title: Investigating temporal fluctuations in tumor vasculature with combined carbogen and ultrasmall superparamagnetic iron oxide particle (CUSPIO) imaging.
abstract: A combined carbogen ultrasmall superparamagnetic iron oxide (USPIO) imaging protocol was developed and applied in vivo in two murine colorectal tumor xenograft models, HCT116 and SW1222, with established disparate vascular morphology, to investigate whether additional information could be extracted from the combination of two susceptibility MRI biomarkers. Tumors were imaged before and during carbogen breathing and subsequently following intravenous administration of USPIO particles. A novel segmentation method was applied to the image data, from which six categories of R(2)* response were identified, and compared with histological analysis of the vasculature. In particular, a strong association between a negative ΔR(2)*(carbogen) followed by positive ΔR(2)*(USPIO) with the uptake of the perfusion marker Hoechst 33342 was determined. Regions of tumor tissue where there was a significant ΔR(2)*(carbogen) but no significant ΔR(2)*(USPIO) were also identified, suggesting these regions became temporally isolated from the vascular supply during the experimental timecourse. These areas correlated with regions of tumor tissue where there was CD31 staining but no Hoechst 33342 uptake. Significantly, different combined carbogen USPIO responses were determined between the two tumor models. Combining ΔR(2)*(carbogen) and ΔR(2)*(USPIO) with a novel segmentation scheme can facilitate the interpretation of susceptibility contrast MRI data and enable a deeper interrogation of tumor vascular function and architecture.
authors.affiliation: Cancer Research UK and EPSRC Cancer Imaging Centre, The Institute of Cancer Research, Belmont, Sutton, Surrey, United Kingdom. Jake.Burrell@icr.ac.uk
authors.forename: Jake S
authors.initials: JS
authors.lastname: Burrell
authors.forename: Simon
authors.initials: S
authors.lastname: Walker-Samuel
authors.forename: Lauren C J
authors.initials: LC
authors.lastname: Baker
authors.forename: Jessica K R
authors.initials: JK
authors.lastname: Boult
authors.forename: Anderson J
authors.initials: AJ
authors.lastname: Ryan
authors.forename: John C
authors.initials: JC
authors.lastname: Waterton
authors.forename: Jane
authors.initials: J
authors.lastname: Halliday
authors.forename: Simon P
authors.initials: SP
authors.lastname: Robinson
mesh_terms: D000818:Animals; D002245:Carbon Dioxide / Q000378:metabolism*; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000098:blood supply / Q000473:pathology* / Q000503:physiopathology; D004195:Disease Models, Animal; D005260:Female; D005290:Ferric Compounds / Q000378:metabolism*; D005453:Fluorescence; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008280:Magnetics; D051379:Mice; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000175:diagnosis*; D010100:Oxygen / Q000378:metabolism*; D011838:Radiation-Sensitizing Agents / Q000378:metabolism; D013997:Time Factors
chemical_list: D005290:Ferric Compounds; D011838:Radiation-Sensitizing Agents; D002245:Carbon Dioxide; C000499:ferric oxide; C011700:carbogen; D010100:Oxygen