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The automatic reconstruction of single neurons from microscopic images is essential to enable large-scale data-driven investigations in neuron morphology research. However, few previous methods were able to generate satisfactory results automatically from 3-D microscopic images without human intervention. In this paper, we developed a new algorithm for automatic 3-D neuron reconstruction. The main idea of the proposed algorithm is to iteratively track backward from the potential neuronal termini to the soma centre. An online confidence score is computed to decide if a tracing iteration should be stopped and discarded from the final reconstruction. The performance improvements comparing with the previous methods are mainly introduced by a more accurate estimation of the traced area and the confidence controlled back-tracking algorithm. The proposed algorithm supports large-scale batch-processing by requiring only one user specified parameter for background segmentation. We bench tested the proposed algorithm on the images obtained from both the DIADEM challenge and the BigNeuron challenge. Our proposed algorithm achieved the state-of-the-art results. [ABSTRACT FROM AUTHOR]

Prostate cancer is the most prevalent cancer among men in Western countries, with 1.1 million new diagnoses every year. The gold standard for the diagnosis of prostate cancer is a pathologists’ evaluation of prostate tissue. To potentially assist pathologists deep $\overline {/}$ learning $\overline {/}$ based cancer detection systems have been developed. Many of the state-of-the-art models are patch $\overline {/}$ based convolutional neural networks, as the use of entire scanned slides is hampered by memory limitations on accelerator cards. Patch-based systems typically require detailed, pixel-level annotations for effective training. However, such annotations are seldom readily available, in contrast to the clinical reports of pathologists, which contain slide-level labels. As such, developing algorithms which do not require manual pixel-wise annotations, but can learn using only the clinical report would be a significant advancement for the field. In this paper, we propose to use a streaming implementation of convolutional layers, to train a modern CNN (ResNet $\overline {/}$ 34) with 21 million parameters end-to-end on 4712 prostate biopsies. The method enables the use of entire biopsy images at high-resolution directly by reducing the GPU memory requirements by 2.4 TB. We show that modern CNNs, trained using our streaming approach, can extract meaningful features from high-resolution images without additional heuristics, reaching similar performance as state-of-the-art patch-based and multiple-instance learning methods. By circumventing the need for manual annotations, this approach can function as a blueprint for other tasks in histopathological diagnosis. The source code to reproduce the streaming models is available at https://github.com/DIAGNijmegen/ pathology-streaming-pipeline. [ABSTRACT FROM AUTHOR]

Breast arterial calcifications (BACs) are part of several benign findings present on some mammograms. Previous studies have indicated that BAC may provide evidence of general atherosclerotic vascular disease, and potentially be a useful marker of cardiovascular disease (CVD). Currently, there is no technique in use for the automatic detection of BAC in mammograms. Since a majority of women over the age of 40 already undergo breast cancer screening with mammography, detecting BAC may offer a method to screen women for CVD in a way that is effective, efficient, and broad reaching, at no additional cost or radiation. In this paper, we present a deep learning approach for detecting BACs in mammograms. Inspired by the promising results achieved using the U-Net model in many biomedical segmentation problems and the DenseNet in semantic segmentation, we extend the U-Net model with dense connectivity to automatically detect BACs in mammograms. The presented model helps to facilitate the reuse of computation and improve the flow of gradients, leading to better accuracy and easier training of the model. We evaluate the performance using a set of full-field digital mammograms collected and prepared for this task from a publicly available dataset. Experimental results demonstrate that the presented model outperforms human experts as well as the other related deep learning models. This confirms the effectiveness of our model in the BACs detection task, which is a promising step in providing a cost-effective risk assessment tool for CVD. [ABSTRACT FROM AUTHOR]

Modeling of brain tumor dynamics has the potential to advance therapeutic planning. Current modeling approaches resort to numerical solvers that simulate the tumor progression according to a given differential equation. Using highly-efficient numerical solvers, a single forward simulation takes up to a few minutes of compute. At the same time, clinical applications of tumor modeling often imply solving an inverse problem, requiring up to tens of thousands of forward model evaluations when used for a Bayesian model personalization via sampling. This results in a total inference time prohibitively expensive for clinical translation. While recent data-driven approaches become capable of emulating physics simulation, they tend to fail in generalizing over the variability of the boundary conditions imposed by the patient-specific anatomy. In this paper, we propose a learnable surrogate for simulating tumor growth which maps the biophysical model parameters directly to simulation outputs, i.e. the local tumor cell densities, whilst respecting patient geometry. We test the neural solver in a Bayesian model personalization task for a cohort of glioma patients. Bayesian inference using the proposed surrogate yields estimates analogous to those obtained by solving the forward model with a regular numerical solver. The near real-time computation cost renders the proposed method suitable for clinical settings. The code is available at https://github.com/IvanEz/tumor-surrogate. [ABSTRACT FROM AUTHOR]

We aim to investigate the counting response variations of positron emission tomography (PET) scanners with different detector configurations in the presence of solitary pulmonary nodule (SPN). Using experimentally validated Monte Carlo simulations, the counting performance of four different scanner models with varying tumor activity, location, and patient obesity is represented using a noise equivalent count rate (NECR). NECR is a well-established quantitative metric which has positive correlation with clinically perceived image quality. The combined effect of tumor displacement and increased activity shows a linear ascending trend for NECR with slope ranges of (12.5–18.2)*10−3 (kBq/cm3)−1 for three-ring (3R) scanners and (15.3–21.5)*10−3 (kBq/cm3)−1 for four-ring (4R). The trend for the combined effect of tumor displacement and patient obesity is exponential decay with 3R configurations weakly dependent on the patient obesity if the tumor is located at the center of the field of view with exponent’s range of (6.6–33.8)*10−2cm−1. The dependence is stronger for 4R scanners (9.6–38.5)*10−2cm−1. The analysis indicates that quantitative PET data from the same SPN patient possibly examined in different time points (e.g., during staging or for the evaluation of treatment response) are affected by the different detector configurations and need to be normalized with patient weight, activity, and tumor location to reduce unwanted bias of the diagnosis. This paper provides also with a proof of concept for the ability of properly tuned simulations to provide additional insights into the counting response variability especially in tumor types where often borderline decisions have to be made regarding their characterization. [ABSTRACT FROM AUTHOR]

Given the outbreak of COVID-19 pandemic and the shortage of medical resource, extensive deep learning models have been proposed for automatic COVID-19 diagnosis, based on 3D computed tomography (CT) scans. However, the existing models independently process the 3D lesion segmentation and disease classification, ignoring the inherent correlation between these two tasks. In this paper, we propose a joint deep learning model of 3D lesion segmentation and classification for diagnosing COVID-19, called DeepSC-COVID, as the first attempt in this direction. Specifically, we establish a large-scale CT database containing 1,805 3D CT scans with fine-grained lesion annotations, and reveal 4 findings about lesion difference between COVID-19 and community acquired pneumonia (CAP). Inspired by our findings, DeepSC-COVID is designed with 3 subnets: a cross-task feature subnet for feature extraction, a 3D lesion subnet for lesion segmentation, and a classification subnet for disease diagnosis. Besides, the task-aware loss is proposed for learning the task interaction across the 3D lesion and classification subnets. Different from all existing models for COVID-19 diagnosis, our model is interpretable with fine-grained 3D lesion distribution. Finally, extensive experimental results show that the joint learning framework in our model significantly improves the performance of 3D lesion segmentation and disease classification in both efficiency and efficacy. [ABSTRACT FROM AUTHOR]

Predicting tumor growth and its response to therapy remains a major challenge in cancer research and strongly relies on tumor growth models. In this paper, we introduce, calibrate, and verify a novel image-driven reaction-diffusion model of avascular tumor growth. The model allows for proliferation, death and spread of tumor cells, and accounts for nutrient distribution and hypoxia. It is constrained by longitudinal time series of dynamic contrast-enhancement-MRI images. Tumor specific parameters are estimated from two early time points and used to predict the spatio-temporal evolution of the tumor volume and cell densities at later time points. We first test our parameter estimation approach on synthetic data from 15 generated tumors. Our in silico study resulted in small volume errors (<5%) and high Dice overlaps (>97%), showing that model parameters can be successfully recovered and used to accurately predict the tumor growth. Encouraged by these results, we apply our model to seven pre-clinical cases of breast carcinoma. We are able to show promising preliminary results, especially for the estimation for early time points. Processes like angiogenesis and apoptosis should be included to further improve predictions for later time points. [ABSTRACT FROM PUBLISHER]

In this paper, we aim to produce a realistic 2-D projection of the breast parenchymal distribution from a 3-D breast magnetic resonance image (MRI). To evaluate the accuracy of our simulation, we compare our results with the local breast density (i.e., density map) obtained from the complementary full-field digital mammogram. To achieve this goal, we have developed a fully automatic framework, which registers MRI volumes to X-ray mammograms using a subject-specific biomechanical model of the breast. The optimization step modifies the position, orientation, and elastic parameters of the breast model to perform the alignment between the images. When the model reaches an optimal solution, the MRI glandular tissue is projected and compared with the one obtained from the corresponding mammograms. To reduce the loss of information during the ray-casting, we introduce a new approach that avoids resampling the MRI volume. In the results, we focus our efforts on evaluating the agreement of the distributions of glandular tissue, the degree of structural similarity, and the correlation between the real and synthetic density maps. Our approach obtained a high-structural agreement regardless the glandularity of the breast, whilst the similarity of the glandular tissue distributions and correlation between both images increase in denser breasts. Furthermore, the synthetic images show continuity with respect to large structures in the density maps. [ABSTRACT FROM PUBLISHER]

The four-dimensional (4-D) eXtended CArdiac-Torso (XCAT) series of phantoms was developed to provide accurate computerized models of the human anatomy and physiology. The XCAT series encompasses a vast population of phantoms of varying ages from newborn to adult, each including parameterized models for the cardiac and respiratory motions. With great flexibility in the XCAT’s design, any number of body sizes, different anatomies, cardiac or respiratory motions or patterns, patient positions and orientations, and spatial resolutions can be simulated. As such, the XCAT phantoms are gaining a wide use in biomedical imaging research. There they can provide a virtual patient base from which to quantitatively evaluate and improve imaging instrumentation, data acquisition, techniques, and image reconstruction and processing methods which can lead to improved image quality and more accurate clinical diagnoses. The phantoms have also found great use in radiation dosimetry, radiation therapy, medical device design, and even the security and defense industry. This review paper highlights some specific areas in which the XCAT phantoms have found use within biomedical imaging and other fields. From these examples, we illustrate the increasingly important role that computerized phantoms and computer simulation are playing in the research community. [ABSTRACT FROM PUBLISHER]

A critical challenge in using longitudinal neuroimaging data to study the progressions of Alzheimer’s Disease (AD) is the varied number of missing records of the patients during the course when AD develops. To tackle this problem, in this paper we propose a novel formulation to learn an enriched representation with fixed length for imaging biomarkers, which aims to simultaneously capture the information conveyed by both baseline neuroimaging record and progressive variations characterized by varied counts of available follow-up records over time. Because the learned biomarker representations are a set of fixed-length vectors, they can be readily used by traditional machine learning models to study AD developments. Take into account that the missing brain scans are not aligned in terms of time in a studied cohort, we develop a new objective that maximizes the ratio of the summations of a number of $\ell _{1}$ -norm distances for improved robustness, which, though, is difficult to efficiently solve in general. Thus, we derive a new efficient and non-greedy iterative solution algorithm and rigorously prove its convergence. We have performed extensive experiments on the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort. A clear performance gain has been achieved in predicting ten different cognitive scores when we compare the original baseline biomarker representations against the learned representations with longitudinal enrichments. We further observe that the top selected biomarkers by our new method are in accordance with known knowledge in AD studies. These promising results have demonstrated improved performances of our new method that validate its effectiveness. [ABSTRACT FROM AUTHOR]

This paper proposes a mixture of linear dynamical systems model for quantifying the heterogeneous progress of Parkinson’s disease from DaTscan Images. The model is fitted to longitudinal DaTscans from the Parkinson’s Progression Marker Initiative. Fitting is accomplished using robust Bayesian inference with collapsed Gibbs sampling. Bayesian inference reveals three image-based progression subtypes which differ in progression speeds as well as progression trajectories. The model reveals characteristic spatial progression patterns in the brain, each pattern associated with a time constant. These patterns can serve as disease progression markers. The subtypes also have different progression rates of clinical symptoms measured by MDS-UPDRS Part III scores. [ABSTRACT FROM AUTHOR]

To obtain a patient-specific cardiac electro-physiological (EP) model, it is important to estimate the 3-D distributed tissue properties of the myocardium. Ideally, the tissue property should be estimated at the resolution of the cardiac mesh. However, such high-dimensional estimation faces major challenges in identifiability and computation. Most existing works reduce this dimension by partitioning the cardiac mesh into a pre-defined set of segments. The resulting low-resolution solutions have a limited ability to represent the underlying heterogeneous tissue properties of varying sizes, locations, and distributions. In this paper, we present a novel framework that, going beyond a uniform low-resolution approach, is able to obtain a higher resolution estimation of tissue properties represented by spatially non-uniform resolution. This is achieved by two central elements: 1) a multi-scale coarse-to-fine optimization that facilitates higher resolution optimization using the lower resolution solution and 2) a spatially adaptive decision criterion that retains lower resolution in homogeneous tissue regions and allows higher resolution in heterogeneous tissue regions. The presented framework is evaluated in estimating the local tissue excitability properties of a cardiac EP model on both synthetic and real data experiments. Its performance is compared with optimization using pre-defined segments. Results demonstrate the feasibility of the presented framework to estimate local parameters and to reveal heterogeneous tissue properties at a higher resolution without using a high number of unknowns. [ABSTRACT FROM AUTHOR]

Classification of clustered breast microcalcifications into benign and malignant categories is an extremely challenging task for computerized algorithms and expert radiologists alike. In this paper we apply a multi-view-classifier for the task. We describe a two-step classification method that is based on a view-level decision, implemented by a logistic regression classifier, followed by a stochastic combination of the two view-level indications into a single benign or malignant decision. The proposed method was evaluated on a large number of cases from a standardized digital database for screening mammography (DDSM). Experimental results demonstrate the advantage of the proposed multi-view classification algorithm that automatically learns the best way to combine the views. [ABSTRACT FROM PUBLISHER]

Registration and fusion of magnetic resonance (MR) and 3D transrectal ultrasound (TRUS) images of the prostate gland can provide high-quality guidance for prostate interventions. However, accurate MR-TRUS registration remains a challenging task, due to the great intensity variation between two modalities, the lack of intrinsic fiducials within the prostate, the large gland deformation caused by the TRUS probe insertion, and distinctive biomechanical properties in patients and prostate zones. To address these challenges, a personalized model-to-surface registration approach is proposed in this study. The main contributions of this paper can be threefold. First, a new personalized statistical deformable model (PSDM) is proposed with the finite element analysis and the patient-specific tissue parameters measured from the ultrasound elastography. Second, a hybrid point matching method is developed by introducing the modality independent neighborhood descriptor (MIND) to weight the Euclidean distance between points to establish reliable surface point correspondence. Third, the hybrid point matching is further guided by the PSDM for more physically plausible deformation estimation. Eighteen sets of patient data are included to test the efficacy of the proposed method. The experimental results demonstrate that our approach provides more accurate and robust MR-TRUS registration than state-of-the-art methods do. The averaged target registration error is 1.44 mm, which meets the clinical requirement of 1.9 mm for the accurate tumor volume detection. It can be concluded that the presented method can effectively fuse the heterogeneous image information in the elastography, MR, and TRUS to attain satisfactory image alignment performance. [ABSTRACT FROM PUBLISHER]

Digital reconstruction (tracing) of tree-like structures, such as neurons, retinal blood vessels, and bronchi, from volumetric images and 2D images is very important to biomedical research. Many existing reconstruction algorithms rely on a set of good seed points. The 2D or 3D terminations are good candidates for such seed points. In this paper, we propose an automatic method to detect terminations for tree-like structures based on a multiscale ray-shooting model and a termination visual prior. The multiscale ray-shooting model detects 2D terminations by extracting and analyzing the multiscale intensity distribution features around a termination candidate. The range of scale is adaptively determined according to the local neurite diameter estimated by the Rayburst sampling algorithm in combination with the gray-weighted distance transform. The termination visual prior is based on a key observation–when observing a 3D termination from three orthogonal directions without occlusion, we can recognize it in at least two views. Using this prior with the multiscale ray-shooting model, we can detect 3D terminations with high accuracies. Experiments on 3D neuron image stacks, 2D neuron images, 3D bronchus image stacks, and 2D retinal blood vessel images exhibit average precision and recall rates of 87.50% and 90.54%. The experimental results confirm that the proposed method outperforms other the state-of-the-art termination detection methods. [ABSTRACT FROM AUTHOR]

This paper presents an approach to predict the deformation of the lungs and surrounding organs during respiration. The framework incorporates a computational model of the respiratory system, which comprises an anatomical model extracted from computed tomography (CT) images at end-expiration (EE), and a biomechanical model of the respiratory physiology, including the material behavior and interactions between organs. A personalization step is performed to automatically estimate patient-specific thoracic pressure, which drives the biomechanical model. The zone-wise pressure values are obtained by using a trust-region optimizer, where the estimated motion is compared to CT images at end-inspiration (EI). A detailed convergence analysis in terms of mesh resolution, time stepping and number of pressure zones on the surface of the thoracic cavity is carried out. The method is then tested on five public datasets. Results show that the model is able to predict the respiratory motion with an average landmark error of 3.40 \pm 1.0 mm over the entire respiratory cycle. The estimated 3-D lung motion may constitute as an advanced 3-D surrogate for more accurate medical image reconstruction and patient respiratory analysis. [ABSTRACT FROM PUBLISHER]

Nonparametric hemodynamic response function (HRF) estimation in functional near-infrared spectroscopy (fNIRS) data plays an important role when investigating the temporal dynamics of a brain region response during activations. Assuming the drift arising from both physical and physiological effects in fNIRS data is Lipschitz continuous; a novel algorithm for joint HRF and drift estimation is derived in this paper. The proposed algorithm estimates the HRF by applying a first-order differencing to the fNIRS time series samples in order to remove the drift effect. An estimate of the drift is then obtained using a wavelet thresholding technique applied to the residuals generated by removing the estimated induced activation response from the fNIRS time-series. It is shown that the proposed HRF estimator is \sqrt N consistent whereas the estimator of the drift is asymptotically optimal. The de-drifted fNIRS oxygenated (HbO) and deoxygenated (HbR) hemoglobin responses are then obtained by removing the corresponding estimated drifts from the fNIRS time-series. Its performance is assessed using both simulated and real fNIRS data sets. The application results reveal that the proposed joint HRF and drift estimation method is efficient both computationally and in terms of accuracy. In comparison to traditional model based methods used for HRF estimation, the proposed novel method avoids the selection of a model to remove the drift component. As a result, the proposed method finds an optimal estimate of the fNIRS drift and offers a model-free approach to de-drift the HbO/HbR responses. [ABSTRACT FROM AUTHOR]

Preoperative diagnostic magnetic resonance (MR) breast images can provide good contrast between different tissues and 3-D information about suspicious tissues. Aligning preoperative diagnostic MR images with a patient in the theatre during breast conserving surgery could assist surgeons in achieving the complete excision of cancer with sufficient margins. Typically, preoperative diagnostic MR breast images of a patient are obtained in the prone position, while surgery is performed in the supine position. The significant shape change of breasts between these two positions due to gravity loading, external forces and related constraints makes the alignment task extremely difficult. Our previous studies have shown that either nonrigid intensity-based image registration or biomechanical modelling alone are limited in their ability to capture such a large deformation. To tackle this problem, we proposed in this paper a nonlinear biomechanical model-based image registration method with a simultaneous optimization procedure for both the material parameters of breast tissues and the direction of the gravitational force. First, finite element (FE) based biomechanical modelling is used to estimate a physically plausible deformation of the pectoral muscle and the major deformation of breast tissues due to gravity loading. Then, nonrigid intensity-based image registration is employed to recover the remaining deformation that FE analyses do not capture due to the simplifications and approximations of biomechanical models and the uncertainties of external forces and constraints. We assess the registration performance of the proposed method using the target registration error of skin fiducial markers and the Dice similarity coefficient (DSC) of fibroglandular tissues. The registration results on prone and supine MR image pairs are compared with those from two alternative nonrigid registration methods for five breasts. Overall, the proposed algorithm achieved the best registration performance on fiducial markers (target registration error, 8.44 \pm 5.5 mm for 45 fiducial markers) and higher overlap rates on segmentation propagation of fibroglandular tissues (DSC value > 82\%). [ABSTRACT FROM PUBLISHER]

Cancer causes deviations in the distribution of cells, leading to changes in biological structures that they form. Correct localization and characterization of these structures are crucial for accurate cancer diagnosis and grading. In this paper, we introduce an effective hybrid model that employs both structural and statistical pattern recognition techniques to locate and characterize the biological structures in a tissue image for tissue quantification. To this end, this hybrid model defines an attributed graph for a tissue image and a set of query graphs as a reference to the normal biological structure. It then locates key regions that are most similar to a normal biological structure by searching the query graphs over the entire tissue graph. Unlike conventional approaches, this hybrid model quantifies the located key regions with two different types of features extracted using structural and statistical techniques. The first type includes embedding of graph edit distances to the query graphs whereas the second one comprises textural features of the key regions. Working with colon tissue images, our experiments demonstrate that the proposed hybrid model leads to higher classification accuracies, compared against the conventional approaches that use only statistical techniques for tissue quantification. [ABSTRACT FROM PUBLISHER]

This paper presents the Virtual Imaging Platform (VIP), a platform accessible at xlink:type="simple" xlink:href="http://vip.creatis.insa-lyon.fr" xmlns:xlink="http://www.w3.org/1999/xlink"http://vip.creatis.insa-lyon.fr to facilitate the sharing of object models and medical image simulators, and to provide access to distributed computing and storage resources. A complete overview is presented, describing the ontologies designed to share models in a common repository, the workflow template used to integrate simulators, and the tools and strategies used to exploit computing and storage resources. Simulation results obtained in four image modalities and with different models show that VIP is versatile and robust enough to support large simulations. The platform currently has 200 registered users who consumed 33 years of CPU time in 2011. [ABSTRACT FROM PUBLISHER]

This paper presents the relevance voxel machine (RVoxM), a dedicated Bayesian model for making predictions based on medical imaging data. In contrast to the generic machine learning algorithms that have often been used for this purpose, the method is designed to utilize a small number of spatially clustered sets of voxels that are particularly suited for clinical interpretation. RVoxM automatically tunes all its free parameters during the training phase, and offers the additional advantage of producing probabilistic prediction outcomes. We demonstrate RVoxM as a regression model by predicting age from volumetric gray matter segmentations, and as a classification model by distinguishing patients with Alzheimer's disease from healthy controls using surface-based cortical thickness data. Our results indicate that RVoxM yields biologically meaningful models, while providing state-of-the-art predictive accuracy. [ABSTRACT FROM PUBLISHER]

During neurosurgery, nonrigid brain deformation may affect the reliability of tissue localization based on preoperative images. To provide accurate surgical guidance in these cases, preoperative images must be updated to reflect the intraoperative brain. This can be accomplished by warping these preoperative images using a biomechanical model. Due to the possible complexity of this deformation, intraoperative information is often required to guide the model solution. In this paper, a linear elastic model of the brain is developed to infer volumetric brain deformation associated with measured intraoperative cortical surface displacement. The developed model relies on known material properties of brain tissue, and does not require further knowledge about intraoperative conditions. To provide an initial estimation of volumetric model accuracy, as well as determine the model's sensitivity to the specified material parameters and surface displacements, a realistic brain phantom was developed. Phantom results indicate that the linear elastic model significantly reduced localization error due to brain shift, from > 16 mm to under 5 mm, on average. In addition, though in vivo quantitative validation is necessary, preliminary application of this approach to images acquired during neocortical epilepsy cases confirms the feasibility of applying the developed model to in vivo data. [ABSTRACT FROM PUBLISHER]

This paper addresses the problem of jointly estimating the statistical distribution and segmenting lesions in multiple-tissue high-frequency skin ultrasound images. The distribution of multiple-tissue images is modeled as a spatially coherent finite mixture of heavy-tailed Rayleigh distributions. Spatial coherence inherent to biological tissues is modeled by enforcing local dependence between the mixture components. An original Bayesian algorithm combined with a Markov chain Monte Carlo method is then proposed to jointly estimate the mixture parameters and a label-vector associating each voxel to a tissue. More precisely, a hybrid Metropolis-within-Gibbs sampler is used to draw samples that are asymptotically distributed according to the posterior distribution of the Bayesian model. The Bayesian estimators of the model parameters are then computed from the generated samples. Simulation results are conducted on synthetic data to illustrate the performance of the proposed estimation strategy. The method is then successfully applied to the segmentation of in vivo skin tumors in high-frequency 2-D and 3-D ultrasound images. [ABSTRACT FROM PUBLISHER]

There is growing clinical demand for image registration techniques that allow multimodal data fusion for accurate targeting of needle biopsy and ablative prostate cancer treatments. However, during procedures where transrectal ultrasound (TRUS) guidance is used, substantial gland deformation can occur due to TRUS probe pressure. In this paper, the ability of a statistical shape/motion model, trained using finite element simulations, to predict and compensate for this source of motion is investigated. Three-dimensional ultrasound images acquired on five patient prostates, before and after TRUS-probe-induced deformation, were registered using a nonrigid, surface-based method, and the accuracy of different deformation models compared. Registration using a statistical motion model was found to outperform alternative elastic deformation methods in terms of accuracy and robustness, and required substantially fewer target surface points to achieve a successful registration. The mean final target registration error (based on anatomical landmarks) using this method was 1.8 mm. We conclude that a statistical model of prostate deformation provides an accurate, rapid and robust means of predicting prostate deformation from sparse surface data, and is therefore well-suited to a number of interventional applications where there is a need for deformation compensation. [ABSTRACT FROM AUTHOR]

In this paper a model selection algorithm for a nonlinear system identification method is proposed to study functional magnetic resonance imaging (fMRI) effective connectivity. Unlike most other methods, this method does not need a pre-defined structure/model for effective connectivity analysis. Instead, it relies on selecting significant nonlinear or linear covariates for the differential equations to describe the mapping relationship between brain output (fMRI response) and input (experiment design). These covariates, as well as their coefficients, are estimated based on a least angle regression (LARS) method. In the implementation of the LARS method, Akaike's information criterion corrected (AICc) algorithm and the leave-one-out (LOO) cross-validation method were employed and compared for model selection. Simulation comparison between the dynamic causal model (DCM), nonlinear identification method, and model selection method for modelling the single-input-single-output (SISO) and multiple-input multiple-output (MIMO) systems were conducted. Results show that the LARS model selection method is faster than DCM and achieves a compact and economic nonlinear model simultaneously. To verify the efficacy of the proposed approach, an analysis of the dorsal and ventral visual pathway networks was carried out based on three real datasets. The results show that LARS can be used for model selection in an fMRI effective connectivity study with phase-encoded, standard block, and random block designs. It is also shown that the LOO cross-validation method for nonlinear model selection has less residual sum squares than the AICc algorithm for the study. [ABSTRACT FROM AUTHOR]

This paper investigates the problem of atlas registration of brain images with gliomas. Multiparametric imaging modalities (T1, T1-CE, T2, and FLAIR) are first utilized for segmentations of different tissues, and to compute the posterior probability map (PBM) of membership to each tissue class, using supervised learning. Similar maps are generated in the initially normal atlas, by modeling the tumor growth, using reaction-diffusion equation. Deformable registration using a demons-like algorithm is used to register the patient images with the tumor bearing atlas. Joint estimation of the simulated tumor parameters (e.g., location, mass effect and degree of infiltration), and the spatial transformation is achieved by maximization of the log-likelihood of observation. An expectation-maximization algorithm is used in registration process to estimate the spatial transformation and other parameters related to tumor simulation are optimized through asynchronous parallel pattern search (APPSPACK). The proposed method has been evaluated on five simulated data sets created by statistically simulated deformations (SSD), and fifteen real multichannel glioma data sets. The performance has been evaluated both quantitatively and qualitatively, and the results have been compared to ORBIT, an alternative method solving a similar problem. The results show that our method outperforms ORBIT, and the warped templates have better similarity to patient images. [ABSTRACT FROM AUTHOR]

Biophysical models are a promising means for interpreting diffusion weighted magnetic resonance imaging (DW-MRI) data, as they can provide estimates of physiologically relevant parameters of microstructure including cell size, volume fraction, or dispersion. However, their application in cardiac microstructure mapping (CMM) has been limited. This study proposes seven new two-compartment models with combination of restricted cylinder models and a diffusion tensor to represent intra- and extracellular spaces, respectively. Three extended versions of the cylinder model are studied here: cylinder with elliptical cross section (ECS), cylinder with Gamma distributed radii (GDR), and cylinder with Bingham distributed axes (BDA). The proposed models were applied to data in two fixed mouse hearts, acquired with multiple diffusion times, q-shells and diffusion encoding directions. The cylinderGDR-pancake model provided the best performance in terms of root mean squared error (RMSE) reducing it by 25% compared to diffusion tensor imaging (DTI). The cylinderBDA-pancake model represented anatomical findings closest as it also allows for modelling dispersion. High-resolution 3D synchrotron X-ray imaging (SRI) data from the same specimen was utilized to evaluate the biophysical models. A novel tensor-based registration method is proposed to align SRI structure tensors to the MR diffusion tensors. The consistency between SRI and DW-MRI parameters demonstrates the potential of compartment models in assessing physiologically relevant parameters. [ABSTRACT FROM AUTHOR]

Imaging genetics is an effective tool used to detect potential biomarkers of Alzheimer’s disease (AD) in imaging and genetic data. Most existing imaging genetics methods analyze the association between brain imaging quantitative traits (QTs) and genetic data [e.g., single nucleotide polymorphism (SNP)] by using a linear model, ignoring correlations between a set of QTs and SNP groups, and disregarding the varied associations between longitudinal imaging QTs and SNPs. To solve these problems, we propose a novel temporal group sparsity regression and additive model (T-GSRAM) to identify associations between longitudinal imaging QTs and SNPs for detection of potential AD biomarkers. We first construct a nonparametric regression model to analyze the nonlinear association between QTs and SNPs, which can accurately model the complex influence of SNPs on QTs. We then use longitudinal QTs to identify the trajectory of imaging genetic patterns over time. Moreover, the SNP information of group and individual levels are incorporated into the proposed method to boost the power of biomarker detection. Finally, we propose an efficient algorithm to solve the whole T-GSRAM model. We evaluated our method using simulation data and real data obtained from AD neuroimaging initiative. Experimental results show that our proposed method outperforms several state-of-the-art methods in terms of the receiver operating characteristic curves and area under the curve. Moreover, the detection of AD-related genes and QTs has been confirmed in previous studies, thereby further verifying the effectiveness of our approach and helping understand the genetic basis over time during disease progression. [ABSTRACT FROM AUTHOR]

The combination of multimodal imaging and genomics provides a more comprehensive way for the study of mental illnesses and brain functions. Deep network-based data fusion models have been developed to capture their complex associations, resulting in improved diagnosis of diseases. However, deep learning models are often difficult to interpret, bringing about challenges for uncovering biological mechanisms using these models. In this work, we develop an interpretable multimodal fusion model to perform automated diagnosis and result interpretation simultaneously. We name it Grad-CAM guided convolutional collaborative learning (gCAM-CCL), which is achieved by combining intermediate feature maps with gradient-based weights. The gCAM-CCL model can generate interpretable activation maps to quantify pixel-level contributions of the input features. Moreover, the estimated activation maps are class-specific, which can therefore facilitate the identification of biomarkers underlying different groups. We validate the gCAM-CCL model on a brain imaging-genetic study, and demonstrate its applications to both the classification of cognitive function groups and the discovery of underlying biological mechanisms. Specifically, our analysis results suggest that during task-fMRI scans, several object recognition related regions of interests (ROIs) are activated followed by several downstream encoding ROIs. In addition, the high cognitive group may have stronger neurotransmission signaling while the low cognitive group may have problems in brain/neuron development due to genetic variations. [ABSTRACT FROM AUTHOR]

Our objective is the calibration of mathematical tumor growth models from a single multiparametric scan. The target problem is the analysis of preoperative Glioblastoma (GBM) scans. To this end, we present a fully automatic tumor-growth calibration methodology that integrates a single-species reaction-diffusion partial differential equation (PDE) model for tumor progression with multiparametric Magnetic Resonance Imaging (mpMRI) scans to robustly extract patient specific biomarkers i.e., estimates for (i) the tumor cell proliferation rate, (ii) the tumor cell migration rate, and (iii) the original, localized site(s) of tumor initiation. Our method is based on a sparse reconstruction algorithm for the tumor initial location (TIL). This problem is particularly challenging due to nonlinearity, ill-posedeness, and ill conditioning. We propose a coarse-to-fine multi-resolution continuation scheme with parameter decomposition to stabilize the inversion. We demonstrate robustness and practicality of our method by applying the proposed method to clinical data of 206 GBM patients. We analyze the extracted biomarkers and relate tumor origin with patient overall survival by mapping the former into a common atlas space. We present preliminary results that suggest improved accuracy for prediction of patient overall survival when a set of imaging features is augmented with estimated biophysical parameters. All extracted features, tumor initial positions, and biophysical growth parameters are made publicly available for further analysis. To our knowledge, this is the first fully automatic scheme that can handle multifocal tumors and can localize the TIL to a few millimeters. [ABSTRACT FROM AUTHOR]

Transplantable kidneys are in very limited supply. Accurate viability assessment prior to transplantation could minimize organ discard. Rapid and accurate evaluation of intra-operative donor kidney biopsies is essential for determining which kidneys are eligible for transplantation. The criterion for accepting or rejecting donor kidneys relies heavily on pathologist determination of the percent of glomeruli (determined from a frozen section) that are normal and sclerotic. This percentage is a critical measurement that correlates with transplant outcome. Inter- and intra-observer variability in donor biopsy evaluation is, however, significant. An automated method for determination of percent global glomerulosclerosis could prove useful in decreasing evaluation variability, increasing throughput, and easing the burden on pathologists. Here, we describe the development of a deep learning model that identifies and classifies non-sclerosed and sclerosed glomeruli in whole-slide images of donor kidney frozen section biopsies. This model extends a convolutional neural network (CNN) pre-trained on a large database of digital images. The extended model, when trained on just 48 whole slide images, exhibits slide-level evaluation performance on par with expert renal pathologists. Encouragingly, the model’s performance is robust to slide preparation artifacts associated with frozen section preparation. The model substantially outperforms a model trained on image patches of isolated glomeruli, in terms of both accuracy and speed. The methodology overcomes the technical challenge of applying a pretrained CNN bottleneck model to whole-slide image classification. The traditional patch-based approach, while exhibiting deceptively good performance classifying isolated patches, does not translate successfully to whole-slide image segmentation in this setting. As the first model reported that identifies and classifies normal and sclerotic glomeruli in frozen kidney sections, and thus the first model reported in the literature relevant to kidney transplantation, it may become an essential part of donor kidney biopsy evaluation in the clinical setting. [ABSTRACT FROM AUTHOR]

We present a multi-scale approach of tumor modeling in order to predict its evolution during radiotherapy. Within this context we focus on three different scales of tumor modeling: microscopic (individual cells in a voxel), mesoscopic (population of cells in a voxel) and macroscopic (whole tumor), with transition interfaces between these three scales. At the cellular level, the description is based on phase transfer probabilities in the cellular cycle. At the mesoscopic scale we represent populations of cells according to different stages in a cell cycle. Finally, at the macroscopic scale, the tumor description is based on the use of FDG PET image voxels. These three scales exist naturally: biological data are collected at the macroscopic scale, but the pathological behavior of the tumor is based on an abnormal cell-cycle at the microscopic scale. On the other hand, the introduction of a mesoscopic scale is essential in order to reduce the gap between the two extreme, in terms of resolution, description levels. It also reduces the computational burden of simulating a large number of individual cells. As an application of the proposed multi-scale model, we simulate the effect of oxygen on tumor evolution during radiotherapy. Two consecutive FDG PET images of 17 rectal cancer patients undergoing radiotherapy are used to simulate the tumor evolution during treatment. The simulated results are compared with those obtained on a third FDG PET image acquired two weeks after the beginning of the treatment. [ABSTRACT FROM PUBLISHER]

We introduce a generative probabilistic model for segmentation of brain lesions in multi-dimensional images that generalizes the EM segmenter, a common approach for modelling brain images using Gaussian mixtures and a probabilistic tissue atlas that employs expectation-maximization (EM), to estimate the label map for a new image. Our model augments the probabilistic atlas of the healthy tissues with a latent atlas of the lesion. We derive an estimation algorithm with closed-form EM update equations. The method extracts a latent atlas prior distribution and the lesion posterior distributions jointly from the image data. It delineates lesion areas individually in each channel, allowing for differences in lesion appearance across modalities, an important feature of many brain tumor imaging sequences. We also propose discriminative model extensions to map the output of the generative model to arbitrary labels with semantic and biological meaning, such as “tumor core” or “fluid-filled structure”, but without a one-to-one correspondence to the hypo- or hyper-intense lesion areas identified by the generative model. We test the approach in two image sets: the publicly available BRATS set of glioma patient scans, and multimodal brain images of patients with acute and subacute ischemic stroke. We find the generative model that has been designed for tumor lesions to generalize well to stroke images, and the extended discriminative -discriminative model to be one of the top ranking methods in the BRATS evaluation. [ABSTRACT FROM AUTHOR]

Radiofrequency ablation (RFA) is an established treatment for liver cancer when resection is not possible. Yet, its optimal delivery is challenged by the presence of large blood vessels and the time-varying thermal conductivity of biological tissue. Incomplete treatment and an increased risk of recurrence are therefore common. A tool that would enable the accurate planning of RFA is hence necessary. This manuscript describes a new method to compute the extent of ablation required based on the Lattice Boltzmann Method (LBM) and patient-specific, pre-operative images. A detailed anatomical model of the liver is obtained from volumetric images. Then a computational model of heat diffusion, cellular necrosis, and blood flow through the vessels and liver is employed to compute the extent of ablated tissue given the probe location, ablation duration and biological parameters. The model was verified against an analytical solution, showing good fidelity. We also evaluated the predictive power of the proposed framework on ten patients who underwent RFA, for whom pre- and post-operative images were available. Comparisons between the computed ablation extent and ground truth, as observed in postoperative images, were promising (DICE index: 42%, sensitivity: 67%, positive predictive value: 38%). The importance of considering liver perfusion while simulating electrical-heating ablation was also highlighted. Implemented on graphics processing units (GPU), our method simulates 1 minute of ablation in 1.14 minutes, allowing near real-time computation. [ABSTRACT FROM AUTHOR]

Functional magnetic resonance imaging (fMRI) is an indirect measure of neural activity which is modeled as a convolution of the latent neuronal response and the hemodynamic response function (HRF). Since the sources of HRF variability can be nonneural in nature, the measured fMRI signal does not faithfully represent underlying neural activity. Therefore, it is advantageous to deconvolve the HRF from the fMRI signal. However, since both latent neural activity and the voxel-specific HRF is unknown, the deconvolution must be blind. Existing blind deconvolution approaches employ highly parameterized models, and it is unclear whether these models have an over fitting problem. In order to address these issues, we 1) present a nonparametric deconvolution method based on homomorphic filtering to obtain the latent neuronal response from the fMRI signal and, 2) compare our approach to the best performing existing parametric model based on the estimation of the biophysical hemodynamic model using the Cubature Kalman Filter/Smoother. We hypothesized that if the results from nonparametric deconvolution closely resembled that obtained from parametric deconvolution, then the problem of over fitting during estimation in highly parameterized deconvolution models of fMRI could possibly be over stated. Both simulations and experimental results demonstrate support for our hypothesis since the estimated latent neural response from both parametric and nonparametric methods were highly correlated in the visual cortex. Further, simulations showed that both methods were effective in recovering the simulated ground truth of the latent neural response. [ABSTRACT FROM AUTHOR]

The ability of dual-energy computed-tomographic (CT) systems to determine the concentration of constituent materials in a mixture, known as material decomposition, is the basis for many of dual-energy CT's clinical applications. However, the complex composition of tissues and organs in the human body poses a challenge for many material decomposition methods, which assume the presence of only two, or at most three, materials in the mixture. We developed a flexible, model-based method that extends dual-energy CT's core material decomposition capability to handle more complex situations, in which it is necessary to disambiguate among and quantify the concentration of a larger number of materials. The proposed method, named multi-material decomposition (MMD), was used to develop two image analysis algorithms. The first was virtual unenhancement (VUE), which digitally removes the effect of contrast agents from contrast-enhanced dual-energy CT exams. VUE has the ability to reduce patient dose and improve clinical workflow, and can be used in a number of clinical applications such as CT urography and CT angiography. The second algorithm developed was liver-fat quantification (LFQ), which accurately quantifies the fat concentration in the liver from dual-energy CT exams. LFQ can form the basis of a clinical application targeting the diagnosis and treatment of fatty liver disease. Using image data collected from a cohort consisting of 50 patients and from phantoms, the application of MMD to VUE and LFQ yielded quantitatively accurate results when compared against gold standards. Furthermore, consistent results were obtained across all phases of imaging (contrast-free and contrast-enhanced). This is of particular importance since most clinical protocols for abdominal imaging with CT call for multi-phase imaging. We conclude that MMD can successfully form the basis of a number of dual-energy CT image analysis algorithms, and has the potential to improve the clinical utility of dual-energy CT in disease management. [ABSTRACT FROM AUTHOR]

The development of biophysical models of the heart has the potential to get insights in the patho-physiology of the heart, which requires to accurately modeling anatomy and function. The electrical activation sequence of the ventricles depends strongly on the cardiac conduction system (CCS). Its morphology and function cannot be observed in vivo, and therefore data available come from histological studies. We present a review on data available of the peripheral CCS including new experiments. In order to build a realistic model of the CCS we designed a procedure to extract morphological characteristics of the CCS from stained calf tissue samples. A CCS model personalized with our measurements has been built using L-systems. The effect of key unknown parameters of the model in the electrical activation of the left ventricle has been analyzed. The CCS models generated share the main characteristics of observed stained Purkinje networks. The timing of the simulated electrical activation sequences were in the physiological range for CCS models that included enough density of PMJs. These results show that this approach is a potential methodology for collecting knowledge-domain data and build improved CCS models of the heart automatically. [ABSTRACT FROM PUBLISHER]

We propose a new approach for the generation of synthetic but visually realistic time series of cardiac images based on an electromechanical model of the heart and real clinical 4-D image sequences. This is achieved by combining three steps. The first step is the simulation of a cardiac motion using an electromechanical model of the heart and the segmentation of the end diastolic image of a cardiac sequence. We use biophysical parameters related to the desired condition of the simulated subject. The second step extracts the cardiac motion from the real sequence using nonrigid image registration. Finally, a synthetic time series of cardiac images corresponding to the simulated motion is generated in the third step by combining the motion estimated by image registration and the simulated one. With this approach, image processing algorithms can be evaluated as we know the ground-truth motion underlying the image sequence. Moreover, databases of visually realistic images of controls and patients can be generated for which the underlying cardiac motion and some biophysical parameters are known. Such databases can open new avenues for machine learning approaches. [ABSTRACT FROM PUBLISHER]

The feasibility of using a stochastic form of Pennes bioheat model within a 3-D finite element based Kalman filter (KF) algorithm is critically evaluated for the ability to provide temperature field estimates in the event of magnetic resonance temperature imaging (MRTI) data loss during laser induced thermal therapy (LITT). The ability to recover missing MRTI data was analyzed by systematically removing spatiotemporal information from a clinical MR-guided LITT procedure in human brain and comparing predictions in these regions to the original measurements. Performance was quantitatively evaluated in terms of a dimensionless L2 (RMS) norm of the temperature error weighted by acquisition uncertainty. During periods of no data corruption, observed error histories demonstrate that the Kalman algorithm does not alter the high quality temperature measurement provided by MR thermal imaging. The KF-MRTI implementation considered is seen to predict the bioheat transfer with \ RMS ~error < 4 for a short period of time, \Delta t < 10~s, until the data corruption subsides. In its present form, the KF-MRTI method currently fails to compensate for consecutive for consecutive time periods of data loss \Delta t > 10~sec. [ABSTRACT FROM PUBLISHER]

The recent advances in meaningful constraining models have resulted in increasingly useful quantitative information recovered from cardiac images. Nevertheless, as most frameworks utilize either functional or structural images, the analyses cannot benefit from the complementary information provided by the other image sources. To better characterize subject-specific cardiac physiology and pathology, data fusion of multiple image sources is essential. Traditional image fusion strategies are performed by fusing information of commensurate images through various mathematical operators. Nevertheless, when image data are dissimilar in physical nature and spatiotemporal quantity, such approaches may not provide meaningful connections between different data. In fact, as different image sources provide partial measurements of the same cardiac system dynamics, it is more natural and suitable to utilize cardiac physiological models for the fusions. Therefore, we propose to use the cardiac physiome model as the central link to fuse functional and structural images for more subject-specific cardiac deformation recovery through state-space filtering. Experiments were performed on synthetic and real data for the characteristics and potential clinical applicability of our framework, and the results show an increase of the overall subject specificity of the recovered deformations. [ABSTRACT FROM AUTHOR]

This article discusses the application of sensitivity analysis (SA) in biomedical models. Sensitivity analysis is widely applied in physics, chemistry, economics, social sciences and other areas where models are developed. By assigning a prior probability distribution to each model variable, the SA framework appeals to the posterior probabilities of the model to evaluate the relative importance of these variables on the output distribution based on the principle of general variance decomposition. Within this framework, the SA paradigm serves as an objective platform to quantify the contributions of each model factor relative to their empirical range. We present statistical derivations of variance-based SA in this context and discuss its detailed properties through some practical examples. Our emphasis is on the application of SA in the biomedical field. As we show, it may provide a useful tool for model quality assessment, model reduction and factor prioritization, and improve our understanding of the model structure and underlying mechanisms. When usual approaches for calculating sensitivity index involve the employment of Monte Carlo analysis, which is computationally expensive in the large-sampling paradigm, we develop two effective numerical approximate methods for quick SA evaluations based on the unscented transformation (UT) that utilize a deterministic sampling approach in place of random sampling to calculate posterior statistics. We show that these methods achieve an excellent compromise between computational burden and calculation precision. In addition, a clear guideline is absent to evaluate the importance of variable for model reduction, we also present an objective statistical criterion to quantitatively decide whether or not a descriptive parameter is nominal and may be discarded in ensuing model-based analysis without significant loss of information on model behavior. [ABSTRACT FROM PUBLISHER]

Previous reports have described the use of magnetic resonance imaging (MRI) to estimate single-kidney extraction fraction (EF) and glomerular filtration rate (GFR), by measuring the concentration difference of intravenously injected Gd-chelate ([Gd]) in the renal artery and renal vein from measurements of blood TI. Problematic is the fact that [Gd] measurements in the renal artery are often inaccurate due to the small size, tortuousness and motion of the vessel. Consequently, the [Gd] in the inferior vena cava (IVC) below the renal veinostia (i.e., the infrarenal IVC) has been used instead of the renal artery [Gd], based on the assumption that the [Gd] in the infrarenal IVC is the same as it is in the renal artery. However, this assumption has neither been theoretically nor experimentally investigated. Herein, we describe new difference and differential equation pharmacological models that can predict the biodistribution of Gd-chelate throughout the extracellular space. Assuming known average normal blood flows and GFR, our models predict that the infrarenal IVC [Gd] is 3.2% to 4.7% greater than the renal artery [Gd], and that the EF estimate using this IVC measurement is overestimated by 14.2%-20.O%. To support these predictions, algebraic equations are derived which show that the infrarenal IVC must develop a relatively high [Gd] in order to satisfy Gd flux constraints within the vascular system. These results suggest that the infrarenal IVC [Gd] is not a valid substitute for the renal artery [Gd]. [ABSTRACT FROM AUTHOR]