Chasing shadows: what determines DTI metrics in gray matter regions? An in vitro and in vivo study

To characterize the relationship between superparamagnetic ferritin-bound iron and diffusion tensor scalars in vitro, and validate the results in vivo.

The in vitro model consisted of a series of 40-mL 1.1% agarose gels doped with ferritin covering and exceeding those concentrations normally found within healthy human gray matter. Additionally, regions of interest were placed in the caudate, putamen, and globus pallidus of 29 healthy volunteer subjects 19-80 years of age. Carr-Purcell-Meiboom-Gill sequence (CPMG) and diffusion tensor imaging (DTI) data were collected at 1.5 Tesla (T) and 3T in vitro, and at 1.5T in vivo.

In vitro, linear relationships were observed between ferritin-bound iron concentration, R2 (1/T2 ) and 1/SNR. Eigenvalue repulsion with increasing R2 (decreasing SNR) was reflected in an artifactual increase of fractional anisotropy. In vivo, similar relationships were observed, with mean diffusivity also decreasing linearly with increasing R2 . Lambda 3 showed the strongest correlation with R2 both in vitro and in vivo.

The observation that DTI metrics correlate with ferritin-bound iron is an important consideration in the design and interpretation of studies exploring the diffusion characteristics of gray matter regions, especially in studies focused on adolescence as well as diseases associated with altered brain-iron load such as pantothenate kinase-associated neurodegeneration, Huntington disease and multiple system atrophy.