Prasanna Parvathaneni

Empirical consideration of the effects of acquisition parameters and analysis model on clinically feasible q-ball imaging

Q-ball imaging (QBI) is a popular high angular resolution diffusion imaging (HARDI) technique used to study brain architecture in vivo. Simulation and phantom-based studies suggest that QBI results are affected by the b-value, the number of diffusion weighting directions, and the signal-to-noise ratio (SNR). However, optimal acquisition schemes for QBI in clinical settings are largely undetermined given empirical (observed) imaging considerations. In this study, we acquire a HARDI dataset at five b-values with 11 repetitions on a single subject to investigate the effects of acquisition scheme and subsequent analysis models on the accuracy and precision of measures of tissue composition and fiber orientation derived from clinically feasible QBI at 3T. Clinical feasibility entails short scan protocols - less than 5minutes in the current study - resulting in lower SNR, lower b-values, and fewer diffusion directions than are typical in most QBI protocols with research applications, where time constraints are less prevalent. In agreement with previous studies, we find that the b-value and number of diffusion directions impact the magnitude and variation of QBI indices in both white matter and gray matter regions; however, QBI indices are most heavily dependent on the maximum order of the spherical harmonic (SH) series used to represent the diffusion orientation distribution function (ODF). Specifically, to ensure numerical stability and reduce the occurrence of false peaks and inflated anisotropy, we recommend oversampling by at least 8-12 more diffusion directions than the number of estimated coefficients for a given SH order. In addition, in an equal scan time comparison of QBI accuracy, we find that increasing the directional resolution of the HARDI dataset is preferable to repeating observations; however, our results indicate that as few as 32 directions at a low b-value (1000s/mm2) captures most of the angular information in the q-ball ODF. Our findings provide guidance for determining an optimal acquisition scheme for QBI in the low SNR and low scan time regime, and suggest that care must be taken when choosing the basis functions used to represent the QBI ODF.

Integrating histology and MRI in the first digital brain of common squirrel monkey, Saimiri sciureus

This effort is a continuation of development of a digital brain atlas of the common squirrel monkey, Saimiri sciureus, a New World monkey with functional and microstructural organization of central nervous system similar to that of humans. Here, we present the integration of histology with multi-modal magnetic resonance imaging (MRI) atlas constructed from the brain of an adult female squirrel monkey. The central concept of this work is to use block face photography to establish an intermediate common space in coordinate system which preserves the high resolution in-plane resolution of histology while enabling 3-D correspondence with MRI. In vivo MRI acquisitions include high resolution T2 structural imaging (300 μm isotropic) and low resolution diffusion tensor imaging (600 um isotropic). Ex vivo MRI acquisitions include high resolution T2 structural imaging and high resolution diffusion tensor imaging (both 300 μm isotropic). Cortical regions were manually annotated on the co-registered volumes based on published histological sections in-plane. We describe mapping of histology and MRI based data of the common squirrel monkey and construction of a viewing tool that enable online viewing of these datasets. The previously descried atlas MRI is used for its deformation to provide accurate conformation to the MRI, thus adding information at the histological level to the MRI volume. This paper presents the mapping of single 2D image slice in block face as a proof of concept and this can be extended to map the atlas space in 3D coordinate system as part of the future work and can be loaded to an XNAT system for further use.

Improved stability of whole brain surface parcellation with multi-atlas segmentation.

Whole brain segmentation and cortical surface parcellation are essential in understanding the brain’s anatomicalfunctional relationships. Multi-atlas segmentation has been regarded as one of the leading segmentation methods for the whole brain segmentation. In our recent work, the multi-atlas technique has been adapted to surface reconstruction using a method called Multi-atlas CRUISE (MaCRUISE). The MaCRUISE method not only performed consistent volumesurface analyses but also showed advantages on robustness compared with the FreeSurfer method. However, a detailed surface parcellation was not provided by MaCRUISE, which hindered the region of interest (ROI) based analyses on surfaces. Herein, the MaCRUISE surface parcellation (MaCRUISEsp) method is proposed to perform the surface parcellation upon the inner, central and outer surfaces that are reconstructed from MaCRUISE. MaCRUISEsp parcellates inner, central and outer surfaces with 98 cortical labels respectively using a volume segmentation based surface parcellation (VSBSP), following a topological correction step. To validate the performance of MaCRUISEsp, 21 scanrescan magnetic resonance imaging (MRI) T1 volume pairs from the Kirby21 dataset were used to perform a reproducibility analyses. MaCRUISEsp achieved 0.948 on median Dice Similarity Coefficient (DSC) for central surfaces. Meanwhile, FreeSurfer achieved 0.905 DSC for inner surfaces and 0.881 DSC for outer surfaces, while the proposed method achieved 0.929 DSC for inner surfaces and 0.835 DSC for outer surfaces. Qualitatively, the results are encouraging, but are not directly comparable as the two approaches use different definitions of cortical labels.

Gray Matter Surface Based Spatial Statistics (GS-BSS) in Diffusion Microstructure

Tract-based spatial statistics (TBSS) has proven to be a popular technique for performing voxel-wise statistical analysis that aims to improve sensitivity and interpretability of analysis of multi-subject diffusion imaging studies in white matter. With the advent of advanced diffusion MRI models - e.g., the neurite orientation dispersion density imaging (NODDI), it is of interest to analyze microstructural changes within gray matter (GM). A recent study has proposed using NODDI in gray matter based spatial statistics (N-GBSS) to perform voxel-wise statistical analysis on GM microstructure. N-GBSS adapts TBSS by skeletonizing the GM and projecting diffusion metrics to a cortical ribbon. In this study, we propose an alternate approach, known as gray matter surface based spatial statistics (GS-BSS), to perform statistical analysis using gray matter surfaces by incorporating established methods of registration techniques of GM surface segmentation on structural images. Diffusion microstructure features from NODDI and GM surfaces are transferred to standard space. All the surfaces are then projected onto a common GM surface non-linearly using diffeomorphic spectral matching on cortical surfaces. Prior post-mortem studies have shown reduced dendritic length in prefrontal cortex region in schizophrenia and bipolar disorder population. To validate the results, statistical tests are compared between GS-BSS and N-GBSS to study the differences between healthy and psychosis population. Significant results confirming the microstructural changes are presented. GS-BSS results show higher sensitivity to group differences between healthy and psychosis population in previously known regions.

A 3D high resolution ex vivo white matter atlas of the common squirrel monkey (saimiri sciureus) based on diffusion tensor imaging

Modern magnetic resonance imaging (MRI) brain atlases are high quality 3-D volumes with specific structures labeled in the volume. Atlases are essential in providing a common space for interpretation of results across studies, for anatomical education, and providing quantitative image-based navigation. Extensive work has been devoted to atlas construction for humans, macaque, and several non-primate species (e.g., rat). One notable gap in the literature is the common squirrel monkey – for which the primary published atlases date from the 1960’s. The common squirrel monkey has been used extensively as surrogate for humans in biomedical studies, given its anatomical neuro-system similarities and practical considerations. This work describes the continued development of a multi-modal MRI atlas for the common squirrel monkey, for which a structural imaging space and gray matter parcels have been previously constructed. This study adds white matter tracts to the atlas. The new atlas includes 49 white matter (WM) tracts, defined using diffusion tensor imaging (DTI) in three animals and combines these data to define the anatomical locations of these tracks in a standardized coordinate system compatible with previous development. An anatomist reviewed the resulting tracts and the inter-animal reproducibility (i.e., the Dice index of each WM parcel across animals in common space) was assessed. The Dice indices range from 0.05 to 0.80 due to differences of local registration quality and the variation of WM tract position across individuals. However, the combined WM labels from the 3 animals represent the general locations of WM parcels, adding basic connectivity information to the atlas.

Limits to anatomical accuracy of diffusion tractography using modern approaches

&NA; Diffusion MRI fiber tractography is widely used to probe the structural connectivity of the brain, with a range of applications in both clinical and basic neuroscience. Despite widespread use, tractography has well‐known pitfalls that limits the anatomical accuracy of this technique. Numerous modern methods have been developed to address these shortcomings through advances in acquisition, modeling, and computation. To test whether these advances improve tractography accuracy, we organized the 3‐D Validation of Tractography with Experimental MRI (3D‐VoTEM) challenge at the ISBI 2018 conference. We made available three unique independent tractography validation datasets – a physical phantom and two ex vivo brain specimens ‐ resulting in 176 distinct submissions from 9 research groups. By comparing results over a wide range of fiber complexities and algorithmic strategies, this challenge provides a more comprehensive assessment of tractographys inherent limitations than has been reported previously. The central results were consistent across all sub‐challenges in that, despite advances in tractography methods, the anatomical accuracy of tractography has not dramatically improved in recent years. Taken together, our results independently confirm findings from decades of tractography validation studies, demonstrate inherent limitations in reconstructing white matter pathways using diffusion MRI data alone, and highlight the need for alternative or combinatorial strategies to accurately map the fiber pathways of the brain. HighlightsOrganized international tractography challenge utilizing three validation datasets.Anatomical accuracy of modern diffusion tractography techniques is limited.Advancements are needed to overcome limited sensitivity/specificity of reconstructions.

Spatially Localized Atlas Network Tiles Enables 3D Whole Brain Segmentation from Limited Data.

Whole brain segmentation on a structural magnetic resonance imaging (MRI) is essential in non-invasive investigation for neuroanatomy. Historically, multi-atlas segmentation (MAS) has been regarded as the de facto standard method for whole brain segmentation. Recently, deep neural network approaches have been applied to whole brain segmentation by learning random patches or 2D slices. Yet, few previous efforts have been made on detailed whole brain segmentation using 3D networks due to the following challenges: (1) fitting entire whole brain volume into 3D networks is restricted by the current GPU memory, and (2) the large number of targeting labels (e.g., > 100 labels) with limited number of training 3D volumes (e.g., 30 hours using MAS to ~15 minutes using the proposed method. The source code is available online this https URL

Constructing statistically unbiased cortical surface templates using feature-space covariance.

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.

SHARD: spherical harmonic-based robust outlier detection for HARDI methods

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.

Evaluation of inter-site bias and variance in diffusion-weighted MRI

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.