Vessel tortuosity and brain tumor malignancy: a blinded study

Abstract

Rationale and objectives: Malignancy provokes regional changes to vessel shape. Characteristic vessel tortuosity abnormalities appear early during tumor development, affect initially healthy vessels, spread beyond the confines of tumor margins, and do not simply mirror tissue perfusion. The ability to detect and quantify tortuosity abnormalities on high-resolution magnetic resonance angiography (MRA) images offers a new approach to the noninvasive diagnosis of malignancy. This report evaluates a computerized, statistical method of analyzing the shapes of vessels extracted from MRA in diagnosing cancer.

Materials and methods: The regional vasculature of 34 healthy subjects was compared with the tumor-associated vasculature of 30 brain tumors before surgical resection. The operator performing the analysis was blinded to the diagnosis. Vessels were segmented from an MRA of each subject, a region of interest was defined in each tumor patient and was mapped to all healthy controls, and a statistical analysis of vessel shape measures was then performed over the region of interest. Many difficult cases were included, such as pinpoint, hemorrhagic, and irradiated tumors, as were hypervascular benign tumors. Tumors were identified as benign or malignant on the basis of histological evaluation.

Results: A discriminant analysis performed at the study's conclusion successfully classified all but one of the 30 tumors as benign or malignant on the basis of vessel tortuosity.

Conclusions: Quantitative, statistical measures of vessel shape offer a new approach to the diagnosis and staging of disease. Although the methods developed under the current report must be tested against a new series of cases, initial results are promising.

Figure 1

Examples of tortuosity types. A: High frequency wiggles resulting in high curvature per unit distance. This type of tortuosity is characterized by elevated SOAM values. B: larger amplitude curve with frequent changes of direction and a short distance between endpoints. This type of tortuosity is characterized by elevated ICM values. C: T1 gadolinium-enhanced slice of a malignant tumor. D: 3D rendering of segmented tumor and vessels. E: Magnification of a cluster of tumor-associated vessels. The smooth vessels in the foreground lie far outside of the lesion and have a normal shape. The vessels within or traversing the tumor exhibit abnormal tortuosity by both metrics (arrows).

Figure 2

Malignant tumor and associated vessels (left) and benign tumor with associated vessels (right) in the same patient. Note that the vessels associated with the malignant tumor have high-frequency wiggles, but that the vessels associated with the benign tumor are smooth.

Figure 3

Tiny malignant melanoma (left) and metastatic lung carcinoma (right). Arrows point to the relevant tumors. Vessel shape abnormalities extend well outside of the tumor surface, enabling the diagnosis of malignancy even if the lesion is too small to contain vessels delineated by MRA.

Figure 4

The shapes of vessels associated with a hypervascular benign tumor (hemangioblastoma). A T1 gadolinium-enhanced slice is shown at left, and a 3D rendering of the tumor-associated vessels at right. Note the relatively smooth shapes of the vessels as compared to those associated with malignancy and shown in Figures 1 and 2.