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Register a new userMarmoNet: a pipeline for automated projection mapping of the common marmoset brain from whole-brain serial two-photon tomography
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Understanding the connectivity in the brain is an important prerequisite for understanding how the brain processes information. In the Brain/MINDS project, a connectivity study on marmoset brains uses two-photon microscopy fluorescence images of axonal projections to collect the neuron connectivity from defined brain regions at the mesoscopic scale. The processing of the images requires the detection and segmentation of the axonal tracer signal. The objective is to detect as much tracer signal as possible while not misclassifying other background structures as the signal. This can be challenging because of imaging noise, a cluttered image background, distortions or varying image contrast cause problems. We are developing MarmoNet, a pipeline that processes and analyzes tracer image data of the common marmoset brain. The pipeline incorporates state-of-the-art machine learning techniques based on artificial convolutional neural networks (CNN) and image registration techniques to extract and map all relevant information in a robust manner. The pipeline processes new images in a fully automated way. This report introduces the current state of the tracer signal analysis part of the pipeline.
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Reconstructing multiple molecularly defined neurons from individual brains and across multiple brain regions can reveal organizational principles of the nervous system. However, high resolution imaging of the whole brain is a technically challenging and slow process. Recently, oblique light sheet microscopy has emerged as a rapid imaging method that can provide whole brain fluorescence microscopy at a voxel size of 0.4 by 0.4 by 2.5 cubic microns. On the other hand, complex image artifacts due to whole-brain coverage produce apparent discontinuities in neuronal arbors. Here, we present connectivity-preserving methods and data augmentation strategies for supervised learning of neuroanatomy from light microscopy using neural networks. We quantify the merit of our approach by implementing an end-to-end automated tracing pipeline. Lastly, we demonstrate a scalable, distributed implementation that can reconstruct the large datasets that sub-micron whole-brain images produce.
This paper describes a scalable active learning pipeline prototype for large-scale brain mapping that leverages high performance computing power. It enables high-throughput evaluation of algorithm results, which, after human review, are used for iterative machine learning model training. Image processing and machine learning are performed in a batch layer. Benchmark testing of image processing using pMATLAB shows that a 100$times$ increase in throughput (10,000%) can be achieved while total processing time only increases by 9% on Xeon-G6 CPUs and by 22% on Xeon-E5 CPUs, indicating robust scalability. The images and algorithm results are provided through a serving layer to a browser-based user interface for interactive review. This pipeline has the potential to greatly reduce the manual annotation burden and improve the overall performance of machine learning-based brain mapping.
Whole brain extraction, also known as skull stripping, is a process in neuroimaging in which non-brain tissue such as skull, eyeballs, skin, etc. are removed from neuroimages. Skull striping is a preliminary step in presurgical planning, cortical reconstruction, and automatic tumor segmentation. Despite a plethora of skull stripping approaches in the literature, few are sufficiently accurate for processing pathology-presenting MRIs, especially MRIs with brain tumors. In this work we propose a deep learning approach for skull striping common MRI sequences in oncology such as T1-weighted with gadolinium contrast (T1Gd) and T2-weighted fluid attenuated inversion recovery (FLAIR) in patients with brain tumors. We automatically created gray matter, white matter, and CSF probability masks using SPM12 software and merged the masks into one for a final whole-brain mask for model training. Dice agreement, sensitivity, and specificity of the model (referred herein as DeepBrain) was tested against manual brain masks. To assess data efficiency, we retrained our models using progressively fewer training data examples and calculated average dice scores on the test set for the models trained in each round. Further, we tested our model against MRI of healthy brains from the LBP40A dataset. Overall, DeepBrain yielded an average dice score of 94.5%, sensitivity of 96.4%, and specificity of 98.5% on brain tumor data. For healthy brains, model performance improved to a dice score of 96.2%, sensitivity of 96.6% and specificity of 99.2%. The data efficiency experiment showed that, for this specific task, comparable levels of accuracy could have been achieved with as few as 50 training samples. In conclusion, this study demonstrated that a deep learning model trained on minimally processed automatically-generated labels can generate more accurate brain masks on MRI of brain tumor patients within seconds.
Converging evidence shows that disease-relevant brain alterations do not appear in random brain locations, instead, its spatial pattern follows large scale brain networks. In this context, a powerful network analysis approach with a mathematical foundation is indispensable to understand the mechanism of neuropathological events spreading throughout the brain. Indeed, the topology of each brain network is governed by its native harmonic waves, which are a set of orthogonal bases derived from the Eigen-system of the underlying Laplacian matrix. To that end, we propose a novel connectome harmonic analysis framework to provide enhanced mathematical insights by detecting frequency-based alterations relevant to brain disorders. The backbone of our framework is a novel manifold algebra appropriate for inference across harmonic waves that overcomes the limitations of using classic Euclidean operations on irregular data structures. The individual harmonic difference is measured by a set of common harmonic waves learned from a population of individual Eigen systems, where each native Eigen-system is regarded as a sample drawn from the Stiefel manifold. Specifically, a manifold optimization scheme is tailored to find the common harmonic waves which reside at the center of Stiefel manifold. To that end, the common harmonic waves constitute the new neuro-biological bases to understand disease progression. Each harmonic wave exhibits a unique propagation pattern of neuro-pathological burdens spreading across brain networks. The statistical power of our novel connectome harmonic analysis approach is evaluated by identifying frequency-based alterations relevant to Alzheimers disease, where our learning-based manifold approach discovers more significant and reproducible network dysfunction patterns compared to Euclidian methods.
There has been huge interest in studying human brain connectomes inferred from different imaging modalities and exploring their relationship with human traits, such as cognition. Brain connectomes are usually represented as networks, with nodes corresponding to different regions of interest (ROIs) and edges to connection strengths between ROIs. Due to the high-dimensionality and non-Euclidean nature of networks, it is challenging to depict their population distribution and relate them to human traits. Current approaches focus on summarizing the network using either pre-specified topological features or principal components analysis (PCA). In this paper, building on recent advances in deep learning, we develop a nonlinear latent factor model to characterize the population distribution of brain graphs and infer the relationships between brain structural connectomes and human traits. We refer to our method as Graph AuTo-Encoding (GATE). We applied GATE to two large-scale brain imaging datasets, the Adolescent Brain Cognitive Development (ABCD) study and the Human Connectome Project (HCP) for adults, to understand the structural brain connectome and its relationship with cognition. Numerical results demonstrate huge advantages of GATE over competitors in terms of prediction accuracy, statistical inference and computing efficiency. We found that structural connectomes have a stronger association with a wide range of human cognitive traits than was apparent using previous approaches.
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