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14. Uncovering the heterogeneity and temporal complexity of neurodegenerative diseases with Subtype and Stage Inference

Author

Young, A. L., Marinescu, R. V., Oxtoby, N. P., Bocchetta, M., Yong, K., Firth, N. C., Cash, D. M., Thomas, D. L., Dick, K. M., Cardoso, J., van Swieten, J., Borroni, B., Galimberti, D., Masellis, M., Tartaglia, M. C., Rowe, J. B., Graff, C., Tagliavini, F., Frisoni, G. B., Laforce, R., Finger, E., de Mendonca, A., Sorbi, S., Warren, J. D., Crutch, S., Fox, N. C., Ourselin, S., Schott, J. M., Rohrer, J. D., Alexander, D. C., Andersson, C., Archetti, S., Arighi, A., Benussi, L., Binetti, G., Black, S., Cosseddu, M., Fallstrom, M., Ferreira, C., Fenoglio, C., Freedman, M., Fumagalli, G. G., Gazzina, S., Ghidoni, R., Grisoli, M., Jelic, V., Jiskoot, L., Keren, R., Lombardi, G., Maruta, C., Meeter, L., Mead, S., van Minkelen, R., Nacmias, B., Oijerstedt, L., Padovani, A., Panman, J., Pievani, M., Polito, C., Premi, E., Prioni, S., Rademakers, R., Redaelli, V., Rogaeva, E., Rossi, G., Rossor, M., Scarpini, E., Tang-Wai, D., Thonberg, H., Tiraboschi, P., Verdelho, A., Weiner, M. W., Aisen, P., Petersen, R., Jack, C. R., Jagust, W., Trojanowki, J. Q., Toga, A. W., Beckett, L., Green, R. C., Saykin, A. J., Morris, J., Shaw, L. M., Khachaturian, Z., Sorensen, G., Kuller, L., Raichle, M., Paul, S., Davies, P., Fillit, H., Hefti, F., Holtzman, D., Mesulam, M. M., Potter, W., Snyder, P., Schwartz, A., Montine, T., Thomas, R. G., Donohue, M., Walter, S., Gessert, D., Sather, T., Jiminez, G., Harvey, D., Bernstein, M., Thompson, P., Schuff, N., Borowski, B., Gunter, J., Senjem, M., Vemuri, P., Jones, D., Kantarci, K., Ward, C., Koeppe, R. A., Foster, N., Reiman, E. M., Chen, K., Mathis, C., Landau, S., Cairns, N. J., Householder, E., Taylor-Reinwald, L., Lee, V., Korecka, M., Figurski, M., Crawford, K., Neu, S., Foroud, T. M., Potkin, S., Shen, L., Faber, K., Kim, S., Nho, K., Thal, L., Buckholtz, N., Albert, M., Frank, R., Hsiao, J., Kaye, J., Quinn, J., Lind, B., Carter, R., Dolen, S., Schneider, L. S., Pawluczyk, S., Beccera, M., Teodoro, L., Spann, B. M., Brewer, J., Vanderswag, H., Fleisher, A., Heidebrink, J. L., Lord, J. L., Mason, S. S., Albers, C. S., Knopman, D., Johnson, K., Doody, R. S., Villanueva-Meyer, J., Chowdhury, M., Rountree, S., Dang, M., Stern, Y., Honig, L. S., Bell, K. L., Ances, B., Carroll, M., Leon, S., Mintun, M. A., Schneider, S., Oliver, A., Marson, D., Griffith, R., Clark, D., Geldmacher, D., Brockington, J., Roberson, E., Grossman, H., Mitsis, E., de Toledo-Morrell, L., Shah, R. C., Duara, R., Varon, D., Greig, M. T., Roberts, P., Onyike, C., D'Agostino, D., Kielb, S., Galvin, J. E., Cerbone, B., Michel, C. A., Rusinek, H., de Leon, M. J., Glodzik, L., De Santi, S., Doraiswamy, P. M., Petrella, J. R., Wong, T. Z., Arnold, S. E., Karlawish, J. H., Wolk, D., Smith, C. D., Jicha, G., Hardy, P., Sinha, P., Oates, E., Conrad, G., Lopez, O. L., Oakley, M. A., Simpson, D. M., Porsteinsson, A. P., Goldstein, B. S., Martin, K., Makino, K. M., Ismail, M. S., Brand, C., Mulnard, R. A., Thai, G., Mc-Adams-Ortiz, C., Womack, K., Mathews, D., Quiceno, M., Diaz-Arrastia, R., King, R., Weiner, M., Martin-Cook, K., Devous, M., Levey, A. I., Lah, J. J., Cellar, J. S., Burns, J. M., Anderson, H. S., Swerdlow, R. H., Apostolova, L., Tingus, K., Woo, E., Silverman, D. H., P. H., Lu, Bartzokis, G., Graff-Radford, N. R., Parfitt, F., Kendall, T., Johnson, H., Farlow, M. R., Hake, A. M., Matthews, B. R., Herring, S., Hunt, C., van Dyck, C. H., Carson, R. E., Macavoy, M. G., Chertkow, H., Bergman, H., Hosein, C., Stefanovic, B., Caldwell, C., Hsiung, G. -Y. R., Feldman, H., Mudge, B., Assaly, M., Kertesz, A., Rogers, J., Bernick, C., Munic, D., Kerwin, D., Mesulam, M. -M., Lipowski, K., C. -K., Wu, Johnson, N., Sadowsky, C., Martinez, W., Villena, T., Turner, R. S., Reynolds, B., Sperling, R. A., Johnson, K. A., Marshall, G., Frey, M., Lane, B., Rosen, A., Tinklenberg, J., Sabbagh, M. N., Belden, C. M., Jacobson, S. A., Sirrel, S. A., Kowall, N., Killiany, R., Budson, A. E., Norbash, A., Johnson, P. L., Allard, J., Lerner, A., Ogrocki, P., Hudson, L., Fletcher, E., Carmichael, O., Olichney, J., Decarli, C., Kittur, S., Borrie, M., Lee, T. -Y., Bartha, R., Johnson, S., Asthana, S., Carlsson, C. M., Potkin, S. G., Preda, A., Nguyen, D., Tariot, P., Reeder, S., Bates, V., Capote, H., Rainka, M., Scharre, D. W., Kataki, M., Adeli, A., Zimmerman, E. A., Celmins, D., Brown, A. D., Pearlson, G. D., Blank, K., Anderson, K., Santulli, R. B., Kitzmiller, T. J., Schwartz, E. S., Sink, K. M., Williamson, J. D., Garg, P., Watkins, F., Ott, B. R., Querfurth, H., Tremont, G., Salloway, S., Malloy, P., Correia, S., Rosen, H. J., Miller, B. L., Mintzer, J., Spicer, K., Bachman, D., Pasternak, S., Rachinsky, I., Drost, D., Pomara, N., Hernando, R., Sarrael, A., Schultz, S. K., Ponto, L. L. B., Shim, H., Smith, K. E., Relkin, N., Chaing, G., Raudin, L., Smith, A., Fargher, K., Raj, B. A., Neylan, T., Grafman, J., Davis, M., Morrison, R., Hayes, J., Finley, S., Friedl, K., Fleischman, D., Arfanakis, K., James, O., Massoglia, D., Fruehling, J. J., Harding, S., Peskind, E. R., Petrie, E. C., Li, G., Yesavage, J. A., Taylor, J. L., and Furst, A. J.

Published
2018

15. Calbindin and parvalbumin are early markers of non-mitotically regenerating hair cells in the bullfrog vestibular otolith organs

Author

Steyger, P. S, Burton, M, Hawkins, J. R, Schuff, N. R, and Baird, R. A

Subjects
Life Sciences (General)
Abstract

Earlier studies have demonstrated hair cell regeneration in the absence of cell proliferation, and suggested that supporting cells could phenotypically convert into hair cells following hair cell loss. Because calcium-binding proteins are involved in gene up-regulation, cell growth, and cell differentiation, we wished to determine if these proteins were up-regulated in scar formations and regenerating hair cells following gentamicin treatment. Calbindin and parvalbumin immunolabeling was examined in control or gentamicin-treated (GT) bullfrog saccular and utricular explants cultured for 3 days in amphibian culture medium or amphibian culture medium supplemented with aphidicolin, a blocker of nuclear DNA replication in eukaryotic cells. In control cultures, calbindin and parvalbumin immunolabeled the hair bundles and, less intensely, the cell bodies of mature hair cells. In GT or mitotically-blocked GT (MBGT) cultures, calbindin and parvalbumin immunolabeling was also seen in the hair bundles, cuticular plates, and cell bodies of hair cells with immature hair bundles. Thus, these antigens were useful markers for both normal and regenerating hair cells. Supporting cell immunolabeling was not seen in control cultures nor in the majority of supporting cells in GT cultures. In MBGT cultures, calbindin and parvalbumin immunolabeling was up-regulated in the cytosol of single supporting cells participating in scar formations and in supporting cells with hair cell-like characteristics. These data provide further evidence that non-mitotic hair cell regeneration in cultures can be accomplished by the conversion of supporting cells into hair cells.

Published
1997
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16. Intracellular distributions and putative functions of calcium-binding proteins in the bullfrog vestibular otolith organs

Author

Baird, R. A, Steyger, P. S, and Schuff, N. R

Subjects
Life Sciences (General)
Abstract

Hair cells in the bullfrog vestibular otolith organs were immunolabeled by monoclonal and polyclonal antisera against calbindin (CaB), calmodulin (CaM), calretinin (CaR), and parvalbumin (PA). S-100, previously shown to immunolabel striolar hair cells in fish vestibular organs, only weakly immunolabeled hair cells in the bullfrog vestibular otolith organs. Immunolabeling was not detected in supporting cells. With the exception of CaR, myelinated axons and unmyelinated nerve terminals were immunolabeled by all of the above antisera. Immunolabeling was seen in all saccular hair cells, although hair cells at the macular margins were immunolabeled more intensely for CaB, CaM, and PA than more centrally located hair cells. As the macula margins are known to be a growth zone, this labeling pattern suggests that marginal hair cells up-regulate their calcium-binding proteins during hair cell development. In the utriculus, immunolabeling for CaM and PA was generally restricted to striolar hair cells. CaR immunolabeling was restricted to the stereociliary array. Immunolabeling for other calcium-binding proteins was generally seen in both the cell body and hair bundles of hair cells, although this labeling was often localized to the stereociliary array and the apical portion of the cell body. CaM and PA immunolabeling in the stereociliary array in saccular and utricular striolar cells suggests a functional role for these proteins in mechanoelectric transduction and adaptation.

Published
1997
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18. Regional differences in lectin binding patterns of vestibular hair cells

Author

Baird, Richard A, Schuff, N. R, and Bancroft, J

Subjects
Life Sciences (General)
Abstract

Surface glycoconjugates of hair cells and supporting cells in the vestibular endorgans of the bullfrog were identified using biotinylated lectins with different carbohydrate specificities. Lectin binding in hair cells was consistent with the presence of glucose and mannose (CON A), galactose (RCA-I), N-acetylgalactosamine (VVA), but not fucose (UEA-I) residues. Hair cells in the bullfrog sacculus, unlike those in the utriculus and semicircular canals, did not stain for N-acetylglucosamine (WGA) or N-acetylgalactosamine (VVA). By contrast, WGA and, to a lesser extent, VVA, differentially stained utricular and semicircular canal hair cells, labeling hair cells located in peripheral, but not central, regions. In mammals, WGA uniformly labeled Type 1 hair cells while labeling, as in the bullfrog, Type 2 hair cells only in peripheral regions. These regional variations were retained after enzymatic digestion. We conclude that vestibular hair cells differ in their surface glycoconjugates and that differences in lectin binding patterns can be used to identify hair cell types and to infer the epithelial origin of isolated vestibular hair cells.

Published
1994

19. Peripheral innervation patterns of vestibular nerve afferents in the bullfrog utriculus

Author

Baird, Richard A and Schuff, N. R

Subjects
Life Sciences (General)
Abstract

Vestibular nerve afferents innervating the bullfrog utriculus differ in their response dynamics and sensitivity to natural stimulation. They also supply hair cells that differ markedly in hair bundle morphology. To examine the peripheral innervation patterns of individual utricular afferents more closely, afferent fibers were labeled by the extracellular injection of horseradish peroxidase (HRP) into the vestibular nerve after sectioning the vestibular nerve medial to Scarpa's ganglion to allow the degeneration of sympathetic and efferent fibers. The peripheral arborizations of individual afferents were then correlated with the diameters of their parent axons, the regions of the macula they innervate, and the number and type of hair cells they supply. The utriculus is divided by the striola, a narrow zone of distinctive morphology, into media and lateral parts. Utiricular afferents were classified as striolar or extrastriolar according to the epithelial entrance of their parent axons and the location of their terminal fields. In general, striolar afferents had thicker parent axons, fewer subepithelial bifurcations, larger terminal fields, and more synaptic endings than afferents in extrstriolar regions. Afferents in a juxtastriolar zone, immediately adjacent to the medial striola, had innervation patterns transitional between those in the striola and more peripheral parts of the medial extrastriola. moast afferents innervated only a single macular zone. The terminal fields of striolar afferents, with the notable exception of a few afferents with thin parent axons, were generally confined to one side of the striola. Hair cells in the bullfrog utriculus have perviously been classified into four types based on hair bundle morphology. Afferents in the extrastriolar and juxtastriolar zones largely or exclusively innervated Type B hair cells, the predominant hair cell type in the utricular macula. Striolar afferents supplied a mixture of four hair cell types, but largely contacted Type B and Type C hair cells, particularly on the outer rows of the medial striola. Afferents supplying more central striolar regions innervated fewer Type B and larger numbers of Type E and Type F hair cells. Striolar afferents with thin parent axons largely supplied Type E hair cells with bulbed kniocilia in the innermost striolar rows.

Published
1994

20. Hair cell regeneration in the bullfrog vestibular otolith organs following aminoglycoside toxicity

Author

Baird, Richard A, Torres, M. A, and Schuff, N. R

Subjects
Life Sciences (General)
Abstract

Adult bullfrogs were given single intraotic injections of the aminoglycoside antibiotic gentamicin sulfate and sacrificed at postinjection times ranging from 0.5 to 9 days. The saccular and utricular maculae of normal and injected animals were examined in wholemount and cross-section. Intraotic 200 (mu) M gentamicin concentrations resulted in the uniform destruction of the hair bundles and, at later times, the cell bodies of saccular hair cells. In the utriculus, striolar hair cells were selectively damaged while extrastriolar hair cells were relatively unaffected. Regenerating hair cells, identified in sectioned material by their small cell bodies and short, well-formed hair bundles, were seen in the saccular and utricular maculae as early as 24-48 h postinjection. Immature versions of mature hair cell types in both otolith organs were recognized by the presence of absence of a bulbed kinocilia and the relative lengths of their kinocilia and longest sterocilia. Utricular hair cell types with kinocilia longer than their longest stereocilia were observed at earlier times than hair cell types with shorter kinocilia. In the same sacculus, the hair bundles of gentamicin-treated animals, even at 9 days postinjection, were significantly smaller than those of normal animals. The hair bundles of utricular hair cells, on the other hand, reached full maturity within the same time period.

Published
1994

21. Regional differences in lectin binding patterns of vestibular hair cells

Author

Baird, R. A, Schuff, N. R, and Bancroft, J

Subjects
Life Sciences (General)
Abstract

Surface glycoconjugates of hair cells and supporting cells in the vestibular endorgans of the bullfrog were identified using biotinylated lectins with different carbohydrate specificities. Lectin binding in hair cells was consistent with the presence of glucose and mannose (CON A), galactose (RCA-I), N-acetylglucosamine (WGA), N-acetylgalactosamine (VVA), but not fucose (UEA-I) residues. Hair cells in the bullfrog sacculus, unlike those in the utriculus and semicircular canals, did not strain for N-acetylglucosamine (WGA) or N-acetylgalactosamine (VVA). By contrast, WGA and, to a lesser extent, VVA, differentially stained utricular and semicircular canal hair cells, labeling hair cells located in peripheral, but not central, regions. In mammals, WGA uniformly labeled Type I hair cells while labeling, as in the bullfrog, Type II hair cells only in peripheral regions. These regional variations were retained after enzymatic digestion. We conclude that vestibular hair cells differ in their surface glycoconjugates and that differences in lectin binding patterns can be used to identify hair cell types and to infer the epithelial origin of isolated vestibular hair cells.

Published
1993
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22. Hair cell regeneration in the bullfrog vestibular otolith organs following aminoglycoside toxicity

Author

Baird, R. A, Torres, M. A, and Schuff, N. R

Subjects
Life Sciences (General)
Abstract

Adult bullfrog were given single intraotic injections of the aminoglycoside antibiotic gentamicin sulfate and sacrificed at postinjection times ranging from 0.5 to 9 days. The saccular and utricular maculae of normal and injected animals were examined in wholemount and cross-section. Intraotic 200 microM gentamicin concentrations resulted in the uniform destruction of the hair bundles and, at later times, the cell bodies of saccular hair cells. In the utriculus, striolar hair cells were selectively damaged while extrastriolar hair cells were relatively unaffected. Regenerating hair cells, identified in sectioned material by their small cell bodies and short, well-formed hair bundles, were seen in the saccular and utricular maculae as early as 24-48 h postinjection. Immature versions of mature hair cell types in both otolith organs were recognized by the presence or absence of a bulbed kinocilia and the relative lengths of their kinocilia and longest stereocilia. Utricular hair cell types with kinocilia longer than their longest stereocilia were observed at earlier than hair cell types with shorter kinocilia. In the sacculus, the hair bundles of gentamicin-treated animals, even at 9 days postinjection, were significantly smaller than those of normal animals. The hair bundles of utricular hair cells, on the other hand, reached full maturity within the same time period.

Published
1993
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23. Association between anticholinergic medication use and cognition, brain metabolism, and brain atrophy in cognitively normal older adults

Author

Risacher, SL, McDonald, BC, Tallman, EF, West, JD, Farlow, MR, Unverzagt, FW, Gao, S, Boustani, M, Crane, PK, Petersen, RC, Jack, CR, Jagust, WJ, Aisen, PS, Weiner, MW, Saykin, AJ, Trojanowki, JQ, Toga, AW, Beckett, L, Green, RC, Morris, J, Shaw, LM, Khachaturian, Z, Sorensen, G, Carrillo, M, Kuller, L, Raichle, M, Paul, S, Davies, P, Fillit, H, Hefti, F, Holtzman, D, Mesulam, MM, Potter, W, Snyder, PJ, Schwartz, A, Montine, T, Thomas, RG, Donohue, M, Walter, S, Gessert, D, Sather, T, Jiminez, G, Balasubramanian, AB, Mason, J, Sim, I, Harvey, D, Bernstein, M, Fox, N, Thompson, P, Schuff, N, DeCarli, C, Borowski, B, Gunter, J, Senjem, M, Vemuri, P, Jones, D, Kantarci, K, Ward, C, Koeppe, RA, Foster, N, Reiman, EM, Chen, K, Mathis, C, Landau, S, Cairns, NJ, Householder, E, Taylor-Reinwald, L, Lee, V, Korecka, M, Figurski, M, Crawford, K, and Neu, S

Abstract

Copyright 2016 American Medical Association. All rights reserved. IMPORTANCE The use of anticholinergic (AC) medication is linked to cognitive impairment and an increased risk of dementia. To our knowledge, this is the first study to investigate the association between AC medication use and neuroimaging biomarkers of brain metabolism and atrophy as a proxy for understanding the underlying biology of the clinical effects of AC medications. OBJECTIVE To assess the association between AC medication use and cognition, glucose metabolism, and brain atrophy in cognitively normal older adults from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and the Indiana Memory and Aging Study (IMAS). DESIGN, SETTING, AND PARTICIPANTS The ADNI and IMAS are longitudinal studies with cognitive, neuroimaging, and other data collected at regular intervals in clinical and academic research settings. For the participants in the ADNI, visits are repeated 3, 6, and 12 months after the baseline visit and then annually. For the participants in the IMAS, visits are repeated every 18 months after the baseline visit (402 cognitively normal older adults in the ADNI and 49 cognitively normal older adults in the IMAS were included in the present analysis). Participants were either taking (hereafter referred to as the AC+ participants [52 from the ADNI and 8 from the IMAS]) or not taking (hereafter referred to as the AC- participants [350 from the ADNI and 41 from the IMAS]) at least 1 medication with medium or high AC activity. Data analysis for this study was performed in November 2015. MAIN OUTCOMES AND MEASURES Cognitive scores, mean fludeoxyglucose F 18 standardized uptake value ratio (participants from the ADNI only), and brain atrophy measures from structural magnetic resonance imaging were compared between AC+ participants and AC- participants after adjusting for potential confounders. The total AC burden score was calculated and was related to target measures. The association of AC use and longitudinal clinical decline (mean [SD] follow-up period, 32.1 [24.7] months [range, 6-108 months]) was examined using Cox regression. RESULTS The 52 AC+ participants (mean [SD] age, 73.3 [6.6] years) from the ADNI showed lower mean scores onWeschler Memory Scale-Revised Logical Memory Immediate Recall (raw mean scores: 13.27 for AC+ participants and 14.16 for AC- participants; P = .04) and the Trail Making Test Part B (raw mean scores: 97.85 seconds for AC+ participants and 82.61 seconds for AC- participants; P = .04) and a lower executive function composite score (raw mean scores: 0.58 for AC+ participants and 0.78 for AC- participants; P = .04) than the 350 AC- participants (mean [SD] age, 73.3 [5.8] years) from the ADNI. Reduced total cortical volume and temporal lobe cortical thickness and greater lateral ventricle and inferior lateral ventricle volumes were seen in the AC+ participants relative to the AC- participants. CONCLUSIONS AND RELEVANCE The use of AC medication was associated with increased brain atrophy and dysfunction and clinical decline. Thus, use of AC medication among older adults should likely be discouraged if alternative therapies are available.

Published
2016

25. Large-scale genomics unveil polygenic architecture of human cortical surface area

Author

Chen, CH, Peng, Q, Schork, AJ, Lo, MT, Fan, CC, Wang, Y, Desikan, RS, Bettella, F, Hagler, DJ, Westlye, LT, Kremen, WS, Jernigan, TL, Le Hellard, S, Steen, VM, Espeseth, T, Huentelman, M, Håberg, AK, Agartz, I, Djurovic, S, Andreassen, OA, Schork, N, Dale, AM, McCabe, C, Chang, L, Akshoomoff, N, Newman, E, Ernst, T, Van Zijl, P, Kuperman, J, Murray, S, Bloss, C, Appelbaum, M, Gamst, A, Thompson, W, Bartsch, H, Weiner, M, Aisen, P, Petersen, R, Jack, CR, Jagust, W, Trojanowki, JQ, Toga, AW, Beckett, L, Green, RC, Saykin, AJ, Morris, J, Shaw, LM, Khachaturian, Z, Sorensen, G, Carrillo, M, Kuller, L, Raichle, M, Paul, S, Davies, P, Fillit, H, Hefti, F, Holtzman, D, Mesulman, MM, Potter, W, Snyder, PJ, Schwartz, A, Montine, T, Thomas, RG, Donohue, M, Walter, S, Gessert, D, Sather, T, Jiminez, G, Harvey, D, Bernstein, M, Fox, N, Thompson, P, Schuff, N, DeCarli, C, Borowski, B, Gunter, J, Senjem, M, Vemuri, P, Jones, D, Kantarci, K, Ward, C, Koeppe, RA, Foster, N, and Reiman, EM

Abstract

© 2015 Macmillan Publishers Limited. All rights reserved. Little is known about how genetic variation contributes to neuroanatomical variability, and whether particular genomic regions comprising genes or evolutionarily conserved elements are enriched for effects that influence brain morphology. Here, we examine brain imaging and single-nucleotide polymorphisms (SNPs) data from ∼ 2,700 individuals. We show that a substantial proportion of variation in cortical surface area is explained by additive effects of SNPs dispersed throughout the genome, with a larger heritable effect for visual and auditory sensory and insular cortices (h2 ∼ 0.45). Genome-wide SNPs collectively account for, on average, about half of twin heritability across cortical regions (N = 466 twins). We find enriched genetic effects in or near genes. We also observe that SNPs in evolutionarily more conserved regions contributed significantly to the heritability of cortical surface area, particularly, for medial and temporal cortical regions. SNPs in less conserved regions contributed more to occipital and dorsolateral prefrontal cortices.

Published
2015

26. Magnetic resonance imaging in Alzheimer's Disease Neuroimaging Initiative 2

Author

Jack, CR, Barnes, J, Bernstein, MA, Borowski, BJ, Brewer, J, Clegg, S, Dale, AM, Carmichael, O, Ching, C, DeCarli, C, Desikan, RS, Fennema-Notestine, C, Fjell, AM, Fletcher, E, Fox, NC, Gunter, J, Gutman, BA, Holland, D, Hua, X, Insel, P, Kantarci, K, Killiany, RJ, Krueger, G, Leung, KK, Mackin, S, Maillard, P, Malone, IB, Mattsson, N, McEvoy, L, Modat, M, Mueller, S, Nosheny, R, Ourselin, S, Schuff, N, Senjem, ML, Simonson, A, Thompson, PM, Rettmann, D, Vemuri, P, Walhovd, K, Zhao, Y, Zuk, S, and Weiner, M

Subjects
mental disorders
Abstract

© 2015 The Authors. Published by Elsevier Inc. Introduction Alzheimer's Disease Neuroimaging Initiative (ADNI) is now in its 10th year. The primary objective of the magnetic resonance imaging (MRI) core of ADNI has been to improve methods for clinical trials in Alzheimer's disease (AD) and related disorders. Methods We review the contributions of the MRI core from present and past cycles of ADNI (ADNI-1, -Grand Opportunity and -2). We also review plans for the future-ADNI-3. Results Contributions of the MRI core include creating standardized acquisition protocols and quality control methods; examining the effect of technical features of image acquisition and analysis on outcome metrics; deriving sample size estimates for future trials based on those outcomes; and piloting the potential utility of MR perfusion, diffusion, and functional connectivity measures in multicenter clinical trials. Discussion Over the past decade the MRI core of ADNI has fulfilled its mandate of improving methods for clinical trials in AD and will continue to do so in the future.

Published
2015

27. Ferritin levels in the cerebrospinal fluid predict Alzheimer's disease outcomes and are regulated by APOE

Author

Ayton, S, Faux, NG, Bush, AI, Weiner, MW, Aisen, P, Petersen, R, Jack, CR, Jagust, W, Trojanowki, JQ, Toga, AW, Beckett, L, Green, RC, Saykin, AJ, Morris, J, Shaw, LM, Khachaturian, Z, Sorensen, G, Kuller, L, Raichle, M, Paul, S, Davies, P, Fillit, H, Hefti, F, Holtzman, D, Mesulam, MM, Potter, W, Snyder, P, Schwartz, A, Montine, T, Thomas, RG, Donohue, M, Walter, S, Gessert, D, Sather, T, Jiminez, G, Harvey, D, Bernstein, M, Fox, N, Thompson, P, Schuff, N, Borowski, B, Gunter, J, Senjem, M, Vemuri, P, Jones, D, Kantarci, K, Ward, C, Koeppe, RA, Foster, N, Reiman, EM, Chen, K, Mathis, C, Landau, S, Cairns, NJ, Householder, E, Taylor-Reinwald, L, Lee, V, Korecka, M, Figurski, M, Crawford, K, Neu, S, Foroud, TM, Potkin, S, Shen, L, Faber, K, Kim, S, Nho, K, Thal, L, Buckholtz, N, Albert, M, Frank, R, Hsiao, J, Kaye, J, Quinn, J, Lind, B, Carter, R, Dolen, S, Schneider, LS, Pawluczyk, S, Beccera, M, Teodoro, L, Spann, BM, Brewer, J, Vanderswag, H, Fleisher, A, Heidebrink, JL, Lord, JL, Mason, SS, Albers, CS, Knopman, D, Johnson, K, Doody, RS, Villanueva-Meyer, J, Chowdhury, M, and Rountree, S

Abstract

© 2015 Macmillan Publishers Limited. All rights reserved. Brain iron elevation is implicated in Alzheimer's disease (AD) pathogenesis, but the impact of iron on disease outcomes has not been previously explored in a longitudinal study. Ferritin is the major iron storage protein of the body; by using cerebrospinal fluid (CSF) levels of ferritin as an index, we explored whether brain iron status impacts longitudinal outcomes in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. We show that baseline CSF ferritin levels were negatively associated with cognitive performance over 7 years in 91 cognitively normal, 144 mild cognitive impairment (MCI) and 67 AD subjects, and predicted MCI conversion to AD. Ferritin was strongly associated with CSF apolipoprotein E levels and was elevated by the Alzheimer's risk allele, APOE-ε4. These findings reveal that elevated brain iron adversely impacts on AD progression, and introduce brain iron elevation as a possible mechanism for APOE-ε4 being the major genetic risk factor for AD.

Published
2015

28. T2-based arterial spin labeling measurements of blood to tissue water transfer in human brain

Author

Gregori, J., Schuff, N., Kern, R., Günther, M., and Publica

Abstract

Purpose: To investigate blood to tissue water transfer in human brain, in vivo and spatially resolved using a T2-based arterial spin labeling (ASL) method with 3D readout. Materials and Methods: A T2-ASL method is introduced to measure the water transfer processes between arterial blood and brain tissue based on a 3D-GRASE (gradient and spin echo) pulsed ASL sequence with multiecho readout. An analytical mathematical model is derived based on the General Kinetic Model, including blood and tissue compartment, T1 and T2 relaxation, and a blood-to-tissue transfer term. Data were collected from healthy volunteers on a 3 T system. The mean transfer time parameter T(ind bl --> ex) (blood to extravascular compartment transfer time) was derived voxelwise by nonlinear least-squares fitting. Results: Whole-brain maps of T(ind bl --> ex) show stable results in cortical regions, yielding different values depending on the brain region. The mean value across subjects and regions of interest (ROIs) in gray matter was 440 ± 30 msec. Conclusion: A novel method to derive whole-brain maps of blood to tissue water transfer dynamics is demonstrated. It is promising for the investigation of underlying physiological mechanisms and development of diagnostic applications in cerebrovascular diseases.

Published
2013

29. Arterial spin labeling MRI study of age and gender effects on brain perfusion hemodynamics

Author

Liu, Y., Zhu, X., Feinberg, D., Guenther, M., Gregori, J., Weiner, M.W., Schuff, N., and Publica

Abstract

Normal aging is associated with diminished brain perfusion measured as cerebral blood flow (CBF), but previously it is difficult to accurately measure various aspects of perfusion hemodynamics including: bolus arrival times and delays through small arterioles, expressed as arterial-arteriole transit time. To study hemodynamics in greater detail, volumetric arterial spin labeling MRI with variable postlabeling delays was used together with a distributed, dual-compartment tracer model. The main goal was to determine how CBF and other perfusion hemodynamics vary with aging. Twenty cognitive normal female and 15 male subjects (age: 23-84 years old) were studied at 4 T. Arterial spin labeling measurements were performed in the posterior cingulate cortex, precuneus, and whole brain gray matter. CBF declined with advancing age (P < 0.001). Separately from variations in bolus arrival times, arterial-arteriole transit time increased with advancing age (P < 0.01). Finally, women had overall higher CBF values (P < 0.01) and shorter arterial-arteriole transit time (P < 0.01) than men, regardless of age. The findings imply that CBF and blood transit times are compromised in aging, and these changes together with differences between genders should be taken into account when studying brain perfusion.

Published
2012

30. Multivariate Statistical Mapping of Spectroscopic Imaging Data

Author

Young, K., Govind, V., Sharma, K., Studholme, C., Maudsley, A.A, and Schuff, N.

Subjects
Adult, Male, Aspartic Acid, Magnetic Resonance Spectroscopy, Amyotrophic Lateral Sclerosis, Brain, Reproducibility of Results, Middle Aged, Sensitivity and Specificity, Article, Choline, Creatinine, Multivariate Analysis, Humans, Algorithms, Biomarkers
Abstract

For magnetic resonance spectroscopic imaging studies of the brain, it is important to measure the distribution of metabolites in a regionally unbiased way; that is, without restrictions to a priori defined regions of interest. Since magnetic resonance spectroscopic imaging provides measures of multiple metabolites simultaneously at each voxel, there is furthermore great interest in utilizing the multidimensional nature of magnetic resonance spectroscopic imaging for gains in statistical power. Voxelwise multivariate statistical mapping is expected to address both of these issues, but it has not been previously employed for spectroscopic imaging (SI) studies of brain. The aims of this study were to (1) develop and validate multivariate voxel-based statistical mapping for magnetic resonance spectroscopic imaging and (2) demonstrate that multivariate tests can be more powerful than univariate tests in identifying patterns of altered brain metabolism. Specifically, we compared multivariate to univariate tests in identifying known regional patterns in simulated data and regional patterns of metabolite alterations due to amyotrophic lateral sclerosis, a devastating brain disease of the motor neurons.

Published
2010

31. Voxel-based T2 relaxation rate measurements in temporal lobe epilepsy (TLE) with and without mesial temporal sclerosis

Author

Mueller, S G, Laxer, K D, Schuff, N, and Weiner, Michael W

Subjects
TLE, relaxation rate, voxel-based, nervous system, mesiotemporal sclerosis, extratemporal, behavioral disciplines and activities, psychological phenomena and processes, nervous system diseases, normal MRI
Abstract

Introduction: Quantitative measurements of T-2 relaxation in the hippocampus for focus lateralization in mesial temporal lobe epilepsy (mTLE) are well established. Less is known to what degree such relaxation abnormalities also affect regions beyond the ipsilateral hippocampus. Therefore, the aim of this study was to characterize extent and distribution pattern of extrahippocampal relaxation abnormalities in TLE with (TLE-MTS) and without MRI evidence of mesial-temporal sclerosis (TLE-no). Methods: Double spin echo images (TE1/2: 20/80 ms) acquired in 24 TLE-MTS and 18 TLE-no were used to calculate relaxation rate maps. These maps were analyzed by SPM2 and by selecting regions of interest (ROI) in the hippocampus and several extrahippocampal brain regions. Results: In TLE-MTS, the results of the SPM and ROI analysis were in good agreement and showed the most severe relaxation rate decreases in the ipsilateral hippocampus but also in other ipsilateral temporal regions, orbitofrontal, and parietal regions and to a lesser degree in contralateral frontal regions. The relaxation rate decreases in TLE-no were confined to small regions in the ipsilateral anterior inferior and medial temporal lobe in the SPM analysis while ROI analysis showed additional regions in the ipsilateral hippocampus, amygdala, and anterior cingulate. Conclusion: TLE-MTS showed extensive, widespread but predominantly ipsilateral temporal and also extratemporal T-2 relaxation rate decreases. In contrast, the findings of the SPM and ROI analyses in TLE-no suggested that if relaxation rate decreases are present, they are less uniform and generally milder than in TLE-MTS. This further supports the hypothesis that TLE-no is a distinct clinicopathological entity from TLE-MTS and probably heterogeneous in itself.

Published
2007

32. Bayesian parallel Imaging with edge-preserving priors

Author

Raj, Ashish, Singh, Gurmeet, Zabih, R, Kressler, B, Wang, Y, Schuff, N, and Weiner, M

Subjects
regularization, SENSE, edge-preserving priors, Bayesian reconstruction, graph cuts, parallel imaging
Abstract

Existing parallel MRI methods are limited by a fundamental trade-off in that suppressing noise introduces aliasing artifacts. Bayesian methods with an appropriately chosen image prior offer a promising alternative; however, previous methods with spatial priors assume that intensities vary smoothly over the entire image, resulting in blurred edges. Here we introduce an edge-preserving prior (EPP) that instead assumes that intensities are piecewise smooth, and propose a new approach to efficiently compute its Bayesian estimate. The estimation task is formulated as an optimization problem that requires a non-convex objective function to be minimized in a space with thousands of dimensions. As a result, traditional continuous minimization methods cannot be applied. This optimization task is closely related to some problems in the field of computer vision for which discrete optimization methods have been developed in the last few years. We adapt these algorithms, which are based on graph cuts, to address our optimization problem. The results of several parallel imaging experiments on brain and torso regions performed under challenging conditions with high acceleration factors are shown and compared with the results of conventional sensitivity encoding (SENSE) methods. An empirical analysis indicates that the proposed method visually improves overall quality compared to conventional methods.

Published
2007

33. Comparison of methods for measuring longitudinal brain change in cognitive impairment and dementia

Author

Cardenas, V A, Du, A T, Hardin, D, Ezekiel, F, Weber, P, Jagust, W J, Chui, H C, Schuff, N, and Weiner, M W

Subjects
longitudinal, neuroradiology, cognitive disorders/dementia, image processing
Abstract

Purpose: The goal of this project was to compare MRI measures of hippocampal, entorhinal cortex (ERC), and whole brain longitudinal change in cognitively normal elderly controls (C), non-demented subjects with cognitive impairment (CI), and demented (D) subjects. Methods: 16 C, 6 CI, and 7 D subjects of comparable age were studied with MRI twice, at least 1 year apart. Longitudinal change in total brain size was measured by several methods, including computerized segmentation, non-linear warping, and change in the fluid/tissue boundaries between cerebrospinal fluid (CSF) and brain. Change in hippocampal volume was measured by semi-automated methods, and ERC volumes were manually measured. Results: The annual rate of atrophy was greater in D versus C and D versus CI for cortical gray matter (cGM) (P = 0.009 and 0.002), hippocampus (P = 0.0001 and 0.002), and for the change in the fluid/tissue boundary (P = 0.03 and 0.03). The annual rate of atrophy of ERC was greater in both CI and D versus C (P = 0.01 and 0.0002). No significant differences between groups were found using non-linear warping. Conclusions: In CI, the greatest annual rates of atrophy were in ERC, while in D the greatest annual rates of atrophy were in hippocampus and cortex. Progressive ERC atrophy was observed with a greater degree of cognitive impairment, while hippocampal and cortical atrophy were only observed in demented subjects. (C) 2002 Elsevier Science Inc. All rights reserved.

Published
2003

41. Improved Arterial Spin Labeling Perfusion Method to Measure White Matter Perfusion at a 4 Tesla MRI.

Author

Kim, Sun I., Suh, Tae Suk, Magjarevic, R., Nagel, J. H., Geon-Ho Jahng, Weiner, M. W., and Schuff, N.

Abstract

Purposes: Measurement of cerebral blood flow (CBF) in white matter (WM) has been a major challenge due to a poor signal-to-noise (SNR) ratio and a long arterial transit time in WM. Therefore, technical improvements of better SNR and greater independence from transit time can play a significant role. The purpose of this work was that a pulsed arterial spin labeling (ASL) method is developed to achieve multislice WM CBF imaging at a high field magnetic resonance imaging (MRI). Methods: In the proposed ASL method, stationary spins in an imaging plane are kept at equilibrium to avoid noise due to T1 relaxation, while blood water is labeled using in-plane double inversion. The proposed method was tested on five subjects and compared with existing ASL MRI methods at a 1.5 Tesla MRI to show improvement and was tested on additional 7 subjects using echo-planar imaging (EPI) and Turbo-Flash (TFL) acquisitions using various post-labeling delay times to test feasibility to measure WM CBF at a 4 Tesla MRI. WM and gray matter (GM) CBF maps were obtained and analyzed within the statistical parametric mapping (SPM) tool. Results: CBF measurements with the proposed method were less confounded by magnetization transfer effects and less dependent on blood velocity than the existing methods studied at the 1.5T MRI. Furthermore, the proposed method yielded excellent gray/white contrast of CBF maps. The ratios of GM to WM CBF were consistently higher on TFL (average 1.61) than on EPI (average 1.45) at the 4T MRI. Furthermore, TFL acquisitions achieved more stable CBF measurements than EPI in various brain regions. Conclusion: The proposed ASL method improved CBF imaging at 1.5T and 4.0T and accomplished to measure CBF of WM at 4T. Therefore, the proposed method should improve accuracy in measuring regional CBF. [ABSTRACT FROM AUTHOR]

Published
2007
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43. MRI of Entorhinal Cortex and Hippocampus in Alzheimer's Disease, Subcortical Ischemic Vascular Dementia and Mixed Dementia.

Author

Schuff, N., Du, A. T., Amend, D., Hsu, Y. Y., Laakso, M. P., Jagust, W., Chui, H. C., and Weiner, M. W.

Subjects
VASCULAR dementia, DIAGNOSTIC imaging, MAGNETIC resonance imaging, ALZHEIMER'S disease, NEUROBEHAVIORAL disorders, NEUROLOGICAL disorders, NEUROLOGY
Abstract

Early in vivo magnetic resonance imaging (MRI) studies of Alzheimer's disease reported hippocampal atrophy that could, to a high degree, distinguish Alzheimer's disease patients from cognitively normal elderly subjects. Additional research has shown that these measurements may not be as accurate at least for patients in mild stages of the disease. [ABSTRACT FROM PUBLISHER]

Published
2001

44. MRI signatures of brain macrostructural atrophy and microstructural degradation in frontotemporal lobar degeneration subtypes.

Author

Zhang Y, Tartaglia MC, Schuff N, Chiang GC, Ching C, Rosen HJ, Gorno-Tempini ML, Miller BL, Weiner MW, Zhang, Yu, Tartaglia, Maria Carmela, Schuff, Norbert, Chiang, Gloria C, Ching, Christopher, Rosen, Howard J, Gorno-Tempini, Maria Luisa, Miller, Bruce L, and Weiner, Michael W

Abstract

Brain magnetic resonance imaging (MRI) studies have demonstrated regional patterns of brain macrostructural atrophy and white matter microstructural alterations separately in the three major subtypes of frontotemporal lobar degeneration (FTLD), which includes behavioral variant frontotemporal dementia (bvFTD), semantic dementia (SD), and progressive nonfluent aphasia (PNFA). This study was to investigate to what extent the pattern of white matter microstructural alterations in FTLD subtypes mirrors the pattern of brain atrophy, and to compare the ability of various diffusion tensor imaging (DTI) indices in characterizing FTLD patients, as well as to determine whether DTI measures provide greater classification power for FTLD than measuring brain atrophy. Twenty-five patients with FTLD (13 with bvFTD, 6 with SD, and 6 with PNFA) and 19 healthy age-matched control subjects underwent both structural MRI and DTI scans. Measurements of regional brain atrophy were based on T1-weighted MRI data and voxel-based morphometry. Measurements of regional white matter degradation were based on voxelwise as well as regions-of-interest tests of DTI variations, expressed as fractional anisotropy, axial diffusivity, and radial diffusivity. Compared to controls, bvFTD, SD, and PNFA patients each exhibited characteristic regional patterns of brain atrophy and white matter damage. DTI overall provided significantly greater accuracy for FTLD classification than brain atrophy. Moreover, radial diffusivity was more sensitive in assessing white matter damage in FTLD than other DTI indices. The findings suggest that DTI in general and radial diffusivity in particular are more powerful measures for the classification of FTLD patients from controls than brain atrophy. [ABSTRACT FROM AUTHOR]

Published
2013
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45. Spatial patterns of brain amyloid-beta burden and atrophy rate associations in mild cognitive impairment.

Author

Tosun D, Schuff N, Mathis CA, Jagust W, Weiner MW, Alzheimer's Disease NeuroImaging Initiative, Tosun, Duygu, Schuff, Norbert, Mathis, Chester A, Jagust, William, and Weiner, Michael W

Abstract

Amyloid-β accumulation in the brain is thought to be one of the earliest events in Alzheimer's disease, possibly leading to synaptic dysfunction, neurodegeneration and cognitive/functional decline. The earliest detectable changes seen with neuroimaging appear to be amyloid-β accumulation detected by (11)C-labelled Pittsburgh compound B positron emission tomography imaging. However, some individuals tolerate high brain amyloid-β loads without developing symptoms, while others progressively decline, suggesting that events in the brain downstream from amyloid-β deposition, such as regional brain atrophy rates, play an important role. The main purpose of this study was to understand the relationship between the regional distributions of increased amyloid-β and the regional distribution of increased brain atrophy rates in patients with mild cognitive impairment. To simultaneously capture the spatial distributions of amyloid-β and brain atrophy rates, we employed the statistical concept of parallel independent component analysis, an effective method for joint analysis of multimodal imaging data. Parallel independent component analysis identified significant relationships between two patterns of amyloid-β deposition and atrophy rates: (i) increased amyloid-β burden in the left precuneus/cuneus and medial-temporal regions was associated with increased brain atrophy rates in the left medial-temporal and parietal regions; and (ii) in contrast, increased amyloid-β burden in bilateral precuneus/cuneus and parietal regions was associated with increased brain atrophy rates in the right medial temporal regions. The spatial distribution of increased amyloid-β and the associated spatial distribution of increased brain atrophy rates embrace a characteristic pattern of brain structures known for a high vulnerability to Alzheimer's disease pathology, encouraging for the use of (11)C-labelled Pittsburgh compound B positron emission tomography measures as early indicators of Alzheimer's disease. These results may begin to shed light on the mechanisms by which amyloid-β deposition leads to neurodegeneration and cognitive decline and the development of a more specific Alzheimer's disease-specific imaging signature for diagnosis and use of this knowledge in the development of new anti-therapies for Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Published
2011
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47. Different regional patterns of cortical thinning in Alzheimer's disease and frontotemporal dementia.

Author

Du A, Schuff N, Kramer JH, Rosen HJ, Gorno-Tempini ML, Rankin K, Miller BL, Weiner MW, Du, An-Tao, Schuff, Norbert, Kramer, Joel H, Rosen, Howard J, Gorno-Tempini, Maria Luisa, Rankin, Katherine, Miller, Bruce L, and Weiner, Michael W

Abstract

Alzheimer's disease and frontotemporal dementia (FTD) can be difficult to differentiate clinically because of overlapping symptoms. Distinguishing the two dementias based on volumetric measurements of brain atrophy with MRI has been only partially successful. Whether MRI measurements of cortical thinning improve the differentiation between Alzheimer's disease and FTD is unclear. In this study, we measured cortical thickness using a set of automated tools (Freesurfer) to reconstruct the brain's cortical surface from T1-weighted structural MRI data in 22 patients with Alzheimer's disease, 19 patients with FTD and 23 cognitively normal subjects. The goals were to detect the characteristic patterns of cortical thinning in these two types of dementia, to test the relationship between cortical thickness and cognitive impairment, to determine if measurement of cortical thickness is better than that of cortical volume for differentiating between these dementias and normal ageing and improving the classification of Alzheimer's disease and FTD based on neuropsychological scores alone. Compared to cognitively normal subjects, Alzheimer's disease patients had a thinner cortex primarily in bilateral, frontal, parietal, temporal and occipital lobes (P < 0.001), while FTD patients had a thinner cortex in bilateral, frontal and temporal regions and some thinning in inferior parietal regions and the posterior cingulate (P < 0.001). Compared to FTD patients, Alzheimer's disease patients had a thinner cortex (P < 0.001) in parts of bilateral parietal and precuneus regions. Cognitive impairment was negatively correlated with cortical thickness of frontal, parietal and temporal lobes in Alzheimer's disease, while similar correlations were not significant in FTD. Measurement of cortical thickness was similar to that of cortical volume in differentiating between normal ageing, Alzheimer's disease and FTD. Furthermore, cortical thickness measurements significantly improved the classification between Alzheimer's disease and FTD based on neuropsychological scores alone, including the Mini-Mental State Examination and a modified version of the Trail-Making Test. In conclusion, the characteristic patterns of cortical thinning in Alzheimer's disease and FTD suggest that cortical thickness may be a useful surrogate marker for these types of dementia. [ABSTRACT FROM AUTHOR]

Published
2007

48. Evaluation of treatment effects in Alzheimer's and other neurodegenerative diseases by MRI and MRS.

Author

Mueller, S. G., Schuff, N., and Weiner, M. W.

Abstract

Neurodegeneration refers to a large clinically and pathologically heterogeneous disease entity associated with slowly progressive neuronal loss in different anatomical and functional systems of the brain. Neurodegenerative diseases often affect cognition, e.g. Alzheimer's disease (AD), dementia with Lewy bodies and vascular dementia, or different aspects of the motor system, e.g., amyotrophic lateral sclerosis, Parkinson's disease and ataxic disorders. Owing to increasing knowledge about the mechanisms leading to neurodegeneration, the development of treatments able to modify the neurodegenerative process becomes possible for the first time. Currently, clinical outcome measures are used to assess the efficacy of such treatments. However, most clinical outcome measures have a low test-retest reliability and thus considerable measurement variance. Therefore, large patient populations and long observation times are needed to detect treatment effects. Furthermore, clinical outcome measures cannot distinguish between symptomatic and disease-modifying treatment effects. Therefore, alternative biomarkers including neuroimaging may take on a more important role in this process. Because MR scanners are widely available and allow for non-invasive detection and quantification of changes in brain structure and metabolism, there is increasing interest in the use of MRI/MRS to monitor objectively treatment effects in clinical trials of neurodegenerative diseases. Particularly volumetric MRI has been used to measure atrophy rates in treatment trials of AD because the relationship between atrophic changes and neuron loss is well established and correlates well with clinical measures. More research is needed to determine the value of other MR modalities, i.e. diffusion, perfusion and functional MRI and MR spectroscopy, for clinical trials with neuroprotective drugs. Copyright © 2006 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Published
2006
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49. Comprehensive processing, display and analysis for in vivo MR spectroscopic imaging.

Author

Maudsley, A. A., Darkazanli, A., Alger, J. R., Hall, L. O., Schuff, N., Studholme, C., Yu, Y., Ebel, A., Frew, A., Goldgof, D., Gu, Y., Pagare, R., Rousseau, F., Sivasankaran, K., Soher, B. J., Weber, P., Young, K., and Zhu, X.

Abstract

Image reconstruction for magnetic resonance spectroscopic imaging (MRSI) requires specialized spatial and spectral data processing methods and benefits from the use of several sources of prior information that are not commonly available, including MRI-derived tissue segmentation, morphological analysis and spectral characteristics of the observed metabolites. In addition, incorporating information obtained from MRI data can enhance the display of low-resolution metabolite images and multiparametric and regional statistical analysis methods can improve detection of altered metabolite distributions. As a result, full MRSI processing and analysis can involve multiple processing steps and several different data types. In this paper, a processing environment is described that integrates and automates these data processing and analysis functions for imaging of proton metabolite distributions in the normal human brain. The capabilities include normalization of metabolite signal intensities and transformation into a common spatial reference frame, thereby allowing the formation of a database of MR-measured human metabolite values as a function of acquisition, spatial and subject parameters. This development is carried out under the MIDAS project (Metabolite Imaging and Data Analysis System), which provides an integrated set of MRI and MRSI processing functions. It is anticipated that further development and distribution of these capabilities will facilitate more widespread use of MRSI for diagnostic imaging, encourage the development of standardized MRSI acquisition, processing and analysis methods and enable improved mapping of metabolite distributions in the human brain. Copyright © 2006 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Published
2006
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50. Robust analysis of short echo time 1H MRSI of human brain.

Author

Zhu, X. P., Young, K., Ebel, A., Soher, B. J., Kaiser, L., Matson, G., Weiner, W. M., and Schuff, N.

Abstract

Short echo time proton MR Spectroscopic Imaging (MRSI) suffers from low signal-to-noise ratio (SNR), limiting accuracy to estimate metabolite intensities. A method to coherently sum spectra in a region of interest of the human brain by appropriate peak alignment was developed to yield a mean spectrum with increased SNR. Furthermore, principal component (PC) spectra were calculated to estimate the variance of the mean spectrum. The mean or alternatively the first PC (PC1) spectrum from the same region can be used for quantitation of peak areas of metabolites in the human brain at increased SNR. Monte Carlo simulations showed that both mean and PC1 spectra were more accurate in estimating regional metabolite concentrations than solutions that regress individual spectra against the tissue compositions of MRSI voxels. Back-to-back MRSI studies on 10 healthy volunteers showed that mean spectra markedly improved reliability of brain metabolite measurements, most notably for myo-inositol, as compared to regression methods. Magn Reson Med, 2006. Published 2006 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Published
2006
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