Individual estimates of age at detectable amyloid onset for risk factor assessment.

INTRODUCTION: Individualized estimates of age at detectable amyloid-beta (Aß) accumulation, distinct from amyloid positivity, allow for analysis of onset age of Aß accumulation as an outcome measure to understand risk factors. METHODS: Using longitudinal Pittsburgh compound B (PiB) positron emission tomography data from Baltimore Longitudinal Study of Aging, we estimated the age at which each PiB+ individual began accumulating Aß. We used survival analysis methods to quantify risk of accumulating Aß and differences in onset age of Aß accumulation in relation to APOE ε4 status and sex among 36 APOE ε4 carriers and 83 noncarriers. RESULTS: Age at onset of Aß accumulation for the APOE ε4- and ε4+ groups was 73.1 and 60.7, respectively. APOE ε4 positivity conferred a threefold risk of accumulating Aß after adjusting for sex and education. DISCUSSION: Estimation of onset age of amyloid accumulation may help gauge treatment efficacy in interventions to delay symptom onset in Alzheimer's disease.

Multi-Output Decision Trees for Lesion Segmentation in Multiple Sclerosis.

Multiple Sclerosis (MS) is a disease of the central nervous system in which the protective myelin sheath of the neurons is damaged. MS leads to the formation of lesions, predominantly in the white matter of the brain and the spinal cord. The number and volume of lesions visible in magnetic resonance (MR) imaging (MRI) are important criteria for diagnosing and tracking the progression of MS. Locating and delineating lesions manually requires the tedious and expensive efforts of highly trained raters. In this paper, we propose an automated algorithm to segment lesions in MR images using multi-output decision trees. We evaluated our algorithm on the publicly available MICCAI 2008 MS Lesion Segmentation Challenge training dataset of 20 subjects, and showed improved results in comparison to state-of-the-art methods. We also evaluated our algorithm on an in-house dataset of 49 subjects with a true positive rate of 0.41 and a positive predictive value 0.36.

A computational method for computing an Alzheimer's disease progression score; experiments and validation with the ADNI data set.

Understanding the time-dependent changes of biomarkers related to Alzheimer's disease (AD) is a key to assessing disease progression and measuring the outcomes of disease-modifying therapies. In this article, we validate an AD progression score model which uses multiple biomarkers to quantify the AD progression of subjects following 3 assumptions: (1) there is a unique disease progression for all subjects; (2) each subject has a different age of onset and rate of progression; and (3) each biomarker is sigmoidal as a function of disease progression. Fitting the parameters of this model is a challenging problem which we approach using an alternating least squares optimization algorithm. To validate this optimization scheme under realistic conditions, we use the Alzheimer's Disease Neuroimaging Initiative cohort. With the help of Monte Carlo simulations, we show that most of the global parameters of the model are tightly estimated, thus enabling an ordering of the biomarkers that fit the model well, ordered as: the Rey auditory verbal learning test with 30 minutes delay, the sum of the 2 lateral hippocampal volumes divided by the intracranial volume, followed (by the clinical dementia rating sum of boxes score and the mini-mental state examination score) in no particular order and at last the AD assessment scale-cognitive subscale.

Reconstruction of high-resolution tongue volumes from MRI.

Magnetic resonance images of the tongue have been used in both clinical studies and scientific research to reveal tongue structure. In order to extract different features of the tongue and its relation to the vocal tract, it is beneficial to acquire three orthogonal image volumes--e.g., axial, sagittal, and coronal volumes. In order to maintain both low noise and high visual detail and minimize the blurred effect due to involuntary motion artifacts, each set of images is acquired with an in-plane resolution that is much better than the through-plane resolution. As a result, any one dataset, by itself, is not ideal for automatic volumetric analyses such as segmentation, registration, and atlas building or even for visualization when oblique slices are required. This paper presents a method of superresolution volume reconstruction of the tongue that generates an isotropic image volume using the three orthogonal image volumes. The method uses preprocessing steps that include registration and intensity matching and a data combination approach with the edge-preserving property carried out by Markov random field optimization. The performance of the proposed method was demonstrated on 15 clinical datasets, preserving anatomical details and yielding superior results when compared with different reconstruction methods as visually and quantitatively assessed.

Assessment of distribution and evolution of mechanical dyssynchrony in a porcine model of myocardial infarction by cardiovascular magnetic resonance.

BACKGROUND: We sought to investigate the relationship between infarct and dyssynchrony post- myocardial infarct (MI), in a porcine model. Mechanical dyssynchrony post-MI is associated with left ventricular (LV) remodeling and increased mortality. METHODS: Cine, gadolinium-contrast, and tagged cardiovascular magnetic resonance (CMR) were performed pre-MI, 9 ± 2 days (early post-MI), and 33 ± 10 days (late post-MI) post-MI in 6 pigs to characterize cardiac morphology, location and extent of MI, and regional mechanics. LV mechanics were assessed by circumferential strain (eC). Electro-anatomic mapping (EAM) was performed within 24 hrs of CMR and prior to sacrifice. RESULTS: Mean infarct size was 21 ± 4% of LV volume with evidence of post-MI remodeling. Global eC significantly decreased post MI (-27 ± 1.6% vs. -18 ± 2.5% (early) and -17 ± 2.7% (late), p < 0.0001) with no significant change in peri-MI and MI segments between early and late time-points. Time to peak strain (TTP) was significantly longer in MI, compared to normal and peri-MI segments, both early (440 ± 40 ms vs. 329 ± 40 ms and 332 ± 36 ms, respectively; p = 0.0002) and late post-MI (442 ± 63 ms vs. 321 ± 40 ms and 355 ± 61 ms, respectively; p = 0.012). The standard deviation of TTP in 16 segments (SD16) significantly increased post-MI: 28 ± 7 ms to 50 ± 10 ms (early, p = 0.012) to 54 ± 19 ms (late, p = 0.004), with no change between early and late post-MI time-points (p = 0.56). TTP was not related to reduction of segmental contractility. EAM revealed late electrical activation and greatly diminished conduction velocity in the infarct (5.7 ± 2.4 cm/s), when compared to peri-infarct (18.7 ± 10.3 cm/s) and remote myocardium (39 ± 20.5 cm/s). CONCLUSIONS: Mechanical dyssynchrony occurs early after MI and is the result of delayed electrical and mechanical activation in the infarct.

Direct segmentation of the major white matter tracts in diffusion tensor images.

Diffusion-weighted images of the human brain are acquired more and more routinely in clinical research settings, yet segmenting and labeling white matter tracts in these images is still challenging. We present in this paper a fully automated method to extract many anatomical tracts at once on diffusion tensor images, based on a Markov random field model and anatomical priors. The approach provides a direct voxel labeling, models explicitly fiber crossings and can handle white matter lesions. Experiments on simulations and repeatability studies show robustness to noise and reproducibility of the algorithm, which has been made publicly available.

Foibles, Follies, and Fusion: Assessment of Statistical Label Fusion Techniques for Web-Based Collaborations using Minimal Training.

Labeling or parcellation of structures of interest on magnetic resonance imaging (MRI) is essential in quantifying and characterizing correlation with numerous clinically relevant conditions. The use of statistical methods using automated methods or complete data sets from several different raters have been proposed to simultaneously estimate both rater reliability and true labels. An extension to these statistical based methodologies was proposed that allowed for missing labels, repeated labels and training trials. Herein, we present and demonstrate the viability of these statistical based methodologies using real world data contributed by minimally trained human raters. The consistency of the statistical estimates, the accuracy compared to the individual observations and the variability of both the estimates and the individual observations with respect to the number of labels are discussed. It is demonstrated that the Gaussian based statistical approach using the previously presented extensions successfully performs label fusion in a variety of contexts using data from online (Internet-based) collaborations among minimally trained raters. This first successful demonstration of a statistically based approach using "wild-type" data opens numerous possibilities for very large scale efforts in collaboration. Extension and generalization of these technologies for new application spaces will certainly present fascinating areas for continuing research.

Prostate brachytherapy seed reconstruction with Gaussian blurring and optimal coverage cost.

Intraoperative dosimetry in prostate brachytherapy requires localization of the implanted radioactive seeds. A tomosynthesis-based seed reconstruction method is proposed. A three-dimensional volume is reconstructed from Gaussian-blurred projection images and candidate seed locations are computed from the reconstructed volume. A false positive seed removal process, formulated as an optimal coverage problem, iteratively removes "ghost" seeds that are created by tomosynthesis reconstruction. In an effort to minimize pose errors that are common in conventional C-arms, initial pose parameter estimates are iteratively corrected by using the detected candidate seeds as fiducials, which automatically "focuses" the collected images and improves successive reconstructed volumes. Simulation results imply that the implanted seed locations can be estimated with a detection rate of > or = 97.9% and > or = 99.3% from three and four images, respectively, when the C-arm is calibrated and the pose of the C-arm is known. The algorithm was also validated on phantom data sets successfully localizing the implanted seeds from four or five images. In a Phase-1 clinical trial, we were able to localize the implanted seeds from five intraoperative fluoroscopy images with 98.8% (STD=1.6) overall detection rate.

Effects of diffusion weighting schemes on the reproducibility of DTI-derived fractional anisotropy, mean diffusivity, and principal eigenvector measurements at 1.5T.

Diffusion tensor imaging (DTI) is used to study tissue composition and architecture in vivo. To increase the signal to noise ratio (SNR) of DTI contrasts, studies typically use more than the minimum of 6 diffusion weighting (DW) directions or acquire repeated observations of the same set of DW directions. Simulation-based studies have sought to optimize DTI acquisitions and suggest that increasing the directional resolution of a DTI dataset (i.e., the number of distinct directions) is preferable to repeating observations, in an equal scan time comparison. However, it is not always clear how to translate these recommendations into practice when considering physiological noise and scanner stability. Furthermore, the effect of different DW schemes on in vivo DTI findings is not fully understood. This study characterizes how the makeup of a DW scheme, in terms of the number of directions, impacts the precision and accuracy of in vivo fractional anisotropy (FA), mean diffusivity (MD), and principal eigenvector (PEV) findings. Orientation dependence of DTI reliability is demonstrated in vivo and a principled theoretical framework is provided to support and interpret findings with simulation results. As long as sampling orientations are well balanced, differences in DTI contrasts due to different DW schemes are shown to be small relative to intra-session variability. These differences are accentuated at low SNR, while minimized at high SNR. This result suggests that typical clinical studies, which use similar protocols but different well-balanced DW schemes, are readily comparable within the experimental precision.