Browsing by Subject "neuroimaging"
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Item [(11)C]PiB PET in Gerstmann-Sträussler-Scheinker disease(e-Century Publishing Corporation, 2016) Deters, Kacie D.; Risacher, Shannon L.; Yoder, Karmen K.; Oblak, Adrian L.; Unverzagt, Frederick W.; Murrell, Jill R.; Epperson, Francine; Tallman, Eileen F.; Quaid, Kimberly A.; Farlow, Martin R.; Saykin, Andrew J.; Ghetti, Bernardino; Department of Pathology & Laboratory Medicine, IU School of MedicineGerstmann-Sträussler-Scheinker Disease (GSS) is a familial neurodegenerative disorder characterized clinically by ataxia, parkinsonism, and dementia, and neuropathologically by deposition of diffuse and amyloid plaques composed of prion protein (PrP). The purpose of this study was to evaluate if [(11)C]Pittsburgh Compound B (PiB) positron emission tomography (PET) is capable of detecting PrP-amyloid in PRNP gene carriers. Six individuals at risk for GSS and eight controls underwent [(11)C]PiB PET scans using standard methods. Approximately one year after the initial scan, each of the three asymptomatic carriers (two with PRNP P102L mutation, one with PRNP F198S mutation) underwent a second [(11)C]PiB PET scan. Three P102L carriers, one F198S carrier, and one non-carrier of the F198S mutation were cognitively normal, while one F198S carrier was cognitively impaired during the course of this study. No [(11)C]PiB uptake was observed in any subject at baseline or at follow-up. Neuropathologic study of the symptomatic individual revealed PrP-immunopositive plaques and tau-immunopositive neurofibrillary tangles in cerebral cortex, subcortical nuclei, and brainstem. PrP deposits were also numerous in the cerebellar cortex. This is the first study to investigate the ability of [(11)C]PiB PET to bind to PrP-amyloid in GSS F198S subjects. This finding suggests that [(11)C]PiB PET is not suitable for in vivo assessment of PrP-amyloid plaques in patients with GSS.Item Age, Sex, and Racial Differences in Neuroimaging Use in Acute Stroke: A Population-Based Study(2017-10) Vagal, A.; Sanelli, P.; Sucharew, H.; Alwell, K. A.; Khoury, J. C.; Khatri, P.; Woo, D.; Flaherty, M.; Kissela, B. M.; Adeoye, O.; Ferioli, S.; De Los Rios La Rosa, F.; Martini, S.; Mackey, Jason; Kleindorfer, D.; Neurology, School of MedicineBACKGROUND AND PURPOSE: Limited information is available regarding differences in neuroimaging use for acute stroke work-up. Our objective was to assess whether race, sex, or age differences exist in neuroimaging use and whether these differences depend on the care center type in a population-based study. MATERIALS AND METHODS: Patients with stroke (ischemic and hemorrhagic) and transient ischemic attack were identified in a metropolitan, biracial population using the Greater Cincinnati/Northern Kentucky Stroke Study in 2005 and 2010. Multivariable regression was used to determine the odds of advanced imaging use (CT angiography/MR imaging/MR angiography) for race, sex, and age. RESULTS: In 2005 and 2010, there were 3471 and 3431 stroke/TIA events, respectively. If one adjusted for covariates, the odds of advanced imaging were higher for younger (55 years or younger) compared with older patients, blacks compared with whites, and patients presenting to an academic center and those seen by a stroke team or neurologist. The observed association between race and advanced imaging depended on age; in the older age group, blacks had higher odds of advanced imaging compared with whites (odds ratio, 1.34; 95% CI, 1.12–1.61; P < .01), and in the younger group, the association between race and advanced imaging was not statistically significant. Age by race interaction persisted in the academic center subgroup (P < .01), but not in the nonacademic center subgroup (P = .58). No significant association was found between sex and advanced imaging. CONCLUSIONS: Within a large, biracial stroke/TIA population, there is variation in the use of advanced neuroimaging by age and race, depending on the care center type.Item Alterations in brain structure related to breast cancer and its treatment: Chemotherapy and other considerations(Springer US, 2013-12) McDonald, Brenna C.; Saykin, Andrew J.; Department of Radiology and Imaging Sciences, School of MedicineCognitive effects of cancer and its treatment have been a topic of increasing investigation over the past ∼30 years. Recent studies have focused on better understanding the neural correlates of these effects, with an emphasis on post-chemotherapy effects in breast cancer patients. Structural MRI studies have utilized both automated and manual approaches to quantify gray and white matter characteristics (e.g., regional volume and density) in breast cancer patients treated with chemotherapy relative to patients who did not receive chemotherapy and/or healthy controls. While most work to date has been retrospective, a small number of baseline (pre-systemic therapy) and prospective longitudinal studies have been conducted. Data have consistently shown lower gray and white matter volume and density in patients treated with chemotherapy, particularly in frontal and temporal brain regions. Host factors and/or the cancer disease process and other therapies (e.g., antiestrogen treatment) also seem likely to contribute to the observed differences, though the relative contributions of these effects have not yet been investigated in detail. These structural abnormalities have been shown to relate to subjective and objective cognitive functioning, as well as to biological factors that may help to elucidate the underlying mechanism(s). This review examines the currently available published observations and discusses the major themes and promising directions for future studies.Item Alterations in White Matter Microstructure and Connectivity in Young Adults with Alcohol Use Disorder(Wiley, 2019) Chumin, Evgeny J.; Grecco, Gregory G.; Dzemidzic, Mario; Cheng, Hu; Finn, Peter; Sporns, Olaf; Newman, Sharlene D.; Yoder, Karmen K.; Radiology and Imaging Sciences, School of MedicineBackground Magnetic resonance imaging (MRI) studies have shown differences in volume and structure in the brains of individuals with alcohol use disorder (AUD). Most research has focused on neuropathological effects of alcohol that appear after years of chronic alcohol misuse. However, few studies have investigated white matter (WM) microstructure and diffusion MRI‐based (DWI) connectivity during early stages of AUD. Therefore, the goal of this work was to investigate WM integrity and structural connectivity in emerging adulthood AUD subjects using both conventional DWI metrics and a novel connectomics approach. Methods Twenty‐two AUD and eighteen controls (CON) underwent anatomical and diffusion MRI. Outcome measures were scalar diffusion metrics and structural network connectomes. Tract Based Spatial Statistics was used to investigate group differences in diffusion measures. Structural connectomes were used as input into a community structure procedure to obtain a co‐classification index matrix (an indicator of community association strength) for each subject. Differences in co‐classification and structural connectivity (indexed by streamline density) were assessed via the Network Based Statistics Toolbox. Results AUD had higher FA values throughout the major WM tracts, but also had lower FA values in WM tracts in the cerebellum and right insula (pTFCE < 0.05). Mean diffusivity was generally lower in the AUD group (pTFCE < 0.05). AUD had lower co‐classification of nodes between ventral attention and default mode networks, and higher co‐classification between nodes of visual, default mode, and somatomotor networks. Additionally, AUD had higher fiber density between an adjacent pair of nodes within the default mode network. Conclusion Our results indicate that emerging adulthood AUD subjects may have differential patterns of FA and distinct differences in structural connectomes compared to CON. These data suggest that such alterations in microstructure and structural connectivity may uniquely characterize early stages of AUD and/or a predisposition for development of AUD.Item Analysis of the Inverse Association between Cancer and Alzheimer’s Disease: Results from the Alzheimer’s Disease Neuroimaging Initiative Cohort(Office of the Vice Chancellor for Research, 2014-04-11) Nudelman, Kelly N. H.; Risacher, Shannon L.; West, John D.; Nho, Kwangsik; Ramanan, Vijay K.; McDonald, Brenna C.; Shen, Li; Foroud, Tatiana M.; Schneider, Bryan P.; Saykin, Andrew J.Although a number of studies support a reciprocal inverse association between diagnoses of cancer and Alzheimer’s disease (AD), to date there has not been any systemic investigation of the neurobiological impact of or genetic risk factors underlying this effect. To facilitate this goal, this study aimed to replicate the inverse association of cancer and AD using data from the NIA Alzheimer’s Disease Neuroimaging Initiative, which includes age-matched cases and controls with information on cancer history, AD progression, neuroimaging, and genomic data. Subjects included individuals with AD (n=234), mild cognitive impairment (MCI, n=542), and healthy controls (HC, n=293). After controlling for sex, education, race/ethnicity, smoking, and apolipoprotein E (APOE) e2/3/4 allele groups, cancer history was protective against baseline AD diagnosis (p=0.042), and was associated with later age of AD onset (p=0.001). Cancer history appears to result in a cumulative protective effect; individuals with more than one cancer had a later age of AD onset compared to those with only one cancer (p=0.001). Finally, a protective effect of AD was also observed in individuals who developed incident cancer after enrolling (post-baseline visit); 20 individuals with MCI and 9 HC developed cancer, while no AD patients had subsequent cancer diagnoses (p=0.013). This supports previous research on the inverse association of cancer and AD, and importantly provides novel evidence that this effect appears to be independent of APOE, the major known genetic risk factor for AD. Future analyses will investigate the neurobiological and genetic basis of this effect.Item Cerebral hypometabolism and grey matter density in MAPT intron 10 +3 mutation carriers(e-Century Publishing Corporation, 2014) Deters, Kacie D.; Risacher, Shannon L.; Farlow, Martin R.; Unverzagt, Frederick W.; Kareken, David A.; Hutchins, Gary D.; Yoder, Karmen K.; Murrell, Jill R.; Spina, Salvatore; Epperson, Francine; Gao, Sujuan; Saykin, Andrew J.; Ghetti, Bernardino; Department of Radiology and Imaging Sciences, IU School of MedicineMultiple systems tauopathy with presenile dementia (MSTD), a form of frontotemporal dementia with parkinsonism-17 with tau inclusions (FTDP-17T), is a neurodegenerative disorder caused by an (a) to (g) transition at position +3 of intron 10 of the microtubule associated protein tau (MAPT) gene. The mutation causes overexpression of 4 repeat (4R) tau isoforms with increased 4R/3R ratio leading to neurodegeneration. Clinically, these patients primarily present with behavioral variant FTD (bvFTD) and show disinhibition, disordered social comportment, and impaired executive function, memory, and speech. While altered glucose metabolism has been reported in subjects with sporadic bvFTD, it has yet to be investigated in an FTDP-17 sample of this size. In this study, eleven mutation carriers (5 males; mean age = 48.0 ± 6.9 years) and eight non-carriers (2 males; mean age = 43.7 ± 12.0 years) from a MSTD family were imaged using [(18)F]fluorodeoxyglucose (FDG) positron emission tomography (PET). Eight of the MAPT intron 10 +3 mutation carriers met diagnostic criteria for bvFTD at the time of the PET scan, while three MAPT intron 10 +3 carriers were not cognitively impaired at the time of scan. Non-carriers had no clinically-relevant cognitive impairment at the time of the PET scan. Additionally, ten mutation carriers (5 males; mean age = 48.04 ± 2.1 years) and seven non-carriers (2 males; mean age 46.1 ± 4.1 years) underwent magnetic resonance imaging (MRI) which is an expanded sample size from a previous study. Seven MAPT mutation carriers met diagnostic criteria for bvFTD at the time of the MRI scan. Images were assessed on a voxel-wise basis for the effect of mutation carrier status. SPM8 was used for preprocessing and statistical analyses. Compared to non-carriers, MAPT mutation carriers showed lower [(18)F]FDG uptake bilaterally in the medial temporal lobe, and the parietal and frontal cortices. Anatomical changes were predominantly seen bilaterally in the medial temporal lobe areas which substantially overlapped with the hypometabolism findings. These anatomical and metabolic changes overlap previously described patterns of neurodegeneration in MSTD patients and are consistent with the characteristics of their cognitive dysfunction. These results suggest that neuroimaging can describe the neuropathology associated with this MAPT mutation.Item Characterization of Cerebral Blood Flow in Older Adults: A Potential Early Biomarker for Alzheimer's Disease(2022-04) Swinford, Cecily Gwinn; Risacher, Shannon L.; Saykin, Andrew J.; Apostolova, Liana G.; Wu, Yu-Chien; Gao, SujuanOver 5 million older adults have Alzheimer's disease (AD) in the US, and this number is projected to double by 2050. Clinical trials of potential pharmacological treatments for AD have largely shown that once cognitive decline has occurred, targeting AD pathology in the brain does not improve cognition. Therefore, it is likely that the most effective treatments for AD will need to be administered before cognitive symptoms occur, necessitating a biomarker for the early, preclinical stages of AD. Cerebral blood flow (CBF) is a promising early biomarker for AD. CBF is decreased in individuals with AD compared to their normally aging counterparts, and it has been shown that CBF is altered in mild cognitive impairment (MCI) and earlier stages and may occur prior to amyloid or tau aggregation. In addition, CBF can be measured using arterial spin labeled (ASL) MRI, a noninvasive imaging technique that can be safely repeated over time to track prognosis or treatment efficacy. The complex temporal and spatial patterns of altered CBF over the course of AD, as well as the relationships between CBF and AD-specific and -nonspecific factors, will be critical to elucidate in order for CBF to be an effective early biomarker of AD. Here, we begin to characterize the relationships between CBF and risk factors, pathologies, and symptoms of AD. Chapter 1 is a systematic review of published literature that compares CBF in individuals with AD and MCI to CBF in cognitively normal (CN) controls and assesses the relationship between CBF and cognitive function. Chapter 2 reports our original research assessing the relationships between CBF, hypertension, and race/ethnicity in older adults without dementia from the the Indiana Alzheimer’s Disease Research Center (IADRC) and Alzheimer’s Disease Neuroimaging Initiative (ADNI). Chapter 3 reports our original research assessing the relationships between CBF and amyloid beta and tau aggregation measured with PET, as well as whether hypertension or APOEε4 positivity affects these relationships, in older adults without dementia from the IADRC. Chapter 4 reports our original research assessing the relationship between the spatial distribution of tau and subjective memory concerns.Item Choroid Plexus of the Fourth Ventricle: Review and Anatomic Study Highlighting Anatomical Variations(Elsevier, 2016-04) Tubbs, R. Shane; Shoja, Mohammadali M.; Aggarwal, Anjali; Gupta, Tulika; Loukas, Marios; Sahni, Daisy; Ansari, Shaheryar F.; Cohen-Gadol, Aaron A.; Department of Neurological Surgery, IU School of MedicineRelatively few studies have been performed that analyze the morphology of the choroid plexus of the fourth ventricle. Due to the importance of this tissue as a landmark on imaging and during surgical intervention of the fourth ventricle, the authors performed a cadaveric study to better characterize this important structure. The choroid plexus of the fourth ventricle of 60 formalin fixed adult human brains was examined and measured. The horizontal distance from the midline to the lateral most point of the protruding tip of the horizontal limbs was measured. In the majority of the 60 brain specimens, right and left horizontal limbs of the choroid plexus were seen extending from the midline and protruding out of their respective lateral apertures of the fourth ventricle and into the subarachnoid space. However, on 3.3% of sides, there was absence of an extension into the foramen of Luschka and in one specimen, this lack of extension into the foramen of Luschka was bilateral. On two sides, there was discontinuity between the midline choroid plexus and the tuft of choroid just outside the foramen of Luschka. For specimens in which the choroid plexus did protrude through the foramen of Luschka (96.7%), these tufts were located anterior to the flocculus and inferolateral to the facial/vestibulocochlear nerve complex and posterosuperior to the glossopharyngeal/vagal/accessory complex. A thorough understanding of the normal and variant anatomy of the fourth ventricular choroid plexus is necessary for those who operate in, or interpret imaging of, this region.Item Feasibility of Functional Neuroimaging to Understand Adolescent Women’s Sexual Decision Making(Elsevier, 2015-04) Hensel, Devon J.; Hummer, Tom A.; Acrurio, Lindsay R.; James, Thomas W.; Fortenberry, J. Dennis; Department of Pediatrics, Indiana University School of MedicinePurpose For young women, new sexual experiences normatively increase after puberty and coincide with extensive changes to brain regions governing self-regulation of risk behavior. These neurodevelopmental changes could leave some young women vulnerable for negative sexual outcomes, including sexually transmitted infection and unintended pregnancy. We evaluated the feasibility of using functional neuroimaging to understand the sexual decision making of adolescent women. Methods Adolescent women (N = 14; 14–15 years) completed enrollment interviews, a neuroimaging task gauging neural activation to appetitive stimuli, and 30 days of prospective diaries following the scan characterizing daily affect and sexual behaviors. Descriptive and inferential statistics assessed the association between imaging and behavioral data. Results Young women were highly compliant with neuroimaging and diary protocol. Neural activity in a cognitive-affective network, including prefrontal and anterior cingulate regions, was significantly greater during low-risk decisions. Compared with other decisions, high-risk sexual decisions elicited greater activity in the anterior cingulate, and low-risk sexual decision elicited greater activity in regions of the visual cortex. Young women's sexual decision ratings were linked to their sexual history characteristics and daily self-reports of sexual emotions and behaviors. Conclusions It is feasible to recruit and retain a cohort of female participants to perform a functional magnetic resonance imaging task focused on making decisions about sex, on the basis of varying levels of hypothetical sexual risk, and to complete longitudinal prospective diaries following this task. Preliminary evidence suggests that risk level differentially impacts brain activity related to sexual decision making in these women, which may be related to past and future sexual behaviors.Item Indiana Center for Brain Rehabilitation, Advanced Imaging, and Neuroscience (ICBRAIN): An IUPUI Signature Center Initiative(Office of the Vice Chancellor for Research, 2012-04-13) Hammond, Flora; Saykin, Andrew J.; Malec, James; Kean, Jacob; Keiski, Michelle; McDonald, Brenna; Neumann, Dawn; Wang, Yang; Yoder, KarmenThe Mission of the Indiana Center for Brain Rehabilitation, Advanced Imaging, and Neuroscience (ICBRAIN) is: to develop and disseminate techniques and methodologies for advanced neuroimaging and precision behavioral measurement to evaluate novel rehabilitation interventions for people with acquired brain injury. Traumatic and other types of acquired brain injury (ABI) affect millions of U.S. citizens each year, many of whom experience persistent disabilities. For example, among the estimated 1.4 million civilians who sustain a traumatic brain injury (TBI) each year, 50,000 die and a minimum of 80,000 sustain injuries of sufficient severity to require extended rehabilitation. The current conflicts in Iraq and Afghanistan have increased awareness and mobilized interest in medical treatment and rehabilitation for returning soldiers with TBI (designated as the “signature injury” of these conflicts). A 2008 study by the RAND corporation based on a random sample of 1,965 veterans estimated that, among 1.64 million returning veterans, approximately 320,000 experienced a probable TBI (19%). Over the past decade there has been a notable rise in research activities to address serious gaps in the knowledge base of ABI, including neuroimaging, outcome measurement, and intervention studies to change function. However, brain injury researchers have not yet established solid links between these research agendas. Such links are crucial for moving the evidence base forward to improve treatment outcomes. ICBRAIN will fill this gap in neuroscience by bringing together an interdisciplinary team of clinical researchers to (1) advance basic science and clinical knowledge to the next level of integration, (2) translate the knowledge gained directly into clinical care for improved patient outcomes, and (3) use the newly integrated knowledge to drive the leading edge of future research. ICBRAIN represents a unique collaboration among established clinical rehabilitation and measurement researchers in PM&R and at RHI and established researchers at the IU Center for Neuroimaging.