Neuropathological and neuroimaging studies have reported significant changes in white matter in psychiatric and neurodegenerative diseases. Diffusion tensor imaging (DTI), a recently developed technique, enables the detection of microstructural changes in white matter. It is a noninvasive in vivo technique that assesses water molecules' diffusion in brain tissues. The most commonly used parameters are axial and radial diffusivity reflecting diffusion along and perpendicular to the axons, as well as mean diffusivity and fractional anisotropy representing global diffusion. Although the combination of these parameters provides valuable information about the integrity of brain circuits, their physiological meaning still remains controversial. After reviewing the basic principles of DTI, we report on recent contributions that used this technique to explore subtle structural changes in white matter occurring in elderly patients with bipolar disorder and Alzheimer disease. 1. Introduction White matter (WM) comprises 40–50% of the adult human brain. At a macroscopical level, it consists of collections of tightly wrapped axons that connect different brain regions. At a biochemical level, WM is mainly formed by myelin, a multilayer sheath of proteins (30%) and lipids (70%) around the axons. Small unwrapped regions called Ranvier nodes serve to mediate the salutatory conduction of the electrical impulse and enhance the velocity of conduction [1]. Neuropathological studies [2] indicate that myelination continues until at least the third decade of life. Other scientists found that WM increases in a roughly linear way until at least the age of 20 [3]. In vivo studies using volumetric imaging showed that WM volume increases in frontal and temporal lobes by the fourth decade of life [4, 5] and then steadily decreases. A neuropathological study found WM volume reduction by 28% as a function of age [6]. Interestingly, an assessment of WM volume in piano players suggests that practicing induces plasticity in early age when fiber tracts are still under maturation [7]. The development of modern MR techniques allowed for documenting WM changes in several neurological and psychiatric entities. In this paper, we describe a recent in vivo noninvasive technique for WM imaging referred to as diffusion tensor imaging (DTI) and explore its relevance in bipolar disorder and Alzheimer disease. The goal of this paper is to develop the different parameters obtained with DTI, the principal analysis methods, as well as the correlation of DTI-derived parameters with clinical and
References
[1]
C. M. Filley, “White matter and behavioral neurology,” Annals of the New York Academy of Sciences, vol. 1064, pp. 162–183, 2005.
[2]
F. M. Benes, M. Turtle, Y. Khan, and P. Farol, “Myelination of a key relay zone in the hippocampal formation occurs in the human brain during childhood, adolescence, and adulthood,” Archives of General Psychiatry, vol. 51, no. 6, pp. 477–484, 1994.
[3]
J. N. Giedd, “Structural magnetic resonance imaging of the adolescent brain,” Annals of the New York Academy of Sciences, vol. 1021, pp. 77–85, 2004.
[4]
G. Bartzokis, M. Beckson, P. H. Lu, K. H. Nuechterlein, N. Edwards, and J. Mintz, “Age-related changes in frontal and temporal lobe volumes in men: a magnetic resonance imaging study,” Archives of General Psychiatry, vol. 58, no. 5, pp. 461–465, 2001.
[5]
E. R. Sowell, B. S. Peterson, P. M. Thompson, S. E. Welcome, A. L. Henkenius, and A. W. Toga, “Mapping cortical change across the human life span,” Nature Neuroscience, vol. 6, no. 3, pp. 309–315, 2003.
[6]
B. Pakkenberg and H. J. G. Gundersen, “Neocortical neuron number in humans: effect of sex and age,” Journal of Comparative Neurology, vol. 384, no. 2, pp. 312–320, 1997.
[7]
S. L. Bengtsson, Z. Nagy, S. Skare, L. Forsman, H. Forssberg, and F. Ullén, “Extensive piano practicing has regionally specific effects on white matter development,” Nature Neuroscience, vol. 8, no. 9, pp. 1148–1150, 2005.
[8]
S. Haller, A. Xekardaki, C. Delaloye, et al., “Combined analysis of grey matter voxel-based morphometry and white matter tract-based spatial statistics in late-life bipolar disorder,” Journal of Psychiatry and Neuroscience, vol. 36, no. 1, p. 100140, 2011.
[9]
P. J. Basser and D. K. Jones, “Diffusion-tensor MRI: theory, experimental design and data analysis—a technical review,” NMR in Biomedicine, vol. 15, no. 7-8, pp. 456–467, 2002.
[10]
P. J. Basser, J. Mattiello, and D. LeBihan, “MR diffusion tensor spectroscopy and imaging,” Biophysical Journal, vol. 66, no. 1, pp. 259–267, 1994.
[11]
D. Le Bihan, J. F. Mangin, C. Poupon et al., “Diffusion tensor imaging: concepts and applications,” Journal of Magnetic Resonance Imaging, vol. 13, no. 4, pp. 534–546, 2001.
[12]
S. Chanraud, N. Zahr, E. V. Sullivan, and A. Pfefferbaum, “MR diffusion tensor imaging: a window into white matter integrity of the working brain,” Neuropsychology Review, vol. 20, no. 2, pp. 209–225, 2010.
[13]
S. K. Song, S. W. Sun, M. J. Ramsbottom, C. Chang, J. Russell, and A. H. Cross, “Dysmyelination revealed through MRI as increased radial (but unchanged axial) diffusion of water,” NeuroImage, vol. 17, no. 3, pp. 1429–1436, 2002.
[14]
S. K. Song, S. W. Sun, W. K. Ju, S. J. Lin, A. H. Cross, and A. H. Neufeld, “Diffusion tensor imaging detects and differentiates axon and myelin degeneration in mouse optic nerve after retinal ischemia,” NeuroImage, vol. 20, no. 3, pp. 1714–1722, 2003.
[15]
S. K. Song, J. Yoshino, T. Q. Le et al., “Demyelination increases radial diffusivity in corpus callosum of mouse brain,” NeuroImage, vol. 26, no. 1, pp. 132–140, 2005.
[16]
G. Thomalla, V. Glauche, M. A. Koch, C. Beaulieu, C. Weiller, and J. R？ther, “Diffusion tensor imaging detects early Wallerian degeneration of the pyramidal tract after ischemic stroke,” NeuroImage, vol. 22, no. 4, pp. 1767–1774, 2004.
[17]
C. Beaulieu, “The basis of anisotropic water diffusion in the nervous system—a technical review,” NMR in Biomedicine, vol. 15, no. 7-8, pp. 435–455, 2002.
[18]
C. Beaulieu and P. S. Allen, “Determinants of anisotropic water diffusion in nerves,” Magnetic Resonance in Medicine, vol. 31, no. 4, pp. 394–400, 1994.
[19]
D. M. Wimberger, T. P. Roberts, A. J. Barkovich, L. M. Prayer, M. E. Moseley, and J. Kucharczyk, “Identification of “premyelination” by diffusion-weighted mri,” Journal of Computer Assisted Tomography, vol. 19, no. 1, pp. 28–33, 1995.
[20]
V. Gulani, A. G. Webb, I. D. Duncan, and P. C. Lauterbur, “Apparent diffusion tensor measurements in myelin-deficient rat spinal cords,” Magnetic Resonance in Medicine, vol. 45, no. 2, pp. 191–195, 2001.
[21]
T. E. Conturo, N. F. Lori, T. S. Cull et al., “Tracking neuronal fiber pathways in the living human brain,” Proceedings of the National Academy of Sciences of the United States of America, vol. 96, no. 18, pp. 10422–10427, 1999.
[22]
S. Mori, B. J. Crain, V. P. Chacko, and P. C. M. Van Zijl, “Three-dimensional tracking of axonal projections in the brain by magnetic resonance imaging,” Annals of Neurology, vol. 45, no. 2, pp. 265–269, 1999.
[23]
T. Taoka, S. Iwasaki, M. Sakamoto et al., “Diffusion anisotropy and diffusivity of white matter tracts within the temporal stem in Alzheimer disease: evaluation of the "tract of interest" by diffusion tensor tractography,” American Journal of Neuroradiology, vol. 27, no. 5, pp. 1040–1045, 2006.
[24]
D. S. Tuch, “Q-ball imaging,” Magnetic Resonance in Medicine, vol. 52, no. 6, pp. 1358–1372, 2004.
[25]
V. J. Wedeen, P. Hagmann, W. Y. I. Tseng, T. G. Reese, and R. M. Weisskoff, “Mapping complex tissue architecture with diffusion spectrum magnetic resonance imaging,” Magnetic Resonance in Medicine, vol. 54, no. 6, pp. 1377–1386, 2005.
[26]
T. E. J. Behrens, M. W. Woolrich, M. Jenkinson et al., “Characterization and Propagation of Uncertainty in Diffusion-Weighted MR Imaging,” Magnetic Resonance in Medicine, vol. 50, no. 5, pp. 1077–1088, 2003.
[27]
S. M. Smith, M. Jenkinson, H. Johansen-Berg et al., “Tract-based spatial statistics: voxelwise analysis of multi-subject diffusion data,” NeuroImage, vol. 31, no. 4, pp. 1487–1505, 2006.
[28]
C. M. Adler, M. P. DelBello, K. Jarvis, A. Levine, J. Adams, and S. M. Strakowski, “Voxel-based study of structural changes in first-episode patients with bipolar disorder,” Biological Psychiatry, vol. 61, no. 6, pp. 776–781, 2007.
[29]
M. Sanches, M. S. Keshavan, P. Brambilla, and J. C. Soares, “Neurodevelopmental basis of bipolar disorder: a critical appraisal,” Progress in Neuro-Psychopharmacology and Biological Psychiatry, vol. 32, no. 7, pp. 1617–1627, 2008.
[30]
H. S. Mayberg, “Limbic-cortical dysregulation: a proposed model of depression,” Journal of Neuropsychiatry and Clinical Neurosciences, vol. 9, no. 3, pp. 471–481, 1997.
[31]
S. M. Strakowski, M. P. DelBello, and C. M. Adler, “The functional neuroanatomy of bipolar disorder: a review of neuroimaging findings,” Molecular Psychiatry, vol. 10, no. 1, pp. 105–116, 2005.
[32]
B. Baumann, P. Danos, D. Krell et al., “Reduced volume of limbic system-affiliated basal ganglia in mood disorders: preliminary data from a postmortem study,” Journal of Neuropsychiatry and Clinical Neurosciences, vol. 11, no. 1, pp. 71–78, 1999.
[33]
C. Bouras, E. K？vari, P. R. Hof, B. M. Riederer, and P. Giannakopoulos, “Anterior cingulate cortex pathology in schizophrenia and bipolar disorder,” Acta Neuropathologica, vol. 102, no. 4, pp. 373–379, 2001.
[34]
G. Rajkowska, A. Halaris, and L. D. Selemon, “Reductions in neuronal and glial density characterize the dorsolateral prefrontal cortex in bipolar disorder,” Biological Psychiatry, vol. 49, no. 9, pp. 741–752, 2001.
[35]
R. M. Dupont, N. Butters, K. Schafer, T. Wilson, J. Hesselink, and J. C. Gillin, “Diagnostic specificity of focal white matter abnormalities in bipolar and unipolar mood disorder,” Biological Psychiatry, vol. 38, no. 7, pp. 482–486, 1995.
[36]
W. M. McDonald, L. A. Tupler, F. A. Marsteller et al., “Hyperintense lesions on magnetic resonance images in bipolar disorder,” Biological Psychiatry, vol. 45, no. 8, pp. 965–971, 1999.
[37]
T. Silverstone, H. McPherson, Q. Li, and T. Doyle, “Deep white matter hyperintensities in patients with bipolar depression, unipolar depression and age-matched control subjects,” Bipolar Disorders, vol. 5, no. 1, pp. 53–57, 2003.
[38]
A. L. Stoll, P. F. Renshaw, D. A. Yurgelun-Todd, and B. M. Cohen, “Neuroimaging in bipolar disorder: what have we learned?” Biological Psychiatry, vol. 48, no. 6, pp. 505–517, 2000.
[39]
J. T. O'Brien, M. J. Firbank, M. S. Krishnan et al., “White matter hyperintensities rather than lacunar infarcts are associated with depressive symptoms in older people: the LADIS study,” American Journal of Geriatric Psychiatry, vol. 14, no. 10, pp. 834–841, 2006.
[40]
B. T. Woods, D. Yurgelun-Todd, D. Mikulis, and S. S. Pillay, “Age-related MRI abnormalities in bipolar illness: a clinical study,” Biological Psychiatry, vol. 38, no. 12, pp. 846–847, 1995.
[41]
K. Lyoo, H. K. Lee, J. H. Jung, G. G. Noam, and P. F. Renshaw, “White matter hyperintensities on magnetic resonance imaging of the brain in children with psychiatric disorders,” Comprehensive Psychiatry, vol. 43, no. 5, pp. 361–368, 2002.
[42]
K. H. Ahn, I. K. Lyoo, H. K. Lee et al., “White matter hyperintensities in subjects with bipolar disorder,” Psychiatry and Clinical Neurosciences, vol. 58, no. 5, pp. 516–521, 2004.
[43]
M. J. Kempton, J. R. Geddes, U. Ettinger, S. C. R. Williams, and P. M. Grasby, “Meta-analysis, database, and meta-regression of 98 structural imaging studies in bipolar disorder,” Archives of General Psychiatry, vol. 65, no. 9, pp. 1017–1032, 2008.
[44]
J. A. Frazier, J. L. Breeze, G. Papadimitriou et al., “White matter abnormalities in children with and at risk for bipolar disorder,” Bipolar Disorders, vol. 9, no. 8, pp. 799–809, 2007.
[45]
V. Kafantaris, P. Kingsley, B. Ardekani et al., “Lower orbital frontal white matter integrity in adolescents with bipolar I disorder,” Journal of the American Academy of Child and Adolescent Psychiatry, vol. 48, no. 1, pp. 79–86, 2009.
[46]
C. M. Adler, J. Adams, M. P. DelBello et al., “Evidence of white matter pathology in bipolar disorder adolescents experiencing their first episode of mania: a diffusion tensor imaging study,” American Journal of Psychiatry, vol. 163, no. 2, pp. 322–324, 2006.
[47]
S. Bruno, M. Cercignani, and M. A. Ron, “White matter abnormalities in bipolar disorder: a voxel-based diffusion tensor imaging study,” Bipolar Disorders, vol. 10, no. 4, pp. 460–468, 2008.
[48]
J. L. Beyer, W. D. Taylor, J. R. MacFall et al., “Cortical white matter microstructural abnormalities in bipolar disorder,” Neuropsychopharmacology, vol. 30, no. 12, pp. 2225–2229, 2005.
[49]
W. T. Regenold, C. A. D'Agostino, N. Ramesh, M. Hasnain, S. Roys, and R. P. Gullapalli, “Diffusion-weighted magnetic resonance imaging of white matter in bipolar disorder: a pilot study,” Bipolar Disorders, vol. 8, no. 2, pp. 188–195, 2006.
[50]
A. Versace, J. R. C. Almeida, S. Hassel et al., “Elevated left and reduced right orbitomedial prefrontal fractional anisotropy in adults with bipolar disorder revealed by tract-based spatial statistics,” Archives of General Psychiatry, vol. 65, no. 9, pp. 1041–1052, 2008.
[51]
M. M. Haznedar, F. Roversi, S. Pallanti et al., “Fronto-thalamo-striatal gray and white matter volumes and anisotropy of their connections in bipolar spectrum illnesses,” Biological Psychiatry, vol. 57, no. 7, pp. 733–742, 2005.
[52]
J. E. Sussmann, G. K. S. Lymer, J. Mckirdy et al., “White matter abnormalities in bipolar disorder and schizophrenia detected using diffusion tensor magnetic resonance imaging,” Bipolar Disorders, vol. 11, no. 1, pp. 11–18, 2009.
[53]
K. Mahon, J. Wu, A. K. Malhotra et al., “A voxel-based diffusion tensor imaging study of white matter in bipolar disorder,” Neuropsychopharmacology, vol. 34, no. 6, pp. 1590–1600, 2009.
[54]
S. M. Strakowski, M. P. Delbello, C. Adler, K. M. Cecil, and K. W. Sax, “Neuroimaging in bipolar disorder,” Bipolar Disorders, vol. 2, no. 3, pp. 148–164, 2000.
[55]
C. Chaddock, G. J. Barker, N. Marshall et al., “White matter microstructural impairments and genetic liability to familial bipolar I disorder,” British Journal of Psychiatry, vol. 194, no. 6, pp. 527–534, 2009.
[56]
M. V. Zanetti, M. P. Jackowski, A. Versace et al., “State-dependent microstructural white matter changes in bipolar I depression,” European Archives of Psychiatry and Clinical Neuroscience, vol. 259, no. 6, pp. 316–328, 2009.
[57]
D. A. Yurgelun-todd, M. M. Silveri, S. A. Gruber, M. L. Rohan, and P. J. Pimentel, “White matter abnormalities observed in bipolar disorder: a diffusion tensor imaging study,” Bipolar Disorders, vol. 9, no. 5, pp. 504–512, 2007.
[58]
D. S. Knopman, B. F. Boeve, and R. C. Petersen, “Essentials of the proper diagnoses of mild cognitive impairment, dementia, and major subtypes of dementia,” Mayo Clinic Proceedings, vol. 78, no. 10, pp. 1290–1308, 2003.
[59]
R. C. Petersen, “Mild cognitive impairment as a diagnostic entity,” Journal of Internal Medicine, vol. 256, no. 3, pp. 183–194, 2004.
[60]
W. R. Markesbery, F. A. Schmitt, R. J. Kryscio, D. G. Davis, C. D. Smith, and D. R. Wekstein, “Neuropathologic substrate of mild cognitive impairment,” Archives of Neurology, vol. 63, no. 1, pp. 38–46, 2006.
[61]
C. Flicker, S. H. Ferris, and B. Reisberg, “A longitudinal study of cognitive function in elderly persons with subjective memory complaints,” Journal of the American Geriatrics Society, vol. 41, no. 10, pp. 1029–1032, 1993.
[62]
R. C. Petersen, G. E. Smith, S. C. Waring, R. J. Ivnik, E. G. Tangalos, and E. Kokmen, “Mild cognitive impairment: clinical characterization and outcome,” Archives of Neurology, vol. 56, no. 3, pp. 303–308, 1999.
[63]
D. A. Bennett, J. A. Schneider, Z. Arvanitakis et al., “Neuropathology of older persons without cognitive impairment from two community-based studies,” Neurology, vol. 66, no. 12, pp. 1837–1844, 2006.
[64]
D. G. Davis, F. A. Schmitt, D. R. Wekstein, and W. R. Markesbery, “Alzheimer neuropathologic alterations in aged cognitively normal subjects,” Journal of Neuropathology and Experimental Neurology, vol. 58, no. 4, pp. 376–388, 1999.
[65]
D. S. Knopman, J. E. Parisi, A. Salviati et al., “Neuropathology of cognitively normal elderly,” Journal of Neuropathology and Experimental Neurology, vol. 62, no. 11, pp. 1087–1095, 2003.
[66]
P. T. Nelson, G. A. Jicha, F. A. Schmitt et al., “Clinicopathologic correlations in a large Alzheimer disease center autopsy cohort: neuritic plaques and neurofibrillary tangles "do count" when staging disease severity,” Journal of Neuropathology and Experimental Neurology, vol. 66, no. 12, pp. 1136–1146, 2007.
[67]
J. L. Price and J. C. Morris, “Tangles and plaques in nondemented aging and 'preclinical' alzheimer's disease,” Annals of Neurology, vol. 45, no. 3, pp. 358–368, 1999.
[68]
F. A. Schmitt, D. G. Davis, D. R. Wekstein, C. D. Smith, J. W. Ashford, and W. R. Markesbery, ““Preclinical” AD revisited: neuropathology of cognitively normal older adults,” Neurology, vol. 55, no. 3, pp. 370–376, 2000.
[69]
B. E. Tomlinson, G. Blessed, and M. Roth, “Observations on the brains of non-demented old people,” Journal of the Neurological Sciences, vol. 7, no. 2, pp. 331–356, 1968.
[70]
C. R. Jack Jr., R. C. Petersen, Y. C. Xu et al., “Prediction of AD with MRI-based hippocampal volume in mild cognitive impairment,” Neurology, vol. 52, no. 7, pp. 1397–1403, 1999.
[71]
A. Brun and E. Englund, “A white matter disorder in dementia of the Alzheimer type: a pathoanatomical study,” Annals of Neurology, vol. 19, no. 3, pp. 253–262, 1986.
[72]
M. Sj？beck and E. Englund, “Glial levels determine severity of white matter disease in Alzheimer's disease: a neuropathological study of glial changes,” Neuropathology and Applied Neurobiology, vol. 29, no. 2, pp. 159–169, 2003.
[73]
M. Sj？beck, M. Haglund, and E. Englund, “Decreasing myelin density reflected increasing white matter pathology in azheimer's disease—a neuropathological study,” International Journal of Geriatric Psychiatry, vol. 20, no. 10, pp. 919–926, 2005.
[74]
G. Bartzokis, J. L. Cummings, D. Sultzer, V. W. Henderson, K. H. Nuechterlein, and J. Mintz, “White matter structural integrity in healthy aging adults and patients with Alzheimer disease: a magnetic resonance imaging study,” Archives of Neurology, vol. 60, no. 3, pp. 393–398, 2003.
[75]
M. Coleman, “Axon degeneration mechanisms: commonality amid diversity,” Nature Reviews Neuroscience, vol. 6, no. 11, pp. 889–898, 2005.
[76]
B. Reisberg, E. H. Franssen, S. M. Hasan et al., “Retrogenesis: clinical, physiologic, and pathologic mechanisms in brain aging, Alzheimer's and other dementing processes,” European Archives of Psychiatry and Clinical Neuroscience, vol. 249, no. 3, pp. III28–III36, 1999.
[77]
J. C. De La Torre, “The vascular hypothesis of Alzheimer's disease: bench to bedside and beyond,” Neurodegenerative Diseases, vol. 7, no. 1–823, pp. 116–121, 2010.
[78]
L. Bracco, C. Piccini, M. Moretti et al., “Alzheimer's disease: role of size and location of white matter changes in determining cognitive deficits,” Dementia and Geriatric Cognitive Disorders, vol. 20, no. 6, pp. 358–366, 2005.
[79]
E. Garde, E. L. Mortensen, K. Krabbe, E. Rostrup, and H. B. W. Larsson, “Relation between age-related decline in intelligence and cerebral white-matter hyperintensities in healthy octogenarians: a longitudinal study,” The Lancet, vol. 356, no. 9230, pp. 628–634, 2000.
[80]
G. Gold, E. K？vari, F. R. Herrmann et al., “Cognitive consequences of thalamic, basal ganglia, and deep white matter lacunes in brain aging and dementia,” Stroke, vol. 36, no. 6, pp. 1184–1188, 2005.
[81]
E. V. Sullivan and A. Pfefferbaum, “Diffusion tensor imaging and aging,” Neuroscience and Biobehavioral Reviews, vol. 30, no. 6, pp. 749–761, 2006.
[82]
M. Bozzali, A. Falini, M. Franceschi et al., “White matter damage in Alzheimer's disease assessed in vivo using diffusion tensor magnetic resonance imaging,” Journal of Neurology Neurosurgery and Psychiatry, vol. 72, no. 6, pp. 742–746, 2002.
[83]
D. H. Salat, D. S. Tuch, A. J. W. van der Kouwe et al., “White matter pathology isolates the hippocampal formation in Alzheimer's disease,” Neurobiology of Aging, vol. 31, no. 2, pp. 244–256, 2010.
[84]
A. Fellgiebel, P. Wille, M. J. Müller et al., “Ultrastructural hippocampal and white matter alterations in mild cognitive impairment: a diffusion tensor imaging study,” Dementia and Geriatric Cognitive Disorders, vol. 18, no. 1, pp. 101–108, 2004.
[85]
D. Head, “Differential vulnerability of anterior white matter in nondemented aging with minimal acceleration in dementia of the Alzheimer type: evidence from diffusion tensor imaging,” Cerebral Cortex, vol. 14, no. 4, pp. 410–423, 2004.
[86]
D. Head, A. Z. Snyder, L. E. Girton, J. C. Morris, and R. L. Buckner, “Frontal-hippocampal double dissociation between normal aging and Alzheimer's disease,” Cerebral Cortex, vol. 15, no. 6, pp. 732–739, 2005.
[87]
R. Stahl, O. Dietrich, S. J. Teipel, H. Hampel, M. F. Reiser, and S. O. Schoenberg, “White matter damage in Alzheimer disease and mild cognitive impairment: assessment with diffusion-tensor MR imaging and parallel imaging techniques,” Radiology, vol. 243, no. 2, pp. 483–492, 2007.
[88]
I. L. H. Choo, D. Y. Lee, J. S. Oh et al., “Posterior cingulate cortex atrophy and regional cingulum disruption in mild cognitive impairment and Alzheimer's disease,” Neurobiology of Aging, vol. 31, no. 5, pp. 772–779, 2010.
[89]
S. E. Rose, K. L. McMahon, A. L. Janke et al., “Diffusion indices on magnetic resonance imaging and neuropsychological performance in amnestic mild cognitive impairment,” Journal of Neurology, Neurosurgery and Psychiatry, vol. 77, no. 10, pp. 1122–1128, 2006.
[90]
D. Medina, L. deToledo-Morrell, F. Urresta et al., “White matter changes in mild cognitive impairment and AD: a diffusion tensor imaging study,” Neurobiology of Aging, vol. 27, no. 5, pp. 663–672, 2006.
[91]
Y. Zhang, N. Schuff, G. H. Jahng et al., “Diffusion tensor imaging of cingulum fibers in mild cognitive impairment and Alzheimer disease,” Neurology, vol. 68, no. 1, pp. 13–19, 2007.
[92]
J. Huang, R. P. Friedland, and A. P. Auchus, “Diffusion tensor imaging of normal-appearing white matter in mild cognitive impairment and early Alzheimer disease: preliminary evidence of axonal degeneration in the temporal lobe,” American Journal of Neuroradiology, vol. 28, no. 10, pp. 1943–1948, 2007.
[93]
M. Taketomi, N. Kinoshita, K. Kimura et al., “Selective reduction of diffusion anisotropy in white matter of Alzheimer disease brains measured by 3.0 Tesla magnetic resonance imaging,” Neuroscience Letters, vol. 332, no. 1, pp. 45–48, 2002.
[94]
M. D. Greicius, K. Supekar, V. Menon, and R. F. Dougherty, “Resting-state functional connectivity reflects structural connectivity in the default mode network,” Cerebral Cortex, vol. 19, no. 1, pp. 72–78, 2009.
[95]
P. Scheltens, F. Barkhof, D. Leys, E. C. Wolters, R. Ravid, and W. Kamphorst, “Histopathologic correlates of white matter changes on MRI in Alzheimer's disease and normal aging,” Neurology, vol. 45, no. 5, pp. 883–888, 1995.
[96]
S. W. Sun, S. K. Song, M. P. Harms et al., “Detection of age-dependent brain injury in a mouse model of brain amyloidosis associated with Alzheimer's disease using magnetic resonance diffusion tensor imaging,” Experimental Neurology, vol. 191, no. 1, pp. 77–85, 2005.
[97]
F. Agosta, M. Pievani, S. Sala et al., “White matter damage in Alzheimer disease and its relationship to gray matter atrophy,” Radiology, vol. 258, no. 3, pp. 853–863, 2011.
[98]
B. Reisberg, E. H. Franssen, L. E. M. Souren, S. R. Auer, I. Akram, and S. Kenowsky, “Evidence and mechanisms of retrogenesis in Alzheimer's and other dementias: management and treatment import,” American Journal of Alzheimer's Disease and other Dementias, vol. 17, no. 4, pp. 202–212, 2002.
[99]
O. Naggara, C. Oppenheim, D. Rieu et al., “Diffusion tensor imaging in early Alzheimer's disease,” Psychiatry Research, vol. 146, no. 3, pp. 243–249, 2006.
[100]
A. Fellgiebel, I. Schermuly, A. Gerhard et al., “Functional relevant loss of long association fibre tracts integrity in early Alzheimer's disease,” Neuropsychologia, vol. 46, no. 6, pp. 1698–1706, 2008.
[101]
N. H. Stricker, B. C. Schweinsburg, L. Delano-Wood et al., “Decreased white matter integrity in late-myelinating fiber pathways in Alzheimer's disease supports retrogenesis,” NeuroImage, vol. 45, no. 1, pp. 10–16, 2009.
[102]
S. J. Teipel, A. L. W. Bokde, C. Born et al., “Morphological substrate of face matching in healthy ageing and mild cognitive impairment: a combined MRI-fMRI study,” Brain, vol. 130, no. 7, pp. 1745–1758, 2007.
[103]
D. Y. Lee, E. Fletcher, O. Martinez et al., “Regional pattern of white matter microstructural changes in normal aging, MCI, and AD,” Neurology, vol. 73, no. 21, pp. 1722–1728, 2009.
[104]
B. Bodini, Z. Khaleeli, M. Cercignani, D. H. Miller, A. J. Thompson, and O. Ciccarelli, “Exploring the relationship between white matter and gray matter damage in early primary progressive multiple sclerosis: an in vivo study with TBSS and VBM,” Human Brain Mapping, vol. 30, no. 9, pp. 2852–2861, 2009.
[105]
C. Pierpaoli, A. Barnett, S. Pajevic et al., “Water diffusion changes in wallerian degeneration and their dependence on white matter architecture,” NeuroImage, vol. 13, no. 6, pp. 1174–1185, 2001.
[106]
S. W. Sun, H. F. Liang, T. Q. Le, R. C. Armstrong, A. H. Cross, and S. K. Song, “Differential sensitivity of in vivo and ex vivo diffusion tensor imaging to evolving optic nerve injury in mice with retinal ischemia,” NeuroImage, vol. 32, no. 3, pp. 1195–1204, 2006.
[107]
S. W. Sun, H. F. Liang, M. Xie, U. Oyoyo, and A. Lee, “Fixation, not death, reduces sensitivity of DTI in detecting optic nerve damage,” NeuroImage, vol. 44, no. 3, pp. 611–619, 2009.
[108]
K. Schmierer, C. A. M. Wheeler-Kingshott, P. A. Boulby et al., “Diffusion tensor imaging of post mortem multiple sclerosis brain,” NeuroImage, vol. 35, no. 2, pp. 467–477, 2007.
[109]
E. C. Klawiter, R. E. Schmidt, K. Trinkaus et al., “Radial diffusivity predicts demyelination in ex vivo multiple sclerosis spinal cords,” NeuroImage, vol. 55, no. 4, pp. 1454–1460, 2011.
[110]
S. Haller, D. Nguyen, C. Rodriguez et al., “Individual prediction of cognitive decline in mild cognitive impairment using support vector machine-based analysis of diffusion tensor imaging data,” Journal of Alzheimer's Disease, vol. 22, no. 1, pp. 315–327, 2010.
[111]
W. S. Noble, “What is a support vector machine?” Nature Biotechnology, vol. 24, no. 12, pp. 1565–1567, 2006.
