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Daniel J. Blezek

Bio: Daniel J. Blezek is an academic researcher from General Electric. The author has contributed to research in topics: Medicine & Imaging phantom. The author has an hindex of 10, co-authored 16 publications receiving 3486 citations.

Papers
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Journal ArticleDOI
TL;DR: The approach taken in ADNI to standardization across sites and platforms of the MRI protocol, postacquisition corrections, and phantom‐based monitoring of all scanners could be used as a model for other multisite trials.
Abstract: Dementia, one of the most feared associates of increasing longevity, represents a pressing public health problem and major research priority. Alzheimer's disease (AD) is the most common form of dementia, affecting many millions around the world. There is currently no cure for AD, but large numbers of novel compounds are currently under development that have the potential to modify the course of the disease and slow its progression. There is a pressing need for imaging biomarkers to improve understanding of the disease and to assess the efficacy of these proposed treatments. Structural magnetic resonance imaging (MRI) has already been shown to be sensitive to presymptomatic disease (1-10) and has the potential to provide such a biomarker. For use in large-scale multicenter studies, however, standardized methods that produce stable results across scanners and over time are needed. The Alzheimer's Disease Neuroimaging Initiative (ADNI) study is a longitudinal multisite observational study of elderly individuals with normal cognition, mild cognitive impairment (MCI), or AD (11,12). It is jointly funded by the National Institutes of Health (NIH) and industry via the Foundation for the NIH. The study will assess how well information (alone or in combination) obtained from MRI, (18F)-fludeoyglucose positron emission tomography (FDG PET), urine, serum, and cerebrospinal fluid (CSF) biomarkers, as well as clinical and neuropsychometric assessments, can measure disease progression in the three groups of elderly subjects mentioned above. At the 55 participating sites in North America, imaging, clinical, and biologic samples will be collected at multiple time points in 200 elderly cognitively normal, 400 MCI, and 200 AD subjects. All subjects will be scanned with 1.5 T MRI at each time point, and half of these will also be scanned with FDG PET. Subjects not assigned to the PET arm of the study will be eligible for 3 T MRI scanning. The goal is to acquire both 1.5 T and 3 T MRI studies at multiple time points in 25% of the subjects who do not undergo PET scanning [R2C1]. CSF collection at both baseline and 12 months is targeted for 50% of the subjects. Sampling varies by clinical group. Healthy elderly controls will be sampled at 0, 6, 12, 24, and 36 months. Subjects with MCI will be sampled at 0, 6, 12, 18, 24, and 36 months. AD subjects will be sampled at 0, 6, 12, and 24 months. Major goals of the ADNI study are: to link all of these data at each time point and make this repository available to the general scientific community; to develop technical standards for imaging in longitudinal studies; to determine the optimum methods for acquiring and analyzing images; to validate imaging and biomarker data by correlating these with concurrent psychometric and clinical assessments; and to improve methods for clinical trials in MCI and AD. The ADNI study overall is divided into cores, with each core managing ADNI-related activities within its sphere of expertise: clinical, informatics, biostatistics, biomarkers, and imaging. The purpose of this report is to describe the MRI methods and decision-making process underlying the selection of the MRI protocol employed in the ADNI study.

3,611 citations

Journal ArticleDOI
TL;DR: To determine whether the promise of high‐density many‐coil MRI receiver arrays for enabling highly accelerated parallel imaging can be realized in practice, a large number of experiments have been conducted with high-density receiver arrays in order to demonstrate the ability of these arrays to accommodate large numbers of patients.
Abstract: Purpose To determine whether the promise of high-density many-coil MRI receiver arrays for enabling highly accelerated parallel imaging can be realized in practice. Materials and Methods A 128-channel body receiver-coil array and custom MRI system were developed. The array comprises two clamshells containing 64 coils each, with the posterior array built to maximize signal-to-noise ratio (SNR) and the anterior array design incorporating considerations of weight and flexibility as well. Phantom imaging and human body imaging were performed using a variety of reduction factors and 2D and 3D pulse sequences. Results The ratio of SNR relative to a 32-element array of similar footprint was 1.03 in the center of an elliptical loading phantom and 1.7 on average in the outer regions. Maximum g-factors dropped from 5.5 (for 32 channels) to 2.0 (for 128 channels) for 4 × 4 acceleration and from 25 to 3.3 for 5 × 5 acceleration. Residual aliasing artifacts for a right/left (R/L) reduction factor of 8 in human body imaging were significantly reduced relative to the 32-channel array. Conclusion MRI with a large number of receiver channels enables significantly higher acceleration factors for parallel imaging and improved SNR, provided losses from the coils and electronics are kept negligible. J. Magn. Reson. Imaging 2008;28:1219–1225. © 2008 Wiley-Liss, Inc.

120 citations

Journal ArticleDOI
TL;DR: MR imaging performed before and after administration of ferumoxtran-10 allows presurgical mapping of lymph nodes and quantitative estimation of T2*-weighted sequences and should be considered to optimize acquisition strategies.
Abstract: Detection of local or regional metastases to lymph nodes is clinically important in virtually any type of primary tumor. Current imaging techniques rely heavily on the size criterion for characterization of nodal disease. However, size can be an ineffective parameter for diagnosis of tumor spread to lymph nodes. Magnetic resonance (MR) imaging performed before and after administration of ferumoxtran-10 is a promising technique for characterization of lymph nodes in patients with various primary tumors. Normal homogeneous uptake of ferumoxtran-10 in nonmetastatic nodes shortens the T2 and T2*, turning these nodes dark, whereas malignant nodes lack uptake and remain hyperintense. To optimize acquisition strategies, the following factors should be considered: the timing of contrast material–enhanced imaging, the section thickness, the imaging plane, and the imaging parameters for T2*-weighted sequences. In addition, MR imaging with ferumoxtran-10 allows presurgical mapping of lymph nodes and quantitative est...

81 citations

Book ChapterDOI
01 Oct 2006
TL;DR: In this article, the authors explore the question of whether a single atlas is appropriate for a given sample or whether there is sufficient image-based evidence from which we can infer multiple atlases, each constructed from a subset of the data.
Abstract: The process of constructing an atlas typically involves selecting one individual from a sample on which to base or root the atlas. If the individual selected is far from the population mean, then the resulting atlas is biased towards this individual. This, in turn, can bias any inferences made with the atlas. Unbiased atlas construction addresses this issue by either basing the atlas on the individual which is the median of the sample or by an iterative technique whereby the atlas converges to the unknown population mean. In this paper, we explore the question of whether a single atlas is appropriate for a given sample or whether there is sufficient image based evidence from which we can infer multiple atlases, each constructed from a subset of the data. We refer to this process as atlas stratification. Essentially, we determine whether the sample, and hence the population, is multi-modal and is best represented by an atlas per mode. We use the mean shift algorithm to identify the modes of the sample and multidimensional scaling to visualize the clustering process.

50 citations

Journal ArticleDOI
TL;DR: The improved workflow associated with the use of the automatic repositioning process, which obviates the need for skilled operator intervention for voxel repositioned, suggests that approaches similar to the one presented here may be a standard element in tomorrow's longitudinal MRI and MRS exams.
Abstract: An automatic procedure, allowing the prospective registration of brain MRI images and the acquisition of nearly identical brain volumes (coverage and orientation) in longitudinal exams, is presented. This procedure, based on a fast registration algorithm and a tailored pulse sequence, is used to reposition single voxels for 1H MRS data acquired in vivo. The impact of the repositioning method on the extent of voxel overlap and on the reproducibility of metabolite concentration measurements is studied. A statistically significant increase in voxel overlap and generally decreased short-term measurement variability (decreased coefficients of variation and increased reproducibility coefficients) are observed. Differences in the long-term variances of metabolite concentrations and concentration ratios measured using the eye and automatic repositioning scheme, however, do not reach statistical significance. The improved workflow associated with the use of the automatic repositioning process, which obviates the need for skilled operator intervention for voxel repositioning, suggests that approaches similar to the one presented here may be a standard element in tomorrow's longitudinal MRI and MRS exams. Copyright © 2005 John Wiley & Sons, Ltd.

38 citations


Cited by
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Journal ArticleDOI
TL;DR: It is found that the most common software packages for fMRI analysis (SPM, FSL, AFNI) can result in false-positive rates of up to 70%.
Abstract: The most widely used task functional magnetic resonance imaging (fMRI) analyses use parametric statistical methods that depend on a variety of assumptions. In this work, we use real resting-state data and a total of 3 million random task group analyses to compute empirical familywise error rates for the fMRI software packages SPM, FSL, and AFNI, as well as a nonparametric permutation method. For a nominal familywise error rate of 5%, the parametric statistical methods are shown to be conservative for voxelwise inference and invalid for clusterwise inference. Our results suggest that the principal cause of the invalid cluster inferences is spatial autocorrelation functions that do not follow the assumed Gaussian shape. By comparison, the nonparametric permutation test is found to produce nominal results for voxelwise as well as clusterwise inference. These findings speak to the need of validating the statistical methods being used in the field of neuroimaging.

2,946 citations

Journal ArticleDOI
TL;DR: These projections suggest a prolonged preclinical phase of AD in which Aβ deposition reaches the authors' threshold of positivity at 17·0 (95% CI 14·9-19·9) years, hippocampal atrophy at 4·2 (3·6-5·1] years, and memory impairment at 3·3 (2·5-4·5) years before the onset of dementia (clinical dementia rating score 1).
Abstract: Summary Background Similar to most chronic diseases, Alzheimer's disease (AD) develops slowly from a preclinical phase into a fully expressed clinical syndrome. We aimed to use longitudinal data to calculate the rates of amyloid β (Aβ) deposition, cerebral atrophy, and cognitive decline. Methods In this prospective cohort study, healthy controls, patients with mild cognitive impairment (MCI), and patients with AD were assessed at enrolment and every 18 months. At every visit, participants underwent neuropsychological examination, MRI, and a carbon-11-labelled Pittsburgh compound B ( 11 C-PiB) PET scan. We included participants with three or more 11 C-PiB PET follow-up assessments. Aβ burden was expressed as 11 C-PiB standardised uptake value ratio (SUVR) with the cerebellar cortex as reference region. An SUVR of 1·5 was used to discriminate high from low Aβ burdens. The slope of the regression plots over 3–5 years was used to estimate rates of change for Aβ deposition, MRI volumetrics, and cognition. We included those participants with a positive rate of Aβ deposition to calculate the trajectory of each variable over time. Findings 200 participants (145 healthy controls, 36 participants with MCI, and 19 participants with AD) were assessed at enrolment and every 18 months for a mean follow-up of 3·8 (95% CI CI 3·6–3·9) years. At baseline, significantly higher Aβ burdens were noted in patients with AD (2·27, SD 0·43) and those with MCI (1·94, 0·64) than in healthy controls (1·38, 0·39). At follow-up, 163 (82%) of the 200 participants showed positive rates of Aβ accumulation. Aβ deposition was estimated to take 19·2 (95% CI 16·8–22·5) years in an almost linear fashion—with a mean increase of 0·043 (95% CI 0·037–0·049) SUVR per year—to go from the threshold of 11 C-PiB positivity (1·5 SUVR) to the levels observed in AD. It was estimated to take 12·0 (95% CI 10·1–14·9) years from the levels observed in healthy controls with low Aβ deposition (1·2 [SD 0·1] SUVR) to the threshold of 11 C-PiB positivity. As AD progressed, the rate of Aβ deposition slowed towards a plateau. Our projections suggest a prolonged preclinical phase of AD in which Aβ deposition reaches our threshold of positivity at 17·0 (95% CI 14·9–19·9) years, hippocampal atrophy at 4·2 (3·6–5·1) years, and memory impairment at 3·3 (2·5–4·5) years before the onset of dementia (clinical dementia rating score 1). Interpretation Aβ deposition is slow and protracted, likely to extend for more than two decades. Such predictions of the rate of preclinical changes and the onset of the clinical phase of AD will facilitate the design and timing of therapeutic interventions aimed at modifying the course of this illness. Funding Science and Industry Endowment Fund (Australia), The Commonwealth Scientific and Industrial Research Organisation (Australia), The National Health and Medical Research Council of Australia Program and Project Grants, the Austin Hospital Medical Research Foundation, Victorian State Government, The Alzheimer's Drug Discovery Foundation, and the Alzheimer's Association.

1,733 citations

Journal ArticleDOI
TL;DR: Evidence from many independent research centers strongly supports the existence of a specific disease, as defined by the presence of A&bgr; plaques and neurofibrillary tangles.
Abstract: Clinicopathologic correlation studies are critically important for the field of Alzheimer disease (AD) research. Studies on human subjects with autopsy confirmation entail numerous potential biases that affect both their general applicability and the validity of the correlations. Many sources of data variability can weaken the apparent correlation between cognitive status and AD neuropathologic changes. Indeed, most persons in advanced old age have significant non-AD brain lesions that may alter cognition independently of AD. Worldwide research efforts have evaluated thousands of human subjects to assess the causes of cognitive impairment in the elderly, and these studies have been interpreted in different ways. We review the literature focusing on the correlation of AD neuropathologic changes (i.e. β-amyloid plaques and neurofibrillary tangles) with cognitive impairment. We discuss the various patterns of brain changes that have been observed in elderly individuals to provide a perspective for understanding AD clinicopathologic correlation and conclude that evidence from many independent research centers strongly supports the existence of a specific disease, as defined by the presence of Aβ plaques and neurofibrillary tangles. Although Aβ plaques may play a key role in AD pathogenesis, the severity of cognitive impairment correlates best with the burden of neocortical neurofibrillary tangles.

1,589 citations

Journal ArticleDOI
TL;DR: Stem cell migration and immune cell trafficking, as well as targeted iron oxide nanoparticles for molecular imaging studies, are at the stage of proof of concept, mainly in animal models.

1,405 citations