Contrast in most human neuroimaging studies is a function of the T1 and T2 relaxation times of the brain tissues. Consequently, regional signal differences in brain images are often caused by differences in the relaxation properties. T1 is the recovery time of the longitudinal magnetization and T2 is the decay constant associated with the transverse magnetization. Both characteristic times are highly sensitive to bulk water of the tissue and tend to increase with water content. Significant changes in both T1 and T2 are observed with early brain maturation (e.g., Miot et al. 1995; Miot-Noirault et al. 1997; Sie et al. 1997; Steen et al. 1997; Paus et al. 2001) and aging (Jernigan et al. 1991; Autti et al. 1994; Salonen et al. 1997). In development, these changes are likely caused by decreased water content and increased water binding and compartmentalization including during premyelination periods when lipids, proteins, and glial cells are increasing. T2 appears to be more sensitive to the changes associated with brain maturation although T1 changes have been reported to be more closely linked to the onset of myelination (e.g., Barkovich et al. 1988; Martin et al. 1988).
There are two principle approaches for measuring T1- inversion recovery and variable saturation. The inversion recovery methods work by inverting the longitudinal magnetization with a 180° pulse and then obtaining measurements with different inversion times. Variable saturation methods work by obtaining measurements with either several RF excitation flip angles or several different TR periods. All methods are highly sensitive to the accuracy of the RF magnetic field, although new analytical methods can retrospectively correct for inhomogeneities (Cheng and Wright 2006).
T2 is generally measured using spin echo pulse sequences, where measurements are obtained at different TE (echo times). The signal decay is governed by the equation S = So exp(-TE/T2). The most efficient method is to use a multiple spin-echo pulse sequence, where measurements are obtained at multiple TE values for a single excitation, although there continue to be lively discussions in the literature concerning the appropriate number and spacing of echos for quantitative T2 calculations (e.g., Duncan et al. 1996; Whittall et al. 1999; Townsend et al. 2004), related primarily to the nature of T2 decay (see below). The measurement of T2 is also highly sensitive to imperfections in the RF and static magnetic fields (Poon and Henkelman 1995). Further, the RF imperfections will also lead to stimulated echoes in multi-echo sequences, which are governed by T1, which can lead to overestimation of the T2. The stimulated echo components can be suppressed using variable amplitude gradient crusher pulses around each 180° refocusing pulse (Poon and Henkelman 1995). As for MT, the accuracy of T2 measurements will depend on these parameters, so if the number of echos possible are limited, they should be chosen with care (Duncan et al. 1996).
In spite of the fact that T1 and T2 are highly sensitive to a wide range of tissue factors, and are therefore likely to be nonspecific, relaxation time measurements have been shown to be affected in many neurological diseases that have impairments in connectivity including epilepsy, substance abuse and neurodegenerative diseases such as M.S., dementia, schizophrenia, Alzheimer's disease, Parkinson's disease. One potentially confounding factor in many of these studies is the presence of edema, which will increase the bulk water content in the tissue. To date, only one study has specifically related relaxation time measurements to measures of brain connectivity (Vaithianathar et al. 2002). In this study of MS patients, DTI was used to identify the pyramidal tracts and fibers passing through the corpus callosum. Histograms of Ti relaxation data along the pathways were generated and indicated decreased Ti relaxivity in patients relative to controls. There was no correlation of Ti relaxation in these paths with standard clinical disability rating scale scores, and no cognitive measures were available for analysis.
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