ALBERT

Description: Accurately recovering the hippocampal shapes against rough and noisy segmentations is as challenging as achieving good anatomical correspondence between the individual shapes. To address these issues, we propose a mesh-to-volume registration approach, characterized by a progressive model deformation. Our model implements flexible weighting scheme for model rigidity under a multi-level neighborhood for vertex connectivity. This method induces a large-to-small scale deformation of a template surface to build the pairwise correspondence by minimizing geometric distortion while robustly restoring the individuals' shape characteristics. We evaluated the proposed method's 1) accuracy and robustness in smooth surface reconstruction, 2) sensitivity in detecting significant shape differences between healthy control and disease groups (mild cognitive impairment and Alzheimer's disease), 3) robustness in constructing the anatomical correspondence between individual shape models, and 4) applicability in identifying subtle shape changes in relation to cognitive abilities in a healthy population. We compared the performance of the proposed method with other well-known methods—SPHARM-PDM, ShapeWorks and LDDMM volume registration with template injection—using various metrics of shape similarity, surface roughness, volume, and shape deformity. The experimental results showed that the proposed method generated smooth surfaces with less volume differences and better shape similarity to input volumes than others. The statistical analyses with clinical variables also showed that it was sensitive in detecting subtle shape changes of hippocampus.

Description: We propose a conditional random field (CRF) based classifier for segmentation of small enhanced pathologies. Specifically, we develop a temporal hierarchical adaptive texture CRF (THAT-CRF) and apply it to the challenging problem of gad enhancing lesion segmentation in brain MRI of patients with multiple sclerosis. In this context, the presence of many nonlesion enhancements (such as blood vessels) renders the problem more difficult. In addition to voxel-wise features, the framework exploits multiple higher order textures to discriminate the true lesional enhancements from the pool of other enhancements. Since lesional enhancements show more variation over time as compared to the nonlesional ones, we incorporate temporal texture analysis in order to study the textures of enhanced candidates over time. The parameters of the THAT-CRF model are learned based on 2380 scans from a multi-center clinical trial. The effect of different components of the model is extensively evaluated on 120 scans from a separate multi-center clinical trial. The incorporation of the temporal textures results in a general decrease of the false discovery rate. Specifically, THAT-CRF achieves overall sensitivity of 95% along with false discovery rate of 20% and average false positive count of 0.5 lesions per scan. The sensitivity of the temporal method to the trained time interval is further investigated on five different intervals of 69 patients. Moreover, superior performance is achieved by the reviewed labelings of our model compared to the fully manual labeling when applied to the context of separating different treatment arms in a real clinical trial.

Description: We present a novel general-purpose compression method for tomographic images, termed 3D adaptive sparse representation based compression (3D-ASRC). In this paper, we focus on applications of 3D-ASRC for the compression of ophthalmic 3D optical coherence tomography (OCT) images. The 3D-ASRC algorithm exploits correlations among adjacent OCT images to improve compression performance, yet is sensitive to preserving their differences. Due to the inherent denoising mechanism of the sparsity based 3D-ASRC, the quality of the compressed images are often better than the raw images they are based on. Experiments on clinical-grade retinal OCT images demonstrate the superiority of the proposed 3D-ASRC over other well-known compression methods.

Description: Accurate segmentation is usually crucial in transrectal ultrasound (TRUS) image based prostate diagnosis; however, it is always hampered by heavy speckles. Contrary to the traditional view that speckles are adverse to segmentation, we exploit intrinsic properties induced by speckles to facilitate the task, based on the observations that sizes and orientations of speckles provide salient cues to determine the prostate boundary. Since the speckle orientation changes in accordance with a statistical prior rule, rotation-invariant texture feature is extracted along the orientations revealed by the rule. To address the problem of feature changes due to different speckle sizes, TRUS images are split into several arc-like strips. In each strip, every individual feature vector is sparsely represented, and representation residuals are obtained. The residuals, along with the spatial coherence inherited from biological tissues, are combined to segment the prostate preliminarily via graph cuts. After that, the segmentation is fine-tuned by a novel level sets model, which integrates 1) the prostate shape prior, 2) dark-to-light intensity transition near the prostate boundary, and 3) the texture feature just obtained. The proposed method is validated on two 2-D image datasets obtained from two different sonographic imaging systems, with the mean absolute distance on the mid gland images only $1.06pm 0.53~{hbox {mm}}$ and $1.25pm 0.77~{hbox {mm}}$ , respectively. The method is also extended to segment apex and base images, producing competitive results over the state of the art.

Description: Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disorder that has recently seen serious increase in the number of affected subjects. In the last decade, neuroimaging has been shown to be a useful tool to understand AD and its prodromal stage, amnestic mild cognitive impairment (MCI). The majority of AD/MCI studies have focused on disease diagnosis, by formulating the problem as classification with a binary outcome of AD/MCI or healthy controls. There have recently emerged studies that associate image scans with continuous clinical scores that are expected to contain richer information than a binary outcome. However, very few studies aim at modeling multiple clinical scores simultaneously, even though it is commonly conceived that multivariate outcomes provide correlated and complementary information about the disease pathology. In this article, we propose a sparse multi-response tensor regression method to model multiple outcomes jointly as well as to model multiple voxels of an image jointly. The proposed method is particularly useful to both infer clinical scores and thus disease diagnosis, and to identify brain subregions that are highly relevant to the disease outcomes. We conducted experiments on the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset, and showed that the proposed method enhances the performance and clearly outperforms the competing solutions.

Description: A plethora of techniques for cardiac deformation imaging with 3D ultrasound, typically referred to as 3D speckle tracking techniques, are available from academia and industry. Although the benefits of single methods over alternative ones have been reported in separate publications, the intrinsic differences in the data and definitions used makes it hard to compare the relative performance of different solutions. To address this issue, we have recently proposed a framework to simulate realistic 3D echocardiographic recordings and used it to generate a common set of ground-truth data for 3D speckle tracking algorithms, which was made available online. The aim of this study was therefore to use the newly developed database to contrast non-commercial speckle tracking solutions from research groups with leading expertise in the field. The five techniques involved cover the most representative families of existing approaches, namely block-matching, radio-frequency tracking, optical flow and elastic image registration. The techniques were contrasted in terms of tracking and strain accuracy. The feasibility of the obtained strain measurements to diagnose pathology was also tested for ischemia and dyssynchrony.

Description: Ultra-high field MRI is an area of great interest for clinical research and basic science due to the increased signal-to-noise, spatial resolution and magnetic-susceptibility-based contrast. However, the fact that the electromagnetic wavelength in tissue is comparable to the relevant body dimensions means that the uniformity of the excitation field is much poorer than at lower field strengths. In addition to techniques such as transmit arrays, one simple but effective method to counteract this effect is to use high permittivity “pads”. Very high permittivities enable thinner, flexible pads to be used, but the limiting factor is wavelength effects within the pads themselves, which can lead to image artifacts. So far, all studies have used simple continuous rectangular/circular pad geometries. In this work we investigate how the wavelength effects can be partially mitigated utilizing shaped pad with holes. Several arrangements have been simulated, including low order pre-fractal geometries, which maintain the overall coverage of the pad, but can provide better image homogeneity in the region of interest or higher sensitivity depending on the setup. Experimental data in the form of in vivo human images at 7T were acquired to validate the simulation results.

Description: In this paper, we consider combined TV denoising and diffusion tensor fitting in DTI using the affine-invariant Riemannian metric on the space of diffusion tensors. Instead of first fitting the diffusion tensors, and then denoising them, we define a suitable TV type energy functional which incorporates the measured DWIs (using an inverse problem setup) and which measures the nearness of neighboring tensors in the manifold. To approach this functional, we propose generalized forward- backward splitting algorithms which combine an explicit and several implicit steps performed on a decomposition of the functional. We validate the performance of the derived algorithms on synthetic and real DTI data. In particular, we work on real 3D data. To our knowledge, the present paper describes the first approach to TV regularization in a combined manifold and inverse problem setup.

Description: We present a generic method for automatic detection of abnormal regions in medical images as deviations from a normative data base. The algorithm decomposes an image, or more broadly a function defined on the image grid, into the superposition of a normal part and a residual term. A statistical model is constructed with regional sparse learning to represent normative anatomical variations among a reference population (e.g., healthy controls), in conjunction with a Markov random field regularization that ensures mutual consistency of the regional learning among partially overlapping image blocks. The decomposition is performed in a principled way so that the normal part fits well with the learned normative model, while the residual term absorbs pathological patterns, which may then be detected through a statistical significance test. The decomposition is applied to multiple image features from an individual scan, detecting abnormalities using both intensity and shape information. We form an iterative scheme that interleaves abnormality detection with deformable registration, gradually improving robustness of the spatial normalization and precision of the detection. The algorithm is evaluated with simulated images and clinical data of brain lesions, and is shown to achieve robust deformable registration and localize pathological regions simultaneously. The algorithm is also applied on images from Alzheimer’s disease patients to demonstrate the generality of the method.

Description: Staining and scanning of tissue samples for microscopic examination is fraught with undesirable color variations arising from differences in raw materials and manufacturing techniques of stain vendors, staining protocols of labs, and color responses of digital scanners. When comparing tissue samples, color normalization and stain separation of the tissue images can be helpful for both pathologists and software. Techniques that are used for natural images fail to utilize structural properties of stained tissue samples and produce undesirable color distortions. The stain concentration cannot be negative. Tissue samples are stained with only a few stains and most tissue regions are characterized by at most one effective stain. We model these physical phenomena that define the tissue structure by first decomposing images in an unsupervised manner into stain density maps that are sparse and non-negative. For a given image, we combine its stain density maps with stain color basis of a pathologist-preferred target image, thus altering only its color while preserving its structure described by the maps. Stain density correlation with ground truth and preference by pathologists were higher for images normalized using our method when compared to other alternatives. We also propose a computationally faster extension of this technique for large whole-slide images that selects an appropriate patch sample instead of using the entire image to compute the stain color basis.

Description: Prospective authors are requested to submit new, unpublished manuscripts for inclusion in the upcoming event described in this call for papers.

Description: We present a methodology to recover the geometrical calibration of conventional X-ray settings with the help of an ordinary video camera and visible fiducials that are present in the scene. After calibration, equivalent points of interest can be easily identifiable with the help of the epipolar geometry. The same procedure also allows the measurement of real anatomic lengths and angles and obtains accurate 3D locations from image points. Our approach completely eliminates the need for X-ray-opaque reference marks (and necessary supporting frames) which can sometimes be invasive for the patient, occlude the radiographic picture, and end up projected outside the imaging sensor area in oblique protocols. Two possible frameworks are envisioned: a spatially shifting X-ray anode around the patient/object and a moving patient that moves/rotates while the imaging system remains fixed. As a proof of concept, experiences with a device under test (DUT), an anthropomorphic phantom and a real brachytherapy session have been carried out. The results show that it is possible to identify common points with a proper level of accuracy and retrieve three-dimensional locations, lengths and shapes with a millimetric level of precision. The presented approach is simple and compatible with both current and legacy widespread diagnostic X-ray imaging deployments and it can represent a good and inexpensive alternative to other radiological modalities like CT.

Description: Fiber based fluorescence lifetime imaging has shown great potential for intraoperative diagnosis and guidance of surgical procedures. Here we describe a novel method addressing a significant challenge for the practical implementation of this technique, i.e., the real-time display of the quantified biochemical or functional tissue properties superimposed on the interrogated area. Specifically, an aiming beam (450 nm) generated by a continuous-wave laser beam was merged with the pulsed fluorescence excitation light in a single delivery/collection fiber and then imaged and segmented using a color-based algorithm. We demonstrate that this approach enables continuous delineation of the interrogated location and dynamic augmentation of the acquired frames with the corresponding fluorescence decay parameters. The method was evaluated on a fluorescence phantom and fresh tissue samples. Current results demonstrate that 34 frames per second can be achieved for augmenting videos of 640 $times $ 512 pixels resolution. Also we show that the spatial resolution of the fluorescence lifetime map depends on the tissue optical properties, the scanning speed, and the frame rate. The dice similarity coefficient between the fluorescence phantom and the reconstructed maps was estimated to be as high as 93%. The reported method could become a valuable tool for augmenting the surgeon's field of view with diagnostic information derived from the analysis of fluorescence lifetime data in real-time using handheld, automated, or endoscopic scanning systems. Current method provides also a means for maintaining the tissue light exposure within safety limits. This study provides a framework for using an aiming beam with other point spectroscopy applications.

Description: Simultaneous Multi-Slice (SMS) magnetic resonance imaging (MRI) is a rapidly evolving technique for increasing imaging speed. Controlled aliasing techniques utilize periodic undersampling patterns to help mitigate the loss in signal-to-noise ratio (SNR) in SMS MRI. To evaluate the performance of different undersampling patterns, a quantitative description of the image SNR loss is needed. Additionally, eddy current effects in echo planar imaging (EPI) lead to slice-specific Nyquist ghosting artifacts. These artifacts cannot be accurately corrected for each individual slice before or after slice-unaliasing. In this work, we propose a hybrid-space sensitivity encoding (SENSE) reconstruction framework for SMS MRI by adopting a three-dimensional representation of the SMS acquisition. Analytical SNR loss maps are derived for SMS acquisitions with arbitrary phase encoding undersampling patterns. Moreover, we propose a matrix-decoding correction method that corrects the slice-specific Nyquist ghosting artifacts in SMS EPI acquisitions. Brain images demonstrate that the proposed hybrid-space SENSE reconstruction generates images with comparable quality to commonly used split-slice-generalized autocalibrating partially parallel acquisition reconstruction. The analytical SNR loss maps agree with those calculated by a Monte Carlo based method, but require less computation time for high quality maps. The analytical maps enable a fair comparison between the performances of coherent and incoherent SMS undersampling patterns. Phantom and brain SMS EPI images show that the matrix-decoding method performs better than the single-slice and slice-averaged Nyquist ghosting correction methods under the hybrid-space SENSE reconstruction framework.

Description: Photoacoustic (PA) images utilize pulsed lasers and ultrasound transducers to visualize targets with higher optical absorption than the surrounding medium. However, they are susceptible to acoustic clutter and background noise artifacts that obfuscate biomedical structures of interest. We investigated three spatial-angular compounding methods to improve PA image quality for biomedical applications, implemented by combining multiple images acquired as an ultrasound probe was rotated about the elevational axis with the laser beam and target fixed. Compounding with conventional averaging was based on the pose information of each PA image, while compounding with weighted and selective averaging utilized both the pose and image content information. Weighted-average compounding enhanced PA images with the least distortion of signal size, particularly when there were large (i.e., 2.5 mm and 7 $^{circ}$ ) perturbations from the initial probe position. Selective-average compounding offered the best improvement in image quality with up 181, 1665, and 1568 times higher contrast, CNR, and SNR, respectively, compared to the mean values of individual PA images. The three presented spatial compounding methods have promising potential to enhance image quality in multiple photoacoustic applications.

Description: Analysis of cranial nerve systems, such as the anterior visual pathway (AVP), from MRI sequences is challenging due to their thin long architecture, structural variations along the path, and low contrast with adjacent anatomic structures. Segmentation of a pathologic AVP (e.g., with low-grade gliomas) poses additional challenges. In this work, we propose a fully automated partitioned shape model segmentation mechanism for AVP steered by multiple MRI sequences and deep learning features. Employing deep learning feature representation, this framework presents a joint partitioned statistical shape model able to deal with healthy and pathological AVP. The deep learning assistance is particularly useful in the poor contrast regions, such as optic tracts and pathological areas. Our main contributions are: 1) a fast and robust shape localization method using conditional space deep learning, 2) a volumetric multiscale curvelet transform-based intensity normalization method for robust statistical model, and 3) optimally partitioned statistical shape and appearance models based on regional shape variations for greater local flexibility. Our method was evaluated on MRI sequences obtained from 165 pediatric subjects. A mean Dice similarity coefficient of 0.779 was obtained for the segmentation of the entire AVP (optic nerve only $=0.791$ ) using the leave-one-out validation. Results demonstrated that the proposed localized shape and sparse appearance-based learning approach significantly outperforms current state-of-the-art segmentation approaches and is as robust as the manual segmentation.

Description: Analytical (closed-form) inversion schemes have been the standard approach for image reconstruction in optoacoustic tomography due to their fast reconstruction abilities and low memory requirements. Yet, the need for quantitative imaging and artifact reduction has led to the development of more accurate inversion approaches, which rely on accurate forward modeling of the optoacoustic wave generation and propagation. In this way, multiple experimental factors can be incorporated, such as the exact detection geometry, spatio-temporal response of the transducers, and acoustic heterogeneities. The model-based inversion commonly results in very large sparse matrix formulations that require computationally extensive and memory demanding regularization schemes for image reconstruction, hindering their effective implementation in real-time imaging applications. Herein, we introduce a new discretization procedure for efficient model-based reconstructions in two-dimensional optoacoustic tomography that allows for parallel implementation on a graphics processing unit (GPU) with a relatively low numerical complexity. By on-the-fly calculation of the model matrix in each iteration of the inversion procedure, the new approach results in imaging frame rates exceeding 10 Hz, thus enabling real-time image rendering using the model-based approach.

Description: This paper introduces a statistical estimation framework for magnetic resonance (MR) fingerprinting, a recently proposed quantitative imaging paradigm. Within this framework, we present a maximum likelihood (ML) formalism to estimate multiple MR tissue parameter maps directly from highly undersampled, noisy ${bf k}$ -space data. A novel algorithm, based on variable splitting, the alternating direction method of multipliers, and the variable projection method, is developed to solve the resulting optimization problem. Representative results from both simulations and in vivo experiments demonstrate that the proposed approach yields significantly improved accuracy in parameter estimation, compared to the conventional MR fingerprinting reconstruction. Moreover, the proposed framework provides new theoretical insights into the conventional approach. We show analytically that the conventional approach is an approximation to the ML reconstruction; more precisely, it is exactly equivalent to the first iteration of the proposed algorithm for the ML reconstruction, provided that a gridding reconstruction is used as an initialization.

Description: We propose a unified Bayesian framework to detect both hyper- and hypo-active communities within whole-brain fMRI data. Specifically, our model identifies dense subgraphs that exhibit population-level differences in functional synchrony between a control and clinical group. We derive a variational EM algorithm to solve for the latent posterior distributions and parameter estimates, which subsequently inform us about the afflicted network topology. We demonstrate that our method provides valuable insights into the neural mechanisms underlying social dysfunction in autism, as verified by the Neurosynth meta-analytic database. In contrast, both univariate testing and community detection via recursive edge elimination fail to identify stable functional communities associated with the disorder.

Description: A recent entry into the rapidly evolving field of integrated PET/MR scanners is presented in this paper: a whole body hybrid PET/MR system (SIGNA PET/MR, GE Healthcare) capable of simultaneous acquisition of both time-of-flight (TOF) PET and high resolution MR data. The PET ring was integrated into an existing 3T MR system resulting in a (patient) bore opening of 60 cm diameter, with a 25 cm axial FOV. PET performance was evaluated both on the standalone PET ring and on the same detector integrated into the MR system, to assess the level of mutual interference between both subsystems. In both configurations we obtained detector performance data. PET detector performance was not significantly affected by integration into the MR system. The global energy resolution was within 2% (10.3% versus 10.5%), and the system coincidence time resolution showed a maximum change of 〈 3% (385 ps versus 394 ps) when measured outside MR and during simultaneous PET/MRI acquisitions, respectively. To evaluate PET image quality and resolution, the NEMA IQ phantom was acquired with MR idle and with MR active. Impact of PET on MR IQ was assessed by comparing SNR with PET acquisition on and off. B0 and B1 homogeneities were acquired before and after the integration of the PET ring inside the magnet. In vivo brain and whole body head-to-thighs data were acquired to demonstrate clinical image quality.

Description: The performance of photoacoustic microscopy (PAM) degrades due to the turbidity of the skull that introduces attenuation and distortion of both laser and stimulated ultrasound. In this manuscript, we demonstrated that a newly developed skull optical clearing solution (SOCS) could enhance not only the transmittance of light, but also that of ultrasound in the skull in vitro. Thus the photoacoustic signal was effectively elevated, and the relative strength of the artifacts induced by the skull could be suppressed. Furthermore in vivo studies demonstrated that SOCS could drastically enhance the performance of photoacoustic microscopy for cerebral microvasculature imaging.

Description: Cryo-balloon catheters have attracted an increasing amount of interest in the medical community as they can reduce patient risk during left atrial pulmonary vein ablation procedures. As cryo-balloon catheters are not equipped with electrodes, they cannot be localized automatically by electro-anatomical mapping systems. As a consequence, X-ray fluoroscopy has remained an important means for guidance during the procedure. Most recently, image guidance methods for fluoroscopy-based procedures have been proposed, but they provide only limited support for cryo-balloon catheters and require significant user interaction. To improve this situation, we propose a novel method for automatic cryo-balloon catheter detection in fluoroscopic images by detecting the cryo-balloon catheter's built-in X-ray marker. Our approach is based on a blob detection algorithm to find possible X-ray marker candidates. Several of these candidates are then excluded using prior knowledge. For the remaining candidates, several catheter specific features are introduced. They are processed using a machine learning approach to arrive at the final X-ray marker position. Our method was evaluated on 75 biplane fluoroscopy images from 40 patients, from two sites, acquired with a biplane angiography system. The method yielded a success rate of 99.0% in plane A and 90.6% in plane B, respectively. The detection achieved an accuracy of $1.00~{rm mm}pm 0.82~{rm mm}$ in plane A and $1.13~{rm mm}pm 0.24~{rm mm}$ in plane B. The localization in 3-D was associated with an average error of $0.36~{rm mm}pm 0.86~{rm mm}$ .

Description: Segmentation of the wrist bones in CT images has been frequently used in different clinical applications including arthritis evaluation, bone age assessment and image-guided interventions. The major challenges include non-uniformity and spongy textures of the bone tissue as well as narrow inter-bone spaces. In this work, we propose an automatic wrist bone segmentation technique for CT images based on a statistical model that captures the shape and pose variations of the wrist joint across 60 example wrists at nine different wrist positions. To establish the correspondences across the training shapes at neutral positions, the wrist bone surfaces are jointly aligned using a group-wise registration framework based on a Gaussian Mixture Model. Principal component analysis is then used to determine the major modes of shape variations. The variations in poses not only across the population but also across different wrist positions are incorporated in two pose models. An intra-subject pose model is developed by utilizing the similarity transforms at all wrist positions across the population. Further, an inter-subject pose model is used to model the pose variations across different wrist positions. For segmentation of the wrist bones in CT images, the developed model is registered to the edge point cloud extracted from the CT volume through an expectation maximization based probabilistic approach. Residual registration errors are corrected by application of a non-rigid registration technique. We validate the proposed segmentation method by registering the wrist model to a total of 66 unseen CT volumes of average voxel size of 0.38 mm. We report a mean surface distance error of 0.33 mm and a mean Jaccard index of 0.86.

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Description: Electron and light microscopy imaging can now deliver high-quality image stacks of neural structures. However, the amount of human annotation effort required to analyze them remains a major bottleneck. While machine learning algorithms can be used to help automate this process, they require training data, which is time-consuming to obtain manually, especially in image stacks. Furthermore, due to changing experimental conditions, successive stacks often exhibit differences that are severe enough to make it difficult to use a classifier trained for a specific one on another. This means that this tedious annotation process has to be repeated for each new stack. In this paper, we present a domain adaptation algorithm that addresses this issue by effectively leveraging labeled examples across different acquisitions and significantly reducing the annotation requirements. Our approach can handle complex, nonlinear image feature transformations and scales to large microscopy datasets that often involve high-dimensional feature spaces and large 3D data volumes. We evaluate our approach on four challenging electron and light microscopy applications that exhibit very different image modalities and where annotation is very costly. Across all applications we achieve a significant improvement over the state-of-the-art machine learning methods and demonstrate our ability to greatly reduce human annotation effort.

Description: Efficient and accurate segmentation of cellular structures in microscopic data is an essential task in medical imaging. Many state-of-the-art approaches to image segmentation use structured models whose parameters must be carefully chosen for optimal performance. A popular choice is to learn them using a large-margin framework and more specifically structured support vector machines (SSVM). Although SSVMs are appealing, they suffer from certain limitations. First, they are restricted in practice to linear kernels because the more powerful nonlinear kernels cause the learning to become prohibitively expensive. Second, they require iteratively finding the most violated constraints, which is often intractable for the loopy graphical models used in image segmentation. This requires approximation that can lead to reduced quality of learning. In this paper, we propose three novel techniques to overcome these limitations. We first introduce a method to “kernelize” the features so that a linear SSVM framework can leverage the power of nonlinear kernels without incurring much additional computational cost. Moreover, we employ a working set of constraints to increase the reliability of approximate subgradient methods and introduce a new way to select a suitable step size at each iteration. We demonstrate the strength of our approach on both 2-D and 3-D electron microscopic (EM) image data and show consistent performance improvement over state-of-the-art approaches.

Description: In this study, we proposed an efficient nonrigid magnetic resonance (MR) to transrectal ultrasound (TRUS) deformable registration method in order to improve the accuracy of targeting suspicious regions during a three dimensional (3-D) TRUS guided prostate biopsy. The proposed deformable registration approach employs the multi-channel modality independent neighborhood descriptor (MIND) as the local similarity feature across the two modalities of MR and TRUS, and a novel and efficient duality-based convex optimization-based algorithmic scheme was introduced to extract the deformations and align the two MIND descriptors. The registration accuracy was evaluated using 20 patient images by calculating the TRE using manually identified corresponding intrinsic fiducials in the whole gland and peripheral zone. Additional performance metrics [Dice similarity coefficient (DSC), mean absolute surface distance (MAD), and maximum absolute surface distance (MAXD)] were also calculated by comparing the MR and TRUS manually segmented prostate surfaces in the registered images. Experimental results showed that the proposed method yielded an overall median TRE of 1.76 mm. The results obtained in terms of DSC showed an average of $80.8pm7.8hbox{%}$ for the apex of the prostate, $92.0pm3.4hbox{%}$ for the mid-gland, $81.7pm6.4hbox{%}$ for the base and $85.7pm4.7hbox{%}$ for the whole gland. The surface distance calculations showed an overall average of $1.84pm0.52$ mm for MAD and $6.90pm2.07$ mm for MAXD.

Description: In this work we present a framework for reliably detecting significant differences in quantitative magnetic resonance imaging and evaluate it with diffusion tensor imaging (DTI) experiments. As part of this framework we propose a new spatially regularized maximum likelihood estimator that simultaneously estimates the quantitative parameters and the spatially-smoothly-varying noise level from the acquisitions. The noise level estimation method does not require repeated acquisitions. We show that the amount of regularization in this method can be set a priori to achieve a desired coefficient of variation of the estimated noise level. The noise level estimate allows the construction of a Cramér-Rao-lower-bound based test statistic that reliably assesses the significance of differences between voxels within a scan or across different scans. We show that the regularized noise level estimate improves upon existing methods and results in a substantially increased precision of the uncertainty estimates of the DTI parameters. It enables correct specification of the null distribution of the test statistic and with it the test statistic obtains the highest sensitivity and specificity. The source code of the estimation framework, test statistic and experiment scripts are made available to the community.

Description: Magnetic particle imaging (MPI) shows promise for medical imaging, particularly in angiography of patients with chronic kidney disease. As the first biomedical imaging technique that truly depends on nanoscale materials properties, MPI requires highly optimized magnetic nanoparticle tracers to generate quality images. Until now, researchers have relied on tracers optimized for MRI ${rm T}2^ {ast} $ -weighted imaging that are sub-optimal for MPI. Here, we describe new tracers tailored to MPI's unique physics, synthesized using an organic-phase process and functionalized to ensure biocompatibility and adequate in vivo circulation time. Tailored tracers showed up to 3 $,times$ greater signal-to-noise ratio and better spatial resolution than existing commercial tracers in MPI images of phantoms.

Description: Prospective authors are requested to submit new, unpublished manuscripts for inclusion in the upcoming event described in this call for papers.

Description: Prospective authors are requested to submit new, unpublished manuscripts for inclusion in the upcoming event described in this call for papers.

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Description: A promising, recently explored, alternative to ultra-high $b$ -value diffusion weighted imaging (UHB-DWI) is apparent ultra-high $b$ -value diffusion-weighted image reconstruction (AUHB-DWR), where a computational model is used to assist in the reconstruction of apparent DW images at ultra-high $b$ -values. Firstly, we present a novel approach to AUHB-DWR that aims to improve image quality. We formulate the reconstruction of an apparent DW image as a hidden conditional random field (HCRF) in which tissue model diffusion parameters act as hidden states in this random field. The second contribution of this paper is a new generation of fully connected conditional random fields, called the hidden stochastically fully connected conditional random fields (HSFCRF) that allows for efficient inference with significantly reduced computational complexity via stochastic clique structures. The proposed AUHB-DWR algorithms, HCRF and HSFCRF, are evaluated quantitatively in nine different patient cases using Fisher's criteria, probability of error, and coefficient of variation metrics to validate its effectiveness for the purpose of improving intensity delineation between expert identified suspected cancerous and healthy tissue within the prostate gland. The proposed methods are also examined using a prostate phantom, where the apparent ultra-high $b$ -value DW images reconstructed using the tested AUHB-DWR methods are compared with real captured UHB-DWI. The results illustrate that the proposed AUHB-DWR methods has improved reconstruction quality and improved intensity delineation compared with existing AUHB-DWR approaches.

Description: A numerical method is shown for calculating the noise correlation coefficient in arrays of magnetic resonance imaging (MRI) coils loaded with capacitively-loaded ring metamaterial lenses, and in the presence of a conducting half-space resembling a sample. This numerical method is validated by comparison with experimental results obtained in two different experimental procedures for double check: noise resistance measurements with a network analyzer and noise correlation measurements in an MRI system. It is found that, for practical array configurations such as overlapping coils or capacitively-decoupled coils, the noise correlation coefficient turns negative for coils loaded with metamaterial lenses. In particular, the analysis is carried out with metamaterial structures known as magnetoinductive lenses, which have been demonstrated in previous works to improve the signal-to-noise ratio of MRI coils. Results are also shown to demonstrate that negative noise correlations have as an effect the improvement of the g-factor in coil arrays for parallel MRI.

Description: 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.

Description: Prospective authors are requested to submit new, unpublished manuscripts for inclusion in the upcoming event described in this call for papers.

Description: In this work, we demonstrated that an optimized detector angular configuration based on the anisotropic energy distribution of background scattered X-rays improves X-ray fluorescence computed tomography (XFCT) detection sensitivity. We built an XFCT imaging system composed of a bench-top fluoroscopy X-ray source, a CdTe X-ray detector, and a phantom motion stage. We imaged a 6.4-cm-diameter phantom containing different concentrations of gold solution and investigated the effect of detector angular configuration on XFCT image quality. Based on our previous theoretical study, three detector angles were considered. The X-ray fluorescence detector was first placed at 145 $^{circ}$ (approximating back-scatter) to minimize scatter X-rays. XFCT image quality was compared to images acquired with the detector at 60 $^{circ}$ (forward-scatter) and 90 $^{circ}$ (side-scatter). The datasets for the three different detector positions were also combined to approximate an isotropically arranged detector. The sensitivity was optimized with detector in the 145 $^{circ}$ back-scatter configuration counting the 78-keV gold ${rm K}beta 1$ X-rays. The improvement arose from the reduced energy of scattered X-ray at the 145 $^{circ}$ position and the large energy separation from gold ${rm K} beta 1$ X-rays. The lowest detected concentration in this configuration was 2.5 mgAu/mL (or 0.25% Au with SNR $ = 4.3$ ). This concentration could not be detected with the 60- formula formulatype="inline"〉 $^{circ}$ , 90 $^{circ}$ , or isotropic configurations (SNRs $ = 1.3$ , 0, 2.3, respectively). XFCT imaging dose of 14 mGy was in the range of typical clinical X-ray CT imaging doses. To our knowledge, the sensitivity achieved in this experiment is the highest in any XFCT experiment using an ordinary bench-top X-ray source in a phantom larger than a mouse ( ${〉} 3$ cm).

Description: We have developed a method for the simultaneous estimation of local diffusion and the global fiber tracts based upon the information entropy flow that computes the maximum entropy trajectories between locations and depends upon the global structure of the multi-dimensional and multi-modal diffusion field. Computation of the entropy spectrum pathways requires only solving a simple eigenvector problem for the probability distribution for which efficient numerical routines exist, and a straight forward integration of the probability conservation through ray tracing of the convective modes guided by a global structure of the entropy spectrum coupled with a small scale local diffusion. The intervoxel diffusion is sampled by multi b-shell multi q-angle diffusion weighted imaging data expanded in spherical waves. This novel approach to fiber tracking incorporates global information about multiple fiber crossings in every individual voxel and ranks it in the most scientifically rigorous way. This method has potential significance for a wide range of applications, including studies of brain connectivity.

Description: The variation between images obtained with different scanners or different imaging protocols presents a major challenge in automatic segmentation of biomedical images. This variation especially hampers the application of otherwise successful supervised-learning techniques which, in order to perform well, often require a large amount of labeled training data that is exactly representative of the target data. We therefore propose to use transfer learning for image segmentation. Transfer-learning techniques can cope with differences in distributions between training and target data, and therefore may improve performance over supervised learning for segmentation across scanners and scan protocols. We present four transfer classifiers that can train a classification scheme with only a small amount of representative training data, in addition to a larger amount of other training data with slightly different characteristics. The performance of the four transfer classifiers was compared to that of standard supervised classification on two magnetic resonance imaging brain-segmentation tasks with multi-site data: white matter, gray matter, and cerebrospinal fluid segmentation; and white-matter-/MS-lesion segmentation. The experiments showed that when there is only a small amount of representative training data available, transfer learning can greatly outperform common supervised-learning approaches, minimizing classification errors by up to 60%.

Description: We present a graph-based framework for airway tree reconstruction from computerized tomography (CT) scans and evaluate the performance of different feature categories and their combinations on five lung cohorts. The approach consists of two main processing steps. First, potential airway branch and connection candidates are identified and represented by a graph structure with weighted nodes and edges, respectively. Second, an optimization algorithm is utilized for generating an airway detection result by selecting a subset of airway branches and connections based on graph weights derived from image features. The performance of the algorithm with different feature categories and their combinations was assessed on a set of 50 lung CT scans from five different cohorts, including normal and diseased lungs. Results show trade-offs between feature categories/combinations in terms of correctly (true positive) and incorrectly (false positive) identified airways. Also, the performance of features in dependence of lung cohort was analyzed. Across all cohorts, a good trade-off with high true positive rate (TPR) and low false positive rate (FPR) was achieved by a combination of gray-value, local shape, and structural features. This combination enabled extracting 91.80% of reference airways (TPR) in combination with a low FPR of 1.00%. In addition, this variant was evaluated on the public EXACT'09 test set, and a comparison with other airway detection approaches is provided. One of the main advantages of the presented method is that it is robust against local disturbances/artifacts or other ambiguities that are frequently occurring in lung CT scans.

Description: In this paper, we discuss about applications of different methods for decomposing a signal over elementary waveforms chosen in a family called a dictionary (atomic representations) in optical coherence tomography (OCT). If the representation is learned from the data, a nonparametric dictionary is defined with three fundamental properties of being data-driven, applicability on 3D, and working in multi-scale, which make it appropriate for processing of OCT images. We discuss about application of such representations including complex wavelet based K-SVD, and diffusion wavelets on OCT data. We introduce complex wavelet based K-SVD to take advantage of adaptability in dictionary learning methods to improve the performance of simple dual tree complex wavelets in speckle reduction of OCT datasets in 2D and 3D. The algorithm is evaluated on 144 randomly selected slices from twelve 3D OCTs taken by Topcon 3D OCT-1000 and Cirrus Zeiss Meditec. Improvement of contrast to noise ratio (CNR) (from 0.9 to 11.91 and from 3.09 to 88.9, respectively) is achieved. Furthermore, two approaches are proposed for image segmentation using diffusion. The first method is designing a competition between extended basis functions at each level and the second approach is defining a new distance for each level and clustering based on such distances. A combined algorithm, based on these two methods is then proposed for segmentation of retinal OCTs, which is able to localize 12 boundaries with unsigned border positioning error of $9.22 pm 3.05 mu {hbox {m}}$ , on a test set of 20 slices selected from 13 3D OCTs.

Description: The spectral graph wavelet transform (SGWT) has recently been developed to compute wavelet transforms of functions defined on non-Euclidean spaces such as graphs. By capitalizing on the established framework of the SGWT, we adopt a fast and efficient computation of a discretized Laplace-Beltrami (LB) operator that allows its extension from arbitrary graphs to differentiable and closed 2-D manifolds (smooth surfaces embedded in the 3-D Euclidean space). This particular class of manifolds are widely used in bioimaging to characterize the morphology of cells, tissues, and organs. They are often discretized into triangular meshes, providing additional geometric information apart from simple nodes and weighted connections in graphs. In comparison with the SGWT, the wavelet bases constructed with the LB operator are spatially localized with a more uniform “spread” with respect to underlying curvature of the surface. In our experiments, we first use synthetic data to show that traditional applications of wavelets in smoothing and edge detectio can be done using the wavelet bases constructed with the LB operator. Second, we show that multi-resolutional capabilities of the proposed framework are applicable in the classification of Alzheimer's patients with normal subjects using hippocampal shapes. Wavelet transforms of the hippocampal shape deformations at finer resolutions registered higher sensitivity (96%) and specificity (90%) than the classification results obtained from the direct usage of hippocampal shape deformations. In addition, the Laplace-Beltrami method requires consistently a smaller number of principal components (to retain a fixed variance) at higher resolution as compared to the binary and weighted graph Laplacians, demonstrating the potential of the wavelet bases in adapting to the geometry of the underlying manifold.

Description: Linear predictive models are applied to functional MRI (fMRI) data to estimate boundaries that predict experimental task states for scans. These boundaries are visualized as statistical parametric maps (SPMs) and range from low to high spatial reproducibility across subjects (e.g., Strother , 2004; LaConte , 2003). Such inter-subject pattern reproducibility is an essential characteristic of interpretable SPMs that generalize across subjects. Therefore, we introduce a flexible hybrid model that optimizes reproducibility by simultaneously enhancing the prediction power and reproducibility. This hybrid model is formed by a weighted summation of the optimization functions of a linear discriminate analysis (LDA) model and a generalized canonical correlation (gCCA) model (Afshin-Pour , 2012). LDA preserves the model’s ability to discriminate the fMRI scans of multiple brain states while gCCA finds a linear combination for each subject’s scans such that the estimated boundary map is reproducible. The hybrid model is implemented in a split-half resampling framework (Strother , 2010) which provides reproducibility (r) and prediction (p) quality metrics. Then the model was compared with LDA, and Gaussian Naive Bayes (GNB). For simulated fMRI data, the hybrid model outperforms the other two techniques in terms of receiver operating characteristic (ROC) curves, particularly for detecting less predictable but spatially reproducible networks. These techniques were applied to real fMRI data to estimate the maps for two task contrasts. Our results indicate that compared to LDA and GNB, the hybrid model can provide maps with large increases in reproducibility for small reductions in prediction, which are jointly closer to the ideal performance point of (p=1, r=1).

Description: This paper introduces a new algorithm for recognizing surgical tasks in real-time in a video stream. The goal is to communicate information to the surgeon in due time during a video-monitored surgery. The proposed algorithm is applied to cataract surgery, which is the most common eye surgery. To compensate for eye motion and zoom level variations, cataract surgery videos are first normalized. Then, the motion content of short video subsequences is characterized with spatiotemporal polynomials: a multiscale motion characterization based on adaptive spatiotemporal polynomials is presented. The proposed solution is particularly suited to characterize deformable moving objects with fuzzy borders, which are typically found in surgical videos. Given a target surgical task, the system is trained to identify which spatiotemporal polynomials are usually extracted from videos when and only when this task is being performed. These key spatiotemporal polynomials are then searched in new videos to recognize the target surgical task. For improved performances, the system jointly adapts the spatiotemporal polynomial basis and identifies the key spatiotemporal polynomials using the multiple-instance learning paradigm. The proposed system runs in real-time and outperforms the previous solution from our group, both for surgical task recognition ( $A_z = 0.851$ on average, as opposed to $A_z = 0.794$ previously) and for the joint segmentation and recognition of surgical tasks ( $A_z = 0.856$ on average, as opposed to $A_z = 0.832$ previously).

Description: Electrical impedance tomography (EIT) is used to image the electrical property distribution of a tissue under test. An EIT system comprises complex hardware and software modules, which are typically designed for a specific application. Upgrading these modules is a time-consuming process, and requires rigorous testing to ensure proper functioning of new modules with the existing ones. To this end, we developed a modular and reconfigurable data acquisition (DAQ) system using National Instruments' (NI) hardware and software modules, which offer inherent compatibility over generations of hardware and software revisions. The system can be configured to use up to 32-channels. This EIT system can be used to interchangeably apply current or voltage signal, and measure the tissue response in a semi-parallel fashion. A novel signal averaging algorithm, and 512-point fast Fourier transform (FFT) computation block was implemented on the FPGA. FFT output bins were classified as signal or noise. Signal bins constitute a tissue's response to a pure or mixed tone signal. Signal bins' data can be used for traditional applications, as well as synchronous frequency-difference imaging. Noise bins were used to compute noise power on the FPGA. Noise power represents a metric of signal quality, and can be used to ensure proper tissue-electrode contact. Allocation of these computationally expensive tasks to the FPGA reduced the required bandwidth between PC, and the FPGA for high frame rate EIT. In 16-channel configuration, with a signal-averaging factor of 8, the DAQ frame rate at 100 kHz exceeded 110 frames ${rm s} ^{-1}$ , and signal-to-noise ratio exceeded 90 dB across the spectrum. Reciprocity error was found to be $〈 1%$ for frequencies up to 1 MHz. Static imaging experiments were performed on a high-conductivity inclusion - laced in a saline filled tank; the inclusion was clearly localized in the reconstructions obtained for both absolute current and voltage mode data.

Description: Iterative image reconstruction for positron emission tomography can improve image quality by using spatial regularization. The most commonly used quadratic penalty often oversmoothes sharp edges and fine features in reconstructed images, while nonquadratic penalties can preserve edges and achieve higher contrast recovery. Existing optimization algorithms such as the expectation maximization (EM) and preconditioned conjugate gradient (PCG) algorithms work well for the quadratic penalty, but are less efficient for high-curvature or nonsmooth edge-preserving regularizations. This paper proposes a new algorithm to accelerate edge-preserving image reconstruction by using two strategies: trust surrogate and optimization transfer descent. Trust surrogate approximates the original penalty by a smoother function at each iteration, but guarantees the algorithm to descend monotonically; Optimization transfer descent accelerates a conventional optimization transfer algorithm by using conjugate gradient and line search. Results of computer simulations and real 3-D data show that the proposed algorithm converges much faster than the conventional EM and PCG for smooth edge-preserving regularization and can also be more efficient than the current state-of-art algorithms for the nonsmooth $ell _{1}$ regularization.

Description: Low-dose-rate brachytherapy is a radiation treatment method for localized prostate cancer. The standard of care for this treatment procedure is to acquire transrectal ultrasound images of the prostate in order to devise a plan to deliver sufficient radiation dose to the cancerous tissue. Brachytherapy planning involves delineation of contours in these images, which closely follow the prostate boundary, i.e., clinical target volume. This process is currently performed either manually or semi-automatically, which requires user interaction for landmark initialization. In this paper, we propose a multi-atlas fusion framework to automatically delineate the clinical target volume in ultrasound images. A dataset of a priori segmented ultrasound images, i.e., atlases, is registered to a target image. We introduce a pairwise atlas agreement factor that combines an image-similarity metric and similarity between a priori segmented contours. This factor is used in an atlas selection algorithm to prune the dataset before combining the atlas contours to produce a consensus segmentation. We evaluate the proposed segmentation approach on a set of 280 transrectal prostate volume studies. The proposed method produces segmentation results that are within the range of observer variability when compared to a semi-automatic segmentation technique that is routinely used in our cancer clinic.

Description: In standard B-mode ultrasound (BMUS), segmentation of the lumen of atherosclerotic carotid arteries and studying the lumen geometry over time are difficult owing to irregular lumen shapes, noise, artifacts, and echolucent plaques. Contrast enhanced ultrasound (CEUS) improves lumen visualization, but lumen segmentation remains challenging owing to varying intensities, CEUS-specific artifacts and lack of tissue visualization. To overcome these challenges, we propose a novel method using simultaneously acquired BMUS&CEUS image sequences. Initially, the method estimates nonrigid motion (NME) from the image sequences, using intensity-based image registration. The motion-compensated image sequence is then averaged to obtain a single “epitome” image with improved signal-to-noise ratio. The lumen is segmented from the epitome image through an intensity joint-histogram classification and a graph-based segmentation. NME was validated by comparing displacements with manual annotations in 11 carotids. The average root mean square error (RMSE) was $112pm 73~mu {rm m}$ . Segmentation results were validated against manual delineations in the epitome images of two different datasets, respectively containing 11 (RMSE $191pm 43~mu {rm m}$ ) and 10 (RMSE $351pm 176~mu {rm m}$ ) carotids. From the deformation fields, we derived arterial distensibility with values comparable to the literature. The average errors in all experiments were in the inter-observer variability range. To the best of our knowledge, this is the first study exploiting combined BMUS&CEUS images for atherosclerotic carotid lumen segmentation.

Description: Prospective authors are requested to submit new, unpublished manuscripts for inclusion in the upcoming event described in this call for papers.

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Description: Multi-channel radio-frequency (RF) transmit coil arrays have been developed to mitigate many of the RF challenges associated with ultra-high field ( $geq$ 7T) magnetic resonance imaging (MRI). These arrays can be used for parallel RF transmission to produce spatially tailored RF excitation over the field of view. However, the realization of such arrays remains a challenge due to significant reactive interaction between the array coils, i.e., mutual coupling. In this paper, a novel bandstop filter (“magnetic wall”) is used in an MRI RF transmit array to decouple individual coils. The proposed decoupling method is inspired by periodic resonator designs commonly used in frequency selective surfaces and is used as a distributed RF filter to suppress the transmission of RF energy between coils in an array. The decoupling of the magnetic wall (MW) is analyzed in terms of equivalent circuits that include terms for both magnetic and electric coupling for an arbitrary number of MW resonant conductors. Both frequency—and time-domain full-wave simulations were performed to analyze a specific MW structure. The performance of the proposed method is experimentally validated for both first-order coupling and higher-order coupling with a three-coil 7T array setup. Analysis and measurements confirm that the rejection band of the MW can be tuned to provide high isolation in the presence of cross coupling between RF array coils.

Description: We develop a new approach to functional brain connectivity analysis, which deals with four fundamental aspects of connectivity not previously jointly treated. These are: temporal correlation, spurious spatial correlation, sparsity, and network construction using trajectory (as opposed to marginal) Mutual Information. We call the new method Sparse Conditional Trajectory Mutual Information (SCoTMI). We demonstrate SCoTMI on simulated and real fMRI data, showing that SCoTMI gives more accurate and more repeatable detection of network links than competing network estimation methods.

Description: The identification of small structures (blobs) from medical images to quantify clinically relevant features, such as size and shape, is important in many medical applications. One particular application explored here is the automated detection of kidney glomeruli after targeted contrast enhancement and magnetic resonance imaging. We propose a computationally efficient algorithm, termed the Hessian-based Difference of Gaussians (HDoG), to segment small blobs (e.g. glomeruli from kidney) from 3D medical images based on local convexity, intensity and shape information. The image is first smoothed and pre-segmented into small blob candidate regions based on local convexity. Two novel 3D regional features (regional blobness and regional flatness) are then extracted from the candidate regions. Together with regional intensity, the three features are used in an unsupervised learning algorithm for auto post-pruning. HDoG is first validated in a 2D form and compared with other three blob detectors from literature, which are generally for 2D images only. To test the detectability of blobs from 3D images, 240 sets of simulated images are rendered for scenarios mimicking the renal nephron distribution observed in contrast-enhanced, 3D MRI. The results show a satisfactory performance of HDoG in detecting large numbers of small blobs. Two sets of real kidney 3D MR images (6 rats, 3 human) are then used to validate the applicability of HDoG for glomeruli detection. By comparing MRI to stereological measurements, we verify that HDoG is a robust and efficient unsupervised technique for 3D blobs segmentation.

Description: 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.

Description: Watershed segmentation is useful for a number of image segmentation problems with a wide range of practical applications. Traditionally, the tracking of the immersion front is done by applying a fast sorting algorithm. In this work, we explore a continuous approach based on a geometric description of the immersion front which gives rise to a partial differential equation. The main advantage of using a partial differential equation to track the immersion front is that the method becomes versatile and may easily be stabilized by introducing regularization terms. Coupling the geometric approach with a proper “merging strategy” creates a robust algorithm which minimizes over- and under-segmentation even without predefined markers. Since reliable markers defined prior to segmentation can be difficult to construct automatically for various reasons, being able to treat marker-free situations is a major advantage of the proposed method over earlier watershed formulations. The motivation for the methods developed in this paper is taken from high-throughput screening of cells. A fully automated segmentation of single cells enables the extraction of cell properties from large data sets, which can provide substantial insight into a biological model system. Applying smoothing to the boundaries can improve the accuracy in many image analysis tasks requiring a precise delineation of the plasma membrane of the cell. The proposed segmentation method is applied to real images containing fluorescently labeled cells, and the experimental results show that our implementation is robust and reliable for a variety of challenging segmentation tasks.

Description: The major advantage of multiple-instance learning (MIL) applied to a computer-aided detection (CAD) system is that it allows optimizing the latter with case-level labels instead of accurate lesion outlines as traditionally required for a supervised approach. As shown in previous work, a MIL-based CAD system can perform comparably to its supervised counterpart considering complex tasks such as chest radiograph scoring in tuberculosis (TB) detection. However, despite this remarkable achievement, the uncertainty inherent to MIL can lead to a less satisfactory outcome if analysis at lower levels (e.g., regions or pixels) is needed. This issue may seriously compromise the applicability of MIL to tasks related to quantification or grading, or detection of highly localized lesions. In this paper, we propose to reduce uncertainty by embedding a MIL classifier within an active learning (AL) framework. To minimize the labeling effort, we develop a novel instance selection mechanism that exploits the MIL problem definition through one-class classification. We adapt this mechanism to provide meaningful regions instead of individual instances for expert labeling, which is a more appropriate strategy given the application domain. In addition, and contrary to usual AL methods, a single iteration is performed. To show the effectiveness of our approach, we compare the output of a MIL-based CAD system trained with and without the proposed AL framework. The task is to detect textural abnormalities related to TB. Both quantitative and qualitative evaluations at the pixel level are carried out. Our method significantly improves the MIL-based classification.

Description: Radiation therapy is an integral part of cancer treatment, but to date it remains highly manual. Plans are created through optimization of dose volume objectives that specify intent to minimize, maximize, or achieve a prescribed dose level to clinical targets and organs. Optimization is NP-hard, requiring highly iterative and manual initialization procedures. We present a proof-of-concept for a method to automatically infer the radiation dose directly from the patient's treatment planning image based on a database of previous patients with corresponding clinical treatment plans. Our method uses regression forests augmented with density estimation over the most informative features to learn an automatic atlas-selection metric that is tailored to dose prediction. We validate our approach on 276 patients from 3 clinical treatment plan sites (whole breast, breast cavity, and prostate), with an overall dose prediction accuracies of 78.68%, 64.76%, 86.83% under the Gamma metric.

Description: The identification of tumors in the internal organs of chest, abdomen, and pelvis anatomic regions can be performed with the analysis of Dynamic Contrast Enhanced Magnetic Resonance Imaging (DCE-MRI) data. The contrast agent is accumulated differently by pathologic and healthy tissues and that results in a temporally varying contrast in an image series. The internal organs are also subject to potentially extensive movements mainly due to breathing, heart beat, and peristalsis. This contributes to making the analysis of DCE-MRI datasets challenging as well as time consuming. To address this problem we propose a novel pairwise non-rigid registration method with a Non-Parametric Bayesian Registration (NParBR) formulation. The NParBR method uses a Bayesian formulation that assumes a model for the effect of the distortion on the joint intensity statistics, a non-parametric prior for the restored statistics, and also applies a spatial regularization for the estimated registration with Gaussian filtering. A minimally biased intra-dataset atlas is computed for each dataset and used as reference for the registration of the time series. The time series registration method has been tested with 20 datasets of liver, lungs, intestines, and prostate. It has been compared to the B-Splines and to the SyN methods with results that demonstrate that the proposed method improves both accuracy and efficiency.

Description: Statistical image reconstruction (SIR) methods are studied extensively for X-ray computed tomography (CT) due to the potential of acquiring CT scans with reduced X-ray dose while maintaining image quality. However, the longer reconstruction time of SIR methods hinders their use in X-ray CT in practice. To accelerate statistical methods, many optimization techniques have been investigated. Over-relaxation is a common technique to speed up convergence of iterative algorithms. For instance, using a relaxation parameter that is close to two in alternating direction method of multipliers (ADMM) has been shown to speed up convergence significantly. This paper proposes a relaxed linearized augmented Lagrangian (AL) method that shows theoretical faster convergence rate with over-relaxation and applies the proposed relaxed linearized AL method to X-ray CT image reconstruction problems. Experimental results with both simulated and real CT scan data show that the proposed relaxed algorithm (with ordered-subsets [OS] acceleration) is about twice as fast as the existing unrelaxed fast algorithms, with negligible computation and memory overhead.

Description: In this paper, we describe a novel and generic approach to address fully-automatic segmentation of brain tumors by using multi-atlas patch-based voting techniques. In addition to avoiding the local search window assumption, the conventional patch-based framework is enhanced through several simple procedures: an improvement of the training dataset in terms of both label purity and intensity statistics, augmented features to implicitly guide the nearest-neighbor-search, multi-scale patches, invariance to cube isometries, stratification of the votes with respect to cases and labels. A probabilistic model automatically delineates regions of interest enclosing high-probability tumor volumes, which allows the algorithm to achieve highly competitive running time despite minimal processing power and resources. This method was evaluated on Multimodal Brain Tumor Image Segmentation challenge datasets. State-of-the-art results are achieved, with a limited learning stage thus restricting the risk of overfit. Moreover, segmentation smoothness does not involve any post-processing.

Description: The development of an automatic telemedicine system for computer-aided screening and grading of diabetic retinopathy depends on reliable detection of retinal lesions in fundus images. In this paper, a novel method for automatic detection of both microaneurysms and hemorrhages in color fundus images is described and validated. The main contribution is a new set of shape features, called Dynamic Shape Features, that do not require precise segmentation of the regions to be classified. These features represent the evolution of the shape during image flooding and allow to discriminate between lesions and vessel segments. The method is validated per-lesion and per-image using six databases, four of which are publicly available. It proves to be robust with respect to variability in image resolution, quality and acquisition system. On the Retinopathy Online Challenge's database, the method achieves a FROC score of 0.420 which ranks it fourth. On the Messidor database, when detecting images with diabetic retinopathy, the proposed method achieves an area under the ROC curve of 0.899, comparable to the score of human experts, and it outperforms state-of-the-art approaches.

Description: We theoretically demonstrated a new optical imaging technique based on reverse-time migration (RTM) for reconstructing optical structures in homogeneous media for the first time. RTM is a powerful wave-equation-based method to reconstruct the image of the structure by modeling the wave propagation inside the media with both forward modeling and reverse-time extrapolation. While RTM is commonly used with acoustic seismic waves, this paper represents the first effort to develop optical RTM imaging method for biomedical research. To refine the image quality, we further developed new methods to suppress the low-wavenumber artifact (LWA). When compared with the conventional means for LWA suppression such as Laplacian filtering, illumination normalization, and the ratio method, our new derivative-based and power-image methods are able to significantly reduce LWA, resulting in high-quality reconstructed images with sufficient contrasts and spatial resolutions for structure identification. The optical RTM imaging technique may provide a new platform for non-invasive optical imaging of structures in deep layers of tissues for biomedical applications.

Description: Noninvasive cardiac electrophysiological (EP) imaging aims to mathematically reconstruct the spatiotemporal dynamics of cardiac sources from body-surface electrocardiographic (ECG) data. This ill-posed problem is often regularized by a fixed constraining model. However, a fixed-model approach enforces the source distribution to follow a pre-assumed structure that does not always match the varying spatiotemporal distribution of actual sources. To understand the model-data relation and examine the impact of prior models, we present a multiple-model approach for volumetric cardiac EP imaging where multiple prior models are included and automatically picked by the available ECG data. Multiple models are incorporated as an $Lp$ -norm prior for sources, where $p$ is an unknown hyperparameter with a prior uniform distribution. To examine how different combinations of models may be favored by different measurement data, the posterior distribution of cardiac sources and hyperparameter $p$ is calculated using a Markov Chain Monte Carlo (MCMC) technique. The importance of multiple-model prior was assessed in two sets of synthetic and real-data experiments, compared to fixed-model priors (using Laplace and Gaussian priors). The results showed that the posterior combination of models (the posterior distribution of $p$ ) as determined by the ECG data differed substantially when reconstructing sources with different sizes and structures. While the use of fixed models is best suited in situations where the prior assumption fits the actual source structures, the use of an automatically adaptive set of models may have the ability to better address model-data mismatch and to provide consistent performance in reconstructing so- rces with different properties.

Description: Magnetic Resonance—Electrical Properties Tomography (MR-EPT) is an imaging modality that maps the spatial distribution of the electrical conductivity and permittivity using standard MRI systems. The presence of a body within the scanner alters the RF field, and by mapping these alterations it is possible to recover the electrical properties. The field is time-harmonic, and can be described by the Helmholtz equation. Approximations to this equation have been previously used to estimate conductivity and permittivity in terms of first or second derivatives of RF field data. Using these same approximations, an inverse approach to solving the MR-EPT problem is presented here that leverages a forward model for describing the magnitude and phase of the field within the imaging domain, and a fitting approach for estimating the electrical properties distribution. The advantages of this approach are that 1) differentiation of the measured data is not required, thus reducing noise sensitivity, and 2) different regularization schemes can be adopted, depending on prior knowledge of the distribution of conductivity or permittivity, leading to improved image quality. To demonstrate the developed approach, both Quadratic (QR) and Total Variation (TV) regularization methods were implemented and evaluated through numerical simulation and experimentally acquired data. The proposed inverse approach to MR-EPT reconstruction correctly identifies contrasts and accurately reconstructs the geometry in both simulations and experiments. The TV regularized scheme reconstructs sharp spatial transitions, which are difficult to reconstruct with other, more traditional approaches.

Description: The accurate segmentation of lung lesions from computed tomography (CT) scans is important for lung cancer research and can offer valuable information for clinical diagnosis and treatment. However, it is challenging to achieve a fully automatic lesion detection and segmentation with acceptable accuracy due to the heterogeneity of lung lesions. Here, we propose a novel toboggan based growing automatic segmentation approach (TBGA) with a three-step framework, which are automatic initial seed point selection, multi-constraints 3D lesion extraction and the final lesion refinement. The new approach does not require any human interaction or training dataset for lesion detection, yet it can provide a high lesion detection sensitivity (96.35%) and a comparable segmentation accuracy with manual segmentation $({rm P}〉0.05)$ , which was proved by a series assessments using the LIDC-IDRI dataset (850 lesions) and in-house clinical dataset (121 lesions). We also compared TBGA with commonly used level set and skeleton graph cut methods, respectively. The results indicated a significant improvement of segmentation accuracy $({rm P}〈0.05)$ . Furthermore, the average time consumption for one lesion segmentation was under 8 s using our new method. In conclusion, we believe that the novel TBGA can achieve robust, efficient and accurate lung lesion segmentation in CT images automatically.

Description: Cardiac Phase-resolved Blood-Oxygen-Level Dependent (CP-BOLD) MRI provides a unique opportunity to image an ongoing ischemia at rest. However, it requires post-processing to evaluate the extent of ischemia. To address this, here we propose an unsupervised ischemia detection (UID) method which relies on the inherent spatio-temporal correlation between oxygenation and wall motion to formalize a joint learning and detection problem based on dictionary decomposition. Considering input data of a single subject, it treats ischemia as an anomaly and iteratively learns dictionaries to represent only normal observations (corresponding to myocardial territories remote to ischemia). Anomaly detection is based on a modified version of One-class Support Vector Machines (OCSVM) to regulate directly the margins by incorporating the dictionary-based representation errors. A measure of ischemic extent (IE) is estimated, reflecting the relative portion of the myocardium affected by ischemia. For visualization purposes an ischemia likelihood map is created by estimating posterior probabilities from the OCSVM outputs, thus obtaining how likely the classification is correct. UID is evaluated on synthetic data and in a 2D CP-BOLD data set from a canine experimental model emulating acute coronary syndromes. Comparing early ischemic territories identified with UID against infarct territories (after several hours of ischemia), we find that IE, as measured by UID, is highly correlated (Pearson’s $r=0.84$ ) with respect to infarct size. When advances in automated registration and segmentation of CP-BOLD images and full coverage 3D acquisitions become available, we hope that this method can enable pixel-level assessment of ischemia with this truly non-invasive imaging technique.

Description: This work provides an insight into positron emission tomography (PET) joint image reconstruction/motion estimation (JRM) by maximization of the likelihood, where the probabilistic model accounts for warped attenuation. Our analysis shows that maximum-likelihood (ML) JRM returns the same reconstructed gates for any attenuation map ( $mu$ -map) that is a deformation of a given $mu$ -map, regardless of its alignment with the PET gates. We derived a joint optimization algorithm accordingly, and applied it to simulated and patient gated PET data. We first evaluated the proposed algorithm on simulations of respiratory gated PET/CT data based on the XCAT phantom. Our results show that independently of which $mu$ -map is used as input to JRM: (i) the warped $mu$ -maps correspond to the gated $mu$ -maps, (ii) JRM outperforms the traditional post-registration reconstruction and consolidation (PRRC) for hot lesion quantification and (iii) reconstructed gated PET images are similar to those obtained with gated $mu$ -maps. This suggests that a breath-held $mu$ -map can be used. We then applied JRM on patient data with a $mu$ -map derived from a breath-held high resolution CT (HRCT), and compared the results with PRRC, where each reconstructed PET image was obtained with a corresponding cine-CT gated $mu$ -map. Results show that JRM with breath-held HRCT achieves similar reconstructi- n to that using PRRC with cine-CT. This suggests a practical low-dose solution for implementation of motion-corrected respiratory gated PET/CT.

Description: The theory and techniques of compressed sensing (CS) have shown their potential as a breakthrough in accelerating $k$ -space data acquisition for parallel magnetic resonance imaging (pMRI). However, the performance of CS reconstruction models in pMRI has not been fully maximized, and CS recovery guarantees for pMRI are largely absent. To improve reconstruction accuracy from parsimonious amounts of $k$ -space data while maintaining flexibility, a new CS SENSitivity Encoding (SENSE) pMRI reconstruction framework promoting joint sparsity (JS) across channels (JS CS SENSE) is proposed in this paper. The recovery guarantee derived for the proposed JS CS SENSE model is demonstrated to be better than that of the conventional CS SENSE model and similar to that of the coil-by-coil CS model. The flexibility of the new model is better than the coil-by-coil CS model and the same as that of CS SENSE. For fast image reconstruction and fair comparisons, all the introduced CS-based constrained optimization problems are solved with split Bregman, variable splitting, and combined-variable splitting techniques. For the JS CS SENSE model in particular, these techniques lead to an efficient algorithm. Numerical experiments show that the reconstruction accuracy is significantly improved by JS CS SENSE compared with the conventional CS SENSE. In addition, an accurate residual-JS regularized sensitivity estimation model is also proposed and extended to calibration-less (CaL) JS CS SENSE. Numerical results show that CaL JS CS SENSE outperforms other state-of-the-art CS-based calibration-less methods in particular for reconstructing non-piecewise constant images.

Description: Most X-ray fluoroscopy systems are stationary and impose restrictions on the measurement of dynamic joint motion; for example, knee-joint kinematics during gait is usually measured with the subject ambulating on a treadmill. We developed a computer-controlled, mobile, biplane, X-ray fluoroscopy system to track human body movement for high-speed imaging of 3D joint motion during overground gait. A robotic gantry mechanism translates the two X-ray units alongside the subject, tracking and imaging the joint of interest as the subject moves. The main aim of the present study was to determine the accuracy with which the mobile imaging system measures 3D knee-joint kinematics during walking. In vitro experiments were performed to measure the relative positions of the tibia and femur in an intact human cadaver knee and of the tibial and femoral components of a total knee arthroplasty (TKA) implant during simulated overground gait. Accuracy was determined by calculating mean, standard deviation and root-mean-squared errors from differences between kinematic measurements obtained using volumetric models of the bones and TKA components and reference measurements obtained from metal beads embedded in the bones. Measurement accuracy was enhanced by the ability to track and image the joint concurrently. Maximum root-mean-squared errors were 0.33 mm and 0.65 $^{circ}$ for translations and rotations of the TKA knee and 0.78 mm and 0.77 $^{circ}$ for translations and rotations of the intact knee, which are comparable to results reported for treadmill walking using stationary biplane systems. System capability for in vivo joint motion measurement was also demonstrated for overground gait.

Description: We present a method that quantifies point-wise changes in surface morphology of the bones of the human wrist. The proposed method, referred to as Registration-based Bone Morphometry (RBM), consists of two steps: an atlas selection step and an atlas warping step. The atlas for individual wrist bones was selected based on the shortest $l^{2}$ distance to the ensemble of wrist bones from a database of a healthy population of subjects. The selected atlas was then warped to the corresponding bones of individuals in the population using a non-linear registration method based on regularized $l^{2}$ distance minimization. The displacement field thus calculated showed local differences in bone shape that then were used for the analysis of group differences. Our results indicate that RBM has potential to provide a standardized approach to shape analysis of bones of the human wrist. We demonstrate the performance of RBM for examining group differences in wrist bone shapes based on sex and between those of the right and left wrists in healthy individuals. We also present data to show the application of RBM for tracking bone erosion status in rheumatoid arthritis.

Description: Quantitative histomorphometry (QH) refers to the process of computationally modeling disease appearance on digital pathology images by extracting hundreds of image features and using them to predict disease presence or outcome. Since constructing a robust and interpretable classifier is challenging in a high dimensional feature space, dimensionality reduction (DR) is often implemented prior to classifier construction. However, when DR is performed it can be challenging to quantify the contribution of each of the original features to the final classification result. We have previously presented a method for scoring features based on their importance for classification on an embedding derived via principal components analysis (PCA). However, nonlinear DR involves the eigen-decomposition of a kernel matrix rather than the data itself, compounding the issue of classifier interpretability. In this paper we present feature importance in nonlinear embeddings (FINE), an extension of our PCA-based feature scoring method to kernel PCA (KPCA), as well as several NLDR algorithms that can be cast as variants of KPCA. FINE is applied to four digital pathology datasets to identify key QH features for predicting the risk of breast and prostate cancer recurrence. Measures of nuclear and glandular architecture and clusteredness were found to play an important role in predicting the likelihood of recurrence of both breast and prostate cancers. Compared to the t-test, Fisher score, and Gini index, FINE was able to identify a stable set of features that provide good classification accuracy on four publicly available datasets from the NIPS 2003 Feature Selection Challenge.

Description: In this work we describe a 4D registration method for on the fly stabilization of ultrasound volumes for improving image guidance for transjugular intrahepatic portosystemic shunt (TIPS) interventions. The purpose of the method is to enable a continuous visualization of the relevant anatomical planes (determined in a planning stage) in a free breathing patient during the intervention. This requires registration of the planning information to the interventional images, which is achieved in two steps. In the first step tracking is performed across the streaming input. An approximate transformation between the reference image and the incoming image is estimated by composing the intermediate transformations obtained from the tracking. In the second step a subsequent registration is performed between the reference image and the approximately transformed incoming image to account for the accumulation of error. The two step approach helps in reducing the search range and is robust under rotation. We additionally present an approach to initialize and verify the registration. Verification is required when the reference image (containing planning information) is acquired in the past and is not part of the (interventional) 4D ultrasound sequence. The verification score will help in invalidating the registration outcome, for instance, in the case of insufficient overlap or information between the registering images due to probe motion or loss of contact, respectively. We evaluate the method over thirteen 4D US sequences acquired from eight subjects. A graphics processing unit implementation runs the 4D tracking at 9 Hz with a mean registration error of 1.7 mm.

Description: Registration of images in the presence of intra-image signal fluctuations is a challenging task. The definition of an appropriate objective function measuring the similarity between the images is crucial for accurate registration. This paper introduces an objective function that embeds local phase features derived from the monogenic signal in the modality independent neighborhood descriptor (MIND). The image similarity relies on the autocorrelation of local structure (ALOST) which has two important properties: 1) low sensitivity to space-variant intensity distortions (e.g., differences in contrast enhancement in MRI); 2) high distinctiveness for ‘salient’ image features such as edges. The ALOST method is quantitatively compared to the MIND approach based on three different datasets: thoracic CT images, synthetic and real abdominal MR images. The proposed method outperformed the NMI and MIND similarity measures on these three datasets. The registration of dynamic contrast enhanced and post-contrast MR images of patients with Crohn's disease led to relative contrast enhancement measures with the highest correlation $({rm r}=0.56)$ to the Crohn's disease endoscopic index of severity.

Description: Variations in properties, active behavior, injury, scarring, and/or disease can all cause a tissue's mechanical behavior to be heterogeneous. Advances in imaging technology allow for accurate full-field displacement tracking of both in vitro and in vivo deformation from an applied load. While detailed strain fields provide some insight into tissue behavior, material properties are usually determined by fitting stress-strain behavior with a constitutive equation. However, the determination of the mechanical behavior of heterogeneous soft tissue requires a spatially varying constitutive equation (i.e., one in which the material parameters vary with position). We present an approach that computationally dissects the sample domain into many homogeneous subdomains, wherein subdomain boundaries are formed by applying a betweenness based graphical analysis to the deformation gradient field to identify locations with large discontinuities. This novel partitioning technique successfully determined the shape, size and location of regions with locally similar material properties for: (1) a series of simulated soft tissue samples prescribed with both abrupt and gradual changes in anisotropy strength, prescribed fiber alignment, stiffness, and nonlinearity, (2) tissue analogs (PDMS and collagen gels) which were tested biaxially and speckle tracked (3) and soft tissues which exhibited a natural variation in properties (cadaveric supraspinatus tendon), a pathologic variation in properties (thoracic aorta containing transmural plaque), and active behavior (contracting cardiac sheet). The routine enables the dissection of samples computationally rather than physically, allowing for the study of small tissues specimens with unknown and irregular inhomogeneity.

Description: This paper presents a new supervised method for vessel segmentation in retinal images. This method remolds the task of segmentation as a problem of cross-modality data transformation from retinal image to vessel map. A wide and deep neural network with strong induction ability is proposed to model the transformation, and an efficient training strategy is presented. Instead of a single label of the center pixel, the network can output the label map of all pixels for a given image patch. Our approach outperforms reported state-of-the-art methods in terms of sensitivity, specificity and accuracy. The result of cross-training evaluation indicates its robustness to the training set. The approach needs no artificially designed feature and no preprocessing step, reducing the impact of subjective factors. The proposed method has the potential for application in image diagnosis of ophthalmologic diseases, and it may provide a new, general, high-performance computing framework for image segmentation.

Description: This paper describes the development and evaluation of a new beamforming strategy based on pixel-based focusing for ultrasound linear array systems. We first implement conventional pixel-based beamforming in which the transmitted wave is assumed as spherical and diverging from the centre of the transmit subaperture. This assumed wave-shape is only valid within a limited angle on each side of the beam and this restricts the number of different subaperture positions from which data can be combined to improve image quality. By analyzing the field patterns, we propose a new unified pixel-based beamforming algorithm that better adapts to the non-spherical wave-shape of the transmit beam. This approach enables us to select the best-possible signal from each transducer waveform for data superposition. In simulations and a phantom study, we show that the unified pixel-based beamformer offers significant improvements in image quality compared to other delay-and-sum methods but at a higher computational cost. The new algorithm also demonstrates robust performance in a limited in vivo study. Overall, the results show that it is potentially of value in clinical applications.

Description: As the right ventricle's (RV) role in cardiovascular diseases is being more widely recognized, interest in RV imaging, function and quantification is growing. However, there are currently few RV quantification methods for 3D echocardiography presented in the literature or commercially available. In this paper we propose an automated RV segmentation method for 3D echocardiographic images. We represent the RV geometry by a Doo-Sabin subdivision surface with deformation modes derived from a training set of manual segmentations. The segmentation is then represented as a state estimation problem and solved with an extended Kalman filter by combining the RV geometry with a motion model and edge detection. Validation was performed by comparing surface-surface distances, volumes and ejection fractions in 17 patients with aortic insufficiency between the proposed method, magnetic resonance imaging (MRI), and a manual echocardiographic reference. The algorithm was efficient with a mean computation time of 2.0 s. The mean absolute distances between the proposed and manual segmentations were 3.6 $pm$ 0.7 mm. Good agreements of end diastolic volume, end systolic volume and ejection fraction with respect to MRI ( $-26pm 24 {rm mL}$ , $-16pm 26 {rm mL}$ and 0 $pm$ 10%, respectively) and a manual echocardiographic reference (7 $pm$ 30 mL, 13 $pm$ 17 mL and $-5pm 7%$ , respectively) were observed.

Description: The presence of high-density objects remains an open problem in medical CT imaging. Data of projections passing through objects of high density, such as metal implants, are dominated by noise and are highly affected by beam hardening and scatter. Reconstructed images become less diagnostically conclusive because of pronounced artifacts that manifest as dark and bright streaks. A new reconstruction algorithm is proposed with the aim to reduce these artifacts by incorporating information about shape and known attenuation coefficients of a metal implant. Image reconstruction is considered as a variational optimization problem. The afore-mentioned prior knowledge is introduced in terms of equality constraints. An augmented Lagrangian approach is adapted in order to minimize the associated log-likelihood function for transmission CT. During iterations, temporally appearing artifacts are reduced with a bilateral filter and new projection values are calculated, which are used later on for the reconstruction. A detailed evaluation in cooperation with radiologists is performed on software and hardware phantoms, as well as on clinically relevant patient data of subjects with various metal implants. Results show that the proposed reconstruction algorithm is able to outperform contemporary metal artifact reduction methods such as normalized metal artifact reduction.

Description: Exploiting redundancies between multiple images of an MRI examination can be formalized as the joint reconstruction of these images. The anatomy is preserved indeed so that specific constraints can be implemented (e.g. most of the features or spatial gradients should be in the same place in all these images) and only the contrast changes from one image to another need to be encoded. The application of this concept is particularly challenging in cardiovascular and body imaging due to the complex organ deformations, especially with the patient breathing. In this study a joint optimization framework is proposed for reconstructing multiple MR images together with a nonrigid motion model. The motion model takes into account both intra-image and inter-image motion and therefore can correct for most ghosting/blurring artifacts and misregistration between images. The framework was validated with free-breathing myocardial ${rm T}_{2}$ mapping experiments from nine heart transplant patients at 1.5 T. Results showed improved image quality and excellent image alignment with the multi-image reconstruction compared to the independent reconstruction of each image. Segment-wise myocardial ${rm T}_{2}$ values were in good agreement with the reference values obtained from multiple breath-holds (62.5 $pm$ 11.1 ms against 62.2 $pm$ 11.2 ms which was not significant with ${rm p}=0.49$ ).

Description: We propose a new method that employs transfer learning techniques to effectively correct sampling selection errors introduced by sparse annotations during supervised learning for automated tumor segmentation. The practicality of current learning-based automated tissue classification approaches is severely impeded by their dependency on manually segmented training databases that need to be recreated for each scenario of application, site, or acquisition setup. The comprehensive annotation of reference datasets can be highly labor-intensive, complex, and error-prone. The proposed method derives high-quality classifiers for the different tissue classes from sparse and unambiguous annotations and employs domain adaptation techniques for effectively correcting sampling selection errors introduced by the sparse sampling. The new approach is validated on labeled, multi-modal MR images of 19 patients with malignant gliomas and by comparative analysis on the BraTS 2013 challenge data sets. Compared to training on fully labeled data, we reduced the time for labeling and training by a factor greater than 70 and 180 respectively without sacrificing accuracy. This dramatically eases the establishment and constant extension of large annotated databases in various scenarios and imaging setups and thus represents an important step towards practical applicability of learning-based approaches in tissue classification.

Description: Computed tomography (CT) imaging is an essential tool in various clinical diagnoses and radiotherapy treatment planning. Since CT image intensities are directly related to positron emission tomography (PET) attenuation coefficients, they are indispensable for attenuation correction (AC) of the PET images. However, due to the relatively high dose of radiation exposure in CT scan, it is advised to limit the acquisition of CT images. In addition, in the new PET and magnetic resonance (MR) imaging scanner, only MR images are available, which are unfortunately not directly applicable to AC. These issues greatly motivate the development of methods for reliable estimate of CT image from its corresponding MR image of the same subject. In this paper, we propose a learning-based method to tackle this challenging problem. Specifically, we first partition a given MR image into a set of patches. Then, for each patch, we use the structured random forest to directly predict a CT patch as a structured output, where a new ensemble model is also used to ensure the robust prediction. Image features are innovatively crafted to achieve multi-level sensitivity, with spatial information integrated through only rigid-body alignment to help avoiding the error-prone inter-subject deformable registration. Moreover, we use an auto-context model to iteratively refine the prediction. Finally, we combine all of the predicted CT patches to obtain the final prediction for the given MR image. We demonstrate the efficacy of our method on two datasets: human brain and prostate images. Experimental results show that our method can accurately predict CT images in various scenarios, even for the images undergoing large shape variation, and also outperforms two state-of-the-art methods.

Description: Lack of classifier robustness is a barrier to widespread adoption of computer-aided diagnosis systems for computed tomography (CT). We propose a novel Robustness-Driven Feature Selection (RDFS) algorithm that preferentially selects features robust to variations in CT technical factors. We evaluated RDFS in CT classification of fibrotic interstitial lung disease using 3D texture features. CTs were collected for 99 adult subjects separated into three datasets: training, multi-reconstruction, testing. Two thoracic radiologists provided cubic volumes of interest corresponding to six classes: pulmonary fibrosis, ground-glass opacity, honeycombing, normal lung parenchyma, airway, vessel. The multi-reconstruction dataset consisted of CT raw sinogram data reconstructed by systematically varying slice thickness, reconstruction kernel, and tube current (using a synthetic reduced-tube-current algorithm). Two support vector machine classifiers were created, one using RDFS (“with-RDFS”) and one not (“without-RDFS”). Classifier robustness was compared on the multi-reconstruction dataset, using Cohen's kappa to assess classification agreement against a reference reconstruction. Classifier performance was compared on the testing dataset using the extended g-mean (EGM) measure. With-RDFS exhibited superior robustness (kappa 0.899–0.989) compared to without-RDFS (kappa 0.827–0.968). Both classifiers demonstrated similar performance on the testing dataset (EGM 0.778 for with-RDFS; 0.785 for without-RDFS), indicating that RDFS does not compromise classifier performance when discarding nonrobust features. RDFS is highly effective at improving classifier robustness against slice thickness, reconstruction kernel, and tube current without sacrificing performance, a result that has implications for multicenter clinical trials that rely on accurate and reproducible quantitative analysis of CT images collected under varied conditions across mu- tiple sites, scanners, and timepoints.

Description: There is a recent interest in using functional magnetic resonance imaging (fMRI) for decoding more naturalistic, cognitive states, in which subjects perform various tasks in a continuous, self-directed manner. In this setting, the set of brain volumes over the entire task duration is usually taken as a single sample with connectivity estimates, such as Pearson's correlation, employed as features. Since covariance matrices live on the positive semidefinite cone, their elements are inherently inter-related. The assumption of uncorrelated features implicit in most classifier learning algorithms is thus violated. Coupled with the usual small sample sizes, the generalizability of the learned classifiers is limited, and the identification of significant brain connections from the classifier weights is nontrivial. In this paper, we present a Riemannian approach for connectivity-based brain decoding. The core idea is to project the covariance estimates onto a common tangent space to reduce the statistical dependencies between their elements. For this, we propose a matrix whitening transport, and compare it against parallel transport implemented via the Schild's ladder algorithm. To validate our classification approach, we apply it to fMRI data acquired from twenty four subjects during four continuous, self-driven tasks. We show that our approach provides significantly higher classification accuracy than directly using Pearson's correlation and its regularized variants as features. To facilitate result interpretation, we further propose a non-parametric scheme that combines bootstrapping and permutation testing for identifying significantly discriminative brain connections from the classifier weights. Using this scheme, a number of neuro-anatomically meaningful connections are detected, whereas no significant connections are found with pure permutation testing.

Description: The aim of this study is about tracing filamentary structures in both neuronal and retinal images. It is often crucial to identify single neurons in neuronal networks, or separate vessel tree structures in retinal blood vessel networks, in applications such as drug screening for neurological disorders or computer-aided diagnosis of diabetic retinopathy. Both tasks are challenging as the same bottleneck issue of filament crossovers is commonly encountered, which essentially hinders the ability of existing systems to conduct large-scale drug screening or practical clinical usage. To address the filament crossovers' problem, a two-step graph-theoretical approach is proposed in this paper. The first step focuses on segmenting filamentary pixels out of the background. This produces a filament segmentation map used as input for the second step, where they are further separated into disjointed filaments. Key to our approach is the idea that the problem can be reformulated as label propagation over directed graphs, such that the graph is to be partitioned into disjoint sub-graphs, or equivalently, each of the neurons (vessel trees) is separated from the rest of the neuronal (vessel) network. This enables us to make the interesting connection between the tracing problem and the digraph matrix-forest theorem in algebraic graph theory for the first time. Empirical experiments on neuronal and retinal image datasets demonstrate the superior performance of our approach over existing methods.

Description: Although modern ultrasound acquisition systems allow recording of 3D echocardiographic images, tracking anatomical structures from them is still challenging. In addition, since these images are typically created from information obtained across several cardiac cycles, it is not yet possible to acquire high-quality 3D images from patients presenting varying heart rhythms. In this paper, we propose a method to estimate the motion field from multi-plane echocardiographic images of the left ventricle, which are acquired simultaneously during a single cardiac cycle. The method integrates tri-plane B-mode and tissue Doppler images acquired at different rotation angles around the long axis of the left ventricle. It uses a diffeomorphic continuous spatio-temporal transformation model with a spherical data representation for a better interpolation in the circumferential direction. This framework allows exploiting the spatial relation among the acquired planes. In addition, higher temporal resolution of the transformation in the beam direction is achieved by uncoupling the estimation of the different components of the velocity field. The method was validated using a realistic synthetic dataset including healthy and ischemic cases, obtaining errors of 0.14 $pm$ 0.09 mm for displacements, 0.96 $pm$ 1.03% for longitudinal strain and 3.94 $pm$ 4.38% for radial strain estimation. In addition, the method was also demonstrated on a healthy volunteer and two patients with ischemia.

Description: Extracting geometrical information from large 2D or 3D biomedical images is important to better understand fundamental phenomena such as morphogenesis. We address the problem of automatically analyzing spatial organization of cells or nuclei in 2D or 3D images of tissues. This problem is challenging due to the usually low quality of microscopy images as well as their typically large sizes. The structure tensor is a simple and robust descriptor that was developed to analyze textures orientation. Contrarily to segmentation methods which rely on an object based modeling of images, the structure tensor considers the sample at a macroscopic scale, like a continuous medium. We show that this tool allows quantifying two important features of nuclei in tissues: their privileged orientation as well as the ratio between the length of their main axes. A quantitative evaluation of the method is provided for synthetic and real 2D and 3D images. As an application, we analyze the nuclei orientation and anisotropy on multicellular tumor spheroids cryosections. This analysis reveals that cells are elongated in a privileged direction that is parallel to the spheroid boundary. A MATLAB toolbox and an Icy plugin are available to use the proposed method.

Description: Purpose: Pathologists often look at whole slide images (WSIs) at low magnification to find potentially important regions and then zoom in to higher magnification to perform more sophisticated analysis of the tissue structures. Many automated methods of WSI analysis attempt to preprocess the down-sampled image in order to select salient regions which are then further analyzed by a more computationally intensive step at full magnification. Although it can greatly reduce processing times, this process may lead to small potentially important regions being overlooked at low magnification. We propose a texture analysis technique to ease the processing of H&E stained WSIs by triaging clinically important regions. Method: Image patches randomly selected from the whole tissue area were divided into smaller tiles and Gaussian-like texture filters were applied to them. Texture filter responses from each tile were combined together and statistical measures were derived from their histograms of responses. Bag of visual words pipeline was then employed to combine extracted features from tiles to form one histogram of words per every image patch. A support vector machine classifier was trained using the calculated histograms of words to be able to distinguish between clinically relevant and irrelevant patches. Result: Experimental analysis on 5151 image patches from 10 patient cases (65 tissue slides) indicated that our proposed texture technique out-performed two previously proposed colour and intensity based methods with an area under the ROC curve of 0.87. Conclusion: Texture features can be employed to triage clinically important areas within large WSIs.