Computer aided diagnosis of Coronary Artery Disease,Myocardial Infarction and carotid atherosclerosis using ultrasound images: A review

The diagnosis of Coronary Artery Disease (CAD), Myocardial Infarction (MI) and carotid atherosclerosis is of paramount importance, as these cardiovascular diseases may cause medical complications and large number of death. Ultrasound (US) is a widely used imaging modality, as it captures moving images and image features correlate well with results obtained from other imaging methods. Furthermore, US does not use ionizing radiation and it is economical when compared to other imaging modalities. However, reading US images takes time and the relationship between image and tissue composition is complex. Therefore, the diagnostic accuracy depends on both time taken to read the images and experience of the screening practitioner. Computer support tools can reduce the inter-operator variability with lower subject specific expertise, when appropriate processing methods are used. In the current review, we analysed automatic detection methods for the diagnosis of CAD, MI and carotid atherosclerosis based on thoracic and Intravascular Ultrasound (IVUS). We found that IVUS is more often used than thoracic US for CAD. But for MI and carotid atherosclerosis IVUS is still in the experimental stage. Furthermore, thoracic US is more often used than IVUS for computer aided diagnosis systems.     

Multiplexed Nanometric 3D Tracking of Microbeads Using an FFT-Phasor Algorithm

Many single-molecule biophysical techniques rely on nanometric tracking of microbeads to obtain quantitative information about the mechanical properties of biomolecules such as chromatin fibers. Their three-dimensional (3D) position can be resolved by holographic analysis of the diffraction pattern in wide-field imaging. Fitting this diffraction pattern to Lorenz-Mie scattering theory yields the bead’s position with nanometer accuracy in three dimensions but is computationally expensive. Real-time multiplexed bead tracking therefore requires a more efficient tracking method, such as comparison with previously measured diffraction patterns, known as look-up tables. Here, we introduce an alternative 3D phasor algorithm that provides robust bead tracking with nanometric localization accuracy in a z range of over 10 μm under nonoptimal imaging conditions. The algorithm is based on a two-dimensional cross correlation using fast Fourier transforms with computer-generated reference images, yielding a processing rate of up to 10,000 regions of interest per second. We implemented the technique in magnetic tweezers and tracked the 3D position of over 100 beads in real time on a generic CPU. The accuracy of 3D phasor tracking was extensively tested and compared to a look-up table approach using Lorenz-Mie simulations, avoiding experimental uncertainties. Its easy implementation, efficiency, and robustness can improve multiplexed biophysical bead-tracking applications, especially when high throughput is required and image artifacts are difficult to avoid.     

Ultrasound tracking for intra-fractional motion compensation in radiation therapy

Modern techniques as ion beam therapy or 4D imaging require precise target position information. However, target motion particularly in the abdomen due to respiration or patient movement is still a challenge and demands methods that detect and compensate this motion. Ultrasound represents a non-invasive, dose-free and model-independent alternative to fluoroscopy, respiration belt or optical tracking of the patient surface. Thus, ultrasound based motion tracking was integrated into irradiation with actively scanned heavy ions. In a first in vitro experiment, the ultrasound tracking system was used to compensate diverse sinusoidal target motions in two dimensions. A time delay of ∼200 ms between target motion and reported position data was compensated by a prediction algorithm (artificial neural network). The irradiated films proved feasibility of the proposed method. Furthermore, a practicable and reliable calibration workflow was developed to enable the transformation of ultrasound tracking data to the coordinates of the treatment delivery or imaging system – even if the ultrasound probe moves due to respiration. A first proof of principle experiment was performed during time-resolved positron emission tomography (4DPET) to test the calibration workflow and to show the accuracy of an ultrasound based motion tracking in vitro. The results showed that optical ultrasound tracking can reach acceptable accuracies and encourage further research.     

Advances in fluorescent tracking of nucleic acids in living cells

Nucleic acids are typically detected in morphologically preserved fixed cells and tissues using in situ hybridization techniques. This review discusses a variety of established and more challenging fluorescence-based methods for the detection and tracking of DNA or RNA sequences in living cells. Over the past few years, various fluorescent in vivo labeling methods have been developed, and dedicated microscope and image analysis tools have been designed. These advances in technologies indicate that live-cell imaging of nucleic acids is likely to become a standard research tool for understanding genome organization and gene expression regulation in the near future. Recent live-cell imaging studies have already provided important insights into the dynamic behaviors of chromatin and RNAs in the cell.     

Concurrent Visualization of Acoustic Radiation Force Displacement and Shear Wave Propagation with 7T MRI

Manual palpation is a common and very informative diagnostic tool based on estimation of changes in the stiffness of tissues that result from pathology. In the case of a small lesion or a lesion that is located deep within the body, it is difficult for changes in mechanical properties of tissue to be detected or evaluated via palpation. Furthermore, palpation is non-quantitative and cannot be used to localize the lesion. Magnetic Resonance-guided Focused Ultrasound (MRgFUS) can also be used to evaluate the properties of biological tissues non-invasively. In this study, an MRgFUS system combines high field (7T) MR and 3 MHz focused ultrasound to provide high resolution MR imaging and a small ultrasonic interrogation region (~0.5 x 0.5 x 2 mm), as compared with current clinical systems. MR-Acoustic Radiation Force Imaging (MR-ARFI) provides a reliable and efficient method for beam localization by detecting micron-scale displacements induced by ultrasound mechanical forces. The first aim of this study is to develop a sequence that can concurrently quantify acoustic radiation force displacements and image the resulting transient shear wave. Our motivation in combining these two measurements is to develop a technique that can rapidly provide both ARFI and shear wave velocity estimation data, making it suitable for use in interventional radiology. Secondly, we validate this sequence in vivo by estimating the displacement before and after high intensity focused ultrasound (HIFU) ablation, and we validate the shear wave velocity in vitro using tissue-mimicking gelatin and tofu phantoms. Such rapid acquisitions are especially useful in interventional radiology applications where minimizing scan time is highly desirable.     

Real-time detection of vessel diameters with ultrasound.

Transcutaneous vessel imaging is a frequently used ultrasound imaging modality in medicine. The measurement of vessel diameters can be done with conventional B-mode imaging systems, which work at frame rates up to 100 Hz. Furthermore, there are special systems available, which can track vessel walls very precisely using the phase of signals that are sent at frame rates up to several thousand Hz. Though, such systems are usually not able to provide the examiner with 2D images of the object. With respect to brachial artery flow-mediated vasodilatation (FMD), which is frequently used as a measure of endothelial function, it is necessary to observe diameter changes of small arterial vessels noninvasively for several minutes at a high resolution. In the past, the diameter had to be measured manually in tedious postprocessing of ECG-gated image sequences. We developed a system composed of a Siemens Omnia ultrasound system with a VF13-5 transducer (9 MHz center frequency) and a personal computer, that is capable of calculating vessel diameter changes with an accuracy below the wavelength of the ultrasound system in real-time at a frame rate of 27 Hz. We implemented a two-dimensional active contour model using the Viter-bi-algorithm and a phase-sensitive vessel wall tracking algorithm, in order to guarantee both, geometric information and accuracy. Results from carotid and brachial arteries show that arterial pulsations below 0.1 mm can be visualized reliably over several minutes. With this system we want to find out, if FMD is suitable for an individual assessment of the risk for cardiovascular diseases.     

Role of visual control during percutaneous sclerosing therapy for soft tissue arteriovenous dysplasias

Based on the current concept of the obvious prevalence of surgical treatment of vascular angiodysplasias over low-invasive methods of interventional radiology, the author assesses the capacities of sclerotic therapy performed by the improved visual controlling procedure. By using the well-known semiotics of ultrasound studies of angiodysplasias, the author has made significant methodological amendments to the techniques of sclerotic therapy. The principle of the proposed procedure is a result of complex use of the potentialities of ultrasound visualization and interventional X-ray contrast studies of the vascular system. The procedure was successfully used in 9 patients. It is concluded that that the study of soft tissue angiodysplasias via direct puncture performed under ultrasound guidance, followed by mass contrasting and sclerotic therapy.     

Reliability and accuracy of an automated tracking algorithm to measure controlled passive and active muscle fascicle length changes from ultrasound

Manual tracking of muscle fascicle length changes from ultrasound images is a subjective and time-consuming process. The purpose of this study was to assess the repeatability and accuracy of an automated algorithm for tracking fascicle length changes in the medial gastrocnemius (MG) muscle during passive length changes and active contractions (isometric, concentric and eccentric) performed on a dynamometer. The freely available, automated tracking algorithm was based on the Lucas–Kanade optical flow algorithm with an affine optic flow extension, which accounts for image translation, dilation, rotation and shear between consecutive frames of an image sequence. Automated tracking was performed by three experienced assessors, and within- and between-examiner repeatability was computed using the coefficient of multiple determination (CMD). Fascicle tracking data were also compared with manual digitisation of the same image sequences, and the level of agreement between the two methods was calculated using the coefficient of multiple correlation (CMC). The CMDs across all test conditions ranged from 0.50 to 0.93 and were all above 0.98 when recomputed after the systematic error due to the estimate of the initial fascicle length on the first ultrasound frame was removed from the individual fascicle length waveforms. The automated and manual tracking approaches produced similar fascicle length waveforms, with an overall CMC of 0.88, which improved to 0.94 when the initial length offset was removed. Overall results indicate that the automated fascicle tracking algorithm was a repeatable, accurate and time-efficient method for estimating fascicle length changes of the MG muscle in controlled passive and active conditions.     

Tendon strain measurements with dynamic ultrasound images: evaluation of digital image correlation

Strain is an essential metric in tissue mechanics. Strains and strain distributions during functional loads can help identify damaged and pathologic regions as well as quantify functional compromise. Noninvasive strain measurement in vivo is difficult to perform. The goal of this in vitro study is to determine the efficacy of digital image correlation (DIC) methods to measure strain in B-mode ultrasound images. The Achilles tendons of eight male Wistar rats were removed and mechanically cycled between 0 and 1% strain. Three cine video images were captured for each specimen: (1) optical video for manual tracking of optical markers; (2) optical video for DIC tracking of optical surface markers; and (3) ultrasound video for DIC tracking of image texture within the tissue. All three imaging modalities were similarly able to measure tendon strain during cyclic testing. Manual/ImageJ-based strain values linearly correlated with DIC (optical marker)-based strain values for all eight tendons with a slope of 0.970. DIC (optical marker)-based strain values linearly correlated with DIC (ultrasound texture)-based strain values for all eight tendons with a slope of 1.003. Strain measurement using DIC was as accurate as manual image tracking methods, and DIC tracking was equally accurate when tracking ultrasound texture as when tracking optical markers. This study supports the use of DIC to calculate strains directly from the texture present in standard B-mode ultrasound images and supports the use of DIC for in vivo strain measurement using ultrasound images without additional markers, either artificially placed (for optical tracking) or anatomically in view (i.e., bony landmarks and/or muscle-tendon junctions).     

Localizing protein-protein interactions by bimolecular fluorescence complementation in planta

The application of novel assays for basic cell research is tightly linked to the development of easy-to-use and versatile tools and protocols for implementing such technologies for a wide range of applications and model species. The bimolecular fluorescence complementation (BiFC) assay is one such novel method for which tools and protocols for its application in plant cell research are still being developed. BiFC is a powerful tool which enables not only detection, but also visualization and subcellular localization of protein–protein interactions in living cells. Here we describe the application of BiFC in plant cells while focusing on the use of our versatile set of vectors which were specifically designed to facilitate the transformation, expression and imaging of protein–protein interactions in various plant species. We discuss the considerations of using our system in various plant model systems, the use of single versus multiple expression cassettes, the application of our vectors using various transformation methods and the use of internal fluorescent markers which can assist in signal localization and easy data acquisition in living cells.     

Creating new fluorescent probes for cell biology

Fluorescent probes are one of the cornerstones of real-time imaging of live cells and a powerful tool for cell biologists. They provide high sensitivity and great versatility while minimally perturbing the cell under investigation. Genetically-encoded reporter constructs that are derived from fluorescent proteins are leading a revolution in the real-time visualization and tracking of various cellular events. Recent advances include the continued development of 'passive' markers for the measurement of biomolecule expression and localization in live cells, and 'active' indicators for monitoring more complex cellular processes such as small-molecule-messenger dynamics, enzyme activation and protein-protein interactions.     

Clinical versus ultrasound examination in the evaluation of hepatosplenic schistosomiasis mansoni in endemic areas

The best way to appraise the size of abdominal organs remains undefined. Herein we compare the size of liver and spleen in hepatosplenic schistosomiasis using clinical and ultrasound (US) examination, and the size of the organs measured by US with their visualization below the costal margin ("palpable by US"). For this study, 411 individuals from an endemic area for schistosomiasis mansoni in Brazil have been selected. We found that palpable spleens and left liver lobes are larger than non palpable ones. Also, 23% of normal spleens measured by US were palpable on clinical examination, and 22% of spleens increased in size on US were non palpable. A total of 21% of normal spleens were "palpable by US". We also found 54% of normal sized right liver lobes palpable on clinical examination, whilst 54% of the increased livers, measured by US, were non palpable. About 76% of normal right liver lobes were "palpable by US". We conclude that the association of clinical, ultrasound and magnetic resonance imaging (MRI) examinations, in the near future, should give the investigators the necessary tools to perform a more accurate clinical diagnosis of hepatosplenic schistosomiasis mansoni.     

Pan and sentinel lymph node visualization using a near-infrared fluorescent probe

A number of different types of agents have been employed to aid in the visualization of lymph nodes, particularly the sentinel lymph node, and to decrease the tissue destruction associated with the diagnosis of nodal metastases. The current study was performed to see if a novel macromolecular near-infrared fluorescent (NIRF) probe could be used to visualize lymph nodes after intravenous administration (pan-node visualization) or subcutaneous administration (sentinel node visualization), and serve as method for guiding dissection with interventional radiologic and surgical procedures. Cy5.5-PGC, the near-infrared dye Cy5.5 coupled to a protected graft copolymer (PGC), was injected (i.v. or s.c.) into nude mice. Twenty-four hours later white light and NIRF images were obtained on (i) the live animal, (ii) a partially dissected animal, and (iii) tissue specimens. With Cy5.5-PGC administered intravenously, axillary nodes were visualized from outside a living mouse. With partial dissection, iliac and aortic nodes were visible as concentrated foci of high-intensity NIRF signals. With subcutaneous injection in the front extremity, axillary and brachial nodes draining the injection site were easily visualized. NIRF imaging provides a nonradioactive method of visualizing lymph nodes through layers of tissue that can be employed with intravenous or subcutaneous injection.     

Tracking a protein following dissociation from a protein–protein complex using a split SNAP-tag system

Protein–protein interactions (PPIs) are important for various biological processes in living cells. Several methods have been developed for the visualization of PPIs in vivo; however, these methods are unsuitable for visualization of post-PPI events such as dissociation and translocation. In this study, we applied a split SNAP-tag system for the visualization of post-PPI events. This method enabled tracking of the protein following dissociation from the protein–protein complex. Thus, the split SNAP-tag system should prove to be a useful tool for visualization of post-PPI events.     

The Detection of Preoperative Parathyroid Lesions: The Success of Ultrasonography,Technetium-99m Methoxyisobutylisonitrile Parathyroid Scintigraphy,and Single-Photon Emission Computed Tomography–Computed Tomography

ObjectiveWe aimed to find and compare the efficacy of ultrasonography (US), technetium-99m methoxyisobutylisonitrile parathyroid scintigraphy (MIBI-S), and single-photon emission computed tomography–computed tomography (SPECT-CT) in detecting the localization of parathyroid adenomas in patients with primary hyperparathyroidism.MethodsIn total, 348 patients were included in this study. Preoperative parathyroid imaging with US, MIBI-S, and SPECT-CT was evaluated and compared with operative findings. The results of the imaging methods were compared with pathology and operation reports.ResultsIn 318 patients (91.3%), one of the imaging methods was able to localize the lesion correctly. US detected the localization of the parathyroid lesions correctly in 268 patients (77%), whereas SPECT-CT and MIBI-S were correct in 254 (73%) and 209 (60%) patients, respectively. There was a statistically significant relationship between the parathyroid hormone (PTH) level and 3 imaging methods’ success rates (P < .05). The PTH cut-off value, which best determined the correct localization, was 152.5 pg/mL for US, 143 pg/mL for MIBI-S, and 143 pg/mL for SPECT-CT. It was observed that the correct localization rate for parathyroid lesions increased with higher PTH levels.ConclusionIn our study population, US was more successful, in most cases, than other imaging methods in localizing parathyroid lesions but SPECT-CT was more accurate in localizing mediastinal lesions. In addition, it was found that preoperative PTH levels affect the accuracy of imaging methods.     

Augmenting intraoperative ultrasound with preoperative magnetic resonance planning models for percutaneous renal access

ABSTRACT: BACKGROUND: Ultrasound (US) is a commonly-used intraoperative imaging modality for guiding percutaneous renal access (PRA). However, the anatomy identification and target localization abilities of the US imaging are limited. This paper evaluates the feasibility and efficiency of a proposed image-guided PRA by augmenting the intraoperative US with preoperative magnetic resonance (MR) planning models. METHODS: First, a preoperative surgical planning approach is presented to define an optimal needle trajectory using MR volume data. Then, a MR to US registration is proposed to transfer the preoperative planning into the intraoperative context. The proposed registration makes use of orthogonal US slices to avoid local minima while reduce processing time. During the registration, a respiratory gating method is used to minimize the impact of kidney deformation. By augmenting the intraoperative US with preoperative MR models and a virtual needle, a visual guidance is provided to guarantee the correct execution of the surgical planning. The accuracy, robustness and processing time of the proposed registration were evaluated by four urologists on human data from four volunteers. Furthermore, the PRA experiments were performed by the same four urologists on a kidney phantom. The puncture accuracy in terms of the needle-target distance was measured, while the perceptual quality in using the proposed image guidance was evaluated according to custom scoring method. RESULTS: The mean registration accuracy in terms of the root mean square (RMS) target registration error (TRE) is 3.53mm. The RMA distance from the registered feature points to their average is 0.81mm. The mean operating time of the registration is 6'4". In the phantom evaluation, the mean needle-target distance is 2.08mm for the left lesion and 1.85mm for the right one. The mean duration for all phantom PRA tests was 4'26". According to the custom scoring method, the mean scores of the Intervention Improvement, Workflow Impact, and Clinical Relevance were 4.0, 3.3 and 3.9 respectively. CONCLUSIONS: The presented image guidance is feasible and promising for PRA procedure. With careful setup it can be efficient for overcoming the limitation of current US-guided PRA.     

Closed-chest cell injections into mouse myocardium guided by high-resolution echocardiography

The mouse is an important model for the development of therapeutic stem cell/bone marrow cell implantation to treat ischemic myocardium. However, its small heart size hampers accurate implantation into the left ventricular (LV) wall. Precise injections have required surgical visualization of the heart, which is subject to complications and is impractical for delayed or repeated injections. Furthermore, the thickness of the myocardium is comparable to the length of a needle bevel, so surgical exposure does not prevent inadvertent injection into the LV cavity. We describe the use of high-resolution echocardiography to guide nonsurgical injections accurately into the mouse myocardial wall. We optimized this system by using a mixture of ultrasound contrast and fluorescent microspheres injected into the myocardium, which enabled us to interpret the ultrasound image of the needle during injection. Quantitative dye injection studies demonstrated that guided closed-chest injections and open-chest injections deliver comparable amounts of injectate to the myocardium. We successfully used this system in a mouse myocardial infarction model to target the injection of labeled cells to a region adjacent to the infarct. Intentional injection of tracer into the LV cavity resulted in a small accumulation in the myocardium, suggesting that non-guided cell injections into mouse hearts may appear to be successful even if the majority of the injectate is lost in the chamber. The use of this system will allow more precise cellular implantation into the mouse myocardium by accurately guiding injections to desired locations, confirming successful implantation of cells, in a clinically relevant time frame.     

Ultrasound-driven cardiac MRI

PurposeOne of the challenges of cardiac MR imaging is the compensation of respiratory motion, which causes the heart and the surrounding tissues to move. Commonly-used methods to overcome this effect, breath-holding and MR navigation, present shortcomings in terms of available acquisition time or need to periodically interrupt the acquisition, respectively. In this work, an implementation of respiratory motion compensation that obtains information from abdominal ultrasound and continuously adapts the imaged slice position in real time is presented.MethodsA custom workflow was developed, comprising an MR-compatible ultrasound acquisition system, a feature-motion-tracking system with polynomial predictive capability, and a custom MR sequence that continuously adapts the position of the acquired slice according to the tracked position. The system was evaluated on a moving phantom by comparing sharpness and image blurring between static and moving conditions, and in vivo by tracking the motion of the blood vessels of the liver to estimate the cardiac motion. Cine images of the heart were acquired during free breathing.ResultsIn vitro, the predictive motion correction yielded significantly better results than non-predictive or non-corrected acquisitions (p ≪ 0.01). In vivo, the predictive correction resulted in an image quality very similar to the breath-hold acquisition, whereas the uncorrected images show noticeable blurring artifacts.ConclusionIn this work, the possibility of using ultrasound navigation with tracking for the real-time adaptation of MR imaging slices was demonstrated. The implemented technique enabled efficient imaging of the heart with resolutions that would not be feasible in a single breath-hold.