Normal Aging and Alzheimers Disease

It is well known that tissue iron content varies among different regions of the brain, and also changes with aging (Hallgren and Sourander, 1958). Paramagnetic tissue iron changes MRI relaxation times due to the diffusion of water molecules in the susceptibility field of the iron inclusions, and ultrahigh field MRI is particularly sensitive in this respect. Comparative contrast differences in T2-weighted brain images of two subjects aged 27 years and 50 years at 1.5 Tand 7 Tare shown in Figure 3.65. For example, gray matter in the motorsensory cortex has a lower signal than adjacent white matter, and this difference is more pronounced in older than in younger subjects, whereas contrast is inverted in the frontal and temporal cortices. The signal is lowest in the globus pallidus, substantia nigra, red nuclei and caudate, all of which have much higher iron contents. Quantitative measurements of T2-values exhibit a linear relationship to iron content computed from published values for iron content versus age. These initial studies suggest that ul-

Fig. 3.65. Axial 1.5 T and 7 T T2-weighted spin echo images of two healthy subjects aged 50 years (A, B) and 27 years (C, D). The 7-T images were acquired using a 7-T MRI (Philips, Cleveland, USA) and a single-echo spin-echo sequence with TR/TE 2000 ms/50

ms, FOV 24 cm, 256 x 192 matrix and 5-mm slice thickness; 1.5-T images used TE = 100 ms. Note the contrast inversion between frontal GM and WM and sensorimotor GM and WM that is especially pronounced in the older subject and at higher field strength.

trahigh field T2-mapping may be more sensitive for assessing brain iron content than standard field strength MRI (Gelman et al., 1999; Georgiades et al., 2001; Zhou et al., 2001; Haacke et al., 2005), and thus is suited to the reliable quantification of iron in different regions of the brain and the assessment of aging.

Changes in brain iron content have also been associated with several neurodegenerative diseases, including Alzheimer's, Parkinson's and Huntington's disease. In Alzheimer's disease, oxidative stress has been implicated as one of the promoting factors, and is linked to brain iron content (Perry et al., 2000; Sayre et al., 2000); iron also appears to be associated with amyloid plaque (Smith et al., 1997). Because of this connection, several groups have attempted to measure brain iron with MRI as a biomarker for noninvasive assessment in Alzheimer's (Ordidge et al., 1994; Ogg et al., 1999; Bartzokis and Tishler, 2000; Schenck and Zimmerman, 2004). Ultrahigh field MRI should be significantly more sensitive than standard clinical field strength MRI, though further investigations in this area are clearly needed.

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