Relationship to Behavioural and Neural Functioning

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As for FA, MTR is a non-specific marker of neural damage, such as demyelina-tion. Many of the published MT studies have focused on patients with multiple sclerosis, who show decreased MT in both ROI and whole-brain histogram analyses. In other diseases, results are similar, indicating MTR is a viable marker for affected white and gray matter. MTR has been shown to increase with brain development during the first several years of life (Rademacher et al. 1999; van Buchem et al. 2001) and regional decreases with aging have been found (Armstrong et al. 2004). Differences in MTR were sufficiently large to distinguish patients with mild cognitive impairment from patients with Alzheimer's disease and controls (Kabani et al. 2002a; Kabani et al. 2002b). A number of published studies have also used magnetization transfer methods to compare the brains in patients with schizophrenia against healthy control subjects (Foong et al. 2001; Bagary et al. 2003; Kiefer et al. 2004; Kubicki et al. 2005). Reduced MTR measurements have also been observed in a small sample of patients with late-life major depressive disorders (Kumar et al. 2004).

Only a few studies have attempted to relate magnetization transfer measurements to measures reflecting brain function. A serial MTR study in the optic nerves of 29 patients with acute optic neuritis was performed with measurements of visual system functioning using visual evoked potentials (VEP) (Hickman et al. 2004). No significant differences in MTR were observed between patients and controls at the onset of optic neuritis, although the MTR did decrease in patients over a period of one year. There did not seem to be any direct relationship between MTR and VEP measurements. Another study of 18 patients with early-stage multiple sclerosis (Au Duong et al. 2005) demonstrated a correlation between functional connectivity between left Brodmann areas 45/46 and 24 using an fMRI working memory task, and the MTR of normal appearing white matter and also with brain T2 lesion load. Consequently, the functional connectivity relationship with MTR suggests that changes in the functional working memory network is related to changes in the white matter pathophysiology. A combined MTR and fMRI study (Filippi et al. 2002) of simple motor function in patients with multiple sclerosis revealed correlations between the MTR histogram features of whole-brain, normal appearing brain tissue (both GM and WM) and fMRI signal strengths in ipsilateral sensori-motor cortex and supplementary motor area (bilaterally). The fMRI signal in contralateral sensorimotor cortex was significantly correlated with MTR histogram features in patients with cervical but not dorsal spinal cord myelitis (Rocca et al. 2005). Finally, a recent study measured diffusion and MT in patients with schizophrenia (Kalus et al. 2005). The amygdala showed lower anisotropy (inter-voxel coherence), and differences in quantitative MT measures (Ti, fraction bound pool), but not MTR. The authors interpreted the findings as indicating a possible increase in neuronal density in the amygdala of schizophrenics. The functional significance of these changes is not clear, however, as there were no significant correlations of any of the quantitative MR measures with disease duration or symptom severity.

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