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We estimate the U.S. temperature response profile (TRP) for COVID-19 and show it is highly sensitive to temperature variation. Replacing the erratic daily death counts U.S. states initially reported with counts based on death certificate date, we build a week-ahead statistical forecasting model that explains most of their daily variation (R2 = 0.97) and isolates COVID-19's TRP (p < 0.001). These counts, normalized at 31 °C (U.S. mid-summer average), scale up to 160% at 5 °C in the static case where the infection pool is held constant. Positive case counts are substantially more temperature sensitive. When temperatures are declining, dynamic feedback through a growing infection pool can substantially amplify these temperature effects. Our estimated TRP can be incorporated into COVID-related planning exercises and used as an input to SEIR models employed for longer run forecasting. For the former, we show how our TRP is predictive of the realized pattern of growth rates in per capita positive cases across states five months after the end of our sample period. For the latter, we show the variation in herd immunity levels implied by temperature-driven, time-varying R0 series for the Alpha and Delta variants of COVID-19 for several representative states. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10640-021-00603-8.
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Cross-scanner and cross-protocol variability of diffusion magnetic resonance imaging (dMRI) data are known to be major obstacles in multi-site clinical studies since they limit the ability to aggregate dMRI data and derived measures. Computational algorithms that harmonize the data and minimize such variability are critical to reliably combine datasets acquired from different scanners and/or protocols, thus improving the statistical power and sensitivity of multi-site studies. Different computational approaches have been proposed to harmonize diffusion MRI data or remove scanner-specific differences. To date, these methods have mostly been developed for or evaluated on single b-value diffusion MRI data. In this work, we present the evaluation results of 19 algorithms that are developed to harmonize the cross-scanner and cross-protocol variability of multi-shell diffusion MRI using a benchmark database. The proposed algorithms rely on various signal representation approaches and computational tools, such as rotational invariant spherical harmonics, deep neural networks and hybrid biophysical and statistical approaches. The benchmark database consists of data acquired from the same subjects on two scanners with different maximum gradient strength (80 and 300 âmT/m) and with two protocols. We evaluated the performance of these algorithms for mapping multi-shell diffusion MRI data across scanners and across protocols using several state-of-the-art imaging measures. The results show that data harmonization algorithms can reduce the cross-scanner and cross-protocol variabilities to a similar level as scan-rescan variability using the same scanner and protocol. In particular, the LinearRISH algorithm based on adaptive linear mapping of rotational invariant spherical harmonics features yields the lowest variability for our data in predicting the fractional anisotropy (FA), mean diffusivity (MD), mean kurtosis (MK) and the rotationally invariant spherical harmonic (RISH) features. But other algorithms, such as DIAMOND, SHResNet, DIQT, CMResNet show further improvement in harmonizing the return-to-origin probability (RTOP). The performance of different approaches provides useful guidelines on data harmonization in future multi-site studies.
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Algoritmos , Encéfalo/diagnóstico por imagem , Aprendizado Profundo , Imagem de Difusão por Ressonância Magnética/métodos , Processamento de Imagem Assistida por Computador/métodos , Neuroimagem/métodos , Adulto , Imagem de Difusão por Ressonância Magnética/instrumentação , Imagem de Difusão por Ressonância Magnética/normas , Humanos , Processamento de Imagem Assistida por Computador/normas , Neuroimagem/instrumentação , Neuroimagem/normas , Análise de RegressãoRESUMO
PURPOSE: In the present work, we describe the correction of diffusion-weighted MRI for site and scanner biases using a novel method based on invariant representation. THEORY AND METHODS: Pooled imaging data from multiple sources are subject to variation between the sources. Correcting for these biases has become very important as imaging studies increase in size and multi-site cases become more common. We propose learning an intermediate representation invariant to site/protocol variables, a technique adapted from information theory-based algorithmic fairness; by leveraging the data processing inequality, such a representation can then be used to create an image reconstruction that is uninformative of its original source, yet still faithful to underlying structures. To implement this, we use a deep learning method based on variational auto-encoders (VAE) to construct scanner invariant encodings of the imaging data. RESULTS: To evaluate our method, we use training data from the 2018 MICCAI Computational Diffusion MRI (CDMRI) Challenge Harmonization dataset. Our proposed method shows improvements on independent test data relative to a recently published baseline method on each subtask, mapping data from three different scanning contexts to and from one separate target scanning context. CONCLUSIONS: As imaging studies continue to grow, the use of pooled multi-site imaging will similarly increase. Invariant representation presents a strong candidate for the harmonization of these data.
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Encéfalo , Imagem de Difusão por Ressonância Magnética , Encéfalo/diagnóstico por imagem , Processamento de Imagem Assistida por ComputadorRESUMO
Purpose: Specular reflections (SRs) are highlight artifacts commonly found in endoscopy videos that can severely disrupt a surgeon's observation and judgment. Despite numerous attempts to restore SR, existing methods are inefficient and time consuming and can lead to false clinical interpretations. Therefore, we propose the first complete deep-learning solution, SpecReFlow, to detect and restore SR regions from endoscopy video with spatial and temporal coherence. Approach: SpecReFlow consists of three stages: (1) an image preprocessing stage to enhance contrast, (2) a detection stage to indicate where the SR region is present, and (3) a restoration stage in which we replace SR pixels with an accurate underlying tissue structure. Our restoration approach uses optical flow to seamlessly propagate color and structure from other frames of the endoscopy video. Results: Comprehensive quantitative and qualitative tests for each stage reveal that our SpecReFlow solution performs better than previous detection and restoration methods. Our detection stage achieves a Dice score of 82.8% and a sensitivity of 94.6%, and our restoration stage successfully incorporates temporal information with spatial information for more accurate restorations than existing techniques. Conclusions: SpecReFlow is a first-of-its-kind solution that combines temporal and spatial information for effective detection and restoration of SR regions, surpassing previous methods relying on single-frame spatial information. Future work will look to optimizing SpecReFlow for real-time applications. SpecReFlow is a software-only solution for restoring image content lost due to SR, making it readily deployable in existing clinical settings to improve endoscopy video quality for accurate diagnosis and treatment.
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Rigid motion tracking is paramount in many medical imaging applications where movements need to be detected, corrected, or accounted for. Modern strategies rely on convolutional neural networks (CNN) and pose this problem as rigid registration. Yet, CNNs do not exploit natural symmetries in this task, as they are equivariant to translations (their outputs shift with their inputs) but not to rotations. Here we propose EquiTrack, the first method that uses recent steerable SE(3)-equivariant CNNs (E-CNN) for motion tracking. While steerable E-CNNs can extract corresponding features across different poses, testing them on noisy medical images reveals that they do not have enough learning capacity to learn noise invariance. Thus, we introduce a hybrid architecture that pairs a denoiser with an E-CNN to decouple the processing of anatomically irrelevant intensity features from the extraction of equivariant spatial features. Rigid transforms are then estimated in closed-form. EquiTrack outperforms state-of-the-art learning and optimisation methods for motion tracking in adult brain MRI and fetal MRI time series. Our code is available at https://github.com/BBillot/EquiTrack.
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Data harmonization is necessary for removing confounding effects in multi-site diffusion image analysis. One such harmonization method, LinearRISH, scales rotationally invariant spherical harmonic (RISH) features from one site ("target") to the second ("reference") to reduce confounding scanner effects. However, reference and target site designations are not arbitrary and resultant diffusion metrics (fractional anisotropy, mean diffusivity) are biased by this choice. In this work we propose MidRISH: rather than scaling reference RISH features to target RISH features, we project both sites to a mid-space. We validate MidRISH with the following experiments: harmonizing scanner differences from 37 matched patients free of cognitive impairment, and harmonizing acquisition and study differences on 117 matched patients free of cognitive impairment. We find that MidRISH reduces bias of reference selection while preserving harmonization efficacy of LinearRISH. Users should be cautious when performing LinearRISH harmonization. To select a reference site is to choose diffusion metric effect-size. Our proposed method eliminates the bias-inducing site selection step.
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Algoritmos , Humanos , Feminino , Masculino , Processamento de Imagem Assistida por Computador/métodos , Reprodutibilidade dos Testes , Encéfalo/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética/métodos , Anisotropia , Idoso , Pessoa de Meia-Idade , Imagem de Tensor de Difusão/métodos , Disfunção Cognitiva/diagnóstico por imagem , Interpretação de Imagem Assistida por Computador/métodosRESUMO
Purpose: In brain diffusion magnetic resonance imaging (dMRI), the volumetric and bundle analyses of whole-brain tissue microstructure and connectivity can be severely impeded by an incomplete field of view (FOV). We aim to develop a method for imputing the missing slices directly from existing dMRI scans with an incomplete FOV. We hypothesize that the imputed image with a complete FOV can improve whole-brain tractography for corrupted data with an incomplete FOV. Therefore, our approach provides a desirable alternative to discarding the valuable brain dMRI data, enabling subsequent tractography analyses that would otherwise be challenging or unattainable with corrupted data. Approach: We propose a framework based on a deep generative model that estimates the absent brain regions in dMRI scans with an incomplete FOV. The model is capable of learning both the diffusion characteristics in diffusion-weighted images (DWIs) and the anatomical features evident in the corresponding structural images for efficiently imputing missing slices of DWIs in the incomplete part of the FOV. Results: For evaluating the imputed slices, on the Wisconsin Registry for Alzheimer's Prevention (WRAP) dataset, the proposed framework achieved PSNR b 0 = 22.397 , SSIM b 0 = 0.905 , PSNR b 1300 = 22.479 , and SSIM b 1300 = 0.893 ; on the National Alzheimer's Coordinating Center (NACC) dataset, it achieved PSNR b 0 = 21.304 , SSIM b 0 = 0.892 , PSNR b 1300 = 21.599 , and SSIM b 1300 = 0.877 . The proposed framework improved the tractography accuracy, as demonstrated by an increased average Dice score for 72 tracts ( p < 0.001 ) on both the WRAP and NACC datasets. Conclusions: Results suggest that the proposed framework achieved sufficient imputation performance in brain dMRI data with an incomplete FOV for improving whole-brain tractography, thereby repairing the corrupted data. Our approach achieved more accurate whole-brain tractography results with an extended and complete FOV and reduced the uncertainty when analyzing bundles associated with Alzheimer's disease.
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Background: As large analyses merge data across sites, a deeper understanding of variance in statistical assessment across the sources of data becomes critical for valid analyses. Diffusion tensor imaging (DTI) exhibits spatially varying and correlated noise, so care must be taken with distributional assumptions. Purpose: We characterize the role of physiology, subject compliance, and the interaction of subject with the scanner in the understanding of DTI variability, as modeled in spatial variance of derived metrics in homogeneous regions. Methods: We analyze DTI data from 1035 subjects in the Baltimore Longitudinal Study of Aging (BLSA), with ages ranging from 22.4 to 103 years old. For each subject, up to 12 longitudinal sessions were conducted. We assess variance of DTI scalars within regions of interest (ROIs) defined by four segmentation methods and investigate the relationships between the variance and covariates, including baseline age, time from the baseline (referred to as "interval"), motion, sex, and whether it is the first scan or the second scan in the session. Results: Covariate effects are heterogeneous and bilaterally symmetric across ROIs. Inter-session interval is positively related (p ⪠0.001) to FA variance in the cuneus and occipital gyrus, but negatively (p ⪠0.001) in the caudate nucleus. Males show significantly (p ⪠0.001) higher FA variance in the right putamen, thalamus, body of the corpus callosum, and cingulate gyrus. In 62 out of 176 ROIs defined by the Eve type-1 atlas, an increase in motion is associated (p < 0.05) with a decrease in FA variance. Head motion increases during the rescan of DTI (Δµ = 0.045 millimeters per volume). Conclusions: The effects of each covariate on DTI variance, and their relationships across ROIs are complex. Ultimately, we encourage researchers to include estimates of variance when sharing data and consider models of heteroscedasticity in analysis. This work provides a foundation for study planning to account for regional variations in metric variance.
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T1-weighted (T1w) MRI has low frequency intensity artifacts due to magnetic field inhomogeneities. Removal of these biases in T1w MRI images is a critical preprocessing step to ensure spatially consistent image interpretation. N4ITK bias field correction, the current state-of-the-art, is implemented in such a way that makes it difficult to port between different pipelines and workflows, thus making it hard to reimplement and reproduce results across local, cloud, and edge platforms. Moreover, N4ITK is opaque to optimization before and after its application, meaning that methodological development must work around the inhomogeneity correction step. Given the importance of bias fields correction in structural preprocessing and flexible implementation, we pursue a deep learning approximation / reinterpretation of the N4ITK bias fields correction to create a method which is portable, flexible, and fully differentiable. In this paper, we trained a deep learning network "DeepN4" on eight independent cohorts from 72 different scanners and age ranges with N4ITK-corrected T1w MRI and bias field for supervision in log space. We found that we can closely approximate N4ITK bias fields correction with naïve networks. We evaluate the peak signal to noise ratio (PSNR) in test dataset against the N4ITK corrected images. The median PSNR of corrected images between N4ITK and DeepN4 was 47.96 dB. In addition, we assess the DeepN4 model on eight additional external datasets and show the generalizability of the approach. This study establishes that incompatible N4ITK preprocessing steps can be closely approximated by naïve deep neural networks, facilitating more flexibility. All code and models are released at https://github.com/MASILab/DeepN4 .
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Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Algoritmos , Redes Neurais de Computação , ViésRESUMO
Purpose: As large analyses merge data across sites, a deeper understanding of variance in statistical assessment across the sources of data becomes critical for valid analyses. Diffusion tensor imaging (DTI) exhibits spatially varying and correlated noise, so care must be taken with distributional assumptions. Here, we characterize the role of physiology, subject compliance, and the interaction of the subject with the scanner in the understanding of DTI variability, as modeled in the spatial variance of derived metrics in homogeneous regions. Approach: We analyze DTI data from 1035 subjects in the Baltimore Longitudinal Study of Aging, with ages ranging from 22.4 to 103 years old. For each subject, up to 12 longitudinal sessions were conducted. We assess the variance of DTI scalars within regions of interest (ROIs) defined by four segmentation methods and investigate the relationships between the variance and covariates, including baseline age, time from the baseline (referred to as "interval"), motion, sex, and whether it is the first scan or the second scan in the session. Results: Covariate effects are heterogeneous and bilaterally symmetric across ROIs. Inter-session interval is positively related ( p ⪠0.001 ) to FA variance in the cuneus and occipital gyrus, but negatively ( p ⪠0.001 ) in the caudate nucleus. Males show significantly ( p ⪠0.001 ) higher FA variance in the right putamen, thalamus, body of the corpus callosum, and cingulate gyrus. In 62 out of 176 ROIs defined by the Eve type-1 atlas, an increase in motion is associated ( p < 0.05 ) with a decrease in FA variance. Head motion increases during the rescan of DTI ( Δ µ = 0.045 mm per volume). Conclusions: The effects of each covariate on DTI variance and their relationships across ROIs are complex. Ultimately, we encourage researchers to include estimates of variance when sharing data and consider models of heteroscedasticity in analysis. This work provides a foundation for study planning to account for regional variations in metric variance.
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Purpose: Diffusion tensor imaging (DTI) is a magnetic resonance imaging technique that provides unique information about white matter microstructure in the brain but is susceptible to confounding effects introduced by scanner or acquisition differences. ComBat is a leading approach for addressing these site biases. However, despite its frequent use for harmonization, ComBat's robustness toward site dissimilarities and overall cohort size have not yet been evaluated in terms of DTI. Approach: As a baseline, we match N=358 participants from two sites to create a "silver standard" that simulates a cohort for multi-site harmonization. Across sites, we harmonize mean fractional anisotropy and mean diffusivity, calculated using participant DTI data, for the regions of interest defined by the JHU EVE-Type III atlas. We bootstrap 10 iterations at 19 levels of total sample size, 10 levels of sample size imbalance between sites, and 6 levels of mean age difference between sites to quantify (i) ßAGE, the linear regression coefficient of the relationship between FA and age; (ii) γ/f*, the ComBat-estimated site-shift; and (iii) δ/f*, the ComBat-estimated site-scaling. We characterize the reliability of ComBat by evaluating the root mean squared error in these three metrics and examine if there is a correlation between the reliability of ComBat and a violation of assumptions. Results: ComBat remains well behaved for ßAGE when N>162 and when the mean age difference is less than 4 years. The assumptions of the ComBat model regarding the normality of residual distributions are not violated as the model becomes unstable. Conclusion: Prior to harmonization of DTI data with ComBat, the input cohort should be examined for size and covariate distributions of each site. Direct assessment of residual distributions is less informative on stability than bootstrap analysis. We caution use ComBat of in situations that do not conform to the above thresholds.
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Connectivity matrices derived from diffusion MRI (dMRI) provide an interpretable and generalizable way of understanding the human brain connectome. However, dMRI suffers from inter-site and between-scanner variation, which impedes analysis across datasets to improve robustness and reproducibility of results. To evaluate different harmonization approaches on connectivity matrices, we compared graph measures derived from these matrices before and after applying three harmonization techniques: mean shift, ComBat, and CycleGAN. The sample comprises 168 age-matched, sex-matched normal subjects from two studies: the Vanderbilt Memory and Aging Project (VMAP) and the Biomarkers of Cognitive Decline Among Normal Individuals (BIOCARD). First, we plotted the graph measures and used coefficient of variation (CoV) and the Mann-Whitney U test to evaluate different methods' effectiveness in removing site effects on the matrices and the derived graph measures. ComBat effectively eliminated site effects for global efficiency and modularity and outperformed the other two methods. However, all methods exhibited poor performance when harmonizing average betweenness centrality. Second, we tested whether our harmonization methods preserved correlations between age and graph measures. All methods except for CycleGAN in one direction improved correlations between age and global efficiency and between age and modularity from insignificant to significant with p-values less than 0.05.
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Imaging findings inconsistent with those expected at specific chronological age ranges may serve as early indicators of neurological disorders and increased mortality risk. Estimation of chronological age, and deviations from expected results, from structural magnetic resonance imaging (MRI) data has become an important proxy task for developing biomarkers that are sensitive to such deviations. Complementary to structural analysis, diffusion tensor imaging (DTI) has proven effective in identifying age-related microstructural changes within the brain white matter, thereby presenting itself as a promising additional modality for brain age prediction. Although early studies have sought to harness DTI's advantages for age estimation, there is no evidence that the success of this prediction is owed to the unique microstructural and diffusivity features that DTI provides, rather than the macrostructural features that are also available in DTI data. Therefore, we seek to develop white-matter-specific age estimation to capture deviations from normal white matter aging. Specifically, we deliberately disregard the macrostructural information when predicting age from DTI scalar images, using two distinct methods. The first method relies on extracting only microstructural features from regions of interest (ROIs). The second applies 3D residual neural networks (ResNets) to learn features directly from the images, which are non-linearly registered and warped to a template to minimize macrostructural variations. When tested on unseen data, the first method yields mean absolute error (MAE) of 6.11 ± 0.19 years for cognitively normal participants and MAE of 6.62 ± 0.30 years for cognitively impaired participants, while the second method achieves MAE of 4.69 ± 0.23 years for cognitively normal participants and MAE of 4.96 ± 0.28 years for cognitively impaired participants. We find that the ResNet model captures subtler, non-macrostructural features for brain age prediction.
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Machine learning provides a valuable tool for analyzing high-dimensional functional neuroimaging data, and is proving effective in predicting various neurological conditions, psychiatric disorders, and cognitive patterns. In functional magnetic resonance imaging (MRI) research, interactions between brain regions are commonly modeled using graph-based representations. The potency of graph machine learning methods has been established across myriad domains, marking a transformative step in data interpretation and predictive modeling. Yet, despite their promise, the transposition of these techniques to the neuroimaging domain has been challenging due to the expansive number of potential preprocessing pipelines and the large parameter search space for graph-based dataset construction. In this paper, we introduce NeuroGraph, a collection of graph-based neuroimaging datasets, and demonstrated its utility for predicting multiple categories of behavioral and cognitive traits. We delve deeply into the dataset generation search space by crafting 35 datasets that encompass static and dynamic brain connectivity, running in excess of 15 baseline methods for benchmarking. Additionally, we provide generic frameworks for learning on both static and dynamic graphs. Our extensive experiments lead to several key observations. Notably, using correlation vectors as node features, incorporating larger number of regions of interest, and employing sparser graphs lead to improved performance. To foster further advancements in graph-based data driven neuroimaging analysis, we offer a comprehensive open-source Python package that includes the benchmark datasets, baseline implementations, model training, and standard evaluation.
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Reconstructing 3D MR volumes from multiple motion-corrupted stacks of 2D slices has shown promise in imaging of moving subjects, e. g., fetal MRI. However, existing slice-to-volume reconstruction methods are time-consuming, especially when a high-resolution volume is desired. Moreover, they are still vulnerable to severe subject motion and when image artifacts are present in acquired slices. In this work, we present NeSVoR, a resolution-agnostic slice-to-volume reconstruction method, which models the underlying volume as a continuous function of spatial coordinates with implicit neural representation. To improve robustness to subject motion and other image artifacts, we adopt a continuous and comprehensive slice acquisition model that takes into account rigid inter-slice motion, point spread function, and bias fields. NeSVoR also estimates pixel-wise and slice-wise variances of image noise and enables removal of outliers during reconstruction and visualization of uncertainty. Extensive experiments are performed on both simulated and in vivo data to evaluate the proposed method. Results show that NeSVoR achieves state-of-the-art reconstruction quality while providing two to ten-fold acceleration in reconstruction times over the state-of-the-art algorithms.
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Imageamento Tridimensional , Imageamento por Ressonância Magnética , Humanos , Imageamento Tridimensional/métodos , Imageamento por Ressonância Magnética/métodos , Movimento (Física) , Feto , Algoritmos , Processamento de Imagem Assistida por Computador/métodos , ArtefatosRESUMO
One area of medical imaging that has recently experienced innovative deep learning advances is diffusion MRI (dMRI) streamline tractography with recurrent neural networks (RNNs). Unlike traditional imaging studies which utilize voxel-based learning, these studies model dMRI features at points in continuous space off the voxel grid in order to propagate streamlines, or virtual estimates of axons. However, implementing such models is non-trivial, and an open-source implementation is not yet widely available. Here, we describe a series of considerations for implementing tractography with RNNs and demonstrate they allow one to approximate a deterministic streamline propagator with comparable performance to existing algorithms. We release this trained model and the associated implementations leveraging popular deep learning libraries. We hope the availability of these resources will lower the barrier of entry into this field, spurring further innovation.
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Diffusion MRI (dMRI) streamline tractography is the gold-standard for in vivo estimation of white matter (WM) pathways in the brain. However, the high angular resolution dMRI acquisitions capable of fitting the microstructural models needed for tractography are often time-consuming and not routinely collected clinically, restricting the scope of tractography analyses. To address this limitation, we build on recent advances in deep learning which have demonstrated that streamline propagation can be learned from dMRI directly without traditional model fitting. Specifically, we propose learning the streamline propagator from T1w MRI to facilitate arbitrary tractography analyses when dMRI is unavailable. To do so, we present a novel convolutional-recurrent neural network (CoRNN) trained in a teacher-student framework that leverages T1w MRI, associated anatomical context, and streamline memory from data acquired for the Human Connectome Project. We characterize our approach under two common tractography paradigms, WM bundle analysis and structural connectomics, and find approximately a 5-15% difference between measures computed from streamlines generated with our approach and those generated using traditional dMRI tractography. When placed in the literature, these results suggest that the accuracy of WM measures computed from T1w MRI with our method is on the level of scan-rescan dMRI variability and raise an important question: is tractography truly a microstructural phenomenon, or has dMRI merely facilitated its discovery and implementation?
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Characterizing how, when and where the human brain changes across the lifespan is fundamental to our understanding of developmental processes of childhood and adolescence, degenerative processes of aging, and divergence from normal patterns in disease and disorders. We aimed to provide detailed descriptions of white matter pathways across the lifespan by thoroughly characterizing white matter microstructure, white matter macrostructure, and morphology of the cortex associated with white matter pathways. We analyzed 4 large, high-quality, publicly-available datasets comprising 2789 total imaging sessions, and participants ranging from 0 to 100 years old, using advanced tractography and diffusion modeling. We first find that all microstructural, macrostructural, and cortical features of white matter bundles show unique lifespan trajectories, with rates and timing of development and degradation that vary across pathways - describing differences between types of pathways and locations in the brain, and developmental milestones of maturation of each feature. Second, we show cross-sectional relationships between different features that may help elucidate biological changes occurring during different stages of the lifespan. Third, we show unique trajectories of age-associations across features. Finally, we find that age associations during development are strongly related to those during aging. Overall, this study reports normative data for several features of white matter pathways of the human brain that will be useful for studying normal and abnormal white matter development and degeneration.
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Objective: Data harmonization is necessary for removing confounding effects in multi-site diffusion image analysis. One such harmonization method, LinearRISH, scales rotationally invariant spherical harmonic (RISH) features from one site ("target") to the second ("reference") to reduce confounding scanner effects. However, reference and target site designations are not arbitrary and resultant diffusion metrics (fractional anisotropy, mean diffusivity) are biased by this choice. In this work we propose MidRISH: rather than scaling reference RISH features to target RISH features, we project both sites to a mid-space. Methods: We validate MidRISH with the following experiments: harmonizing scanner differences from 37 matched patients free of cognitive impairment, and harmonizing acquisition and study differences on 117 matched patients free of cognitive impairment. Conclusion: MidRISH reduces bias of reference selection while preserving harmonization efficacy of LinearRISH. Significance: Users should be cautious when performing LinearRISH harmonization. To select a reference site is to choose diffusion metric effect-size. Our proposed method eliminates the bias-inducing site selection step.
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T1-weighted (T1w) MRI has low frequency intensity artifacts due to magnetic field inhomogeneities. Removal of these biases in T1w MRI images is a critical preprocessing step to ensure spatially consistent image interpretation. N4ITK bias field correction, the current state-of-the-art, is implemented in such a way that makes it difficult to port between different pipelines and workflows, thus making it hard to reimplement and reproduce results across local, cloud, and edge platforms. Moreover, N4ITK is opaque to optimization before and after its application, meaning that methodological development must work around the inhomogeneity correction step. Given the importance of bias fields correction in structural preprocessing and flexible implementation, we pursue a deep learning approximation / reinterpretation of the N4ITK bias fields correction to create a method which is portable, flexible, and fully differentiable. In this paper, we trained a deep learning network "DeepN4" on eight independent cohorts from 72 different scanners and age ranges with N4ITK-corrected T1w MRI and bias field for supervision in log space. We found that we can closely approximate N4ITK bias fields correction with naïve networks. We evaluate the peak signal to noise ratio (PSNR) in test dataset against the N4ITK corrected images. The median PSNR of corrected images between N4ITK and DeepN4 was 47.96 dB. In addition, we assess the DeepN4 model on eight additional external datasets and show the generalizability of the approach. This study establishes that incompatible N4ITK preprocessing steps can be closely approximated by naïve deep neural networks, facilitating more flexibility. All code and models are released at https://github.com/MASILab/DeepN4.