Abnormal vessel tortuosity as a marker of treatment response of malignant gliomas: preliminary report

Abstract

Despite multiple advances in medical imaging, noninvasive monitoring of therapeutic efficacy for malignant gliomas remains problematic. An underutilized observation is that malignancy induces characteristic abnormalities of vessel shape. These characteristic shape abnormalities affect both capillaries and much larger vessels in the tumor vicinity, involve larger vessels prior to sprout formation, and are generally not present in hypervascular benign tumors. Vessel shape abnormalities associated with malignancy thus may appear independently of increase in vessel density. We hypothesize that an automated, computerized analysis of vessel shape as defined from high-resolution MRA can provide valuable information about tumor activity during the treatment of malignant gliomas. This report describes vessel shape properties in 10 malignant gliomas prior to treatment, in 2 patients in remission during treatment, and in 2 patients with recurrent disease. One subject was scanned multiple times. The method involves an automated, statistical analysis of vessel shape within a region of interest for each tumor, normalized by the values obtained from the vessels within the same region of interest of 34 healthy subjects. Results indicate that untreated tumors display statistically significant vessel tortuosity abnormalities. These abnormalities involve vessels not only within the tumor margins as defined from MR but also vessels in the surrounding tissue. The abnormalities resolve during effective treatment and recur with tumor recurrence. We conclude that vessel shape analysis could provide an important means of assessing tumor activity.

Figure 1

Registration of a subject’s images into a common coordinate system using both rigid and affine transformations. By a combination of forward and backward mapping, a region of interest defined from any image can then be mapped into the undeformed space of any other image that has been also mapped to the same common coordinate system.

Figure 2

Hollow shell dilation about tumor surface. Far left: T1-GAD slice. Subsequent images show the same slice with the region of interest superimposed in white. From left to right, the region of interest is the tumor and then ring dilation 1, ring dilation 2, ring dilation 5, and ring dilation 10. Note that the dilations cover a large volume of the head.

Figure 3

Malignant tumor vasculature is characterized by “many smaller bends upon each larger bend” (left). An abnormal increase in larger bends (center) can be detected by the ICM, and an abnormal increase in smaller bends (right) can be detected by SOAM. Malignant tumor vasculature tends to exhibit increased tortuosity by both metrics, with the SOAM of greatest prognostic significance.

Figure 4

Terminal branches. The oval represents the region of interest. The two thick vessels are vessels of passage. The three fine vessels are terminal branches that, by definition, are entirely contained within the region of interest.

Figure 5

Tortuosity abnormality in malignancy. There are many small, sharp bends superimposed upon each larger bend in the abnormal vessels. Arrows point to examples of the small, sharp bends.

Figure 6

Vessel tortuosity abnormalities in untreated glioblastoma.

Figure 7

Tortuosity abnormalities in an untreated glioma grade III.

Figure 8

Progressive resolution of abnormal vessel tortuosity patterns in a GBM patient undergoing successful therapy.

Figure 9

Vessel shape was within normal range in this glioma III patient responsive to treatment.

Figure 10

Vessel shape measures were abnormal with recurrent glioblastoma.