Fully automatic left ventricular myocardial strain estimation in 2D short-axis tagged magnetic resonance imaging

Cardiovascular diseases are among the leading causes of death and frequently result in local myocardial dysfunction. Among the numerous imaging modalities available to detect these dysfunctional regions, cardiac deformation imaging through tagged magnetic resonance imaging (t-MRI) has been an attractive approach. Nevertheless, fully automatic analysis of these data sets is still challenging. In this work, we present a fully automatic framework to estimate left ventricular myocardial deformation from t-MRI. This strategy performs automatic myocardial segmentation based on B-spline explicit active surfaces, which are initialized using an annular model. A non-rigid image-registration technique is then used to assess myocardial deformation. Three experiments were set up to validate the proposed framework using a clinical database of 75 patients. First, automatic segmentation accuracy was evaluated by comparing against manual delineations at one specific cardiac phase. The proposed solution showed an average perpendicular distance error of 2.35 +/- 1.21 mm and 2.27 +/- 1.02 mm for the endo- and epicardium, respectively. Second, starting from either manual or automatic segmentation, myocardial tracking was performed and the resulting strain curves were compared. It is shown that the automatic segmentation adds negligible differences during the strain-estimation stage, corroborating its accuracy. Finally, segmental strain was compared with scar tissue extent determined by delay-enhanced MRI. The results proved that both strain components were able to distinguish between normal and infarct regions. Overall, the proposed framework was shown to be accurate, robust, and attractive for clinical practice, as it overcomes several limitations of a manual analysis.FCT—Fundacão para a Ciência e a Tecnologia, Portugal, and the European Social Found, European Union, for funding support through the Programa Operacional Capital Humano (POCH) in the scope of the PhD grants SFRH/BD/95438/2013 (P Morais) and SFRH/BD/93443/2013 (S Queirós). This work was supported by the projects NORTE-07-0124-FEDER-000017 and NORTE-01-0145-FEDER-000013, co-funded by Programa Operacional Regional do Norte, Quadro de Referência Estratégico Nacional, through Fundo Europeu de Desenvolvimento Regional (FEDER). The authors would also like to acknowledge the EU (FP7) framework program, for the financial support of the DOPPLER-CIP project (grant no. 223615)info:eu-repo/semantics/publishedVersio

A novel MRA-based framework for the detection of changes in cerebrovascular blood pressure.

Background: High blood pressure (HBP) affects 75 million adults and is the primary or contributing cause of mortality in 410,000 adults each year in the United States. Chronic HBP leads to cerebrovascular changes and is a significant contributor for strokes, dementia, and cognitive impairment. Non-invasive measurement of changes in cerebral vasculature and blood pressure (BP) may enable physicians to optimally treat HBP patients. This manuscript describes a method to non-invasively quantify changes in cerebral vasculature and BP using Magnetic Resonance Angiography (MRA) imaging. Methods: MRA images and BP measurements were obtained from patients (n=15, M=8, F=7, Age= 49.2 ± 7.3 years) over a span of 700 days. A novel segmentation algorithm was developed to identify brain vasculature from surrounding tissue. The data was processed to calculate the vascular probability distribution function (PDF); a measure of the vascular diameters in the brain. The initial (day 0) PDF and final (day 700) PDF were used to correlate the changes in cerebral vasculature and BP. Correlation was determined by a mixed effects linear model analysis. Results: The segmentation algorithm had a 99.9% specificity and 99.7% sensitivity in identifying and delineating cerebral vasculature. The PDFs had a statistically significant correlation to BP changes below the circle of Willis (p-value = 0.0007), but not significant (p-value = 0.53) above the circle of Willis, due to smaller blood vessels. Conclusion: Changes in cerebral vasculature and pressure can be non-invasively obtained through MRA image analysis, which may be a useful tool for clinicians to optimize medical management of HBP

Myocardial tagging by Cardiovascular Magnetic Resonance: evolution of techniques--pulse sequences, analysis algorithms, and applications

Cardiovascular magnetic resonance (CMR) tagging has been established as an essential technique for measuring regional myocardial function. It allows quantification of local intramyocardial motion measures, e.g. strain and strain rate. The invention of CMR tagging came in the late eighties, where the technique allowed for the first time for visualizing transmural myocardial movement without having to implant physical markers. This new idea opened the door for a series of developments and improvements that continue up to the present time. Different tagging techniques are currently available that are more extensive, improved, and sophisticated than they were twenty years ago. Each of these techniques has different versions for improved resolution, signal-to-noise ratio (SNR), scan time, anatomical coverage, three-dimensional capability, and image quality. The tagging techniques covered in this article can be broadly divided into two main categories: 1) Basic techniques, which include magnetization saturation, spatial modulation of magnetization (SPAMM), delay alternating with nutations for tailored excitation (DANTE), and complementary SPAMM (CSPAMM); and 2) Advanced techniques, which include harmonic phase (HARP), displacement encoding with stimulated echoes (DENSE), and strain encoding (SENC). Although most of these techniques were developed by separate groups and evolved from different backgrounds, they are in fact closely related to each other, and they can be interpreted from more than one perspective. Some of these techniques even followed parallel paths of developments, as illustrated in the article. As each technique has its own advantages, some efforts have been made to combine different techniques together for improved image quality or composite information acquisition. In this review, different developments in pulse sequences and related image processing techniques are described along with the necessities that led to their invention, which makes this article easy to read and the covered techniques easy to follow. Major studies that applied CMR tagging for studying myocardial mechanics are also summarized. Finally, the current article includes a plethora of ideas and techniques with over 300 references that motivate the reader to think about the future of CMR tagging

MR imaging of left-ventricular function : novel image acquisition and analysis techniques.

Many cardiac diseases, such as myocardial ischemia, secondary to coronary artery disease, may be identified and localized through the analysis of cardiac deformations. Early efforts for quantifying ventricular wall motion used surgical implantation and tracking of radiopaque markers with X-ray imaging in canine hearts [1]. Such techniques are invasive and affect the regional motion pattern of the ventricular wall during the marker tracking process and, clearly are not feasible clinically. Noninvasive imaging techniques are vital and have been widely applied to the clinic. MRI is a noninvasive imaging technique with the capability to monitor and assess the progression of cardiovascular diseases (CVD) so that effective procedures for the care and treatment of patients can be developed by physicians and researchers. It is capable of providing 3D analysis of global and regional cardiac function with great accuracy and reproducibility. In the past few years, numerous efforts have been devoted to cardiac motion recovery and deformation analysis from MR imaging sequences. In order to assess cardiac function, there are two categories of indices that are used: global and regional indices. Global indices include ejection fraction, cavity volume, and myocardial mass [2]. They are important indices for cardiac disease diagnosis. However, these global indices are not specific for regional analysis. A quantitative assessment of regional parameters may prove beneficial for the diagnosis of disease and evaluation of severity and the quantification of treatment [3]. Local measures, such as wall deformation and strain in all regions of the heart, can provide objective regional quantification of ventricular wall function and relate to the location and extent of ischemic injury. This dissertation is concerned with the development of novel MR imaging techniques and image postprocessing algorithms to analyze left ventricular deformations. A novel pulse sequence, termed Orthogonal CSPAMM (OCSPAMM), has been proposed which results in the same acquisition time as SPAMM for 2D deformation estimation while keeping the main advantages of CSPAMM [4,5]: i.e., maintaining tag contrast through-out the ECG cycle. Different from CSPAMM, in OCSPAMM the second tagging pulse orientation is rotated 90 degrees relative to the first one so that motion information can be obtained simultaneously in two directions. This reduces the acquisition time by a factor of two as compared to the traditional CSPAMM, in which two separate imaging sequences are applied per acquisition. With the application of OCSPAMM, the effect of tag fading encountered in SPAMM tagging due to Tl relaxation is mitigated and tag deformations can be visualized for the entire cardiac cycle, including diastolic phases. A multilevel B-spline fitting method (MBS) has been proposed which incorporates phase-based displacement information for accurate calculation of 2D motion and strain from tagged MRI [6, 7]. The proposed method combines the advantages of continuity and smoothness of MBS, and makes use of phase information derived from tagged MR images. Compared to previous 2D B-spline-based deformation analysis methods, MBS has the following advantages: 1) It can simultaneously achieve a smooth deformation while accurately approximating the given data set; 2) Computationally, it is very fast; and 3) It can produce more accurate deformation results. Since the tag intersections (intersections between two tag lines) can be extracted accurately and are more or less distributed evenly over the myocardium, MBS has proven effective for 2D cardiac motion tracking. To derive phase-based displacements, 2D HARP and SinMod analysis techniques [8,9] were employed. By producing virtual tags from HARP /SinMod and calculating intersections of virtual tag lines, more data points are obtained. In the reference frame, virtual tag lines are the isoparametric curves of an undeformed 2D B-spline model. In subsequent frames, the locations of intersections of virtual tag lines over the myocardium are updated with phase-based displacement. The advantage of the technique is that in acquiring denser myocardial displacements, it uses both real and virtual tag line intersections. It is fast and more accurate than 2D HARP and SinMod tracking. A novel 3D sine wave modeling (3D SinMod) approach for automatic analysis of 3D cardiac deformations has been proposed [10]. An accelerated 3D complementary spatial modulation of magnetization (CSPAMM) tagging technique [11] was used to acquire complete 3D+t tagged MR data sets of the whole heart (3 dynamic CSPAMM tagged MRI volume with tags in different orientations), in-vivo, in 54 heart beats and within 3 breath-holds. In 3D SinMod, the intensity distribution around each pixel is modeled as a cosine wave front. The principle behind 3D SinMod tracking is that both phase and frequency for each voxel are determined directly from the frequency analysis and the displacement is calculated from the quotient of phase difference and local frequency. The deformation fields clearly demonstrate longitudinal shortening during systole. The contraction of the LV base towards the apex as well as the torsional motion between basal and apical slices is clearly observable from the displacements. 3D SinMod can automatically process the image data to derive measures of motion, deformations, and strains between consecutive pair of tagged volumes in 17 seconds. Therefore, comprehensive 4D imaging and postprocessing for determination of ventricular function is now possible in under 10 minutes. For validation of 3D SinMod, 7 3D+t CSPAMM data sets of healthy subjects have been processed. Comparison of mid-wall contour deformations and circumferential shortening results by 3D SinMod showed good agreement with those by 3D HARP. Tag lines tracked by the proposed technique were also compared with manually delineated ones. The average errors calculated for the systolic phase of the cardiac cycles were in the sub-pixel range

An image segmentation and registration approach to cardiac function analysis using MRI

Cardiovascular diseases (CVDs) are one of the major causes of death in the world. In recent years, significant progress has been made in the care and treatment of patients with such diseases. A crucial factor for this progress has been the development of magnetic resonance (MR) imaging which makes it possible to diagnose and assess the cardiovascular function of the patient. The ability to obtain high-resolution, cine volume images easily and safely has made it the preferred method for diagnosis of CVDs. MRI is also unique in its ability to introduce noninvasive markers directly into the tissue being imaged(MR tagging) during the image acquisition process. With the development of advanced MR imaging acquisition technologies, 3D MR imaging is more and more clinically feasible. This recent development has allowed new potentially 3D image analysis technologies to be deployed. However, quantitative analysis of cardiovascular system from the images remains a challenging topic. The work presented in this thesis describes the development of segmentation and motion analysis techniques for the study of the cardiac anatomy and function in cardiac magnetic resonance (CMR) images. The first main contribution of the thesis is the development of a fully automatic cardiac segmentation technique that integrates and combines a series of state-of-the-art techniques. The proposed segmentation technique is capable of generating an accurate 3D segmentation from multiple image sequences. The proposed segmentation technique is robust even in the presence of pathological changes, large anatomical shape variations and locally varying contrast in the images. Another main contribution of this thesis is the development of motion tracking techniques that can integrate motion information from different sources. For example, the radial motion of the myocardium can be tracked easily in untagged MR imaging since the epi- and endocardial surfaces are clearly visible. On the other hand, tagged MR imaging allows easy tracking of both longitudinal and circumferential motion. We propose a novel technique based on non-rigid image registration for the myocardial motion estimation using both untagged and 3D tagged MR images. The novel aspect of our technique is its simultaneous use of complementary information from both untagged and 3D tagged MR imaging. The similarity measure is spatially weighted to maximise the utility of information from both images. The thesis also proposes a sparse representation for free-form deformations (FFDs) using the principles of compressed sensing. The sparse free-form deformation (SFFD) model can capture fine local details such as motion discontinuities without sacrificing robustness. We demonstrate the capabilities of the proposed framework to accurately estimate smooth as well as discontinuous deformations in 2D and 3D CMR image sequences. Compared to the standard FFD approach, a significant increase in registration accuracy can be observed in datasets with discontinuous motion patterns. Both the segmentation and motion tracking techniques presented in this thesis have been applied to clinical studies. We focus on two important clinical applications that can be addressed by the techniques proposed in this thesis. The first clinical application aims at measuring longitudinal changes in cardiac morphology and function during the cardiac remodelling process. The second clinical application aims at selecting patients that positively respond to cardiac resynchronization therapy (CRT). The final chapter of this thesis summarises the main conclusions that can be drawn from the work presented here and also discusses possible avenues for future research

Segmentation, tracking, and kinematics of lung parenchyma and lung tumors from 4D CT with application to radiation treatment planning.

This thesis is concerned with development of techniques for efficient computerized analysis of 4-D CT data. The goal is to have a highly automated approach to segmentation of the lung boundary and lung nodules inside the lung. The determination of exact lung tumor location over space and time by image segmentation is an essential step to track thoracic malignancies. Accurate image segmentation helps clinical experts examine the anatomy and structure and determine the disease progress. Since 4-D CT provides structural and anatomical information during tidal breathing, we use the same data to also measure mechanical properties related to deformation of the lung tissue including Jacobian and strain at high resolutions and as a function of time. Radiation Treatment of patients with lung cancer can benefit from knowledge of these measures of regional ventilation. Graph-cuts techniques have been popular for image segmentation since they are able to treat highly textured data via robust global optimization, avoiding local minima in graph based optimization. The graph-cuts methods have been used to extract globally optimal boundaries from images by s/t cut, with energy function based on model-specific visual cues, and useful topological constraints. The method makes N-dimensional globally optimal segmentation possible with good computational efficiency. Even though the graph-cuts method can extract objects where there is a clear intensity difference, segmentation of organs or tumors pose a challenge. For organ segmentation, many segmentation methods using a shape prior have been proposed. However, in the case of lung tumors, the shape varies from patient to patient, and with location. In this thesis, we use a shape prior for tumors through a training step and PCA analysis based on the Active Shape Model (ASM). The method has been tested on real patient data from the Brown Cancer Center at the University of Louisville. We performed temporal B-spline deformable registration of the 4-D CT data - this yielded 3-D deformation fields between successive respiratory phases from which measures of regional lung function were determined. During the respiratory cycle, the lung volume changes and five different lobes of the lung (two in the left and three in the right lung) show different deformation yielding different strain and Jacobian maps. In this thesis, we determine the regional lung mechanics in the Lagrangian frame of reference through different respiratory phases, for example, Phase10 to 20, Phase10 to 30, Phase10 to 40, and Phase10 to 50. Single photon emission computed tomography (SPECT) lung imaging using radioactive tracers with SPECT ventilation and SPECT perfusion imaging also provides functional information. As part of an IRB-approved study therefore, we registered the max-inhale CT volume to both VSPECT and QSPECT data sets using the Demon\u27s non-rigid registration algorithm in patient subjects. Subsequently, statistical correlation between CT ventilation images (Jacobian and strain values), with both VSPECT and QSPECT was undertaken. Through statistical analysis with the Spearman\u27s rank correlation coefficient, we found that Jacobian values have the highest correlation with both VSPECT and QSPECT

Multi-Modal Regualtion of Actin Networks

Eukaryotic cells employ the actin cytoskeleton to maintain cell shape, support motility, and sense and respond to external mechanical stimuli. An intricate network of actin filaments constitutes the foundation of tissue architecture by forming key cellular structures including the muscle fiber, the filopodium, the lamellipodium, and the cell cortex. Cellular and tissue level studies have shown that more than 150 actin-binding proteins regulate almost every single aspect of actin physiology, such as actin polymerization, actin severing, and actin crosslinking, but at the molecular level, the structural mechanisms by which different actin binding proteins bind, assemble, and regulate different actin networks remain largely elusive. It is also known that the actin cytoskeleton mediates mechanical coupling between eukaryotic cells and their tissue microenvironments. Although cellular and tissue level studies suggest the architecture and composition of actin networks are modulated by force, it is still unclear how interactions between actin filaments and associated proteins are mechanically regulated. Force-sensitive actin binding interactions are fundamental for cells to sense and respond to mechanical stimuli by converting mechanical cues into biochemical signals, a key process known as cellular mechanotransduction. In this thesis, single molecule biophysical techniques including simultaneous optical trapping and confocal microscopy assays and in vitro reconstituted myosin motor-based total internal reflection fluorescence microscopy assays were employed to study how mechanical forces applied on actin filaments can regulate actin binding. A case study on a homologous pair of essential adhesion actin-binding proteins, α-catenin and vinculin, reveals α-catenin directly senses force on actin, while vinculin does not. Near atomic-resolution cryo-electron microscopy structures of both proteins bound to Factin, structure-guided protein engineering, and ongoing nuclear magnetic resonance and force reconstitution cryo-electron microscopy studies demonstrate that α-catenin’s C-terminus is a modular detector of F-actin tension and suggest a force-sensing mechanism. Cryo-electron microscopy was also employed to study how adhesion actinbinding proteins and the calponin-homology domain actin-binding proteins assemble cellular actin networks by binding and crosslinking actin filaments. Actin binding by another essential adhesion actin-binding protein talin, and actin bundling by both α- catenin and vinculin were additionally structurally characterized. Using a unique calponin-homology domain actin-binding protein, T-plastin, as an example, the thesis established the structural mechanism by which T-plastin crosslinks actin filaments. In summary, with biochemical, biophysical, and structural methods, this thesis systematically studied the molecular mechanisms for the multi-modal regulation of actin networks by actin binding proteins

Semantic multimedia modelling & interpretation for annotation

The emergence of multimedia enabled devices, particularly the incorporation of cameras in mobile phones, and the accelerated revolutions in the low cost storage devices, boosts the multimedia data production rate drastically. Witnessing such an iniquitousness of digital images and videos, the research community has been projecting the issue of its significant utilization and management. Stored in monumental multimedia corpora, digital data need to be retrieved and organized in an intelligent way, leaning on the rich semantics involved. The utilization of these image and video collections demands proficient image and video annotation and retrieval techniques. Recently, the multimedia research community is progressively veering its emphasis to the personalization of these media. The main impediment in the image and video analysis is the semantic gap, which is the discrepancy among a user’s high-level interpretation of an image and the video and the low level computational interpretation of it. Content-based image and video annotation systems are remarkably susceptible to the semantic gap due to their reliance on low-level visual features for delineating semantically rich image and video contents. However, the fact is that the visual similarity is not semantic similarity, so there is a demand to break through this dilemma through an alternative way. The semantic gap can be narrowed by counting high-level and user-generated information in the annotation. High-level descriptions of images and or videos are more proficient of capturing the semantic meaning of multimedia content, but it is not always applicable to collect this information. It is commonly agreed that the problem of high level semantic annotation of multimedia is still far from being answered. This dissertation puts forward approaches for intelligent multimedia semantic extraction for high level annotation. This dissertation intends to bridge the gap between the visual features and semantics. It proposes a framework for annotation enhancement and refinement for the object/concept annotated images and videos datasets. The entire theme is to first purify the datasets from noisy keyword and then expand the concepts lexically and commonsensical to fill the vocabulary and lexical gap to achieve high level semantics for the corpus. This dissertation also explored a novel approach for high level semantic (HLS) propagation through the images corpora. The HLS propagation takes the advantages of the semantic intensity (SI), which is the concept dominancy factor in the image and annotation based semantic similarity of the images. As we are aware of the fact that the image is the combination of various concepts and among the list of concepts some of them are more dominant then the other, while semantic similarity of the images are based on the SI and concept semantic similarity among the pair of images. Moreover, the HLS exploits the clustering techniques to group similar images, where a single effort of the human experts to assign high level semantic to a randomly selected image and propagate to other images through clustering. The investigation has been made on the LabelMe image and LabelMe video dataset. Experiments exhibit that the proposed approaches perform a noticeable improvement towards bridging the semantic gap and reveal that our proposed system outperforms the traditional systems

Three Dimensional Tissue Motion Analysis from Tagged Magnetic Resonance Imaging

Motion estimation of soft tissues during organ deformation has been an important topic in medical imaging studies. Its application involves a variety of internal and external organs including the heart, the lung, the brain, and the tongue. Tagged magnetic resonance imaging has been used for decades to observe and quantify motion and strain of deforming tissues. It places temporary noninvasive markers—so called "tags"—in the tissue of interest that deform together with the tissue during motion, producing images that carry motion information in the deformed tagged patterns. These images can later be processed using phase-extraction algorithms to achieve motion estimation and strain computation. In this dissertation, we study three-dimensional (3D) motion estimation and analysis using tagged magnetic resonance images with applications focused on speech studies and traumatic brain injury modeling. Novel algorithms are developed to assist tagged motion analysis. Firstly, a pipeline of methods—TMAP—is proposed to compute 3D motion from tagged and cine images of the tongue during speech. TMAP produces an estimation of motion along with a multi-subject analysis of motion pattern differences between healthy control subjects and post-glossectomy patients. Secondly, an enhanced 3D motion estimation algorithm—E-IDEA—is proposed. E-IDEA tackles the incompressible motion both on the internal tissue region and the tissue boundaries, reducing the boundary errors and yielding a motion estimate that is more accurate overall. Thirdly, a novel 3D motion estimation algorithm—PVIRA—is developed. Based on image registration and tracking, PVIRA is a faster and more robust method that performs phase extraction in a novel way. Lastly, a method to reveal muscles' activity using strain in the line of action of muscle fiber directions is presented. It is a first step toward relating motion production with individual muscles and provides a new tool for future clinical and scientific use