Generalizability is an important problem in deep neural networks, especially in the context of the variability of data acquisition in clinical magnetic resonance imaging (MRI). Recently, the Spatially Localized Atlas Network Tiles (SLANT) approach has been shown to effectively segment whole brain non-contrast T1w MRI with 132 volumetric labels. Enhancing generalizability of SLANT would enable broader application of volumetric assessment in multi-site studies. Transfer learning (TL) is commonly to update neural network weights for local factors; yet, it is commonly recognized to risk degradation of performance on the original validation/test cohorts. Here, we explore TL by data augmentation to address these concerns in the context of adapting SLANT to anatomical variation (e.g., adults versus children) and scanning protocol (e.g., non-contrast research T1w MRI versus contrast-enhanced clinical T1w MRI). We consider two datasets: First, 30 T1w MRI of young children with manually corrected volumetric labels, and accuracy of automated segmentation defined relative to the manually provided truth. Second, 36 paired datasets of pre- and post-contrast clinically acquired T1w MRI, and accuracy of the post-contrast segmentations assessed relative to the pre-contrast automated assessment. For both studies, we augment the original TL step of SLANT with either only the new data or with both original and new data. Over baseline SLANT, both approaches yielded significantly improved performance (pediatric: 0.89 vs. 0.82 DSC, p<0.001; contrast: 0.80 vs 0.76, p<0.001 ). The performance on the original test set decreased with the new-data only transfer learning approach, so data augmentation was superior to strict transfer learning.
Some veterans with a history of mild traumatic brain injury (mTBI) have reported experiencing auditory and visual dysfunction that persist beyond the acute phase of the incident. The etiology behind these symptoms is difficult to characterize, since mTBI is defined by negative imaging findings on current clinical imaging. There are several competing hypotheses that could explain functional deficits; one example is shear injury, which may manifest in diffusion-weighted magnetic resonance (MR) imaging (DWI). Herein, we explore this alternative hypothesis in a pilot study of multiparametric MR imaging. Briefly, we consider a cohort of 8 mTBI patients relative to 22 control subjects using structural T1-weighted imaging (T1w) and connectivity with DWI. 1,344 metrics were extracted per subject from whole brain regions and connectivity patterns in sensory networks. For each set of imaging-derived metrics, the control subject metrics were embedded in a low-dimensional manifold with principal component analysis, after which mTBI subject metrics were projected into the same space. These manifolds were employed to train support vector machines (SVM) to classify subjects as controls or mTBI. Two of the SVMs trained achieved near-perfect accuracy averaged across four-fold cross-validation. Additionally, we present correlations between manifold dimensions and 22 self-reported mTBI symptoms and find that five principal components from the manifolds (one component from the T1w manifold and four components from the DWI manifold) are significantly correlated with symptoms (p<0.05, uncorrected). The novelty of this work is that the DWI and T1w imaging metrics seem to contain information critical for distinguishing between mTBI and control subjects. This work presents an analysis of the pilot phase of data collection of the Quantitative Evaluation of Visual and Auditory Dysfunction and Multi-Sensory Integration in Complex TBI Patients study and defines specific hypotheses to be tested in the full sample.
Diffusion weighted magnetic resonance imaging (DW-MRI) is interpreted as a quantitative method that is sensitive to tissue microarchitecture at a millimeter scale. However, the sensitization is dependent on acquisition sequences (e.g., diffusion time, gradient strength, etc.) and susceptible to imaging artifacts. Hence, comparison of quantitative DW-MRI biomarkers across field strengths (including different scanners, hardware performance, and sequence design considerations) is a challenging area of research. We propose a novel method to estimate microstructure using DW-MRI that is robust to scanner difference between 1.5T and 3T imaging. We propose to use a null space deep network (NSDN) architecture to model DW-MRI signal as fiber orientation distributions (FOD) to represent tissue microstructure. The NSDN approach is consistent with histologically observed microstructure (on previously acquired ex vivo squirrel monkey dataset) and scan-rescan data. The contribution of this work is that we incorporate identical dual networks (IDN) to minimize the influence of scanner effects via scan-rescan data. Briefly, our estimator is trained on two datasets. First, a histology dataset was acquired on three squirrel monkeys with corresponding DW-MRI and confocal histology (512 independent voxels). Second, 37 control subjects from the Baltimore Longitudinal Study of Aging (67-95 y/o) were identified who had been scanned at 1.5T and 3T scanners (b-value of 700 s/mm2 , voxel resolution at 2.2mm, 30-32 gradient volumes) with an average interval of 4 years (standard deviation 1.3 years). After image registration, we used paired white matter (WM) voxels for 17 subjects and 440 histology voxels for training and 20 subjects and 72 histology voxels for testing. We compare the proposed estimator with super-resolved constrained spherical deconvolution (CSD) and a previously presented regression deep neural network (DNN). NSDN outperformed CSD and DNN in angular correlation coefficient (ACC) 0.81 versus 0.28 and 0.46, mean squared error (MSE) 0.001 versus 0.003 and 0.03, and general fractional anisotropy (GFA) 0.05 versus 0.05 and 0.09. Further validation and evaluation with contemporaneous imaging are necessary, but the NSDN is promising avenue for building understanding of microarchitecture in a consistent and deviceindependent manner.
Machine learning models are becoming commonplace in the domain of medical imaging, and with these methods comes an ever-increasing need for more data. However, to preserve patient anonymity it is frequently impractical or prohibited to transfer protected health information (PHI) between institutions. Additionally, due to the nature of some studies, there may not be a large public dataset available on which to train models. To address this conundrum, we analyze the efficacy of transferring the model itself in lieu of data between different sites. By doing so we accomplish two goals: 1) the model gains access to training on a larger dataset that it could not normally obtain and 2) the model better generalizes, having trained on data from separate locations. In this paper, we implement multi-site learning with disparate datasets from the National Institutes of Health (NIH) and Vanderbilt University Medical Center (VUMC) without compromising PHI. Three neural networks are trained to convergence on a computed tomography (CT) brain hematoma segmentation task: one only with NIH data, one only with VUMC data, and one multi-site model alternating between NIH and VUMC data. Resultant lesion masks with the multi-site model attain an average Dice similarity coefficient of 0.64 and the automatically segmented hematoma volumes correlate to those done manually with a Pearson correlation coefficient of 0.87, corresponding to an 8% and 5% improvement, respectively, over the single-site model counterparts.
Diffusion weighted MRI (DW-MRI) depends on accurate quantification signal intensities that reflect directional apparent diffusion coefficients (ADC). Signal drift and fluctuations during imaging can cause systematic non-linearities that manifest as ADC changes if not corrected. Here, we present a case study on a large longitudinal dataset of typical diffusion tensor imaging. We investigate observed variation in the cerebral spinal fluid (CSF) regions of the brain, which should represent compartments with isotropic diffusivity. The study contains 3949 DW-MRI acquisitions of the human brain with 918 subjects and 542 with repeated scan sessions. We provide an analysis of the inter-scan, inter-session, and intra-session variation and an analysis of the associations with the applied diffusion gradient directions. We investigate a hypothesis that CSF models could be used in lieu of an interspersed minimally diffusion-weighted image (b0) correction. Variation in CSF signal is not largely attributable to within-scan dynamic anatomical changes (3.6%), but rather has substantial variation across scan sessions (10.6%) and increased variation across individuals (26.6%). Unfortunately, CSF intensity is not solely explained by a main drift model or a gradient model, but rather has statistically significant associations with both possible explanations. Further exploration is necessary for CSF drift to be used as an effective harmonization technique.
Gradient coils in magnetic resonance imaging do not produce perfectly linear gradient fields. For diffusion imaging, the field nonlinearities cause the amplitude and direction of the applied diffusion gradients to vary over the field of view. This leads to site- and scan-specific systematic errors in estimated diffusion parameters such as diffusivity and anisotropy, reducing reliability especially in studies that take place over multiple sites. These errors can be substantially reduced if the actual scanner-specific gradient coil magnetic fields are known. The nonlinearity of the coil fields is measured by scanner manufacturers and used internally for geometric corrections, but obtaining and using the information for a specific scanner may be impractical for many sites that operate without special-purpose local engineering and research support. We have implemented an empirical field-mapping procedure using a large phantom combined with a solid harmonic approximation to the coil fields that is simple to perform and apply. Here we describe the accuracy and precision of the approach in reproducing manufacturer gold standard field maps and in reducing spatially varying errors in quantitative diffusion imaging for a specific scanner. Before correction, median B value error ranged from 33 - 41 relative to manufacturer specification at 100 mm from isocenter; correction reduced this to 0 - 4. On-axis spatial variation in the estimated mean diffusivity of an isotropic phantom was 2.2% - 4.1% within 60 mm of isocenter before correction, 0.5% - 1.6% after. Expected fractional anisotropy in the phantom was 0; highest estimated fractional anisotropy within 60 mm of isocenter was reduced from 0.024 to 0.012 in the phase encoding direction (48% reduction) and from 0.020 to 0.006 in the frequency encoding direction (72% reduction).
KEYWORDS: Diffusion, Gold, Signal to noise ratio, Data modeling, Magnetic resonance imaging, Biological research, Brain, Spherical lenses, In vivo imaging, Data acquisition
The diffusion tensor model is nonspecific in regions where micrometer structural patterns are inconsistent at the millimeter scale (i.e., brain regions with pathways that cross, bend, branch, fan, etc.). Numerous models have been proposed to represent crossing fibers and complex intravoxel structure from in vivo diffusion weighted magnetic resonance imaging (e.g., high angular resolution diffusion imaging—HARDI). Here, we present an empirical comparison of two HARDI approaches—persistent angular structure MRI (PAS-MRI) and Q-ball—using a newly acquired reproducibility dataset. Briefly, a single subject was scanned 11 times with 96 diffusion weighted directions and 10 reference volumes for each of two b values (1000 and 3000 s / mm2 for a total of 2144 volumes). Empirical reproducibility of intravoxel fiber fractions (number/strength of peaks), angular orientation, and fractional anisotropy was compared with metrics from a traditional tensor analysis approach, focusing on b values of 1000 and 3000 s / mm2. PAS-MRI is shown to be more reproducible than Q-ball and offers advantages at low b values. However, there are substantial and biologically meaningful differences between the intravoxel structures estimated both in terms of analysis method as well as by b value. The two methods suggest a fundamentally different microarchitecture of the human brain; therefore, it is premature to perform meta-analysis or combine results across HARDI studies using a different analysis model or acquisition sequences.
The choice of surface template plays an important role in cross-sectional subject analyses involving cortical brain surfaces because there is a tendency toward registration bias given variations in inter-individual and inter-group sulcal and gyral patterns. In order to account for the bias and spatial smoothing, we propose a feature-based unbiased average template surface. In contrast to prior approaches, we factor in the sample population covariance and assign weights based on feature information to minimize the influence of covariance in the sampled population. The mean surface is computed by applying the weights obtained from an inverse covariance matrix, which guarantees that multiple representations from similar groups (e.g., involving imaging, demographic, diagnosis information) are down-weighted to yield an unbiased mean in feature space. Results are validated by applying this approach in two different applications. For evaluation, the proposed unbiased weighted surface mean is compared with un-weighted means both qualitatively and quantitatively (mean squared error and absolute relative distance of both the means with baseline). In first application, we validated the stability of the proposed optimal mean on a scan-rescan reproducibility dataset by incrementally adding duplicate subjects. In the second application, we used clinical research data to evaluate the difference between the weighted and unweighted mean when different number of subjects were included in control versus schizophrenia groups. In both cases, the proposed method achieved greater stability that indicated reduced impacts of sampling bias. The weighted mean is built based on covariance information in feature space as opposed to spatial location, thus making this a generic approach to be applicable to any feature of interest.
An understanding of the bias and variance of diffusion weighted magnetic resonance imaging (DW-MRI) acquisitions across scanners, study sites, or over time is essential for the incorporation of multiple data sources into a single clinical study. Studies that combine samples from various sites may be introducing confounding factors due to site-specific artifacts and patterns. Differences in bias and variance across sites may render the scans incomparable, and, without correction, inferences obtained from these data may be misleading. We present an analysis of the bias and variance of scans of the same subjects across different sites and evaluate their impact on statistical analyses. In previous work, we presented a simulation extrapolation (SIMEX) technique for bias estimation as well as a wild bootstrap technique for variance estimation in metrics obtained from a Q-ball imaging (QBI) reconstruction of empirical high angular resolution diffusion imaging (HARDI) data. We now apply those techniques to data acquired from 5 healthy volunteers on 3 independent scanners under closely matched acquisition protocols. The bias and variance of GFA measurements were estimated on a voxel-wise basis for each scan and compared across study sites to identify site-specific differences. Further, we provide model recommendations that can be used to determine the extent of the impact of bias and variance as well as aspects of the analysis to account for these differences. We include a decision tree to help researchers determine if model adjustments are necessary based on the bias and variance results.
High Angular Resolution Diffusion Imaging (HARDI) models are used to capture complex intra-voxel microarchitectures. The magnetic resonance imaging sequences that are sensitized to diffusion are often highly accelerated and prone to motion, physiologic, and imaging artifacts. In diffusion tensor imaging, robust statistical approaches have been shown to greatly reduce these adverse factors without human intervention. Similar approaches would be possible with HARDI methods, but robust versions of each distinct HARDI approach would be necessary. To avoid the computational and pragmatic burdens of creating individual robust HARDI analysis variants, we propose a robust outlier imputation model to mitigate outliers prior to traditional HARDI analysis. This model uses a weighted spherical harmonic fit of diffusion weighted magnetic resonance imaging scans to estimate the values which had been corrupted during acquisition to restore them. Briefly, spherical harmonics of 6th order were used to generate basis function which were weighted by diffusion signal for detection of outliers. For validation, a single healthy volunteer was scanned for a single session comprising of two scans one without head movement and the other with deliberate head movement at a b-value of 3000 s/mm2 with 64 diffusion weighted directions with a single b0 (5 averages) per scan. The deliberate motion from the volunteer created natural artifacts in the acquisition of one of the scans. The imputation model shows reduction in root mean squared error of the raw signal intensities and improvement for the HARDI method Q-ball in terms of the Angular Correlation Coefficient. The results reveal that there is quantitative and qualitative improvement. The proposed model can be used as general pre-processing model before implementing any HARDI model in general to restore the artifacts which are created because of the outlier diffusion signal in certain gradient volumes.
In magnetic resonance diffusion imaging, gradient nonlinearity causes significant bias in the estimation of quantitative diffusion parameters such as diffusivity, anisotropy, and diffusion direction in areas away from the magnet isocenter. This bias can be substantially reduced if the scanner- and coil-specific gradient field nonlinearities are known. Using a set of field map calibration scans on a large (29 cm diameter) phantom combined with a solid harmonic approximation of the gradient fields, we predicted the obtained b-values and applied gradient directions throughout a typical field of view for brain imaging for a typical 32-direction diffusion imaging sequence. We measured the stability of these predictions over time. At 80 mm from scanner isocenter, predicted b-value was 1-6% different than intended due to gradient nonlinearity, and predicted gradient directions were in error by up to 1 degree. Over the course of one month the change in these quantities due to calibration-related factors such as scanner drift and variation in phantom placement was <0.5% for b-values, and <0.5 degrees for angular deviation. The proposed calibration procedure allows the estimation of gradient nonlinearity to correct b-values and gradient directions ahead of advanced diffusion image processing for high angular resolution data, and requires only a five-minute phantom scan that can be included in a weekly or monthly quality assurance protocol.
Crossing fibers are prevalent in human brains and a subject of intense interest for neuroscience. Diffusion tensor imaging (DTI) can resolve tissue orientation but is blind to crossing fibers. Many advanced diffusion-weighted magnetic resolution imaging (MRI) approaches have been presented to extract crossing-fibers from high angular resolution diffusion imaging (HARDI), but the relative sensitivity and specificity of approaches remains unclear. Here, we examine two leading approaches (PAS and q-ball) in the context of a large-scale, single subject reproducibility study. A single healthy individual was scanned 11 times with 96 diffusion weighted directions and 10 reference volumes for each of five b-values (1000, 1500, 2000, 2500, 3000 s/mm2) for a total of 5830 volumes (over the course of three sessions). We examined the reproducibility of the number of fibers per voxel, volume fraction, and crossing-fiber angles. For each method, we determined the minimum resolvable angle for each acquisition. Reproducibility of fiber counts per voxel was generally high (~80% consensus for PAS and ~70% for q-ball), but there was substantial bias between individual repetitions and model estimated with all data (~10% lower consensus for PAS and ~15% lower for q-ball). Both PAS and q-ball predominantly discovered fibers crossing at near 90 degrees, but reproducibility was higher for PAS across most measures. Within voxels with low anisotropy, q-ball finds more intra-voxel structure; meanwhile, PAS resolves multiple fibers at greater than 75 degrees for more voxels. These results can inform researchers when deciding between HARDI approaches or interpreting findings across studies.
High-angular-resolution diffusion-weighted imaging (HARDI) MRI acquisitions have become common for use with
higher order models of diffusion. Despite successes in resolving complex fiber configurations and probing
microstructural properties of brain tissue, there is no common consensus on the optimal b-value and number of
diffusion directions to use for these HARDI methods. While this question has been addressed by analysis of the
diffusion-weighted signal directly, it is unclear how this translates to the information and metrics derived from the
HARDI models themselves. Using a high angular resolution data set acquired at a range of b-values, and repeated 11
times on a single subject, we study how the b-value and number of diffusion directions impacts the reproducibility
and precision of metrics derived from Q-ball imaging, a popular HARDI technique. We find that Q-ball metrics
associated with tissue microstructure and white matter fiber orientation are sensitive to both the number of diffusion
directions and the spherical harmonic representation of the Q-ball, and often are biased when under sampled. These
results can advise researchers on appropriate acquisition and processing schemes, particularly when it comes to
optimizing the number of diffusion directions needed for metrics derived from Q-ball imaging.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
INSTITUTIONAL Select your institution to access the SPIE Digital Library.
PERSONAL Sign in with your SPIE account to access your personal subscriptions or to use specific features such as save to my library, sign up for alerts, save searches, etc.