The Use of Magnetic Resonance Imaging to Noninvasively Detect Genetic Signatures in Oligodendroglioma Robert Brown, 1 Magdalena Zlatescu, 2,7 Angelique Sijben, 2 Gloria Roldan, 2,3 Jay Easaw, 3,7 Peter Forsyth, 3,7 Ian Parney, 2,7 Robert Sevick, 4,6,8 ElizabethYan, 3 Douglas Demetrick, 5 David Schiff, 9 Gregory Cairncross, 2,7,8 and Ross Mitchell 1,4,6,8 Abstract Background: Some patients with low-grade glioma have extraordinarily long survival times; current, early treatment does not prolong their lives. For this reason, therapies that sometimes have neurologic side effects are often deferred intentionally. Methods: In a study of oligodendrogliomas, we used a quantitative method of MR analysis based on the S-transform to investigate whether codeletion of chromosomes 1p and 19q, a marker of good prognosis, could be predicted accurately by measuring image texture. Results: Differences in texture were seen between tumors with codeletion of chromosomes 1p and 19q and those with intact 1p and 19q alleles on contrast-enhanced T1-weighted and T2-weighted MR images. Quantitative MR texture onT2 images predicted codeletion of chromo- somes 1p and 19q with high sensitivity and specificity. Conclusions: This new method of MR image interpretation may have the potential to augment the diagnostic assessment of patients with suspected low-grade glioma. In neuro-oncology, a sensitive and specific imaging-based molecular test that reliably detects important genetic signatures in gliomas would be a helpful diagnostic adjunct. Such a capa- bility would be especially useful in the case of a young adult with a first seizure, a normal neurologic examination, and a probable low-grade glioma on magnetic resonance (MR) imaging, a common clinical scenario. Many such patients have slow-growing oligodendrogliomas with codeletion of chromo- somes 1p and 19q, a favorable genetic feature. Understandably, neurologically intact patients destined to have long survival, and without compelling reasons for early interventions that do not prolong length of life, might wish to defer therapeutic maneuvers that could have neurologic side effects, especially if a genetic signature associated with excellent prognosis, like codeletion of 1p and 19q, could be detected noninvasively. The ability to ascertain on an imaging study that a probable low-grade glioma has a favorable genetic profile and will behave in an indolent manner would give patients and clinicians greater confidence and flexibility in designing a disease management strategy. Furthermore, an imaging-based molecular test would complement the results of a stereotactic biopsy; up to 5% of tumor biopsies are not definitive because the volume of tissue retrieved is too small for histologic or genetic evaluation. MR imaging is a staple of brain tumor diagnosis. Although MR cannot yet resolve features on the scale of chromosomes, several advanced techniques can detect clinically relevant molecular processes in glioma. Spectroscopy can measure important tumor metabolites (1) and perfusion-weighted MR can detect angiogenesis (2); both correlate with glioma grade and prognosis. In this study, we use a quantitative method of image analysis developed by our group, S-transform – based texture analysis, to test the hypothesis that 1p and 19q codeletion in oligodendrogliomas can be detected using MR (3). This study builds on earlier work in which we used standard visual analysis of MR images to describe signal characteristics associated with 1p/19q loss (4). The texture of a feature in an MR image can be defined as a local characteristic pattern of visual intensities. Aspects of texture can be quantified by assessing the local spatial- frequency content: strong lower frequencies appear as homo- geneous smooth regions, whereas strong higher frequencies are Imaging, Diagnosis, Prognosis Authors’ Affiliations: Departments of 1 Electrical and Computer Engineering, 2 Clinical Neurosciences, 3 Oncology, 4 Radiology, and 5 Pathology and Laboratory Medicine, 6 Seaman Family MR Research Centre, 7 Clark Smith Brain Tumor Centre of the Southern Alberta Cancer Research Institute, and 8 Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta; and 9 Department of Neurology, University of Virginia, Charlottesville,Virginia Received 8/9/07; revised 12/31/07; accepted 1/14/08. Grant support: Alberta Heritage Foundation for Medical Research, the Alberta Cancer Foundation Chair in Brain Tumour Research, the Hotchkiss Brain Institute, the Canadian Institutes of Health Research, the Canadian Natural Sciences and Engineering Research Council, and the Alberta Informatics Circle of Research Excellence. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Note: All authors contributed to the design and execution of the study. In particular, R. Brown performed the texture, statistical, and ROC analysis and D. Demetrick performed the molecular genetic analysis. All authors contributed to the data analysis and interpretation. The paper was written by R. Brown, G. Cairncross, and R. Mitchell, with significant input from all authors. G. Cairncross and R. Mitchell share senior authorship. Conflict of Interest: R. Brown, G. Cairncross, and R. Mitchell have a financial interest in Calgary Scientific, Inc., which holds a patent on MR applications of the S-transform. Requests for reprints: Gregory Cairncross, Foothills Medical Centre, 1403 29th Street Northwest, Calgary, Alberta, Canada T2N 2T9. Phone: 403-944-1260; Fax: 403-270-7878; E-mail: jgcairnx@ucalgary.ca. F 2008 American Association for Cancer Research. doi:10.1158/1078-0432.CCR-07-1964 www.aacrjournals.org Clin Cancer Res 2008;14(8) April 15, 2008 2357