Corinna M. Bauer

The EADC-ADNI Harmonized Protocol for manual hippocampal segmentation on magnetic resonance: Evidence of validity

An international Delphi panel has defined a harmonized protocol (HarP) for the manual segmentation of the hippocampus on MR. The aim of this study is to study the concurrent validity of the HarP toward local protocols, and its major sources of variance.

Whole brain quantitative T2 MRI across multiple scanners with dual echo FSE: Applications to AD, MCI, and normal aging

The ability to pool data from multiple MRI scanners is becoming increasingly important with the influx in multi-site research studies. Fast spin echo (FSE) dual spin echo sequences are often chosen for such studies based principally on their short acquisition time and the clinically useful contrasts they provide for assessing gross pathology. The practicality of measuring FSE-T2 relaxation properties has rarely been assessed. Here, FSE-T2 relaxation properties are examined across the three main scanner vendors (General Electric (GE), Philips, and Siemens). The American College of Radiology (ACR) phantom was scanned on four 1.5T platforms (two GE, one Philips, and one Siemens) to determine if the dual echo pulse sequence is susceptible to vendor-based variance. In addition, data from 85 subjects spanning the spectrum of normal aging, mild cognitive impairment (MCI), and Alzheimers disease (AD) was obtained from the Alzheimers Disease Neuroimaging Initiative (ADNI) to affirm the presence of any phantom based between vendor variance and determine the relationship between this variance and disease. FSE-T2 relaxation properties, including peak FSE-T2 and histogram width, were calculated for each phantom and human subject. Direct correspondence was found between the phantom and human subject data. Peak FSE-T2 of Siemens scanners was consistently at least 20ms prolonged compared to GE and Philips. Siemens scanners showed broader FSE-T2 histograms than the other scanners. Greater variance was observed across GE scanners than either Philips or Siemens. FSE-T2 differences were much greater with scanner vendor than between diagnostic groups, as no significant changes in peak FSE-T2 or histogram width between normal aged, MCI, and AD subject groups were observed. These results indicate that whole brain histogram measures are not sensitive enough to detect FSE-T2 changes between normal aging, MCI, and AD and that FSE-T2 is highly variable across scanner vendors.

Neural correlates associated with superior tactile symmetry perception in the early blind

Symmetry is an organizational principle that is ubiquitous throughout the visual world. However, this property can also be detected through non-visual modalities such as touch. The role of prior visual experience on detecting tactile patterns containing symmetry remains unclear. We compared the behavioral performance of early blind and sighted (blindfolded) controls on a tactile symmetry detection task. The tactile patterns used were similar in design and complexity as in previous visual perceptual studies. The neural correlates associated with this behavioral task were identified with functional magnetic resonance imaging (fMRI). In line with growing evidence demonstrating enhanced tactile processing abilities in the blind, we found that early blind individuals showed significantly superior performance in detecting tactile symmetric patterns compared to sighted controls. Furthermore, comparing patterns of activation between these two groups identified common areas of activation (e.g. superior parietal cortex) but key differences also emerged. In particular, tactile symmetry detection in the early blind was also associated with activation that included peri-calcarine cortex, lateral occipital (LO), and middle temporal (MT) cortex, as well as inferior temporal and fusiform cortex. These results contribute to the growing evidence supporting superior behavioral abilities in the blind, and the neural correlates associated with crossmodal neuroplasticity following visual deprivation.

Differentiating between Normal Aging, Mild Cognitive Impairment, and AlzheimerâÂÂs disease with FDG-PET: Effects of Normalization Region and Partial Volume Correction Method

Objective: In Alzheimer’s FDG PET research, the choice of reference region for normalization and use of partial volume correction are inconsistent and have not been studied in a large multi-center study. Herein, we identified which normalization region provided the highest degree of discrimination between subjects who were classified as normal aging, mild cognitive impairment, or Alzheimer’s disease. The effects of partial volume correction using either a gray matter mask or cortical thickness and subcortical volume residuals were also examined. Methods: Stepwise logistic regression models were used to identify the optimal normalization region and partial volume correction method to discriminate between disease stages in over 400 subjects from research sites across North America. Normalization region candidates were the brainstem, precentral gyrus, postcentral gyrus, cerebellum, and thalamus. Partial volume correction methods tested were anatomically or statistically based. Results: Pre- and post- central gyri, and the thalamus showed AD-related changes in FDG PET and did not qualify for further testing. Normalizing to the cerebellum while using the gray matter mask for partial volume correction provided the highest indicator of discrimination. Conclusions: Normalization region and partial volume correction are critical to FDG PET analysis and candidate normalization regions should be tested for disease effects in the study sample prior to use. Cerebellar normalization and gray matter mask partial volume correction are recommended for use with the ADNI dataset.

Cerebral versus Ocular Visual Impairment: The Impact on Developmental Neuroplasticity.

Cortical/cerebral visual impairment (CVI) is clinically defined as significant visual dysfunction caused by injury to visual pathways and structures occurring during early perinatal development. Depending on the location and extent of damage, children with CVI often present with a myriad of visual deficits including decreased visual acuity and impaired visual field function. Most striking, however, are impairments in visual processing and attention which have a significant impact on learning, development, and independence. Within the educational arena, current evidence suggests that strategies designed for individuals with ocular visual impairment are not effective in the case of CVI. We propose that this variance may be related to differences in compensatory neuroplasticity related to the type of visual impairment, as well as underlying alterations in brain structural connectivity. We discuss the etiology and nature of visual impairments related to CVI, and how advanced neuroimaging techniques (i.e., diffusion-based imaging) may help uncover differences between ocular and cerebral causes of visual dysfunction. Revealing these differences may help in developing future strategies for the education and rehabilitation of individuals living with visual impairment.

Age-related relaxo-volumetric quantitative magnetic resonance imaging of the major salivary glands.

Objective To study age-related characteristics of T1 and T2 relaxation times and volume of the major salivary glands. Methods Thirty-five subjects (0.5–87 years old) with normal salivary glands were imaged with mixed turbo spin-echo pulse sequences at 1.5-T magnetic resonance units. Bilateral parotid, submandibular, and sublingual glands were segmented manually. Histograms for each salivary gland were generated and modeled with Gaussian functions for every parameter. Results Seventy parotid glands, 52 submandibular glands, and 50 sublingual glands were segmented and the histograms were analyzed. The parotid gland exhibited shorter-peak T1s and longer-peak T2s relative to the submandibular and sublingual glands. The peak T2s for all glands showed a minimum value between 2 and 4 years of age and increased monotonically thereafter. From birth to early adulthood, all glands increased in size logarithmically. Conclusion Age-related relaxo-volumetric changes of the major salivary glands show clear T2 and volumetric age-related patterns for all glands.

Abnormal white matter tractography of visual pathways detected by high-angular-resolution diffusion imaging (HARDI) corresponds to visual dysfunction in cortical/cerebral visual impairment.

Cortical (cerebral) visual impairment (CVI) is characterized by visual dysfunction associated with damage to the optic radiations and/or visual cortex. Typically it results from pre- or perinatal hypoxic damage to postchiasmal visual structures and pathways. The neuroanatomical basis of this condition remains poorly understood, particularly with regard to how the resulting maldevelopment of visual processing pathways relates to observations in the clinical setting. We report our investigation of 2 young adults diagnosed with CVI and visual dysfunction characterized by difficulties related to visually guided attention and visuospatial processing. Using high-angular-resolution diffusion imaging (HARDI), we characterized and compared their individual white matter projections of the extrageniculo-striate visual system with a normal-sighted control. Compared to a sighted control, both CVI cases revealed a striking reduction in association fibers, including the inferior frontal-occipital fasciculus as well as superior and inferior longitudinal fasciculi. This reduction in fibers associated with the major pathways implicated in visual processing may provide a neuroanatomical basis for the visual dysfunctions observed in these patients.

Multimodal MR-imaging reveals large-scale structural and functional connectivity changes in profound early blindness

In the setting of profound ocular blindness, numerous lines of evidence demonstrate the existence of dramatic anatomical and functional changes within the brain. However, previous studies based on a variety of distinct measures have often provided inconsistent findings. To help reconcile this issue, we used a multimodal magnetic resonance (MR)-based imaging approach to provide complementary structural and functional information regarding this neuroplastic reorganization. This included gray matter structural morphometry, high angular resolution diffusion imaging (HARDI) of white matter connectivity and integrity, and resting state functional connectivity MRI (rsfcMRI) analysis. When comparing the brains of early blind individuals to sighted controls, we found evidence of co-occurring decreases in cortical volume and cortical thickness within visual processing areas of the occipital and temporal cortices respectively. Increases in cortical volume in the early blind were evident within regions of parietal cortex. Investigating white matter connections using HARDI revealed patterns of increased and decreased connectivity when comparing both groups. In the blind, increased white matter connectivity (indexed by increased fiber number) was predominantly left-lateralized, including between frontal and temporal areas implicated with language processing. Decreases in structural connectivity were evident involving frontal and somatosensory regions as well as between occipital and cingulate cortices. Differences in white matter integrity (as indexed by quantitative anisotropy, or QA) were also in general agreement with observed pattern changes in the number of white matter fibers. Analysis of resting state sequences showed evidence of both increased and decreased functional connectivity in the blind compared to sighted controls. Specifically, increased connectivity was evident between temporal and inferior frontal areas. Decreases in functional connectivity were observed between occipital and frontal and somatosensory-motor areas and between temporal (mainly fusiform and parahippocampus) and parietal, frontal, and other temporal areas. Correlations in white matter connectivity and functional connectivity observed between early blind and sighted controls showed an overall high degree of association. However, comparing the relative changes in white matter and functional connectivity between early blind and sighted controls did not show a significant correlation. In summary, these findings provide complimentary evidence, as well as highlight potential contradictions, regarding the nature of regional and large scale neuroplastic reorganization resulting from early onset blindness.

Characterizing Visual Field Deficits in Cerebral/Cortical Visual Impairment (CVI) Using Combined Diffusion Based Imaging and Functional Retinotopic Mapping: A Case Study

Cortical/cerebral visual impairment (CVI) is the leading cause of pediatric visual impairment in children in developed countries and has become a significant public health concern (Kong et al., 2012). CVI is clinically defined as significant visual dysfunction resulting primarily from perinatal injury to visual pathways and structures rather than ocular pathology alone (Dutton, 2003). Perinatal hypoxia is the most common cause resulting in impaired maturation of key visual pathways such as the optic radiations; a general condition referred to as white matter damage of immaturity (WMDI). In preterm infants, this maldevelopment is often associated with periventricular leukomalacia (PVL), which is characterized by an enlargement of the lateral ventricles and focal gliosis of surrounding white matter pathways coursing on to the visual cortex (Good et al., 2001; Hoyt, 2007). Depending on the location and extent of the damage, children with CVI often present with a broad range and combination of visual dysfunctions such as decreased visual acuity, visual field deficits, and also impairments in oculomotor, visuomotor, and cognitive visual processing (Good et al., 2001; Dutton, 2003; Hoyt, 2007). The variability in the location and extent of brain injury across individuals makes the prediction of visual functional outcomes and recovery in CVI patients particularly challenging (McKillop and Dutton, 2008). Despite the increasing prevalence of this condition, the relationship between observed visual deficits in CVI and the underlying structural and functional changes resulting from damage to key visual pathways, remains poorly understood. Specifically, it remains unknown how the maldevelopment of key visual pathways relates to the organization of the visual cortex and further, how these structural and functional changes relate to visual impairments observed within the clinical setting. Standard clinical neuroimaging techniques such as computerized tomography (CT) and magnetic resonance imaging (MRI) can help characterize gross changes in cerebral structure. However, the underlying micro-architecture of key white matter pathways (such as the optic radiations) cannot be fully ascertained, nor can the function of visual cortical areas be assessed. Advances in diffusion based imaging (i.e., diffusion MRI) modalities such as high angular resolution diffusion based imaging (HARDI) combined with tractography analysis techniques can be used to reveal the organization of specific white matter projections (Jones, 2008) see also (Ffytche et al., 2010). At the same time, retinotopic mapping using functional magnetic resonance imaging (fMRI) can be employed to assess the organizational and functional integrity of early visual cortical areas (Wandell, 1999). In this study, we used a combined structural and functional multi-modal neuroimaging approach to characterize the underlying maldevelopment of the geniculo-striate pathway in an adolescent with CVI. The patient presented here had a documented inferior visual field deficit determined on clinical ophthalmic examination. Despite her diagnosis of CVI and associated visual impairments, she was able to participate in formal testing and provide reliable data (including maintaining fixation during perimetry and retinotopic stimulation) and also remain immobile in the scanner environment without the need of anesthesia. Thus, (and contrary to prior imaging studies with CVI individuals), we had the opportunity to obtain high quality structural and functional imaging data on the same subject in order to investigate the relationship between the structural integrity of the optic radiations and the functional organization of early visual cortical areas with respect to her clinical visual field impairment. We demonstrate the feasibility of combining this structural and functional imaging approach in a patient with CVI along with an age/gender matched normal developed control for comparison. By combining these imaging modalities, it is possible to provide further insight regarding the functional manifestations of early onset developmental damage to key visual pathways and their relation to specific impairments of visual function.

Multimodal Discrimination between Normal Aging, Mild Cognitive Impairment and Alzheimer’s Disease and Prediction of Cognitive Decline

Alzheimer’s Disease (AD) and mild cognitive impairment (MCI) are associated with widespread changes in brain structure and function, as indicated by magnetic resonance imaging (MRI) morphometry and 18-fluorodeoxyglucose position emission tomography (FDG PET) metabolism. Nevertheless, the ability to differentiate between AD, MCI and normal aging groups can be difficult. Thus, the goal of this study was to identify the combination of cerebrospinal fluid (CSF) biomarkers, MRI morphometry, FDG PET metabolism and neuropsychological test scores to that best differentiate between a sample of normal aging subjects and those with MCI and AD from the Alzheimer’s Disease Neuroimaging Initiative. The secondary goal was to determine the neuroimaging variables from MRI, FDG PET and CSF biomarkers that can predict future cognitive decline within each group. To achieve these aims, a series of multivariate stepwise logistic and linear regression models were generated. Combining all neuroimaging modalities and cognitive test scores significantly improved the index of discrimination, especially at the earliest stages of the disease, whereas MRI gray matter morphometry variables best predicted future cognitive decline compared to other neuroimaging variables. Overall these findings demonstrate that a multimodal approach using MRI morphometry, FDG PET metabolism, neuropsychological test scores and CSF biomarkers may provide significantly better discrimination than any modality alone.