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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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Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Procesamiento de Imagen Asistido por Computador/métodos , Imagen por Resonancia Magnética/métodos , Algoritmos , Redes Neurales de la Computación , SesgoRESUMEN
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 , Femenino , Masculino , Procesamiento de Imagen Asistido por Computador/métodos , Reproducibilidad de los Resultados , Encéfalo/diagnóstico por imagen , Imagen de Difusión por Resonancia Magnética/métodos , Anisotropía , Anciano , Persona de Mediana Edad , Imagen de Difusión Tensora/métodos , Disfunción Cognitiva/diagnóstico por imagen , Interpretación de Imagen Asistida por Computador/métodosRESUMEN
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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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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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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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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Nonlinear gradients impact diffusion weighted MRI by introducing spatial variation in estimated diffusion tensors. Recent studies have shown that increasing signal-to-noise ratios and the use of ultra-strong gradients may lead to clinically significant impacts on analyses due to these nonlinear gradients in microstructural measures. These effects can potentially bias tractography results and cause misinterpretation of data. Herein, we characterize the impact of an "approximate" gradient nonlinearity correction technique in tractography using empirically derived gradient nonlinear fields. This technique scales the diffusion signal by the change in magnitude due to the gradient nonlinearities, without concomitant correction of gradient direction errors. The impact of this correction on tractography is assessed through white matter bundle segmentation and connectomics via bundle-wise volume, fractional anisotropy, mean diffusivity, radial diffusivity, axial diffusivity, primary eigenvector, and length; as well as the modularity, global efficiency, and characteristic path length connectomics graph measures. We investigate the differences between (1) these measures directly and (2) the within session variability of these measures before and after approximate correction in 61 subjects from the MASiVar pediatric reproducibility dataset. We find approximate correction results is little to no differences on the population level, but large differences on the subject-specific level for both the measures directly and their within session variability. Thus, this study suggests though approximate correction of gradient nonlinearities may not change tractography findings on the population level, subject-specific interpretations may exhibit large fluctuations. A limitation is the lack of comparison with the empirical voxel-wise gradient table correction.
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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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Estimating structural connectivity from diffusion-weighted magnetic resonance imaging is a challenging task, partly due to the presence of false-positive connections and the misestimation of connection weights. Building on previous efforts, the MICCAI-CDMRI Diffusion-Simulated Connectivity (DiSCo) challenge was carried out to evaluate state-of-the-art connectivity methods using novel large-scale numerical phantoms. The diffusion signal for the phantoms was obtained from Monte Carlo simulations. The results of the challenge suggest that methods selected by the 14 teams participating in the challenge can provide high correlations between estimated and ground-truth connectivity weights, in complex numerical environments. Additionally, the methods used by the participating teams were able to accurately identify the binary connectivity of the numerical dataset. However, specific false positive and false negative connections were consistently estimated across all methods. Although the challenge dataset doesn't capture the complexity of a real brain, it provided unique data with known macrostructure and microstructure ground-truth properties to facilitate the development of connectivity estimation methods.
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Imagen de Difusión por Resonancia Magnética , Procesamiento de Imagen Asistido por Computador , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Imagen de Difusión por Resonancia Magnética/métodos , Encéfalo/diagnóstico por imagen , Método de Montecarlo , Fantasmas de ImagenRESUMEN
In diffusion weighted MRI (DW-MRI), hardware nonlinearities lead to spatial variations in the orientation and magnitude of diffusion weighting. While the correction of these spatial distortions has been well established for analyses of DW-MRI, the existing voxel-wise empirical correction for gradient nonlinearities requires reimplementation of existing models, as the resultant gradients vary by voxel. Herein, we propose a two-step signal approximation after voxel-wise correction of gradient nonlinearity effects in DW-MRI. The proposed technique (1) scales the diffusion signal and (2) resamples the gradient orientations. This results in uniform gradients across the corrected image and provides the key advantage of seamless integration into current diffusion workflows. We investigated the validity of our technique by fitting a multi-compartment neurite orientation dispersion and density imaging (NODDI) model to the empirical correction and proposed approximation in five subjects from the MASiVar pediatric dataset. We evaluated intra-cellular volume fraction (iVF), CSF volume fraction (cVF), and orientation dispersion index (ODI) from NODDI. The Cohen's d of iVF, cVF and ODI between the techniques was <0.2 indicating the proposed technique does not exhibit significant differences from the voxel-wise correction technique. Our two-step signal approximation is an efficient representation of the voxel-wise gradient table correction. Using this approximation, correction of gradient nonlinearities can be easily incorporated into existing diffusion preprocessing pipelines and is implemented in "PreQual: An automated pipeline for integrated preprocessing and quality assurance of diffusion weighted MRI images".
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Imagen de Difusión por Resonancia Magnética , Neuritas , Humanos , Niño , Imagen de Difusión por Resonancia Magnética/métodos , Encéfalo/diagnóstico por imagenRESUMEN
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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In diffusion MRI, gradient nonlinearities cause spatial variations in the magnitude and direction of diffusion gradients. Studies have shown artifacts from these distortions can results in biased diffusion tensor information and tractography. Here, we investigate the impact of gradient nonlinearity correction in the presence of noise. We introduced empirically derived gradient nonlinear fields at different signal-to-noise ratio (SNR) levels in two experiments: tensor field simulation and simulation of the brain. For each experiment, this work compares two techniques empirically: voxel-wise gradient table correction and approximate correction by scaling the signal directly. The impact was assessed through diffusion metrics including mean diffusivity (MD), fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), and principal eigen vector (V1). The study shows (1) the correction of gradient nonlinearities will not lead to substantively incorrect estimation of diffusion metrics in a linear system, (2) gradient nonlinearity correction does not interact adversely with noise, (3) nonlinearity correction suppresses the impact of nonlinearities in typical SNR data, (4) for SNR below 30, the performance of both the gradient nonlinearity correction techniques were similar, and (5) larger impacts are seen in regions where the gradient nonlinearities are distinct. Thus, this study suggests that there were greater beneficial effects than adverse effects due to the correction of nonlinearities. Additionally, correction of nonlinearities is recommended when region of interests are in areas with pronounced nonlinearities.
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Encéfalo , Imagen de Difusión por Resonancia Magnética , Imagen de Difusión por Resonancia Magnética/métodos , Encéfalo/diagnóstico por imagen , Relación Señal-Ruido , Simulación por Computador , AnisotropíaRESUMEN
Non-linear gradients impact diffusion weighted (DW) MRI by corrupting the experimental setup and lead to problems during image encoding including the effects in-plane distortion, in-plane shifts, intensity modulations and phase errors. Recent studies have been shown this may present significant complication in the interpretation of results and conclusion while studying tractography and tissue microstructure in data. To interpret the degree in consequences of gradient non-linearities between the desired and achieved gradients, we introduced empirically derived gradient nonlinear fields at different orientations and different tensor properties. The impact is assessed through diffusion tensor properties including mean diffusivity (MD), fractional anisotropy (FA) and principal eigen vector (PEV). The study shows lower FA are more susceptible to LR fields and LR fields with determinant <1 or >1 corrupt tensor more. The corruption can result in significantly different FA based on true-FA and LR field. Apparent MD decreases for negative determinant, on the other hand positive determinant shows the opposite effect. LR field have a larger impact on PEV when FA value is small. The results are dependent on the underlying orientation, non-linear field corruption can cause both increase and decrease of estimated FA, MD and PEV value. This work provides insight into characterizing the non-linear gradient error and aid in selecting correction techniques to address the inaccuracies in b-values.
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A robust medical image computing infrastructure must host massive multimodal archives, perform extensive analysis pipelines, and execute scalable job management. An emerging data format standard, the Brain Imaging Data Structure (BIDS), introduces complexities for interfacing with XNAT archives. Moreover, workflow integration is combinatorically problematic when matching large amount of processing to large datasets. Historically, workflow engines have been focused on refining workflows themselves instead of actual job generation. However, such an approach is incompatible with data centric architecture that hosts heterogeneous medical image computing. Distributed automation for XNAT toolkit (DAX) provides large-scale image storage and analysis pipelines with an optimized job management tool. Herein, we describe developments for DAX that allows for integration of XNAT and BIDS standards. We also improve DAX's efficiencies of diverse containerized workflows in a high-performance computing (HPC) environment. Briefly, we integrate YAML configuration processor scripts to abstract workflow data inputs, data outputs, commands, and job attributes. Finally, we propose an online database-driven mechanism for DAX to efficiently identify the most recent updated sessions, thereby improving job building efficiency on large projects. We refer the proposed overall DAX development in this work as DAX-1 (DAX version 1). To validate the effectiveness of the new features, we verified (1) the efficiency of converting XNAT data to BIDS format and the correctness of the conversion using a collection of BIDS standard containerized neuroimaging workflows, (2) how YAML-based processor simplified configuration setup via a sequence of application pipelines, and (3) the productivity of DAX-1 on generating actual HPC processing jobs compared with earlier DAX baseline method. The empirical results show that (1) DAX-1 converting XNAT data to BIDS has similar speed as accessing XNAT data only; (2) YAML can integrate to the DAX-1 with shallow learning curve for users, and (3) DAX-1 reduced the job/assessor generation latency by finding recent modified sessions. Herein, we present approaches for efficiently integrating XNAT and modern image formats with a scalable workflow engine for the large-scale dataset access and processing.
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Neuroimagen , Programas Informáticos , Humanos , Encéfalo , Neuroimagen/métodos , Flujo de TrabajoRESUMEN
The field of artificial intelligence (AI) in medical imaging is undergoing explosive growth, and Radiology is a prime target for innovation. The American College of Radiology Data Science Institute has identified more than 240 specific use cases where AI could be used to improve clinical practice. In this context, thousands of potential methods are developed by research labs and industry innovators. Deploying AI tools within a clinical enterprise, even on limited retrospective evaluation, is complicated by security and privacy concerns. Thus, innovation must be weighed against the substantive resources required for local clinical evaluation. To reduce barriers to AI validation while maintaining rigorous security and privacy standards, we developed the AI Imaging Incubator. The AI Imaging Incubator serves as a DICOM storage destination within a clinical enterprise where images can be directed for novel research evaluation under Institutional Review Board approval. AI Imaging Incubator is controlled by a secure HIPAA-compliant front end and provides access to a menu of AI procedures captured within network-isolated containers. Results are served via a secure website that supports research and clinical data formats. Deployment of new AI approaches within this system is streamlined through a standardized application programming interface. This manuscript presents case studies of the AI Imaging Incubator applied to randomizing lung biopsies on chest CT, liver fat assessment on abdomen CT, and brain volumetry on head MRI.
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Inteligencia Artificial , Radiología , Hospitales , Humanos , Radiología/métodos , Estudios Retrospectivos , Flujo de TrabajoRESUMEN
PURPOSE: Diffusion-weighted imaging allows investigators to identify structural, microstructural, and connectivity-based differences between subjects, but variability due to session and scanner biases is a challenge. METHODS: To investigate DWI variability, we present MASiVar, a multisite data set consisting of 319 diffusion scans acquired at 3 T from b = 1000 to 3000 s/mm2 across 14 healthy adults, 83 healthy children (5 to 8 years), three sites, and four scanners as a publicly available, preprocessed, and de-identified data set. With the adult data, we demonstrate the capacity of MASiVar to simultaneously quantify the intrasession, intersession, interscanner, and intersubject variability of four common DWI processing approaches: (1) a tensor signal representation, (2) a multi-compartment neurite orientation dispersion and density model, (3) white-matter bundle segmentation, and (4) structural connectomics. Respectively, we evaluate region-wise fractional anisotropy, mean diffusivity, and principal eigenvector; region-wise CSF volume fraction, intracellular volume fraction, and orientation dispersion index; bundle-wise shape, volume, fractional anisotropy, and length; and whole connectome correlation and maximized modularity, global efficiency, and characteristic path length. RESULTS: We plot the variability in these measures at each level and find that it consistently increases with intrasession to intersession to interscanner to intersubject effects across all processing approaches and that sometimes interscanner variability can approach intersubject variability. CONCLUSIONS: This study demonstrates the potential of MASiVar to more globally investigate DWI variability across multiple levels and processing approaches simultaneously and suggests harmonization between scanners for multisite analyses should be considered before inference of group differences on subjects.
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Imagen de Difusión Tensora , Sustancia Blanca , Adulto , Anisotropía , Encéfalo/diagnóstico por imagen , Niño , Imagen de Difusión por Resonancia Magnética , Humanos , NeuritasRESUMEN
Diffusion magnetic resonance images may suffer from geometric distortions due to susceptibility induced off resonance fields, which cause geometric mismatch with anatomical images and ultimately affect subsequent quantification of microstructural or connectivity indices. State-of-the art diffusion distortion correction methods typically require data acquired with reverse phase encoding directions, resulting in varying magnitudes and orientations of distortion, which allow estimation of an undistorted volume. Alternatively, additional field maps acquisitions can be used along with sequence information to determine warping fields. However, not all imaging protocols include these additional scans and cannot take advantage of state-of-the art distortion correction. To avoid additional acquisitions, structural MRI (undistorted scans) can be used as registration targets for intensity driven correction. In this study, we aim to (1) enable susceptibility distortion correction with historical and/or limited diffusion datasets that do not include specific sequences for distortion correction and (2) avoid the computationally intensive registration procedure typically required for distortion correction using structural scans. To achieve these aims, we use deep learning (3D U-nets) to synthesize an undistorted b0 image that matches geometry of structural T1w images and intensity contrasts from diffusion images. Importantly, the training dataset is heterogenous, consisting of varying acquisitions of both structural and diffusion. We apply our approach to a withheld test set and show that distortions are successfully corrected after processing. We quantitatively evaluate the proposed distortion correction and intensity-based registration against state-of-the-art distortion correction (FSL topup). The results illustrate that the proposed pipeline results in b0 images that are geometrically similar to non-distorted structural images, and more closely match state-of-the-art correction with additional acquisitions. In addition, we show generalizability of the proposed approach to datasets that were not in the original training / validation / testing datasets. These datasets included varying populations, contrasts, resolutions, and magnitudes and orientations of distortion and show efficacious distortion correction. The method is available as a Singularity container, source code, and an executable trained model to facilitate evaluation.
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Encéfalo/diagnóstico por imagen , Imagen de Difusión por Resonancia Magnética/métodos , Procesamiento de Imagen Asistido por Computador/métodos , Algoritmos , Artefactos , Imagen Eco-Planar/métodos , HumanosRESUMEN
3D organ contouring is an essential step in radiation therapy treatment planning for organ dose estimation as well as for optimizing plans to reduce organs-at-risk doses. Manual contouring is time-consuming and its inter-clinician variability adversely affects the outcomes study. Such organs also vary dramatically on sizes - up to two orders of magnitude difference in volumes. In this paper, we present BrainSegNet, a novel 3D fully convolutional neural network (FCNN) based approach for automatic segmentation of brain organs. BrainSegNet takes a multiple resolution paths approach and uses a weighted loss function to solve the major challenge of the large variability in organ sizes. We evaluated our approach with a dataset of 46 Brain CT image volumes with corresponding expert organ contours as reference. Compared with those of LiviaNet and V-Net, BrainSegNet has a superior performance in segmenting tiny or thin organs, such as chiasm, optic nerves, and cochlea, and outperforms these methods in segmenting large organs as well. BrainSegNet can reduce the manual contouring time of a volume from an hour to less than two minutes, and holds high potential to improve the efficiency of radiation therapy workflow.