Malignancy-associated vessel tortuosity: a computer-assisted, MR angiographic study of choroid plexus carcinoma in genetically engineered mice

Abstract

Background and purpose: The ability to assess tumor malignancy and monitor treatment response noninvasively would be of value to both clinicians and animal investigators. This report describes the MR imaging characteristics of a genetically engineered mouse model of choroid plexus carcinoma (CPC) during tumor growth and progression to malignancy. We assess the ability of vessel tortuosity measurements, as calculated from high-resolution MR angiographic (MRA) images, to detect emerging CPC cancers.

Methods: MR images of 9 healthy mice and of 20 CPC mice with precancerous choroid dysplasia or with cancer over a wide range of sizes were analyzed. Two vessel tortuosity measures and a measure of vessel attenuation (vessel count) were calculated from MRA images. Malignancy assessment was based upon a statistical analysis of vessel tortuosity, by using an equation derived from an earlier study of human brain tumor patients.

Results: Choroid dysplasia was correctly judged nonmalignant. On the basis of vessel count, neoangiogenesis could not be detected until cancers were full-blown and had reached a volume of approximately 80 mm3. Vessel tortuosity measurements, however, correctly identified emerging malignancy in lesions larger than 0.3 mm3.

Conclusion: To the best of our knowledge, this report provides the first description of in vivo, MR imaging characteristics of genetically engineered CPC mice during the progression from dysplasia to cancer. Vessel tortuosity measurements offer promise of correctly defining even tiny tumors as malignant.

Fig 1.

Choroid dysplasia. Top row, left to right, coronal T1, T2, T1-GAD, and MRA sections. Bottom row, left, H&E–stained coronal histologic section. Bar = 200 μm. Note the thickened and somewhat disorganized choroid at left (arrows). Center and right, 3D segmented vessels with the ventricular system shown at full opacity (center) and no opacity (right). Vessels are shown from an anteroposterior (AP) view and are color-coded relative to the ventricular system with blue (outside), gold (traverse), red (inside), and cyan (exit or enter). Vessel analysis was performed upon all red vessels and upon the segments of the gold and cyan vessels lying within the region of interest. This case is tumor 19 in Table.

Fig 2.

Emerging cancer. Top row, left to right, T1, T2, T1-GAD, and MRA sections. Arrow points to multiple, tiny cancers visible in the T2 image. Bottom row, left, H&E histologic section. Note the tiny cancer foci (arrows). Bar = 200 μm. Center and right, 3D rendering of segmented vessels with the segmented ventricular system shown at full (center) and no (right) opacity from an AP view. Vessel color coding is as outlined in Fig 2. This case is tumor 15 in the Table.

Fig 3.

Typical vessel tortuosity abnormality in one of the CPC mice during early cancer development. Note the “many bends upon each larger bend” present in the highlighted (red) vessel.

Fig 4.

Terminal CPC tumor. Top row, a massive tumor is shown from left to right in T1, T2, T1-GAD, and MRA sections. Arrow points to the tumor as seen on T1-Gad. The contralateral ventricular system is dilated. Bottom row, left, H&E histologic section from this animal. Bar = 200 μm. Center and right, 3D rendering of an AP view of segmented vessels and with the segmented tumor shown at full (center) and no (right) opacity. Vessel color coding is outlined in Fig 2. This tumor is case 5 in the Table.