Parnesh Raniga

Amyloid imaging results, from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging

The Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging, a participant of the worldwide Alzheimers Disease Neuroimaging Initiative (ADNI), performed (11)C-Pittsburgh Compound B (PiB) scans in 177 healthy controls (HC), 57 mild cognitive impairment (MCI) subjects, and 53 mild Alzheimers disease (AD) patients. High PiB binding was present in 33% of HC (49% in ApoE-epsilon4 carriers vs 21% in noncarriers) and increased with age, most strongly in epsilon4 carriers. 18% of HC aged 60-69 had high PiB binding rising to 65% in those over 80 years. Subjective memory complaint was only associated with elevated PiB binding in epsilon4 carriers. There was no correlation with cognition in HC or MCI. PiB binding in AD was unrelated to age, hippocampal volume or memory. Beta-amyloid (Abeta) deposition seems almost inevitable with advanced age, amyloid burden is similar at all ages in AD, and secondary factors or downstream events appear to play a more direct role than total beta amyloid burden in hippocampal atrophy and cognitive decline.

Appearance modeling of 11C PiB PET images : Characterizing amyloid deposition in Alzheimer's disease, mild cognitive impairment and healthy aging

Beta-amyloid (Abeta) deposition is one of the neuropathological hallmarks of Alzheimers disease (AD), Abeta burden can be quantified using (11)C PiB PET. Neuropathological studies have shown that the initial plaques are located in the temporal and orbitofrontal cortices, extending later to the cingulate, frontal and parietal cortices (Braak and Braak, 1997). Previous studies have shown an overlap in (11)C PiB PET retention between AD, mild cognitive impairment (MCI) patients and normal elderly control (NC) participants. It has also been shown that there is a relationship between Abeta deposition and memory impairment in MCI patients. In this paper we explored the variability seen in 15 AD, 15 MCI and 18 NC by modeling the voxel data from spatially and uptake normalized PiB images using principal component analysis. The first two principal components accounted for 80% of the variability seen in the data, providing a clear separation between AD and NC, and allowing subsequent classification. The MCI cases were distributed along an apparent axis between the AD and NC group, closely aligned with the first principal component axis. The NC cases that were PiB(+) formed a distinct cluster that was between, but separated from the AD and PiB(-) NC clusters. The PiB(+) MCI were found to cluster with the AD cases, and exhibited a similar deposition pattern. The primary principal component score was found to correlate with episodic memory scores and mini mental status examination and it was observed that by varying the first principal component, a change in amyloid deposition could be derived that is similar to the expected progression of amyloid deposition observed from post mortem studies.

Patient Specific Prostate Segmentation in 3-D Magnetic Resonance Images

Accurate localization of the prostate and its surrounding tissue is essential in the treatment of prostate cancer. This paper presents a novel approach to fully automatically segment the prostate, including its seminal vesicles, within a few minutes of a magnetic resonance (MR) scan acquired without an endorectal coil. Such MR images are important in external beam radiation therapy, where using an endorectal coil is highly undesirable. The segmentation is obtained using a deformable model that is trained on-the-fly so that it is specific to the patients scan. This case specific deformable model consists of a patient specific initialized triangulated surface and image feature model that are trained during its initialization. The image feature model is used to deform the initialized surface by template matching image features (via normalized cross-correlation) to the features of the scan. The resulting deformations are regularized over the surface via well established simple surface smoothing algorithms, which is then made anatomically valid via an optimized shape model. Mean and median Dices similarity coefficients (DSCs) of 0.85 and 0.87 were achieved when segmenting 3T MR clinical scans of 50 patients. The median DSC result was equal to the inter-rater DSC and had a mean absolute surface error of 1.85 mm. The approach is showed to perform well near the apex and seminal vesicles of the prostate.

18F-florbetaben Aβ imaging in mild cognitive impairment

Introduction18F-florbetaben and positron emission tomography were used to examine the relationships between β-amyloid (Aβ) deposition, cognition, hippocampal volume, and white matter hyperintensities in mild cognitive impairment (MCI).MethodsForty-five MCI participants were evaluated. A neocortical standardized uptake value ratio threshold ≥ 1.45 was used to discriminate high from low Aβ burden. Correlations were adjusted for age, gender and years of education.ResultsHigh Aβ burden was found in 53% of MCI. Regression analyses showed standardized uptake value ratio (r = -0.51, P = 0.0015) and hippocampal volume (r = 0.60, P = 0.024) both contributing to episodic memory impairment in independent fashion. White matter hyperintensities correlated with nonmemory cognition, and this correlation was particularly associated with Aβ burden.ConclusionHigher Aβ deposition in MCI is associated with more severe memory impairment and is contributing to early amnestic symptoms independent of hippocampal atrophy.

MR-Less Surface-Based Amyloid Assessment Based on 11C PiB PET

Background β-amyloid (Aβ) plaques in brains grey matter (GM) are one of the pathological hallmarks of Alzheimers disease (AD), and can be imaged in vivo using Positron Emission Tomography (PET) with 11C or 18F radiotracers. Estimating Aβ burden in cortical GM has been shown to improve diagnosis and monitoring of AD. However, lacking structural information in PET images requires such assessments to be performed with anatomical MRI scans, which may not be available at different clinical settings or being contraindicated for particular reasons. This study aimed to develop an MR-less Aβ imaging quantification method that requires only PET images for reliable Aβ burden estimations. Materials and Methods The proposed method has been developed using a multi-atlas based approach on 11C-PiB scans from 143 subjects (75 PiB+ and 68 PiB- subjects) in AIBL study. A subset of 20 subjects (PET and MRI) were used as atlases: 1) MRI images were co-registered with tissue segmentation; 2) 3D surface at the GM-WM interfacing was extracted and registered to a canonical space; 3) Mean PiB retention within GM was estimated and mapped to the surface. For other participants, each atlas PET image (and surface) was registered to the subjects PET image for PiB estimation within GM. The results are combined by subject-specific atlas selection and Bayesian fusion to generate estimated surface values. Results All PiB+ subjects (N = 75) were highly correlated between the MR-dependent and the PET-only methods with Intraclass Correlation (ICC) of 0.94, and an average relative difference error of 13% (or 0.23 SUVR) per surface vertex. All PiB- subjects (N = 68) revealed visually akin patterns with a relative difference error of 16% (or 0.19 SUVR) per surface vertex. Conclusion The demonstrated accuracy suggests that the proposed method could be an effective clinical inspection tool for Aβ imaging scans when MRI images are unavailable.

Cerebral quantitative susceptibility mapping predicts amyloid-β-related cognitive decline

See Derry and Kent (doi:10.1093/awx167) for a scientific commentary on this article.The large variance in cognitive deterioration in subjects who test positive for amyloid-β by positron emission tomography indicates that convergent pathologies, such as iron accumulation, might combine with amyloid-β to accelerate Alzheimers disease progression. Here, we applied quantitative susceptibility mapping, a relatively new magnetic resonance imaging method sensitive to tissue iron, to assess the relationship between iron, amyloid-β load, and cognitive decline in 117 subjects who underwent baseline magnetic resonance imaging and amyloid-β positron emission tomography from the Australian Imaging, Biomarkers and Lifestyle study (AIBL). Cognitive function data were collected every 18 months for up to 6 years from 100 volunteers who were either cognitively normal (n = 64) or diagnosed with mild cognitive impairment (n = 17) or Alzheimers disease (n = 19). Among participants with amyloid pathology (n = 45), higher hippocampal quantitative susceptibility mapping levels predicted accelerated deterioration in composite cognition tests for episodic memory [β(standard error) = -0.169 (0.034), P = 9.2 × 10-7], executive function [β(standard error) = -0.139 (0.048), P = 0.004), and attention [β(standard error) = -0.074 (0.029), P = 0.012]. Deteriorating performance in a composite of language tests was predicted by higher quantitative susceptibility mapping levels in temporal lobe [β(standard error) = -0.104 (0.05), P = 0.036] and frontal lobe [β(standard error) = -0.154 (0.055), P = 0.006]. These findings indicate that brain iron might combine with amyloid-β to accelerate clinical progression and that quantitative susceptibility mapping could be used in combination with amyloid-β positron emission tomography to stratify individuals at risk of decline.

Automated 11C-PiB Standardized Uptake Value Ratio

RATIONALE AND OBJECTIVES Radiotracers such as (11)C-PiB have enabled the in vivo imaging of amyloid-beta plaques in the brain, one of the histopathologic hallmarks of Alzheimers disease (AD). Standardized uptake value ratio (SUVR) has become the most common normalization for (11)C-PiB as it does not require dynamic scans or blood sampling. Normalization is performed by computing the ratio of (11)C-PiB retention in the whole brain to that in cerebellar gray matter. However, SUVR is still conducted manually and is time consuming. An automated normalization algorithm is proposed. MATERIALS AND METHODS Sixty participants from the Australian Imaging Biomarkers and Lifestyle (AIBL) study were used to test the developed algorithm and compare it against manual SUVR. The cohort consisted of participants likely to have AD (n = 20), those with mild cognitive impairment (MCI; n = 20), and normal controls (NC; n = 20). The participants underwent (11)C-PiB PET scans. A subset (n = 15) also underwent magnetic resonance imaging scans. (11)C-PET scans were segmented using an expectation maximization approach with inhomogeneity correction using three-dimensional cubic B-Splines. A cerebellar region was propagated and constrained by segmentation. Comparisons were made between manual and automated SUVR using regional analysis. Receiver-operating characteristic curves were computed for the task of AD-NC classification. Positron emission tomographic segmentations were also compared to co-registered magnetic resonance images of the same patient. RESULTS Significant differences in regional means were observed between manual and automated SUVR. However, these changes were highly correlated (r > 0.8 for most regions). Significant differences (P < .05) in regional variances were also observed for the AD and NC subgroups. Area under the curve was 0.84 and 0.89 for manual and automated SUVR, respectively. CONCLUSIONS The automated normalization technique results in less within-group variance and better discrimination between AD and NC participants.

The multi-modal Australian ScienceS Imaging and Visualization Environment (MASSIVE) high performance computing infrastructure: applications in neuroscience and neuroinformatics research

The Multi-modal Australian ScienceS Imaging and Visualization Environment (MASSIVE) is a national imaging and visualization facility established by Monash University, the Australian Synchrotron, the Commonwealth Scientific Industrial Research Organization (CSIRO), and the Victorian Partnership for Advanced Computing (VPAC), with funding from the National Computational Infrastructure and the Victorian Government. The MASSIVE facility provides hardware, software, and expertise to drive research in the biomedical sciences, particularly advanced brain imaging research using synchrotron x-ray and infrared imaging, functional and structural magnetic resonance imaging (MRI), x-ray computer tomography (CT), electron microscopy and optical microscopy. The development of MASSIVE has been based on best practice in system integration methodologies, frameworks, and architectures. The facility has: (i) integrated multiple different neuroimaging analysis software components, (ii) enabled cross-platform and cross-modality integration of neuroinformatics tools, and (iii) brought together neuroimaging databases and analysis workflows. MASSIVE is now operational as a nationally distributed and integrated facility for neuroinfomatics and brain imaging research.

Cortical surface mapping using topology correction, partial flattening and 3D shape context-based non-rigid registration for use in quantifying atrophy in Alzheimer's disease

Magnetic resonance (MR) provides a non-invasive way to investigate changes in the brain resulting from aging or neurodegenerative disorders such as Alzheimers disease (AD). Performing accurate analysis for population studies is challenging because of the interindividual anatomical variability. A large set of tools is found to perform studies of brain anatomy and population analysis (FreeSurfer, SPM, FSL). In this paper we present a newly developed surface-based processing pipeline (MILXCTE) that allows accurate vertex-wise statistical comparisons of brain modifications, such as cortical thickness (CTE). The brain is first segmented into the three main tissues: white matter, gray matter and cerebrospinal fluid, after CTE is computed, a topology corrected mesh is generated. Partial inflation and non-rigid registration of cortical surfaces to a common space using shape context are then performed. Each of the steps was firstly validated using MR images from the OASIS database. We then applied the pipeline to a sample of individuals randomly selected from the AIBL study on AD and compared with FreeSurfer. For a population of 50 individuals we found correlation of cortical thickness in all the regions of the brain (average r=0.62 left and r=0.64 right hemispheres). We finally computed changes in atrophy in 32 AD patients and 81 healthy elderly individuals. Significant differences were found in regions known to be affected in AD. We demonstrated the validity of the method for use in clinical studies which provides an alternative to well established techniques to compare different imaging biomarkers for the study of neurodegenerative diseases.

MR-Less High Dimensional Spatial Normalization of 11C PiB PET Images on a Population of Elderly, Mild Cognitive Impaired and Alzheimer Disease Patients

Beta-amyloid (Abeta) plaques are one of the neuropathological hallmarks of Alzheimers disease (AD) and can be quantified using the marker 11C PiB. As l1C PiB PET images have limited anatomical information, an Magnetic Resonance Image (MRI) is usually acquired to perform the spatial normalization needed for population analysis. We designed and evaluated a high dimensional spatial normalization approach that only uses the 11C PiB PET image. The non-rigid registration (NRR) is based on free form deformation (FFD) modelled using B-splines. To compensate for the limited anatomical information, the FFD is constrained to an allowable transform space using a model trained from MR registrations. Abeta deposition is dependent on disease staging, so a spatially normalized 11C PiB PET appearance model selects and refines the atlas. The approach was compared with MR NRR using data from healthy elderly, mild cognitive impaired and Alzheimer disease participants. Using segmentation propagation, an average Dice similarity coefficient of 0.64 and 0.73 was obtained for white and gray matter. The R-squared correlation between the uptake obtained in the frontal, parietal, occipital and temporal was 0.789, 0.843, 0.871 and 0.964. These are very promising results, considering the low resolution of 11C PiB PET images.