Tumor vascular architecture and function evaluated by non-invasive susceptibility MRI methods and immunohistochemistry.
OBJECTIVE
To investigate the physiological origins responsible for the varying blood oxygenation level dependent (BOLD) magnetic resonance imaging (MRI) responses to carbogen (95% O(2)/5% CO(2)) breathing observed with different tumor types.


METHODS
Susceptibility contrast-enhanced MRI using the exogenous blood pool contrast agent NC100150 to determine blood volume and vessel size, and immunohistochemical-derived morphometric parameters, were determined in GH3 prolactinomas and RIF-1 fibrosarcomas, both grown in mice, which exhibited very different BOLD responses to carbogen.


RESULTS
Administration of NC100150 increased the R(2)* and R(2) rates of both tumor types, and indicated a significant four-fold larger blood volume in the GH3 tumor. The ratio deltaR(2)*/deltaR(2) showed that the capillaries in the GH3 were two-fold larger than those in the RIF-1, in agreement with morphometric analysis. Carbogen breathing induced a significant 25% decrease in R(2)* in the GH3 prolactinoma, whereas the response in the RIF-1 fibrosarcoma was negligible.


CONCLUSIONS
Low blood volume and small vessel size (and hence reduced hematocrit) are two reasons for the lack of R(2)* change in the RIF-1 with carbogen breathing. BOLD MRI is sensitive to erythrocyte-perfused vessels, whereas exogenous contrast agents interrogate the total perfused vascular volume. BOLD MRI, coupled with a carbogen challenge, provides information on functional, hemodynamic tumor vasculature.
Robinson
Simon P
SP
Department of Basic Medical Sciences, St George's Hospital Medical School, London, UK. s.robinson@sghms.ac.uk
Rijken
Paul F J W
PF
Howe
Franklyn A
FA
McSheehy
Paul M J
PM
van der Sanden
Boudewijn P J
BP
Heerschap
Arend
A
Stubbs
Marion
M
van der Kogel
Albert J
AJ
Griffiths
John R
JR
D000818:Animals; D002245:Carbon Dioxide / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D003911:Dextrans; D005260:Female; D052203:Ferrosoferric Oxide; D005354:Fibrosarcoma / Q000378:metabolism; D007150:Immunohistochemistry; D007501:Iron; D008279:Magnetic Resonance Imaging / Q000379:methods*; D058185:Magnetite Nanoparticles; D015674:Mammary Neoplasms, Animal / Q000378:metabolism; D051379:Mice; D009369:Neoplasms / Q000378:metabolism*; D010087:Oxides; D010100:Oxygen / Q000378:metabolism*; D015175:Prolactinoma / Q000378:metabolism
D003911:Dextrans; D058185:Magnetite Nanoparticles; D010087:Oxides; C097921:ferumoxtran-10; D002245:Carbon Dioxide; D007501:Iron; D010100:Oxygen; D052203:Ferrosoferric Oxide