Susceptibility contrast in high field MRI of human brain as a function of tissue iron content

Magnetic susceptibility provides an important contrast mechanism for MRI. Increasingly, susceptibility-based contrast is being exploited to investigate brain tissue microstructure and to detect abnormal levels of brain iron as these have been implicated in a variety of neuro-degenerative diseases. However, it remains unclear to what extent magnetic susceptibility-related contrast at high field relates to actual brain iron concentrations. In this study, we performed susceptibility weighted imaging as a function of field strength on healthy brains in vivo and post-mortem brain tissues at 1.5 T, 3 T and 7 T. Iron histology was performed on the tissue samples for comparison. The calculated susceptibility-related parameters R2⁎ and signal frequency shift in four iron-rich regions (putamen, globus pallidus, caudate, and thalamus) showed an almost linear dependence (r ≥ 0.90 for R2⁎; r ≥ 0.83 for phase, p < 0.01) on field strength, suggesting that potential ferritin saturation effects are not relevant to susceptibility-weighted contrast for field strengths up to 7 T. The R2⁎ dependence on the putative (literature-based) iron concentration was 0.048 Hz/T/ppm. The histological data from brain samples confirmed the linear dependence of R2⁎ on field strength and showed a slope against iron concentration of 0.0099 Hz/T/ppm dry-weight, which is equivalent to 0.05 Hz/T/ppm wet-weight and closely matched the calculated value in vivo. These results confirm the validity of using susceptibility-weighted contrast as an indicator of iron content in iron-rich brain regions. The absence of saturation effects opens the way to exploit the benefits of MRI at high field strengths for the detection of iron distributions with high sensitivity and resolution.