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Sample records for disease neuroimaging initiative

  1. Worldwide Alzheimer's disease neuroimaging initiative.

    PubMed

    Carrillo, Maria C; Bain, Lisa J; Frisoni, Giovanni B; Weiner, Michael W

    2012-07-01

    The Alzheimer's Disease Neuroimaging Initiative (ADNI) was launched in 2003 to speed drug development by validating imaging and blood/cerebrospinal fluid biomarkers for Alzheimer's disease clinical treatment trials. ADNI is a naturalistic (nontreatment) multisite longitudinal study. A true public-private partnership, the first phase of ADNI (ADNI 1) set a new standard for data sharing without embargo. In addition, it has been extended to 2017 by additional funding (North American-ADNI Grand Opportunities and ADNI 2) as well as multiple projects around the world, collectively known as Worldwide ADNI (WW-ADNI). The goal of WW-ADNI is to harmonize projects and results across different geographical sites and to encourage and harmonize data management and availability to investigators around the world. WW-ADNI projects are currently underway in North America, Europe, Japan, Australia, Korea, Taiwan, and Argentina, with a nascent program in China and a possible future program in Brazil. PMID:22748939

  2. The Worldwide Alzheimer's Disease Neuroimaging Initiative: An update.

    PubMed

    Hendrix, James A; Finger, Brad; Weiner, Michael W; Frisoni, Giovanni B; Iwatsubo, Takeshi; Rowe, Christopher C; Kim, Seong Yoon; Guinjoan, Salvador M; Sevlever, Gustavo; Carrillo, Maria C

    2015-07-01

    The Alzheimer's Disease Neuroimaging Initiative (ADNI), launched in 2004, has worked to accelerate drug development by validating imaging and blood/cerebrospinal fluid biomarkers for Alzheimer's disease clinical treatment trials. ADNI is a naturalistic (nontreatment) multisite longitudinal study. A true public-private partnership, the initiative has set a new standard for data sharing without embargo and for the use of biomarkers in dementia research. The ADNI effort in North America is not the only such effort in the world. The Alzheimer's Association recognized these global efforts and formed Worldwide ADNI (WW-ADNI). By creating a platform for international collaboration and cooperation, WW-ADNI's goals are to harmonize projects and results across geographical regions and to facilitate data management and availability to investigators around the world. WW-ADNI projects include those based in North America, Europe, Japan, Australia, Korea, and Argentina. PMID:26194318

  3. The Alzheimer’s Disease Neuroimaging Initiative Informatics Core: A Decade in Review

    PubMed Central

    Toga, Arthur W.; Crawford, Karen L.

    2015-01-01

    The Informatics Core of the Alzheimer’s Diseases Neuroimaging Initiative (ADNI) has coordinated data integration and dissemination for a continually growing and complex dataset in which both data contributors and recipients span institutions, scientific disciplines and geographic boundaries. This article provides an update on the accomplishments and future plans. PMID:26194316

  4. Alzheimer’s Disease Neuroimaging Initiative biomarkers as quantitative phenotypes: Genetics core aims, progress, and plans

    PubMed Central

    Saykin, Andrew J.; Shen, Li; Foroud, Tatiana M.; Potkin, Steven G.; Swaminathan, Shanker; Kim, Sungeun; Risacher, Shannon L.; Nho, Kwangsik; Huentelman, Matthew J.; Craig, David W.; Thompson, Paul M.; Stein, Jason L.; Moore, Jason H.; Farrer, Lindsay A.; Green, Robert C.; Bertram, Lars; Jack, Clifford R.; Weiner, Michael W.

    2010-01-01

    The role of the Alzheimer’s Disease Neuroimaging Initiative Genetics Core is to facilitate the investigation of genetic influences on disease onset and trajectory as reflected in structural, functional, and molecular imaging changes; fluid biomarkers; and cognitive status. Major goals include (1) blood sample processing, genotyping, and dissemination, (2) genome-wide association studies (GWAS) of longitudinal phenotypic data, and (3) providing a central resource, point of contact and planning group for genetics within Alzheimer’s Disease Neuroimaging Initiative. Genome-wide array data have been publicly released and updated, and several neuroimaging GWAS have recently been reported examining baseline magnetic resonance imaging measures as quantitative phenotypes. Other preliminary investigations include copy number variation in mild cognitive impairment and Alzheimer’s disease and GWAS of baseline cerebrospinal fluid biomarkers and longitudinal changes on magnetic resonance imaging. Blood collection for RNA studies is a new direction. Genetic studies of longitudinal phenotypes hold promise for elucidating disease mechanisms and risk, development of therapeutic strategies, and refining selection criteria for clinical trials. PMID:20451875

  5. Clinical Core of the Alzheimer's Disease Neuroimaging Initiative: progress and plans.

    PubMed

    Aisen, Paul S; Petersen, Ronald C; Donohue, Michael C; Gamst, Anthony; Raman, Rema; Thomas, Ronald G; Walter, Sarah; Trojanowski, John Q; Shaw, Leslie M; Beckett, Laurel A; Jack, Clifford R; Jagust, William; Toga, Arthur W; Saykin, Andrew J; Morris, John C; Green, Robert C; Weiner, Michael W

    2010-05-01

    The Clinical Core of the Alzheimer's Disease Neuroimaging Initiative (ADNI) has provided clinical, operational, and data management support to ADNI since its inception. This article reviews the activities and accomplishments of the core in support of ADNI aims. These include the enrollment and follow-up of more than 800 subjects in the three original cohorts: healthy controls, amnestic mild cognitive impairment (now referred to as late MCI, or LMCI), and mild Alzheimer's disease (AD) in the first phase of ADNI (ADNI 1), with baseline longitudinal, clinical, and cognitive assessments. These data, when combined with genetic, neuroimaging, and cerebrospinal fluid measures, have provided important insights into the neurobiology of the AD spectrum. Furthermore, these data have facilitated the development of novel clinical trial designs. ADNI has recently been extended with funding from an NIH Grand Opportunities (GO) award, and the new ADNI GO phase has been launched; this includes the enrollment of a new cohort, called early MCI, with milder episodic memory impairment than the LMCI group. An application for a further 5 years of ADNI funding (ADNI 2) was recently submitted. This funding would support ongoing follow-up of the original ADNI 1 and ADNI GO cohorts, as well as additional recruitment into all categories. The resulting data would provide valuable data on the earliest stages of AD, and support the development of interventions in these critically important populations. PMID:20451872

  6. Impact of the Alzheimer’s Disease Neuroimaging Initiative, 2004 to 2014

    PubMed Central

    Weiner, Michael W.; Veitch, Dallas P.; Aisen, Paul S.; Beckett, Laurel A.; Cairns, Nigel J.; Cedarbaum, Jesse; Donohue, Michael C.; Green, Robert C.; Harvey, Danielle; Jack, Clifford R.; Jagust, William; Morris, John C.; Petersen, Ronald C.; Saykin, Andrew J.; Shaw, Leslie; Thompson, Paul M.; Toga, Arthur W.; Trojanowski, John Q.

    2015-01-01

    Introduction The Alzheimer’s Disease Neuroimaging Initiative (ADNI) was established in 2004 to facilitate the development of effective treatments for Alzheimer’s disease (AD) by validating biomarkers for AD clinical trials. Methods We searched for ADNI publications using established methods. Results ADNI has (1) developed standardized biomarkers for use in clinical trial subject selection and as surrogate outcome measures; (2) standardized protocols for use across multiple centers; (3) initiated worldwide ADNI; (4) inspired initiatives investigating traumatic brain injury and post-traumatic stress disorder in military populations, and depression, respectively, as an AD risk factor; (5) acted as a data-sharing model; (6) generated data used in over 600 publications, leading to the identification of novel AD risk alleles, and an understanding of the relationship between biomarkers and AD progression; and (7) inspired other public-private partnerships developing biomarkers for Parkinson’s disease and multiple sclerosis. Discussion ADNI has made myriad impacts in its first decade. A competitive renewal of the project in 2015 would see the use of newly developed tau imaging ligands, and the continued development of recruitment strategies and outcome measures for clinical trials. PMID:26194320

  7. The Alzheimer’s Disease Neuroimaging Initiative: Progress report and future plans

    PubMed Central

    Weiner, Michael W.; Aisen, Paul S.; Jack, Clifford R.; Jagust, William J.; Trojanowski, John Q.; Shaw, Leslie; Saykin, Andrew J.; Morris, John C.; Cairns, Nigel; Beckett, Laurel A.; Toga, Arthur; Green, Robert; Walter, Sarah; Soares, Holly; Snyder, Peter; Siemers, Eric; Potter, William; Cole, Patricia E.; Schmidt, Mark

    2010-01-01

    The Alzheimer’s Disease Neuroimaging Initiative (ADNI) beginning in October 2004, is a 6-year re-search project that studies changes of cognition, function, brain structure and function, and biomarkers in elderly controls, subjects with mild cognitive impairment, and subjects with Alzheimer’s disease (AD). A major goal is to determine and validate MRI, PET images, and cerebrospinal fluid (CSF)/blood biomarkers as predictors and outcomes for use in clinical trials of AD treatments. Structural MRI, FDG PET, C-11 Pittsburgh compound B (PIB) PET, CSF measurements of amyloid β (Aβ) and species of tau, with clinical/cognitive measurements were performed on elderly controls, subjects with mild cognitive impairment, and subjects with AD. Structural MRI shows high rates of brain atrophy, and has high statistical power for determining treatment effects. FDG PET, C-11 Pittsburgh compound B PET, and CSF measurements of Aβ and tau were significant predictors of cognitive decline and brain atrophy. All data are available at UCLA/LONI/ADNI, without embargo. ADNI-like projects started in Australia, Europe, Japan, and Korea. ADNI provides significant new information concerning the progression of AD. PMID:20451868

  8. Intrinsic Functional Component Analysis via Sparse Representation on Alzheimer's Disease Neuroimaging Initiative Database

    PubMed Central

    Jiang, Xi; Zhang, Xin

    2014-01-01

    Abstract Alzheimer's disease (AD) is the most common type of dementia (accounting for 60% to 80%) and is the fifth leading cause of death for those people who are 65 or older. By 2050, one new case of AD in United States is expected to develop every 33 sec. Unfortunately, there is no available effective treatment that can stop or slow the death of neurons that causes AD symptoms. On the other hand, it is widely believed that AD starts before development of the associated symptoms, so its prestages, including mild cognitive impairment (MCI) or even significant memory concern (SMC), have received increasing attention, not only because of their potential as a precursor of AD, but also as a possible predictor of conversion to other neurodegenerative diseases. Although these prestages have been defined clinically, accurate/efficient diagnosis is still challenging. Moreover, brain functional abnormalities behind those alterations and conversions are still unclear. In this article, by developing novel sparse representations of whole-brain resting-state functional magnetic resonance imaging signals and by using the most updated Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset, we successfully identified multiple functional components simultaneously, and which potentially represent those intrinsic functional networks involved in the resting-state activities. Interestingly, these identified functional components contain all the resting-state networks obtained from traditional independent-component analysis. Moreover, by using the features derived from those functional components, it yields high classification accuracy for both AD (94%) and MCI (92%) versus normal controls. Even for SMC we can still have 92% accuracy. PMID:24846640

  9. Neuroimaging of neurocutaneous diseases.

    PubMed

    Nandigam, Kaveer; Mechtler, Laszlo L; Smirniotopoulos, James G

    2014-02-01

    An in-depth knowledge of the imaging characteristics of the common neurocutaneous diseases (NCD) described in this article will help neurologists understand the screening imaging modalities in these patients. The future of neuroimaging is geared towards developing and refining magnetic resonance imaging (MRI) sequences. The detection of tumors in NCD has greatly improved with availability of high-field strength 3T MRI machines. Neuroimaging will remain at the heart and soul of the multidisciplinary care of such complex diagnoses to guide early detection and monitor treatment. PMID:24287389

  10. The Alzheimer’s Disease Neuroimaging Initiative: A review of papers published since its inception

    PubMed Central

    Weiner, Michael W.; Veitch, Dallas P.; Aisen, Paul S.; Beckett, Laurel A.; Cairns, Nigel J.; Green, Robert C.; Harvey, Danielle; Jack, Clifford R.; Jagust, William; Liu, Enchi; Morris, John C.; Petersen, Ronald C.; Saykin, Andrew J.; Schmidt, Mark E.; Shaw, Leslie; Siuciak, Judith A.; Soares, Holly; Toga, Arthur W.; Trojanowski, John Q.

    2012-01-01

    The Alzheimer’s Disease Neuroimaging Initiative (ADNI) is an ongoing, longitudinal, multicenter study designed to develop clinical, imaging, genetic and biochemical biomarkers for the early detection and tracking of Alzheimer’s disease (AD). The study aimed to enroll 400 subjects with early mild cognitive impairment (MCI), 200 subjects with early AD and 200 normal controls and $67 million funding was provided by both the public and private sectors including the National Institutes on Aging, thirteen pharmaceutical companies and two Foundations that provided support through the Foundation for NIH (FNIH). This article reviews all papers published since the inception of the initiative and summarizes the results as of February, 2011. The major accomplishments of ADNI have been 1) the development of standardized methods for clinical, magnetic resonance imaging (MRI) and positron emission tomography (PET) and cerebrospinal fluid (CSF) biomarkers in a multi-center setting; 2) elucidation of the patterns and rates of change of imaging and CSF biomarker measurements in control, MCI and AD patients. CSF biomarkers are consistent with disease trajectories predicted by β amyloid (Aβ) cascade [1] and tau mediated neurodegeneration hypotheses for AD while brain atrophy and hypometabolism levels show predicted patterns but exhibit differing rates of change depending on region and disease severity; 3) the assessment of alternative methods of diagnostic categorization. Currently, the best classifiers combine optimum features from multiple modalities including MRI, FDG-PET, CSF biomarkers and clinical tests; 4) the development of methods for the early detection of AD. CSF biomarkers, Aβ42 and tau as well as amyloid PET may reflect the earliest steps in AD pathology in mildly or even non-symptomatic subjects and are leading candidates for the detection of AD in its preclinical stages; 5) the improvement of clinical trial efficiency through the identification of subjects most

  11. The Alzheimer's Disease Neuroimaging Initiative: A review of papers published since its inception

    PubMed Central

    Weiner, Michael W.; Veitch, Dallas P.; Aisen, Paul S.; Beckett, Laurel A.; Cairns, Nigel J.; Green, Robert C.; Harvey, Danielle; Jack, Clifford R.; Jagust, William; Liu, Enchi; Morris, John C.; Petersen, Ronald C.; Saykin, Andrew J.; Schmidt, Mark E.; Shaw, Leslie; Shen, Li; Siuciak, Judith A.; Soares, Holly; Toga, Arthur W.; Trojanowski, John Q.

    2014-01-01

    The Alzheimer's Disease Neuroimaging Initiative (ADNI) is an ongoing, longitudinal, multicenter study designed to develop clinical, imaging, genetic, and biochemical biomarkers for the early detection and tracking of Alzheimer's disease (AD). The study aimed to enroll 400 subjects with early mild cognitive impairment (MCI), 200 subjects with early AD, and 200 normal control subjects; $67 million funding was provided by both the public and private sectors, including the National Institute on Aging, 13 pharmaceutical companies, and 2 foundations that provided support through the Foundation for the National Institutes of Health. This article reviews all papers published since the inception of the initiative and summarizes the results as of February 2011. The major accomplishments of ADNI have been as follows: (1) the development of standardized methods for clinical tests, magnetic resonance imaging (MRI), positron emission tomography (PET), and cerebrospinal fluid (CSF) biomarkers in a multicenter setting; (2) elucidation of the patterns and rates of change of imaging and CSF biomarker measurements in control subjects, MCI patients, and AD patients. CSF biomarkers are consistent with disease trajectories predicted by β-amyloid cascade (Hardy, J Alzheimers Dis 2006;9(Suppl 3):151–3) and tau-mediated neurodegeneration hypotheses for AD, whereas brain atrophy and hypometabolism levels show predicted patterns but exhibit differing rates of change depending on region and disease severity; (3) the assessment of alternative methods of diagnostic categorization. Currently, the best classifiers combine optimum features from multiple modalities, including MRI, [18F]-fluorodeoxyglucose-PET, CSF biomarkers, and clinical tests; (4) the development of methods for the early detection of AD. CSF biomarkers, β-amyloid 42 and tau, as well as amyloid PET may reflect the earliest steps in AD pathology in mildly symptomatic or even nonsymptomatic subjects, and are leading candidates

  12. Perspective: The Alzheimer's Disease Neuroimaging Initiative and the role and contributions of the Private Partner Scientific Board (PPSB).

    PubMed

    Liu, Enchi; Luthman, Johan; Cedarbaum, Jesse M; Schmidt, Mark E; Cole, Patricia E; Hendrix, James; Carrillo, Maria C; Jones-Davis, Dorothy; Tarver, Erika; Novak, Gerald; De Santi, Susan; Soares, Holly D; Potter, William Z; Siemers, Eric; Schwarz, Adam J

    2015-07-01

    The Alzheimer's Disease Neuroimaging Initiative (ADNI) Private Partner Scientific Board (PPSB) is comprised of representatives of private, for-profit entities (including pharmaceutical, biotechnology, diagnostics, imaging companies, and imaging contract research organizations), and nonprofit organizations that provide financial and scientific support to ADNI through the Foundation for the National Institutes of Health. The PPSB serves as an independent, open, and precompetitive forum in which all private sector and not-for-profit partners in ADNI can collaborate, share information, and offer scientific and private-sector perspectives and expertise on issues relating to the ADNI project. In this article, we review and highlight the role, activities, and contributions of the PPSB within the ADNI project, and provide a perspective on remaining unmet needs and future directions. PMID:26194317

  13. Higher homocysteine associated with thinner cortical gray matter in 803 participants from the Alzheimer's Disease Neuroimaging Initiative.

    PubMed

    Madsen, Sarah K; Rajagopalan, Priya; Joshi, Shantanu H; Toga, Arthur W; Thompson, Paul M

    2015-01-01

    A significant portion of our risk for dementia in old age is associated with lifestyle factors (diet, exercise, and cardiovascular health) that are modifiable, at least in principle. One such risk factor, high-homocysteine levels in the blood, is known to increase risk for Alzheimer's disease and vascular disorders. Here, we set out to understand how homocysteine levels relate to 3D surface-based maps of cortical gray matter distribution (thickness, volume, and surface area) computed from brain magnetic resonance imaging in 803 elderly subjects from the Alzheimer's Disease Neuroimaging Initiative data set. Individuals with higher plasma levels of homocysteine had lower gray matter thickness in bilateral frontal, parietal, occipital, and right temporal regions and lower gray matter volumes in left frontal, parietal, temporal, and occipital regions, after controlling for diagnosis, age, and sex and after correcting for multiple comparisons. No significant within-group associations were found in cognitively healthy people, patients with mild cognitive impairment, or patients with Alzheimer's disease. These regional differences in gray matter structure may be useful biomarkers to assess the effectiveness of interventions, such as vitamin B supplements, that aim to prevent homocysteine-related brain atrophy by normalizing homocysteine levels. PMID:25444607

  14. Cognitive reserve and Aβ1-42 in mild cognitive impairment (Argentina-Alzheimer’s Disease Neuroimaging Initiative)

    PubMed Central

    Harris, Paula; Fernandez Suarez, Marcos; Surace, Ezequiel I; Chrem Méndez, Patricio; Martín, María Eugenia; Clarens, María Florencia; Tapajóz, Fernanda; Russo, Maria Julieta; Campos, Jorge; Guinjoan, Salvador M; Sevlever, Gustavo; Allegri, Ricardo F

    2015-01-01

    Background The purpose of this study was to investigate the relationship between cognitive reserve and concentration of Aβ1-42 in the cerebrospinal fluid (CSF) of patients with mild cognitive impairment, those with Alzheimer’s disease, and in control subjects. Methods Thirty-three participants from the Argentina-Alzheimer’s Disease Neuroimaging Initiative database completed a cognitive battery, the Cognitive Reserve Questionnaire (CRQ), and an Argentinian accentuation reading test (TAP-BA) as a measure of premorbid intelligence, and underwent lumbar puncture for CSF biomarker quantification. Results The CRQ significantly correlated with TAP-BA, education, and Aβ1-42. When considering Aβ1-42 levels, significant differences were found in CRQ scores; higher levels of CSF Aβ1-42 were associated with higher CRQ scores. Conclusion Reduced Aβ1-42 in CSF is considered as evidence of amyloid deposition in the brain. Previous results suggest that individuals with higher education, higher occupational attainment, and participation in leisure activities (cognitive reserve) have a reduced risk of developing Alzheimer’s disease. Our results support the notion that enhanced neural activity has a protective role in mild cognitive impairment, as evidenced by higher CSF Aβ1-42 levels in individuals with more cognitive reserve. PMID:26504392

  15. Disease progression model for Clinical Dementia Rating–Sum of Boxes in mild cognitive impairment and Alzheimer’s subjects from the Alzheimer’s Disease Neuroimaging Initiative

    PubMed Central

    Samtani, Mahesh N; Raghavan, Nandini; Novak, Gerald; Nandy, Partha; Narayan, Vaibhav A

    2014-01-01

    Background The objective of this analysis was to develop a nonlinear disease progression model, using an expanded set of covariates that captures the longitudinal Clinical Dementia Rating Scale–Sum of Boxes (CDR–SB) scores. These were derived from the Alzheimer’s Disease Neuroimaging Initiative ADNI-1 study, of 301 Alzheimer’s disease and mild cognitive impairment patients who were followed for 2–3 years. Methods The model describes progression rate and baseline disease score as a function of covariates. The covariates that were tested fell into five groups: a) hippocampal volume; b) serum and cerebrospinal fluid (CSF) biomarkers; c) demographics and apolipoprotein Epsilon 4 (ApoE4) allele status; d) baseline cognitive tests; and e) disease state and comedications. Results Covariates associated with baseline disease severity were disease state, hippocampal volume, and comedication use. Disease progression rate was influenced by baseline CSF biomarkers, Trail-Making Test part A score, delayed logical memory test score, and current level of impairment as measured by CDR–SB. The rate of disease progression was dependent on disease severity, with intermediate scores around the inflection point score of 10 exhibiting high disease progression rate. The CDR–SB disease progression rate in a typical patient, with late mild cognitive impairment and mild Alzheimer’s disease, was estimated to be approximately 0.5 and 1.4 points/year, respectively. Conclusions In conclusion, this model describes disease progression in terms of CDR–SB changes in patients and its dependency on novel covariates. The CSF biomarkers included in the model discriminate mild cognitive impairment subjects as progressors and nonprogressors. Therefore, the model may be utilized for optimizing study designs, through patient population enrichment and clinical trial simulations. PMID:24926196

  16. Neuroimaging Biomarkers of Neurodegenerative Diseases and Dementia

    PubMed Central

    Risacher, Shannon L.; Saykin, Andrew J.

    2014-01-01

    Neurodegenerative disorders leading to dementia are common diseases that affect many older and some young adults. Neuroimaging methods are important tools for assessing and monitoring pathological brain changes associated with progressive neurodegenerative conditions. In this review, the authors describe key findings from neuroimaging studies (magnetic resonance imaging and radionucleotide imaging) in neurodegenerative disorders, including Alzheimer’s disease (AD) and prodromal stages, familial and atypical AD syndromes, frontotemporal dementia, amyotrophic lateral sclerosis with and without dementia, Parkinson’s disease with and without dementia, dementia with Lewy bodies, Huntington’s disease, multiple sclerosis, HIV-associated neurocognitive disorder, and prion protein associated diseases (i.e., Creutzfeldt-Jakob disease). The authors focus on neuroimaging findings of in vivo pathology in these disorders, as well as the potential for neuroimaging to provide useful information for differential diagnosis of neurodegenerative disorders. PMID:24234359

  17. Low plasma ApoE levels are associated with smaller hippocampal size in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort

    PubMed Central

    Teng, Edmond; Chow, Nicole; Hwang, Kristy S.; Thompson, Paul M.; Gylys, Karen H.; Cole, Gregory M.; Jack, Clifford R.; Shaw, Leslie M.; Trojanowski, John Q.; Soares, Holly D.; Weiner, Michael W.; Apostolova, Liana G.

    2014-01-01

    Apoliproprotein E (APOE) genotype is the strongest known genetic risk factor for sporadic Alzheimer’s disease (AD), but the utility of plasma ApoE levels for assessing the severity of underlying neurodegenerative changes remains uncertain. Here we examined cross-sectional associations between plasma ApoE levels and volumetric magnetic resonance imaging (MRI) indices of the hippocampus from 541 participants [57 with normal cognition (NC), 375 with mild cognitive impairment (MCI), and 109 with mild AD] who were enrolled in the Alzheimer’s Disease Neuroimaging Initiative. Across the NC and MCI groups, lower plasma ApoE levels were significantly correlated with smaller hippocampal size, as measured by either hippocampal volume or hippocampal radial distance. These associations were driven primarily by findings from carriers of an APOE ε4 allele, and are consistent with prior reports that lower plasma ApoE levels correlate with greater global cortical Pittsburgh Compound B retention. In this high-risk group, plasma ApoE levels may represent a peripheral marker of underlying AD neuropathology in nondemented elderly individuals. PMID:25547651

  18. Neuropathologic assessment of participants in two multi-center longitudinal observational studies: the Alzheimer Disease Neuroimaging Initiative (ADNI) and the Dominantly Inherited Alzheimer Network (DIAN).

    PubMed

    Cairns, Nigel J; Perrin, Richard J; Franklin, Erin E; Carter, Deborah; Vincent, Benjamin; Xie, Mingqiang; Bateman, Randall J; Benzinger, Tammie; Friedrichsen, Karl; Brooks, William S; Halliday, Glenda M; McLean, Catriona; Ghetti, Bernardino; Morris, John C

    2015-08-01

    It has been hypothesized that the relatively rare autosomal dominant Alzheimer disease (ADAD) may be a useful model of the more frequent, sporadic, late-onset AD (LOAD). Individuals with ADAD have a predictable age at onset and the biomarker profile of ADAD participants in the preclinical stage may be used to predict disease progression and clinical onset. However, the extent to which the pathogenesis and neuropathology of ADAD overlaps with that of LOAD is equivocal. To address this uncertainty, two multicenter longitudinal observational studies, the Alzheimer Disease Neuroimaging Initiative (ADNI) and the Dominantly Inherited Alzheimer Network (DIAN), leveraged the expertise and resources of the existing Knight Alzheimer Disease Research Center (ADRC) at Washington University School of Medicine, St. Louis, Missouri, USA, to establish a Neuropathology Core (NPC). The ADNI/DIAN-NPC is systematically examining the brains of all participants who come to autopsy at the 59 ADNI sites in the USA and Canada and the 14 DIAN sites in the USA (eight), Australia (three), UK (one) and Germany (two). By 2014, 41 ADNI and 24 DIAN autopsies (involving nine participants and 15 family members) had been performed. The autopsy rate in the ADNI cohort in the most recent year was 93% (total since NPC inception: 70%). In summary, the ADNI/DIAN NPC has implemented a standard protocol for all sites to solicit permission for brain autopsy and to send brain tissue to the NPC for a standardized, uniform and state-of-the-art neuropathologic assessment. The benefit to ADNI and DIAN of the implementation of the NPC is very clear. The NPC provides final "gold standard" neuropathological diagnoses and data against which the antecedent observations and measurements of ADNI and DIAN can be compared. PMID:25964057

  19. Neuropathologic assessment of participants in two multi-center longitudinal observational studies: the Alzheimer Disease Neuroimaging Initiative (ADNI) and the Dominantly Inherited Alzheimer Network (DIAN)

    PubMed Central

    Cairns, Nigel J.; Perrin, Richard J.; Franklin, Erin E.; Carter, Deborah; Vincent, Benjamin; Xie, Mingqiang; Bateman, Randall J.; Benzinger, Tammie; Friedrichsen, Karl; Brooks, William S; Halliday, Glenda M.; McLean, Catriona; Ghetti, Bernardino; Morris, John C.

    2015-01-01

    It has been hypothesized that the relatively rare autosomal dominant Alzheimer disease (ADAD) may be a useful model of the more frequent, sporadic, late-onset AD (LOAD). Individuals with ADAD have a predictable age at onset and the biomarker profile of ADAD participants in the preclinical stage may be used to predict disease progression and clinical onset. However, the extent to which the pathogenesis and neuropathology of ADAD overlaps with that of LOAD is equivocal. To address this uncertainty, two multicenter longitudinal observational studies, the Alzheimer Disease Neuroimaging Initiative (ADNI) and the Dominantly Inherited Alzheimer Network (DIAN), leveraged the expertise and resources of the existing Knight Alzheimer Disease Research Center (ADRC) at Washington University School of Medicine, St. Louis, Missouri, USA, to establish a Neuropathology Core (NPC). The ADNI/DIAN-NPC is systematically examining the brains of all participants who come to autopsy at the 59 ADNI sites in the USA and Canada and the 14 DIAN sites in the USA (8), Australia (3), UK (1), and Germany (2). By 2014, 41 ADNI and 24 DIAN autopsies (involving 9 participants and 15 family members) had been performed. The autopsy rate in the ADNI cohort in the most recent year was 93% (total since NPC inception: 70%). In summary, the ADNI/DIAN NPC has implemented a standard protocol for all sites to solicit permission for brain autopsy and to send brain tissue to the NPC for a standardized, uniform, and state-of-the-art neuropathologic assessment. The benefit to ADNI and DIAN of the implementation of the NPC is very clear. The NPC provides final ‘gold standard’ neuropathological diagnoses and data against which the antecedent observations and measurements of ADNI and DIAN can be compared. PMID:25964057

  20. Atypical neuroimaging in Wilson’s disease

    PubMed Central

    Patell, Rushad; Dosi, Rupal; Joshi, Harshal K; Storz, Dennis

    2014-01-01

    Wilson's disease is a rare metabolic disease involving copper metabolism. Neuroimaging plays an important part in evaluation of patients with a neuropsychiatric presentation. We present a case of a 14-year-old girl with atypical confluent white matter disease and cystic degeneration on MRI, with a rapidly progressive course, who succumbed to complications despite treatment with trientine. Wilson's disease should be considered as a differential for leucoencephalopathy in young patients with progressive neurological disease for its early recognition and optimum outcome. PMID:24907221

  1. Early neuroimaging diagnosis of Alzheimer's disease

    NASA Astrophysics Data System (ADS)

    Jiao, Jianling; Liu, Timon C.; Li, Yan; Liu, Songhao

    2002-04-01

    Neuroimaging has played an important role in evaluating the Alzheimer's disease (AD) patients, and its uses are growing. Magnetic resonance imaging (MRI) may show the presence of cerebral infarcts and white matter disease. Single photon emission computed tomography (SPECT) and positron emission tomography (PET), which visualize such cerebral functions as glucose metabolism and blood flow, may provide positive evidence to support the diagnosis of AD. Electrical impedance tomography (EIT) is a recently developed technique which enables the internal impedance of an object to be imaged noninvasively.

  2. Graphical neuroimaging informatics: application to Alzheimer's disease.

    PubMed

    Van Horn, John Darrell; Bowman, Ian; Joshi, Shantanu H; Greer, Vaughan

    2014-06-01

    The Informatics Visualization for Neuroimaging (INVIZIAN) framework allows one to graphically display image and meta-data information from sizeable collections of neuroimaging data as a whole using a dynamic and compelling user interface. Users can fluidly interact with an entire collection of cortical surfaces using only their mouse. In addition, users can cluster and group brains according in multiple ways for subsequent comparison using graphical data mining tools. In this article, we illustrate the utility of INVIZIAN for simultaneous exploration and mining a large collection of extracted cortical surface data arising in clinical neuroimaging studies of patients with Alzheimer's Disease, mild cognitive impairment, as well as healthy control subjects. Alzheimer's Disease is particularly interesting due to the wide-spread effects on cortical architecture and alterations of volume in specific brain areas associated with memory. We demonstrate INVIZIAN's ability to render multiple brain surfaces from multiple diagnostic groups of subjects, showcase the interactivity of the system, and showcase how INVIZIAN can be employed to generate hypotheses about the collection of data which would be suitable for direct access to the underlying raw data and subsequent formal statistical analysis. Specifically, we use INVIZIAN show how cortical thickness and hippocampal volume differences between group are evident even in the absence of more formal hypothesis testing. In the context of neurological diseases linked to brain aging such as AD, INVIZIAN provides a unique means for considering the entirety of whole brain datasets, look for interesting relationships among them, and thereby derive new ideas for further research and study. PMID:24203652

  3. Early detection of Alzheimer's disease using neuroimaging.

    PubMed

    Mosconi, Lisa; Brys, Miroslaw; Glodzik-Sobanska, Lidia; De Santi, Susan; Rusinek, Henry; de Leon, Mony J

    2007-01-01

    Neuroimaging is being increasingly used to complement clinical assessments in the early detection of Alzheimer's disease (AD). Structural magnetic resonance imaging (MRI) and metabolic positron emission tomography (FDG-PET) are the most clinically used and promising modalities to detect brain abnormalities in individuals who might be at risk for AD but who have not yet developed symptoms. The knowledge of established risk factors for AD enabled investigators to develop enrichment strategies for longitudinal imaging studies to reduce the sample sizes and study duration. The present review focuses on the results obtained by MRI and FDG-PET studies that examined the preclinical AD stages in several at risk populations: (1) individuals from families with autosomal dominant early-onset AD (FAD), (2) patients with mild cognitive impairment (MCI), particularly in memory, who are at very high risk for declining to AD with an estimated decline rate of 10-30% per year, (3) normal young and middle-age subjects carriers of known susceptibility genes for late-onset AD such as the Apolipoprotein E (ApoE) E4 allele, and (4) as age is the main risk factor for AD, normal elderly individuals followed to the onset of MCI and AD. Overall, these studies show that the use of imaging for the early detection of AD is successful even in the earlier stages of disease when clinical symptoms are not fully expressed and the regional brain damage may be limited. PMID:16839732

  4. A review of neuroimaging biomarkers of Alzheimer’s disease

    PubMed Central

    Varghese, Tinu; Sheelakumari, R; James, Jija S; Mathuranath, PS

    2014-01-01

    Neuroimaging biomarkers have potential role in the early diagnosis as well as periodic follow-up of neurodegenerative diseases such as Alzheimer’s disease (AD). Structural imaging biomarkers can be used to predict those who are at risk or in preclinical stages of AD. It could possibly be useful even in predicting the conversion of Mild Cognitive Impairment (MCI) an early stage of AD to AD. In addition there has been a lot of progress in molecular imaging in AD. This article presents a review of recent progress in selected imaging biomarkers for early diagnosis, classification, and progression, of AD. A comprehensive integrative strategy initiated early in the cognitive decline is perhaps the most effective method of controlling progression to Alzheimer’s disease. PMID:25431627

  5. Effects of traumatic brain injury and posttraumatic stress disorder on Alzheimer’s disease in veterans, using the Alzheimer’s Disease Neuroimaging Initiative

    PubMed Central

    Weiner, Michael W.; Veitch, Dallas P.; Hayes, Jacqueline; Neylan, Thomas; Grafman, Jordan; Aisen, Paul S.; Petersen, Ronald C.; Jack, Clifford; Jagust, William; Trojanowski, John Q.; Shaw, Leslie M.; Saykin, Andrew J.; Green, Robert C.; Harvey, Danielle; Toga, Arthur W.; Friedl, Karl E.; Pacifico, Anthony; Sheline, Yvette; Yaffe, Kristine; Mohlenoff, Brian

    2015-01-01

    Both traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) are common problems resulting from military service, and both have been associated with increased risk of cognitive decline and dementia resulting from Alzheimer’s disease (AD) or other causes. This study aims to use imaging techniques and biomarker analysis to determine whether traumatic brain injury (TBI) and/or PTSD resulting from combat or other traumas increase the risk for AD and decrease cognitive reserve in Veteran subjects, after accounting for age. Using military and Department of Veterans Affairs records, 65 Vietnam War veterans with a history of moderate or severe TBI with or without PTSD, 65 with ongoing PTSD without TBI, and 65 control subjects are being enrolled in this study at 19 sites. The study aims to select subject groups that are comparable in age, gender, ethnicity, and education. Subjects with mild cognitive impairment (MCI) or dementia are being excluded. However, a new study just beginning, and similar in size, will study subjects with TBI, subjects with PTSD, and control subjects with MCI. Baseline measurements of cognition, function, blood, and cerebrospinal fluid bio-markers; magnetic resonance images (structural, diffusion tensor, and resting state blood-level oxygen dependent (BOLD) functional magnetic resonance imaging); and amyloid positron emission tomographic (PET) images with florbetapir are being obtained. One-year follow-up measurements will be collected for most of the baseline procedures, with the exception of the lumbar puncture, the PET imaging, and apolipoprotein E genotyping. To date, 19 subjects with TBI only, 46 with PTSD only, and 15 with TBI and PTSD have been recruited and referred to 13 clinics to undergo the study protocol. It is expected that cohorts will be fully recruited by October 2014. This study is a first step toward the design and statistical powering of an AD prevention trial using at-risk veterans as subjects, and provides the

  6. Soluble BACE-1 Activity and sAβPPβ Concentrations in Alzheimer's Disease and Age-Matched Healthy Control Cerebrospinal Fluid from the Alzheimer's Disease Neuroimaging Initiative-1 Baseline Cohort.

    PubMed

    Savage, Mary J; Holder, Daniel J; Wu, Guoxin; Kaplow, June; Siuciak, Judith A; Potter, William Z

    2015-01-01

    β-site amyloid precursor protein-cleaving enzyme 1 (BACE1) plays an important role in the development of Alzheimer's disease (AD), freeing the amyloid-β (Aβ) N-terminus from the amyloid-β protein precursor (AβPP), the first step in Aβ formation. Increased BACE1 activity in AD brain or cerebrospinal fluid (CSF) has been reported. Other studies, however, found either no change or a decrease with AD diagnosis in either BACE1 activity or sAβPPβ, the N-terminal secreted product of BACE1 (sBACE1) activity on AβPP. Here, sBACE1 enzymatic activity and secreted AβPPβ (sAβPPβ) were measured in Alzheimer's Disease Neuroimaging Initiative-1 (ADNI-1) baseline CSF samples and no statistically significant changes were found in either measure comparing healthy control, mild cognitively impaired, or AD individual samples. While CSF sBACE1 activity and sAβPPβ demonstrated a moderate yet significant degree of correlation with each other, there was no correlation of either analyte to CSF Aβ peptide ending at residue 42. Surprisingly, a stronger correlation was demonstrated between CSF sBACE1 activity and tau, which was comparable to that between CSF Aβ₄₂ and tau. Unlike for these latter two analytes, receiver-operator characteristic curves demonstrate that neither CSF sBACE1 activity nor sAβPPβ concentrations can be used to differentiate between healthy elderly and AD individuals. PMID:25790831

  7. Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging

    PubMed Central

    Wardlaw, JM; Smith, C; Dichgans, M

    2013-01-01

    The term “cerebral small vessel disease” (SVD) describes a range of neuroimaging, pathological and associated clinical features. The latter range from none, to discrete focal neurological symptoms (stroke), to insidious global neurological dysfunction and dementia. The public health burden is considerable. The pathogenesis is largely unknown. Although associated with vascular risk factors, and generally considered to result from an intrinsic cerebral arteriolar occlusive disease, the pathological processes leading to the arteriolar disease, how these result in brain disease, how SVD lesions contribute to neurological or cognitive symptoms and the relationship to risk factors, have been the subject of much speculation. Pathology often reflects end-stage disease making determination of the earliest stages difficult. Neuroimaging provides considerable insights: the small vessels are not easily seen themselves, but the effects of their malfunction on the brain can be tracked on detailed brain imaging. We review the growing evidence for the most likely mechanisms. PMID:23602162

  8. A review of β-amyloid neuroimaging in Alzheimer's disease

    PubMed Central

    Adlard, Paul A.; Tran, Bob A.; Finkelstein, David I.; Desmond, Patricia M.; Johnston, Leigh A.; Bush, Ashley I.; Egan, Gary F.

    2014-01-01

    Alzheimer's disease (AD) is the most common cause of dementia worldwide. As advancing age is the greatest risk factor for developing AD, the number of those afflicted is expected to increase markedly with the aging of the world's population. The inability to definitively diagnose AD until autopsy remains an impediment to establishing effective targeted treatments. Neuroimaging has enabled in vivo visualization of pathological changes in the brain associated with the disease, providing a greater understanding of its pathophysiological development and progression. However, neuroimaging biomarkers do not yet offer clear advantages over current clinical diagnostic criteria for them to be accepted into routine clinical use. Nonetheless, current insights from neuroimaging combined with the elucidation of biochemical and molecular processes in AD are informing the ongoing development of new imaging techniques and their application. Much of this research has been greatly assisted by the availability of transgenic mouse models of AD. In this review we summarize the main efforts of neuroimaging in AD in humans and in mouse models, with a specific focus on β-amyloid, and discuss the potential of new applications and novel approaches. PMID:25400539

  9. Neuroimaging in Alzheimer's disease: preclinical challenges toward clinical efficacy.

    PubMed

    Dustin, Derek; Hall, Benjamin M; Annapragada, Ananth; Pautler, Robia G

    2016-09-01

    The scope of this review focuses on recent applications in preclinical and clinical magnetic resonance imaging (MRI) toward accomplishing the goals of early detection and responses to therapy in animal models of Alzheimer's disease (AD). Driven by the outstanding efforts of the Alzheimer's Disease Neuroimaging Initiative (ADNI), a truly invaluable resource, the initial use of MRI in AD imaging has been to assess changes in brain anatomy, specifically assessing brain shrinkage and regional changes in white matter tractography using diffusion tensor imaging. However, advances in MRI have led to multiple efforts toward imaging amyloid beta plaques first without and then with the use of MRI contrast agents. These technological advancements have met with limited success and are not yet appropriate for the clinic. Recent developments in molecular imaging inclusive of high-power liposomal-based MRI contrast agents as well as fluorine 19 ((19)F) MRI and manganese enhanced MRI have begun to propel promising advances toward not only plaque imaging but also using MRI to detect perturbations in subcellular processes occurring within the neuron. This review concludes with a discussion about the necessity for the development of novel preclinical models of AD that better recapitulate human AD for the imaging to truly be meaningful and for substantive progress to be made toward understanding and effectively treating AD. Furthermore, the continued support of outstanding programs such as ADNI as well as the development of novel molecular imaging agents and MRI fast scanning sequences will also be requisite to effectively translate preclinical findings to the clinic. PMID:27033146

  10. Neuroimaging findings in sickle cell disease

    PubMed Central

    Burke, C; Siddiqui, A

    2014-01-01

    At least 25% of individuals with sickle cell disease will have a neurological complication over their lifetime, often as early as in childhood. Neuroradiological findings in patients with sickle cell disease are common and include acute territorial infarction, silent ischaemia and intracranial haemorrhage. Imaging abnormalities are typically, but not always, manifestations of the underlying vasculopathy. Coexisting acute and chronic pathology may pose challenges to interpretation. PMID:24847772

  11. Cross-View Neuroimage Pattern Analysis in Alzheimer's Disease Staging

    PubMed Central

    Liu, Sidong; Cai, Weidong; Pujol, Sonia; Kikinis, Ron; Feng, Dagan D.

    2016-01-01

    The research on staging of pre-symptomatic and prodromal phase of neurological disorders, e.g., Alzheimer's disease (AD), is essential for prevention of dementia. New strategies for AD staging with a focus on early detection, are demanded to optimize potential efficacy of disease-modifying therapies that can halt or slow the disease progression. Recently, neuroimaging are increasingly used as additional research-based markers to detect AD onset and predict conversion of MCI and normal control (NC) to AD. Researchers have proposed a variety of neuroimaging biomarkers to characterize the patterns of the pathology of AD and MCI, and suggested that multi-view neuroimaging biomarkers could lead to better performance than single-view biomarkers in AD staging. However, it is still unclear what leads to such synergy and how to preserve or maximize. In an attempt to answer these questions, we proposed a cross-view pattern analysis framework for investigating the synergy between different neuroimaging biomarkers. We quantitatively analyzed nine types of biomarkers derived from FDG-PET and T1-MRI, and evaluated their performance in a task of classifying AD, MCI, and NC subjects obtained from the ADNI baseline cohort. The experiment results showed that these biomarkers could depict the pathology of AD from different perspectives, and output distinct patterns that are significantly associated with the disease progression. Most importantly, we found that these features could be separated into clusters, each depicting a particular aspect; and the inter-cluster features could always achieve better performance than the intra-cluster features in AD staging. PMID:26941639

  12. The use of neuroimaging in the diagnosis of mitochondrial disease.

    PubMed

    Friedman, Seth D; Shaw, Dennis W W; Ishak, Gisele; Gropman, Andrea L; Saneto, Russell P

    2010-01-01

    Mutations in nuclear and mitochondrial DNA impacting mitochondrial function result in disease manifestations ranging from early death to abnormalities in all major organ systems and to symptoms that can be largely confined to muscle fatigue. The definitive diagnosis of a mitochondrial disorder can be difficult to establish. When the constellation of symptoms is suggestive of mitochondrial disease, neuroimaging features may be diagnostic and suggestive, can help direct further workup, and can help to further characterize the underlying brain abnormalities. Magnetic resonance imaging changes may be nonspecific, such as atrophy (both general and involving specific structures, such as cerebellum), more suggestive of particular disorders such as focal and often bilateral lesions confined to deep brain nuclei, or clearly characteristic of a given disorder such as stroke-like lesions that do not respect vascular boundaries in mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episode (MELAS). White matter hyperintensities with or without associated gray matter involvement may also be observed. Across patients and discrete disease subtypes (e.g., MELAS, Leigh syndrome, etc.), patterns of these features are helpful for diagnosis. However, it is also true that marked variability in expression occurs in all mitochondrial disease subtypes, illustrative of the complexity of the disease process. The present review summarizes the role of neuroimaging in the diagnosis and characterization of patients with suspected mitochondrial disease. PMID:20818727

  13. Graphical Neuroimaging Informatics: Application to Alzheimer’s Disease

    PubMed Central

    Bowman, Ian; Joshi, Shantanu H.; Greer, Vaughan

    2013-01-01

    The Informatics Visualization for Neuroimaging (INVIZIAN) framework allows one to graphically display image and meta-data information from sizeable collections of neuroimaging data as a whole using a dynamic and compelling user interface. Users can fluidly interact with an entire collection of cortical surfaces using only their mouse. In addition, users can cluster and group brains according in multiple ways for subsequent comparison using graphical data mining tools. In this article, we illustrate the utility of INVIZIAN for simultaneous exploration and mining a large collection of extracted cortical surface data arising in clinical neuroimaging studies of patients with Alzheimer’s Disease, mild cognitive impairment, as well as healthy control subjects. Alzheimer’s Disease is particularly interesting due to the wide-spread effects on cortical architecture and alterations of volume in specific brain areas associated with memory. We demonstrate INVIZIAN’s ability to render multiple brain surfaces from multiple diagnostic groups of subjects, showcase the interactivity of the system, and showcase how INVIZIAN can be employed to generate hypotheses about the collection of data which would be suitable for direct access to the underlying raw data and subsequent formal statistical analysis. Specifically, we use INVIZIAN show how cortical thickness and hippocampal volume differences between group are evident even in the absence of more formal hypothesis testing. In the context of neurological diseases linked to brain aging such as AD, INVIZIAN provides a unique means for considering the entirety of whole brain datasets, look for interesting relationships among them, and thereby derive new ideas for further research and study. PMID:24203652

  14. Structural neuroimaging in Altheimer's disease: do white matter hyperintensities matter?

    PubMed

    Brickman, Adam M; Muraskin, Jordan; Zimmerman, Molly E

    2009-01-01

    The targeted brain dysfunction that accompanies aging can have a devastating effect on cognitive and intellectual abilities. A significant proportion of older adults experience precipitous cognitive decline that negatively impacts functional activities. Such individuals meet clinical diagnostic criteria for dementia, which is commonly attributed to Alzheimer's disease (AD). Structural neuroimaging, including magnetic resonance imaging (MRI), has contributed significantly to our understanding of the morphological and pathology-related changes that may underlie normal and disease-associated cognitive change in aging. White matter hyperintensities (WMH), which are distributed patches of increased hyperintense signal on T2-weighted MRI, are among the most common structural neuroimaging findings in older adults. In recent years, WMH have emerged as robust radiological correlates of cognitive decline. Studies suggest that WMH distributed in anterior brain regions are related to decline in executive abilities that is typical of normal aging, whereas WMH distributed in more posterior brain regions are common in AD. Although epidemiological, observational, and pathological studies suggest that WMH may be ischemic in origin and caused by consistent or variable hypoperfusion, there is emerging evidence that they may also reflect vascular deposition of beta-amyloid, particularly when they are distributed in posterior areas and are present in patients with AD. Findings from the literature highlight the potential contribution of small-vessel cerebrovascular disease to the pathogenesis of AD, and suggest a mechanistic interaction, but future longitudinal studies using multiple imaging modalities are required to fully understand the complex role of WMH in AD. PMID:19585953

  15. Structural Neuroimaging Markers of Cognitive Decline in Parkinson's Disease

    PubMed Central

    Hanganu, Alexandru; Monchi, Oury

    2016-01-01

    Cognitive impairment in patients with Parkinson's disease is a major challenge since it has been established that 25 to 40% of patients will develop cognitive impairment early in the disease. Furthermore, it has been reported that up to 80% of Parkinsonian patients will eventually develop dementia. Thus, it is important to improve the diagnosing procedures in order to detect cognitive impairment at early stages of development and to delay as much as possible the developing of dementia. One major challenge is that patients with mild cognitive impairment exhibit measurable cognitive deficits according to recently established criteria, yet those deficits are not severe enough to interfere with daily living, hence being avoided by patients, and might be overseen by clinicians. Recent advances in neuroimaging brain analysis allowed the establishment of several anatomical markers that have the potential to be considered for early detection of cognitive impairment in Parkinsonian patients. This review aims to outline the neuroimaging possibilities in diagnosing cognitive impairment in patients with Parkinson's disease and to take into consideration the near-future possibilities of their implementation into clinical practice. PMID:27190672

  16. Neuroimaging studies of striatum in cognition part II: Parkinson's disease

    PubMed Central

    Hanganu, Alexandru; Provost, Jean-Sebastien; Monchi, Oury

    2015-01-01

    In recent years a gradual shift in the definition of Parkinson's disease (PD) has been established, from a classical akinetic-rigid movement disorder to a multi-system neurodegenerative disease. While the pathophysiology of PD is complex and goes much beyond the nigro-striatal degeneration, the striatum has been shown to be responsible for many cognitive functions. Patients with PD develop impairments in multiple cognitive domains and the PD model is probably the most extensively studied regarding striatum dysfunction and its influence on cognition. Up to 40% of PD patients present cognitive impairment even in the early stages of disease development. Thus, understanding the key patterns of striatum and connecting regions' influence on cognition will help develop more specific approaches to alleviate cognitive impairment and slow down its decline. This review focuses on the contribution of neuroimaging studies in understanding how striatum impairment affects cognition in PD. PMID:26500512

  17. Clinical neuroimaging

    SciTech Connect

    Theodore, W.H.

    1988-01-01

    This book contains chapters on neuroimaging. Included are the following chapters: diagnostic neuroimaging in stroke, position emission tomography in cerebrovascular disease: clinical applications, and neuroradiologic work-up of brain tumors.

  18. Neuroimaging biomarkers for Parkinson disease: facts and fantasy.

    PubMed

    Perlmutter, Joel S; Norris, Scott A

    2014-12-01

    In this grand rounds, we focus on development, validation, and application of neuroimaging biomarkers for Parkinson disease (PD). We cover whether such biomarkers can be used to identify presymptomatic individuals (probably yes), provide a measure of PD severity (in a limited fashion, but frequently done poorly), investigate pathophysiology of parkinsonian disorders (yes, if done carefully), play a role in differential diagnosis of parkinsonism (not well), and investigate pathology underlying cognitive impairment (yes, in conjunction with postmortem data). Along the way, we clarify several issues about definitions of biomarkers and surrogate endpoints. The goal of this lecture is to provide a basis for interpreting current literature and newly proposed clinical tools in PD. In the end, one should be able to critically distinguish fact from fantasy. PMID:25363872

  19. Multiple Effect of APOE Genotype on Clinical and Neuroimaging Biomarkers Across Alzheimer's Disease Spectrum.

    PubMed

    Liu, Ying; Tan, Lan; Wang, Hui-Fu; Liu, Yong; Hao, Xiao-Ke; Tan, Chen-Chen; Jiang, Teng; Liu, Bing; Zhang, Dao-Qiang; Yu, Jin-Tai

    2016-09-01

    The apolipoprotein E ε4 (APOE ε4) allele is the most important genetic risk factor for Alzheimer's disease (AD); however, the underlying mechanisms responsible for it remain controversial. We used the Alzheimer's Disease Neuroimaging Initiative (ADNI) database to examine the influence of APOE ε4 dose on clinical and neuroimaging biomarkers across the AD spectrum (from cognitive normal to AD patients with severe cognitive impairment). A total of 1718 participants from the ADNI cohort were selected, and we evaluated the impact of ε4 dose on cerebrospinal fluid (CSF) levels' Abeta1-42 (Aβ1-42), tau, and phosphorylated-tau (p-tau); cortical amyloid deposition (Florbetapir-PET-AV45); brain atrophy (MRI); brain metabolism (FDG-PET); hippocampal metabolism; and cognitive declines, through different cognitive subgroups. We found that (1) ε4 was associated with decreased CSF beta-amyloid (Aβ1-42) and increased cerebral Aβ deposition across the AD spectrum; (2) increased CSF tau, P-tau and cerebral hypometabolism, hippocampal atrophy, and cognition decline were all associated with APOE ε4 in prodromal AD stage; (3) increased CSF tau, P-tau and cerebral hypometabolism appear to begin earlier than hippocampal atrophy and cognitive decline. We hypothesized that APOE ε4 increases cerebral amyloid-β (Aβ) deposition in all the stages of AD development, and also influences Aβ-initiated cascade of downstream neurodegenerative effects, thereby increasing the risk of AD. PMID:26298664

  20. Current neuroimaging techniques in Alzheimer's disease and applications in animal models

    PubMed Central

    Zhang, Linda; Chang, Raymond Chuen-Chung; Chu, Leung-Wing; Mak, Henry Ka-Fung

    2012-01-01

    With Alzheimer’s disease (AD) quickly becoming the most costly disease to society, and with no disease-modifying treatment currently, prevention and early detection have become key points in AD research. Important features within this research focus on understanding disease pathology, as well as finding biomarkers that can act as early indicators and trackers of disease progression or potential treatment. With the advances in neuroimaging technology and the development of new imaging techniques, the search for cheap, noninvasive, sensitive biomarkers becomes more accessible. Modern neuroimaging techniques are able to cover most aspects of disease pathology, including visualization of senile plaques and neurofibrillary tangles, cortical atrophy, neuronal loss, vascular damage, and changes in brain biochemistry. These methods can provide complementary information, resulting in an overall picture of AD. Additionally, applying neuroimaging to animal models of AD could bring about greater understanding in disease etiology and experimental treatments whilst remaining in vivo. In this review, we present the current neuroimaging techniques used in AD research in both their human and animal applications, and discuss how this fits in to the overall goal of understanding AD. PMID:23133824

  1. Neuroimaging and Genetic Risk for Alzheimer’s Disease and Addiction-Related Degenerative Brain Disorders

    PubMed Central

    Jahanshad, Neda; Leonardo, Cassandra D.; Thompson, Paul M.

    2014-01-01

    Neuroimaging offers a powerful means to assess the trajectory of brain degeneration in a variety of disorders, including Alzheimer’s disease (AD). Here we describe how multimodal imaging can be used to study the changing brain during the different stages of AD. We integrate findings from a range of studies using magnetic resonance imaging (MRI), positron emission tomography (PET), functional MRI (fMRI) and diffusion weighted imaging (DWI). Neuroimaging reveals how risk genes for degenerative disorders affect the brain, including several recently discovered genetic variants that may disrupt brain connectivity. We review some recent neuroimaging studies of genetic polymorphisms associated with increased risk for late-onset Alzheimer’s disease (LOAD). Some genetic variants that increase risk for drug addiction may overlap with those associated with degenerative brain disorders. These common associations offer new insight into mechanisms underlying neurodegeneration and addictive behaviors, and may offer new leads for treating them before severe and irreversible neurological symptoms appear. PMID:24142306

  2. Relationships between cognitive performance, neuroimaging, and vascular disease: the DHS-Mind Study

    PubMed Central

    Hsu, Fang-Chi; Raffield, Laura M.; Hugenschmidt, Christina E.; Cox, Amanda; Xu, Jianzhao; Carr, J. Jeffery; Freedman, Barry I.; Maldjian, Joseph A.; Williamson, Jeff D.; Bowden, Donald W.

    2015-01-01

    Background Type 2 diabetes mellitus increases risk for cognitive decline and dementia; elevated burdens of vascular disease are hypothesized to contribute to this risk. These relationships were examined in the Diabetes Heart Study-Mind using a battery of cognitive tests, neuroimaging measures, and subclinical cardiovascular disease (CVD) burden assessed by coronary artery calcified plaque (CAC). We hypothesized that CAC would attenuate the association between neuroimaging measures and cognition performance. Methods Associations were examined using marginal models in this family-based cohort of 572 European Americans from 263 families. All models were adjusted for age, gender, education, type 2 diabetes, and hypertension, with some neuroimaging measures additionally adjusted for intracranial volume. Results Higher total brain volume (TBV) was associated with better performance on the Digit Symbol Substitution Task (DSST) and Semantic Fluency (both p≤7.0 x 10−4). Higher gray matter volume (GMV) was associated with better performance on the Modified Mini-Mental State Examination and Semantic Fluency (both p≤9.0 x 10−4). Adjusting for CAC caused minimal changes to the results. Conclusions Relationships exist between neuroimaging measures and cognitive performance in a type 2 diabetes-enriched European American cohort. Associations were minimally attenuated after adjusting for subclinical CVD. Additional work is needed to understand how subclinical CVD burden interacts with other factors and impacts relationships between neuroimaging and cognitive testing measures. PMID:26185004

  3. A review of neuroimaging findings of apathy in Alzheimer’s Disease

    PubMed Central

    Theleritis, Christos; Politis, Antonios; Siarkos, Kostas; Lyketsos, Costantine G

    2014-01-01

    Background Apathy is one of the most frequent ‘behavioral and psychological signs and symptoms of dementia’ (BPSD) encountered in Alzheimer’s Disease (AD). There is a growing interest in the early diagnosis of apathetic elderly patients in the community since apathy has been associated with reduced daily functioning, caregiver distress, and poor outcome. The generalization of neuroimaging techniques might be able to offer help in this domain. Methods Within this context we conducted an extensive electronic search from the databases included in the National Library of Medicine as well as PsychInfo and Google Scholar for neuroimaging findings of apathy in Alzheimer’s Disease. Results Neuroimaging findings lend support to the notion that frontal-subcortical networks are involved in the occurrence of apathy in AD. Conclusions Longitudinal studies comparing patients and normal individuals might allow us to infer on the association between apathy and neurodegenerative diseases and what can brain imaging markers tell us about the characterization of this association, thus revealing disease patterns, helping to distinguish clinically distinct cognitive syndromes, and allowing predictions. PMID:24135083

  4. Aging, Neurodegenerative Disease, and Traumatic Brain Injury: The Role of Neuroimaging

    PubMed Central

    Levine, Brian

    2015-01-01

    Abstract Traumatic brain injury (TBI) is a highly prevalent condition with significant effects on cognition and behavior. While the acute and sub-acute effects of TBI recover over time, relatively little is known about the long-term effects of TBI in relation to neurodegenerative disease. This issue has recently garnered a great deal of attention due to publicity surrounding chronic traumatic encephalopathy (CTE) in professional athletes, although CTE is but one of several neurodegenerative disorders associated with a history of TBI. Here, we review the literative on neurodegenerative disorders linked to remote TBI. We also review the evidence for neuroimaging changes associated with unhealthy brain aging in the context of remote TBI. We conclude that neuroimaging biomarkers have significant potential to increase understanding of the mechanisms of unhealthy brain aging and neurodegeneration following TBI, with potential for identifying those at risk for unhealthy brain aging prior to the clinical manifestation of neurodegenerative disease. PMID:25192426

  5. The Use of Neuroimaging in the Diagnosis of Mitochondrial Disease

    ERIC Educational Resources Information Center

    Friedman, Seth D.; Shaw, Dennis W. W.; Ishak, Gisele; Gropman, Andrea L.; Saneto, Russell P.

    2010-01-01

    Mutations in nuclear and mitochondrial DNA impacting mitochondrial function result in disease manifestations ranging from early death to abnormalities in all major organ systems and to symptoms that can be largely confined to muscle fatigue. The definitive diagnosis of a mitochondrial disorder can be difficult to establish. When the constellation…

  6. Correlations of clinical, neuroimaging, and electrophysiological features in Hirayama disease

    PubMed Central

    Liao, Ming-Feng; Chang, Hong-Shiu; Chang, Kuo-Hsuan; Ro, Long-Sun; Chu, Chun-Che; Kuo, Hung-Chou; Lyu, Rong-Kuo

    2016-01-01

    Abstract Hirayama disease (HD) is characterized by development of asymmetric forearm muscle atrophy during adolescence with or without focal cervical spinal cord atrophy. The purpose of this study is to assess the correlation of clinical symptoms, disease progression, and electrophysiological findings with cervical spine magnetic resonance imaging (MRI) findings. The medical records, cervical spine MRIs, and electrophysiological findings of 44 HD patients were retrospectively reviewed and analyzed. Denervation changes in any single C5 to C7 root-innervated muscle (deltoid, biceps, triceps, or extensor digitorum communis) occurred more frequently in the 25 patients with cord atrophy than the 19 patients without cord atrophy (88% vs 53%, P = 0.02). Onset age, duration of disease progression, neurological examinations, nerve conduction study, and electromyographic findings from individual muscles were similar between patient groups. Compared with HD patients without cord atrophy, HD patients with cord atrophy experience a more severe denervation change in C5 to C7 root-innervated muscles. PMID:27428223

  7. Effect of HMGCR genetic variation on neuroimaging biomarkers in healthy, mild cognitive impairment and Alzheimer's disease cohorts

    PubMed Central

    Tan, Lin; Sun, Fu-Rong; Tan, Meng-Shan; Tan, Chen-Chen; Jiang, Teng; Yu, Jin-Tai; Tan, Lan

    2016-01-01

    Alzheimer's disease (AD) has become a considerable public health issue. The mechanisms underlying AD onset and progression remain largely unclear. 3-Hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) is a strong functional AD candidate gene because it encodes part of the statin-binding domain of the enzyme, which serves as the rate-limiting step in cholesterol synthesis in all mammalian cells. Here, we evaluated the potential role of HMGCR (rs3846662) in AD-related pathology by assessing neuroimaging biomarkers. We enrolled in 812 subjects from the Alzheimer's disease Neuroimaging Initiative dataset. In general, it is possible that HMGCR (rs3846662) could be involved in preventing the atrophy of right entorhinal (P=0.03385) and left hippocampus (P=0.01839) in the follow-up research of two years. What's more, it lowered the drop rate of glucose metabolism in right temporal. We then further validated them in the AD, mild cognitive impairment (MCI), normal control (NC) sub-groups. All the results in the MCI groups confirmed the association. The results of our study indicated that HMGCR (rs3846662) plays a vital role in AD pathology mainly by influencing brain structure and glucose metabolism during AD progression. PMID:26950278

  8. Structural neuroimaging of Alzheimer's disease and other dementias.

    PubMed

    Scheltens, P H

    2001-06-01

    This paper reviews the use of imaging techniques to aid in the clinical diagnosis of dementia. Two approaches are distinguished. One is the exclusionary approach in which imaging is used to rule out diseases that would mimic or cause dementia; based on the literature, this approach yields very little, if any, information that was not identified clinically. The more positive approach uses imaging as a diagnostic tool to identify changes specific for causes of dementia; any assessment of medial temporal lobe atrophy on Magnetic Resonance Imaging (MRI) will result in a reasonably high positive likelihood ratio distinguishing AD patients from non-demented individuals, but fails to distinguish AD patients from patients with other dementias. For a diagnosis of vascular dementia imaging is necessary, although not all vascular changes fulfill requirements of being relevant to dementia. Potentially of more importance, given the higher prevalence of AD, is the identification of concomitant vascular changes in AD that may be amenable to therapy, and may be used to identify subgroups. Structural and functional MRI techniques have great potential in identifying patients at risk for AD, which will allow for a very early treatment with drugs that slow or even halt progression. PMID:11442302

  9. Multivariate and univariate neuroimaging biomarkers of Alzheimer's disease

    PubMed Central

    Habeck, Christian; Foster, Norman L.; Perneczky, Robert; Kurz, Alexander; Alexopoulos, Panagiotis; Koeppe, Robert A.; Drzezga, Alexander; Stern, Yaakov

    2008-01-01

    We performed univariate and multivariate discriminant analysis of FDG-PET scans to evaluate their ability to identify Alzheimer’s disease (AD). FDG-PET scans came from two sources: 17 AD patients and 33 healthy elderly controls were scanned at the University of Michigan; 102 early AD patients and 20 healthy elderly controls were scanned at the Technical University of Munich, Germany. We selected a derivation sample of 20 AD patients and 20 healthy controls matched on age with the remainder divided into 5 replication samples. The sensitivity and specificity of diagnostic AD-markers and threshold criteria from the derivation sample were determined in the replication samples. Although both univariate and multivariate analyses produced markers with high classification accuracy in the derivation sample, the multivariate marker’s diagnostic performance in the replication samples was superior. Further, supplementary analysis showed its performance to be unaffected by the loss of key regions. Multivariate measures of AD utilize the covariance structure of imaging data and provide complementary, clinically relevant information that may be superior to univariate measures. PMID:18343688

  10. Structural and functional neuroimaging in patients with Parkinson's disease and visual hallucinations: A critical review.

    PubMed

    Lenka, Abhishek; Jhunjhunwala, Ketan Ramakant; Saini, Jitender; Pal, Pramod Kumar

    2015-07-01

    Patients with Parkinson's disease (PD) may develop various non-motor symptoms (NMS) during the course of the illness and psychosis is one of the common NMS of PD. Visual hallucinations (VH) are the most common manifestation of psychosis in PD. The exact pathogenesis of VH in patients with PD is not clearly understood. Presence of VH has been described to be associated with rapid cognitive decline and increased nursing home placements in PD patients. A large number of structural and functional neuroimaging studies have been conducted to understand the cerebral basis of VH in PD. Structural imaging studies (Voxel Based Morphometry) have reported grey matter atrophy in multiple regions of the brain such as primary visual cortex, visual association cortex, limbic regions, cholinergic structures such as pedunculopontine nucleus and substantia innominata, which conclude possible alterations of brain regions associated with functions such as visuospatial-perception, attention control and memory. Most functional neuroimaging studies (functional MRI, positron emission tomography and single photon emission computerized tomography) have reported altered activation, blood flow, or reduced metabolism in both dorsal and ventral visual pathways, which probably indicates an alteration in the normal bottom-top visual processing and the presence of an aberrant top-down visual processing. This review critically analyzes the published studies on the structural and functional neuroimaging in PD patients with VH. PMID:25920541

  11. Alzheimer's Disease Cerebrospinal Fluid and Neuroimaging Biomarkers: Diagnostic Accuracy and Relationship to Drug Efficacy.

    PubMed

    Khan, Tapan K; Alkon, Daniel L

    2015-01-01

    Widely researched Alzheimer's disease (AD) biomarkers include in vivo brain imaging with PET and MRI, imaging of amyloid plaques, and biochemical assays of Aβ 1 - 42, total tau, and phosphorylated tau (p-tau-181) in cerebrospinal fluid (CSF). In this review, we critically evaluate these biomarkers and discuss their clinical utility for the differential diagnosis of AD. Current AD biomarker tests are either highly invasive (requiring CSF collection) or expensive and labor-intensive (neuroimaging), making them unsuitable for use in the primary care, clinical office-based setting, or to assess drug efficacy in clinical trials. In addition, CSF and neuroimaging biomarkers continue to face challenges in achieving required sensitivity and specificity and minimizing center-to-center variability (for CSF-Aβ 1 - 42 biomarkers CV = 26.5% ; http://www.alzforum.org/news/conference-coverage/paris-standardization-hurdle-spinal-fluid-imaging-markers). Although potentially useful for selecting patient populations for inclusion in AD clinical trials, the utility of CSF biomarkers and neuroimaging techniques as surrogate endpoints of drug efficacy needs to be validated. Recent trials of β- and γ-secretase inhibitors and Aβ immunization-based therapies in AD showed no significant cognitive improvements, despite changes in CSF and neuroimaging biomarkers. As we learn more about the dysfunctional cellular and molecular signaling processes that occur in AD, and how these processes are manifested in tissues outside of the brain, new peripheral biomarkers may also be validated as non-invasive tests to diagnose preclinical and clinical AD. PMID:26402622

  12. Applied Neuroimaging to the Diagnosis of Alzheimer's Disease: A Multicriteria Model

    NASA Astrophysics Data System (ADS)

    Tamanini, Isabelle; de Castro, Ana Karoline; Pinheiro, Plácido Rogério; Pinheiro, Mirian Calíope Dantas

    In the last few years, Alzheimer's disease has been the most frequent cause of dementia and it is responsible, alone or in association with other diseases, for 50% of the cases in western countries. Dementias are syndromes characterized by a decline in memory and other neuropsychological changes, especially occurring in elderly people and increasing exponentially along the aging process. The main focus of this work is to develop a multicriteria model for aiding in decision making on the diagnosis of Alzheimer's disease by using the Aranau Tool, structured on the Verbal Decision Analysis. In this work, the modeling and evaluation processes were conducted with the aid of a medical expert, bibliographic sources and questionnaires. The questionnaires taken into account were based mainly on patients' neuroimaging tests, and we analyzed wheter or not there were problems in the patients' brain that could be relevant to the diagnosis of Alzheimer's disease.

  13. DIAGNOSIS-GUIDED METHOD FOR IDENTIFYING MULTI-MODALITY NEUROIMAGING BIOMARKERS ASSOCIATED WITH GENETIC RISK FACTORS IN ALZHEIMER'S DISEASE.

    PubMed

    Hao, Xiaoke; Yan, Jingwen; Yao, Xiaohui; Risacher, Shannon L; Saykin, Andrew J; Zhang, Daoqiang; Shen, Li

    2016-01-01

    Many recent imaging genetic studies focus on detecting the associations between genetic markers such as single nucleotide polymorphisms (SNPs) and quantitative traits (QTs). Although there exist a large number of generalized multivariate regression analysis methods, few of them have used diagnosis information in subjects to enhance the analysis performance. In addition, few of models have investigated the identification of multi-modality phenotypic patterns associated with interesting genotype groups in traditional methods. To reveal disease-relevant imaging genetic associations, we propose a novel diagnosis-guided multi-modality (DGMM) framework to discover multi-modality imaging QTs that are associated with both Alzheimer's disease (AD) and its top genetic risk factor (i.e., APOE SNP rs429358). The strength of our proposed method is that it explicitly models the priori diagnosis information among subjects in the objective function for selecting the disease-relevant and robust multi-modality QTs associated with the SNP. We evaluate our method on two modalities of imaging phenotypes, i.e., those extracted from structural magnetic resonance imaging (MRI) data and fluorodeoxyglucose positron emission tomography (FDG-PET) data in the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. The experimental results demonstrate that our proposed method not only achieves better performances under the metrics of root mean squared error and correlation coefficient but also can identify common informative regions of interests (ROIs) across multiple modalities to guide the disease-induced biological interpretation, compared with other reference methods. PMID:26776178

  14. Diagnosis-Guided Method For Identifying Multi-Modality Neuroimaging Biomarkers Associated With Genetic Risk Factors In Alzheimer's Disease

    PubMed Central

    Hao, Xiaoke; Yan, Jingwen; Yao, Xiaohui; Risacher, Shannon L.; Saykin, Andrew J.; Zhang, Daoqiang; Shen, Li

    2015-01-01

    Many recent imaging genetic studies focus on detecting the associations between genetic markers such as single nucleotide polymorphisms (SNPs) and quantitative traits (QTs). Although there exist a large number of generalized multivariate regression analysis methods, few of them have used diagnosis information in subjects to enhance the analysis performance. In addition, few of models have investigated the identification of multi-modality phenotypic patterns associated with interesting genotype groups in traditional methods. To reveal disease-relevant imaging genetic associations, we propose a novel diagnosis-guided multi-modality (DGMM) framework to discover multi-modality imaging QTs that are associated with both Alzheimer's disease (AD) and its top genetic risk factor (i.e., APOE SNP rs429358). The strength of our proposed method is that it explicitly models the priori diagnosis information among subjects in the objective function for selecting the disease-relevant and robust multi-modality QTs associated with the SNP. We evaluate our method on two modalities of imaging phenotypes, i.e., those extracted from structural magnetic resonance imaging (MRI) data and fluorodeoxyglucose positron emission tomography (FDG-PET) data in the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. The experimental results demonstrate that our proposed method not only achieves better performances under the metrics of root mean squared error and correlation coefficient but also can identify common informative regions of interests (ROIs) across multiple modalities to guide the disease-induced biological interpretation, compared with other reference methods. PMID:26776178

  15. Association between α-synuclein blood transcripts and early, neuroimaging-supported Parkinson's disease.

    PubMed

    Locascio, Joseph J; Eberly, Shirley; Liao, Zhixiang; Liu, Ganqiang; Hoesing, Ashley N; Duong, Karen; Trisini-Lipsanopoulos, Ana; Dhima, Kaltra; Hung, Albert Y; Flaherty, Alice W; Schwarzschild, Michael A; Hayes, Michael T; Wills, Anne-Marie; Shivraj Sohur, U; Mejia, Nicte I; Selkoe, Dennis J; Oakes, David; Shoulson, Ira; Dong, Xianjun; Marek, Ken; Zheng, Bin; Ivinson, Adrian; Hyman, Bradley T; Growdon, John H; Sudarsky, Lewis R; Schlossmacher, Michael G; Ravina, Bernard; Scherzer, Clemens R

    2015-09-01

    There are no cures for neurodegenerative diseases and this is partially due to the difficulty of monitoring pathogenic molecules in patients during life. The Parkinson's disease gene α-synuclein (SNCA) is selectively expressed in blood cells and neurons. Here we show that SNCA transcripts in circulating blood cells are paradoxically reduced in early stage, untreated and dopamine transporter neuroimaging-supported Parkinson's disease in three independent regional, national, and international populations representing 500 cases and 363 controls and on three analogue and digital platforms with P < 0.0001 in meta-analysis. Individuals with SNCA transcripts in the lowest quartile of counts had an odds ratio for Parkinson's disease of 2.45 compared to individuals in the highest quartile. Disease-relevant transcript isoforms were low even near disease onset. Importantly, low SNCA transcript abundance predicted cognitive decline in patients with Parkinson's disease during up to 5 years of longitudinal follow-up. This study reveals a consistent association of reduced SNCA transcripts in accessible peripheral blood and early-stage Parkinson's disease in 863 participants and suggests a clinical role as potential predictor of cognitive decline. Moreover, the three independent biobank cohorts provide a generally useful platform for rapidly validating any biological marker of this common disease. PMID:26220939

  16. Bilateral occipital calcification, epilepsy and coeliac disease: clinical and neuroimaging features of a new syndrome.

    PubMed Central

    Magaudda, A; Dalla Bernardina, B; De Marco, P; Sfaello, Z; Longo, M; Colamaria, V; Daniele, O; Tortorella, G; Tata, M A; Di Perri, R

    1993-01-01

    Twenty patients affected by bilateral occipital cortical-subcortical calcification (BOC) are described, 19 (95%) had epilepsy. In 8 of 16 cases studied, intestinal biopsy revealed coeliac disease. Fourteen patients had occipital partial epilepsy with a relatively benign outcome, while 4 patients were affected by a severe form of epilepsy, with very frequent, drug-resistant, generalised and partial seizures with mental deterioration. One patient had a single episode of convulsive status epilepticus at four months of age. The neurological examination was normal in all patients. CT showed flocculo-nodular, cortico-subcortical BOC, without enhancement and without lobar or hemispheric atrophy. MRI was normal. The clinical and neuroimaging features of these patients are different therefore from those with the Sturge-Weber Syndrome. The study confirms a high prevalence of coliac disease in patients with BOC, but the relationship between these two pathologies still needs to be clarified. Images PMID:8350105

  17. Contribution of neuroimaging to the diagnosis of Alzheimer's disease and vascular dementia.

    PubMed

    Román, Gustavo; Pascual, Belén

    2012-11-01

    The aim of this study was to review, summarize and analyze recent findings relevant to the contribution of neuroimaging to the diagnosis of Alzheimer's disease (AD) and vascular dementia (VaD). Computerized tomography (CT) or magnetic resonance imaging (MRI) provide accurate demonstration of the location and rate of progression of atrophic changes affecting the brain in AD and the different types of vascular lesions observed in mixed dementias and in pure VaD. Quantification of cortical thickness allows early diagnosis and rate of progression from mild cognitive impairment (MCI) to dementia. White matter involvement can also be quantified with diffusion tensor imaging (DTI) and functional methods including fMRI, functional connectivity, and MR spectroscopy (MRS). Isotope-based techniques such as positron emission tomography (PET) allow measurement of regional cerebral glucose metabolism using (18)F-2-fluoro-deoxy-D-glucose (FDG). Cerebral blood flow can be measured using PET with H(2)(15)O or with single photon emission computerized tomography (SPECT) with technetium ((99m)Tc-HMPAO) or, more recently, arterial spin label (ASL) imaging. There are isotope markers for amyloid-beta ((11)O-PIB, (18)F-florbetapir), tau ((18)FDDNP) and activated microglia ((11)C-PK11195). Neuroimaging markers are particularly useful at the early symptomatic and preclinical asymptomatic phases of AD, as well as serving as endpoints in clinical trials. PMID:23142262

  18. The behavioural/dysexecutive variant of Alzheimer's disease: clinical, neuroimaging and pathological features.

    PubMed

    Ossenkoppele, Rik; Pijnenburg, Yolande A L; Perry, David C; Cohn-Sheehy, Brendan I; Scheltens, Nienke M E; Vogel, Jacob W; Kramer, Joel H; van der Vlies, Annelies E; La Joie, Renaud; Rosen, Howard J; van der Flier, Wiesje M; Grinberg, Lea T; Rozemuller, Annemieke J; Huang, Eric J; van Berckel, Bart N M; Miller, Bruce L; Barkhof, Frederik; Jagust, William J; Scheltens, Philip; Seeley, William W; Rabinovici, Gil D

    2015-09-01

    A 'frontal variant of Alzheimer's disease' has been described in patients with predominant behavioural or dysexecutive deficits caused by Alzheimer's disease pathology. The description of this rare Alzheimer's disease phenotype has been limited to case reports and small series, and many clinical, neuroimaging and neuropathological characteristics are not well understood. In this retrospective study, we included 55 patients with Alzheimer's disease with a behavioural-predominant presentation (behavioural Alzheimer's disease) and a neuropathological diagnosis of high-likelihood Alzheimer's disease (n = 17) and/or biomarker evidence of Alzheimer's disease pathology (n = 44). In addition, we included 29 patients with autopsy/biomarker-defined Alzheimer's disease with a dysexecutive-predominant syndrome (dysexecutive Alzheimer's disease). We performed structured chart reviews to ascertain clinical features. First symptoms were more often cognitive (behavioural Alzheimer's disease: 53%; dysexecutive Alzheimer's disease: 83%) than behavioural (behavioural Alzheimer's disease: 25%; dysexecutive Alzheimer's disease: 3%). Apathy was the most common behavioural feature, while hyperorality and perseverative/compulsive behaviours were less prevalent. Fifty-two per cent of patients with behavioural Alzheimer's disease met diagnostic criteria for possible behavioural-variant frontotemporal dementia. Overlap between behavioural and dysexecutive Alzheimer's disease was modest (9/75 patients). Sixty per cent of patients with behavioural Alzheimer's disease and 40% of those with the dysexecutive syndrome carried at least one APOE ε4 allele. We also compared neuropsychological test performance and brain atrophy (applying voxel-based morphometry) with matched autopsy/biomarker-defined typical (amnestic-predominant) Alzheimer's disease (typical Alzheimer's disease, n = 58), autopsy-confirmed/Alzheimer's disease biomarker-negative behavioural variant frontotemporal dementia (n = 59

  19. Depression, anxiety, and apathy in Parkinson's disease: insights from neuroimaging studies.

    PubMed

    Wen, M-C; Chan, L L; Tan, L C S; Tan, E K

    2016-06-01

    Depression, anxiety and apathy are common mood disturbances in Parkinson's disease (PD) but their pathophysiology is unclear. Advanced neuroimaging has been increasingly used to unravel neural substrates linked to these disturbances. A systematic review is provided of neuroimaging findings in depression, anxiety and apathy in PD. A PubMed, MEDLINE and EMBASE search of peer-reviewed original research articles on these mood disturbances in PD identified 38 studies on depression, eight on anxiety and 14 on apathy in PD. Most of the imaging studies used either position emission tomography or single-photon emission computed tomography techniques. These studies generally suggest increased neural activity in the prefrontal regions and decreased functional connectivity between the prefrontal-limbic networks in depressed patients. Functional imaging studies revealed an inverse correlation between dopaminergic density in the caudate and putamen with the severity of anxiety in PD. There was no consistent correlation between dopaminergic density of thalamus and anxiety. Studies demonstrated both positive and inverse correlations between apathy and metabolism or activity in the striatum, amygdalar, prefrontal, temporal and parietal regions. The clinical variability of study subjects and differences in image pre-processing and analytical strategies may contribute to discrepant findings in these studies. Both nigrostriatal and extra-nigrostriatal pathways (in particular the frontal region and its connecting areas) are affected in mood disorders in PD. Identifying the relative contributions of these neural pathways in PD patients with overlapping motor and mood symptoms could provide new pathophysiological clues for the development of better therapeutic targets for affected patients. PMID:27141858

  20. Looking for Neuroimaging Markers in Frontotemporal Lobar Degeneration Clinical Trials: A Multi-Voxel Pattern Analysis Study in Granulin Disease.

    PubMed

    Premi, Enrico; Cauda, Franco; Costa, Tommaso; Diano, Matteo; Gazzina, Stefano; Gualeni, Vera; Alberici, Antonella; Archetti, Silvana; Magoni, Mauro; Gasparotti, Roberto; Padovani, Alessandro; Borroni, Barbara

    2016-01-01

    In light of future pharmacological interventions, neuroimaging markers able to assess the response to treatment would be crucial. In Granulin (GRN) disease, preclinical data will prompt pharmacological trials in the future. Two main points need to be assessed: (1) to identify target regions in different disease stages and (2) to determine the most accurate functional and structural neuroimaging index to be used. To this aim, we have taken advantage of the multivariate approach of multi-voxel pattern analysis (MVPA) to explore the information of brain activity patterns in a cohort of GRN Thr272fs carriers at different disease stages (14 frontotemporal dementia (FTD) patients and 17 asymptomatic carriers) and a group of 33 healthy controls. We studied structural changes by voxel-based morphometry (VBM), functional connectivity by assessing salience, default mode, fronto-parietal, dorsal attentional, executive networks, and local connectivity by regional homogeneity, amplitude of low frequency fluctuations (ALFF), fractional ALFF (fALFF), degree centrality, and voxel-mirrored homotopic connectivity. In FTD patients with GRN mutation, the most predictive measure was VBM structural analysis, while in asymptomatic carriers the best predictor marker was the local connectivity measure (fALFF). Altogether, all indexes demonstrated fronto-temporo-parietal damage in GRN pathology, with widespread structural damage of fronto-parietal and temporal regions when disease is overt. MVPA could be of aid in identifying the most accurate neuroimaging marker for clinical trials. This approach was able to identify both the target region and the best neuroimaging approach, which would be specific in the different disease stages. Further studies are needed to simultaneously integrate multimodal indexes in a classifier able to trace the disease progression moving from preclinical to clinical stage of the disease. PMID:26836150

  1. Examining the relationship between head trauma and neurodegenerative disease: A review of epidemiology, pathology and neuroimaging techniques

    PubMed Central

    Sundman, Mark H; Hall, Eric E; Chen, Nan-kuei

    2014-01-01

    Traumatic brain injuries (TBI) are induced by sudden acceleration-deceleration and/or rotational forces acting on the brain. Diffuse axonal injury (DAI) has been identified as one of the chief underlying causes of morbidity and mortality in head trauma incidents. DAIs refer to microscopic white matter (WM) injuries as a result of shearing forces that induce pathological and anatomical changes within the brain, which potentially contribute to significant impairments later in life. These microscopic injuries are often unidentifiable by the conventional computed tomography (CT) and magnetic resonance (MR) scans employed by emergency departments to initially assess head trauma patients and, as a result, TBIs are incredibly difficult to diagnose. The impairments associated with TBI may be caused by secondary mechanisms that are initiated at the moment of injury, but often have delayed clinical presentations that are difficult to assess due to the initial misdiagnosis. As a result, the true consequences of these head injuries may go unnoticed at the time of injury and for many years thereafter. The purpose of this review is to investigate these consequences of TBI and their potential link to neurodegenerative disease (ND). This review will summarize the current epidemiological findings, the pathological similarities, and new neuroimaging techniques that may help delineate the relationship between TBI and ND. Lastly, this review will discuss future directions and propose new methods to overcome the limitations that are currently impeding research progress. It is imperative that improved techniques are developed to adequately and retrospectively assess TBI history in patients that may have been previously undiagnosed in order to increase the validity and reliability across future epidemiological studies. The authors introduce a new surveillance tool (Retrospective Screening of Traumatic Brain Injury Questionnaire, RESTBI) to address this concern. PMID:25324979

  2. Initial treatment of Parkinson's disease.

    PubMed

    Tarsy, Daniel

    2006-05-01

    Initial treatment of early idiopathic Parkinson's disease (PD) begins with diagnosis based on clinical evaluation supplemented by laboratory studies and brain imaging to exclude causes of secondary parkinsonism. In most cases, testing is normal and the diagnosis of PD rests on clinical criteria. In patients with mild symptoms and signs, the diagnosis of PD may not initially be apparent, and follow-up evaluation is needed to arrive at a diagnosis. Once the diagnosis is made, pharmacologic treatment may not be the first step. First, patient education is essential, especially because PD is a high-profile disease for which information and misinformation are readily available to patients and families. Counseling concerning prognosis, future symptoms, future disability, and treatment must be provided. Questions from patients concerning diet, lifestyle, and exercise are especially common at this point. The decision of when to initiate treatment is the next major consideration. Much controversy but relatively little light has been brought to bear on this issue. L-dopa was the first major antiparkinson medication to be introduced and remains the "gold standard" of treatment. Next in efficacy are the dopamine agonists (DAs). A debate has raged concerning whether initial dopaminergic treatment should be with L-dopa or DAs. Physicians have been concerned about forestalling the appearance of dyskinesias and motor fluctuations, whereas patients have incorrectly understood that L-dopa and possibly other antiparkinson drugs have a finite duration of usefulness, making it important to defer treatment for as long as possible. This has created "L-dopa phobia," which may stand in the way of useful treatment. In spite of this controversy, there is uniform agreement that the appropriate time to treat is when the patient is beginning to be disabled. This varies from patient to patient and depends on age, employment status, nature of job, level of physical activity, concern about

  3. Pseudotumoral hemicerebellitis as a mimicker of Lhermitte-Duclos disease in children: does neuroimaging help to differentiate them?

    PubMed

    Bosemani, Thangamadhan; Steinlin, Maja; Toelle, Sandra P; Beck, Jürgen; Boltshauser, Eugen; Huisman, Thierry A G M; Poretti, Andrea

    2016-05-01

    The clinical presentation and neuroimaging findings of children with pseudotumoral hemicerebellitis (PTHC) and Lhermitte-Duclos disease (LDD) may be very similar. The differentiation between these entities, however, is important because their management and prognosis are different. We report on three children with PTHC. For all three children, in the acute situation, the differentiation between PTHC and LDD was challenging. A review of the literature shows that a detailed evaluation of conventional and neuroimaging data may help to differentiate between these two entities. A striated folial pattern, brainstem involvement, and prominent veins surrounding the thickened cerebellar foliae on susceptibility weighted imaging favor LDD, while post-contrast enhancement and an increased choline peak on (1)H-Magnetic resonance spectroscopy suggest PTHC. PMID:26649682

  4. Clinical and neuroimaging differences between posterior cortical atrophy and typical amnestic Alzheimer's disease patients at an early disease stage.

    PubMed

    Peng, Guoping; Wang, Jianqin; Feng, Zhan; Liu, Ping; Zhang, Yafei; He, Fangping; Chen, Zhongqin; Zhao, Kui; Luo, Benyan

    2016-01-01

    To identify clinical and neuroimaging characteristics between posterior cortical atrophy (PCA) and typical amnestic Alzheimer's disease (tAD) patients at an early disease stage, 16 PCA and 13 age-matched tAD patients were enrolled. Compared with tAD patients, PCA patients showed higher mean recognition and recall test scores, and lower mean calculation, spatial attention, shape discrimination, and writing test scores. Mean right hippocampal volume was larger in PCA patients compared with tAD patients, while cortical gray matter (GM) volume of bilateral parietal and occipital lobes was smaller in PCA patients. Further, when compared with tAD patients, significant hypometabolism was observed in bilateral parietal and occipital lobes, particularly the right occipitotemporal junction in PCA patients. Additionally, there were significant positive correlations in recognition and recall scores with hippocampal volumes. In PCA patients, calculation and visuospatial ability scores are positively associated with GM volume of parietal and occipital lobes. And only spatial attention and shape discrimination scores are positively associated with regional glucose metabolism of parietal and occipital lobes. Therefore, PCA patients display better recognition and recall scores, which are associated with larger hippocampal volumes and poorer performance in visual spatial tasks because of marked GM atrophy and hypometabolism of parietal and occipital lobes. PMID:27377199

  5. [Initial symptomatology of Parkinson disease].

    PubMed

    Fuhr, P; Maritz, D; Bernatik, J; Steck, A J

    1995-01-01

    The early diagnosis of Parkinson's disease (idiopathic parkinsonism) is important for two reasons. Some never drugs possibly have a neuroprotective effect, which can be utilized maximally only with early onset of treatment. Moreover, diagnostic mistakes may occur early in the course of the disease. Although the hallmark of Parkinson's disease is a syndrome of movement disorders, slight cognitive deficits, depression, or pain with or without paresthesias can be present at an early stage. Therefore, symptoms at the time of the first diagnosis and at the beginning of the first clinical manifestation of Parkinson's disease are often not identical. The diagnosis can be made only clinically, since no biological marker is available up to now. However, in unclear cases pharmacological tests constitute a valuable extension of the clinical examination. PMID:8533059

  6. Neuroimaging of scoliosis in childhood.

    PubMed

    Kim, F M; Poussaint, T Y; Barnes, P D

    1999-02-01

    A curvature abnormality may be the initial or major presenting feature in a child with disease of the spinal column or spinal neuraxis. A simplified classification of common spinal curvature abnormalities of childhood include idiopathic, congenital/dysraphic, skeletal dysplasia, neurofibromatosis, and painful. The great majority of childhood scoliosis falls into the idiopathic category. Atypical clinical or radiographic features in a presumed idiopathic scoliosis may indicate an otherwise occult tumor or hydrosyringomyelia, or may be a consequence of increasing curvature with disk protrusion, nerve impingement, or cord attenuation. Neuroimaging beyond plain films is commonly necessary for atypical idiopathic scoliosis and for the other categories of scoliosis listed. PMID:9974506

  7. The clinical value of large neuroimaging data sets in Alzheimer's disease.

    PubMed

    Toga, Arthur W

    2012-02-01

    Rapid advances in neuroimaging and cyberinfrastructure technologies have brought explosive growth in the Web-based warehousing, availability, and accessibility of imaging data on a variety of neurodegenerative and neuropsychiatric disorders and conditions. There has been a prolific development and emergence of complex computational infrastructures that serve as repositories of databases and provide critical functionalities such as sophisticated image analysis algorithm pipelines and powerful three-dimensional visualization and statistical tools. The statistical and operational advantages of collaborative, distributed team science in the form of multisite consortia push this approach in a diverse range of population-based investigations. PMID:22284737

  8. Tensor-Based Morphometry as a Neuroimaging Biomarker for Alzheimer’s Disease: An MRI Study of 676 AD, MCI, and Normal Subjects

    PubMed Central

    Hua, Xue; Leow, Alex D.; Parikshak, Neelroop; Lee, Suh; Chiang, Ming-Chang; Toga, Arthur W.; Jack, Clifford R.; Weiner, Michael W.; Thompson, Paul M.

    2011-01-01

    In one of the largest brain MRI studies to date, we used tensor-based morphometry (TBM) to create 3D maps of structural atrophy in 676 subjects with Alzheimer’s disease (AD), mild cognitive impairment (MCI), and healthy elderly controls, scanned as part of the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Using inverse-consistent 3D non-linear elastic image registration, we warped 676 individual brain MRI volumes to a population mean geometric template. Jacobian determinant maps were created, revealing the 3D profile of local volumetric expansion and compression. We compared the anatomical distribution of atrophy in 165 AD patients (age: 75.6 ± 7.6 years), 330 MCI subjects (74.8 ± 7.5), and 181 controls (75.9 ± 5.1). Brain atrophy in selected regions-of-interest was correlated with clinical measurements - the sum-of-boxes clinical dementia rating (CDR-SB), mini-mental state examination (MMSE), and the logical memory test scores - at voxel level followed by correction for multiple comparisons. Baseline temporal lobe atrophy correlated with current cognitive performance, future cognitive decline, and conversion from MCI to AD over the following year; it predicted future decline even in healthy subjects. Over half of the AD and MCI subjects carried the ApoE4 (apolipoprotein E4) gene, which increases risk for AD; they showed greater hippocampal and temporal lobe deficits than non-carriers. ApoE2 gene carriers - 1/6 of the normal group - showed reduced ventricular expansion, suggesting a protective effect. As an automated image analysis technique, TBM reveals 3D correlations between neuroimaging markers, genes, and future clinical changes, and is highly efficient for large-scale MRI studies. PMID:18691658

  9. Effect of CLU genetic variants on cerebrospinal fluid and neuroimaging markers in healthy, mild cognitive impairment and Alzheimer's disease cohorts.

    PubMed

    Tan, Lin; Wang, Hui-Fu; Tan, Meng-Shan; Tan, Chen-Chen; Zhu, Xi-Chen; Miao, Dan; Yu, Wan-Jiang; Jiang, Teng; Tan, Lan; Yu, Jin-Tai

    2016-01-01

    The Clusterin (CLU) gene, also known as apolipoprotein J (ApoJ), is currently the third most associated late-onset Alzheimer's disease (LOAD) risk gene. However, little was known about the possible effect of CLU genetic variants on AD pathology in brain. Here, we evaluated the interaction between 7 CLU SNPs (covering 95% of genetic variations) and the role of CLU in β-amyloid (Aβ) deposition, AD-related structure atrophy, abnormal glucose metabolism on neuroimaging and CSF markers to clarify the possible approach by that CLU impacts AD. Finally, four loci (rs11136000, rs1532278, rs2279590, rs7982) showed significant associations with the Aβ deposition at the baseline level while genotypes of rs9331888 (P = 0.042) increased Aβ deposition. Besides, rs9331888 was significantly associated with baseline volume of left hippocampus (P = 0.014). We then further validated the association with Aβ deposition in the AD, mild cognitive impairment (MCI), normal control (NC) sub-groups. The results in sub-groups confirmed the association between CLU genotypes and Aβ deposition further. Our findings revealed that CLU genotypes could probably modulate the cerebral the Aβ loads on imaging and volume of hippocampus. These findings raise the possibility that the biological effects of CLU may be relatively confined to neuroimaging trait and hence may offer clues to AD. PMID:27229352

  10. The importance of combining MRI and large-scale digital histology in neuroimaging studies of brain connectivity and disease

    PubMed Central

    Annese, Jacopo

    2012-01-01

    One of the major issues hindering a comprehensive connectivity model for the human brain is the difficulty in linking Magnetic Resonance Imaging (MRI) measurements to anatomical evidence produced by histological methods. In vivo and postmortem neuroimaging methodologies are still largely incompatible in terms of sample size, scale, and resolution. To help bridge the hiatus between different approaches we have established a program that characterizes the brain of individual subjects, combining MRI with postmortem neuroanatomy. The direct correlation of MRI and histological features is possible, because registered images from different modalities represent the same regions in the same brain. Comparisons are also facilitated by large-scale, digital microscopy techniques that afford images of the whole-brain sections at cellular resolution. The goal is to create a neuroimaging catalog representative of discrete age groups and specific neurological conditions. Individually, the datasets allow for investigating the relationship between different modalities; combined, they provide sufficient predictive power to inform analyses and interpretations made in the context of non-invasive studies of brain connectivity and disease. PMID:22536182

  11. Prognostic serum miRNA biomarkers associated with Alzheimer's disease shows concordance with neuropsychological and neuroimaging assessment.

    PubMed

    Cheng, L; Doecke, J D; Sharples, R A; Villemagne, V L; Fowler, C J; Rembach, A; Martins, R N; Rowe, C C; Macaulay, S L; Masters, C L; Hill, A F

    2015-10-01

    There is no consensus for a blood-based test for the early diagnosis of Alzheimer's disease (AD). Expression profiling of small non-coding RNA's, microRNA (miRNA), has revealed diagnostic potential in human diseases. Circulating miRNA are found in small vesicles known as exosomes within biological fluids such as human serum. The aim of this work was to determine a set of differential exosomal miRNA biomarkers between healthy and AD patients, which may aid in diagnosis. Using next-generation deep sequencing, we profiled exosomal miRNA from serum (N=49) collected from the Australian Imaging, Biomarkers and Lifestyle Flagship Study (AIBL). Sequencing results were validated using quantitative reverse transcription PCR (qRT-PCR; N=60), with predictions performed using the Random Forest method. Additional risk factors collected during the 4.5-year AIBL Study including clinical, medical and cognitive assessments, and amyloid neuroimaging with positron emission tomography were assessed. An AD-specific 16-miRNA signature was selected and adding established risk factors including age, sex and apolipoprotein ɛ4 (APOE ɛ4) allele status to the panel of deregulated miRNA resulted in a sensitivity and specificity of 87% and 77%, respectively, for predicting AD. Furthermore, amyloid neuroimaging information for those healthy control subjects incorrectly classified with AD-suggested progression in these participants towards AD. These data suggest that an exosomal miRNA signature may have potential to be developed as a suitable peripheral screening tool for AD. PMID:25349172

  12. Data sharing in neuroimaging research

    PubMed Central

    Poline, Jean-Baptiste; Breeze, Janis L.; Ghosh, Satrajit; Gorgolewski, Krzysztof; Halchenko, Yaroslav O.; Hanke, Michael; Haselgrove, Christian; Helmer, Karl G.; Keator, David B.; Marcus, Daniel S.; Poldrack, Russell A.; Schwartz, Yannick; Ashburner, John; Kennedy, David N.

    2012-01-01

    Significant resources around the world have been invested in neuroimaging studies of brain function and disease. Easier access to this large body of work should have profound impact on research in cognitive neuroscience and psychiatry, leading to advances in the diagnosis and treatment of psychiatric and neurological disease. A trend toward increased sharing of neuroimaging data has emerged in recent years. Nevertheless, a number of barriers continue to impede momentum. Many researchers and institutions remain uncertain about how to share data or lack the tools and expertise to participate in data sharing. The use of electronic data capture (EDC) methods for neuroimaging greatly simplifies the task of data collection and has the potential to help standardize many aspects of data sharing. We review here the motivations for sharing neuroimaging data, the current data sharing landscape, and the sociological or technical barriers that still need to be addressed. The INCF Task Force on Neuroimaging Datasharing, in conjunction with several collaborative groups around the world, has started work on several tools to ease and eventually automate the practice of data sharing. It is hoped that such tools will allow researchers to easily share raw, processed, and derived neuroimaging data, with appropriate metadata and provenance records, and will improve the reproducibility of neuroimaging studies. By providing seamless integration of data sharing and analysis tools within a commodity research environment, the Task Force seeks to identify and minimize barriers to data sharing in the field of neuroimaging. PMID:22493576

  13. Predicting beneficial effects of atomoxetine and citalopram on response inhibition in Parkinson's disease with clinical and neuroimaging measures

    PubMed Central

    Ye, Zheng; Rae, Charlotte L.; Nombela, Cristina; Ham, Timothy; Rittman, Timothy; Jones, Peter Simon; Rodríguez, Patricia Vázquez; Coyle‐Gilchrist, Ian; Regenthal, Ralf; Altena, Ellemarije; Housden, Charlotte R.; Maxwell, Helen; Sahakian, Barbara J.; Barker, Roger A.; Robbins, Trevor W.

    2016-01-01

    Abstract Recent studies indicate that selective noradrenergic (atomoxetine) and serotonergic (citalopram) reuptake inhibitors may improve response inhibition in selected patients with Parkinson's disease, restoring behavioral performance and brain activity. We reassessed the behavioral efficacy of these drugs in a larger cohort and developed predictive models to identify patient responders. We used a double‐blind randomized three‐way crossover design to investigate stopping efficiency in 34 patients with idiopathic Parkinson's disease after 40 mg atomoxetine, 30 mg citalopram, or placebo. Diffusion‐weighted and functional imaging measured microstructural properties and regional brain activations, respectively. We confirmed that Parkinson's disease impairs response inhibition. Overall, drug effects on response inhibition varied substantially across patients at both behavioral and brain activity levels. We therefore built binary classifiers with leave‐one‐out cross‐validation (LOOCV) to predict patients’ responses in terms of improved stopping efficiency. We identified two optimal models: (1) a “clinical” model that predicted the response of an individual patient with 77–79% accuracy for atomoxetine and citalopram, using clinically available information including age, cognitive status, and levodopa equivalent dose, and a simple diffusion‐weighted imaging scan; and (2) a “mechanistic” model that explained the behavioral response with 85% accuracy for each drug, using drug‐induced changes of brain activations in the striatum and presupplementary motor area from functional imaging. These data support growing evidence for the role of noradrenaline and serotonin in inhibitory control. Although noradrenergic and serotonergic drugs have highly variable effects in patients with Parkinson's disease, the individual patient's response to each drug can be predicted using a pattern of clinical and neuroimaging features. Hum Brain Mapp 37:1026–1037

  14. Predicting beneficial effects of atomoxetine and citalopram on response inhibition in Parkinson's disease with clinical and neuroimaging measures.

    PubMed

    Ye, Zheng; Rae, Charlotte L; Nombela, Cristina; Ham, Timothy; Rittman, Timothy; Jones, Peter Simon; Rodríguez, Patricia Vázquez; Coyle-Gilchrist, Ian; Regenthal, Ralf; Altena, Ellemarije; Housden, Charlotte R; Maxwell, Helen; Sahakian, Barbara J; Barker, Roger A; Robbins, Trevor W; Rowe, James B

    2016-03-01

    Recent studies indicate that selective noradrenergic (atomoxetine) and serotonergic (citalopram) reuptake inhibitors may improve response inhibition in selected patients with Parkinson's disease, restoring behavioral performance and brain activity. We reassessed the behavioral efficacy of these drugs in a larger cohort and developed predictive models to identify patient responders. We used a double-blind randomized three-way crossover design to investigate stopping efficiency in 34 patients with idiopathic Parkinson's disease after 40 mg atomoxetine, 30 mg citalopram, or placebo. Diffusion-weighted and functional imaging measured microstructural properties and regional brain activations, respectively. We confirmed that Parkinson's disease impairs response inhibition. Overall, drug effects on response inhibition varied substantially across patients at both behavioral and brain activity levels. We therefore built binary classifiers with leave-one-out cross-validation (LOOCV) to predict patients' responses in terms of improved stopping efficiency. We identified two optimal models: (1) a "clinical" model that predicted the response of an individual patient with 77-79% accuracy for atomoxetine and citalopram, using clinically available information including age, cognitive status, and levodopa equivalent dose, and a simple diffusion-weighted imaging scan; and (2) a "mechanistic" model that explained the behavioral response with 85% accuracy for each drug, using drug-induced changes of brain activations in the striatum and presupplementary motor area from functional imaging. These data support growing evidence for the role of noradrenaline and serotonin in inhibitory control. Although noradrenergic and serotonergic drugs have highly variable effects in patients with Parkinson's disease, the individual patient's response to each drug can be predicted using a pattern of clinical and neuroimaging features. PMID:26757216

  15. Multiple testing for neuroimaging via hidden Markov random field.

    PubMed

    Shu, Hai; Nan, Bin; Koeppe, Robert

    2015-09-01

    Traditional voxel-level multiple testing procedures in neuroimaging, mostly p-value based, often ignore the spatial correlations among neighboring voxels and thus suffer from substantial loss of power. We extend the local-significance-index based procedure originally developed for the hidden Markov chain models, which aims to minimize the false nondiscovery rate subject to a constraint on the false discovery rate, to three-dimensional neuroimaging data using a hidden Markov random field model. A generalized expectation-maximization algorithm for maximizing the penalized likelihood is proposed for estimating the model parameters. Extensive simulations show that the proposed approach is more powerful than conventional false discovery rate procedures. We apply the method to the comparison between mild cognitive impairment, a disease status with increased risk of developing Alzheimer's or another dementia, and normal controls in the FDG-PET imaging study of the Alzheimer's Disease Neuroimaging Initiative. PMID:26012881

  16. Identification of disease-related spatial covariance patterns using neuroimaging data.

    PubMed

    Spetsieris, Phoebe; Ma, Yilong; Peng, Shichun; Ko, Ji Hyun; Dhawan, Vijay; Tang, Chris C; Eidelberg, David

    2013-01-01

    The scaled subprofile model (SSM)(1-4) is a multivariate PCA-based algorithm that identifies major sources of variation in patient and control group brain image data while rejecting lesser components (Figure 1). Applied directly to voxel-by-voxel covariance data of steady-state multimodality images, an entire group image set can be reduced to a few significant linearly independent covariance patterns and corresponding subject scores. Each pattern, termed a group invariant subprofile (GIS), is an orthogonal principal component that represents a spatially distributed network of functionally interrelated brain regions. Large global mean scalar effects that can obscure smaller network-specific contributions are removed by the inherent logarithmic conversion and mean centering of the data(2,5,6). Subjects express each of these patterns to a variable degree represented by a simple scalar score that can correlate with independent clinical or psychometric descriptors(7,8). Using logistic regression analysis of subject scores (i.e. pattern expression values), linear coefficients can be derived to combine multiple principal components into single disease-related spatial covariance patterns, i.e. composite networks with improved discrimination of patients from healthy control subjects(5,6). Cross-validation within the derivation set can be performed using bootstrap resampling techniques(9). Forward validation is easily confirmed by direct score evaluation of the derived patterns in prospective datasets(10). Once validated, disease-related patterns can be used to score individual patients with respect to a fixed reference sample, often the set of healthy subjects that was used (with the disease group) in the original pattern derivation(11). These standardized values can in turn be used to assist in differential diagnosis(12,13) and to assess disease progression and treatment effects at the network level(7,14-16). We present an example of the application of this methodology to

  17. Immunity factor contributes to altered brain functional networks in individuals at risk for Alzheimer's disease: Neuroimaging-genetic evidence.

    PubMed

    Bai, Feng; Shi, Yongmei; Yuan, Yonggui; Xie, Chunming; Zhang, Zhijun

    2016-08-01

    Clusterin (CLU) is recognized as a secreted protein that is related to the processes of inflammation and immunity in the pathogenesis of Alzheimer's disease (AD). The effects of the risk variant of the C allele at the rs11136000 locus of the CLU gene are associated with variations in the brain structure and function. However, the relationship of the CLU-C allele to architectural disruptions in resting-state networks in amnestic mild cognitive impairment (aMCI) subjects (i.e., individuals with elevated risk of AD) remains relatively unknown. Using resting-state functional magnetic resonance imaging and an imaging genetic approach, this study investigated whether individual brain functional networks, i.e., the default mode network (DMN) and the task-positive network, were modulated by the CLU-C allele (rs11136000) in 50 elderly participants, including 26 aMCI subjects and 24 healthy controls. CLU-by-aMCI interactions were associated with the information-bridging regions between resting-state networks rather than with the DMN itself, especially in cortical midline regions. Interestingly, the complex communications between resting-state networks were enhanced in aMCI subjects with the CLU rs11136000 CC genotype and were modulated by the degree of memory impairment, suggesting a reconstructed balance of the resting-state networks in these individuals with an elevated risk of AD. The neuroimaging-genetic evidence indicates that immunity factors may contribute to alterations in brain functional networks in aMCI. These findings add to the evidence that the CLU gene may represent a potential therapeutic target for slowing disease progression in AD. PMID:26899953

  18. Evaluation of multi-modal, multi-site neuroimaging measures in Huntington's disease: Baseline results from the PADDINGTON study☆

    PubMed Central

    Hobbs, Nicola Z.; Cole, James H.; Farmer, Ruth E.; Rees, Elin M.; Crawford, Helen E.; Malone, Ian B.; Roos, Raymund A.C.; Sprengelmeyer, Reiner; Durr, Alexandra; Landwehrmeyer, Bernhard; Scahill, Rachael I.; Tabrizi, Sarah J.; Frost, Chris

    2012-01-01

    Background Macro- and micro-structural neuroimaging measures provide valuable information on the pathophysiology of Huntington's disease (HD) and are proposed as biomarkers. Despite theoretical advantages of microstructural measures in terms of sensitivity to pathology, there is little evidence directly comparing the two. Methods 40 controls and 61 early HD subjects underwent 3 T MRI (T1- and diffusion-weighted), as part of the PADDINGTON study. Macrostructural volumetrics were obtained for the whole brain, caudate, putamen, corpus callosum (CC) and ventricles. Microstructural diffusion metrics of fractional anisotropy (FA), mean-, radial- and axial-diffusivity (MD, RD, AD) were computed for white matter (WM), CC, caudate and putamen. Group differences were examined adjusting for age, gender and site. A formal comparison of effect sizes determined which modality and metrics provided a statistically significant advantage over others. Results Macrostructural measures showed decreased regional and global volume in HD (p < 0.001); except the ventricles which were enlarged (p < 0.01). In HD, FA was increased in the deep grey-matter structures (p < 0.001), and decreased in the WM (CC, p = 0.035; WM, p = 0.053); diffusivity metrics (MD, RD, AD) were increased for all brain regions (p < 0.001). The largest effect sizes were for putamen volume, caudate volume and putamen diffusivity (AD, RD and MD); each was significantly larger than those for all other metrics (p < 0.05). Conclusion The highest performing macro- and micro-structural metrics had similar sensitivity to HD pathology quantified via effect sizes. Region-of-interest may be more important than imaging modality, with deep grey-matter regions outperforming the CC and global measures, for both volume and diffusivity. FA appears to be relatively insensitive to disease effects. PMID:24179770

  19. A Pilot Study on Clinical and Neuroimaging Characteristics of Chinese Posterior Cortical Atrophy: Comparison with Typical Alzheimer’s Disease

    PubMed Central

    Shi, Zhihong; Cai, Li; Liu, Shuai; Liu, Shuling; Han, Tong; Wang, Ying; Zhou, Yuying; Wang, Xinping; Gao, Shuo; Ji, Yong

    2015-01-01

    Posterior cortical atrophy (PCA) is a clinicoradiologic neurodegenerative syndrome characterized by predominant impairment of higher visual functions. Neuroimaging and neuropathological studies show that PCA is probably an atypical presentation of Alzheimer’s disease. However, in China PCA has rarely been studied and remains largely unknown. Our study therefore aimed to analyze the clinical manifestations and patterns of cerebral atrophy, amyloid beta deposition and regional glucose metabolism in Chinese PCA patients, comparing them directly with those of typical Alzheimer’s disease (TAD). Seven PCA patients, 6 TAD patients and 5 controls underwent neuropsychological assessment, MRI scan, 11C-PIB PET scan and 18F-FDG PET scan. Cerebral atrophy including ventricular enlargement, posterior atrophy and medial temporal lobe atrophy were evaluated with MRI. The uptake of 11C-PIB was quantified at the voxel level using the standardized uptake value ratio. Comparisons of regional cerebral glucose metabolism were calculated with statistical parametric mapping. PCA patients showed significant impairment on visuospatial function in neuropsychological assessment. And PCA patients showed more severe posterior atrophy and less severe left medial temporal lobe atrophy compared with TAD patients. The data from 11C-PIB PET scanning showed that amyloid beta deposition in PCA was comparable to TAD. Moreover, in PCA the results from 18F-FDG PET scanning revealed significant hypometabolism in the temporoparietooccipital region and identified specific hypometabolism in the right occipital lobe, compared with TAD. Our study thus provides a preliminary view of PCA in Chinese patients. A further study with a larger number of subjects would be recommended to confirm these findings. PMID:26267071

  20. Clinical and neuroimaging features as diagnostic guides in neonatal neurology diseases with cerebellar involvement.

    PubMed

    Klein, Jessica L; Lemmon, Monica E; Northington, Frances J; Boltshauser, Eugen; Huisman, Thierry A G M; Poretti, Andrea

    2016-01-01

    Cerebellar abnormalities are encountered in a high number of neurological diseases that present in the neonatal period. These disorders can be categorized broadly as inherited (e.g. malformations, inborn errors of metabolism) or acquired (e.g. hemorrhages, infections, stroke). In some disorders such as Dandy-Walker malformation or Joubert syndrome, the main abnormalities are located within the cerebellum and brainstem. In other disorders such as Krabbe disease or sulfite oxidase deficiency, the main abnormalities are found within the supratentorial brain, but the cerebellar involvement may be helpful for diagnostic purposes. In In this article, we review neurological disorders with onset in the neonatal period and cerebellar involvement with a focus on how characterization of cerebellar involvement can facilitate accurate diagnosis and improved accuracy of neuro-functional prognosis. PMID:26770813

  1. Delirium and hypovitaminosis D: neuroimaging findings.

    PubMed

    Bourgeois, James A; Hategan, Ana; Ford, Jennifer; Tisi, Daniel K; Xiong, Glen L

    2015-01-01

    The authors examined the frequency of neuroimaging findings of cortical atrophy and/or cerebrovascular disease in patients with delirium with hypovitaminosis D and normal vitamin D levels. Of 32 patients with delirium with hypovitaminosis D who were neuroimaged, 91.4% had neuroimaging findings, despite only five cases having a comorbid diagnosis of dementia. Similar frequencies of cortical atrophy and/or cerebrovascular disease were found in patients with delirium with normal vitamin D levels. Further research with a larger sample size is needed to compare neuroimaging findings between normal patients and patients with hypovitaminosis D with delirium. PMID:25111282

  2. Homocysteine and cognitive impairment in Parkinson's disease: a biochemical, neuroimaging, and genetic study.

    PubMed

    Rodriguez-Oroz, Maria C; Lage, Pablo Martínez; Sanchez-Mut, Jose; Lamet, Isabel; Pagonabarraga, Javier; Toledo, Jon B; García-Garcia, David; Clavero, Pedro; Samaranch, Lluis; Irurzun, Cecilia; Matsubara, Juan M; Irigoien, Jaione; Bescos, Emilia; Kulisevsky, Jaime; Pérez-Tur, Jordi; Obeso, Jose A

    2009-07-30

    The role of the plasma level of homocysteine (Hcy), as a primary outcome, and the effect of silent cerebrovascular lesions and genetic variants related to Hcy metabolism, as secondary outcomes, in the cognitive decline and dementia in Parkinson's disease (PD) were studied. This case-control study focused on 89 PD patients of minimum 10 years of evolution and older than 60 years, who were neuropsychologically classified either as cognitively normal (n = 37), having mild cognitive impairment (Petersen criteria) (n = 22), or suffering from dementia (DSM-IV) (n = 30), compared with cognitively normal age-matched control subjects (n = 30). Plasma levels of Hcy, vitamins B12 and B6, folic acid, polymorphisms in genes related to Hcy metabolism (MTHFR, MTR, MTRR, and CBS) and silent cerebrovascular events were analyzed. Plasma levels of Hcy were increased in PD patients (P = 0.0001). There were no differences between the groups of patients. The brain vascular burden was similar among PD groups. There was no association between polymorphisms in the studied genes and the Hcy plasma levels or cognitive status in PD patients. We found no evidence for a direct relationship between Hcy plasma levels and cognitive impairment and dementia in PD. No indirect effect through cerebrovascular disease or genetic background was found either. PMID:19452554

  3. Chagas disease: Central American initiative launched.

    PubMed

    1998-02-01

    An initiative to interrupt the transmission of Chagas disease in Central America was launched at a meeting held October 22-24, 1997, in Tegucigalpa, Honduras. Sponsored by the UNDP/World Bank/WHO Special Program for Research and Training in Tropical Diseases (TDR), the meeting was attended by government delegates from Belize, Costa Rica, El Salvador, Guatemala, Honduras, Nicaragua, and Panama. The initiative was launched within the framework of Resolution 13 of the Meeting of Ministers of Health of the Central American Countries, held in Belize in September 1997. Detailed plans of activities were prepared for each country for the period 1998-2001, for approval by the various ministries of health, while operational, epidemiological, and entomological research priorities were also agreed upon. Research projects to help improve disease control will be sponsored by TDR. The first meeting of the Technical Intergovernment Commission established to meet annually to assess progress in control activities will occur in October 1998 in Guatemala. Vector and infection rate data are briefly presented on each country represented at the meeting. PMID:12348564

  4. Neuroimaging features of tuberculous meningitis.

    PubMed

    Sobri, M; Merican, J S; Nordiyana, M; Valarmathi, S; Ai-Edrus, S A

    2006-03-01

    Tuberculous meningitis leads to a high mortality rate. However, it responds well to chemotherapy if the treatment is started early. Neuroimaging is one of the most important initial investigations. There were 42 patients diagnosed with tuberculous meningitis in Kuala Lumpur Hospital based on clinical criteria, cerebrospinal fluid analysis and response to anti-tuberculous treatment over a 7 year period. Relevant information was obtained from patients' medical case notes and neuroimaging findings were evaluated. Male to female ratio was 3:1. The three major ethnics and the immigrant groups in Malaysia were represented in this study. The majority of the cases involved the Malays followed by immigrants, Chinese and Indians. The patients' age ranged from 18 to 62 years old with the mean age of 34.4 years. There were 95.2% (n = 40) of patients who presented with various neuroimaging abnormalities and only 2 (4.8%) patients had normal neuroimaging findings. Hydrocephalus and meningeal enhancement were the two commonest neuroimaging features. Other features include infarction, enhancing lesion, tuberculoma, abcess, oedema and calcification. Contrasted CT scan is an adequate neuroimaging tool to unmask abnormal findings in tuberculous meningitis. PMID:16708732

  5. The Co-evolution of Neuroimaging and Psychiatric Neurosurgery.

    PubMed

    Dyster, Timothy G; Mikell, Charles B; Sheth, Sameer A

    2016-01-01

    The role of neuroimaging in psychiatric neurosurgery has evolved significantly throughout the field's history. Psychiatric neurosurgery initially developed without the benefit of information provided by modern imaging modalities, and thus lesion targets were selected based on contemporary theories of frontal lobe dysfunction in psychiatric disease. However, by the end of the 20th century, the availability of structural and functional magnetic resonance imaging (fMRI) allowed for the development of mechanistic theories attempting to explain the anatamofunctional basis of these disorders, as well as the efficacy of stereotactic neuromodulatory treatments. Neuroimaging now plays a central and ever-expanding role in the neurosurgical management of psychiatric disorders, by influencing the determination of surgical candidates, allowing individualized surgical targeting and planning, and identifying network-level changes in the brain following surgery. In this review, we aim to describe the coevolution of psychiatric neurosurgery and neuroimaging, including ways in which neuroimaging has proved useful in elucidating the therapeutic mechanisms of neuromodulatory procedures. We focus on ablative over stimulation-based procedures given their historical precedence and the greater opportunity they afford for post-operative re-imaging, but also discuss important contributions from the deep brain stimulation (DBS) literature. We conclude with a discussion of how neuroimaging will transition the field of psychiatric neurosurgery into the era of precision medicine. PMID:27445706

  6. The Co-evolution of Neuroimaging and Psychiatric Neurosurgery

    PubMed Central

    Dyster, Timothy G.; Mikell, Charles B.; Sheth, Sameer A.

    2016-01-01

    The role of neuroimaging in psychiatric neurosurgery has evolved significantly throughout the field’s history. Psychiatric neurosurgery initially developed without the benefit of information provided by modern imaging modalities, and thus lesion targets were selected based on contemporary theories of frontal lobe dysfunction in psychiatric disease. However, by the end of the 20th century, the availability of structural and functional magnetic resonance imaging (fMRI) allowed for the development of mechanistic theories attempting to explain the anatamofunctional basis of these disorders, as well as the efficacy of stereotactic neuromodulatory treatments. Neuroimaging now plays a central and ever-expanding role in the neurosurgical management of psychiatric disorders, by influencing the determination of surgical candidates, allowing individualized surgical targeting and planning, and identifying network-level changes in the brain following surgery. In this review, we aim to describe the coevolution of psychiatric neurosurgery and neuroimaging, including ways in which neuroimaging has proved useful in elucidating the therapeutic mechanisms of neuromodulatory procedures. We focus on ablative over stimulation-based procedures given their historical precedence and the greater opportunity they afford for post-operative re-imaging, but also discuss important contributions from the deep brain stimulation (DBS) literature. We conclude with a discussion of how neuroimaging will transition the field of psychiatric neurosurgery into the era of precision medicine. PMID:27445706

  7. Clinical and neuroimaging differences between posterior cortical atrophy and typical amnestic Alzheimer’s disease patients at an early disease stage

    PubMed Central

    Peng, Guoping; Wang, Jianqin; Feng, Zhan; Liu, Ping; Zhang, Yafei; He, Fangping; Chen, Zhongqin; Zhao, Kui; Luo, Benyan

    2016-01-01

    To identify clinical and neuroimaging characteristics between posterior cortical atrophy (PCA) and typical amnestic Alzheimer’s disease (tAD) patients at an early disease stage, 16 PCA and 13 age-matched tAD patients were enrolled. Compared with tAD patients, PCA patients showed higher mean recognition and recall test scores, and lower mean calculation, spatial attention, shape discrimination, and writing test scores. Mean right hippocampal volume was larger in PCA patients compared with tAD patients, while cortical gray matter (GM) volume of bilateral parietal and occipital lobes was smaller in PCA patients. Further, when compared with tAD patients, significant hypometabolism was observed in bilateral parietal and occipital lobes, particularly the right occipitotemporal junction in PCA patients. Additionally, there were significant positive correlations in recognition and recall scores with hippocampal volumes. In PCA patients, calculation and visuospatial ability scores are positively associated with GM volume of parietal and occipital lobes. And only spatial attention and shape discrimination scores are positively associated with regional glucose metabolism of parietal and occipital lobes. Therefore, PCA patients display better recognition and recall scores, which are associated with larger hippocampal volumes and poorer performance in visual spatial tasks because of marked GM atrophy and hypometabolism of parietal and occipital lobes. PMID:27377199

  8. Advances in neuroimaging in frontotemporal dementia.

    PubMed

    Gordon, Elizabeth; Rohrer, Jonathan D; Fox, Nick C

    2016-08-01

    Frontotemporal dementia (FTD) is a clinically and neuroanatomically heterogeneous neurodegenerative disorder with multiple underlying genetic and pathological causes. Whilst initial neuroimaging studies highlighted the presence of frontal and temporal lobe atrophy or hypometabolism as the unifying feature in patients with FTD, more detailed studies have revealed diverse patterns across individuals, with variable frontal or temporal predominance, differing degrees of asymmetry, and the involvement of other cortical areas including the insula and cingulate, as well as subcortical structures such as the basal ganglia and thalamus. Recent advances in novel imaging modalities including diffusion tensor imaging, resting-state functional magnetic resonance imaging and molecular positron emission tomography imaging allow the possibility of investigating alterations in structural and functional connectivity and the visualisation of pathological protein deposition. This review will cover the major imaging modalities currently used in research and clinical practice, focusing on the key insights they have provided into FTD, including the onset and evolution of pathological changes and also importantly their utility as biomarkers for disease detection and staging, differential diagnosis and measurement of disease progression. Validating neuroimaging biomarkers that are able to accomplish these tasks will be crucial for the ultimate goal of powering upcoming clinical trials by correctly stratifying patient enrolment and providing sensitive markers for evaluating the effects and efficacy of disease-modifying therapies. This review describes the key insights provided by research into the major neuroimaging modalities currently used in research and clinical practice, including what they tell us about the onset and evolution of FTD and how they may be used as biomarkers for disease detection and staging, differential diagnosis and measurement of disease progression. This article is

  9. Initial Staging of Hodgkin’s Disease

    PubMed Central

    Chiaravalloti, Agostino; Danieli, Roberta; Caracciolo, Cristiana Ragano; Travascio, Laura; Cantonetti, Maria; Gallamini, Andrea; Guazzaroni, Manlio; Orlacchio, Antonio; Simonetti, Giovanni; Schillaci, Orazio

    2014-01-01

    Abstract The objective of this study was to compare the diagnostic accuracy of positron emission tomography/low-dose computed tomography (PET/ldCT) versus the same technique implemented by contrast-enhanced computed tomography (ceCT) in staging Hodgkin’s disease (HD). Forty patients (18 men and 22 women, mean age 30 ± 9.6) with biopsy-proven HD underwent a PET/ldCT study for initial staging including an unenhanced low-dose computed tomography for attenuation correction with positron emission tomography acquisition and a ceCT, performed at the end of the PET/ldCT scan, in the same exam session. A detailed datasheet was generated for illness locations for separate imaging modality comparison and then merged in order to compare the separate imaging method results (PET/ldCT and ceCT) versus merged results positron emission tomography/contrast-enhanced computed tomography (PET/ceCT). The nodal and extranodal lesions detected by each technique were then compared with follow-up data that served as the reference standard. No significant differences were found at staging between PET/ldCT and PET/ceCT in our series. One hundred and eighty four stations of nodal involvement have been found with no differences in both modalities. Extranodal involvement was identified in 26 sites by PET/ldCT and in 28 by PET/ceCT. We did not find significant differences concerning the stage (Ann Arbor). Our study shows a good concordance and conjunction between PET/ldCT and ceCT in both nodal and extranodal sites in the initial staging of HD, suggesting that PET/ldCT could suffice in most of these patients. PMID:25121354

  10. Neuroimaging of Graves' orbitopathy.

    PubMed

    Müller-Forell, Wibke; Kahaly, George J

    2012-06-01

    Neuroimaging of Graves' orbitopathy (GO) plays an important role in the differential diagnosis and interdisciplinary management of patients with GO. Orbital imaging is required in unclear or asymmetric proptosis, in suspected optic neuropathy and prior to decompression surgery. Especially computed tomography and magnetic resonance (MR) imaging show the actual objective morphological findings, quantitative MR imaging giving additional information concerning the acuteness or chronicity of the disease. Major morphological diagnostic criteria include a spindle like spreading of the rectus muscles without involvement of the tendon, a compression of the optic nerve in the orbital apex (crowded orbital apex syndrome) and the absence of any space occupying intraorbital process. A longer lasting course of the disease may lead to a corresponding impression of the lamina papyracae, the normally parallel configured medial wall of the orbit, similar to a spontaneous decompression. PMID:22632363

  11. Effect of CLU genetic variants on cerebrospinal fluid and neuroimaging markers in healthy, mild cognitive impairment and Alzheimer’s disease cohorts

    PubMed Central

    Tan, Lin; Wang, Hui-Fu; Tan, Meng-Shan; Tan, Chen-Chen; Zhu, Xi-Chen; Miao, Dan; Yu, Wan-Jiang; Jiang, Teng; Tan, Lan; Yu, Jin-Tai; Weiner, Michael W.; Aisen, Paul; Petersen, Ronald; Jack, Clifford R.; Jagust, William; Trojanowki, John Q.; Toga, Arthur W.; Beckett, Laurel; Green, Robert C.; Saykin, Andrew J.; Morris, John; Shaw, Leslie M.; Kaye, Jeffrey; Quinn, Joseph; Silbert, Lisa; Lind, Betty; Carter, Raina; Dolen, Sara; Schneider, Lon S.; Pawluczyk, Sonia; Beccera, Mauricio; Teodoro, Liberty; Spann, Bryan M.; Brewer, James; Vanderswag, Helen; Fleisher, Adam; Heidebrink, Judith L.; Lord, Joanne L.; Mason, Sara S.; Albers, Colleen S.; Knopman, David; Johnson, Kris; Doody, Rachelle S.; Villanueva-Meyer, Javier; Chowdhury, Munir; Rountree, Susan; Dang, Mimi; Stern, Yaakov; Honig, Lawrence S.; Bell, Karen L.; Ances, Beau; Morris, John C.; Carroll, Maria; Creech, Mary L.; Franklin, Erin; Mintun, Mark A.; Schneider, Stacy; Oliver, Angela; Marson, Daniel; Griffith, Randall; Clark, David; Geldmacher, David; Brockington, John; Roberson, Erik; Love, Marissa Natelson; Grossman, Hillel; Mitsis, Effie; Shah, Raj C.; deToledo-Morrell, Leyla; Duara, Ranjan; Varon, Daniel; Greig, Maria T.; Roberts, Peggy; Albert, Marilyn; Onyike, Chiadi; D’Agostino, Daniel; Kielb, Stephanie; Galvin, James E.; Cerbone, Brittany; Michel, Christina A.; Pogorelec, Dana M.; Rusinek, Henry; de Leon, Mony J.; Glodzik, Lidia; De Santi, Susan; Doraiswamy, P. Murali; Petrella, Jeffrey R.; Borges-Neto, Salvador; Wong, Terence Z.; Coleman, Edward; Smith, Charles D.; Jicha, Greg; Hardy, Peter; Sinha, Partha; Oates, Elizabeth; Conrad, Gary; Porsteinsson, Anton P.; Goldstein, Bonnie S.; Martin, Kim; Makino, Kelly M.; Ismail, M. Saleem; Brand, Connie; Mulnard, Ruth A.; Thai, Gaby; Mc-Adams-Ortiz, Catherine; Womack, Kyle; Mathews, Dana; Quiceno, Mary; Levey, Allan I.; Lah, James J.; Cellar, Janet S.; Burns, Jeffrey M.; Swerdlow, Russell H.; Brooks, William M.; Apostolova, Liana; Tingus, Kathleen; Woo, Ellen; Silverman, Daniel H. S.; Lu, Po H.; Bartzokis, George; Graff-Radford, Neill R.; Parfitt, Francine; Kendall, Tracy; Johnson, Heather; Farlow, Martin R.; Hake, Ann Marie; Matthews, Brandy R.; Brosch, Jared R.; Herring, Scott; Hunt, Cynthia; van Dyck, Christopher H.; Carson, Richard E.; MacAvoy, Martha G.; Varma, Pradeep; Chertkow, Howard; Bergman, Howard; Hosein, Chris; Black, Sandra; Stefanovic, Bojana; Caldwell, Curtis; Hsiung, Ging-Yuek Robin; Feldman, Howard; Mudge, Benita; Assaly, Michele; Finger, Elizabeth; Pasternack, Stephen; Rachisky, Irina; Trost, Dick; Kertesz, Andrew; Bernick, Charles; Munic, Donna; Mesulam, Marek-Marsel; Lipowski, Kristine; Weintraub, Sandra; Bonakdarpour, Borna; Kerwin, Diana; Wu, Chuang-Kuo; Johnson, Nancy; Sadowsky, Carl; Villena, Teresa; Turner, Raymond Scott; Johnson, Kathleen; Reynolds, Brigid; Sperling, Reisa A.; Johnson, Keith A.; Marshall, Gad; Yesavage, Jerome; Taylor, Joy L.; Lane, Barton; Rosen, Allyson; Tinklenberg, Jared; Sabbagh, Marwan N.; Belden, Christine M.; Jacobson, Sandra A.; Sirrel, Sherye A.; Kowall, Neil; Killiany, Ronald; Budson, Andrew E.; Norbash, Alexander; Johnson, Patricia Lynn; Obisesan, Thomas O.; Wolday, Saba; Allard, Joanne; Lerner, Alan; Ogrocki, Paula; Tatsuoka, Curtis; Fatica, Parianne; Fletcher, Evan; Maillard, Pauline; Olichney, John; DeCarli, Charles; Carmichael, Owen; Kittur, Smita; Borrie, Michael; Lee, T -Y; Bartha, Rob; Johnson, Sterling; Asthana, Sanjay; Carlsson, Cynthia M.; Potkin, Steven G.; Preda, Adrian; Nguyen, Dana; Tariot, Pierre; Burke, Anna; Trncic, Nadira; Fleisher, Adam; Reeder, Stephanie; Bates, Vernice; Capote, Horacio; Rainka, Michelle; Scharre, Douglas W.; Kataki, Maria; Adeli, Anahita; Zimmerman, Earl A.; Celmins, Dzintra; Brown, Alice D.; Pearlson, Godfrey D.; Blank, Karen; Anderson, Karen; Flashman, Laura A.; Seltzer, Marc; Hynes, Mary L.; Santulli, Robert B.; Sink, Kaycee M.; Gordineer, Leslie; Williamson, Jeff D.; Garg, Pradeep; Watkins, Franklin; Ott, Brian R.; Querfurth, Henry; Tremont, Geoffrey; Salloway, Stephen; Malloy, Paul; Correia, Stephen; Rosen, Howard J.; Miller, Bruce L.; Perry, David; Mintzer, Jacobo; Spicer, Kenneth; Bachman, David; Pomara, Nunzio; Hernando, Raymundo; Sarrael, Antero; Relkin, Norman; Chaing, Gloria; Lin, Michael; Ravdin, Lisa; Smith, Amanda; Raj, Balebail Ashok; Fargher, Kristin

    2016-01-01

    The Clusterin (CLU) gene, also known as apolipoprotein J (ApoJ), is currently the third most associated late-onset Alzheimer’s disease (LOAD) risk gene. However, little was known about the possible effect of CLU genetic variants on AD pathology in brain. Here, we evaluated the interaction between 7 CLU SNPs (covering 95% of genetic variations) and the role of CLU in β-amyloid (Aβ) deposition, AD-related structure atrophy, abnormal glucose metabolism on neuroimaging and CSF markers to clarify the possible approach by that CLU impacts AD. Finally, four loci (rs11136000, rs1532278, rs2279590, rs7982) showed significant associations with the Aβ deposition at the baseline level while genotypes of rs9331888 (P = 0.042) increased Aβ deposition. Besides, rs9331888 was significantly associated with baseline volume of left hippocampus (P = 0.014). We then further validated the association with Aβ deposition in the AD, mild cognitive impairment (MCI), normal control (NC) sub-groups. The results in sub-groups confirmed the association between CLU genotypes and Aβ deposition further. Our findings revealed that CLU genotypes could probably modulate the cerebral the Aβ loads on imaging and volume of hippocampus. These findings raise the possibility that the biological effects of CLU may be relatively confined to neuroimaging trait and hence may offer clues to AD. PMID:27229352

  12. Clinical neuroimaging

    SciTech Connect

    Gilman, S.; Mazziotta, J.C.

    1989-01-01

    Designed for practicing neurologists and neurosurgeons, this reference focuses on the newest techniques in computed assisted tomography. Text material covers basic principles of computed tomography, as well as the clinical advantages and disadvantages of each modality. The anatomical and/or physiological processes measured by XCT, PET, SPECT and MRI are first discussed in terms of the normal patient, and then applied to the diagnosis and treatment of patients with neurological disease (primarily of the brain). Emphasis is placed on areas of difficult diagnosis, such as differentiating recurrent tumor from radiation necrosis, early diagnosis of dementia, selection of patients for extracranial-intracranial bypass procedures, and localization of epileptic foci.

  13. Parkinson's disease: initial treatment of motor disorders.

    PubMed

    2015-09-01

    Parkinson's disease is characterised by three main symptoms: slowness and paucity of movements, rigidity, and resting tremor. Rapid improvement in these symptoms after levodopa administration supports the diagnosis of Parkinson's disease. It is important to inform the patient tactfully, allowing him or her to control the pace at which information on the diagnosis, symptoms and prognosis is conveyed. Patients with minimal discomfort or mild disability derive little benefit from drug therapy. Physiotherapy and physical exercises are sometimes useful. Previously untreated patients with marked functional impairment should receive medication. The choice is essentially between levodopa and ropinirole, and mainly depends on the patient's age. PMID:26417634

  14. Recurrent Kawasaki disease resistant to initial treatment with intravenous immunoglobulin

    PubMed Central

    2012-01-01

    Kawasaki disease (mucocutaneous lymph node syndrome) is a disease of unknown etiology characterized by vasculitis which may affect the coronary arteries. Young children are most commonly affected although the disease has been described in adults. Kawasaki disease (KD) was first described by Dr Tomisaku Kawasaki in 1967. Since then, more cases have been reported worldwide, the majority being from Japan. We report on a 6-year-old child with recurrent attacks of Kawasaki disease which was initially resistant to the conventional treatment.

  15. Neuroimaging in tuberculous meningitis.

    PubMed

    Garg, Ravindra Kumar; Malhotra, Hardeep Singh; Jain, Amita

    2016-01-01

    Tuberculous meningitis is a serious infection caused by Mycobacterium tuberculosis. Early diagnosis is the key to success of treatment. Neuroimaging plays a crucial role in the early and accurate diagnosis of tuberculous meningitis and its disabling complications. Magnetic resonance imaging is considered superior to computed tomography. Neuroimaging characteristics include leptomeningeal and basal cisternal enhancement, hydrocephalus, periventricular infarcts, and tuberculoma. Partially treated pyogenic meningitis, cryptococcal meningitis, viral encephalitis, carcinomatous, and lymphomatous meningitis may have many similar neuroimaging characteristics, and differentiation from tuberculous meningitis at times on the basis of neuroimaging characteristics becomes difficult. PMID:26954796

  16. Throat clicking as the initial symptom of Parkinson's disease.

    PubMed

    Iyer, Sanjay S; Morgan, John C; Glover, Andrea L; Sethi, Kapil D

    2005-10-01

    The presenting manifestations of Parkinson's disease (PD) are variable, but a majority of patients note tremor as the initial symptom. Others complain of slowing of movements, loss of dexterity, fatigue, or changes in handwriting as initial symptoms. We describe a patient who developed an unusual clicking sound emanating from his throat as the initial manifestation of PD. PMID:16001408

  17. Neuroimaging of the Philadelphia Neurodevelopmental Cohort

    PubMed Central

    Satterthwaite, Theodore D.; Elliott, Mark A.; Ruparel, Kosha; Loughead, James; Prabhakaran, Karthik; Calkins, Monica E.; Hopson, Ryan; Jackson, Chad; Keefe, Jack; Riley, Marisa; Mensh, Frank D.; Sleiman, Patrick; Verma, Ragini; Davatzikos, Christos; Hakonarson, Hakon; Gur, Ruben C.; Gur, Raquel E.

    2013-01-01

    The Philadelphia Neurodevelopmental Cohort (PNC) is a large-scale, NIMH funded initiative to understand how brain maturation mediates cognitive development and vulnerability to psychiatric illness, and understand how genetics impacts this process. As part of this study, 1,445 adolescents ages 8–21 at enrollment underwent multimodal neuroimaging. Here, we highlight the conceptual basis for the effort, the study design, and measures available in the dataset. We focus on neuroimaging measures obtained, including T1-weighted structural neuroimaging, diffusion tensor imaging, perfusion neuroimaging using arterial spin labeling, functional imaging tasks of working memory and emotion identification, and resting state imaging of functional connectivity. Furthermore, we provide characteristics regarding the final sample acquired. Finally, we describe mechanisms in place for data sharing that will allow the PNC to become a freely available public resource to advance our understanding of normal and pathological brain development. PMID:23921101

  18. FUNCTIONAL NEUROIMAGING IN GERIATRIC DEPRESSION

    PubMed Central

    Gunning, Faith M.; Smith, Gwenn S.

    2012-01-01

    Synopsis Abnormalities in specific cerebral networks likely confer vulnerability that increases the susceptibility for development of geriatric depression and impact the course of symptoms. Functional neuroimaging enables the in vivo identification of alterations in cerebral function that not only characterize disease vulnerability, but also may contribute to variability in depressive symptoms and antidepressant response. Judicious use of functional neuroimaging tools can advance pathophysiological models of geriatric depression. Furthermore, due to the age-related vulnerability of specific brain systems that have been implicated in mood disorders, geriatric depression provides a logical context within which to study the role of specific functional abnormalities in both antidepressant response and key behavioral and cognitive abnormalities of mood disorders. PMID:21536165

  19. Computer-assisted initial diagnosis of rare diseases

    PubMed Central

    Piñol, Marc; Vilaplana, Jordi; Teixidó, Ivan; Cruz, Joaquim; Comas, Jorge; Vilaprinyo, Ester; Sorribas, Albert

    2016-01-01

    Introduction. Most documented rare diseases have genetic origin. Because of their low individual frequency, an initial diagnosis based on phenotypic symptoms is not always easy, as practitioners might never have been exposed to patients suffering from the relevant disease. It is thus important to develop tools that facilitate symptom-based initial diagnosis of rare diseases by clinicians. In this work we aimed at developing a computational approach to aid in that initial diagnosis. We also aimed at implementing this approach in a user friendly web prototype. We call this tool Rare Disease Discovery. Finally, we also aimed at testing the performance of the prototype. Methods. Rare Disease Discovery uses the publicly available ORPHANET data set of association between rare diseases and their symptoms to automatically predict the most likely rare diseases based on a patient’s symptoms. We apply the method to retrospectively diagnose a cohort of 187 rare disease patients with confirmed diagnosis. Subsequently we test the precision, sensitivity, and global performance of the system under different scenarios by running large scale Monte Carlo simulations. All settings account for situations where absent and/or unrelated symptoms are considered in the diagnosis. Results. We find that this expert system has high diagnostic precision (≥80%) and sensitivity (≥99%), and is robust to both absent and unrelated symptoms. Discussion. The Rare Disease Discovery prediction engine appears to provide a fast and robust method for initial assisted differential diagnosis of rare diseases. We coupled this engine with a user-friendly web interface and it can be freely accessed at http://disease-discovery.udl.cat/. The code and most current database for the whole project can be downloaded from https://github.com/Wrrzag/DiseaseDiscovery/tree/no_classifiers. PMID:27547534

  20. Computer-assisted initial diagnosis of rare diseases.

    PubMed

    Alves, Rui; Piñol, Marc; Vilaplana, Jordi; Teixidó, Ivan; Cruz, Joaquim; Comas, Jorge; Vilaprinyo, Ester; Sorribas, Albert; Solsona, Francesc

    2016-01-01

    Introduction. Most documented rare diseases have genetic origin. Because of their low individual frequency, an initial diagnosis based on phenotypic symptoms is not always easy, as practitioners might never have been exposed to patients suffering from the relevant disease. It is thus important to develop tools that facilitate symptom-based initial diagnosis of rare diseases by clinicians. In this work we aimed at developing a computational approach to aid in that initial diagnosis. We also aimed at implementing this approach in a user friendly web prototype. We call this tool Rare Disease Discovery. Finally, we also aimed at testing the performance of the prototype. Methods. Rare Disease Discovery uses the publicly available ORPHANET data set of association between rare diseases and their symptoms to automatically predict the most likely rare diseases based on a patient's symptoms. We apply the method to retrospectively diagnose a cohort of 187 rare disease patients with confirmed diagnosis. Subsequently we test the precision, sensitivity, and global performance of the system under different scenarios by running large scale Monte Carlo simulations. All settings account for situations where absent and/or unrelated symptoms are considered in the diagnosis. Results. We find that this expert system has high diagnostic precision (≥80%) and sensitivity (≥99%), and is robust to both absent and unrelated symptoms. Discussion. The Rare Disease Discovery prediction engine appears to provide a fast and robust method for initial assisted differential diagnosis of rare diseases. We coupled this engine with a user-friendly web interface and it can be freely accessed at http://disease-discovery.udl.cat/. The code and most current database for the whole project can be downloaded from https://github.com/Wrrzag/DiseaseDiscovery/tree/no_classifiers. PMID:27547534

  1. Neuroimaging of epilepsy.

    PubMed

    Cendes, Fernando; Theodore, William H; Brinkmann, Benjamin H; Sulc, Vlastimil; Cascino, Gregory D

    2016-01-01

    Imaging is pivotal in the evaluation and management of patients with seizure disorders. Elegant structural neuroimaging with magnetic resonance imaging (MRI) may assist in determining the etiology of focal epilepsy and demonstrating the anatomical changes associated with seizure activity. The high diagnostic yield of MRI to identify the common pathological findings in individuals with focal seizures including mesial temporal sclerosis, vascular anomalies, low-grade glial neoplasms and malformations of cortical development has been demonstrated. Positron emission tomography (PET) is the most commonly performed interictal functional neuroimaging technique that may reveal a focal hypometabolic region concordant with seizure onset. Single photon emission computed tomography (SPECT) studies may assist performance of ictal neuroimaging in patients with pharmacoresistant focal epilepsy being considered for neurosurgical treatment. This chapter highlights neuroimaging developments and innovations, and provides a comprehensive overview of the imaging strategies used to improve the care and management of people with epilepsy. PMID:27430454

  2. [Network analyses in neuroimaging studies].

    PubMed

    Hirano, Shigeki; Yamada, Makiko

    2013-06-01

    Neurons are anatomically and physiologically connected to each other, and these connections are involved in various neuronal functions. Multiple important neural networks involved in neurodegenerative diseases can be detected using network analyses in functional neuroimaging. First, the basic methods and theories of voxel-based network analyses, such as principal component analysis, independent component analysis, and seed-based analysis, are described. Disease- and symptom-specific brain networks have been identified using glucose metabolism images in patients with Parkinson's disease. These networks enable us to objectively evaluate individual patients and serve as diagnostic tools as well as biomarkers for therapeutic interventions. Many functional MRI studies have shown that "hub" brain regions, such as the posterior cingulate cortex and medial prefrontal cortex, are deactivated by externally driven cognitive tasks; such brain regions form the "default mode network." Recent studies have shown that this default mode network is disrupted from the preclinical phase of Alzheimer's disease and is associated with amyloid deposition in the brain. Some recent studies have shown that the default mode network is also impaired in Parkinson's disease, whereas other studies have shown inconsistent results. These incongruent results could be due to the heterogeneous pharmacological status, differences in mesocortical dopaminergic impairment status, and concomitant amyloid deposition. Future neuroimaging network analysis studies will reveal novel and interesting findings that will uncover the pathomechanisms of neurological and psychiatric disorders. PMID:23735528

  3. Functional neuroimaging in psychiatry.

    PubMed Central

    Fu, C H; McGuire, P K

    1999-01-01

    Functional neuroimaging is one of the most powerful means available for investigating the pathophysiology of psychiatric disorders. In this review, we shall focus on the different ways that it can be employed to this end, describing the major findings in the field in the context of different methodological approaches. We will also discuss practical issues that are particular to studying psychiatric disorders and the potential contribution of functional neuroimaging to future psychiatric research. PMID:10466156

  4. The Receiver Operational Characteristic for Binary Classification with Multiple Indices and Its Application to the Neuroimaging Study of Alzheimer’s Disease

    PubMed Central

    Wu, Xia; Li, Juan; Ayutyanont, Napatkamon; Protas, Hillary; Jagust, William; Fleisher, Adam; Reiman, Eric; Yao, Li; Chen, Kewei

    2014-01-01

    Given a single index, the receiver operational characteristic (ROC) curve analysis is routinely utilized for characterizing performances in distinguishing two conditions/groups in terms of sensitivity and specificity. Given the availability of multiple data sources (referred to as multi-indices), such as multimodal neuroimaging data sets, cognitive tests, and clinical ratings and genomic data in Alzheimer’s disease (AD) studies, the single-index-based ROC underutilizes all available information. For a long time, a number of algorithmic/analytic approaches combining multiple indices have been widely used to simultaneously incorporate multiple sources. In this study, we propose an alternative for combining multiple indices using logical operations, such as “AND,” “OR,” and “at least n” (where n is an integer), to construct multivariate ROC (multiV-ROC) and characterize the sensitivity and specificity statistically associated with the use of multiple indices. With and without the “leave-one-out” cross-validation, we used two data sets from AD studies to showcase the potentially increased sensitivity/specificity of the multiV-ROC in comparison to the single-index ROC and linear discriminant analysis (an analytic way of combining multi-indices). We conclude that, for the data sets we investigated, the proposed multiV-ROC approach is capable of providing a natural and practical alternative with improved classification accuracy as compared to univariate ROC and linear discriminant analysis. PMID:23702553

  5. PET neuroimaging studies of [(18)F]CABS13 in a double transgenic mouse model of Alzheimer's disease and nonhuman primates.

    PubMed

    Liang, Steven H; Holland, Jason P; Stephenson, Nickeisha A; Kassenbrock, Alina; Rotstein, Benjamin H; Daignault, Cory P; Lewis, Rebecca; Collier, Lee; Hooker, Jacob M; Vasdev, Neil

    2015-04-15

    Fluorine-18 labeled 2-fluoro-8-hydroxyquinoline ([(18)F]CABS13) is a promising positron emission tomography (PET) radiopharmaceutical based on a metal chelator developed to probe the "metal hypothesis of Alzheimer's disease". Herein, a practical radiosynthesis of [(18)F]CABS13 was achieved by radiofluorination followed by deprotection of an O-benzyloxymethyl group. Automated production and formulation of [(18)F]CABS13 resulted in 19 ± 5% uncorrected radiochemical yield, relative to starting [(18)F]fluoride, with ≥95% chemical and radiochemical purities, and high specific activity (>2.5 Ci/μmol) within 80 min. Temporal PET neuroimaging studies were carried out in female transgenic B6C3-Tg(APPswe,PSEN 1dE9)85Dbo/J (APP/PS1) and age-matched wild-type (WT) B6C3F1/J control mice at 3, 7, and 10 months of age. [(18)F]CABS13 showed an overall higher uptake and retention of radioactivity in the central nervous system of APP/PS1 mice versus WT mice with increasing age. However, PET/magnetic resonance imaging in normal nonhuman primates revealed that the tracer had low uptake in the brain and rapid formation of a hydrophilic radiometabolite. Identification of more metabolically stable (18)F-hydroxyquinolines that can be readily accessed by the radiochemical strategy presented herein is underway. PMID:25776827

  6. A review of neuroimaging studies of stressor-evoked blood pressure reactivity: Emerging evidence for a brain-body pathway to coronary heart disease risk

    PubMed Central

    Gianaros, Peter J.; Sheu, Lei K.

    2009-01-01

    An individual's tendency to show exaggerated or otherwise dysregulated cardiovascular reactions to acute stressors has long been associated with increased risk for clinical and preclinical endpoints of coronary heart disease (CHD). However, the ‘brain-body’ pathways that link stressor-evoked cardiovascular reactions to CHD risk remain uncertain. This review summarizes emerging neuroimaging research indicating that individual differences in stressor-evoked blood pressure reactivity (a particular form of cardiovascular reactivity) are associated with activation patterns in corticolimbic brain areas that are jointly involved in processing stressors and regulating the cardiovascular system. As supported empirically by activation likelihood estimates derived from a meta-analysis, these corticolimbic areas include divisions of the cingulate cortex, insula, and amygdala—as well as networked cortical and subcortical areas involved in mobilizing hemodynamic and metabolic support for stress-related behavioral responding. Contextually, the research reviewed here illustrates how behavioral medicine and health neuroscience methods can be integrated to help characterize the ‘brain-body’ pathways that mechanistically link stressful experiences with CHD risk. PMID:19410652

  7. Miniaturized optical neuroimaging in unrestrained animals.

    PubMed

    Yu, Hang; Senarathna, Janaka; Tyler, Betty M; Thakor, Nitish V; Pathak, Arvind P

    2015-06-01

    The confluence of technological advances in optics, miniaturized electronic components and the availability of ever increasing and affordable computational power have ushered in a new era in functional neuroimaging, namely, an era in which neuroimaging of cortical function in unrestrained and unanesthetized rodents has become a reality. Traditional optical neuroimaging required animals to be anesthetized and restrained. This greatly limited the kinds of experiments that could be performed in vivo. Now one can assess blood flow and oxygenation changes resulting from functional activity and image functional response in disease models such as stroke and seizure, and even conduct long-term imaging of tumor physiology, all without the confounding effects of anesthetics or animal restraints. These advances are shedding new light on mammalian brain organization and function, and helping to elucidate loss of this organization or 'dysfunction' in a wide array of central nervous system disease models. In this review, we highlight recent advances in the fabrication, characterization and application of miniaturized head-mounted optical neuroimaging systems pioneered by innovative investigators from a wide array of disciplines. We broadly classify these systems into those based on exogenous contrast agents, such as single- and two-photon microscopy systems; and those based on endogenous contrast mechanisms, such as multispectral or laser speckle contrast imaging systems. Finally, we conclude with a discussion of the strengths and weaknesses of these approaches along with a perspective on the future of this exciting new frontier in neuroimaging. PMID:25791782

  8. The Relationship Between Parkinson's Disease and Essential Tremor: Review of Clinical, Epidemiologic, Genetic, Neuroimaging and Neuropathological Data, and Data on the Presence of Cardinal Signs of Parkinsonism in Essential Tremor

    PubMed Central

    Jiménez-Jiménez, Félix Javier; Alonso-Navarro, Hortensia; García-Martín, Elena; Agúndez, José A. G.

    2012-01-01

    Background The possible relationship between essential tremor (ET) and Parkinson's disease (PD) has been controversial since the first description of PD. However, there is increasing evidence suggesting an overlap between these two disorders. The aim of this review is to examine the relationship between PD and ET, focusing on clinical, epidemiologic, genetic, neuroimaging, and neuropathological data, and the presence of cardinal parkinsonism symptoms in ET. Methods We conducted a PubMed search for articles published between 1966 and November 2011 regarding the relationship between ET and PD and the presence of postural tremor in PD patients; the presence of rest tremor, rigidity, and slowed movements in ET patients is reviewed. Results Clinical series, follow-up studies of ET patients, and case–control and genetic epidemiological studies indicate that ET is associated with increased risk for PD. Some neuroimaging studies and neuropathological reports suggest an association between the two diseases. ET patients show high prevalence of rest tremor, and at least seven studies described slowed movements (possibly related to cerebellar dysfunction and/or bradykinesia) in patients with ET. Discussion There is reasonable epidemiological and clinical evidence to support a link between ET and PD, although it is not clear what factors predict ET patient risk for developing PD or, more rarely, of PD patients developing ET. Future multicentric and multidisciplinary studies including epidemiological, clinical, neuroimaging, genetic, and neuropathological assessments are required to understand these associations. PMID:23439992

  9. [Textural research on the initiator of "new contracted warm disease"].

    PubMed

    Lu, Xiang

    2011-05-01

    Most scholars of the contemporary age thought that WANG Ji was the initiator of "new contracted warm disease". But no evidence was found in Shang Han Xuan Lu to support the viewpoint. New contracted warm disease was not mentioned in the book, even without significant narratives. It is the wrong quotation of Shang Han Xuan Lu by HE Lianchen in his book Chong Ding Guang Wen Re Lun, which is the root cause of the incorrect viewpoint. Therefore, the wrong statement spread among scholars. Actually, GUO Yong had proposed the theory of "new contracted warm disease" in the Southern Song Dynasty. This wrong statement should be corrected. PMID:21781546

  10. The Road Ahead to Cure Alzheimer’s Disease: Development of Biological Markers and Neuroimaging Methods for Prevention Trials Across all Stages and Target Populations

    PubMed Central

    Cavedo, E.; Lista, S.; Khachaturian, Z.; Aisen, P.; Amouyel, P.; Herholz, K.; Jack, C.R.; Sperling, R.; Cummings, J.; Blennow, K.; O’Bryant, S.; Frisoni, G.B.; Khachaturian, A.; Kivipelto, M.; Klunk, W.; Broich, K.; Andrieu, S.; de Schotten, M. Thiebaut; Mangin, J.-F.; Lammertsma, A.A.; Johnson, K.; Teipel, S.; Drzezga, A.; Bokde, A.; Colliot, O.; Bakardjian, H.; Zetterberg, H.; Dubois, B.; Vellas, B.; Schneider, L.S.; Hampel, H.

    2015-01-01

    Alzheimer’s disease (AD) is a slowly progressing non-linear dynamic brain disease in which pathophysiological abnormalities, detectable in vivo by biological markers, precede overt clinical symptoms by many years to decades. Use of these biomarkers for the detection of early and preclinical AD has become of central importance following publication of two international expert working group’s revised criteria for the diagnosis of AD dementia, mild cognitive impairment (MCI) due to AD, prodromal AD and preclinical AD. As a consequence of matured research evidence six AD biomarkers are sufficiently validated and partly qualified to be incorporated into operationalized clinical diagnostic criteria and use in primary and secondary prevention trials. These biomarkers fall into two molecular categories: biomarkers of amyloid-beta (Aβ) deposition and plaque formation as well as of tau-protein related hyperphosphorylation and neurodegeneration. Three of the six gold-standard (“core feasible) biomarkers are neuroimaging measures and three are cerebrospinal fluid (CSF) analytes. CSF Aβ1-42 (Aβ1-42), also expressed as Aβ1-42 : Aβ1-40 ratio, T-tau, and P-tau Thr181 & Thr231 proteins have proven diagnostic accuracy and risk enhancement in prodromal MCI and AD dementia. Conversely, having all three biomarkers in the normal range rules out AD. Intermediate conditions require further patient follow-up. Magnetic resonance imaging (MRI) at increasing field strength and resolution allows detecting the evolution of distinct types of structural and functional abnormality pattern throughout early to late AD stages. Anatomical or volumetric MRI is the most widely used technique and provides local and global measures of atrophy. The revised diagnostic criteria for “prodromal AD” and “mild cognitive impairment due to AD” include hippocampal atrophy (as the fourth validated biomarker), which is considered an indicator of regional neuronal injury. Advanced image analysis

  11. Neuroimaging and Fetal Alcohol Spectrum Disorders

    ERIC Educational Resources Information Center

    Norman, Andria L.; Crocker, Nicole; Mattson, Sarah N.; Riley, Edward P.

    2009-01-01

    The detrimental effects of prenatal alcohol exposure on the developing brain include structural brain anomalies as well as cognitive and behavioral deficits. Initial neuroimaging studies of fetal alcohol spectrum disorders (FASD) using magnetic resonance imaging (MRI) confirmed previous autopsy reports of overall reduction in brain volume and…

  12. Pharmacist initiation of postexposure doxycycline for Lyme disease prophylaxis.

    PubMed

    Jackson, Anita N; Orr, K Kelly; Bratberg, Jeffrey P; Silverblatt, Frederic

    2014-01-01

    OBJECTIVES To enhance public access to prophylaxis for Lyme disease following an identified Ixodes scapularis tick bite through pharmacist-initiated antibiotic therapy and to assess patient satisfaction with the pharmacy-based service provided. SETTING Independent community pharmacy in Charlestown, RI, from May to October 2012. PRACTICE DESCRIPTION Under a collaborative practice agreement, trained pharmacists at an independent pharmacy identified patients eligible for postexposure antibiotic prophylaxis following attachment and removal of an I. scapularis tick (commonly known as a deer tick) and dispensed two 100 mg tablets of doxycycline. Patients were included if they were 18 years or older, provided informed consent, had an estimated time of tick attachment of 36 hours or more, had the tick removed within 72 hours of visit, denied contraindications to doxycycline therapy, and reported telephone access for follow-up. Patients enrolled in the study protocol were given counseling related to doxycycline, signs and symptoms of Lyme disease, and future tick prevention strategies. PRACTICE INNOVATION Pharmacist initiation of doxycycline prophylaxis has not been described in the literature previously. Successful pharmacist initiation of antibiotic prophylaxis may have broader implications for states with endemic Lyme disease or other infectious disease public health concerns. MAIN OUTCOME MEASURES Patient self-reported adverse outcomes and satisfaction with the pharmacy-based service. RESULTS Eight patients enrolled in the study and completed the follow-up survey. The results indicated a high level of satisfaction with the pharmacy services provided, with no reports of the subsequent development of Lyme disease symptoms or major adverse events. CONCLUSION The project has expanded to three community pharmacy sites in southern Rhode Island based on this experience. Similar pharmacy-based collaborative practice models should be considered in highly endemic Lyme disease

  13. Neuroimaging and Psychopharmacology

    ERIC Educational Resources Information Center

    Semrud-Clikeman, Margaret; Pliszka, Steve R.

    2005-01-01

    This review presents the most recent research concerning neuroimaging in developmental disabilities. Changes in structure and activation have been found in children with ADHD and learning disabilities, following intervention. For the children with learning disabilities changes in activation have been found following intensive behavioral and…

  14. Introduction to neuroimaging

    SciTech Connect

    Orrison, W.W.

    1989-01-01

    The author focuses on neuroradiology with emphasis on the current imaging modalities. There are chapters on angiography, myelography, nuclear medicine, ultrasonography, computer tomography (CT), and magnetic resonance (MR) imaging. The other chapters are dedicated to the spine, skull, head and neck, and pediatric neuroimaging.

  15. Why we should study gait initiation in Parkinson's disease.

    PubMed

    Delval, A; Tard, C; Defebvre, L

    2014-01-01

    The gait initiation process is of particular interest in Parkinson's disease because it combines motor and cognitive components of movement preparation (referred to as anticipatory postural adjustments) and movement execution (the step by itself). Moreover, gait initiation in Parkinson's disease is often affected by motor blocks (a subtype of the "freezing of gait" phenomenon). Gait initiation disturbances in Parkinson's disease include delayed release of anticipatory postural adjustments, hypokinetic anticipatory postural adjustments (reduced scaling) and bradykinetic anticipatory postural adjustments (abnormal timing). The most extreme form is freezing of gait with sometimes the absence of anticipatory postural adjustments. Other phenomena can be also described in some freezing patients (such as multiple anticipatory postural adjustments, described clinically as "knee trembling"). The fact that emotion, attention, external triggers and dopaminergic drugs can all modify this motor program suggests the existence of a complex pathophysiological mechanism that involves not only locomotor networks but also cortical areas and the basal ganglia system. Abnormal coupling between standing posture and anticipatory postural adjustments and between the latter and step execution appears to be a crucial part of the pathophysiological mechanism. Although external cueing appears to be of interest, few studies have provided evidence of the efficacy of various rehabilitation methods in routine care. PMID:24502907

  16. Tobacco-Related Disease Burden and Preventive Initiatives in China

    PubMed Central

    Niu, Bolin

    2011-01-01

    The burden of chronic diseases in global health is a surging area of research. The Global Health Initiative at the National Heart, Lung, and Blood Institute brings together investigators from developing countries with those from the developed world to study these diseases. In China, approximately 83 percent of all deaths in 2000 were attributed to chronic illnesses, which are the research focuses of the Chinese center of the Global Health Initiative. Tobacco use as well as passive smoking are modifiable risk factors in a large number of such chronic conditions. The prevalence of smoking in China is extensive and has inseparable ties to the economy, with tobacco taxes making up a large portion of government revenue in poorer provinces. Methods of smoking prevention have been piloted in some Chinese schools, which have mitigated the increase in smoking rate but have not resulted in a primary preventive effect. Efforts by the Yale Global Health Initiative and the Yale-China Association are bringing researchers together to address chronic disease in China as Yale School of Medicine enters its 200th year. PMID:21698050

  17. Structural neuroimaging correlates of cognitive status in older adults: A person-oriented approach.

    PubMed

    Malpas, Charles B

    2016-08-01

    Person-oriented approaches to clinical research aim to uncover subgroups of patients with different patterns of clinically relevant variables. Such approaches, however, are not yet widely employed in clinical neuroimaging research. This paper demonstrates an accessible approach to person-oriented research using model-based clustering in high-dimensional structural neuroimaging data. Cortical thickness measurements for 369 older adults (182 women, 187 men) were obtained from the Alzheimer's Disease Neuroimaging Initiative. Model-based cluster analysis was performed on these imaging variables and then validated using variables that were not used in the clustering process. Variable selection identified two specific regions that contributed to cluster formation: the left and right entorhinal cortices. Two subgroups were uncovered: a "typical" cluster with higher entorhinal thickness (M=3.59mm, 95% confidence interval=3.57, 3.62), and an "atypical" cluster with relatively lower thickness (M=2.84mm, 95% confidence interval=2.75, 2.92). Members of the atypical cluster also had lower hippocampal volumes, memory scores, and executive function scores, and were also more likely to be clinically classified as cognitively impaired. These findings demonstrate the utility of model-based clustering of structural neuroimaging data in studies of ageing. The role of the entorhinal cortices in cluster formation is consistent with the known pathological substrate of Alzheimer's disease. The entorhinal cortices are implicated in the early genesis of the disease and atrophy of these regions is strongly associated with the cognitive phenotype. Overall, this approach can be readily applied to future neuroimaging investigations. PMID:27056675

  18. Smoking and Neuroimaging: A Review

    PubMed Central

    Kober, Hedy; DeLeone, Cameron M.

    2013-01-01

    Cigarette smoking is a significant public health concern, often resulting in nicotine dependence, a chronic-relapsing psychiatric diagnosis that is responsible for up to 10% of the global cardiovascular disease burden. Due to its significantly deleterious effects on health, much research has been dedicated to elucidating the underlying neurobiology of smoking. This brief article is intended to provide a digestible synopsis of the considerable research being conducted on the underlying neural bases of cigarette smoking and nicotine dependence, especially for cardiologists who are often at the front lines of treating nicotine dependence. To this end, we first review some of the most common neuroimaging methodologies used in the study of smoking, as well as the most recent findings from this exciting area of research. Then, we focus on several fundamental topics including the acute pharmacological effects, acute neurocognitive effects, and the long-term neurobiological effects associated with smoking. We finally review recent findings regarding the neuropsychological processes associated with smoking cessation, including cue-induced craving and regulation of craving. Research in this field beginning to uncover how some of these neuropsychological processes are similar across clinical disorders which cardiologists also encounter frequently, such as craving for food resulting in overeating. We conclude with recommendations for future neuroimaging work on these topics. PMID:24432182

  19. Retrospective study on structural neuroimaging in first-episode psychosis.

    PubMed

    Coentre, Ricardo; Silva-Dos-Santos, Amilcar; Talina, Miguel Cotrim

    2016-01-01

    Background. No consensus between guidelines exists regarding neuroimaging in first-episode psychosis. The purpose of this study is to assess anomalies found in structural neuroimaging exams (brain computed tomography (CT) and magnetic resonance imaging (MRI)) in the initial medical work-up of patients presenting first-episode psychosis. Methods. The study subjects were 32 patients aged 18-48 years (mean age: 29.6 years), consecutively admitted with first-episode psychosis diagnosis. Socio-demographic and clinical data and neuroimaging exams (CT and MRI) were retrospectively studied. Diagnostic assessments were made using the Operational Criteria Checklist +. Neuroimaging images (CT and MRI) and respective reports were analysed by an experienced consultant psychiatrist. Results. None of the patients had abnormalities in neuroimaging exams responsible for psychotic symptoms. Thirty-seven percent of patients had incidental brain findings not causally related to the psychosis (brain atrophy, arachnoid cyst, asymmetric lateral ventricles, dilated lateral ventricles, plagiocephaly and falx cerebri calcification). No further medical referral was needed for any of these patients. No significant differences regarding gender, age, diagnosis, duration of untreated psychosis, in-stay and cannabis use were found between patients who had neuroimaging abnormalities versus those without. Discussion. This study suggests that structural neuroimaging exams reveal scarce abnormalities in young patients with first-episode psychosis. Structural neuroimaging is especially useful in first-episode psychosis patients with neurological symptoms, atypical clinical picture and old age. PMID:27257547

  20. Retrospective study on structural neuroimaging in first-episode psychosis

    PubMed Central

    Silva-dos-Santos, Amilcar; Talina, Miguel Cotrim

    2016-01-01

    Background. No consensus between guidelines exists regarding neuroimaging in first-episode psychosis. The purpose of this study is to assess anomalies found in structural neuroimaging exams (brain computed tomography (CT) and magnetic resonance imaging (MRI)) in the initial medical work-up of patients presenting first-episode psychosis. Methods. The study subjects were 32 patients aged 18–48 years (mean age: 29.6 years), consecutively admitted with first-episode psychosis diagnosis. Socio-demographic and clinical data and neuroimaging exams (CT and MRI) were retrospectively studied. Diagnostic assessments were made using the Operational Criteria Checklist +. Neuroimaging images (CT and MRI) and respective reports were analysed by an experienced consultant psychiatrist. Results. None of the patients had abnormalities in neuroimaging exams responsible for psychotic symptoms. Thirty-seven percent of patients had incidental brain findings not causally related to the psychosis (brain atrophy, arachnoid cyst, asymmetric lateral ventricles, dilated lateral ventricles, plagiocephaly and falx cerebri calcification). No further medical referral was needed for any of these patients. No significant differences regarding gender, age, diagnosis, duration of untreated psychosis, in-stay and cannabis use were found between patients who had neuroimaging abnormalities versus those without. Discussion. This study suggests that structural neuroimaging exams reveal scarce abnormalities in young patients with first-episode psychosis. Structural neuroimaging is especially useful in first-episode psychosis patients with neurological symptoms, atypical clinical picture and old age. PMID:27257547

  1. [Functional neuroimaging of addiction].

    PubMed

    Takahashi, Hidehiko

    2015-09-01

    Positron emission tomography studies investigating dopamine release by drug or reward demonstrated blunted dopamine release in relation to addiction to psychostimulants such as cocaine and amphetamine. However, recent studies reported that nicotine and gambling addiction showed opposite results. Several factors such as illness stage or neurotoxicity of substances could be considered for this discrepancy. Behavioral addiction such as gambling disorder is a good target of neuroimaging because it is free from overt neurotoxicity. However, even in gambling disorder, the results of fMRI studies investigating neural response to reward are mixed. Neuroimaging together with taking the various backgrounds of patients into account should contribute not only to a better understanding of the neurobiology of addiction but also to the development of more effective and individually tailored treatment strategies for addiction. PMID:26394506

  2. Atherosclerotic cardiovascular disease: a review of initiators and protective factors.

    PubMed

    Ellulu, Mohammed S; Patimah, Ismail; Khaza'ai, Huzwah; Rahmat, Asmah; Abed, Yehia; Ali, Faisal

    2016-02-01

    Atherosclerotic cardiovascular disease (CVD) is a collective term comprising of a group of disorders of the heart and blood vessels. These diseases are the largest cause of morbidity and premature death worldwide. Coronary heart disease and cerebrovascular disease (stroke) are the most frequently occurring diseases. The two major initiators involved in the development of atherosclerotic CVD are vascular production of reactive oxygen species (ROS) and lipid oxidation. In atherosclerosis development, ROS is associated with rapid loss of anti-inflammatory and anti-atherogenic activities of the endothelium-derived nitric oxide (NO(·)) resulting in endothelial dysfunction. In part involving activation of the transcription factor NF-κB, ROS have been involved in signaling cascades leading to vascular pro-inflammatory and pro-thrombotic gene expression. ROS is also a potent activator of matrix metalloproteinases (MMPs), which indicate plaque destabilization and rupture. The second initiator involved in atherosclerotic CVD is the oxidation of low-density lipoproteins (LDL). Oxidation of LDL in vessel wall leads to an inflammatory cascade that activates atherogenic pathway leading to foam cell formation. The accumulation of foam cells leads to fatty streak formation, which is the earliest visible atherosclerotic lesion. In contrast, the cardiac sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA2a) and hepatic apolipoprotein E (apoE) expression can improve cardiovascular function. SERCA2a regulates the cardiac contractile function by lowering cytoplasmic calcium levels during relaxation, and affecting NO(·) action in vascular cells, while apoE is a critical ligand in the plasma clearance of triglyceride- and cholesterol-rich lipoproteins. PMID:26750181

  3. Neuroimaging Study Designs, Computational Analyses and Data Provenance Using the LONI Pipeline

    PubMed Central

    Dinov, Ivo; Lozev, Kamen; Petrosyan, Petros; Liu, Zhizhong; Eggert, Paul; Pierce, Jonathan; Zamanyan, Alen; Chakrapani, Shruthi; Van Horn, John; Parker, D. Stott; Magsipoc, Rico; Leung, Kelvin; Gutman, Boris; Woods, Roger; Toga, Arthur

    2010-01-01

    Modern computational neuroscience employs diverse software tools and multidisciplinary expertise to analyze heterogeneous brain data. The classical problems of gathering meaningful data, fitting specific models, and discovering appropriate analysis and visualization tools give way to a new class of computational challenges—management of large and incongruous data, integration and interoperability of computational resources, and data provenance. We designed, implemented and validated a new paradigm for addressing these challenges in the neuroimaging field. Our solution is based on the LONI Pipeline environment [3], [4], a graphical workflow environment for constructing and executing complex data processing protocols. We developed study-design, database and visual language programming functionalities within the LONI Pipeline that enable the construction of complete, elaborate and robust graphical workflows for analyzing neuroimaging and other data. These workflows facilitate open sharing and communication of data and metadata, concrete processing protocols, result validation, and study replication among different investigators and research groups. The LONI Pipeline features include distributed grid-enabled infrastructure, virtualized execution environment, efficient integration, data provenance, validation and distribution of new computational tools, automated data format conversion, and an intuitive graphical user interface. We demonstrate the new LONI Pipeline features using large scale neuroimaging studies based on data from the International Consortium for Brain Mapping [5] and the Alzheimer's Disease Neuroimaging Initiative [6]. User guides, forums, instructions and downloads of the LONI Pipeline environment are available at http://pipeline.loni.ucla.edu. PMID:20927408

  4. Neuroimaging biomarkers for early drug development in schizophrenia.

    PubMed

    Tregellas, Jason R

    2014-07-15

    Given the relative inability of currently available antipsychotic treatments to adequately provide sustained recovery and improve quality of life for patients with schizophrenia, new treatment strategies are urgently needed. One way to improve the therapeutic development process may be an increased use of biomarkers in early clinical trials. Reliable biomarkers that reflect aspects of disease pathophysiology can be used to determine if potential treatment strategies are engaging their desired biological targets. This review evaluates three potential neuroimaging biomarkers: hippocampal hyperactivity, gamma-band deficits, and default network abnormalities. These deficits have been widely replicated in the illness, correlate with measures of positive symptoms, are consistent with models of disease pathology, and have shown initial promise as biomarkers of biological response in early studies of potential treatment strategies. Two key features of these deficits, and a guiding rationale for the focus of this review, are that the deficits are not dependent upon patients' performance of specific cognitive tasks and they have analogues in animal models of schizophrenia, greatly increasing their appeal for use as biomarkers. Using neuroimaging biomarkers such as those proposed here to establish early in the therapeutic development process if treatment strategies are having their intended biological effect in humans may facilitate development of new treatments for schizophrenia. PMID:24094513

  5. Neuroimaging Biomarkers for Early Drug Development in Schizophrenia

    PubMed Central

    Tregellas, Jason R.

    2013-01-01

    Given the relative inability of currently available antipsychotic treatments to adequately provide sustained recovery and improve quality of life for patients with schizophrenia, new treatment strategies are urgently needed. One way to improve the therapeutic development process may be an increased use of biomarkers in early clinical trials. Reliable biomarkers that reflect aspects of disease pathophysiology can be used to determine if potential treatment strategies are engaging their desired biological targets. This review evaluates three potential neuroimaging biomarkers: hippocampal hyperactivity, gamma-band deficits and default network abnormalities. These deficits have been widely replicated in the illness, correlate with measures of positive symptoms, are consistent with models of disease pathology, and have shown initial promise as biomarkers of biological response in early studies of potential treatment strategies. Two key features of these deficits, and a guiding rational for the focus of this review, is that the deficits are not dependent upon patients' performance of specific cognitive tasks, and have analogues in animal models of schizophrenia, greatly increasing their appeal for use as biomarkers. Using neuroimaging biomarkers such as those proposed here to establish early in the therapeutic development process if treatment strategies are having their intended biological effect in humans may facilitate development of new treatments for schizophrenia. PMID:24094513

  6. Psychiatric Symptoms in the Initial Motor Stage of Parkinson's Disease.

    PubMed

    Stanković, Iva; Stefanova, Elka; Tomić, Aleksandra; Lukić, Milica Ječmenica; Stojković, Tanja; Marković, Vladana; Stojmenović, Gorana Mandić; Kresojević, Nikola; Svetel, Marina; Kostić, Vladimir

    2016-01-01

    Neuropsychiatric symptoms (NPS) are common in Parkinson's disease (PD). The aim of this study was to estimate the correlates of NPS in patients with PD in the initial motor stage of the disease (hemiparkinsonism). A total of 111 patients with PD and 105 healthy control participants were assessed. Patients with PD experienced apathy, depression, and anxiety more frequently compared with healthy controls. Sleep disturbances occurred commonly in early PD patients. Patients with PD and mild cognitive impairment (MCI) had depression and anxiety more frequently, but not apathy, compared with patients with PD without MCI. The results of this study confirm a high burden of NPS even in the earliest motor stage of PD. PMID:26900739

  7. Systematic Redaction for Neuroimage Data

    PubMed Central

    Matlock, Matt; Schimke, Nakeisha; Kong, Liang; Macke, Stephen; Hale, John

    2013-01-01

    In neuroscience, collaboration and data sharing are undermined by concerns over the management of protected health information (PHI) and personal identifying information (PII) in neuroimage datasets. The HIPAA Privacy Rule mandates measures for the preservation of subject privacy in neuroimaging studies. Unfortunately for the researcher, the management of information privacy is a burdensome task. Wide scale data sharing of neuroimages is challenging for three primary reasons: (i) A dearth of tools to systematically expunge PHI/PII from neuroimage data sets, (ii) a facility for tracking patient identities in redacted datasets has not been produced, and (iii) a sanitization workflow remains conspicuously absent. This article describes the XNAT Redaction Toolkit—an integrated redaction workflow which extends a popular neuroimage data management toolkit to remove PHI/PII from neuroimages. Quickshear defacing is also presented as a complementary technique for deidentifying the image data itself. Together, these tools improve subject privacy through systematic removal of PII/PHI. PMID:24179597

  8. Neuroimaging of Cognition

    PubMed Central

    Dolan, R.J.

    2009-01-01

    Neuroimaging, particularly that based upon functional magnetic resonance (fMRI), has become a dominant tool in cognitive neuroscience. This review provides a personal and selective perspective on its past, present, and future. Two trends currently characterize the field that broadly reflect a pursuit of “where”- and “how”-type questions. The latter addresses basic mechanisms related to the expression of task-induced neural activity and is likely to be an increasingly important theme in the future. This trend entails an enhanced symbiosis among investigators pursuing similar questions in fields such as computational and theoretical neuroscience as well as through the detailed analysis of microcircuitry. PMID:18995825

  9. Development of a disease registry for autoimmune bullous diseases: initial analysis of the pemphigus vulgaris subset.

    PubMed

    Shah, Amit Aakash; Seiffert-Sinha, Kristina; Sirois, David; Werth, Victoria P; Rengarajan, Badri; Zrnchik, William; Attwood, Kristopher; Sinha, Animesh A

    2015-01-01

    Pemphigus vulgaris (PV) is a rare, potentially life threatening, autoimmune blistering skin disease. The International Pemphigus and Pemphigoid Foundation (IPPF) has recently developed a disease registry with the aim to enhance our understanding of autoimmune bullous diseases with the long-term goal of acquiring information to improve patient care. Patients were recruited to the IPPF disease registry through direct mail, e-mail, advertisements, and articles in the IPPF-quarterly, -website, -Facebook webpage, and IPPF Peer Health Coaches to complete a 38-question survey. We present here the initial analysis of detailed clinical information collected on 393 PV patients. We report previously unrecognized gender differences in terms of lesion location, autoimmune comorbidity, and delay in diagnosis. The IPPF disease registry serves as a useful resource and guide for future clinical investigation. PMID:24691863

  10. Acute Warfarin Toxicity as Initial Manifestation of Metastatic Liver Disease

    PubMed Central

    Jani, Nihar; Niazi, Masooma; Lvovsky, Dmitry

    2016-01-01

    Near complete infiltration of the liver secondary to metastasis from the head and neck cancer is a rare occurrence. The prognosis of liver failure associated with malignant infiltration is extremely poor; the survival time of patients is extremely low. We present a case of acute warfarin toxicity as initial manifestation of metastatic liver disease. Our patient is a 64-year-old woman presenting with epigastric pain and discomfort, found to have unrecordable International Normalized Ratio. She rapidly deteriorated with acute respiratory failure requiring mechanical ventilation, profound shock requiring high dose vasopressor infusion, severe coagulopathy, worsening liver enzymes with worsening of lactic acidosis and severe metabolic abnormalities, and refractory to aggressive supportive care and died in less than 48 hours. Autopsy revealed that >90% of the liver was replaced by tumor masses. PMID:27042361

  11. [Neuroimaging of psychiatric and pedopsychiatric disorders].

    PubMed

    Martinot, Jean-Luc; Mana, Stéphanie

    2011-01-01

    Over the last two decades, imaging techniques have allowed to establish the cerebral neurophysiologic correlates of psychiatric disorders and have highlighted the impact of psychopathologic events, therapeutic drugs, addictions, on the growth and plasticity of brain. In this review, we intend to illustrate how neuroimaging has improved our knowledge of such alterations in brain maturation (schizophrenia, autistic disorders), fronto-limbic (depressive syndromes) or fronto-striatal (compulsive disorders) regions in psychiatric illnesses, but also in psychopharmacology, or pedopsychiatry. Statistically significant alterations in the structure and/or function of brain are detected in all psychiatric disorders and these are often detectable already during childhood or teenage. Furthermore, neuroimaging has allowed to underline the importance of cerebral networks specific to each disorder, but also to uncover those which are common to different diseases provided that they share common clinical or cognitive features. Besides their value in basic research, neuroimaging findings have been key in changing the perception that society has of these diseases which contributed to their therapeutic approach. PMID:21718649

  12. Neuroimaging distinction between neurological and psychiatric disorders†

    PubMed Central

    Crossley, Nicolas A.; Scott, Jessica; Ellison-Wright, Ian; Mechelli, Andrea

    2015-01-01

    Background It is unclear to what extent the traditional distinction between neurological and psychiatric disorders reflects biological differences. Aims To examine neuroimaging evidence for the distinction between neurological and psychiatric disorders. Method We performed an activation likelihood estimation meta-analysis on voxel-based morphometry studies reporting decreased grey matter in 14 neurological and 10 psychiatric disorders, and compared the regional and network-level alterations for these two classes of disease. In addition, we estimated neuroanatomical heterogeneity within and between the two classes. Results Basal ganglia, insula, sensorimotor and temporal cortex showed greater impairment in neurological disorders; whereas cingulate, medial frontal, superior frontal and occipital cortex showed greater impairment in psychiatric disorders. The two classes of disorders affected distinct functional networks. Similarity within classes was higher than between classes; furthermore, similarity within class was higher for neurological than psychiatric disorders. Conclusions From a neuroimaging perspective, neurological and psychiatric disorders represent two distinct classes of disorders. PMID:26045351

  13. Provenance in neuroimaging.

    PubMed

    Mackenzie-Graham, Allan J; Van Horn, John D; Woods, Roger P; Crawford, Karen L; Toga, Arthur W

    2008-08-01

    Provenance, the description of the history of a set of data, has grown more important with the proliferation of research consortia-related efforts in neuroimaging. Knowledge about the origin and history of an image is crucial for establishing data and results quality; detailed information about how it was processed, including the specific software routines and operating systems that were used, is necessary for proper interpretation, high fidelity replication and re-use. We have drafted a mechanism for describing provenance in a simple and easy to use environment, alleviating the burden of documentation from the user while still providing a rich description of an image's provenance. This combination of ease of use and highly descriptive metadata should greatly facilitate the collection of provenance and subsequent sharing of data. PMID:18519166

  14. Neuroimaging in ophthalmology

    PubMed Central

    Kim, James D.; Hashemi, Nafiseh; Gelman, Rachel; Lee, Andrew G.

    2012-01-01

    In the past three decades, there have been countless advances in imaging modalities that have revolutionized evaluation, management, and treatment of neuro-ophthalmic disorders. Non-invasive approaches for early detection and monitoring of treatments have decreased morbidity and mortality. Understanding of basic methods of imaging techniques and choice of imaging modalities in cases encountered in neuro-ophthalmology clinic is critical for proper evaluation of patients. Two main imaging modalities that are often used are computed tomography (CT) and magnetic resonance imaging (MRI). However, variations of these modalities and appropriate location of imaging must be considered in each clinical scenario. In this article, we review and summarize the best neuroimaging studies for specific neuro-ophthalmic indications and the diagnostic radiographic findings for important clinical entities. PMID:23961025

  15. STGP: Spatio-temporal Gaussian process models for longitudinal neuroimaging data.

    PubMed

    Hyun, Jung Won; Li, Yimei; Huang, Chao; Styner, Martin; Lin, Weili; Zhu, Hongtu

    2016-07-01

    Longitudinal neuroimaging data plays an important role in mapping the neural developmental profile of major neuropsychiatric and neurodegenerative disorders and normal brain. The development of such developmental maps is critical for the prevention, diagnosis, and treatment of many brain-related diseases. The aim of this paper is to develop a spatio-temporal Gaussian process (STGP) framework to accurately delineate the developmental trajectories of brain structure and function, while achieving better prediction by explicitly incorporating the spatial and temporal features of longitudinal neuroimaging data. Our STGP integrates a functional principal component model (FPCA) and a partition parametric space-time covariance model to capture the medium-to-large and small-to-medium spatio-temporal dependence structures, respectively. We develop a three-stage efficient estimation procedure as well as a predictive method based on a kriging technique. Two key novelties of STGP are that it can efficiently use a small number of parameters to capture complex non-stationary and non-separable spatio-temporal dependence structures and that it can accurately predict spatio-temporal changes. We illustrate STGP using simulated data sets and two real data analyses including longitudinal positron emission tomography data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and longitudinal lateral ventricle surface data from a longitudinal study of early brain development. PMID:27103140

  16. Schizophrenia, neuroimaging and connectomics.

    PubMed

    Fornito, Alex; Zalesky, Andrew; Pantelis, Christos; Bullmore, Edward T

    2012-10-01

    Schizophrenia is frequently characterized as a disorder of brain connectivity. Neuroimaging has played a central role in supporting this view, with nearly two decades of research providing abundant evidence of structural and functional connectivity abnormalities in the disorder. In recent years, our understanding of how schizophrenia affects brain networks has been greatly advanced by attempts to map the complete set of inter-regional interactions comprising the brain's intricate web of connectivity; i.e., the human connectome. Imaging connectomics refers to the use of neuroimaging techniques to generate these maps which, combined with the application of graph theoretic methods, has enabled relatively comprehensive mapping of brain network connectivity and topology in unprecedented detail. Here, we review the application of these techniques to the study of schizophrenia, focusing principally on magnetic resonance imaging (MRI) research, while drawing attention to key methodological issues in the field. The published findings suggest that schizophrenia is associated with a widespread and possibly context-independent functional connectivity deficit, upon which are superimposed more circumscribed, context-dependent alterations associated with transient states of hyper- and/or hypo-connectivity. In some cases, these changes in inter-regional functional coupling dynamics can be related to measures of intra-regional dysfunction. Topological disturbances of functional brain networks in schizophrenia point to reduced local network connectivity and modular structure, as well as increased global integration and network robustness. Some, but not all, of these functional abnormalities appear to have an anatomical basis, though the relationship between the two is complex. By comprehensively mapping connectomic disturbances in patients with schizophrenia across the entire brain, this work has provided important insights into the highly distributed character of neural

  17. International union against tuberculosis and lung disease (IUATLD): initiatives in non-tuberculous lung disease.

    PubMed

    Becklake, M R

    1995-12-01

    IUATLD initiatives in non-tuberculous lung disease developed in the late 1970s, coincident with improving tuberculosis control, and have targeted acute respiratory infections in children and chronic airways disease in adults and in children. The focus has been on methodology and the tools required to document the distribution and determinants of disease, and is illustrated in data gathered in African populations. Instruments developed include a simplified method of measuring bronchial hyper-reactivity and an asthma questionnaire Non-standard methods of questionnaire administration have also been validated, methods which are appropriate for use in the burgeoning urban communities and workforces of sub-Saharan Africa made up of rural migrants from different tribes and language groups. In addition, a review of reference values available for interpreting lung function in sub-Saharan African populations indicates a need to take into account a secular trend over the last two decades towards higher spirometric values. In the published data from Africa, not inconsiderable between-country differences are evident in the prevalence of chronic bronchitis in adults and of asthma in children. In addition, rates for childhood asthma were consistently higher in urban vs rural communities, with environmental factors playing an important role as well as being locally specific. Not only does the burden of morbidity attributable to both the chronic airway diseases reviewed justify past IUATLD initiatives in non-tuberculous lung disease, but it also argues that future initiatives should focus on investigating between- and within-country differences using a standardized methodology, with a view to identifying local environmental determinants susceptible to intervention and control. Curbing tobacco use is clearly important, not only to benefit the health of adult smokers for whom the ill-health consequences have long been recognized, but, and more important, to protect the health of

  18. Traumatic brain injury, neuroimaging, and neurodegeneration

    PubMed Central

    Bigler, Erin D.

    2012-01-01

    Depending on severity, traumatic brain injury (TBI) induces immediate neuropathological effects that in the mildest form may be transient but as severity increases results in neural damage and degeneration. The first phase of neural degeneration is explainable by the primary acute and secondary neuropathological effects initiated by the injury; however, neuroimaging studies demonstrate a prolonged period of pathological changes that progressively occur even during the chronic phase. This review examines how neuroimaging may be used in TBI to understand (1) the dynamic changes that occur in brain development relevant to understanding the effects of TBI and how these relate to developmental stage when the brain is injured, (2) how TBI interferes with age-typical brain development and the effects of aging thereafter, and (3) how TBI results in greater frontotemporolimbic damage, results in cerebral atrophy, and is more disruptive to white matter neural connectivity. Neuroimaging quantification in TBI demonstrates degenerative effects from brain injury over time. An adverse synergistic influence of TBI with aging may predispose the brain injured individual for the development of neuropsychiatric and neurodegenerative disorders long after surviving the brain injury. PMID:23964217

  19. Recent Advances in Neuroimaging Biomarkers in Geriatric Psychiatry

    PubMed Central

    Khandai, Abhisek C.; Aizenstein, Howard J.

    2013-01-01

    Neuroimaging, both structural and functional, serve as useful adjuncts to clinical assessment, and can provide objective, reliable means of assessing disease presence and process in the aging population. In the following review we briefly explain current imaging methodologies. Then, we analyze recent developments in developing neuroimaging biomarkers for two highly prevalent disorders in the elderly population- Alzheimer's disease (AD) and late-life depression (LLD). In AD, efforts are focused on early diagnosis through in vivo visualization of disease pathophysiology. In LLD, recent imaging evidence supports the role of white matter ischemic changes in the pathogenesis of depression in the elderly, the “vascular hypothesis.” Finally, we discuss potential roles for neuroimaging biomarkers in geriatric psychiatry in the future. PMID:23636984

  20. Human Neuroimaging as a “Big Data” Science

    PubMed Central

    Van Horn, John Darrell; Toga, Arthur W.

    2013-01-01

    The maturation of in vivo neuroimaging has lead to incredible quantities of digital information about the human brain. While much is made of the data deluge in science, neuroimaging represents the leading edge of this onslaught of “big data”. A range of neuroimaging databasing approaches has streamlined the transmission, storage, and dissemination of data from such brain imaging studies. Yet few, if any, common solutions exist to support the science of neuroimaging. In this article, we discuss how modern neuroimaging research represents a mutifactorial and broad ranging data challenge, involving the growing size of the data being acquired; sociologial and logistical sharing issues; infrastructural challenges for multi-site, multi-datatype archiving; and the means by which to explore and mine these data. As neuroimaging advances further, e.g. aging, genetics, and age-related disease, new vision is needed to manage and process this information while marshalling of these resources into novel results. Thus, “big data” can become “big” brain science. PMID:24113873

  1. Heart Rate and Initial Presentation of Cardiovascular Diseases (Caliber)

    ClinicalTrials.gov

    2013-09-17

    Abdominal Aortic Aneurysm; Coronary Heart Disease NOS; Unheralded Coronary Death; Intracerebral Haemorrhage; Heart Failure; Ischemic Stroke; Myocardial Infarction; Stroke; Peripheral Arterial Disease; Stable Angina Pectoris; Subarachnoid Haemorrhage; Transient Ischemic Attack; Unstable Angina; Cardiac Arrest, Sudden Cardiac Death

  2. Neuroimaging in anxiety disorders.

    PubMed

    Fredrikson, Mats; Faria, Vanda

    2013-01-01

    Neuroimaging studies using functional magnetic resonance imaging (fMRI), positron emission tomography (PET) and single-photon emission computed tomography (SPECT) to evaluate neurofunctional and neurochemical alterations related to the generation and control of affect in patients with anxiety disorders are reviewed. We performed a meta-analysis of symptom provocation studies, where neural activity was measured using fMRI, PET or SPECT to test the hypothesis that prefrontal regions modulate amygdala activity. Data revealed that reactivity in the amygdala was enhanced in patients with phobia as well as posttraumatic stress disorder (PTSD). The dorsal anterior cingulate cortex was activated in concert with the amygdala, both in PTSD and in phobic states, suggesting a role in fear expression, rather than emotional control. Activity in emotion-regulating areas in the ventromedial prefrontal cortex including the subgenual anterior cingulate cortex and the medial orbitofrontal cortex was compromised in the symptomatic state in PTSD and phobic disorders, respectively. Increased amygdala reactivity was restored with psychological treatment. Treatment effects across different modalities including pharmacological and psychological interventions as well as with placebo regimens support that reduction of neural activity in the amygdala may be a final common pathway for successful therapeutic interventions irrespective of method, thereby linking neurotransmission to plasticity in a pivotal node of the core fear network of the brain. PMID:25225017

  3. Neuroimaging of spine tumors.

    PubMed

    Pinter, Nandor K; Pfiffner, Thomas J; Mechtler, Laszlo L

    2016-01-01

    Intramedullary, intradural/extramedullary, and extradural spine tumors comprise a wide range of neoplasms with an even wider range of clinical symptoms and prognostic features. Magnetic resonance imaging (MRI), commonly used to evaluate the spine in patients presenting with pain, can further characterize lesions that may be encountered on other imaging studies, such as bone scintigraphy or computed tomography (CT). The advantage of the MRI is its multiplane capabilities, superior contrast agent resolution, and flexible protocols that play an important role in assessing tumor location, extent in directing biopsy, in planning proper therapy, and in evaluating therapeutic results. A multimodality approach can be used to fully characterize the lesion and the combination of information obtained from the different modalities usually narrows the diagnostic possibilities significantly. The diagnosis of spinal tumors is based on patient age, topographic features of the tumor, and lesion pattern, as seen at CT and MRI. The shift to high-end imaging incorporating diffusion-weighted imaging, diffusion tensor imaging, magnetic resonance spectroscopy, whole-body short tau inversion recovery, positron emission tomography, intraoperative and high-field MRI as part of the mainstream clinical imaging protocol has provided neurologists, neuro-oncologists, and neurosurgeons a window of opportunity to assess the biologic behavior of spine neoplasms. This chapter reviews neuroimaging of spine tumors, primary and secondary, discussing routine and newer modalities that can reduce the significant morbidity associated with these neoplasms. PMID:27430436

  4. 78 FR 9926 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-12

    ... Incidence of Inflammatory Bowel Disease, FOA DP 13-001, initial review. In accordance with Section 10(a)(2... meeting will include the initial review, discussion, and evaluation of applications received in response to ``Prevalence and Incidence of Inflammatory Bowel Disease, FOA DP 13-001, initial review.''...

  5. PET neuroimaging studies of [18F]CABS13 in a double transgenic mouse model of Alzheimer’s disease and non-human primates

    PubMed Central

    Liang, Steven H.; Holland, Jason P.; Stephenson, Nickeisha A.; Kassenbrock, Alina; Rotstein, Benjamin H.; Daignault, Cory P.; Lewis, Rebecca; Collier, Lee; Hooker, Jacob M.; Vasdev, Neil

    2016-01-01

    Fluorine-18 labeled 2-fluoro-8-hydroxyquinoline ([18F]CABS13) is a promising positron emission tomography (PET) radiopharmaceutical based on a metal chelator developed to probe the “metal hypothesis of Alzheimer’s disease”. Herein, a practical radiosynthesis of [18F]CABS13 was achieved by radiofluorination followed by deprotection of an O-benzyloxymethyl group. Automated production and formulation of [18F]CABS13 resulted in 19 ± 5% uncorrected radiochemical yield, relative to starting [18F]fluoride, with ≥95% chemical and radiochemical purities, and high specific activity (>2.5 Ci/μmol) within 80 minutes. Temporal PET neuroimaging studies were carried out in female transgenic B6C3- Tg(APPswe,PSEN1dE9)85Dbo/J (APP/PS1) and age-matched wild-type (WT) B6C3F1/J control mice at 3, 7 and 10 months of age. [18F]CABS13 showed an overall higher uptake and retention of radioactivity in the central nervous system of APP/PS1 mice versus WT mice with increasing age. However, PET/magnetic resonance imaging in normal non-human primates revealed that the tracer had low uptake in the brain and rapid formation of a hydrophilic radiometabolite. Identification of more metabolically stable 18F-hydroxyquinolines that can be readily accessed by the radiochemical strategy presented herein is underway. PMID:25776827

  6. Hybrid MR-PET in Neuroimaging.

    PubMed

    Bisdas, S; Lá Fougere, C; Ernemann, U

    2015-10-01

    Hybrid magnetic resonance (MR)-positron emission tomography (MR-PET) is a novel technology with advantages over sequential MR and PET imaging, allowing maintain full individual diagnostic performance with negligible mutual interference between the two hardware settings. Obvious synergies between MR and PET in acquisition of anatomical, functional, and molecular information for neurological diseases into one single image pave the way for establishing clear clinical indications for hybrid MR-PET as well as addressing unmet neuroimaging needs in future clinics and research. Further developments in attenuation correction, quantification, workflow, and effective MR-PET data management might unfold the full potential of integrated multimodality imaging. PMID:26227618

  7. 78 FR 17412 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-21

    ... Diseases in Africa, FOA GH13-002, initial review. In accordance with Section 10(a)(2) of the Federal... and Evaluation of Programs for the Elimination and Control of Neglected Tropical Diseases in...

  8. 78 FR 24751 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-26

    ... HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review The meeting announced below concerns Continuing Prospective Birth Cohort Study Involving Environmental Uranium Exposure in the Navajo Nation,...

  9. 77 FR 61756 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-11

    ... From the Federal Register Online via the Government Publishing Office ] DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review The meeting announced below concerns...

  10. 78 FR 66937 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-07

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review The meeting announced below concerns...

  11. 78 FR 9926 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-12

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review The meeting announced below concerns...

  12. 78 FR 37542 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-21

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review The meeting announced below concerns...

  13. 78 FR 19490 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panels (SEP): Initial Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-01

    ... From the Federal Register Online via the Government Publishing Office ] DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and Control Special Emphasis Panels (SEP): Initial Review The meeting announced below concerns...

  14. 77 FR 36544 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-19

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review The meeting announced below concerns...

  15. 78 FR 60875 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-02

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review The meeting announced below concerns...

  16. 78 FR 60877 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-02

    ... From the Federal Register Online via the Government Publishing Office ] DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review The meeting announced below concerns...

  17. 78 FR 66937 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-07

    ... Control Special Emphasis Panel (SEP): Initial Review The meeting announced below concerns Capacity...), the Centers for Disease Control and Prevention (CDC) announces the aforementioned SEP: Times and...

  18. 78 FR 57391 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-18

    ... Control Special Emphasis Panel (SEP): Initial Review The meeting announced below concerns Capacity...), the Centers for Disease Control and Prevention (CDC) announces the aforementioned SEP: Times and...

  19. Efficient, Distributed and Interactive Neuroimaging Data Analysis Using the LONI Pipeline.

    PubMed

    Dinov, Ivo D; Van Horn, John D; Lozev, Kamen M; Magsipoc, Rico; Petrosyan, Petros; Liu, Zhizhong; Mackenzie-Graham, Allan; Eggert, Paul; Parker, Douglas S; Toga, Arthur W

    2009-01-01

    The LONI Pipeline is a graphical environment for construction, validation and execution of advanced neuroimaging data analysis protocols (Rex et al., 2003). It enables automated data format conversion, allows Grid utilization, facilitates data provenance, and provides a significant library of computational tools. There are two main advantages of the LONI Pipeline over other graphical analysis workflow architectures. It is built as a distributed Grid computing environment and permits efficient tool integration, protocol validation and broad resource distribution. To integrate existing data and computational tools within the LONI Pipeline environment, no modification of the resources themselves is required. The LONI Pipeline provides several types of process submissions based on the underlying server hardware infrastructure. Only workflow instructions and references to data, executable scripts and binary instructions are stored within the LONI Pipeline environment. This makes it portable, computationally efficient, distributed and independent of the individual binary processes involved in pipeline data-analysis workflows. We have expanded the LONI Pipeline (V.4.2) to include server-to-server (peer-to-peer) communication and a 3-tier failover infrastructure (Grid hardware, Sun Grid Engine/Distributed Resource Management Application API middleware, and the Pipeline server). Additionally, the LONI Pipeline provides three layers of background-server executions for all users/sites/systems. These new LONI Pipeline features facilitate resource-interoperability, decentralized computing, construction and validation of efficient and robust neuroimaging data-analysis workflows. Using brain imaging data from the Alzheimer's Disease Neuroimaging Initiative (Mueller et al., 2005), we demonstrate integration of disparate resources, graphical construction of complex neuroimaging analysis protocols and distributed parallel computing. The LONI Pipeline, its features, specifications

  20. Efficient, Distributed and Interactive Neuroimaging Data Analysis Using the LONI Pipeline

    PubMed Central

    Dinov, Ivo D.; Van Horn, John D.; Lozev, Kamen M.; Magsipoc, Rico; Petrosyan, Petros; Liu, Zhizhong; MacKenzie-Graham, Allan; Eggert, Paul; Parker, Douglas S.; Toga, Arthur W.

    2009-01-01

    The LONI Pipeline is a graphical environment for construction, validation and execution of advanced neuroimaging data analysis protocols (Rex et al., 2003). It enables automated data format conversion, allows Grid utilization, facilitates data provenance, and provides a significant library of computational tools. There are two main advantages of the LONI Pipeline over other graphical analysis workflow architectures. It is built as a distributed Grid computing environment and permits efficient tool integration, protocol validation and broad resource distribution. To integrate existing data and computational tools within the LONI Pipeline environment, no modification of the resources themselves is required. The LONI Pipeline provides several types of process submissions based on the underlying server hardware infrastructure. Only workflow instructions and references to data, executable scripts and binary instructions are stored within the LONI Pipeline environment. This makes it portable, computationally efficient, distributed and independent of the individual binary processes involved in pipeline data-analysis workflows. We have expanded the LONI Pipeline (V.4.2) to include server-to-server (peer-to-peer) communication and a 3-tier failover infrastructure (Grid hardware, Sun Grid Engine/Distributed Resource Management Application API middleware, and the Pipeline server). Additionally, the LONI Pipeline provides three layers of background-server executions for all users/sites/systems. These new LONI Pipeline features facilitate resource-interoperability, decentralized computing, construction and validation of efficient and robust neuroimaging data-analysis workflows. Using brain imaging data from the Alzheimer's Disease Neuroimaging Initiative (Mueller et al., 2005), we demonstrate integration of disparate resources, graphical construction of complex neuroimaging analysis protocols and distributed parallel computing. The LONI Pipeline, its features, specifications

  1. High-dose thiamine as initial treatment for Parkinson's disease

    PubMed Central

    Costantini, Antonio; Pala, Maria Immacolata; Compagnoni, Laura; Colangeli, Marco

    2013-01-01

    Parkinson's disease (PD) is a systemic disease with motor and non-motor deficits. We recruited three patients with newly diagnosed PD. They were not under anti-Parkinson's therapy. Plasmatic thiamine was within healthy reference range. We performed the Unified Parkinson's Disease Rating Scale (UPDRS) and started a parenteral therapy with high doses of thiamine. The therapy led to a considerable improvement in the motor part of the UPDRS ranging from 31.3% to 77.3%. From this clinical observation, it is reasonable to infer that a focal, severe thiamine deficiency due to a dysfunction of thiamine metabolism could cause a selective neuronal damage in the centres that are typically hit in this disease. Injection of high doses of thiamine was effective in reversing the symptoms, suggesting that the abnormalities in thiamine-dependent processes could be overcome by diffusion-mediated transport at supranormal thiamine concentrations. PMID:23986125

  2. LSTGEE: longitudinal analysis of neuroimaging data

    NASA Astrophysics Data System (ADS)

    Li, Yimei; Zhu, Hongtu; Chen, Yasheng; An, Hongyu; Gilmore, John; Lin, Weili; Shen, Dinggang

    2009-02-01

    Longitudinal imaging studies are essential to understanding the neural development of neuropsychiatric disorders, substance use disorders, and normal brain. Using appropriate image processing and statistical tools to analyze the imaging, behavioral, and clinical data is critical for optimally exploring and interpreting the findings from those imaging studies. However, the existing imaging processing and statistical methods for analyzing imaging longitudinal measures are primarily developed for cross-sectional neuroimaging studies. The simple use of these cross-sectional tools to longitudinal imaging studies will significantly decrease the statistical power of longitudinal studies in detecting subtle changes of imaging measures and the causal role of time-dependent covariate in disease process. The main objective of this paper is to develop longitudinal statistics toolbox, called LSTGEE, for the analysis of neuroimaging data from longitudinal studies. We develop generalized estimating equations for jointly modeling imaging measures with behavioral and clinical variables from longitudinal studies. We develop a test procedure based on a score test statistic and a resampling method to test linear hypotheses of unknown parameters, such as associations between brain structure and function and covariates of interest, such as IQ, age, gene, diagnostic groups, and severity of disease. We demonstrate the application of our statistical methods to the detection of the changes of the fractional anisotropy across time in a longitudinal neonate study. Particularly, our results demonstrate that the use of longitudinal statistics can dramatically increase the statistical power in detecting the changes of neuroimaging measures. The proposed approach can be applied to longitudinal data with multiple outcomes and accommodate incomplete and unbalanced data, i.e., subjects with different number of measurements.

  3. Molecular neuroimaging in degenerative dementias.

    PubMed

    Jiménez Bonilla, J F; Carril Carril, J M

    2013-01-01

    In the context of the limitations of structural imaging, brain perfusion and metabolism using SPECT and PET have provided relevant information for the study of cognitive decline. The introduction of the radiotracers for cerebral amyloid imaging has changed the diagnostic strategy regarding Alzheimer's disease, which is currently considered to be a "continuum." According to this new paradigm, the increasing amyloid load would be associated to the preclinical phase and mild cognitive impairment. It has been possible to observe "in vivo" images using 11C-PIB and PET scans. The characteristics of the 11C-PIB image include specific high brain cortical area retention in the positive cases with typical distribution pattern and no retention in the negative cases. This, in combination with 18F-FDG PET, is the basis of molecular neuroimaging as a biomarker. At present, its prognostic value is being evaluated in longitudinal studies. 11C-PIB-PET has become the reference radiotracer to evaluate the presence of cerebral amyloid. However, its availability is limited due to the need for a nearby cyclotron. Therefore, 18F labeled radiotracers are being introduced. Our experience in the last two years with 11C-PIB, first in the research phase and then as being clinically applied, has shown the utility of the technique in the clinical field, either alone or in combination with FDG. Thus, amyloid image is a useful tool for the differential diagnosis of dementia and it is a potentially useful method for early diagnosis and evaluation of future treatments. PMID:23933381

  4. Neuroimaging training among neuropsychologists: A survey of the state of current training and recommendations for trainees

    PubMed Central

    Benitez, Andreana; Hassenstab, Jason; Bangen, Katherine J.

    2013-01-01

    Neuroimaging has gained widespread use in neuropsychological research and practice. However, there are neither established guidelines on how neuropsychologists might become competent researchers or consumers of neuroimaging data, nor any published studies describing the state of neuroimaging training among neuropsychologists. We report the results of two online surveys, one of 13 expert neuropsychologist-neuroimagers, whose responses informed the formulation of a second, larger survey to neuropsychologists-at-large that were a random selection of a third of the members of the International Neuropsychological Society and American Academy of Clinical Neuropsychology. 237 doctoral-level neuropsychologists, or 15.3% of potential participants, provided complete responses. Most respondents (69.2%) received training in neuroimaging, mostly at the post-doctoral level, largely through independent study, clinical conferences, instruction by clinical supervisors, and individualized mentoring, on topics such as neuroimaging modalities in neurology, neuroanatomy, and the appropriate information to glean from neuroradiology reports. Of the remaining respondents who did not receive training in neuroimaging, 64.4% indicated that such training would be very or extremely beneficial to one’s career as a neuropsychologist. Both neuropsychologist-neuroimagers and neuropsychologists-at-large provided specific recommendations for training. Findings from this initial effort will guide trainees who seek to develop competence in neuroimaging, and inform future formulations of neuropsychological training. PMID:24215451

  5. Neuroimaging, culture, and forensic psychiatry.

    PubMed

    Aggarwal, Neil K

    2009-01-01

    The spread of neuroimaging technologies around the world has led to diverse practices of forensic psychiatry and the emergence of neuroethics and neurolaw. This article surveys the neuroethics and neurolegal literature on the use of forensic neuroimaging within the courtroom. Next, the related literature within medical anthropology and science and technology studies is reviewed to show how debates about forensic neuroimaging reflect cultural tensions about attitudes regarding the self, mental illness, and medical expertise. Finally, recommendations are offered on how forensic psychiatrists can add to this research, given their professional interface between law and medicine. At stake are the fundamental concerns that surround changing conceptions of the self, sickness, and expectations of medicine. PMID:19535562

  6. [What happens in the brain of my patients? Neuroimaging and neurogenetics as ethical challenges in medicine].

    PubMed

    Synofzik, M

    2007-12-01

    Precise diagnosis of many neurological or psychiatric diseases has for long been one of the main problems in medicine. New diagnostic procedures like neuroimaging or neurogenetics seem now able to change thi situation but evoke new ethical questions. How should we cope with the fact that we may be able to diagnose and even predict diseases like schizophrenia or Alzheimer's Disease? How should we deal with incidental findings in neuroimaging? Can and should we use neuroimaging or neurogenetic procedures to detect certain behavioral dispositions? A new interdisciplinary research programme, called "neuroethics", can provide an ethical orientation for such questions. PMID:18050032

  7. Dracunculiasis (Guinea Worm Disease) and the Eradication Initiative

    PubMed Central

    Cairncross, Sandy; Muller, Ralph; Zagaria, Nevio

    2002-01-01

    Dracunculiasis, also known as guinea worm disease, is caused by the large female of the nematode Dracunculus medinensis, which emerges painfully and slowly from the skin, usually on the lower limbs. The disease can infect animals, and sustainable animal cycles occur in North America and Central Asia but do not act as reservoirs of human infection. The disease is endemic across the Sahel belt of Africa from Mauritania to Ethiopia, having been eliminated from Asia and some African countries. It has a significant socioeconomic impact because of the temporary disability that it causes. Dracunculiasis is exclusively caught from drinking water, usually from ponds. A campaign to eradicate the disease was launched in the 1980s and has made significant progress. The strategy of the campaign is discussed, including water supply, health education, case management, and vector control. Current issues including the integration of the campaign into primary health care and the mapping of cases by using geographic information systems are also considered. Finally, some lessons for other disease control and eradication programs are outlined. PMID:11932231

  8. 78 FR 66937 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-07

    ..., initial review, published in the Federal Register on October 2, 2013 (FR Volume 78, Number 191, Page 60877... HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review Notice of Cancellation: This notice...

  9. Vitamin D and Risk of Neuroimaging Abnormalities.

    PubMed

    Littlejohns, Thomas J; Kos, Katarina; Henley, William E; Lang, Iain A; Annweiler, Cedric; Beauchet, Olivier; Chaves, Paulo H M; Kestenbaum, Bryan R; Kuller, Lewis H; Langa, Kenneth M; Lopez, Oscar L; Llewellyn, David J

    2016-01-01

    Vitamin D deficiency has been linked with an increased risk of incident all-cause dementia and Alzheimer's disease. The aim of the current study was to explore the potential mechanisms underlying these associations by determining whether low vitamin D concentrations are associated with the development of incident cerebrovascular and neurodegenerative neuroimaging abnormalities. The population consisted of 1,658 participants aged ≥65 years from the US-based Cardiovascular Health Study who were free from prevalent cardiovascular disease, stroke and dementia at baseline in 1992-93. Serum 25-hydroxyvitamin D (25(OH)D) concentrations were determined by liquid chromatography-tandem mass spectrometry from blood samples collected at baseline. The first MRI scan was conducted between 1991-1994 and the second MRI scan was conducted between 1997-1999. Change in white matter grade, ventricular grade and presence of infarcts between MRI scan one and two were used to define neuroimaging abnormalities. During a mean follow-up of 5.0 years, serum 25(OH)D status was not significantly associated with the development of any neuroimaging abnormalities. Using logistic regression models, the multivariate adjusted odds ratios (95% confidence interval) for worsening white matter grade in participants who were severely 25(OH)D deficient (<25 nmol/L) and deficient (≥25-50 nmol/L) were 0.76 (0.35-1.66) and 1.09 (0.76-1.55) compared to participants with sufficient concentrations (≥50 nmol/L). The multivariate adjusted odds ratios for ventricular grade in participants who were severely 25(OH)D deficient and deficient were 0.49 (0.20-1.19) and 1.12 (0.79-1.59) compared to those sufficient. The multivariate adjusted odds ratios for incident infarcts in participants who were severely 25(OH)D deficient and deficient were 1.95 (0.84-4.54) and 0.73 (0.47-1.95) compared to those sufficient. Overall, serum vitamin D concentrations could not be shown to be associated with the development of

  10. Vitamin D and Risk of Neuroimaging Abnormalities

    PubMed Central

    Littlejohns, Thomas J.; Kos, Katarina; Henley, William E.; Lang, Iain A.; Annweiler, Cedric; Beauchet, Olivier; Chaves, Paulo H. M.; Kestenbaum, Bryan R.; Kuller, Lewis H.; Langa, Kenneth M.; Lopez, Oscar L.; Llewellyn, David J.

    2016-01-01

    Vitamin D deficiency has been linked with an increased risk of incident all-cause dementia and Alzheimer’s disease. The aim of the current study was to explore the potential mechanisms underlying these associations by determining whether low vitamin D concentrations are associated with the development of incident cerebrovascular and neurodegenerative neuroimaging abnormalities. The population consisted of 1,658 participants aged ≥65 years from the US-based Cardiovascular Health Study who were free from prevalent cardiovascular disease, stroke and dementia at baseline in 1992–93. Serum 25-hydroxyvitamin D (25(OH)D) concentrations were determined by liquid chromatography-tandem mass spectrometry from blood samples collected at baseline. The first MRI scan was conducted between 1991–1994 and the second MRI scan was conducted between 1997–1999. Change in white matter grade, ventricular grade and presence of infarcts between MRI scan one and two were used to define neuroimaging abnormalities. During a mean follow-up of 5.0 years, serum 25(OH)D status was not significantly associated with the development of any neuroimaging abnormalities. Using logistic regression models, the multivariate adjusted odds ratios (95% confidence interval) for worsening white matter grade in participants who were severely 25(OH)D deficient (<25 nmol/L) and deficient (≥25–50 nmol/L) were 0.76 (0.35–1.66) and 1.09 (0.76–1.55) compared to participants with sufficient concentrations (≥50 nmol/L). The multivariate adjusted odds ratios for ventricular grade in participants who were severely 25(OH)D deficient and deficient were 0.49 (0.20–1.19) and 1.12 (0.79–1.59) compared to those sufficient. The multivariate adjusted odds ratios for incident infarcts in participants who were severely 25(OH)D deficient and deficient were 1.95 (0.84–4.54) and 0.73 (0.47–1.95) compared to those sufficient. Overall, serum vitamin D concentrations could not be shown to be associated with

  11. Initial studies on "six months disease" in sheep.

    PubMed

    Pyakural, S; Singh, N B

    1976-01-17

    Enterotoxaemia in sheep due to Clostridium welchii type D was indicated by field and laboratory investigations in Nepal. Morphological, cultural, biochemical, biological and toxin-producing characteristics observed were used to type the isolates. In anaerobic meat medium, all isolates produced pinkish discoloration of meat. All the strains fermented lactose, maltose, dextrose and sucrose whereas, salicine was fermented only by 17 strains. All but five strains were MR negative. Out of 200 isolated, 166 produced both alpha and epsilon toxins and the remaining 34 non-toxogenic strains are likely to be variants which have lost their toxogenicity. Epidemiologically the local name "Six months disease" and enterotoxaemia are considered to be identical diseases. PMID:176766

  12. 78 FR 60878 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-02

    ... HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review The meeting announced below concerns Health Promotion... Centers for Disease Control and Prevention (CDC) announces the aforementioned meeting: Times And Dates 8...

  13. 78 FR 9926 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-12

    ... HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review The meeting announced below concerns Medicaid... 10(a)(2) of the Federal Advisory Committee Act (Pub. L. 92-463), the Centers for Disease Control...

  14. 77 FR 25485 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-30

    ... HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review The meeting announced below concerns Research Grants...), the Centers for Disease Control and Prevention (CDC) announces the aforementioned meeting: DATES:...

  15. [Schizophrenia, cognition and neuroimaging].

    PubMed

    Kaladjian, A; Fakra, E; Adida, M; Belzeaux, R; Cermolacce, M; Azorin, J-M

    2011-12-01

    Schizophrenia is a complex illness whose mechanisms are still largely unknown. Functional brain imaging, by making the link between psyche and brain, has recently become an indispensable tool to study in vivo the neural bases underlying cognitive dysfunction in this disease. But despite the proliferation of data coming from this approach, the exact impact of functional imaging on our understanding of the disease remains blurry. In general, studies of the brain functioning of patients with schizophrenia found activation abnormalities which vary in nature and localization depending of the cognitive paradigm used. However, it appears that neurofunctional abnormalities observed in patients cannot be reduced to a simple well-localized deficit. It would be rather an alteration of the dynamics of the interactions between different brain regions that underlie the cognitive disturbances encountered in the disease. Functional brain imaging now offers new perspectives to clarify the dynamics of the brain networks, and particularly those involved in high-level cognitive functions, such as cognitive control or social cognition which seem to play a crucial role in the disease. The characterization of these features is an important issue not only to develop new hypotheses on the pathophysiology of the disorder, but also more pragmatically to identify potential therapeutic targets. PMID:22212841

  16. The Role of Air Pollutants in Initiating Liver Disease

    PubMed Central

    Kim, Jong Won; Park, Surim; Lim, Chae Woong; Lee, Kyuhong

    2014-01-01

    Recent episodes of severe air pollution in eastern Asia have been reported in the scientific literature and news media. Therefore, there is growing concern about the systemic effects of air pollution on human health. Along with the other well-known harmful effects of air pollution, recently, several animal models have provided strong evidence that air pollutants can induce liver toxicity and act to accelerate liver inflammation and steatosis. This review briefly describes examples where exposure to air pollutants was involved in liver toxicity, focusing on how particulate matter (PM) or carbon black (CB) may be translocated from lung to liver and what liver diseases are closely associated with these air pollutants. PMID:25071914

  17. Ileoileal intussusception as initial manifestation of Crohn’s disease

    PubMed Central

    López-Tomassetti Fernández, E. M.; Lorenzo Rocha, N.; Arteaga González, I.; Carrillo Pallarés, A

    2006-01-01

    Intussusception is usually considered a childhood condition, but it may also be present in adults, where it is more often associated with an underlying pathology. There is no agreement upon the correct treatment of adult intussusception, although surgical intervention is considered necessary. Resection without prior reduction has been the traditional treatment of choice due to the significant risk for malignancy found in most series. We describe an unusual case of intestinal necrosis secondary to ileoileal intussusception caused by Crohn’s disease. A long intestinal resection was necessary and the patient was discharged without major complications. Based on the details of this case, the authors emphasize the potential importance of considering individualized treatment of adult intussusception. The practical benefit for reduction of viable bowel in Crohn′s patients is the preservation of bowel length. PMID:19529808

  18. CSF biomarkers associated with disease heterogeneity in early Parkinson's disease: the Parkinson's Progression Markers Initiative study.

    PubMed

    Kang, Ju-Hee; Mollenhauer, Brit; Coffey, Christopher S; Toledo, Jon B; Weintraub, Daniel; Galasko, Douglas R; Irwin, David J; Van Deerlin, Vivianna; Chen-Plotkin, Alice S; Caspell-Garcia, Chelsea; Waligórska, Teresa; Taylor, Peggy; Shah, Nirali; Pan, Sarah; Zero, Pawel; Frasier, Mark; Marek, Kenneth; Kieburtz, Karl; Jennings, Danna; Tanner, Caroline M; Simuni, Tanya; Singleton, Andrew; Toga, Arthur W; Chowdhury, Sohini; Trojanowski, John Q; Shaw, Leslie M

    2016-06-01

    The development of biomarkers to predict the progression of Parkinson's disease (PD) from its earliest stage through its heterogeneous course is critical for research and therapeutic development. The Parkinson's Progression Markers Initiative (PPMI) study is an ongoing international multicenter, prospective study to validate biomarkers in drug-naïve PD patients and matched healthy controls (HC). We quantified cerebrospinal fluid (CSF) alpha-synuclein (α-syn), amyloid-beta1-42 (Aβ1-42), total tau (t-tau), and tau phosphorylated at Thr181 (p-tau) in 660 PPMI subjects at baseline, and correlated these data with measures of the clinical features of these subjects. We found that CSF α-syn, t-tau and p-tau levels, but not Aβ1-42, were significantly lower in PD compared with HC, while the diagnostic value of the individual CSF biomarkers for PD diagnosis was limited due to large overlap. The level of α-syn, but not other biomarkers, was significantly lower in PD patients with non-tremor-dominant phenotype compared with tremor-dominant phenotype. In addition, in PD patients the lowest Aβ1-42, or highest t-tau/Aβ1-42 and t-tau/α-syn quintile in PD patients were associated with more severe non-motor dysfunction compared with the highest or lowest quintiles, respectively. In a multivariate regression model, lower α-syn was significantly associated with worse cognitive test performance. APOE ε4 genotype was associated with lower levels of Aβ1-42, but neither with PD diagnosis nor cognition. Our data suggest that the measurement of CSF biomarkers in early-stage PD patients may relate to disease heterogeneity seen in PD. Longitudinal observations in PPMI subjects are needed to define their prognostic performance. PMID:27021906

  19. Nanoparticles for neuroimaging

    NASA Astrophysics Data System (ADS)

    Re, F.; Moresco, R.; Masserini, M.

    2012-02-01

    The advent of nanotechnology has introduced a variety of novel exciting possibilities into the medical and clinical field. Nanoparticles, ultra-small object sized between 100 and 1 nm, are promising diagnostic tools for various diseases among other devices, thanks to the possibility of their functionalization allowing the selective targeting of organs, tissues and cells and to facilitate their transport to primary target organs. However, brain targeting represents a still unresolved challenge due to the presence of the blood-brain barrier, a tightly packed layer of endothelial cells that prevents unwanted substances entering the central nervous system. We review a range of nanoparticles suitable for in vivo diagnostic imaging of neurodegenerative diseases and brain disorders, highlighting the possibility to potentially increase their efficiency and kinetics of brain-targeting. We also review a range of imaging techniques with an emphasis on most recently introduced molecular imaging modalities, their current status and future potential.

  20. Neuroimaging for psychotherapy research: Current trends

    PubMed Central

    WEINGARTEN, CAROL P.; STRAUMAN, TIMOTHY J.

    2014-01-01

    Objective This article reviews neuroimaging studies that inform psychotherapy research. An introduction to neuroimaging methods is provided as background for the increasingly sophisticated breadth of methods and findings appearing in psychotherapy research. Method We compiled and assessed a comprehensive list of neuroimaging studies of psychotherapy outcome, along with selected examples of other types of studies that also are relevant to psychotherapy research. We emphasized magnetic resonance imaging (MRI) since it is the dominant neuroimaging modality in psychological research. Results We summarize findings from neuroimaging studies of psychotherapy outcome, including treatment for depression, obsessive-compulsive disorder (OCD), and schizophrenia. Conclusions The increasing use of neuroimaging methods in the study of psychotherapy continues to refine our understanding of both outcome and process. We suggest possible directions for future neuroimaging studies in psychotherapy research. PMID:24527694

  1. Neuroimaging in Leukemia.

    PubMed

    Nabavizadeh, Seyed Ali; Stein, Joel; Mohan, Suyash

    2016-08-01

    Leukemias are a heterogeneous group of hematologic malignancies that results from uncontrolled neoplastic proliferation of undifferentiated or partially differentiated hematopoietic cells. Patients with acute leukemia can have a variety of craniocerebral complications, which can result from direct leukemic involvement, secondary to cerebrovascular or infectious complications of leukemia, or can be treatment related. Imaging plays a central role in evaluating the central nervous system during treatment in patients with leukemia. CT scan is usually considered an effective initial imaging modality to evaluate for cerebrovascular complications. MRI is considered the imaging modality of choice due to its versatility. PMID:27443999

  2. 25 years of neuroimaging in amyotrophic lateral sclerosis

    PubMed Central

    Foerster, Bradley R.; Welsh, Robert C.; Feldman, Eva L.

    2014-01-01

    Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease for which a precise cause has not yet been identified. Standard CT or MRI evaluation does not demonstrate gross structural nervous system changes in ALS, so conventional neuroimaging techniques have provided little insight into the pathophysiology of this disease. Advanced neuroimaging techniques—such as structural MRI, diffusion tensor imaging and proton magnetic resonance spectroscopy—allow evaluation of alterations of the nervous system in ALS. These alterations include focal loss of grey and white matter and reductions in white matter tract integrity, as well as changes in neural networks and in the chemistry, metabolism and receptor distribution in the brain. Given their potential for investigation of both brain structure and function, advanced neuroimaging methods offer important opportunities to improve diagnosis, guide prognosis, and direct future treatment strategies in ALS. In this article, we review the contributions made by various advanced neuroimaging techniques to our understanding of the impact of ALS on different brain regions, and the potential role of such measures in biomarker development. PMID:23917850

  3. Advanced Neuroimaging of Tinnitus.

    PubMed

    Raghavan, Prashant; Steven, Andrew; Rath, Tanya; Gandhi, Dheeraj

    2016-05-01

    Although tinnitus may originate in damage to the peripheral auditory apparatus, its perception and distressing symptomatology are consequences of alterations to auditory, sensory, and limbic neural networks. This has been described in several studies, some using advanced structural MR imaging techniques such as diffusion tensor imaging. An understanding of these complex changes could enable development of targeted treatment. New MR imaging techniques enabling detailed depiction of the labyrinth may be useful when diagnosis of Meniere disease is equivocal. Advances in computed tomography and MR imaging have enabled noninvasive diagnosis of dural arteriovenous fistulae. PMID:27154611

  4. Impact of Common Variations in PLD3 on Neuroimaging Phenotypes in Non-demented Elders.

    PubMed

    Wang, Chong; Wang, Hui-Fu; Tan, Meng-Shan; Liu, Ying; Jiang, Teng; Zhang, Dao-Qiang; Tan, Lan; Yu, Jin-Tai

    2016-09-01

    Rare variants of phospholipase D3 (PLD3) have been identified as Alzheimer's disease (AD) susceptibility loci, whereas little is known about the potential role of common variants in the progression of AD. To examine the impact of genetic variations in PLD3 on neuroimaging phenotypes in a large non-demented population. A total of 261 normal cognition (NC) and 456 mild cognitive impairment (MCI) individuals from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database are included in our analysis. Multiple linear regression models were applied to examine the association between four single-nucleotide polymorphisms (SNPs; rs7249146, rs4490097, rs12151243, and rs10407447) with the florbetapir retention on florbetapir 18F amyloid positron emission tomography (AV45-PET), the cerebral metabolic rate for glucose (CMRgl) on 18F-fluorodeoxyglucose PET (FDG-PET), and regional volume on magnetic resonance imaging (MRI) at baseline and in the cohort study. We did not detect any significant associations of PLD3 SNPs with florbetapir retention on AV45-PET. In the analysis of FDG-PET, rs10407447 was associated with the CMRgl in the left angular gyrus and bilateral posterior cingulate cortex in the MCI group. Regarding the MRI analysis, rs10407447 was also associated with bilateral inferior lateral ventricle and lateral ventricle volume in MCI group. The main findings of our study provide evidence that support the possible role of PLD3 common variants in influencing AD-related neuroimaging phenotypes. Nevertheless, further work is necessary to explain the functional mechanisms of differences and confirm the causal variants. PMID:26232066

  5. Testing for association with multiple traits in generalized estimation equations, with application to neuroimaging data.

    PubMed

    Zhang, Yiwei; Xu, Zhiyuan; Shen, Xiaotong; Pan, Wei

    2014-08-01

    There is an increasing need to develop and apply powerful statistical tests to detect multiple traits-single locus associations, as arising from neuroimaging genetics and other studies. For example, in the Alzheimer's Disease Neuroimaging Initiative (ADNI), in addition to genome-wide single nucleotide polymorphisms (SNPs), thousands of neuroimaging and neuropsychological phenotypes as intermediate phenotypes for Alzheimer's disease, have been collected. Although some classic methods like MANOVA and newly proposed methods may be applied, they have their own limitations. For example, MANOVA cannot be applied to binary and other discrete traits. In addition, the relationships among these methods are not well understood. Importantly, since these tests are not data adaptive, depending on the unknown association patterns among multiple traits and between multiple traits and a locus, these tests may or may not be powerful. In this paper we propose a class of data-adaptive weights and the corresponding weighted tests in the general framework of generalized estimation equations (GEE). A highly adaptive test is proposed to select the most powerful one from this class of the weighted tests so that it can maintain high power across a wide range of situations. Our proposed tests are applicable to various types of traits with or without covariates. Importantly, we also analytically show relationships among some existing and our proposed tests, indicating that many existing tests are special cases of our proposed tests. Extensive simulation studies were conducted to compare and contrast the power properties of various existing and our new methods. Finally, we applied the methods to an ADNI dataset to illustrate the performance of the methods. We conclude with the recommendation for the use of the GEE-based Score test and our proposed adaptive test for their high and complementary performance. PMID:24704269

  6. 78 FR 15015 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panels (SEP): Initial Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-08

    ..., Prevention and Treatment of Influenza and other Respiratory Infections in Panama and Central America Region... Activities for Avian Influenza and other Zoonotic Diseases, FOA CK13-002, initial review. Correction:...

  7. Mechanisms of Cognitive Impairment in Cerebral Small Vessel Disease: Multimodal MRI Results from the St George's Cognition and Neuroimaging in Stroke (SCANS) Study

    PubMed Central

    Lawrence, Andrew J.; Patel, Bhavini; Morris, Robin G.; MacKinnon, Andrew D.; Rich, Philip M.; Barrick, Thomas R.; Markus, Hugh S.

    2013-01-01

    Cerebral small vessel disease (SVD) is a common cause of vascular cognitive impairment. A number of disease features can be assessed on MRI including lacunar infarcts, T2 lesion volume, brain atrophy, and cerebral microbleeds. In addition, diffusion tensor imaging (DTI) is sensitive to disruption of white matter ultrastructure, and recently it has been suggested that additional information on the pattern of damage may be obtained from axial diffusivity, a proposed marker of axonal damage, and radial diffusivity, an indicator of demyelination. We determined the contribution of these whole brain MRI markers to cognitive impairment in SVD. Consecutive patients with lacunar stroke and confluent leukoaraiosis were recruited into the ongoing SCANS study of cognitive impairment in SVD (n = 115), and underwent neuropsychological assessment and multimodal MRI. SVD subjects displayed poor performance on tests of executive function and processing speed. In the SVD group brain volume was lower, white matter hyperintensity volume higher and all diffusion characteristics differed significantly from control subjects (n = 50). On multi-predictor analysis independent predictors of executive function in SVD were lacunar infarct count and diffusivity of normal appearing white matter on DTI. Independent predictors of processing speed were lacunar infarct count and brain atrophy. Radial diffusivity was a stronger DTI predictor than axial diffusivity, suggesting ischaemic demyelination, seen neuropathologically in SVD, may be an important predictor of cognitive impairment in SVD. Our study provides information on the mechanism of cognitive impairment in SVD. PMID:23613774

  8. A transformation similarity constraint for groupwise nonlinear registration in longitudinal neuroimaging studies

    NASA Astrophysics Data System (ADS)

    Fleishman, Greg M.; Gutman, Boris A.; Fletcher, P. Thomas; Thompson, Paul

    2015-03-01

    Patients with Alzheimer's disease and other brain disorders often show a similar spatial distribution of volume change throughout the brain over time, but this information is not yet used in registration algorithms to refine the quantification of change. Here, we develop a mathematical basis to incorporate that prior information into a longitudinal structural neuroimaging study. We modify the canonical minimization problem for non-linear registration to include a term that couples a collection of registrations together to enforce group similarity. More specifically, throughout the computation we maintain a group-level representation of the transformations and constrain updates to individual transformations to be similar to this representation. The derivations necessary to produce the Euler-Lagrange equations for the coupling term are presented and a gradient descent algorithm based on the formulation was implemented. We demonstrate using 57 longitudinal image pairs from the Alzheimer's Disease Neuroimaging Initiative (ADNI) that longitudinal registration with such a groupwise coupling prior is more robust to noise in estimating change, suggesting such change maps may have several important applications.

  9. Neuroimaging in Animal Seizure Models with 18FDG-PET

    PubMed Central

    Mirrione, Martine M.; Tsirka, Stella E.

    2011-01-01

    Small animal neuroimaging has become increasingly available to researchers, expanding the breadth of questions studied with these methods. Applying these noninvasive techniques to the open questions underlying epileptogenesis is no exception. A major advantage of small animal neuroimaging is its translational appeal. Studies can be well controlled and manipulated, examining the living brain in the animal before, during, and after the disease onset or disease treatment. The results can also be compared to data collected on human patients. Over the past decade, we and others have explored metabolic patterns in animal models of epilepsy to gain insight into the circuitry underlying development of the disease. In this paper, we provide technical details on how metabolic imaging that uses 2-deoxy-2[18F]fluoro-D-glucose (18FDG) and positron emission tomography (PET) is performed and explain the strengths and limitations of these studies. We will also highlight recent advances toward understanding epileptogenesis through small animal imaging. PMID:22937232

  10. 78 FR 66938 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-07

    ... review, published in the Federal Register on September 18, 2013 (FR Volume 78, Number 181, Page 57391... HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review Notice of Cancellation: This notice...

  11. 77 FR 20822 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

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    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review The meeting announced below concerns Identifying Modifiable Protective Factors for...

  12. 78 FR 78966 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

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    ... HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review The meeting announced below concerns Epidemiology, Prevention, and Treatment of Influenza and Other Respiratory Infections in a Malaria- Endemic Area of...

  13. 78 FR 17411 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

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    2013-03-21

    ... Evaluation of Malaria Control and Elimination Activities, FOA GH13-005, initial review. In accordance with... in response to ``Monitoring and Evaluation of Malaria Control and Elimination Activities, FOA GH13... HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention...

  14. 78 FR 17410 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panels (SEP): Initial review

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    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and Control Special Emphasis Panels (SEP): Initial review The meeting announced below concerns Epi-Centers for the Prevention of...

  15. 77 FR 31358 - Disease, Disability, and Injury Prevention and Control Special Interest Projects (SIPs): Initial...

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    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and Control Special Interest Projects (SIPs): Initial Review The meeting announced below concerns Research...

  16. 77 FR 29351 - Disease, Disability, and Injury Prevention and Control; Special Interest Projects (SIPs): Initial...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-17

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and Control; Special Interest Projects (SIPs): Initial Review The meeting announced below concerns Examination of Environmental Characteristics...

  17. 77 FR 291 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

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    2012-01-04

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review The meeting announced below concerns National HIV Behavioral Surveillance For Young Men...

  18. 76 FR 28790 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial review.

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    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial review. The meeting announced below concerns Affordable Care Act (ACA): Childhood Obesity...

  19. 76 FR 29756 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

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    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review The meeting announced below concerns Centers...

  20. 77 FR 44618 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

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    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review The meeting announced below concerns the World...

  1. 77 FR 48986 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

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    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review The meeting announced below concerns Member...

  2. 78 FR 19490 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

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    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review The meeting announced below concerns Development...

  3. 77 FR 22326 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

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    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review The meeting announced below concerns Extension of...

  4. 76 FR 28790 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

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    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review The meeting announced below concerns Member...

  5. 78 FR 60878 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

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    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review The meeting announced below concerns Health...

  6. 78 FR 19490 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

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    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review Notice of Cancellation: A notice was published in...

  7. 78 FR 35035 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial review

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    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial review The meeting announced below concerns Centers...

  8. 77 FR 7164 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

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    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review The meeting announced below concerns Member...

  9. 78 FR 25743 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

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    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review The meeting announced below concerns Member...

  10. 76 FR 52330 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

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    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review The meeting announced below concerns Member...

  11. 78 FR 78966 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

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    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review The meeting announced below concerns Capacity Building Assistance for High Impact...

  12. 77 FR 34045 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel: Initial Review

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    ... HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and Control Special Emphasis Panel: Initial Review The meeting announced below concerns Cooperative Research... Control and Prevention (CDC) announces the aforementioned meeting: Times and Dates: 8 a.m.-5 p.m., July...

  13. 78 FR 23768 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

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    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review The meeting announced below concerns Developing Research Capacity to Assess Health...

  14. 77 FR 39497 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

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  15. 76 FR 33305 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

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    2011-06-08

    ... From the Federal Register Online via the Government Publishing Office ] DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review The meeting announced below concerns Program to Support New Implementation of State...

  16. The Human Connectome Project's neuroimaging approach.

    PubMed

    Glasser, Matthew F; Smith, Stephen M; Marcus, Daniel S; Andersson, Jesper L R; Auerbach, Edward J; Behrens, Timothy E J; Coalson, Timothy S; Harms, Michael P; Jenkinson, Mark; Moeller, Steen; Robinson, Emma C; Sotiropoulos, Stamatios N; Xu, Junqian; Yacoub, Essa; Ugurbil, Kamil; Van Essen, David C

    2016-08-26

    Noninvasive human neuroimaging has yielded many discoveries about the brain. Numerous methodological advances have also occurred, though inertia has slowed their adoption. This paper presents an integrated approach to data acquisition, analysis and sharing that builds upon recent advances, particularly from the Human Connectome Project (HCP). The 'HCP-style' paradigm has seven core tenets: (i) collect multimodal imaging data from many subjects; (ii) acquire data at high spatial and temporal resolution; (iii) preprocess data to minimize distortions, blurring and temporal artifacts; (iv) represent data using the natural geometry of cortical and subcortical structures; (v) accurately align corresponding brain areas across subjects and studies; (vi) analyze data using neurobiologically accurate brain parcellations; and (vii) share published data via user-friendly databases. We illustrate the HCP-style paradigm using existing HCP data sets and provide guidance for future research. Widespread adoption of this paradigm should accelerate progress in understanding the brain in health and disease. PMID:27571196

  17. Nutrient intake and brain biomarkers of Alzheimer's disease in at-risk cognitively normal individuals: a cross-sectional neuroimaging pilot study

    PubMed Central

    Mosconi, Lisa; Murray, John; Davies, Michelle; Williams, Schantel; Pirraglia, Elizabeth; Spector, Nicole; Tsui, Wai H; Li, Yi; Butler, Tracy; Osorio, Ricardo S; Glodzik, Lidia; Vallabhajosula, Shankar; McHugh, Pauline; Marmar, Charles R; de Leon, Mony J

    2014-01-01

    Objective There is increasing evidence to suggest that diet, one of the most important modifiable environmental factors, may play a role in preventing or delaying cognitive decline and Alzheimer's disease (AD). This study examines the relationship between dietary nutrients and brain biomarkers of AD in cognitively normal individuals (NL) with and without AD risk factors. Design As part of an ongoing brain imaging study, participants received clinical and laboratory examinations, a neurocognitive test battery, positron emission tomography (PET) with 11C-Pittsburgh Compound-B (PiB; a measure of amyloid-β (Aβ) load) and 18F-fluorodeoxyglucose (FDG; a proxy of neuronal activity), and completed semiquantitative food frequency questionnaires. Setting Research centre affiliated with the Alzheimer's disease Core Center at New York University School of Medicine. Participants 49 NL individuals (age 25–72 years, 69% women) with dietary information, 11C-PiB and 18F-FDG PET scans were examined. Results Controlling for age and total caloric intake, higher intake of vitamin B12, vitamin D and ω-3 polyunsaturated fatty acid (PUFA) was associated with lower Aβ load in AD regions on PiB-PET, while higher intake of β-carotene and folate was associated with higher glucose metabolism on FDG-PET. β-carotene and folate were associated with reduced glucose metabolism for women, apolipoprotein E epsilon 4 (APOE4) carriers and participants with positive AD family history, but not for their risk-free counterparts. The associations of vitamin B12, vitamin D and ω-3 PUFA with PiB retention were independent of gender, APOE and family history. The identified nutrient combination was associated with higher intake of vegetables, fruit, whole grains, fish and legumes, and lower intake of high-fat dairies, meat and sweets. Conclusions Our data provide a potential pathophysiological mechanism for epidemiological findings showing that dietary interventions may play a role in the prevention

  18. [Adult onset Still's disease with the initial symptom of pharyngalgia: a case report].

    PubMed

    Zhou, Enhui; Chen, Xiaoping; Zhang, Jingfei

    2015-09-01

    Adult onset Still's disease is a rare inflammatory disease characterized by spiking fevers, arthritis/ arthralgias, typical salmon-colored bumpy rash, pharyngalgia, myalgia and possible involvement of visceral organs. The diagnosis is exclusively based on clinical symptoms, according to the criteria, after the exclusion of well-known infectious, neoplastic, or other autoimmune/autoinflammatory disorders. This report includes one case of adult onset Still's disease with the initial symptom of pharyngalgia. PMID:26647549

  19. A review of neuroimaging findings in repetitive brain trauma.

    PubMed

    Koerte, Inga K; Lin, Alexander P; Willems, Anna; Muehlmann, Marc; Hufschmidt, Jakob; Coleman, Michael J; Green, Isobel; Liao, Huijun; Tate, David F; Wilde, Elisabeth A; Pasternak, Ofer; Bouix, Sylvain; Rathi, Yogesh; Bigler, Erin D; Stern, Robert A; Shenton, Martha E

    2015-05-01

    Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease confirmed at postmortem. Those at highest risk are professional athletes who participate in contact sports and military personnel who are exposed to repetitive blast events. All neuropathologically confirmed CTE cases, to date, have had a history of repetitive head impacts. This suggests that repetitive head impacts may be necessary for the initiation of the pathogenetic cascade that, in some cases, leads to CTE. Importantly, while all CTE appears to result from repetitive brain trauma, not all repetitive brain trauma results in CTE. Magnetic resonance imaging has great potential for understanding better the underlying mechanisms of repetitive brain trauma. In this review, we provide an overview of advanced imaging techniques currently used to investigate brain anomalies. We also provide an overview of neuroimaging findings in those exposed to repetitive head impacts in the acute/subacute and chronic phase of injury and in more neurodegenerative phases of injury, as well as in military personnel exposed to repetitive head impacts. Finally, we discuss future directions for research that will likely lead to a better understanding of the underlying mechanisms separating those who recover from repetitive brain trauma vs. those who go on to develop CTE. PMID:25904047

  20. Neuroimaging findings in late-onset schizophrenia and bipolar disorder.

    PubMed

    Hahn, Changtae; Lim, Hyun Kook; Lee, Chang Uk

    2014-03-01

    In recent years, there has been an increasing interest in late-onset mental disorders. Among them, geriatric schizophrenia and bipolar disorder are significant health care risks and major causes of disability. We discussed whether late-onset schizophrenia (LOS) and late-onset bipolar (LOB) disorder can be a separate entity from early-onset schizophrenia (EOS) and early-onset bipolar (EOB) disorder in a subset of late-life schizophrenia or late-life bipolar disorder through neuroimaging studies. A literature search for imaging studies of LOS or LOB was performed in the PubMed database. Search terms used were "(imaging OR MRI OR CT OR SPECT OR DTI OR PET OR fMRI) AND (schizophrenia or bipolar disorder) AND late onset." Articles that were published in English before October 2013 were included. There were a few neuroimaging studies assessing whether LOS and LOB had different disease-specific neural substrates compared with EOS and EOB. These researches mainly observed volumetric differences in specific brain regions, white matter hyperintensities, diffusion tensor imaging, or functional neuroimaging to explore the differences between LOS and LOB and EOS and EOB. The aim of this review was to highlight the neural substrates involved in LOS and LOB through neuroimaging studies. The exploration of neuroanatomical markers may be the key to the understanding of underlying neurobiology in LOS and LOB. PMID:24401535

  1. Neuroimaging Week: A Novel, Engaging, and Effective Curriculum for Teaching Neuroimaging to Junior Psychiatric Residents

    ERIC Educational Resources Information Center

    Downar, Jonathan; Krizova, Adriana; Ghaffar, Omar; Zaretsky, Ari

    2010-01-01

    Objective: Neuroimaging techniques are increasingly important in psychiatric research and clinical practice, but few postgraduate psychiatry programs offer formal training in neuroimaging. To address this need, the authors developed a course to prepare psychiatric residents to use neuroimaging techniques effectively in independent practice.…

  2. Tinnitus: perspectives from human neuroimaging.

    PubMed

    Elgoyhen, Ana Belén; Langguth, Berthold; De Ridder, Dirk; Vanneste, Sven

    2015-10-01

    Tinnitus is the perception of phantom sound in the absence of a corresponding external source. It is a highly prevalent disorder, and most cases are caused by cochlear injury that leads to peripheral deafferentation, which results in adaptive changes in the CNS. In this article we critically assess the recent neuroimaging studies in individuals with tinnitus that suggest that the disorder is accompanied by functional and structural brain abnormalities in distributed auditory and non-auditory brain regions. Moreover, we consider how the identification of the neuronal mechanisms underlying the different forms of tinnitus would benefit from larger studies, replication and comprehensive clinical assessment of patients. PMID:26373470

  3. [Relevance of neuroimaging findings for diagnoses and treatment of adolescent anorexia nervosa].

    PubMed

    Konrad, Kerstin

    2015-01-01

    Anorexia nervosa is associated with a marked loss of brain volumes during the acute stage of the disease. Due to the advances in neuroimaging methods during the last years our understanding of the consequences of starvation and the etiology of eating disorders has increased considerably, however, still the clinical relevance of these findings is limited. Thus, some future perspectives of neuroimaging findings for diagnoses and treatment of anorexia nervosa are summarized in the current review. PMID:25594269

  4. A simple tool for neuroimaging data sharing

    PubMed Central

    Haselgrove, Christian; Poline, Jean-Baptiste; Kennedy, David N.

    2014-01-01

    Data sharing is becoming increasingly common, but despite encouragement and facilitation by funding agencies, journals, and some research efforts, most neuroimaging data acquired today is still not shared due to political, financial, social, and technical barriers to sharing data that remain. In particular, technical solutions are few for researchers that are not a part of larger efforts with dedicated sharing infrastructures, and social barriers such as the time commitment required to share can keep data from becoming publicly available. We present a system for sharing neuroimaging data, designed to be simple to use and to provide benefit to the data provider. The system consists of a server at the International Neuroinformatics Coordinating Facility (INCF) and user tools for uploading data to the server. The primary design principle for the user tools is ease of use: the user identifies a directory containing Digital Imaging and Communications in Medicine (DICOM) data, provides their INCF Portal authentication, and provides identifiers for the subject and imaging session. The user tool anonymizes the data and sends it to the server. The server then runs quality control routines on the data, and the data and the quality control reports are made public. The user retains control of the data and may change the sharing policy as they need. The result is that in a few minutes of the user’s time, DICOM data can be anonymized and made publicly available, and an initial quality control assessment can be performed on the data. The system is currently functional, and user tools and access to the public image database are available at http://xnat.incf.org/. PMID:24904398

  5. Neuroimaging.

    PubMed

    Pope, Whitney B; Djoukhadar, Ibrahim; Jackson, Alan

    2016-01-01

    Imaging is integral to the management of patients with brain tumors. Conventional structural imaging provides exquisite anatomic detail but remains limited in the evaluation of molecular characteristics of intracranial neoplasms. Quantitative and physiologic biomarkers derived from advanced imaging techniques have been increasingly utilized as problem-solving tools to identify glioma grade and assess response to therapy. This chapter provides a comprehensive overview of the imaging strategies used in the clinical assessment of patients with gliomas and describes how novel imaging biomarkers have the potential to improve patient management. PMID:26948347

  6. The down syndrome biomarker initiative (DSBI) pilot: proof of concept for deep phenotyping of Alzheimer’s disease biomarkers in down syndrome

    PubMed Central

    Rafii, Michael S.; Wishnek, Hannah; Brewer, James B.; Donohue, Michael C.; Ness, Seth; Mobley, William C.; Aisen, Paul S.; Rissman, Robert A.

    2015-01-01

    To gain further knowledge on the preclinical phase of Alzheimer’s disease (AD), we sought to characterize cognitive performance, neuroimaging and plasma-based AD biomarkers in a cohort of non-demented adults with down syndrome (DS). The goal of the down syndrome biomarker Initiative (DSBI) pilot is to test feasibility of this approach for future multicenter studies. We enrolled 12 non-demented participants with DS between the ages of 30–60 years old. Participants underwent extensive cognitive testing, volumetric MRI, amyloid positron emission tomography (PET; 18F-florbetapir), fluorodeoxyglucose (FDG) PET (18F-fluorodeoxyglucose) and retinal amyloid imaging. In addition, plasma beta-amyloid (Aβ) species were measured and Apolipoprotein E (ApoE) genotyping was performed. Results from our multimodal analysis suggest greater hippocampal atrophy with amyloid load. Additionally, we identified an inverse relationship between amyloid load and regional glucose metabolism. Cognitive and functional measures did not correlate with amyloid load in DS but did correlate with regional FDG PET measures. Biomarkers of AD can be readily studied in adults with DS as in other preclinical AD populations. Importantly, all subjects in this feasibility study were able to complete all test procedures. The data indicate that a large, multicenter longitudinal study is feasible to better understand the trajectories of AD biomarkers in this enriched population. This trial is registered with ClinicalTrials.gov, number NCT02141971. PMID:26441570

  7. Neuroimaging of Freezing of Gait

    PubMed Central

    Fasano, Alfonso; Herman, Talia; Tessitore, Alessandro; Strafella, Antonio P.; Bohnen, Nicolaas I.

    2015-01-01

    Abstract Functional brain imaging techniques appear ideally suited to explore the pathophysiology of freezing of gait (FOG). In the last two decades, techniques based on magnetic resonance or nuclear medicine imaging have found a number of structural changes and functional disconnections between subcortical and cortical regions of the locomotor network in patients with FOG. FOG seems to be related in part to disruptions in the “executive-attention” network along with regional tissue loss including the premotor area, inferior frontal gyrus, precentral gyrus, the parietal and occipital areas involved in visuospatial functions of the right hemisphere. Several subcortical structures have been also involved in the etiology of FOG, principally the caudate nucleus and the locomotor centers in the brainstem. Maladaptive neural compensation may present transiently in the presence of acute conflicting motor, cognitive or emotional stimulus processing, thus causing acute network overload and resulting in episodic impairment of stepping. In this review we will summarize the state of the art of neuroimaging research for FOG. We will also discuss the limitations of current approaches and delineate the next steps of neuroimaging research to unravel the pathophysiology of this mysterious motor phenomenon. PMID:25757831

  8. What's new in neuroimaging methods?

    PubMed Central

    Bandettini, Peter A.

    2009-01-01

    The rapid advancement of neuroimaging methodology and availability has transformed neuroscience research. The answers to many questions that we ask about how the brain is organized depend on the quality of data that we are able to obtain about the locations, dynamics, fluctuations, magnitudes, and types of brain activity and structural changes. In this review, an attempt is made to take a snapshot of the cutting edge of a small component of the very rapidly evolving field of neuroimaging. For each area covered, a brief context is provided along with a summary of a few of the current developments and issues. Then, several outstanding papers, published in the past year or so, are described, providing an example of the directions in which each area is progressing. The areas covered include functional MRI (fMRI), voxel based morphometry (VBM), diffusion tensor imaging (DTI), electroencephalography (EEG), magnetoencephalography (MEG), optical imaging, and positron emission tomography (PET). More detail is included on fMRI, as subsections include: functional MRI interpretation, new functional MRI contrasts, MRI technology, MRI paradigms and processing, and endogenous oscillations in functional MRI. PMID:19338512

  9. Neuroimaging and plasticity in schizophrenia.

    PubMed

    Meyer-Lindenberg, Andreas; Tost, Heike

    2014-01-01

    Schizophrenia is a frequent and highly heritable brain disorder that typically manifests around or after puberty and has a fluctuating course. Multiple lines of evidence point to a neurodevelopmental origin of the illness and suggest that its (post) pubertal manifestation is related to genetic and environmental risk factors that interfere with the structural and functional reorganization of neural networks at this time. Longitudinal structural neuroimaging studies point to a progressive reduction in gray matter volume in many brain regions in schizophrenia. It has been proposed that these neuroimaging observations reflect an enduring disturbance of experience-dependent synaptic plasticity arising from developmental abnormalities in key neural circuits implicated in schizophrenia, including dorsolateral prefrontal cortex and hippocampal formation. Recent work has identified genetic variants linked to neural plasticity that are associated with changes in these circuits. Furthermore, non-invasive interventions such as transcranial magnetic stimulation have been shown to impact some of these systems-level intermediate phenotypes, suggesting a modifiability of these core pathophysiological processes of schizophrenia that may be exploited by therapy. PMID:23902983

  10. Neuroimaging in repetitive brain trauma

    PubMed Central

    2014-01-01

    Sports-related concussions are one of the major causes of mild traumatic brain injury. Although most patients recover completely within days to weeks, those who experience repetitive brain trauma (RBT) may be at risk for developing a condition known as chronic traumatic encephalopathy (CTE). While this condition is most commonly observed in athletes who experience repetitive concussive and/or subconcussive blows to the head, such as boxers, football players, or hockey players, CTE may also affect soldiers on active duty. Currently, the only means by which to diagnose CTE is by the presence of phosphorylated tau aggregations post-mortem. Non-invasive neuroimaging, however, may allow early diagnosis as well as improve our understanding of the underlying pathophysiology of RBT. The purpose of this article is to review advanced neuroimaging methods used to investigate RBT, including diffusion tensor imaging, magnetic resonance spectroscopy, functional magnetic resonance imaging, susceptibility weighted imaging, and positron emission tomography. While there is a considerable literature using these methods in brain injury in general, the focus of this review is on RBT and those subject populations currently known to be susceptible to RBT, namely athletes and soldiers. Further, while direct detection of CTE in vivo has not yet been achieved, all of the methods described in this review provide insight into RBT and will likely lead to a better characterization (diagnosis), in vivo, of CTE than measures of self-report. PMID:25031630

  11. A Case of Polyarteritis Nodosa Presenting Initially as Peripheral Vascular Disease

    PubMed Central

    Parikh, Sameer; Lu, Lee

    2008-01-01

    Polyarteritis nodosa is a rare necrotizing vasculitis that can be progressive and fatal, and its initial presenting symptom may be leg claudication due to peripheral vascular ischemia. To date, there have been fewer than ten case reports of polyarteritis nodosa presenting as peripheral vascular disease. We report a case of a 38-year-old man initially diagnosed to have premature peripheral vascular disease who presented 1 year later with symptoms consistent with giant cell arteritis and subsequently developed bowel ischemia leading to a fatal outcome. Based on the autopsy and the patient’s clinical course, the final diagnosis was polyarteritis nodosa. This case illustrates the challenges in diagnosing polyarteritis nodosa and the importance of considering vasculitis in young patients presenting with atypical presentations of diseases such as peripheral vascular disease or giant cell arteritis. PMID:18560943

  12. Neuroimaging of Cognitive Load in Instructional Multimedia

    ERIC Educational Resources Information Center

    Whelan, Robert R.

    2007-01-01

    This paper reviews research literature on cognitive load measurement in learning and neuroimaging, and describes a mapping between the main elements of cognitive load theory and findings in functional neuroanatomy. It is argued that these findings may lead to the improved measurement of cognitive load using neuroimaging. The paper describes how…

  13. Neuroimaging and Research into Second Language Acquisition

    ERIC Educational Resources Information Center

    Sabourin, Laura

    2009-01-01

    Neuroimaging techniques are becoming not only more and more sophisticated but are also coming to be increasingly accessible to researchers. One thing that one should take note of is the potential of neuroimaging research within second language acquisition (SLA) to contribute to issues pertaining to the plasticity of the adult brain and to general…

  14. Gene Interactions and Structural Brain Change in Early-Onset Alzheimer's Disease Subjects Using the Pipeline Environment

    PubMed Central

    Dinov, Ivo D.; Zamanyan, Alen; Shi, Ran; Genco, Alex; Hobel, Sam; Thompson, Paul M.; Toga, Arthur W.

    2015-01-01

    Objective This article investigates subjects aged 55 to 65 from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database to broaden our understanding of early-onset (EO) cognitive impairment using neuroimaging and genetics biomarkers. Methods Nine of the subjects had EO-AD (Alzheimer's disease) and 27 had EO-MCI (mild cognitive impairment). The 15 most important neuroimaging markers were extracted with the Global Shape Analysis (GSA) Pipeline workflow. The 20 most significant single nucleotide polymorphisms (SNPs) were chosen and were associated with specific neuroimaging biomarkers. Results We identified associations between the neuroimaging phenotypes and genotypes for a total of 36 subjects. Our results for all the subjects taken together showed the most significant associations between rs7718456 and L_hippocampus (volume), and between rs7718456 and R_hippocampus (volume). For the 27 MCI subjects, we found the most significant associations between rs6446443 and R_superior_frontal_gyrus (volume), and between rs17029131 and L_Precuneus (volume). For the nine AD subjects, we found the most significant associations between rs16964473 and L_rectus gyrus (surface area), and between rs12972537 and L_rectus_gyrus (surface area). Conclusion We observed significant correlations between the SNPs and the neuroimaging phenotypes in the 36 EO subjects in terms of neuroimaging genetics. However, larger sample sizes are needed to ensure that the effects will be detectable for a reasonable false-positive error rate using the GSA and Plink Pipeline workflows. PMID:25670955

  15. Persistence and compliance with newly initiated antihypertensive drug treatment in patients with chronic kidney disease

    PubMed Central

    Truong, Viet Thanh; Moisan, Jocelyne; Kröger, Edeltraut; Langlois, Serge; Grégoire, Jean-Pierre

    2016-01-01

    Background Patients with chronic kidney disease initiating an antihypertensive drug (AH) treatment must persist and comply with it to slow disease progression and benefit from the reduction of cardiovascular morbidity and mortality. Objectives This study evaluates the persistence and compliance with AH treatment and identifies the associated factors among chronic kidney disease patients who initiated AH treatment. Methods A population-based cohort study using Quebec administrative data was conducted. Patients who still take any AH 1 year after initiation were considered persistent. Of these patients, those who had ≥80% of days covered with an AH in the year after initiation were considered compliant. Factors associated with persistence and compliance were identified using a modified Poisson regression. Results Of the 7,119 eligible patients, 78.8% were persistent, 87.7% of whom were compliant with their AH treatment. Compared with patients on diuretic monotherapy, those who initially used angiotensin-converting enzyme inhibitor monotherapy, angiotensin II receptor blocker monotherapy, calcium channel blocker monotherapy, β-blocker monotherapy, or multidrug therapy were more likely to be persistent. In contrast, individuals who visited their physicians ≥17 times were less likely to be persistent than those who visited between 0 and 8 times. The patients who were more likely to be compliant had initially used an angiotensin-converting enzyme inhibitor, β-blocker, calcium channel blocker, or multitherapy as opposed to a diuretic. Conclusion A year after initiating AH treatment, nearly a third of chronic kidney disease patients were either not taking an AH or had not been compliant. Factors associated with persistence and compliance could help identify patients who need help in managing their AH treatment. PMID:27382260

  16. Bayesian Generalized Low Rank Regression Models for Neuroimaging Phenotypes and Genetic Markers

    PubMed Central

    Zhu, Hongtu; Khondker, Zakaria; Lu, Zhaohua; Ibrahim, Joseph G.

    2014-01-01

    We propose a Bayesian generalized low rank regression model (GLRR) for the analysis of both high-dimensional responses and covariates. This development is motivated by performing searches for associations between genetic variants and brain imaging phenotypes. GLRR integrates a low rank matrix to approximate the high-dimensional regression coefficient matrix of GLRR and a dynamic factor model to model the high-dimensional covariance matrix of brain imaging phenotypes. Local hypothesis testing is developed to identify significant covariates on high-dimensional responses. Posterior computation proceeds via an efficient Markov chain Monte Carlo algorithm. A simulation study is performed to evaluate the finite sample performance of GLRR and its comparison with several competing approaches. We apply GLRR to investigate the impact of 1,071 SNPs on top 40 genes reported by AlzGene database on the volumes of 93 regions of interest (ROI) obtained from Alzheimer's Disease Neuroimaging Initiative (ADNI). PMID:25349462

  17. How can neuroimaging facilitate the diagnosis and stratification of patients with psychosis?

    PubMed Central

    Kempton, Matthew J.; McGuire, Philip

    2015-01-01

    Early diagnosis and treatment of patients with psychosis are associated with improved outcome in terms of future functioning, symptoms and treatment response. Identifying neuroimaging biomarkers for illness onset and treatment response would lead to immediate clinical benefits. In this review we discuss if neuroimaging may be utilised to diagnose patients with psychosis, predict those who will develop the illness in those at high risk, and stratify patients. State-of-the-art developments in the field are critically examined including multicentre studies, longitudinal designs, multimodal imaging and machine learning as well as some of the challenges in utilising future neuroimaging biomarkers in clinical trials. As many of these developments are already being applied in neuroimaging studies of Alzheimer׳s disease, we discuss what lessons have been learned from this field and how they may be applied to research in psychosis. PMID:25092428

  18. Failure-free survival after initial systemic treatment of chronic graft-versus-host disease

    PubMed Central

    Flowers, Mary E. D.; Sandmaier, Brenda M.; Aki, Sahika Z.; Carpenter, Paul A.; Lee, Stephanie J.; Storer, Barry E.; Martin, Paul J.

    2014-01-01

    This study was designed to characterize failure-free survival (FFS) as a novel end point for clinical trials of chronic graft-versus-host disease (GVHD). The study cohort included 400 consecutive patients who received initial systemic treatment of chronic GVHD at our center. FFS was defined by the absence of second-line treatment, nonrelapse mortality, and recurrent malignancy during initial treatment. The FFS rate was 68% at 6 months and 54% at 12 months after initial treatment. Multivariate analysis identified 4 risk factors associated with treatment failure: time interval <12 months from transplantation to initial treatment, patient age ≥60 years, severe involvement of the gastrointestinal tract, liver, or lungs, and Karnofsky score <80% at initial treatment. Initial steroid doses and the type of initial treatment were not associated with risk of treatment failure. Lower steroid doses after 12 months of initial treatment were associated with long-term success in withdrawing all systemic treatment. FFS offers a potentially useful basis for interpreting results of initial treatment of chronic GVHD. Incorporation of steroid doses at 12 months would increase clinical benefit associated with the end point. Studies using FFS as the primary end point should measure changes in GVHD-related symptoms, activity, damage, and disability as secondary end points. PMID:24876566

  19. CATI: A Large Distributed Infrastructure for the Neuroimaging of Cohorts.

    PubMed

    Operto, Grégory; Chupin, Marie; Batrancourt, Bénédicte; Habert, Marie-Odile; Colliot, Olivier; Benali, Habib; Poupon, Cyril; Champseix, Catherine; Delmaire, Christine; Marie, Sullivan; Rivière, Denis; Pélégrini-Issac, Mélanie; Perlbarg, Vincent; Trebossen, Régine; Bottlaender, Michel; Frouin, Vincent; Grigis, Antoine; Orfanos, Dimitri Papadopoulos; Dary, Hugo; Fillon, Ludovic; Azouani, Chabha; Bouyahia, Ali; Fischer, Clara; Edward, Lydie; Bouin, Mathilde; Thoprakarn, Urielle; Li, Jinpeng; Makkaoui, Leila; Poret, Sylvain; Dufouil, Carole; Bouteloup, Vincent; Chételat, Gaël; Dubois, Bruno; Lehéricy, Stéphane; Mangin, Jean-François; Cointepas, Yann

    2016-07-01

    This paper provides an overview of CATI, a platform dedicated to multicenter neuroimaging. Initiated by the French Alzheimer's plan (2008-2012), CATI is a research project called on to provide service to other projects like an industrial partner. Its core mission is to support the neuroimaging of large populations, providing concrete solutions to the increasing complexity involved in such projects by bringing together a service infrastructure, the know-how of its expert academic teams and a large-scale, harmonized network of imaging facilities. CATI aims to make data sharing across studies easier and promotes sharing as much as possible. In the last 4 years, CATI has assisted the clinical community by taking charge of 35 projects so far and has emerged as a recognized actor at the national and international levels. PMID:27066973

  20. 78 FR 9055 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-07

    ..., Prevention and Treatment of Influenza and other Respiratory Infections in Panama and Central America Region... Activities for Avian Influenza and other Zoonotic Diseases, FOA CK13-002, initial review. In accordance with... received in response to ``Epidemiology, Prevention and Treatment of Influenza and other...

  1. Dietary patterns are associated with disease risk among participants in the women's health initiative observational study

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Coronary heart disease (CHD) is the leading cause of death in women. A nested case-control study tested whether dietary patterns predicted CHD events among 1224 participants in the Women’s Health Initiative-Observational Study (WHI-OS) with centrally confirmed CHD, fatal or nonfatal myocardial infar...

  2. Functional neuroimaging of autobiographical memory.

    PubMed

    Cabeza, Roberto; St Jacques, Peggy

    2007-05-01

    Functional neuroimaging studies of autobiographical memory have grown dramatically in recent years. These studies are important because they can investigate the neural correlates of processes that are difficult to study using laboratory stimuli, including: (i) complex constructive processes, (ii) recollective qualities of emotion and vividness, and (iii) remote memory retrieval. Constructing autobiographical memories involves search, monitoring and self-referential processes that are associated with activity in separable prefrontal regions. The contributions of emotion and vividness have been linked to the amygdala and visual cortex respectively. Finally, there is evidence that recent and remote autobiographical memories might activate the hippocampus equally, which has implications for memory-consolidation theories. The rapid development of innovative methods for eliciting personal memories in the scanner provides the opportunity to delve into the functional neuroanatomy of our personal past. PMID:17382578

  3. Analysis of residual disease following preoperative radiotherapy versus initial surgery in endometrial carcinoma

    SciTech Connect

    Chung, C.K.; Stryker, J.A.; Nahhas, W.A.; Cunningham, D.E.; Mortel, R.

    1982-02-01

    A clinicopathologic study of residual disease following pre-operative radiotherapy (RT) in 67 patients and initial surgery in 40 patients with early invasive endometrial carcinoma is presented. In 10%, extrauterine spread was found at operation. In 10% of patients, the histologic type, and in 19% the grade of tumor, differed between the curettage and hysterectomy specimens. Pre-op RT altered the depth of myometrial invasion and frequency of vascular invasion, but there was no evidence that irradiation itself affected the histologic type or grade of tumor. The patients with residual tumor after pre-op RT had significantly more cancer-related deaths than those without residual disease. The high risk factors were deep myometrial invasion and residual disease outside the uterus. Vascular invasion did not affect the prognosis in this series. The importance of surgical-pathologic staging by initial surgery is discussed.

  4. Visual Attention and the Neuroimage Bias

    PubMed Central

    Baker, D. A.; Schweitzer, N. J.; Risko, Evan F.; Ware, Jillian M.

    2013-01-01

    Several highly-cited experiments have presented evidence suggesting that neuroimages may unduly bias laypeople’s judgments of scientific research. This finding has been especially worrisome to the legal community in which neuroimage techniques may be used to produce evidence of a person’s mental state. However, a more recent body of work that has looked directly at the independent impact of neuroimages on layperson decision-making (both in legal and more general arenas), and has failed to find evidence of bias. To help resolve these conflicting findings, this research uses eye tracking technology to provide a measure of attention to different visual representations of neuroscientific data. Finding an effect of neuroimages on the distribution of attention would provide a potential mechanism for the influence of neuroimages on higher-level decisions. In the present experiment, a sample of laypeople viewed a vignette that briefly described a court case in which the defendant’s actions might have been explained by a neurological defect. Accompanying these vignettes was either an MRI image of the defendant’s brain, or a bar graph depicting levels of brain activity–two competing visualizations that have been the focus of much of the previous research on the neuroimage bias. We found that, while laypeople differentially attended to neuroimagery relative to the bar graph, this did not translate into differential judgments in a way that would support the idea of a neuroimage bias. PMID:24040251

  5. Neuroimaging studies of word reading

    PubMed Central

    Fiez, Julie A.; Petersen, Steven E.

    1998-01-01

    This review discusses how neuroimaging can contribute to our understanding of a fundamental aspect of skilled reading: the ability to pronounce a visually presented word. One contribution of neuroimaging is that it provides a tool for localizing brain regions that are active during word reading. To assess the extent to which similar results are obtained across studies, a quantitative review of nine neuroimaging investigations of word reading was conducted. Across these studies, the results converge to reveal a set of areas active during word reading, including left-lateralized regions in occipital and occipitotemporal cortex, the left frontal operculum, bilateral regions within the cerebellum, primary motor cortex, and the superior and middle temporal cortex, and medial regions in the supplementary motor area and anterior cingulate. Beyond localization, the challenge is to use neuroimaging as a tool for understanding how reading is accomplished. Central to this challenge will be the integration of neuroimaging results with information from other methodologies. To illustrate this point, this review will highlight the importance of spelling-to-sound consistency in the transformation from orthographic (word form) to phonological (word sound) representations, and then explore results from three neuroimaging studies in which the spelling-to-sound consistency of the stimuli was deliberately varied. Emphasis is placed on the pattern of activation observed within the left frontal cortex, because the results provide an example of the issues and benefits involved in relating neuroimaging results to behavioral results in normal and brain damaged subjects, and to theoretical models of reading. PMID:9448259

  6. Replication Validity of Initial Association Studies: A Comparison between Psychiatry, Neurology and Four Somatic Diseases

    PubMed Central

    Dumas-Mallet, Estelle; Button, Katherine; Boraud, Thomas; Munafo, Marcus; Gonon, François

    2016-01-01

    Context There are growing concerns about effect size inflation and replication validity of association studies, but few observational investigations have explored the extent of these problems. Objective Using meta-analyses to measure the reliability of initial studies and explore whether this varies across biomedical domains and study types (cognitive/behavioral, brain imaging, genetic and “others”). Methods We analyzed 663 meta-analyses describing associations between markers or risk factors and 12 pathologies within three biomedical domains (psychiatry, neurology and four somatic diseases). We collected the effect size, sample size, publication year and Impact Factor of initial studies, largest studies (i.e., with the largest sample size) and the corresponding meta-analyses. Initial studies were considered as replicated if they were in nominal agreement with meta-analyses and if their effect size inflation was below 100%. Results Nominal agreement between initial studies and meta-analyses regarding the presence of a significant effect was not better than chance in psychiatry, whereas it was somewhat better in neurology and somatic diseases. Whereas effect sizes reported by largest studies and meta-analyses were similar, most of those reported by initial studies were inflated. Among the 256 initial studies reporting a significant effect (p<0.05) and paired with significant meta-analyses, 97 effect sizes were inflated by more than 100%. Nominal agreement and effect size inflation varied with the biomedical domain and study type. Indeed, the replication rate of initial studies reporting a significant effect ranged from 6.3% for genetic studies in psychiatry to 86.4% for cognitive/behavioral studies. Comparison between eight subgroups shows that replication rate decreases with sample size and “true” effect size. We observed no evidence of association between replication rate and publication year or Impact Factor. Conclusion The differences in reliability

  7. Drugs for Neglected Diseases initiative model of drug development for neglected diseases: current status and future challenges.

    PubMed

    Ioset, Jean-Robert; Chang, Shing

    2011-09-01

    The Drugs for Neglected Diseases initiative (DNDi) is a patients' needs-driven organization committed to the development of new treatments for neglected diseases. Created in 2003, DNDi has delivered four improved treatments for malaria, sleeping sickness and visceral leishmaniasis. A main DNDi challenge is to build a solid R&D portfolio for neglected diseases and to deliver preclinical candidates in a timely manner using an original model based on partnership. To address this challenge DNDi has remodeled its discovery activities from a project-based academic-bound network to a fully integrated process-oriented platform in close collaboration with pharmaceutical companies. This discovery platform relies on dedicated screening capacity and lead-optimization consortia supported by a pragmatic, structured and pharmaceutical-focused compound sourcing strategy. PMID:21879842

  8. Burning Tongue as Initial Presentation of Celiac Disease in an Elderly Woman: A Case Report.

    PubMed

    Sherman, Andrea; Zamulko, Alla

    2016-06-01

    There are few reports in the literature where celiac disease presents with tongue manifestations, although atypical presentations of celiac disease are not uncommon. This case report highlights an atypical presentation of celiac disease in an elderly female. Our patient presented to clinic with complaints of a burning tongue for the past two years as well as occasional loose stools and fatigue. Work-up revealed iron deficiency anemia, zinc deficiency and an abnormal celiac panel. Complete symptom improvement was noted by 10 weeks into the initiation of a gluten free diet. Celiac disease can present at any age and should be considered as a differential in findings of malabsorption and gastrointestinal symptoms. PMID:27443108

  9. Defining the neurocircuitry of borderline personality disorder: functional neuroimaging approaches.

    PubMed

    Brendel, Gary R; Stern, Emily; Silbersweig, David A

    2005-01-01

    Functional neuroimaging recently has been used to localize brain dysfunction in borderline personality disorder (BPD). Initial studies have examined baseline activity or emotional reactivity, and our group has investigated what we consider to be a crucial interaction between negative emotion and behavioral (dys)control. This research is beginning to identify abnormal frontolimbic circuitry likely underlying core clinical features of this condition. We review the evidence for dysfunction in specific frontolimbic regions, leading to a mechanistic model of symptom formation in BPD. In addition, we offer an integration of these neuroimaging findings with developmental perspectives on the emergence of borderline psychopathology, focusing on the ways in which early psychosocial experience may interact with developing brain systems. We also consider possible mechanisms of psychotherapeutic change at the neural systems level in BPD. Finally, we propose that future neuroimaging studies of BPD should integrate multiple levels of observation (structural, functional, neurochemical, genetic, and clinical) in a model-driven fashion to further understand the dynamic relationship between biological and psychological factors in the development and treatment of this difficult condition. PMID:16613437

  10. Visual Systems for Interactive Exploration and Mining of Large-Scale Neuroimaging Data Archives

    PubMed Central

    Bowman, Ian; Joshi, Shantanu H.; Van Horn, John D.

    2012-01-01

    While technological advancements in neuroimaging scanner engineering have improved the efficiency of data acquisition, electronic data capture methods will likewise significantly expedite the populating of large-scale neuroimaging databases. As they do and these archives grow in size, a particular challenge lies in examining and interacting with the information that these resources contain through the development of compelling, user-driven approaches for data exploration and mining. In this article, we introduce the informatics visualization for neuroimaging (INVIZIAN) framework for the graphical rendering of, and dynamic interaction with the contents of large-scale neuroimaging data sets. We describe the rationale behind INVIZIAN, detail its development, and demonstrate its usage in examining a collection of over 900 T1-anatomical magnetic resonance imaging (MRI) image volumes from across a diverse set of clinical neuroimaging studies drawn from a leading neuroimaging database. Using a collection of cortical surface metrics and means for examining brain similarity, INVIZIAN graphically displays brain surfaces as points in a coordinate space and enables classification of clusters of neuroanatomically similar MRI images and data mining. As an initial step toward addressing the need for such user-friendly tools, INVIZIAN provides a highly unique means to interact with large quantities of electronic brain imaging archives in ways suitable for hypothesis generation and data mining. PMID:22536181