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Abstract The International Society for the Biological Therapy of Cancer (iSBTc) has initiated in collaboration with the United States Food and Drug Administration (FDA) a programmatic look at innovative avenues for the identification of relevant parameters to assist clinical and basic scientists who study the natural course of host/tumor interactions or their response to immune manipulation. The task force has two primary goals: 1) identify best practices of standardized and validated immune monitoring procedures and assays to promote inter-trial comparisons and 2) develop strategies for the identification of novel biomarkers that may enhance our understating of principles governing human cancer immune biology and, consequently, implement their clinical application. Two working groups were created that will report the developed best practices at an NCI/FDA/iSBTc sponsored workshop tied to the annual meeting of the iSBTc to be held in Washington DC in the Fall of 2009. This foreword provides an overview of the task force and invites feedback from readers that might be incorporated in the discussions and in the final document.

30-60% of traumatic brain injury (TBI) patients suffer from long-term balance deficit. Even though motor preparation and execution are altered and slowed in TBI, their relative contribution and importance to posture instability remain poorly understood. This study investigates the impaired cortical dynamics and neuromuscular response in TBI in response to balance perturbation and its relation to balance deficit. 12 TBI and 6 healthy control (HC) participants took the Berg Balance Scale (BBS) test and participated in a balance perturbation task where they were subjected to random anterior/posterior translation, while brain (EEG), muscle (EMG) activities, and center of pressure (COP) were continuously recorded. Using independent component analysis (ICA), the component most responsible for the N1 component of the perturbation evoked potential (PEP) was selected and its amplitude and latency were extracted. Balance task performance was measured by computing the COP displacement during the task. TBI had a significantly lower BBS, larger COP displacement and lower N1 amplitude compared to the HC group. No group differences was found for N1 latency and muscle activity onset delay to the perturbation. BBS was correlated with the COP displacement and N1 amplitude, and COP displacement was correlated with N1 latency. TBI balance deficit may be associated with more impaired than delayed cortical response to balance perturbation.

Surface electromyographic (sEMG) data impart valuable information concerning muscle function and neuromuscular diseases especially under human movement conditions. However, they are subject to trial-wise and subject-wise variations, which would pose challenges for investigators engaged in precisely estimating the onset of muscle activation. To this end, we posited two unsupervised statistical approaches- scree-plot elbow detection (SPE) heavily relying on the threshold choice and the more robust profile likelihood maximization (PLM) that obviates parameter tuning-for accurately detecting muscle activation onsets (MAOs). The performance of these algorithms was evaluated using the sEMG dataset provided in the article by Tenan et al. and the simulated sEMG created as explained therein. These sEMG signals are reported to have been collected from the biceps brachii and vastus lateralis of 18 participants while performing a biceps curl or knee extension, respectively. The acquired sEMG signals were first preconditioned with the Teager-Kaiser energy operator, and then, either supplied to the SPE or to the PLM or to a state-of-the-art algorithm. The mean and median errors, between the MAO time in milliseconds estimated by each of the algorithms and the gold standard onset time, were computed. The outcome of a PLM variant, namely, PLM-Laplacian, has been found to have good agreement with the gold standard, i.e., an absolute median error of 9 and 21 ms in the simulated and the actual sEMG data, respectively; whereas, the errors produced by the other algorithms are statistically significantly larger than that incurred by the PLM-Laplacian according to Wilcoxon rank-sum test. In addition, the advocated approach does not necessitate parameter settings, lending itself to be flexible and adaptable to any application, which is a unique advantage over several other methods. Research is underway to further validate this technique by imposing various experimental conditions.

Surface electromyography (sEMG) data acquired during lower limb movements has the potential for investigating knee pathology. Nevertheless, a major challenge encountered with sEMG signals generated by lower limb movements is the intersubject variability, because the signals recorded from the leg or thigh muscles are contingent on the characteristics of a subject such as gait activity and muscle structure. In order to cope with this difficulty, we have designed a three-step classification scheme. First, the multichannel sEMG is decomposed into activities of the underlying sources by means of independent component analysis via entropy bound minimization. Next, a set of time-domain features, which would best discriminate various movements, are extracted from the source estimates. Finally, the feature selection is performed with the help of the Fisher score and a scree-plot-based statistical technique, prior to feeding the dimension-reduced features to the linear discriminant analysis. The investigation involves 11 healthy subjects and 11 individuals with knee pathology performing three different lower limb movements, namely, walking, sitting, and standing, which yielded an average classification accuracy of 96.1% and 86.2%, respectively. While the outcome of this study per se is very encouraging, with suitable improvement, the clinical application of such an sEMG-based pattern recognition system that distinguishes healthy and knee pathological subjects would be an attractive consequence.

Content-based image retrieval plays an increasing role in the clinical process for supporting diagnosis. This paper proposes a neighbourhood search method to select the near-optimal feature subsets for the retrieval of mammograms from the Mammographic Image Analysis Society (MIAS) database. The features based on grey level cooccurrence matrix, Daubechies-4 wavelet, Gabor, Cohen-Daubechies-Feauveau 9/7 wavelet and Zernike moments are extracted from mammograms available in the MIAS database to form the combined or fused feature set for testing various feature selection methods. The performance of feature selection methods is evaluated using precision, storage requirement and retrieval time measures. Using the proposed method, a significant improvement is achieved in mean precision rate and feature dimension. The results show that the proposed method outperforms the state-of-the-art feature selection methods.

Even though the Hartley-entropy-based contrast function guarantees an unmixing local minimum, the reported nonsmooth optimization techniques that minimize this nondifferentiable function encounter computational bottlenecks. Toward this, Powell's derivative-free optimization method has been extended to a Riemannian manifold, namely, oblique manifold, for the recovery of quasi-correlated sources by minimizing this contrast function. The proposed scheme has been demonstrated to converge faster than the related algorithms in the literature, besides the impressive source separation results in simulations involving synthetic sources having finite-support distributions and correlated images.

An accurate and computationally efficient quantitative analysis of electromyography (EMG) signals plays an inevitable role in the diagnosis of neuromuscular disorders, prosthesis, and several related applications. Since it is often the case that the measured signals are the mixtures of electric potentials that emanate from surrounding muscles (sources), many EMG signal processing approaches rely on linear source separation techniques such as the independent component analysis (ICA). Nevertheless, naive implementations of ICA algorithms do not comply with the task of extracting the underlying sources from a single-channel EMG measurement. In this respect, the present work focuses on a classification method for neuromuscular disorders that deals with the data recorded using a single-channel EMG sensor. The ensemble empirical mode decomposition algorithm decomposes the single-channel EMG signal into a set of noise-canceled intrinsic mode functions, which in turn are separated by the FastICA algorithm. A reduced set of five time domain features extracted from the separated components are classified using the linear discriminant analysis, and the classification results are fine-tuned with a majority voting scheme. The performance of the proposed method has been validated with a clinical EMG database, which reports a higher classification accuracy (98%). The outcome of this study encourages possible extension of this approach to real settings to assist the clinicians in making correct diagnosis of neuromuscular disorders.

Independent component analysis (ICA) aims at separating a multivariate signal into independent nongaussian signals by optimizing a contrast function with no knowledge on the mixing mechanism. Despite the availability of a constellation of contrast functions, a Hartley-entropy-based ICA contrast endowed with the discriminacy property makes it an appealing choice as it guarantees the absence of mixing local optima. Fueled by an outstanding source separation performance of this contrast function in practical instances, a succession of optimization techniques has recently been adopted to solve the ICA problem. Nevertheless, the nondifferentiability of the considered contrast restricts the choice of the optimizer to the class of derivative-free methods. On the contrary, this letter concerns a Riemannian quasi-Newton scheme involving an explicit expression for the gradient to optimize the contrast function that is differentiable almost everywhere. Furthermore, the inexact line search insisting on the weak Wolfe condition and a terminating criterion befitting the partly smooth function optimization have been generalized to manifold settings, leaving the previous results intact. The investigations with diversified images and the electroencephalographic (EEG) data acquired from 45 focal epileptic subjects demonstrate the efficacy of our approach in terms of computational savings and reliable EEG source localization, respectively. Additional experimental results are available in the online supplement.

This brief concerns the design and application of a Riemannian Nelder-Mead algorithm to minimize a Hartley-entropybased contrast function to reliably estimate the sources from their mixtures. Despite its nondifferentiability, the contrast function is endowed with attractive properties such as discriminacy, and hence warrants an effort to be effectively handled by a derivative-free optimizer. Aside from tailoring the Nelder-Mead technique to the constraint set, namely, oblique manifold, the source separation results attained in an empirical study with quasi-correlated synthetic signals and digital images are presented, which favor the proposed method on a comparative basis.

This work investigates the capability of supervised classification methods in detecting both major tissues and subcortical structures using multispectral brain magnetic resonance images. First, by means of a realistic digital brain phantom, we investigated the classification performance of various Discriminant Analysis methods, K-Nearest Neighbor and Support Vector Machine. Then, using phantom and real data, we quantitatively assessed the benefits of integrating anatomical information in the classification, in the form of voxels coordinates as additional features to the intensities or tissue probabilistic atlases as priors. In addition we tested the effect of spatial correlations between neighboring voxels and image denoising. For each brain tissue we measured the classification performance in terms of global agreement percentage, false positive and false negative rates and kappa coefficient. The effectiveness of integrating spatial information or a tissue probabilistic atlas has been demonstrated for the aim of accurately classifying brain magnetic resonance images., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

It is seemingly paradoxical to the classical definition of the independent component analysis (ICA), that in reality, the true sources are often not strictly uncorrelated. With this in mind, this letter concerns a framework to extract quasi-uncorrelated sources with finite supports by optimizing a range-based contrast function under unit-norm constraints (to handle the inherent scaling indeterminacy of ICA) but without orthogonality constraints. Albeit the appealing contrast properties of the range-based function (e.g., the absence of mixing local optima), the function is not differentiable everywhere. Unfortunately, there is a dearth of literature on derivative-free optimizers that effectively handle such a nonsmooth yet promising contrast function. This is the compelling reason for the design of a nonsmooth optimization algorithm on a manifold of matrices having unit-norm columns with the following objectives: to ascertain convergence to a Clarke stationary point of the contrast function and adhere to the necessary unit-norm constraints more naturally. The proposed nonsmooth optimization algorithm crucially relies on the design and analysis of an extension of the mesh adaptive direct search (MADS) method to handle locally Lipschitz objective functions defined on the sphere. The applicability of the algorithm in the ICA domain is demonstrated with simulations involving natural, face, aerial, and texture images.

A Riemannian manifold optimization strategy is proposed to facilitate the relaxation of the orthonormality constraint in a more natural way in the course of performing independent component analysis (ICA) that employs a mutual information-based source-adaptive contrast function. Despite the extensive development of manifold techniques catering to the orthonormality constraint, only a limited number of works have been dedicated to oblique manifold (OB) algorithms to intrinsically handle the normality constraint, which has been empirically shown to be superior to other Riemannian and Euclidean approaches. Imposing the normality constraint implicitly, in line with the ICA definition, essentially guarantees a substantial improvement in the solution accuracy, by way of increased degrees of freedom while searching for an optimal unmixing ICA matrix, in contrast with the orthonormality constraint. Designs of the steepest descent, conjugate gradient with Hager-Zhang or a hybrid update parameter, quasi-Newton, and cost-effective quasi-Newton methods intended for OB are presented in this paper. Their performance is validated using natural images and systematically compared with the popular state-of-the-art approaches in order to assess the performance effects of the choice of algorithm and the use of a Riemannian rather than Euclidean framework. We surmount the computational challenge associated with the direct estimation of the source densities using the improved fast Gauss transform in the evaluation of the contrast function and its gradient. The proposed OB schemes may find applications in the offline image/signal analysis, wherein, on one hand, the computational overhead can be tolerated, and, on the other, the solution quality holds paramount interest.

Knowledge of the exact spatial distribution of brain tissues in images acquired by magnetic resonance imaging (MRI) is necessary to measure and compare the performance of segmentation algorithms. Currently available physical phantoms do not satisfy this requirement. State-of-the-art digital brain phantoms also fall short because they do not handle separately anatomical structures (e.g. basal ganglia) and provide relatively rough simulations of tissue fine structure and inhomogeneity. We present a software procedure for the construction of a realistic MRI digital brain phantom. The phantom consists of hydrogen nuclear magnetic resonance spin-lattice relaxation rate (R1), spin-spin relaxation rate (R2), and proton density (PD) values for a 24 × 19 × 15.5 cm volume of a "normal" head. The phantom includes 17 normal tissues, each characterized by both mean value and variations in R1, R2, and PD. In addition, an optional tissue class for multiple sclerosis (MS) lesions is simulated. The phantom was used to create realistic magnetic resonance (MR) images of the brain using simulated conventional spin-echo (CSE) and fast field-echo (FFE) sequences. Results of mono-parametric segmentation of simulations of sequences with different noise and slice thickness are presented as an example of possible applications of the phantom. The phantom data and simulated images are available online at http://lab.ibb.cnr.it/., (Copyright © 2011 Elsevier B.V. All rights reserved.)

This paper presents a new stochastic algorithm to optimize the independence criterion-mutual information-among multivariate data using local, global, and hybrid optimizers, in conjunction with techniques involving a Lie group and its corresponding Lie algebra, for implicit imposition of the orthonormality constraint among the estimated sources. The major advantage of the proposed algorithm is the increased accuracy with which the weight matrix in the independent component analysis (ICA) model is estimated, compared to conventional schemes. When the local optimizer with Lie group techniques and the fast fixed-point (fastICA) algorithm were experimented by inputting the same set of random vectors, the former method superseded the conventional one by producing accurate weight matrix estimates in a majority of the test cases. Importantly, in our approach, the use of a Lie group to "lock" the weight matrix estimates onto the constraint surface enabled easy realization of the hybrid optimizers to yield near-global-optimum solutions consistently in most of the test cases, compared to well-known global optimizers. The inherent computational overhead in the hybrid optimizers was lowered by preprocessing the input data and periodically integrating the local optimizers with the global one. The proposed algorithms were applied to six-dimensional multispectral satellite image data to emphasize their usefulness in terms of accurate ICA weight matrix estimation.

The appearance of disproportionately large amounts of high-density breast parenchyma in mammograms has been found to be a strong indicator of the risk of developing breast cancer. Hence, the breast density model is popular for risk estimation or for monitoring breast density change in prevention or intervention programs. However, the efficiency of such a stochastic model depends on the accuracy of estimation of the model's parameter set. We propose a new approach-heuristic optimization-to estimate more accurately the model parameter set as compared to the conventional and popular expectation-maximization (EM) algorithm. After initial segmentation of a given mammogram, the finite generalized Gaussian mixture (FGGM) model is constructed by computing the statistics associated with different image regions. The model parameter set thus obtained is estimated by particle swarm optimization (PSO) and evolutionary programming (EP) techniques, where the objective function to be minimized is the relative entropy between the image histogram and the estimated density distributions. When our heuristic approach was applied to different categories of mammograms from the Mini-MIAS database, it yielded lower floor of estimation error in 109 out of 112 cases (97.3 %), and 101 out of 102 cases (99.0%), for the number of image regions being five and eight, respectively, with the added advantage of faster convergence rate, when compared to the EM approach. Besides, the estimated density model preserves the number of regions specified by the information-theoretic criteria in all the test cases, and the assessment of the segmentation results by radiologists is promising.