Separable nonlinear least squares fitting with linear bound constraints and its application in magnetic resonance spectroscopy data quantification

AbstractAn application in magnetic resonance spectroscopy quantification models a signal as a linear combination of nonlinear functions. It leads to a separable nonlinear least squares fitting problem, with linear bound constraints on some variables. The variable projection (VARPRO) technique can be applied to this problem, but needs to be adapted in several respects. If only the nonlinear variables are subject to constraints, then the Levenberg–Marquardt minimization algorithm that is classically used by the VARPRO method should be replaced with a version that can incorporate those constraints. If some of the linear variables are also constrained, then they cannot be projected out via a closed-form expression as is the case for the classical VARPRO technique. We show how quadratic programming problems can be solved instead, and we provide details on efficient function and approximate Jacobian evaluations for the inequality constrained VARPRO method

Deep learning pipeline for quality filtering of MRSI spectra.

With the rise of novel 3D magnetic resonance spectroscopy imaging (MRSI) acquisition protocols in clinical practice, which are capable of capturing a large number of spectra from a subject's brain, there is a need for an automated preprocessing pipeline that filters out bad-quality spectra and identifies contaminated but salvageable spectra prior to the metabolite quantification step. This work introduces such a pipeline based on an ensemble of deep-learning classifiers. The dataset consists of 36,338 spectra from one healthy subject and five brain tumor patients, acquired with an EPSI variant, which implemented a novel type of spectral editing named SLOtboom-Weng (SLOW) editing on a 7T MR scanner. The spectra were labeled manually by an expert into four classes of spectral quality as follows: (i) noise, (ii) spectra greatly influenced by lipid-related artifacts (deemed not to contain clinical information), (iii) spectra containing metabolic information slightly contaminated by lipid signals, and (iv) good-quality spectra. The AI model consists of three pairs of networks, each comprising a convolutional autoencoder and a multilayer perceptron network. In the classification step, the encoding half of the autoencoder is kept as a dimensionality reduction tool, while the fully connected layers are added to its output. Each of the three pairs of networks is trained on different representations of spectra (real, imaginary, or both), aiming at robust decision-making. The final class is assigned via a majority voting scheme. The F1 scores obtained on the test dataset for the four previously defined classes are 0.96, 0.93, 0.82, and 0.90, respectively. The arguably lower value of 0.82 was reached for the least represented class of spectra mildly influenced by lipids. Not only does the proposed model minimise the required user interaction, but it also greatly reduces the computation time at the metabolite quantification step (by selecting a subset of spectra worth quantifying) and enforces the display of only clinically relevant information

AIFNet: Automatic Vascular Function Estimation for Perfusion Analysis Using Deep Learning

Perfusion imaging is crucial in acute ischemic stroke for quantifying the salvageable penumbra and irreversibly damaged core lesions. As such, it helps clinicians to decide on the optimal reperfusion treatment. In perfusion CT imaging, deconvolution methods are used to obtain clinically interpretable perfusion parameters that allow identifying brain tissue abnormalities. Deconvolution methods require the selection of two reference vascular functions as inputs to the model: the arterial input function (AIF) and the venous output function, with the AIF as the most critical model input. When manually performed, the vascular function selection is time demanding, suffers from poor reproducibility and is subject to the professionals' experience. This leads to potentially unreliable quantification of the penumbra and core lesions and, hence, might harm the treatment decision process. In this work we automatize the perfusion analysis with AIFNet, a fully automatic and end-to-end trainable deep learning approach for estimating the vascular functions. Unlike previous methods using clustering or segmentation techniques to select vascular voxels, AIFNet is directly optimized at the vascular function estimation, which allows to better recognise the time-curve profiles. Validation on the public ISLES18 stroke database shows that AIFNet reaches inter-rater performance for the vascular function estimation and, subsequently, for the parameter maps and core lesion quantification obtained through deconvolution. We conclude that AIFNet has potential for clinical transfer and could be incorporated in perfusion deconvolution software.Comment: Preprint submitted to Elsevie

Unsupervised 3D Brain Anomaly Detection

Anomaly detection (AD) is the identification of data samples that do not fit a learned data distribution. As such, AD systems can help physicians to determine the presence, severity, and extension of a pathology. Deep generative models, such as Generative Adversarial Networks (GANs), can be exploited to capture anatomical variability. Consequently, any outlier (i.e., sample falling outside of the learned distribution) can be detected as an abnormality in an unsupervised fashion. By using this method, we can not only detect expected or known lesions, but we can even unveil previously unrecognized biomarkers. To the best of our knowledge, this study exemplifies the first AD approach that can efficiently handle volumetric data and detect 3D brain anomalies in one single model. Our proposal is a volumetric and high-detail extension of the 2D f-AnoGAN model obtained by combining a state-of-the-art 3D GAN with refinement training steps. In experiments using non-contrast computed tomography images from traumatic brain injury (TBI) patients, the model detects and localizes TBI abnormalities with an area under the ROC curve of ~75%. Moreover, we test the potential of the method for detecting other anomalies such as low quality images, preprocessing inaccuracies, artifacts, and even the presence of post-operative signs (such as a craniectomy or a brain shunt). The method has potential for rapidly labeling abnormalities in massive imaging datasets, as well as identifying new biomarkers.Comment: Accepted at BrainLes Workshop in MICCAI 202

A Radiomics Approach to Traumatic Brain Injury Prediction in CT Scans

Computer Tomography (CT) is the gold standard technique for brain damage evaluation after acute Traumatic Brain Injury (TBI). It allows identification of most lesion types and determines the need of surgical or alternative therapeutic procedures. However, the traditional approach for lesion classification is restricted to visual image inspection. In this work, we characterize and predict TBI lesions by using CT-derived radiomics descriptors. Relevant shape, intensity and texture biomarkers characterizing the different lesions are isolated and a lesion predictive model is built by using Partial Least Squares. On a dataset containing 155 scans (105 train, 50 test) the methodology achieved 89.7 % accuracy over the unseen data. When a model was build using only texture features, a 88.2 % accuracy was obtained. Our results suggest that selected radiomics descriptors could play a key role in brain injury prediction. Besides, the proposed methodology is close to reproduce radiologists decision making. These results open new possibilities for radiomics-inspired brain lesion detection, segmentation and prediction.Comment: Submitted to ISBI 201

"Silver" mode for the heavy Higgs search in the presence of a fourth SM family

We investigate the possible enhancement to the discovery of the heavy Higgs boson through the possible fourth SM family heavy neutrino. Using the channel h-> v4 v4->mu W mu W, it is found that for certain ranges of Higgs boson and v4 masses LHC could discover both of them simultaneously with 1 fb^-1 integrated luminosity

Machine Learning Approach for Classifying Multiple Sclerosis Courses by Combining Clinical Data with Lesion Loads and Magnetic Resonance Metabolic Features

Purpose: The purpose of this study is classifying multiple sclerosis (MS) patients in the four clinical forms as defined by the McDonald criteria using machine learning algorithms trained on clinical data combined with lesion loads and magnetic resonance metabolic features.Materials and Methods: Eighty-seven MS patients [12 Clinically Isolated Syndrome (CIS), 30 Relapse Remitting (RR), 17 Primary Progressive (PP), and 28 Secondary Progressive (SP)] and 18 healthy controls were included in this study. Longitudinal data available for each MS patient included clinical (e.g., age, disease duration, Expanded Disability Status Scale), conventional magnetic resonance imaging and spectroscopic imaging. We extract N-acetyl-aspartate (NAA), Choline (Cho), and Creatine (Cre) concentrations, and we compute three features for each spectroscopic grid by averaging metabolite ratios (NAA/Cho, NAA/Cre, Cho/Cre) over good quality voxels. We built linear mixed-effects models to test for statistically significant differences between MS forms. We test nine binary classification tasks on clinical data, lesion loads, and metabolic features, using a leave-one-patient-out cross-validation method based on 100 random patient-based bootstrap selections. We compute F1-scores and BAR values after tuning Linear Discriminant Analysis (LDA), Support Vector Machines with gaussian kernel (SVM-rbf), and Random Forests.Results: Statistically significant differences were found between the disease starting points of each MS form using four different response variables: Lesion Load, NAA/Cre, NAA/Cho, and Cho/Cre ratios. Training SVM-rbf on clinical and lesion loads yields F1-scores of 71–72% for CIS vs. RR and CIS vs. RR+SP, respectively. For RR vs. PP we obtained good classification results (maximum F1-score of 85%) after training LDA on clinical and metabolic features, while for RR vs. SP we obtained slightly higher classification results (maximum F1-score of 87%) after training LDA and SVM-rbf on clinical, lesion loads and metabolic features.Conclusions: Our results suggest that metabolic features are better at differentiating between relapsing-remitting and primary progressive forms, while lesion loads are better at differentiating between relapsing-remitting and secondary progressive forms. Therefore, combining clinical data with magnetic resonance lesion loads and metabolic features can improve the discrimination between relapsing-remitting and progressive forms

Two Time Point MS Lesion Segmentation in Brain MRI:An Expectation-Maximization Framework

Purpose: Lesion volume is a meaningful measure in multiple sclerosis (MS) prognosis. Manual lesion segmentation for computing volume in a single or multiple time points is time consuming and suffers from intra and inter-observer variability. Methods: In this paper, we present MSmetrix-long: a joint expectation-maximization (EM) framework for two time point white matter (WM) lesion segmentation. MSmetrix-long takes as input a 3D T1-weighted and a 3D FLAIR MR image and segments lesions in three steps: (1) cross-sectional lesion segmentation of the two time points; (2) creation of difference image, which is used to model the lesion evolution; (3) a joint EM lesion segmentation framework that uses output of step (1) and step (2) to provide the final lesion segmentation. The accuracy (Dice score) and reproducibility (absolute lesion volume difference) of MSmetrix-long is evaluated using two datasets. Results: On the first dataset, the median Dice score between MSmetrix-long and expert lesion segmentation was 0.63 and the Pearson correlation coefficient (PCC) was equal to 0.96. On the second dataset, the median absolute volume difference was 0.11 ml. Conclusions: MSmetrix-long is accurate and consistent in segmenting MS lesions. Also, MSmetrix-long compares favorably with the publicly available longitudinal MS lesion segmentation algorithm of Lesion Segmentation Toolbox

Brain age as a biomarker for pathological versus healthy ageing – a REMEMBER study

Objectives: This study aimed to evaluate the potential clinical value of a new brain age prediction model as a single interpretable variable representing the condition of our brain. Among many clinical use cases, brain age could be a novel outcome measure to assess the preventive effect of life-style interventions. Methods: The REMEMBER study population (N = 742) consisted of cognitively healthy (HC,N = 91), subjective cognitive decline (SCD,N = 65), mild cognitive impairment (MCI,N = 319) and AD dementia (ADD,N = 267) subjects. Automated brain volumetry of global, cortical, and subcortical brain structures computed by the CE-labeled and FDA-cleared software icobrain dm (dementia) was retrospectively extracted from T1-weighted MRI sequences that were acquired during clinical routine at participating memory clinics from the Belgian Dementia Council. The volumetric features, along with sex, were combined into a weighted sum using a linear model, and were used to predict ‘brain age’ and ‘brain predicted age difference’ (BPAD = brain age–chronological age) for every subject. Results: MCI and ADD patients showed an increased brain age compared to their chronological age. Overall, brain age outperformed BPAD and chronological age in terms of classification accuracy across the AD spectrum. There was a weak-to-moderate correlation between total MMSE score and both brain age (r = -0.38,p < .001) and BPAD (r = -0.26,p < .001). Noticeable trends, but no significant correlations, were found between BPAD and incidence of conversion from MCI to ADD, nor between BPAD and conversion time from MCI to ADD. BPAD was increased in heavy alcohol drinkers compared to non-/sporadic (p = .014) and moderate (p = .040) drinkers. Conclusions: Brain age and associated BPAD have the potential to serve as indicators for, and to evaluate the impact of lifestyle modifications or interventions on, brain health