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Item Alzheimer disease brain atrophy subtypes are associated with cognition and rate of decline(American Academy of Neurology, 2017-11-21) Risacher, Shannon L.; Anderson, Wesley H.; Charil, Arnaud; Castelluccio, Peter F.; Shcherbinin, Sergey; Saykin, Andrew J.; Schwarz, Adam J.; Radiology and Imaging Sciences, School of MedicineOBJECTIVE: To test the hypothesis that cortical and hippocampal volumes, measured in vivo from volumetric MRI (vMRI) scans, could be used to identify variant subtypes of Alzheimer disease (AD) and to prospectively predict the rate of clinical decline. METHODS: Amyloid-positive participants with AD from the Alzheimer's Disease Neuroimaging Initiative (ADNI) 1 and ADNI2 with baseline MRI scans (n = 229) and 2-year clinical follow-up (n = 100) were included. AD subtypes (hippocampal sparing [HpSpMRI], limbic predominant [LPMRI], typical AD [tADMRI]) were defined according to an algorithm analogous to one recently proposed for tau neuropathology. Relationships between baseline hippocampal volume to cortical volume ratio (HV:CTV) and clinical variables were examined by both continuous regression and categorical models. RESULTS: When participants were divided categorically, the HpSpMRI group showed significantly more AD-like hypometabolism on 18F-fluorodeoxyglucose-PET (p < 0.05) and poorer baseline executive function (p < 0.001). Other baseline clinical measures did not differ across the 3 groups. Participants with HpSpMRI also showed faster subsequent clinical decline than participants with LPMRI on the Alzheimer's Disease Assessment Scale, 13-Item Subscale (ADAS-Cog13), Mini-Mental State Examination (MMSE), and Functional Assessment Questionnaire (all p < 0.05) and tADMRI on the MMSE and Clinical Dementia Rating Sum of Boxes (CDR-SB) (both p < 0.05). Finally, a larger HV:CTV was associated with poorer baseline executive function and a faster slope of decline in CDR-SB, MMSE, and ADAS-Cog13 score (p < 0.05). These associations were driven mostly by the amount of cortical rather than hippocampal atrophy. CONCLUSIONS: AD subtypes with phenotypes consistent with those observed with tau neuropathology can be identified in vivo with vMRI. An increased HV:CTV ratio was predictive of faster clinical decline in participants with AD who were clinically indistinguishable at baseline except for a greater dysexecutive presentation.Item Deep Tissue Fluorescent Imaging in Scattering Specimens Using Confocal Microscopy(Cambridge University Press, 2011-08) Clendenon, Sherry G.; Young, Pamela A.; Ferkowicz, Michael; Phillips, Carrie; Dunn, Kenneth W.; Department of Pediatrics, IU School of MedicineIn scattering specimens, multiphoton excitation and nondescanned detection improve imaging depth by a factor of 2 or more over confocal microscopy; however, imaging depth is still limited by scattering. We applied the concept of clearing to deep tissue imaging of highly scattering specimens. Clearing is a remarkably effective approach to improving image quality at depth using either confocal or multiphoton microscopy. Tissue clearing appears to eliminate the need for multiphoton excitation for deep tissue imaging.Item Effects of rapid maxillary expansion on the cranial and circummaxillary sutures(Elsevier, 2011-10) Ghoneima, Ahmed; Abdel-Fattah, Ezzat; Hartsfield, James; El-Bedwehi, Ashraf; Kamel, Ayman; Kula, Katherine; Department of Orthodontics and Oral Facial Genetics, IU School of DentistryINTRODUCTION: The aim of this study was to determine whether the orthopedic forces of rapid maxillary expansion cause significant quantitative changes in the cranial and the circummaxillary sutures. METHODS: Twenty patients (mean age, 12.3 ± 1.9 years) who required rapid maxillary expansion as a part of their comprehensive orthodontic treatment had preexpansion and postexpansion computed tomography scans. Ten cranial and circummaxillary sutures were located and measured on one of the axial, coronal, or sagittal sections of each patient's preexpansion and postexpansion computed tomography scans. Quantitative variables between the 2 measurements were compared by using the Wilcoxon signed rank test. A P value less than 0.05 was considered statistically significant. RESULTS: Rapid maxillary expansion produced significant width increases in the intermaxillary, internasal, maxillonasal, frontomaxillary, and frontonasal sutures, whereas the frontozygomatic, zygomaticomaxillary, zygomaticotemporal, and pterygomaxillary sutures showed nonsignificant changes. The greatest increase in width was recorded for the intermaxillary suture (1.7 ± 0.9 mm), followed by the internasal suture (0.6 ± 0.3 mm), and the maxillonasal suture (0.4 ± 0.2 mm). The midpalatal suture showed the greatest increase in width at the central incisor level (1.6 ± 0.8 mm) followed by the increases in width at the canine level (1.5 ± 0.8 mm) and the first molar level (1.2 ± 0.6 mm). CONCLUSIONS: Forces elicited by rapid maxillary expansion affect primarily the anterior sutures (intermaxillary and maxillary frontal nasal interfaces) compared with the posterior (zygomatic interface) craniofacial structures.Item Evaluation of the Treatment Effects of the Functional Regulator of Fränkel in the Correction of Angle Class II Malocclusions(2003) White, Ben G.; Roberts, W. Eugene; Baldwin, James J.; Hartsfield, James K.; Hohlt, William F.; Shanks, James C.One of the greatest challenges an orthodontist faces is the correction of Angle Class II malocclusions. Several different treatment options are available to correct saggital jaw discrepancies that often exist in these individuals. Traditionally, headgear has been used to restrain forward maxillary growth, or to distalize the maxilla. However, there is evidence that suggests that the majority of Class II skeletal relationships are due to a retrusive mandible, rather than a protrusive maxilla. Functional appliances are designed to alter the soft tissue environment of the oral facial capsule creating an environment that allows for optimal growth and development of the teeth, bones, and soft tissue. The functional regulator of Frankel (FR) is a functional appliance that is thought to act through modification of muscle and soft tissue patterns. The design of the FR has a lingual hyperpropulser subjacent to the lingual alveolar mucosa that causes a more forward posture of the mandible. It is thought by some investigators that this forward posture results in enhanced mandibular growth at the condyle which enables correction of Class II skeletal relationships. There is conflicting data regarding the efficacy of the FR at enhancing mandibular growth. Several studies show that the primary mechanisms of Class II molar correction with the FR are restrained maxillary growth, and an increase in the occlusal plane angle. Other investigations have shown enhanced mandibular growth (measured from condylion to gnathion) to be the primary mechanism of Class II correction with the FR. Due to the conflicting data that exists regarding the FR, the current study was conducted to further elucidate the treatment effects of this appliance. Fifty cases that met the inclusion criteria of the study were randomly selected from the patient files of a private practitioner experienced with the clinical management of the FR. In order to determine the treatment effects of the FR, cephalometric analysis, as well as composite and regional superimpositions were completed. The mean change from pre- to posttreatment of the experimental group was compared to the published data of untreated Class II individuals from the University of Michigan Growth Study using a two sample t-test. The radiographs were also scanned and digitized using the Dolphin™ imaging software to determine whether the manual tracing technique was similar to the digital tracing technique by using an ANOVA with fixed effects for method, time point, method by time point interaction, and a random effect for patient. The null hypotheses for this investigation were: 1) There are no statistically significant differences (p<0.05) in the cephalometric measurements between the experimental FR group and an untreated Class II control group. In particular, there are no significant differences (P<0.05) in mean mandibular length change (Condylion-Gnathion) from pre-treatment to post-treatment between the FR treated group and controls. 2) There is no statistically significant difference (p<0.05) between the cephalometric measurements obtained from manually traced and measured cephalograms, and those obtained utilizing the Dolphin™ imaging system. The results of this study showed a statistically significant difference (p<0.02) in all cephalometric parameters indicative of enhanced mandibular growth in the FR group. Additionally, the intermaxillary relationship was found to be significantly improved in the FR treated group (p<0.01) relative to controls. These findings are similar to those reported by other investigators who have found that the FR is capable of improving the sagittal jaw relationship of Class II individuals, and that a large portion of this correction is due to enhanced mandibular growth. The present study also found statistically significant differences between the experimental group and controls for several other cephalometric categories. The appliance had a statistically significant (p<0.05) restraining influence on the forward growth of the maxilla which has been previously described as the "headgear effect". The effect the FR has on the dentition was also assessed. The present investigation found that the FR causes significant (p<0.01) flaring of the lower incisors (2.0° from pre- to posttreatment), as well as a significant (p<0.0001) reduction in the axial inclination of the upper incisors (-3.2° from pre- to post-treatment). Further, it was found through regional superimpositions that the FR resulted in significant (p<0.05) posterior movement of the upper incisors (-0.4mm from pre- to post-treatment), as well as forward movement of the lower incisors (0.8mm from pre- to post-treatment). It was found that the appliance had no statistically significant (p<0.05) effect on the sagittal movement of the upper or lower molars. The FR treated group also showed statistically significant changes in vertical cephalometric measurements. The FR group had a significantly (p<0.05) increased posterior face height (2 .5mm from pre- to post-treatment), mandibular plane angle (0.4° from pre-to post-treatment), and occlusal plane angle (0.7° from pre- to post-treatment) relative to the control group. With the exception of increased posterior face height, the increases in the other vertical cephalometric measurements are thought to be deleterious side-effects of FR therapy that may impact Class II correction, and facial esthetics. The results of the comparison of the two measurement techniques showed that in general the measurements between the two methods were similar. Only one cephalometric measurement (Co-Gn) showed a significant difference (p<0.0001) between the two methods at both time points. The intraclass correlation coefficients were found to be greater than 0.80 for all cephalometric measurements made with the exception of the occlusal plane angle (OP), and upper incisor to the SN line (1/-SN). The present study further demonstrates the ability of functional appliances to increase mandibular length. The present investigation is one of the few studies that have conducted pre- to post-treatment superimpositions to determine the treatment effects of the functional regulator of Frankel. To the author's knowledge this investigation is the first to make a comparison between manually traced and measured cephalometric measurements and those made with Dolphin™ imaging. Although several measurements were found to be statistically different between the two measurement techniques, these differences are generally less than 1 mm or 1 degree. Therefore, the difference between the two measurement techniques is not likely to be clinically significant.Item Identifying the neuroanatomical basis of cognitive impairment in Alzheimer's disease by correlation- and nonlinearity-aware sparse Bayesian learning(Institute of Electrical and Electronics Engineers, 2014-07) Wan, Jing; Zhang, Zhilin; Rao, Bhaskar D.; Fang, Shiaofen; Yan, Jingwen; Saykin, Andrew J.; Shen, Li; Department of Medicine, IU School of MedicinePredicting cognitive performance of subjects from their magnetic resonance imaging (MRI) measures and identifying relevant imaging biomarkers are important research topics in the study of Alzheimer's disease. Traditionally, this task is performed by formulating a linear regression problem. Recently, it is found that using a linear sparse regression model can achieve better prediction accuracy. However, most existing studies only focus on the exploitation of sparsity of regression coefficients, ignoring useful structure information in regression coefficients. Also, these linear sparse models may not capture more complicated and possibly nonlinear relationships between cognitive performance and MRI measures. Motivated by these observations, in this work we build a sparse multivariate regression model for this task and propose an empirical sparse Bayesian learning algorithm. Different from existing sparse algorithms, the proposed algorithm models the response as a nonlinear function of the predictors by extending the predictor matrix with block structures. Further, it exploits not only inter-vector correlation among regression coefficient vectors, but also intra-block correlation in each regression coefficient vector. Experiments on the Alzheimer's Disease Neuroimaging Initiative database showed that the proposed algorithm not only achieved better prediction performance than state-of-the-art competitive methods, but also effectively identified biologically meaningful patterns.Item International Cognition and Cancer Task Force Recommendations for Neuroimaging Methods in the Study of Cognitive Impairment in Non-CNS Cancer Patients(Oxford University Press, 2018-03) Deprez, Sabine; Kesler, Shelli R.; Saykin, Andrew J.; Silverman, Daniel H. S.; de Ruiter, Michiel B.; McDonald, Brenna C.; Radiology & Imaging Sciences, IU School of MedicineCancer- and treatment-related cognitive changes have been a focus of increasing research since the early 1980s, with meta-analyses demonstrating poorer performance in cancer patients in cognitive domains including executive functions, processing speed, and memory. To facilitate collaborative efforts, in 2011 the International Cognition and Cancer Task Force (ICCTF) published consensus recommendations for core neuropsychological tests for studies of cancer populations. Over the past decade, studies have used neuroimaging techniques, including structural and functional magnetic resonance imaging (fMRI) and positron emission tomography, to examine the underlying brain basis for cancer- and treatment-related cognitive declines. As yet, however, there have been no consensus recommendations to guide researchers new to this field or to promote the ability to combine data sets. We first discuss important methodological issues with regard to neuroimaging study design, scanner considerations, and sequence selection, focusing on concerns relevant to cancer populations. We propose a minimum recommended set of sequences, including a high-resolution T1-weighted volume and a resting state fMRI scan. Additional advanced imaging sequences are discussed for consideration when feasible, including task-based fMRI and diffusion tensor imaging. Important image data processing and analytic considerations are also reviewed. These recommendations are offered to facilitate increased use of neuroimaging in studies of cancer- and treatment-related cognitive dysfunction. They are not intended to discourage investigator-initiated efforts to develop cutting-edge techniques, which will be helpful in advancing the state of the knowledge. Use of common imaging protocols will facilitate multicenter and data-pooling initiatives, which are needed to address critical mechanistic research questions.Item Robust estimation of fractal measures for characterizing the structural complexity of the human brain: optimization and reproducibility(Elsevier, 2013-12) Goñi, Joaquín; Sporns, Olaf; Cheng, Hu; Aznárez-Sanado, Maite; Wang, Yang; Josa, Santiago; Arrondo, Gonzalo; Mathews, Vincent P; Hummer, Tom A; Kronenberger, William G; Avena-Koenigsberger, Andrea; Saykin, Andrew J.; Pastor, María A.; Department of Radiology and Imaging Sciences, IU School of MedicineHigh-resolution isotropic three-dimensional reconstructions of human brain gray and white matter structures can be characterized to quantify aspects of their shape, volume and topological complexity. In particular, methods based on fractal analysis have been applied in neuroimaging studies to quantify the structural complexity of the brain in both healthy and impaired conditions. The usefulness of such measures for characterizing individual differences in brain structure critically depends on their within-subject reproducibility in order to allow the robust detection of between-subject differences. This study analyzes key analytic parameters of three fractal-based methods that rely on the box-counting algorithm with the aim to maximize within-subject reproducibility of the fractal characterizations of different brain objects, including the pial surface, the cortical ribbon volume, the white matter volume and the grey matter/white matter boundary. Two separate datasets originating from different imaging centers were analyzed, comprising, 50 subjects with three and 24 subjects with four successive scanning sessions per subject, respectively. The reproducibility of fractal measures was statistically assessed by computing their intra-class correlations. Results reveal differences between different fractal estimators and allow the identification of several parameters that are critical for high reproducibility. Highest reproducibility with intra-class correlations in the range of 0.9–0.95 is achieved with the correlation dimension. Further analyses of the fractal dimensions of parcellated cortical and subcortical gray matter regions suggest robustly estimated and region-specific patterns of individual variability. These results are valuable for defining appropriate parameter configurations when studying changes in fractal descriptors of human brain structure, for instance in studies of neurological diseases that do not allow repeated measurements or for disease-course longitudinal studies.