Serial Reaction Time Task Performance in Older Adults with Neuropsychologically Defined Mild Cognitive Impairment.

BACKGROUND: Studies have found that individuals with mild cognitive impairment (MCI) exhibit a range of deficits outside the realm of primary explicit memory, yet the role of response speed and implicit learning in older adults with MCI have not been established. OBJECTIVE: The current study aims to explore and document response speed and implicit learning in older adults with neuropsychologically defined MCI using a simple serial reaction (SRT) task. In addition, the study aims to explore the feasibility of a novel utilization of the simple cognitive task using machine learning procedures as a proof of concept. METHOD: Participants were 22 cognitively healthy older adults and 20 older adults with MCI confirmed through comprehensive neuropsychological evaluation. Two-sample t-test, multivariate regression, and mixed-effect models were used to investigate group difference in response speed and implicit learning on the SRT task. We also explored the potential utility of SRT feature analysis through random forest classification. RESULTS: With demographic variables controlled, the MCI group showed overall slower reaction time and higher error rate compared to the cognitively healthy volunteers. Both groups showed significant simple motor learning and implicit learning. The learning patterns were not statistically different between the two groups. Random forest classification achieved overall accuracy of 80.9%. CONCLUSIONS: Individuals with MCI demonstrated slower reaction time and higher error rate compared to cognitively healthy volunteers but demonstrated largely preserved motor learning and implicit sequence learning. Preliminary results from random forest classification using features from SRT performance supported further research in this area.

PSACNN: Pulse sequence adaptive fast whole brain segmentation.

With the advent of convolutional neural networks (CNN), supervised learning methods are increasingly being used for whole brain segmentation. However, a large, manually annotated training dataset of labeled brain images required to train such supervised methods is frequently difficult to obtain or create. In addition, existing training datasets are generally acquired with a homogeneous magnetic resonance imaging (MRI) acquisition protocol. CNNs trained on such datasets are unable to generalize on test data with different acquisition protocols. Modern neuroimaging studies and clinical trials are necessarily multi-center initiatives with a wide variety of acquisition protocols. Despite stringent protocol harmonization practices, it is very difficult to standardize the gamut of MRI imaging parameters across scanners, field strengths, receive coils etc., that affect image contrast. In this paper we propose a CNN-based segmentation algorithm that, in addition to being highly accurate and fast, is also resilient to variation in the input acquisition. Our approach relies on building approximate forward models of pulse sequences that produce a typical test image. For a given pulse sequence, we use its forward model to generate plausible, synthetic training examples that appear as if they were acquired in a scanner with that pulse sequence. Sampling over a wide variety of pulse sequences results in a wide variety of augmented training examples that help build an image contrast invariant model. Our method trains a single CNN that can segment input MRI images with acquisition parameters as disparate as T1-weighted and T2-weighted contrasts with only T1-weighted training data. The segmentations generated are highly accurate with state-of-the-art results (overall Dice overlap=0.94), with a fast run time (≈ 45 s), and consistent across a wide range of acquisition protocols.

Multi-atlas-based CT synthesis from conventional MRI with patch-based refinement for MRI-based radiotherapy planning.

Accurate CT synthesis, sometimes called electron density estimation, from MRI is crucial for successful MRI-based radiotherapy planning and dose computation. Existing CT synthesis methods are able to synthesize normal tissues but are unable to accurately synthesize abnormal tissues (i.e., tumor), thus providing a suboptimal solution. We propose a multi-atlas-based hybrid synthesis approach that combines multi-atlas registration and patch-based synthesis to accurately synthesize both normal and abnormal tissues. Multi-parametric atlas MR images are registered to the target MR images by multi-channel deformable registration, from which the atlas CT images are deformed and fused by locally-weighted averaging using a structural similarity measure (SSIM). Synthetic MR images are also computed from the registered atlas MRIs by using the same weights used for the CT synthesis; these are compared to the target patient MRIs allowing for the assessment of the CT synthesis fidelity. Poor synthesis regions are automatically detected based on the fidelity measure and refined by a patch-based synthesis. The proposed approach was tested on brain cancer patient data, and showed a noticeable improvement for the tumor region.

Longitudinal multiple sclerosis lesion segmentation data resource.

The data presented in this article is related to the research article entitled "Longitudinal multiple sclerosis lesion segmentation: Resource and challenge" (Carass et al., 2017) [1]. In conjunction with the 2015 International Symposium on Biomedical Imaging, we organized a longitudinal multiple sclerosis (MS) lesion segmentation challenge providing training and test data to registered participants. The training data consists of five subjects with a mean of 4.4 (±0.55) time-points, and test data of fourteen subjects with a mean of 4.4 (±0.67) time-points. All 82 data sets had the white matter lesions associated with multiple sclerosis delineated by two human expert raters. The training data including multi-modal scans and manually delineated lesion masks is available for download. In addition, the testing data is also being made available in conjunction with a website for evaluating the automated analysis of the testing data.

Longitudinal multiple sclerosis lesion segmentation: Resource and challenge.

In conjunction with the ISBI 2015 conference, we organized a longitudinal lesion segmentation challenge providing training and test data to registered participants. The training data consisted of five subjects with a mean of 4.4 time-points, and test data of fourteen subjects with a mean of 4.4 time-points. All 82 data sets had the white matter lesions associated with multiple sclerosis delineated by two human expert raters. Eleven teams submitted results using state-of-the-art lesion segmentation algorithms to the challenge, with ten teams presenting their results at the conference. We present a quantitative evaluation comparing the consistency of the two raters as well as exploring the performance of the eleven submitted results in addition to three other lesion segmentation algorithms. The challenge presented three unique opportunities: (1) the sharing of a rich data set; (2) collaboration and comparison of the various avenues of research being pursued in the community; and (3) a review and refinement of the evaluation metrics currently in use. We report on the performance of the challenge participants, as well as the construction and evaluation of a consensus delineation. The image data and manual delineations will continue to be available for download, through an evaluation website2 as a resource for future researchers in the area. This data resource provides a platform to compare existing methods in a fair and consistent manner to each other and multiple manual raters.

A supervoxel based random forest synthesis framework for bidirectional MR/CT synthesis.

Synthesizing magnetic resonance (MR) and computed tomography (CT) images (from each other) has important implications for clinical neuroimaging. The MR to CT direction is critical for MRI-based radiotherapy planning and dose computation, whereas the CT to MR direction can provide an economic alternative to real MRI for image processing tasks. Additionally, synthesis in both directions can enhance MR/CT multi-modal image registration. Existing approaches have focused on synthesizing CT from MR. In this paper, we propose a multi-atlas based hybrid method to synthesize T1-weighted MR images from CT and CT images from T1-weighted MR images using a common framework. The task is carried out by: (a) computing a label field based on supervoxels for the subject image using joint label fusion; (b) correcting this result using a random forest classifier (RF-C); (c) spatial smoothing using a Markov random field; (d) synthesizing intensities using a set of RF regressors, one trained for each label. The algorithm is evaluated using a set of six registered CT and MR image pairs of the whole head.

Cross contrast multi-channel image registration using image synthesis for MR brain images.

Multi-modal deformable registration is important for many medical image analysis tasks such as atlas alignment, image fusion, and distortion correction. Whereas a conventional method would register images with different modalities using modality independent features or information theoretic metrics such as mutual information, this paper presents a new framework that addresses the problem using a two-channel registration algorithm capable of using mono-modal similarity measures such as sum of squared differences or cross-correlation. To make it possible to use these same-modality measures, image synthesis is used to create proxy images for the opposite modality as well as intensity-normalized images from each of the two available images. The new deformable registration framework was evaluated by performing intra-subject deformation recovery, intra-subject boundary alignment, and inter-subject label transfer experiments using multi-contrast magnetic resonance brain imaging data. Three different multi-channel registration algorithms were evaluated, revealing that the framework is robust to the multi-channel deformable registration algorithm that is used. With a single exception, all results demonstrated improvements when compared against single channel registrations using the same algorithm with mutual information.

Random forest regression for magnetic resonance image synthesis.

By choosing different pulse sequences and their parameters, magnetic resonance imaging (MRI) can generate a large variety of tissue contrasts. This very flexibility, however, can yield inconsistencies with MRI acquisitions across datasets or scanning sessions that can in turn cause inconsistent automated image analysis. Although image synthesis of MR images has been shown to be helpful in addressing this problem, an inability to synthesize both T2-weighted brain images that include the skull and FLuid Attenuated Inversion Recovery (FLAIR) images has been reported. The method described herein, called REPLICA, addresses these limitations. REPLICA is a supervised random forest image synthesis approach that learns a nonlinear regression to predict intensities of alternate tissue contrasts given specific input tissue contrasts. Experimental results include direct image comparisons between synthetic and real images, results from image analysis tasks on both synthetic and real images, and comparison against other state-of-the-art image synthesis methods. REPLICA is computationally fast, and is shown to be comparable to other methods on tasks they are able to perform. Additionally REPLICA has the capability to synthesize both T2-weighted images of the full head and FLAIR images, and perform intensity standardization between different imaging datasets.

Effects of Spatial Resolution on Image Registration.

This paper presents a theoretical analysis of the effect of spatial resolution on image registration. Based on the assumption of additive Gaussian noise on the images, the mean and variance of the distribution of the sum of squared differences (SSD) were estimated. Using these estimates, we evaluate a distance between the SSD distributions of aligned images and non-aligned images. The experimental results show that by matching the resolutions of the moving and fixed images one can get a better image registration result. The results agree with our theoretical analysis of SSD, but also suggest that it may be valid for mutual information as well.

Patch Based Synthesis of Whole Head MR Images: Application to EPI Distortion Correction.

Different magnetic resonance imaging pulse sequences are used to generate image contrasts based on physical properties of tissues, which provide different and often complementary information about them. Therefore multiple image contrasts are useful for multimodal analysis of medical images. Often, medical image processing algorithms are optimized for particular image contrasts. If a desirable contrast is unavailable, contrast synthesis (or modality synthesis) methods try to "synthesize" the unavailable constrasts from the available ones. Most of the recent image synthesis methods generate synthetic brain images, while whole head magnetic resonance (MR) images can also be useful for many applications. We propose an atlas based patch matching algorithm to synthesize T2-w whole head (including brain, skull, eyes etc) images from T1-w images for the purpose of distortion correction of diffusion weighted MR images. The geometric distortion in diffusion MR images due to in-homogeneous B0 magnetic field are often corrected by non-linearly registering the corresponding b = 0 image with zero diffusion gradient to an undistorted T2-w image. We show that our synthetic T2-w images can be used as a template in absence of a real T2-w image. Our patch based method requires multiple atlases with T1 and T2 to be registeLowRes to a given target T1. Then for every patch on the target, multiple similar looking matching patches are found on the atlas T1 images and corresponding patches on the atlas T2 images are combined to generate a synthetic T2 of the target. We experimented on image data obtained from 44 patients with traumatic brain injury (TBI), and showed that our synthesized T2 images produce more accurate distortion correction than a state-of-the-art registration based image synthesis method.

Self Super-resolution for Magnetic Resonance Images.

It is faster and therefore cheaper to acquire magnetic resonance images (MRI) with higher in-plane resolution than through-plane resolution. The low resolution of such acquisitions can be increased using post-processing techniques referred to as super-resolution (SR) algorithms. SR is known to be an ill-posed problem. Most state-of-the-art SR algorithms rely on the presence of external/training data to learn a transform that converts low resolution input to a higher resolution output. In this paper an SR approach is presented that is not dependent on any external training data and is only reliant on the acquired image. Patches extracted from the acquired image are used to estimate a set of new images, where each image has increased resolution along a particular direction. The final SR image is estimated by combining images in this set via the technique of Fourier Burst Accumulation. Our approach was validated on simulated low resolution MRI images, and showed significant improvement in image quality and segmentation accuracy when compared to competing SR methods. SR of FLuid Attenuated Inversion Recovery (FLAIR) images with lesions is also demonstrated.

Using image synthesis for multi-channel registration of different image modalities.

This paper presents a multi-channel approach for performing registration between magnetic resonance (MR) images with different modalities. In general, a multi-channel registration cannot be used when the moving and target images do not have analogous modalities. In this work, we address this limitation by using a random forest regression technique to synthesize the missing modalities from the available ones. This allows a single channel registration between two different modalities to be converted into a multi-channel registration with two mono-modal channels. To validate our approach, two openly available registration algorithms and five cost functions were used to compare the label transfer accuracy of the registration with (and without) our multi-channel synthesis approach. Our results show that the proposed method produced statistically significant improvements in registration accuracy (at an α level of 0.001) for both algorithms and all cost functions when compared to a standard multi-modal registration using the same algorithms with mutual information.

Tree-Encoded Conditional Random Fields for Image Synthesis.

Magnetic resonance imaging (MRI) is the dominant modality for neuroimaging in clinical and research domains. The tremendous versatility of MRI as a modality can lead to large variability in terms of image contrast, resolution, noise, and artifacts. Variability can also manifest itself as missing or corrupt imaging data. Image synthesis has been recently proposed to homogenize and/or enhance the quality of existing imaging data in order to make them more suitable as consistent inputs for processing. We frame the image synthesis problem as an inference problem on a 3-D continuous-valued conditional random field (CRF). We model the conditional distribution as a Gaussian by defining quadratic association and interaction potentials encoded in leaves of a regression tree. The parameters of these quadratic potentials are learned by maximizing the pseudo-likelihood of the training data. Final synthesis is done by inference on this model. We applied this method to synthesize T2-weighted images from T1-weighted images, showing improved synthesis quality as compared to current image synthesis approaches. We also synthesized Fluid Attenuated Inversion Recovery (FLAIR) images, showing similar segmentations to those obtained from real FLAIRs. Additionally, we generated super-resolution FLAIRs showing improved segmentation.

MR image synthesis by contrast learning on neighborhood ensembles.

Automatic processing of magnetic resonance images is a vital part of neuroscience research. Yet even the best and most widely used medical image processing methods will not produce consistent results when their input images are acquired with different pulse sequences. Although intensity standardization and image synthesis methods have been introduced to address this problem, their performance remains dependent on knowledge and consistency of the pulse sequences used to acquire the images. In this paper, an image synthesis approach that first estimates the pulse sequence parameters of the subject image is presented. The estimated parameters are then used with a collection of atlas or training images to generate a new atlas image having the same contrast as the subject image. This additional image provides an ideal source from which to synthesize any other target pulse sequence image contained in the atlas. In particular, a nonlinear regression intensity mapping is trained from the new atlas image to the target atlas image and then applied to the subject image to yield the particular target pulse sequence within the atlas. Both intensity standardization and synthesis of missing tissue contrasts can be achieved using this framework. The approach was evaluated on both simulated and real data, and shown to be superior in both intensity standardization and synthesis to other established methods.

MRBrainS Challenge: Online Evaluation Framework for Brain Image Segmentation in 3T MRI Scans.

Many methods have been proposed for tissue segmentation in brain MRI scans. The multitude of methods proposed complicates the choice of one method above others. We have therefore established the MRBrainS online evaluation framework for evaluating (semi)automatic algorithms that segment gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF) on 3T brain MRI scans of elderly subjects (65-80 y). Participants apply their algorithms to the provided data, after which their results are evaluated and ranked. Full manual segmentations of GM, WM, and CSF are available for all scans and used as the reference standard. Five datasets are provided for training and fifteen for testing. The evaluated methods are ranked based on their overall performance to segment GM, WM, and CSF and evaluated using three evaluation metrics (Dice, H95, and AVD) and the results are published on the MRBrainS13 website. We present the results of eleven segmentation algorithms that participated in the MRBrainS13 challenge workshop at MICCAI, where the framework was launched, and three commonly used freeware packages: FreeSurfer, FSL, and SPM. The MRBrainS evaluation framework provides an objective and direct comparison of all evaluated algorithms and can aid in selecting the best performing method for the segmentation goal at hand.

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.

An Example-Based Brain MRI Simulation Framework.

The simulation of magnetic resonance (MR) images plays an important role in the validation of image analysis algorithms such as image segmentation, due to lack of sufficient ground truth in real MR images. Previous work on MRI simulation has focused on explicitly modeling the MR image formation process. However, because of the overwhelming complexity of MR acquisition these simulations must involve simplifications and approximations that can result in visually unrealistic simulated images. In this work, we describe an example-based simulation framework, which uses an "atlas" consisting of an MR image and its anatomical models derived from the hard segmentation. The relationships between the MR image intensities and its anatomical models are learned using a patch-based regression that implicitly models the physics of the MR image formation. Given the anatomical models of a new brain, a new MR image can be simulated using the learned regression. This approach has been extended to also simulate intensity inhomogeneity artifacts based on the statistical model of training data. Results show that the example based MRI simulation method is capable of simulating different image contrasts and is robust to different choices of atlas. The simulated images resemble real MR images more than simulations produced by a physics-based model.

IMPROVING MAGNETIC RESONANCE RESOLUTION WITH SUPERVISED LEARNING.

Despite ongoing improvements in magnetic resonance (MR) imaging (MRI), considerable clinical and, to a lesser extent, research data is acquired at lower resolutions. For example 1 mm isotropic acquisition of T1-weighted (T1-w) Magnetization Prepared Rapid Gradient Echo (MPRAGE) is standard practice, however T2-weighted (T2-w)-because of its longer relaxation times (and thus longer scan time)-is still routinely acquired with slice thicknesses of 2-5 mm and in-plane resolution of 2-3 mm. This creates obvious fundamental problems when trying to process T1-w and T2-w data in concert. We present an automated supervised learning algorithm to generate high resolution data. The framework is similar to the brain hallucination work of Rousseau, taking advantage of new developments in regression based image reconstruction. We present validation on phantom and real data, demonstrating the improvement over state-of-the-art super-resolution techniques.

RANDOM FOREST FLAIR RECONSTRUCTION FROM T1, T2, AND PD -WEIGHTED MRI.

Fluid Attenuated Inversion Recovery (FLAIR) is a commonly acquired pulse sequence for multiple sclerosis (MS) patients. MS white matter lesions appear hyperintense in FLAIR images and have excellent contrast with the surrounding tissue. Hence, FLAIR images are commonly used in automated lesion segmentation algorithms to easily and quickly delineate the lesions. This expedites the lesion load computation and correlation with disease progression. Unfortunately for numerous reasons the acquired FLAIR images can be of a poor quality and suffer from various artifacts. In the most extreme cases the data is absent, which poses a problem when consistently processing a large data set. We propose to fill in this gap by reconstructing a FLAIR image given the corresponding T1-weighted, T2-weighted, and PD -weighted images of the same subject using random forest regression. We show that the images we produce are similar to true high quality FLAIR images and also provide a good surrogate for tissue segmentation.

MR to CT Registration of Brains using Image Synthesis.

Computed tomography (CT) is the standard imaging modality for patient dose calculation for radiation therapy. Magnetic resonance (MR) imaging (MRI) is used along with CT to identify brain structures due to its superior soft tissue contrast. Registration of MR and CT is necessary for accurate delineation of the tumor and other structures, and is critical in radiotherapy planning. Mutual information (MI) or its variants are typically used as a similarity metric to register MRI to CT. However, unlike CT, MRI intensity does not have an accepted calibrated intensity scale. Therefore, MI-based MR-CT registration may vary from scan to scan as MI depends on the joint histogram of the images. In this paper, we propose a fully automatic framework for MR-CT registration by synthesizing a synthetic CT image from MRI using a co-registered pair of MR and CT images as an atlas. Patches of the subject MRI are matched to the atlas and the synthetic CT patches are estimated in a probabilistic framework. The synthetic CT is registered to the original CT using a deformable registration and the computed deformation is applied to the MRI. In contrast to most existing methods, we do not need any manual intervention such as picking landmarks or regions of interests. The proposed method was validated on ten brain cancer patient cases, showing 25% improvement in MI and correlation between MR and CT images after registration compared to state-of-the-art registration methods.