Glymphatic System Assessment Using Diffusion Tensor Images: Introducing the New-ALPS Index Through Genetic Programming

The glymphatic system is essential for the clearance of waste products from the brain, and its dysfunction is associated with cognitive decline in neurodegenerative diseases such as Alzheimer's Disease (AD) and Mild Cognitive Impairment (MCI). In literature, the along perivascular space (ALPS) index was employed to assess the activity of the human glymphatic system using diffusion tensor images (DTI). In this research, a new ALPS index (called New-ALPS), is introduced which in fact is the optimized version of ALPS through Genetic Programming. The New-ALPS for left and right hemispheres are calculated separately. For the whole brain two ways are presented: taking the average values of the left and right hemisphere called New-ALPS(avg) or taking their sum, called New-ALPS(sum). In comparison to the classic ALPS index, the New-ALPS index exhibits a stronger correlation with cognitive measures, including the Mini-Mental State Examination (MMSE) (2.78% improvement), Clinical Dementia Rating (CDR) (5.13% improvement), and Functional Activities Questionnaire (FAQ) (10% improvement), as demonstrated by the analysis of fiber diffusivities in DTI data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset. Furthermore, the New-ALPS index exhibits enhanced sensitivity in identifying the effects of aging (5.78 times improvement in AD individuals, negative 3 times improvement in MCI individuals, and 12.42 times improvement in normal controls) and sleep disorders (28.57% improvement in MMSE, and 11.11% improvement in the Pittsburgh Sleep Quality Index (PSQI) using the Human Connectome Project (HCP) DTI dataset. Our results indicate that the New-ALPS index may be a more reliable metric for evaluating glymphatic system, providing novel insights into the pathophysiology of neurodegenerative diseases.