Can Ceritoglu

YNICL Journal 2023 Journal Article

Early amygdala and ERC atrophy linked to 3D reconstruction of rostral neurofibrillary tau tangle pathology in Alzheimer’s disease

• Kaitlin M. Stouffer
• Claire Chen
• Sue Kulason
• Eileen Xu
• Menno P. Witter
• Can Ceritoglu
• Marilyn S. Albert
• Susumu Mori

Previous research has emphasized the unique impact of Alzheimer's Disease (AD) pathology on the medial temporal lobe (MTL), a reflection that tau pathology is particularly striking in the entorhinal and transentorhinal cortex (ERC, TEC) early in the course of disease. However, other brain regions are affected by AD pathology during its early phases. Here, we use longitudinal diffeomorphometry to measure the atrophy rate from MRI of the amygdala compared with that in the ERC and TEC in cognitively unimpaired (CU) controls, CU individuals who progressed to mild cognitive impairment (MCI), and individuals with MCI who progressed to dementia of the AD type (DAT), using a dataset from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Our results show significantly higher atrophy rates of the amygdala in both groups of 'converters' (CU→MCI, MCI→DAT) compared to controls, with rates of volume loss comparable to rates of thickness loss in the ERC and TEC. We localize atrophy within the amygdala within each of these groups using fixed effects modeling. Controlling for the familywise error rate highlights the medial regions of the amygdala as those with significantly higher atrophy in both groups of converters than in controls. Using our recently developed method, referred to as Projective LDDMM, we map measures of neurofibrillary tau tangles (NFTs) from digital pathology to MRI atlases and reconstruct dense 3D spatial distributions of NFT density within regions of the MTL. The distribution of NFTs is consistent with the spatial distribution of MR measured atrophy rates, revealing high densities (and atrophy) in the amygdala (particularly medial), ERC, and rostral third of the MTL. The similarity of the location of NFTs in AD and shape changes in a well-defined clinical population suggests that amygdalar atrophy rate, as measured through MRI may be a viable biomarker for AD.

YNIMG Journal 2019 Journal Article

Multi-atlas tool for automated segmentation of brain gray matter nuclei and quantification of their magnetic susceptibility

• Xu Li
• Lin Chen
• Kwame Kutten
• Can Ceritoglu
• Yue Li
• Ningdong Kang
• John T. Hsu
• Ye Qiao

Quantification of tissue magnetic susceptibility using MRI offers a non-invasive measure of important tissue components in the brain, such as iron and myelin, potentially providing valuable information about normal and pathological conditions during aging. Despite many advances made in recent years on imaging techniques of quantitative susceptibility mapping (QSM), accurate and robust automated segmentation tools for QSM images that can help generate universal and sharable susceptibility measures in a biologically meaningful set of structures are still not widely available. In the present study, we developed an automated process to segment brain nuclei and quantify tissue susceptibility in these regions based on a susceptibility multi-atlas library, consisting of 10 atlases with T1-weighted images, gradient echo (GRE) magnitude images and QSM images of brains with different anatomic patterns. For each atlas in this library, 10 regions of interest in iron-rich deep gray matter structures that are better defined by QSM contrast were manually labeled, including caudate, putamen, globus pallidus internal/external, thalamus, pulvinar, subthalamic nucleus, substantia nigra, red nucleus and dentate nucleus in both left and right hemispheres. We then tested different pipelines using different combinations of contrast channels to bring the set of labels from the multi-atlases to each target brain and compared them with the gold standard manual delineation. The results showed that the segmentation accuracy using dual contrasts QSM/T1 pipeline outperformed other dual-contrast or single-contrast pipelines. The dice values of 0. 77 ± 0. 09 using the QSM/T1 multi-atlas pipeline rivaled with the segmentation reliability obtained from multiple evaluators with dice values of 0. 79 ± 0. 07 and gave comparable or superior performance in segmenting subcortical nuclei in comparison with standard FSL FIRST or recent multi-atlas package of volBrain. The segmentation performance of the QSM/T1 multi-atlas was further tested on QSM images acquired using different acquisition protocols and platforms and showed good reliability and reproducibility with average dice of 0. 79 ± 0. 08 to manual labels and 0. 89 ± 0. 04 in an inter-protocol manner. The extracted quantitative magnetic susceptibility values in the deep gray matter nuclei also correlated well between different protocols with inter-protocol correlation constants all larger than 0. 97. Such reliability and performance was ultimately validated in an external dataset acquired at another study site with consistent susceptibility measures obtained using the QSM/T1 multi-atlas approach in comparison to those using manual delineation. In summary, we designed a susceptibility multi-atlas tool for automated and reliable segmentation of QSM images and for quantification of magnetic susceptibilities. It is publicly available through our cloud-based platform (www. mricloud. org). Further improvement on the performance of this multi-atlas tool is expected by increasing the number of atlases in the future.

YNICL Journal 2016 Journal Article

Direct estimation of patient attributes from anatomical MRI based on multi-atlas voting

• Dan Wu
• Can Ceritoglu
• Michael I. Miller
• Susumu Mori

MRI brain atlases are widely used for automated image segmentation, and in particular, recent developments in multi-atlas techniques have shown highly accurate segmentation results. In this study, we extended the role of the atlas library from mere anatomical reference to a comprehensive knowledge database with various patient attributes, such as demographic, functional, and diagnostic information. In addition to using the selected (heavily-weighted) atlases to achieve high segmentation accuracy, we tested whether the non-anatomical attributes of the selected atlases could be used to estimate patient attributes. This can be considered a context-based image retrieval (CBIR) approach, embedded in the multi-atlas framework. We first developed an image similarity measurement to weigh the atlases on a structure-by-structure basis, and then, the attributes of the multiple atlases were weighted to estimate the patient attributes. We tested this concept first by estimating age in a normal population; we then performed functional and diagnostic estimations in Alzheimer's disease patients. The accuracy of the estimated patient attributes was measured against the actual clinical data, and the performance was compared to conventional volumetric analysis. The proposed CBIR framework by multi-atlas voting would be the first step toward a knowledge-based support system for quantitative radiological image reading and diagnosis.

YNIMG Journal 2016 Journal Article

Resource atlases for multi-atlas brain segmentations with multiple ontology levels based on T1-weighted MRI

• Dan Wu
• Ting Ma
• Can Ceritoglu
• Yue Li
• Jill Chotiyanonta
• Zhipeng Hou
• John Hsu
• Xin Xu

Technologies for multi-atlas brain segmentation of T1-weighted MRI images have rapidly progressed in recent years, with highly promising results. This approach, however, relies on a large number of atlases with accurate and consistent structural identifications. Here, we introduce our atlas inventories (n=90), which cover ages 4–82years with unique hierarchical structural definitions (286 structures at the finest level). This multi-atlas library resource provides the flexibility to choose appropriate atlases for various studies with different age ranges and structure-definition criteria. In this paper, we describe the details of the atlas resources and demonstrate the improved accuracy achievable with a dynamic age-matching approach, in which atlases that most closely match the subject's age are dynamically selected. The advanced atlas creation strategy, together with atlas pre-selection principles, is expected to support the further development of multi-atlas image segmentation.

YNIMG Journal 2014 Journal Article

A Bayesian approach to the creation of a study-customized neonatal brain atlas

• Yajing Zhang
• Linda Chang
• Can Ceritoglu
• Jon Skranes
• Thomas Ernst
• Susumu Mori
• Michael I. Miller
• Kenichi Oishi

Atlas-based image analysis (ABA), in which an anatomical “parcellation map” is used for parcel-by-parcel image quantification, is widely used to analyze anatomical and functional changes related to brain development, aging, and various diseases. The parcellation maps are often created based on common MRI templates, which allow users to transform the template to target images, or vice versa, to perform parcel-by-parcel statistics, and report the scientific findings based on common anatomical parcels. The use of a study-specific template, which represents the anatomical features of the study population better than common templates, is preferable for accurate anatomical labeling; however, the creation of a parcellation map for a study-specific template is extremely labor intensive, and the definitions of anatomical boundaries are not necessarily compatible with those of the common template. In this study, we employed a volume-based template estimation (VTE) method to create a neonatal brain template customized to a study population, while keeping the anatomical parcellation identical to that of a common MRI atlas. The VTE was used to morph the standardized parcellation map of the JHU-neonate-SS atlas to capture the anatomical features of a study population. The resultant “study-customized” T1-weighted and diffusion tensor imaging (DTI) template, with three-dimensional anatomical parcellation that defined 122 brain regions, was compared with the JHU-neonate-SS atlas, in terms of the registration accuracy. A pronounced increase in the accuracy of cortical parcellation and superior tensor alignment were observed when the customized template was used. With the customized atlas-based analysis, the fractional anisotropy (FA) detected closely approximated the manual measurements. This tool provides a solution for achieving normalization-based measurements with increased accuracy, while reporting scientific findings in a consistent framework.

YNIMG Journal 2014 Journal Article

Tools for multiple granularity analysis of brain MRI data for individualized image analysis

• Aigerim Djamanakova
• Xiaoying Tang
• Xin Li
• Andreia V. Faria
• Can Ceritoglu
• Kenichi Oishi
• Argye E. Hillis
• Marilyn Albert

Voxel-based analysis is widely used for quantitative analysis of brain MRI. While this type of analysis provides the highest granularity level of spatial information (i. e. , each voxel), the sheer number of voxels and noisy information from each voxel often lead to low sensitivity for detection of abnormalities. To ameliorate this issue, granularity reduction is commonly performed by applying isotropic spatial filtering. This study proposes a systematic reduction of the spatial information using ontology-based hierarchical structural relationships. The 254 brain structures were first defined in multiple (n =29) geriatric atlases. The multiple atlases were then applied to T1-weighted MR images of each subject's data for automated brain parcellation and five levels of ontological relationships were established, which further reduced the spatial dimension to as few as 11 structures. At each ontology level, the amount of atrophy was evaluated, providing a unique view of low-granularity analysis. This reduction of spatial information allowed us to investigate the anatomical features of each patient, demonstrated in an Alzheimer's disease group.

YNIMG Journal 2009 Journal Article

Multi-contrast large deformation diffeomorphic metric mapping for diffusion tensor imaging

• Can Ceritoglu
• Kenichi Oishi
• Xin Li
• Ming-Chung Chou
• Laurent Younes
• Marilyn Albert
• Constantine Lyketsos
• Peter C.M. van Zijl