Proceedings of the 50th Annual ASTRO Meeting S529

2805 Diffusion Tensor Imaging as a Biomarker for Neurotoxicity of Radiation

V. Nagesh, C. I. Tsien, P. C. Sundgren, H. A. Buchtel, T. L. Chenevert, L. Junck, L. Rogers, T. S. Lawrence, Y. Cao

University of Michigan, Ann Arbor, MI

Purpose/Objective(s): Radiation response is dynamic, extending beyond the targeted tumor volume and influencing normal tis-sue. Although the dose delivered by 3D conformal radiation therapy (RT) or intensity modulated RT is focal, some critical neu-roanatomic structures could be affected by moderate or low radiation doses, even if remote to the tumor, resulting in compromisedneurocognitive function. We hypothesize that neurostructural changes in specific neural structures of functional pathways couldproduce neurocognitive dysfunction.

Materials/Methods: Eleven patients, diagnosed with low-grade glioma, meningioma or suprasellar lesion participated in an IRB-approved MRI study. All patients received 28 to 33 fractions of 1.8 Gy. The MRI protocol included T1, T2 and diffusion tensorimaging (DTI). MRI studies were performed before RT, at week 3 and 6 during RT, and 1 and 6 months after RT. Neurocognitivetests were administered to evaluate executive function, attention, learning and memory before and after RT concurrent with MRIstudies. Fractional anisotropy (FA) of diffusion, an indicator of structural integrity, was calculated in the left and right hemispheresto characterize the time and dose-dependent radiation response in both hippocampi and both temporal lobes.

Results: FA in the left hippocampus did not change significantly during RT, but decreased significantly (� 13%) 1 month after RT,and the decrease was still seen 6 months after RT. In the left temporal lobe, FA exhibited a transient decrease (4%) at week 3 duringRT (p = 0.02), returned to the pre-RT values at the end of RT, and began decreasing after RT (�4%) and became significant 6 monthsafter RT (p = 0.04). The temporal profiles in the right hippocampus and temporal lobe were similar to the respective left homologues,but the changes were not significant, and the dose to the right side was similar to the left side (18.9 Gy vs. 19.2 Gy). Neither tumorprogression nor any other anatomical changes were evident on visual analysis of T2-weighted MRI up to 6 months after RT. Thedecreases in FA in the left hippocampus at 1 month (p = 0.04) and 6 months (p = 0.03) after RT were correlated with the changes inverbal learning scores at corresponding times. Also, the decrease in FA in the left temporal lobe at 6 months after RT correlated withthe decrease in verbal fluency at 6 month after RT (p = 0.03). No correlation was found between the decrease in FA of the right hip-pocampus or right temporal lobe and changes in verbal learning or fluency at corresponding times.

Conclusions: Our data indicate that DTI is sensitive to subtle structural changes, and the loss of structural integrity after irradiationlikely contributes to the neurocognitive dysfunction.

Author Disclosure: V. Nagesh, None; C.I. Tsien, None; P.C. Sundgren, None; H.A. Buchtel, None; T.L. Chenevert, None; L.Junck, None; L. Rogers, None; T.S. Lawrence, None; Y. Cao, None.

2806 Metabolic Volume Analysis for Evaluation of Chemical Shift Imaging (CSI) of Gliomas

T. Fox, E. Schreibmann, A. Waller, S. Keilholz, P. Pantalone, I. Crocker

Emory University School of Medicine, Atlanta, GA

Purpose/Objective(s): The response of gliomas to therapy is generally assessed by conventional magnetic resonance imagingtechniques which accurately delineate the size and location of the mass within the brain. MR spectroscopy (MRS) allows oneto assess a variety of metabolites (Choline/Creatine/N-acetyl aspartate(NAA)/lactate) within a glioma tumor. Increasing cho-line/creatine (Cho/Cr) and choline/NAA ratios (Cho/NAA) have correlated with the grade of the tumor and have been useful indifferentiating tumor from normal tissue. Chemical Shift Imaging (CSI) has been used to characterize the biology of the entire tu-mor using multi-voxel MRS acquisitions but no tools have been described to enable one to evaluate the response beyond associ-ating the metabolite maps with the anatomical images. The purpose of this study is to describe a volumetric analysis method and itsapplication as a quantitative treatment assessment tool to a radiotherapy glioma patient.

Materials/Methods: A high resolution MR T2 planning scan and a CSI acquisition were acquired (Siemens 3T MR system) oneweek before treatment and six weeks after radiation treatment. The levels of the above metabolites in each voxel were determinedusing the CSI workstation software (Siemens Medical Systems). The Cho/Cr ratios registered to the corresponding planning imageswere imported into a departmental software tool for further retrospective analysis. In this software, the pre and post treatment plan-ning images were then rigidly registered, and a volume of interest was created which encompassed the spectroscopic informationfrom each scan. A cumulative metabolic volume histogram (MVH) was then calculated for each set of images. These results werethen compared to the response as assessed by conventional MRI imaging alone.

Results: MVH method proved to be feasible although the MRS metabolite values needed to be manually processed at the scannerlevel. The example patient’s MRS evaluation indicated a clear response to therapy with the post treatment MVH less than the pre-treatment MVH beyond a Cho/Cr ratio of 1 with a reduction in the maximum Cho/Cr ratio. Corresponding conventional MR im-aging at this time point revealed new contrast enhancement within the tumor suggesting tumor progression despite combined ra-diation therapy and temozolomide. Without a change in treatment, further follow-up imaging revealed a clear response to treatmentconfirming the MRS evaluation.

Conclusions: MVH analysis of 3D MRS information was feasible and useful in this patient in ruling out progressive disease. Giventhe prevalence of pseudoprogression following combined radiation therapy and temozolomide for high grade gliomas 3D MRSevaluation before and after treatment may be particularly useful.

Author Disclosure: T. Fox, Velocity Medical Solutions, E. Ownership Interest; E. Schreibmann, None; A. Waller, None; S. Keil-holz, None; P. Pantalone, Velocity Medical Solutions, E. Ownership Interest; I. Crocker, Velocity Medical Solutions, E. Owner-ship Interest.

2807 Comparative Monte Carlo Treatment Planning Studies with Low Energy-enhanced Megavoltage Photon

Beams

S. H. Cho

Georgia Institute of Technology, Atlanta, GA

Purpose/Objective(s): An idea of enhancing tumor dose using high atomic number materials such as gold and kilovoltage X-raysin particular has been well demonstrated through in vitro, in vivo, and computational studies over the years. Based on these studies,