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12 Chapter 1 Introduction background to sequence design is found in the classical introduction by Haacke et al. (1999). 1.1.3.2 Structural MR in AD Clinical and research of structural MRI imaging marker in AD are recently re- viewed by Frisoni et al. (2010) and McEvoy and Brewer (2010). The identification of medial temporal lobe atrophy and especially hippocampal atrophy of particular interest in MR studies into AD, which are well established markers of the neurodegeneration process in Alzheimer’s disease. Pathologically, the development of hippocampal atrophy is correlated with the deposition of neurofibrillary tangles (Whitwell et al., 2008; Vemuri et al., 2008b, 2009), and neuronal counts (Bobinski et al., 1999; Gosche et al., 2002; Jack et al., 2002). In terms of neuropsychological measurements, the degree of atrophy is also found linked to the memory decline (Thompson et al., 2004; Morra et al., 2009; Kovacevic et al., 2009; Walhovd et al., 2010). In high resolution MR images, visible changes of atrophies are observed. Visual rating on T1-weighted MR image is one way to assess the hippocampal lobe atrophy (Scheltens et al., 1992; Korf et al., 2004; DeCarli et al., 2007; Duara et al., 2008). Quantitative measurements on MR images with manual tracing or auto- mated segmentation show a reduction of hippocampal volume by 15-30% in AD in contrast to 10-15% in MCI (van der Flier et al., 2005; Shi et al., 2009). Lon- gitudinally, the rates of hippocampal atrophy measured in AD are 4.66% (95% confidence interval 3.92, 5.40) and 1.41% (0.52, 2.30) for MCI subjects (Barnes et al., 2009a). Apart from hippocampus, whole brain atrophy (Fox et al., 1999; Josephs et al., 2008; Schott et al., 2008; Sluimer et al., 2008, 2010) and ventricular enlargement (Jack et al., 2003; Thompson et al., 2004; Jack et al., 2004; Ridha et al., 2008) also indicate the progression of the neurodegeneration. Higher rate of atrophy and faster expansion of ventricle are present in advance of the onset of dementia.
Chapter 1 Introduction 13 Figure 1.5: A theoretical model of natural progression of cognitive and biological markers of Alzheimer disease and the sensitivity of markers to disease state. Amyloid markers (cerebrospinal fluid amyloid-β42 and PET amyloid tracer uptake) represent the earliest detectable changes in the Alzheimer disease course but have already plateaued by the MCI stage Functional and metabolic markers detected by task-dependent activation on functional MRI and 18 F-fluorodeoxyglucose PET are abnormal by the MCI stage and continue to change well into the dementia stage. Structural changes come later, following a temporal pattern mirroring tau pathology deposition. Source: Frisoni et al. (2010). Based on the structural MR imaging markers of medial temporal lobe and hippocampal atrophy, the prediction of MCI patients converting into AD gives on av- erage 81% sensitivity and 73% specificity (see meta-analysis by Yuan et al., 2009). However, it has been pointed out that other markers, such as CSF biomarkers, have to be take into consideration for the diagnosis due to the lack of specificity in predicting AD at MCI stage solely on the ground of medial temporal lobe atrophy. Hippocampal atrophy, as well as whole brain atrophy and ventricular enlargement, is not specific to AD, and may well occur in the natural process of normal aging. Patterns of atrophy in hippocampal subfields and cortical areas may provide specificity to the disease. Because of the non-linearity in the progress of the atrophy, the rate of atrophy accelerates in the transition stage from MCI to AD, and slows
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144 LIST OF PUBLICATIONS using dive
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146 BIBLIOGRAPHY Alzheimer, A. (191
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148 BIBLIOGRAPHY Baillard, C., Hell
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150 BIBLIOGRAPHY of post mortem mag
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152 BIBLIOGRAPHY B. (2008). Three-d
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154 BIBLIOGRAPHY Cootes, T. F., Tay
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156 BIBLIOGRAPHY head in MR images
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158 BIBLIOGRAPHY Evans, A. C., Coll
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BIBLIOGRAPHY 161 Ghanei, A., Soltan
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BIBLIOGRAPHY 163 Heckemann, R. A.,
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BIBLIOGRAPHY 165 R. C. (2003). MRI
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BIBLIOGRAPHY 167 Konrad, C., Ukas,
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BIBLIOGRAPHY 169 Mahony, R. and Man
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BIBLIOGRAPHY 171 disease, mild cogn
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BIBLIOGRAPHY 177 Shen, K., Bourgeat
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BIBLIOGRAPHY 179 Barillot, C., Hayn
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BIBLIOGRAPHY 181 Tzourio-Mazoyer, N
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BIBLIOGRAPHY 183 Vos, F. M., de Bru
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BIBLIOGRAPHY 185 Woolrich, M. W., J
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