Computerized assessment of vessel morphological changes during treatment of glioblastoma multiforme: report of a case imaged serially by MRA over four years

Abstract

A patient with glioblastoma multiforme underwent serial computerized analysis of tumor-associated vasculature defined from magnetic resonance angiographic (MRA) scans obtained over almost a four year period. The clinical course included tumor resection with subsequent radiation therapy, a long symptom-free interval, emergence of a new malignant focus, resection of that focus, a stroke, and treatment with chemotherapy and anti-angiogenic therapy. Image analysis methods included segmentation of vessels from each MRA and statistical comparison of vessel morphology over 4 regions of interest (the initial tumor site, the second tumor site, a distant control region, and the entire brain) to the same 4 regions of interest in 50 healthy volunteers (26 females and 24 males; mean age 39 years). Results suggested that following completion of focal radiation therapy (RT) vessel shape abnormalities, if elevated at the time of RT completion, may progressively normalize for months in focal regions, that progressively severe vessel shape abnormalities can precede the emergence of a gadolinium enhancing lesion by months, that lesion resection can produce a dramatic but highly transient drop in abnormal vessel tortuosity both focally and globally, and that treatment with anti-angiogenic agents does not necessarily normalize vessel shape. Quantitative measurements of vessel morphology as defined from MRA may provide useful insights into tumor development and response to therapy.

Figure 1

T1-gadolinium enhanced (left) and T2 (right) MR slices obtained over time. A: Initial scan (month 0). Ring-enhancing tumor with a small amount of surrounding edema. B: Month 3. The tumor has been resected and radiation therapy delivered. There is no gadolinium enhancement and no edema. Arrow points to a gliadel wafer. C: Month 32. Development of a second lesion. D: Month 34. Enlargement of the second lesion and expansion of edema. E: Month 37. The second lesion has been resected. There is an emerging occipital lobe infarction. F: Month 48. Old occipital lobe infarction with patchy surrounding enhancement.

Figure 2

Vessels and segmented tumor/edema from Region 2. Red = anterior cerebral group, cyan = left middle cerebral group, blue = right middle cerebral group, gold = posterior cerebral group. Grey = tumor + edema as defined from T1 and registered into the coordinate system of the vessels. Arrows point to two vessels close to but outside of the apparent tumor confines and that exhibit abnormal, high-frequency, low-amplitude oscillations detectable by SOAM.

Figure 3

Malignancy Probability (MP) over time (months since diagnosis) in the region of the initial lesion. Black arrow: time of completion of radiation therapy. Red arrow: time at which a new gadolinium-enhancing lesion was first noted. Gold arrow: Total gross resection of new lesion. Blue arrow: initiation of bevacizumab therapy. An increase or decrease of 20 in the MP is viewed as significant.

Figure 4

Malignancy Probability (MP) over time (months since diagnosis) in the region of the second lesion. Arrows provide the same time points as Figure 3. Two data points are missing because the patient suffered a stroke involving this region and an insufficient number of vessels were present for analysis.

Figure 5

Malignancy Probability (MP) over time (months since diagnosis) in the control right frontal region. Arrows provide the same time points as Figure 3.

Figure 6

Malignancy Probability (MP) over time (months since diagnosis) in the entire brain. Arrows provide the same time points as Figure 3.