Background Iron accumulation and neuroinflammation are both pathological processes that are associated with disease progression of Huntington’s Disease (HD). However, their intercorrelation remains unclear, in both HD and other neurodegenerative diseases.

Aims This study aims to investigate the correlation between altered brain iron content and altered neuroinflammatory markers in the basal ganglia of HD gene expansion carriers.

Methods A total of 30 participants (11 premanifest, 7 manifest and 12 healthy controls) were scanned on a 7T MRI scanner (Philips, Netherlands), as part of a larger (EHDN seed fund) project (n=70). Quantitative susceptibility mapping (QSM) was used to quantify iron concentration in the brain. ¹H Magnetic Resonance Spectroscopy (MRS) was used to measure levels of myoinositol (Ins) and choline (Cho) in a volume-of-interest (VOI) located in the basal ganglia. Ins and Cho are two metabolites that are preferentially located in glial cells and astrocytes and can serve as neuroinflammation markers.

Outcome As a first step, a subpopulation, consisting of 3 age- and sex-matched subjects per group (9 in total), will be analyzed with QSM and MRS. Magnetic susceptibility and metabolite concentrations within the MRS-VOI will be quantified and correlated.

Conclusions Our unique protocol will lead us one step closer to the missing link between neuroinflammation and iron accumulation, using QSM and MRS. This could help determining the order and distribution of these pathological processes in the different stages of HD. This novel approach could create new opportunities for biomarker development and therapeutic interventions.