Evaluation of primary brain tumors using 11C-methionine PET with reference to a normal methionine uptake map

C-11-Methionine PET is a well-established technique for evaluating tumor extent for diagnosis and treatment planning in neurooncology. Image interpretation is typically performed using the ratio of uptake within the tumor to a reference region. The precise location of this reference region is important as local variations in methionine uptake may significantly alter the result, particularly for lesions at the border of gray and white matter. Selection of a reference region can be highly user dependant, and identifying a representative normal region may be complicated by midline or multifocal tumors. We hypothesized that current coregistration methods would enable interpretation of methionine PET images with reference to an averaged normal uptake map, allowing better standardization of scan analysis and increasing the sensitivity to tumor infiltration, particularly of white matter regions. Methods: A normal methionine uptake map was prepared from the normal hemispheres of 20 scans performed on patients with benign or low-grade lesions. Affine and nonlinear coregistration algorithms were evaluated for spatial normalization of the images to a previously developed PET template. A standardized method for applying the normal uptake map in brain tumors was developed and evaluated in a sample of 18 scans (6 grade 11, 6 grade 111, and 6 grade IV gliomas). Tumor extent was compared with that derived from a mirrored contralateral reference region method. Correlation coefficients were calculated between the uptake ratios for tumor to normal uptake map versus tumor to mirrored reference region. Results: "RatioMap" images depicting voxel-by-voxel ratios of a patient scan to the normal uptake map revealed increased methionine uptake in white matter regions that could not be identified using the standard method. Uptake ratios within the tumor varied slightly with the normalization methods used but correlated closely with the ratio to a single reference value. Nonlinear coregistration with median ratio intensity normalization gave the strongest correlation (r = 0.97, P < 0.001, n = 17). Conclusion: Evaluation of methionine PET data with reference to normal uptake data may improve sensitivity to white matter infiltration. The tumor uptake ratios obtained correlated closely with a standard reference value technique, whereas the described method allowed for better standardization of the image analysis.