Tracy McKnight

Research Interests

In vivo and ex vivo investigation of brain tumors using molecular imaging techniques

Research Summary

The aims of the current project are to use MR spectroscopy, immunocytochemistry (ICC), and genetic assays to characterize the metabolic, biochemical, and genetic properties of low-grade human glial tumors. In vivo magnetic resonance spectroscopic (MRS) parameters of brain tumors will be correlated with ex vivo measures of malignancy in surgically resected tissue specimens from low- and mid-grade gliomas in an effort define the onset of anaplasia at both a macroscopic and microscopic level. The overall goal is to ascertain features of low-grade tumors that correlate with increased growth rate and invasiveness that may be detected with in vivo MRS. Surgical specimens obtained from various regions within the tumor that exhibit different in vivo MRS profiles are analyzed with high-resolution magic angle spinning (HRMAS) MRS in a 500 MHz (7.9T) vertical bore magnet. The HRMAS MRS data provides a more detailed picture of the underlying chemical makeup of the tissue due to the gain in chemical dispersion that is achieved at higher magnetic fields. An additional benefit of the HRMAS method is that it is non-destructive allowing for subsequent analysis of the specimens using other assays. We use digital fluorescence microscopy and ICC to probe the cellularity, mitotic activity, and vascularity of the tissue specimens after they are analyzed with HRMAS MRS. Additional molecular assays will include measurements of the apoptotic/necrotic fraction, expression of various molecular markers of gliomas (e.g. p53, EGFR, PDGF-beta, PTEN), and chromosome analyses (fluorescence in-situ hybridization, FISH). Correlations between the HRMAS, ICC, genetic data will be explored in an effort to find new markers of malignancy that can be detected with high-field MRS.

Selected Publications

1. McKnight, T.R., S.M. Noworolski,, D.B. Vigneron, and S.J. Nelson. An automated technique for the quantitative assessment of 3D-MRSI data from patients with glioma. J. Magn. Reson. Imaging 13:167-177, 2001.

2. Pirzkall, A., T.R. McKnight, E.E. Graves, M.P. Carol, P.K. Sneed, W.W. Wara, S.J. Nelson, L.J. Verhey, D.A. Larson. MR-spectroscopy guided target delineation for high-grade gliomas, Int. J. Radiation Oncology Biol. Phys., Vol. 50:4 915-928, 2001

3. McKnight, T.R., M, von dem Bussche, D.B. Vigneron, M.S. Berger, M.W. McDermott, W.P. Dillon, S.J. Nelson. Validation of a Cho-NAA index of likelihood of tumor presence: a comparison of 1H-MRSI data and histopathology from patients with untreated glioma. J Neurosurgery, in press.

4. McKnight, T.R. and Curry, F.E. Mechanisms of heterogeneous endothelial cytoplasmic calcium increases in venular microvessels. Microcirculation, submitted.