Comparison of Quantitative Histologic Micro Vessel Density and 8 Tesla MR Imaging in Patients with Gliomas

D. W. Chakeres, G. A. Christoforidis, A. RayChaudhury, A. Abduljalil, A. Kangarlu, M. Yang The Ohio State University College of Medicine and School of Public Health, Columbus, Ohio, United States Synopsis This study compares the quantitative histologic density of micro vessels ranging from 10-200 microns in five human glioma subjects to corresponding 8 Tesla (T) high resolution gradient echo (GE) MR images. A substantial increase in the histologic density of vessels ranging from 10-100 microns was observed in the higher grade tumors. This correlated with an increase in tumor microvascularity on 8 T images. Methods The MR images were acquired with an 80 cm bore MagnexGeneral Electric (Abingdon, U.K.) 8T system with a water-cooled asymmetric gradient controlled by a Bruker Avance (Billerica, MA, U.S.A.) console. Five subjects were evaluated (ages 31-53 year, average 38, males 3, females 2, 4 in vivo, 1 post mortem). In vivo subjects signed informed consent forms and were studied under IRB supervision. Typical imaging parameters were TR 600, TE 10, slice thickness of 2 mm, fields of view of 20 cm, flip-angle approximately 20 o and a matrix of 1024 or 512. Two Neuroradiologists reviewed the 8T MR images. Areas of increased microvascularity within the tumor bed on the 8 T images were analyzed on a semi-quantitative 3-tier scale (high, medium and low). The relative size and density of the tumor vessels were compared to normal cortical penetrating vessels and determined to be small if they were smaller in diameter than cortical penetrating vessels, medium if they were equal in size to the cortical penetrating vessels and large if they were larger than cortical penetrating vessels. Histological sections were stained with reticulum to highlight the blood vessels (arteries and veins). Two normal cortical regions were evaluated as controls. At least four photographs of 40x and 450x microscopic magnification were acquired for each histological specimen. Only intra-parenchymal vessels were counted. On the 40x magnification the number of vessels per field (VPF) larger than 100 microns and those measuring 20-100 microns were recorded. Vessels per 450x magnification field greater than 10 microns were also counted. The histological vessel densities were compared to the World Health Organization (WHO) tumor grade and the 8 T MRI qualitative grading scales (Table 1). Results The average normal and abnormal VPF densities are shown in Table 1. High-grade tumors demonstrated increased vessel densities for all sizes. The VPF differences were greatest for the 450x magnification 10-micron vessels, but there were significant increases in the VPF for the 20-100 microns on the 40x magnification fields. In general the low-grade tumors demonstrated low vessel densities, but some of the higher-grade tumors also had low VPF densities. Apparent vessel densities on the 8 T images varied widely throughout the tumor mass. The low-grade tumors had few vessels seen on 8 T imaging (Figure 1). The glioblastoma multiforme subjects did demonstrate regions of high vessel densities on 8 T imaging. The correlation between 8 T imaging and the histologic VPF densities was not exact. Discussion Magnetic susceptibility changes induced by venous deoxyhemoglobin allows for definition of small veins with GE techniques (1,2). One important application of such microscopic visualization is in the monitoring of microvasculature formation in brain tumors. High field high-resolution GE MR imaging has demonstrated multiple pathologically large and tortuous micro vessels within in vivo human brain tumors. This pattern is similar to the known microscopic distortions of brain tumor vasculature at the histological level (3,4). High-grade tumors demonstrate regions of high microvascular density of vessels in the range of 10 μm. Evaluation of vessels in the range visible with 8 T MRI has not been the focus of histological studies so there is little data available. 8 T GE imaging is able to define micro vessels in the range of 200 microns and possibly smaller due to vessel paramagnetic susceptibility effect. Data presented here suggests that there may be a concomitant increase in the density of vessels 20-100 microns in size and >100 microns in high-grade tumors which may also be identified on 8 T high resolution GE MRI. Brain tumors are known to be quite variable so two different biopsy locations may demonstrate different vessel densities and grades for the same tumor.