Andrew J. Asman

Formulating Spatially Varying Performance in the Statistical Fusion Framework

To date, label fusion methods have primarily relied either on global [e.g., simultaneous truth and performance level estimation (STAPLE), globally weighted vote] or voxelwise (e.g., locally weighted vote) performance models. Optimality of the statistical fusion framework hinges upon the validity of the stochastic model of how a rater errs (i.e., the labeling process model). Hitherto, approaches have tended to focus on the extremes of potential models. Herein, we propose an extension to the STAPLE approach to seamlessly account for spatially varying performance by extending the performance level parameters to account for a smooth, voxelwise performance level field that is unique to each rater. This approach, Spatial STAPLE, provides significant improvements over state-of-the-art label fusion algorithms in both simulated and empirical data sets.

Robust Statistical Label Fusion Through Consensus Level, Labeler Accuracy, and Truth Estimation (COLLATE)

Segmentation and delineation of structures of interest in medical images is paramount to quantifying and characterizing structural, morphological, and functional correlations with clinically relevant conditions. The established gold standard for performing segmentation has been manual voxel-by-voxel labeling by a neuroanatomist expert. This process can be extremely time consuming, resource intensive and fraught with high inter-observer variability. Hence, studies involving characterizations of novel structures or appearances have been limited in scope (numbers of subjects), scale (extent of regions assessed), and statistical power. Statistical methods to fuse data sets from several different sources (e.g., multiple human observers) have been proposed to simultaneously estimate both rater performance and the ground truth labels. However, with empirical datasets, statistical fusion has been observed to result in visually inconsistent findings. So, despite the ease and elegance of a statistical approach, single observers and/or direct voting are often used in practice. Hence, rater performance is not systematically quantified and exploited during label estimation. To date, statistical fusion methods have relied on characterizations of rater performance that do not intrinsically include spatially varying models of rater performance. Herein, we present a novel, robust statistical label fusion algorithm to estimate and account for spatially varying performance. This algorithm, COnsensus Level, Labeler Accuracy and Truth Estimation (COLLATE), is based on the simple idea that some regions of an image are difficult to label (e.g., confusion regions: boundaries or low contrast areas) while other regions are intrinsically obvious (e.g., consensus regions: centers of large regions or high contrast edges). Unlike its predecessors, COLLATE estimates the consensus level of each voxel and estimates differing models of observer behavior in each region. We show that COLLATE provides significant improvement in label accuracy and rater assessment over previous fusion methods in both simulated and empirical datasets.

Groupwise multi-atlas segmentation of the spinal cord's internal structure

The spinal cord is an essential and vulnerable component of the central nervous system. Differentiating and localizing the spinal cord internal structure (i.e., gray matter vs. white matter) is critical for assessment of therapeutic impacts and determining prognosis of relevant conditions. Fortunately, new magnetic resonance imaging (MRI) sequences enable clinical study of the in vivo spinal cords internal structure. Yet, low contrast-to-noise ratio, artifacts, and imaging distortions have limited the applicability of tissue segmentation techniques pioneered elsewhere in the central nervous system. Additionally, due to the inter-subject variability exhibited on cervical MRI, typical deformable volumetric registrations perform poorly, limiting the applicability of a typical multi-atlas segmentation framework. Thus, to date, no automated algorithms have been presented for the spinal cords internal structure. Herein, we present a novel slice-based groupwise registration framework for robustly segmenting cervical spinal cord MRI. Specifically, we provide a method for (1) pre-aligning the slice-based atlases into a groupwise-consistent space, (2) constructing a model of spinal cord variability, (3) projecting the target slice into the low-dimensional space using a model-specific registration cost function, and (4) estimating robust segmentation susing geodesically appropriate atlas information. Moreover, the proposed framework provides a natural mechanism for performing atlas selection and initializing the free model parameters in an informed manner. In a cross-validation experiment using 67 MR volumes of the cervical spinal cord, we demonstrate sub-millimetric accuracy, significant quantitative and qualitative improvement over comparable multi-atlas frameworks, and provide insight into the sensitivity of the associated model parameters.

Robust Statistical Fusion of Image Labels

Image labeling and parcellation (i.e., assigning structure to a collection of voxels) are critical tasks for the assessment of volumetric and morphometric features in medical imaging data. The process of image labeling is inherently error prone as images are corrupted by noise and artifacts. Even expert interpretations are subject to subjectivity and the precision of the individual raters. Hence, all labels must be considered imperfect with some degree of inherent variability. One may seek multiple independent assessments to both reduce this variability and quantify the degree of uncertainty. Existing techniques have exploited maximum a posteriori statistics to combine data from multiple raters and simultaneously estimate rater reliabilities. Although quite successful, wide-scale application has been hampered by unstable estimation with practical datasets, for example, with label sets with small or thin objects to be labeled or with partial or limited datasets. As well, these approaches have required each rater to generate a complete dataset, which is often impossible given both human foibles and the typical turnover rate of raters in a research or clinical environment. Herein, we propose a robust approach to improve estimation performance with small anatomical structures, allow for missing data, account for repeated label sets, and utilize training/catch trial data. With this approach, numerous raters can label small, overlapping portions of a large dataset, and rater heterogeneity can be robustly controlled while simultaneously estimating a single, reliable label set and characterizing uncertainty. The proposed approach enables many individuals to collaborate in the construction of large datasets for labeling tasks (e.g., human parallel processing) and reduces the otherwise detrimental impact of rater unavailability

Characterizing spatially varying performance to improve multi-atlas multi-label segmentation

Segmentation of medical images has become critical to building understanding of biological structure-functional relationships. Atlas registration and label transfer provide a fully-automated approach for deriving segmentations given atlas training data. When multiple atlases are used, statistical label fusion techniques have been shown to dramatically improve segmentation accuracy. However, these techniques have had limited success with complex structures and atlases with varying similarity to the target data. Previous approaches have parameterized raters by a single confusion matrix, so that spatially varying performance for a single rater is neglected. Herein, we reformulate the statistical fusion model to describe raters by regional confusion matrices so that co-registered atlas labels can be fused in an optimal, spatially varying manner, which leads to an improved label fusion estimation with heterogeneous atlases. The advantages of this approach are characterized in a simulation and an empirical whole-brain labeling task.

Simultaneous Analysis and Quality Assurance for Diffusion Tensor Imaging

Diffusion tensor imaging (DTI) enables non-invasive, cyto-architectural mapping of in vivo tissue microarchitecture through voxel-wise mathematical modeling of multiple magnetic resonance imaging (MRI) acquisitions, each differently sensitized to water diffusion. DTI computations are fundamentally estimation processes and are sensitive to noise and artifacts. Despite widespread adoption in the neuroimaging community, maintaining consistent DTI data quality remains challenging given the propensity for patient motion, artifacts associated with fast imaging techniques, and the possibility of hardware changes/failures. Furthermore, the quantity of data acquired per voxel, the non-linear estimation process, and numerous potential use cases complicate traditional visual data inspection approaches. Currently, quality inspection of DTI data has relied on visual inspection and individual processing in DTI analysis software programs (e.g. DTIPrep, DTI-studio). However, recent advances in applied statistical methods have yielded several different metrics to assess noise level, artifact propensity, quality of tensor fit, variance of estimated measures, and bias in estimated measures. To date, these metrics have been largely studied in isolation. Herein, we select complementary metrics for integration into an automatic DTI analysis and quality assurance pipeline. The pipeline completes in 24 hours, stores statistical outputs, and produces a graphical summary quality analysis (QA) report. We assess the utility of this streamlined approach for empirical quality assessment on 608 DTI datasets from pediatric neuroimaging studies. The efficiency and accuracy of quality analysis using the proposed pipeline is compared with quality analysis based on visual inspection. The unified pipeline is found to save a statistically significant amount of time (over 70%) while improving the consistency of QA between a DTI expert and a pool of research associates. Projection of QA metrics to a low dimensional manifold reveal qualitative, but clear, QA-study associations and suggest that automated outlier/anomaly detection would be feasible.

Multi-atlas learner fusion: An efficient segmentation approach for large-scale data.

We propose multi-atlas learner fusion (MLF), a framework for rapidly and accurately replicating the highly accurate, yet computationally expensive, multi-atlas segmentation framework based on fusing local learners. In the largest whole-brain multi-atlas study yet reported, multi-atlas segmentations are estimated for a training set of 3464 MR brain images. Using these multi-atlas estimates we (1) estimate a low-dimensional representation for selecting locally appropriate example images, and (2) build AdaBoost learners that map a weak initial segmentation to the multi-atlas segmentation result. Thus, to segment a new target image we project the image into the low-dimensional space, construct a weak initial segmentation, and fuse the trained, locally selected, learners. The MLF framework cuts the runtime on a modern computer from 36 h down to 3-8 min - a 270× speedup - by completely bypassing the need for deformable atlas-target registrations. Additionally, we (1) describe a technique for optimizing the weak initial segmentation and the AdaBoost learning parameters, (2) quantify the ability to replicate the multi-atlas result with mean accuracies approaching the multi-atlas intra-subject reproducibility on a testing set of 380 images, (3) demonstrate significant increases in the reproducibility of intra-subject segmentations when compared to a state-of-the-art multi-atlas framework on a separate reproducibility dataset, (4) show that under the MLF framework the large-scale data model significantly improve the segmentation over the small-scale model under the MLF framework, and (5) indicate that the MLF framework has comparable performance as state-of-the-art multi-atlas segmentation algorithms without using non-local information.

Robust optic nerve segmentation on clinically acquired computed tomography.

Abstract. The optic nerve (ON) plays a critical role in many devastating pathological conditions. Segmentation of the ON has the ability to provide understanding of anatomical development and progression of diseases of the ON. Recently, methods have been proposed to segment the ON but progress toward full automation has been limited. We optimize registration and fusion methods for a new multi-atlas framework for automated segmentation of the ONs, eye globes, and muscles on clinically acquired computed tomography (CT) data. Briefly, the multi-atlas approach consists of determining a region of interest within each scan using affine registration, followed by nonrigid registration on reduced field of view atlases, and performing statistical fusion on the results. We evaluate the robustness of the approach by segmenting the ON structure in 501 clinically acquired CT scan volumes obtained from 183 subjects from a thyroid eye disease patient population. A subset of 30 scan volumes was manually labeled to assess accuracy and guide method choice. Of the 18 compared methods, the ANTS Symmetric Normalization registration and nonlocal spatial simultaneous truth and performance level estimation statistical fusion resulted in the best overall performance, resulting in a median Dice similarity coefficient of 0.77, which is comparable with inter-rater (human) reproducibility at 0.73.

Foibles, follies, and fusion: web-based collaboration for medical image labeling.

Labels that identify specific anatomical and functional structures within medical images are essential to the characterization of the relationship between structure and function in many scientific and clinical studies. Automated methods that allow for high throughput have not yet been developed for all anatomical targets or validated for exceptional anatomies, and manual labeling remains the gold standard in many cases. However, manual placement of labels within a large image volume such as that obtained using magnetic resonance imaging (MRI) is exceptionally challenging, resource intensive, and fraught with intra- and inter-rater variability. The use of statistical methods to combine labels produced by multiple raters has grown significantly in popularity, in part, because it is thought that by estimating and accounting for rater reliability estimates of the true labels will be more accurate. This paper demonstrates the performance of a class of these statistical label combination 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 presented. It is demonstrated that statistical fusion successfully combines label information using data from online (Internet-based) collaborations among minimally trained raters. This first successful demonstration of a statistically based approach using minimally trained raters opens numerous possibilities for very large scale efforts in collaboration. Extension and generalization of these technologies for new applications will certainly present fascinating areas for continuing research.

Simultaneous total intracranial volume and posterior fossa volume estimation using multi-atlas label fusion

Total intracranial volume (TICV) is an essential covariate in brain volumetric analyses. The prevalent brain imaging software packages provide automatic TICV estimates. FreeSurfer and FSL estimate TICV using a scaling factor while SPM12 accumulates probabilities of brain tissues. None of the three provide explicit skull/CSF boundary (SCB) since it is challenging to distinguish these dark structures in a T1‐weighted image. However, explicit SCB not only leads to a natural way of obtaining TICV (i.e., counting voxels inside the skull) but also allows sub‐definition of TICV, for example, the posterior fossa volume (PFV). In this article, they proposed to use multi‐atlas label fusion to obtain TICV and PFV simultaneously. The main contributions are: (1) TICV and PFV are simultaneously obtained with explicit SCB from a single T1‐weighted image. (2) TICV and PFV labels are added to the widely used BrainCOLOR atlases. (3) Detailed mathematical derivation of non‐local spatial STAPLE (NLSS) label fusion is presented. As the skull is clearly distinguished in CT images, we use a semi‐manual procedure to obtain atlases with TICV and PFV labels using 20 subjects who both have a MR and CT scan. The proposed method provides simultaneous TICV and PFV estimation while achieving more accurate TICV estimation compared with FreeSurfer, FSL, SPM12, and the previously proposed STAPLE based approach. The newly developed TICV and PFV labels for the OASIS BrainCOLOR atlases provide acceptable performance, which enables simultaneous TICV and PFV estimation during whole brain segmentation. The NLSS method and the new atlases have been made freely available. Hum Brain Mapp 38:599–616, 2017.