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Multispectral Quantitative Magnetic Resonance Imaging of Brain Iron Stores: A Theoretical Perspective

Objectives: To review published magnetic resonance imaging (MRI) iron quantification techniques in the context of quantitative MRI and MR relaxation theories. To analyze comparatively and as a function of age the simultaneous measurements of the proton density (PD), the relaxation times (T1 and T2), and the longitudinal to transverse relaxation times ratio (T1/T2) of brain regions known to accumulate iron preferentially. Methods: Twenty-seven human subjects were scanned with the mixed turbo spin echo pulse sequence, which is multispectral in PD, T1, and T2. Quantitative MRI (Q-MRI) maps of PD, T1, T2, and T1/T2 were generated, and region of interest measurements were performed in 5 brain regions, namely, frontal white matter (WM), genu of corpus callosum, caudate nucleus, putamen, and globus pallidus. Results: Relaxation time measurements are consistent with results of others and provide further confirmation to our basic understanding of the relaxation effects of iron stores in the brain. Specifically, we found that the iron-rich globus pallidus exhibits enhanced T1 and T2 relaxation relative the iron poorer gray matter tissues (caudate nucleus and putamen) and also relative to the WM matter tissues (frontal WM and genu of the corpus callosum). We also observe that under riding this hypothesis-because we do not have independent confirmation-that iron caused relaxation enhancement, are the normal brain aging patterns, which suggest that the brain tissues become wetter with increasing age. Also noted is the virtual removal of age dependence observed for the T1/T2 ratio of WM tissues, further suggesting that this ratio may become of clinical significance in the diagnosis of neoplastic processes as well as for quantifying iron in tissue. Conclusions: The theoretical underpinnings of published brain iron Q-MRI techniques have been reviewed. We also examined MR relaxation theory essentials in relation to 1H-proton relaxation phenomena in diamagnetic tissues as well as theoretical extensions to describe relaxation effects in tissues containing iron deposits with a focus on ferritin. Also reported are in vivo Q-MRI results of 27 human brains obtained with a multispectral technique that uses the mixed turbo spin echo pulse sequence and a model conforming Q-MRI algorithms.