Insights from the Characterisation of the NAD+ Biosynthesis Pathway via in-vitro CEST MRI

Motivation: Neurodegenerative diseases, particularly Alzheimer's, involve disrupted NAD+ and purine metabolic pathways. Understanding these disruptions can improve diagnostic sensitivity for clinical applications, especially using CEST MRI. Goal(s): To characterise in-vitro CEST MRI properties of NAD+ and its biosynthesis precursors, focusing on sensitivity for neurodegenerative disease biomarkers linked to NAD+/purine metabolism. Approach: In-vitro CEST MRI was used to analyse NAD+ and biosynthesis precursors, quantifying, characterising, and assigning distinct proton peaks to assess sensitivity as neurodegenerative disease biomarkers. Results: High CEST contrast was achieved for NMN and NAD+, with NAD+ showing pH-dependent effects and up to 15% CEST contrast for its amine moiety (2.03ppm). Impact: This study may impact neurodegenerative disease research by enabling precise CEST MRI-based tracking of NAD+ metabolism, specifically adenosine-linked pathways as elucidated (2.03ppm). This could deepen understanding of metabolic disruptions, opening new avenues for early diagnosis and targeted therapeutic monitoring.