Objectives: Semi-quantitative image analysis methods in Alzheimer's Disease (AD) require normalization of positron emission tomography (PET) images. However, recent studies have found variabilities associated with reference region selection of amyloid PET images. Haralick features (HFs) generated from the Gray Level Co-occurrence Matrix (GLCM) quantify spatial characteristics of amyloid PET radiotracer uptake without the need for intensity normalization. The objective of this study is to calculate several HFs in different diagnostic groups and determine the group differences.
Methods: All image and metadata were acquired through the Alzheimer's Disease Neuroimaging Initiative database. Subjects were grouped in three ways: by clinical diagnosis, by APOE e4 allele, and by Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-Cog) score. Several GLCM matrices were calculated for different direction and distances (1-4 mm) from multiple regions on PET images. The HFs, contrast, correlation, dissimilarity, energy, entropy, and homogeneity, were calculated from these GLCMs. Wilcoxon tests and Student t-tests were performed on Haralick features and standardized uptake value ratio (SUVR) values, respectively, to determine group differences. In addition to statistical testing, receiver operating characteristic (ROC) curves were generated to determine the discrimination performance of the selected regional HFs and the SUVR values.
Results: Preliminary results from statistical testing indicate that HFs were capable of distinguishing groups at baseline and follow-up (false discovery rate corrected p<0.05) in particular regions at much higher occurrences than SUVR (81 of 252). Conversely, we observed nearly no significant differences between all groups within ROIs at baseline or follow-up utilizing SUVR. From the ROC analysis, we found that the Energy and Entropy offered the best performance to distinguish Normal versus mild cognitive impairment and ADAS-Cog negative versus ADAS-Cog positive groups.
Conclusion: These results suggest that this technique could improve subject stratification in AD drug trials and help to evaluate the disease progression and treatment effects longitudinally without the disadvantages associated with intensity normalization.
Keywords: Haralick features; energy; entropy; florbetapir; gray level co-occurrence matrix.