Hui-Kuo Shu, MD, PhD
Department of Radiation Oncology
Although advances have been made in imaging techniques for patients with glioblastoma multiforme (GBM), new tools are needed to supplement standard imaging sequences. Researchers at the Winship Cancer Institute of Emory University are helping to develop the next generation of imaging strategies for this highly aggressive malignancy.
GBM, the most common primary malignant brain tumor in adults, remains relatively resistant to therapy. Standard treatment for GBM, including resection followed by radiation therapy (RT) and concurrent/adjuvant temozolomide (TMZ) chemotherapy, results in 15 months’ median survival and <10% 5-year survival.1,2
These tumors are locally aggressive, displaying significant brain parenchymal infiltration. Conventional imaging for these tumors consists of magnetic resonance imaging (MRI) with and without contrast, which allows visualization of the enhancing tumor on a T1-weighted contrast-enhanced (T1W
-CE) sequence and of surrounding regions of edema that contain infiltrating tumor on T2-weighted (T2W
) or FLAIR sequences.
However, these standard techniques may be insufficient to fully evaluate GBMs. Enhanced regions on T1W
-CE images represent areas with leaky vasculature where contrast extravasates and is not necessarily tumor specific. Increased signaling on T2W
or FLAIR images, which shows increased water signal, may or may not represent regions with nonenhancing tumor infiltration.
Spectroscopy for Brain Imaging
Magnetic resonance spectroscopic imaging (MRSI), a specialized technique performed on clinical MRI scanners that does not require intravenous contrast, offers additional information. It determines relative concentrations of certain metabolites in interrogated regions of the brain.
With MRSI, detection of certain metabolites such as choline (Cho) have been associated with GBMs, while the presence of others such as N-acetylaspartate (NAA) have been associated with normal brain tissue This technology, because it is based on metabolite content, may distinguish a malignant tumor from a more benign process that could not be differentiated by conventional MRIs.
Current commercially available packages for performing MRSI involve either single voxel techniques that assess a relatively large region (eg, 8 cm3
) or 2D multivoxel techniques that assess along a plane (eg, 2 cm thick) at individual 2 cm3
(1 x 1 x 2 cm) regions. These implementations require relatively long scan times (2-5 min/voxel with single voxel techniques and 6-8 min/slab with multivoxel techniques), have poor signal-to-noise ratios and resolutions, and are unable to assess the entire brain within a clinically acceptable time frame.
3D Whole Brain Spectroscopic MRI
At Winship, we are developing the clinical utility of a more advanced MRSI technique that permits quantitative assessment of metabolite content throughout the brain at significantly higher resolutions (~0.1 cm3) while maintaining reasonable scan times (~14-15 minutes).
Working with Andrew Maudsley, PhD, and his group at the University of Miami, the original developer of the spectroscopic imaging sequence we are using,3,4
we have implemented this advanced sequence, now termed spectroscopic MRI (sMRI), on our Siemens Tim Trio and Prisma 3T MRI scanners to acquire whole brain metabolite maps.
The output is further assessed/visualized on Velocity AI from Varian Medical Systems in Palo Alto, California, a software originally developed at Emory to evaluate patient imaging charts with easy tools for image set registration.