correlation was observed between CEUS-derived vascularity measurements and both PA indicators of blood volume (r = 0.49 for HbT, r = 0.50 for SO2 Tot). Cox-2 showed significant negative correlation with SO2 Avg (r = -0.49, p = 0.020) and SO2 Tot (r = -0.43, p = 0.047), while CD31 showed significant negative correlation with CEUS-derived vascularity (r = -0.47, p = 0.036). However, no significant correlation was observed between VEGF expression and any imaging modality (p > 0.08). Photoacoustically derived HbT and SO2 Tot may be a good indicator of tumor fractional vascularity. While CEUS correlates with CD31 expression, photoacoustically derived SO2 Avg appears to be a better predictor of Cox-2 expression.
authors.affiliation: Department of Radiology, Thomas Jefferson University, Philadelphia, PA, USA.
authors.forename: John R
authors.initials: JR
authors.lastname: Eisenbrey
authors.affiliation: Department of Radiology, Thomas Jefferson University, Philadelphia, PA, USA.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Merton
authors.affiliation: Department of Radiology, Thomas Jefferson University, Philadelphia, PA, USA School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, PA, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Marshall
authors.affiliation: Department of Radiology, Thomas Jefferson University, Philadelphia, PA, USA.
authors.forename: Ji-Bin
authors.initials: JB
authors.lastname: Liu
authors.affiliation: Department of Radiological Sciences, Jefferson School of Health Professions, Thomas Jefferson University, Philadelphia, PA, USA.
authors.forename: Traci B
authors.initials: TB
authors.lastname: Fox
authors.affiliation: Department of Radiology, Thomas Jefferson University, Philadelphia, PA, USA Department of Electrical and Computer Engineering, Drexel University, Philadelphia, PA, USA.
authors.forename: Anush
authors.initials: A
authors.lastname: Sridharan
authors.affiliation: Department of Radiology, Thomas Jefferson University, Philadelphia, PA, USA flemming.forsberg@jefferson.edu.
authors.forename: Flemming
authors.initials: F
authors.lastname: Forsberg
mesh_terms: D000818:Animals; D051546:Cyclooxygenase 2 / Q000378:metabolism; D005260:Female; D006801:Humans; D007089:Image Enhancement; D007150:Immunohistochemistry; D008325:Mammary Neoplasms, Experimental / Q000098:blood supply / Q000000981:diagnostic imaging* / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000000981:diagnostic imaging*; D010100:Oxygen / Q000097:blood; D061088:Photoacoustic Techniques; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D011923:Rats, Nude; D014463:Ultrasonography; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D019408:Platelet Endothelial Cell Adhesion Molecule-1; D042461:Vascular Endothelial Growth Factor A; D051546:Cyclooxygenase 2; D010100:Oxygen
keywords: Cox-2; angiogenesis; oxygenation; photoacoustics; ultrasound contrast agents