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PurposeTo improve the performance of neural networks for parameter estimation in quantitative MRI, in particular when the noise propagation varies throughout the space of biophysical parameters. Theory and MethodsA theoretically well‐founded loss function is proposed that normalizes the squared error of each estimate with respective Cramér–Rao bound (CRB)—a theoretical lower bound for the variance of an unbiased estimator. This avoids a dominance of hard‐to‐estimate parameters and areas in parameter space, which are often of little interest. The normalization with corresponding CRB balances the large errors of fundamentally more noisy estimates and the small errors of fundamentally less noisy estimates, allowing the network to better learn to estimate the latter. Further, proposed loss function provides an absolute evaluation metric for performance: A network has an average loss of 1 if it is a maximally efficient unbiased estimator, which can be considered the ideal performance. The performance gain with proposed loss function is demonstrated at the example of an eight‐parameter magnetization transfer model that is fitted to phantom and in vivo data. ResultsNetworks trained with proposed loss function perform close to optimal, that is, their loss converges to approximately 1, and their performance is superior to networks trained with the standard mean‐squared error (MSE). The proposed loss function reduces the bias of the estimates compared to the MSE loss, and improves the match of the noise variance to the CRB. This performance gain translates to in vivo maps that align better with the literature. ConclusionNormalizing the squared error with the CRB during the training of neural networks improves their performance in estimating biophysical parameters. 

Abstract We address the question of how to use a machine learned (ML) parameterization in a general circulation model (GCM), and assess its performance both computationally and physically. We take one particular ML parameterization (Guillaumin & Zanna, 2021,https://doi.org/10.1002/essoar.10506419.1) and evaluate the online performance in a different model from which it was previously tested. This parameterization is a deep convolutional network that predicts parameters for a stochastic model of subgrid momentum forcing by mesoscale eddies. We treat the parameterization as we would a conventional parameterization once implemented in the numerical model. This includes trying the parameterization in a different flow regime from that in which it was trained, at different spatial resolutions, and with other differences, all to test generalization. We assess whether tuning is possible, which is a common practice in GCM development. We find the parameterization, without modification or special treatment, to be stable and that the action of the parameterization to be diminishing as spatial resolution is refined. We also find some limitations of the machine learning model in implementation: (a) tuning of the outputs from the parameterization at various depths is necessary; (b) the forcing near boundaries is not predicted as well as in the open ocean; (c) the cost of the parameterization is prohibitively high on central processing units. We discuss these limitations, present some solutions to problems, and conclude that this particular ML parameterization does inject energy, and improve backscatter, as intended but it might need further refinement before we can use it in production mode in contemporary climate models. 

Abstract Early diagnosis of Alzheimer’s disease plays a pivotal role in patient care and clinical trials. In this study, we have developed a new approach based on 3D deep convolutional neural networks to accurately differentiate mild Alzheimer’s disease dementia from mild cognitive impairment and cognitively normal individuals using structural MRIs. For comparison, we have built a reference model based on the volumes and thickness of previously reported brain regions that are known to be implicated in disease progression. We validate both models on an internal held-out cohort from The Alzheimer's Disease Neuroimaging Initiative (ADNI) and on an external independent cohort from The National Alzheimer's Coordinating Center (NACC). The deep-learning model is accurate, achieved an area-under-the-curve (AUC) of 85.12 when distinguishing between cognitive normal subjects and subjects with either MCI or mild Alzheimer’s dementia. In the more challenging task of detecting MCI, it achieves an AUC of 62.45. It is also significantly faster than the volume/thickness model in which the volumes and thickness need to be extracted beforehand. The model can also be used to forecast progression: subjects with mild cognitive impairment misclassified as having mild Alzheimer’s disease dementia by the model were faster to progress to dementia over time. An analysis of the features learned by the proposed model shows that it relies on a wide range of regions associated with Alzheimer's disease. These findings suggest that deep neural networks can automatically learn to identify imaging biomarkers that are predictive of Alzheimer's disease, and leverage them to achieve accurate early detection of the disease. 

Ocean mesoscale eddies are often poorly represented in climate models, and therefore, their effects on the large scale circulation must be parameterized. Traditional parameterizations, which represent the bulk effect of the unresolved eddies, can be improved with new subgrid models learned directly from data. Zanna and Bolton (ZB20) applied an equation‐discovery algorithm to reveal an interpretable expression parameterizing the subgrid momentum fluxes by mesoscale eddies through the components of the velocity‐gradient tensor. In this work, we implement the ZB20 parameterization into the primitive‐equation GFDL MOM6 ocean model and test it in two idealized configurations with significantly different dynamical regimes and topography. The original parameterization was found to generate excessive numerical noise near the grid scale. We propose two filtering approaches to avoid the numerical issues and additionally enhance the strength of large‐scale energy backscatter. The filtered ZB20 parameterizations led to improved climatological mean state and energy distributions, compared to the current state‐of‐the‐art energy backscatter parameterizations. The filtered ZB20 parameterizations are scale‐aware and, consequently, can be used with a single value of the non‐dimensional scaling coefficient for a range of resolutions. The successful application of the filtered ZB20 parameterizations to parameterize mesoscale eddies in two idealized configurations offers a promising opportunity to reduce long‐standing biases in global ocean simulations in future studies. 

Subgrid parameterizations of mesoscale eddies continue to be in demand for climate simulations. These subgrid parameterizations can be powerfully designed using physics and/or data‐driven methods, with uncertainty quantification. For example, Guillaumin and Zanna (2021) proposed a Machine Learning (ML) model that predicts subgrid forcing and its local uncertainty. The major assumption and potential drawback of this model is the statistical independence of stochastic residuals between grid points. Here, we aim to improve the simulation of stochastic forcing with generative models of ML, such as Generative adversarial network (GAN) and Variational autoencoder (VAE). Generative models learn the distribution of subgrid forcing conditioned on the resolved flow directly from data and they can produce new samples from this distribution. Generative models can potentially capture not only the spatial correlation but any statistically significant property of subgrid forcing. We test the proposed stochastic parameterizations offline and online in an idealized ocean model. We show that generative models are able to predict subgrid forcing and its uncertainty with spatially correlated stochastic forcing. Online simulations for a range of resolutions demonstrated that generative models are superior to the baseline ML model at the coarsest resolution.