title: Perfusion CT assessment of tissue hemodynamics following hepatic arterial infusion of increasing doses of angiotensin II in a rabbit liver tumor model.
abstract: OBJECTIVE
  To investigate the effects of increasing doses of angiotensin II on hepatic hemodynamics in the normal rabbit liver and in hepatic VX2 tumors by using dynamic contrast material-enhanced perfusion computed tomography (CT).
  
  
  METHODS
  This study was approved by the institutional animal care and use committee. Solitary hepatic VX2 tumors were implanted into 12 rabbits. In each animal, perfusion CT of the liver was performed before (at baseline) and after hepatic arterial infusion of varying doses (0.1-50.0 μg/mL) of angiotensin II. Images were acquired continuously for 80 seconds after the start of the intravenous contrast material administration. Blood flow (BF), blood volume (BV), mean transit time (MTT), and capillary permeability-surface area product were calculated for the tumor and the adjacent and distant normal liver tissue. Generalized linear mixed models were used to estimate the effects of angiotensin II dose on outcome measures.
  
  
  RESULTS
  Angiotensin II infusion increased contrast enhancement of the tumor and distal liver vessels. Tumor BF increased in a dose-dependent manner after administration of 0.5-25.0 μg/mL angiotensin II, but only the 2.5 μg/mL dose induced a significant increase in tumor BF compared with BF in the adjacent (68.0 vs 26.3 mL/min/100 g, P < .0001) and distant (68.0 vs 28.3 mL/min/100 g, P = .02) normal liver tissue. Tumor BV varied with angiotensin II dose but was greater than the BV of the adjacent and distant liver tissue at only the 2.5 μg/mL (4.8 vs 3.5 mL/100 g for adjacent liver [P < .0001], 4.8 vs 3.3 mL/100 g for distant liver [P = .0006]) and 10.0 μg/mL (4.9 vs 4.4 mL/100 g for adjacent liver [P = .007], 4.9 vs 4.3 mL/100 g for distant liver [P = .04]) doses. Tumor MTT was significantly shorter than the adjacent liver tissue MTT at angiotensin II doses of 2.5 μg/mL (9.7 vs 15.8 sec, P = .001) and 10.0 μg/mL (5.1 vs 13.2 sec, P = .007) and significantly shorter than the distant liver tissue MTT at 2.5 μg/mL only (9.7 vs 15.3 sec, P = .0006). The capillary permeability-surface area product for the tumor was higher than that for the adjacent liver tissue at the 2.5 μg/mL angiotensin II dose only (11.5 vs 8.1 mL/min/100 g, P = .01).
  
  
  CONCLUSIONS
  Perfusion CT enables a mechanistic understanding of angiotensin II infusion in the liver and derivation of the optimal effective dose. The 2.5 μg/mL angiotensin II dose increases perfusion in hepatic VX2 tumors versus that in adjacent and distant normal liver tissue primarily by constricting normal distal liver vessels and in turn increasing tumor BF and BV.
authors.affiliation: Department of Diagnostic Radiology, Section of Interventional Radiology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030-4009, USA. kwright@mdanderson.org
authors.forename: Kenneth C
authors.initials: KC
authors.lastname: Wright
authors.forename: Murali K
authors.initials: MK
authors.lastname: Ravoori
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Dixon
authors.forename: Lin
authors.initials: L
authors.lastname: Han
authors.forename: Sheela P
authors.initials: SP
authors.lastname: Singh
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
authors.forename: Sanjay
authors.initials: S
authors.lastname: Gupta
authors.forename: Valen E
authors.initials: VE
authors.lastname: Johnson
authors.forename: Zuxing
authors.initials: Z
authors.lastname: Kan
authors.forename: Vikas
authors.initials: V
authors.lastname: Kundra
mesh_terms: D000804:Angiotensin II / Q000008:administration & dosage*; D000818:Animals; D001783:Blood Flow Velocity; D003287:Contrast Media / Q000008:administration & dosage; D007089:Image Enhancement / Q000379:methods; D036502:Infusions, Intralesional; D008102:Liver Circulation; D008114:Liver Neoplasms, Experimental / Q000000981:diagnostic imaging* / Q000503:physiopathology*; D055420:Perfusion Imaging / Q000379:methods*; D011817:Rabbits; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014057:Tomography, X-Ray Computed / Q000379:methods*; D014662:Vasoconstrictor Agents / Q000008:administration & dosage
chemical_list: D003287:Contrast Media; D014662:Vasoconstrictor Agents; D000804:Angiotensin II