MRI R2* and quantitative susceptibility mapping in brain tissue with extreme iron overload.

Abstract

Background: R2* and quantitative susceptibility mapping (QSM) are regarded as robust techniques for assessing iron content in the brain. While these techniques are established for normal or moderate iron levels, their usability in extreme iron overload, as seen in aceruloplasminemia (ACP), is unclear. We aimed to evaluate various R2* and QSM algorithms in assessing brain iron levels in patients with ACP compared to healthy controls.

Materials and methods: We acquired a three-dimensional multiecho gradient-echo sequence for R2* and QSM in three patients with ACP and three healthy subjects. Six algorithms each for R2* and QSM were compared. QSM was performed with referencing to whole brain, to cerebrospinal fluid and without referencing. R2* and QSM values were assessed in the caudate nucleus, putamen, globus pallidus, and thalamus.

Results: R2* values varied significantly across algorithms, particularly in the putamen (F(5,50) = 16.51, p < 0.001). For QSM, reference region choice (F(5,150) = 264, p < 0.001) and algorithm selection (F(2,9) = 10, p < 0.001) had an impact on susceptibility values. In patients, referencing to whole brain yielded lower susceptibility values than cerebrospinal fluid (median = 0.147 ppm, range = 0.527 ppm versus median = 0.279 ppm, range = 0.593 ppm).

Conclusion: Extreme iron overload amplifies variability in R2* and QSM measurements. QSM referencing is particularly challenging in diffuse whole-brain iron accumulation; thus, analysis with multiple reference regions might mitigate bias. Both algorithm selection and referencing approaches play a pivotal role in determining measurement accuracy and clinical interpretation under extreme brain iron overload.

Relevance statement: As QSM transitions into clinical use, it will encounter cases of extreme iron overload. Our study in patients with aceruloplasminemia revealed that the choice of reference region significantly influences susceptibility values, with variations exceeding algorithm-dependent differences.

Key points: R2* and QSM vary across algorithms in brain tissue with iron overload. Whole-brain referenced QSM leads to lower susceptibility values in aceruloplasminemia patients. QSM, if properly processed, provides reliable maps in iron overload brain regions. In brain regions with extremely high iron content, R2* mapping might fail.