Genetically engineered mice offer a substrate to study tumors and tumor-associated vasculature under conditions in which cohorts of animals can be studied at one time, in which therapy can be standardized, in which genetic manipulation can provide insights into tumor pathogenesis and treatment, and, importantly, in which whole-brain histology is available at arbitrary moments in time. It is therefore possible to address questions relevant to tumor treatment and to the roles of individual molecular pathways in ways that cannot be addressed directly in human subjects.

We have developed methods to image mice by 3T MR so as to include good quality T1, T2, T1-GAD, and MRA images of the brain, and have collected a "healthy mouse database" of 10 mice. One early study addressed the question as to how large a tiny cancer must be before the surrounding vessels develop vessel shape abnormalities indicative of malignancy. Results in mice with carcinoma indicate that an increase in vessel number is not apparent by MRA until tumor volume is approximately 80 cubic mm3, but that vessel shape abnormalities become evident for cancerss greater than 1 cubic mm with imaging performed at 100 x 100 x 100 microns. The same "Malignancy Probability" equation used in human patients appears applicable to the mouse.

We believe that this approach to tumor-vessel analysis in genetically engineered mice offers high promise of providing better understanding of tumor development and growth and of devising effective treatments extensible to human subjects.

Partially supported by a Whitaker award to Terry Van Dyke, with methods developed under R01 EB000219 NIH-NIBIB. Newer work has been/will be supported by R01 CA124608 NIH-NCI.

Brubaker L, Bullitt E, Yin C, Van Dyke T, Lin W (2005) MRA visualization of abnormal tumor vasculature in genetically engineered mice. Cancer Research 65: 8218-8223 <pdf>. Cancer Research Highlight.

Bullitt E, Wolthusen A, Brubaker L, Lin W, Zeng D, Van Dyke T (2006) Malignancy-associated vessel tortuosity: A computer-assisted, MRA study of choroid plexus carcinoma in genetically engineered mice. AJNR 27: 612-619. <pdf>

Bullitt E, Aylward SR, Van Dyke T, Lin W (2007) Computer-Assisted Measurement of Vessel Shape from 3T Magnetic Resonance Angiography of Mouse Brain. Elsevier Methods 43:29-34. <pdf>