Intelligent scanning: automated standard plane selection and biometric measurement of early gestational sac in routine ultrasound examination.

PURPOSE: To assist radiologists and decrease interobserver variability when using 2D ultrasonography (US) to locate the standardized plane of early gestational sac (SPGS) and to perform gestational sac (GS) biometric measurements. METHODS: In this paper, the authors report the design of the first automatic solution, called "intelligent scanning" (IS), for selecting SPGS and performing biometric measurements using real-time 2D US. First, the GS is efficiently and precisely located in each ultrasound frame by exploiting a coarse to fine detection scheme based on the training of two cascade AdaBoost classifiers. Next, the SPGS are automatically selected by eliminating false positives. This is accomplished using local context information based on the relative position of anatomies in the image sequence. Finally, a database-guided multiscale normalized cuts algorithm is proposed to generate the initial contour of the GS, based on which the GS is automatically segmented for measurement by a modified snake model. RESULTS: This system was validated on 31 ultrasound videos involving 31 pregnant volunteers. The differences between system performance and radiologist performance with respect to SPGS selection and length and depth (diameter) measurements are 7.5% ± 5.0%, 5.5% ± 5.2%, and 6.5% ± 4.6%, respectively. Additional validations prove that the IS precision is in the range of interobserver variability. Our system can display the SPGS along with biometric measurements in approximately three seconds after the video ends, when using a 1.9 GHz dual-core computer. CONCLUSIONS: IS of the GS from 2D real-time US is a practical, reproducible, and reliable approach.

Rapid rotational magneto-acousto-electrical tomography with filtered back-projection algorithm based on plane waves.

Magneto-acousto-electrical tomography (MAET) is designed to produce conductivity images with high spatial resolution for a conducting object. In a previous study, for an irregular conductor, transverse scanning and rotational methods with a focus transducer were combined to collect complete electrical information. This kind of method, however, is time-consuming because of the transverse scanning procedure. In this study, we proposed a novel imaging method based on plane ultrasound waves and a new aspect of projection in rotational MAET. In the proposed method, we achieved the projection in each rotation angle by using plane waves rather than mechanical scanning of the focus waves along the transverse direction. Thus, the imaging time was significantly saved. To verify the proposed method, we derived a measurement formula containing a lateral integration, which built the relationship between the measurement formula and the projection under each rotation angle. Next, we constructed two different numerical models to compute magneto-acousto-electrical signals by using a finite element method and reconstructed the corresponding conductivity parameter images based on a filtered back-projection algorithm. Then, simulated signals under different signal-to-ratios (6, 20, 40, and 60 dB) were generated to test the performance of the proposed algorithm. To improve the image quality, we further analysed the influence of the filters and the frequency scaling factors embedded in the filtered back-projection algorithm. Moreover, we computed the L2norm of the error in case of different frequency scaling factors and measurement noises. Finally, we conducted a phantom experiment with a 64-element linear phased array transducer (center frequency of 2.7 MHz) and reconstructed the conductivity parameter images of the circular phantom with an elliptical hole. The experimental results demonstrated the feasibility and time-efficiency of the proposed rapid rotational MAET.

Optimization of multi-angle Magneto-Acousto-Electrical Tomography (MAET) based on a numerical method.

Magneto-Acousto-Electrical Tomography (MAET) is a novel multi-physics imaging method, which promises to offer a unique biophysical property of tissue electrical impedance with the additional benefit of excellent spatial resolution of the ultrasonic imaging. It opens the potential for early diagnosis of cancer by revealing changes of dielectric characteristics. However, direct MAET is unable to image the irregularly-shaped lesions fully due to the dependence on the angle between conductivity boundary and ultrasound beam direction. In this paper, a numerical simulation of multi-angle MAET is presented for an improved image reconstruction for MAET in order to discern irregularly-shaped tumors in different positions. The results show that the conductivity boundary interfaces are invisible in single angle B-mode reconstructed image, wherever the ultrasound beam and conductivity boundary are nearly parallel. When the multi-angle scanning was adopted, the image reconstructed with image rotation method reproduced the original object pattern. Furthermore, the relationship between reconstruction error and the number of angles was also discussed. It is found that 12 angles would be necessary to achieve nearly the optimal reconstruction. Finally, reconstructed images in L2 norm of the error with the measurement noise are presented.

Focused ultrasound-induced stimulation of microbubbles augments site-targeted engraftment of mesenchymal stem cells after acute myocardial infarction.

Intravascular transplantation of bone marrow-derived mesenchymal stem cells (MSCs) is a promising therapeutic approach after acute myocardial infarction. Efficacy and targeting of myocardial cell engraftment are crucial variables determining the therapeutic value of MSC transplantation. Highly focused ultrasound-mediated stimulation of microbubbles (hf-UMS) allows locoregional pre-treatment of target tissue. In a "proof of concept" study, we investigated augmentation of site-targeted MSC engraftment with hf-UMS. We further evaluated the ability of transplanted MSCs to transmigrate across the endothelial barrier into non-ischemic and post-ischemic myocardium in vivo. After acute myocardial ischemia and reperfusion, rats received hf-UMS focused on the anterior left-ventricular wall followed by intravascular transplantation of MSCs. Global and regional myocardial engraftment of MSCs was quantified by means of confocal laser-scanning microscopy; endothelial adhesion, transendothelial migration and invasion of basement membrane were distinguished. Targeted myocardium exhibited higher amount of transplanted MSCs vs. non-targeted tissue. The rate of transendothelial migration was lowest in non-ischemic (41.2+/-2%) compared to post-ischemic myocardium (53+/-5.7%, p<0.01). Hf-UMS significantly increased the transmigration rate to 50+/-6.1% (p<0.05) and 64+/-8.9% (p<0.05), respectively. Additionally, myocardial segments exposed to hf-UMS revealed an onset of protease activity. Signs of undesired biological effects, such as induction of apoptosis and/or myocardial necrosis were not observed. This study provides the first evidence of the migration of MSCs across the myocardial endothelium in vivo. Hf-UMS not only improves myocardial engraftment of MSCs but also allows locoregional targeting of post-ischemic myocardium.

"Compression-only" behavior of phospholipid-coated contrast bubbles.

Ultrasound contrast agents oscillate approximately linearly up to a certain pressure range where nonlinearity sets in. Nonlinear microbubble oscillations are exploited in ultrasound pulse-echo imaging as this improves the contrast-to-tissue ratio. Here we report the observation of a highly nonlinear response of phospholipid-coated contrast agents at pressures as low as 50 kPa, termed "compression-only" behavior, where the microbubbles only compress, yet hardly expand. Time-resolved bubble dynamics recorded through ultra high-speed imaging revealed that nearly 40% of the coated bubbles show "compression-only" behavior.

Delivery of Liposomes with Different Sizes to Mice Brain after Sonication by Focused Ultrasound in the Presence of Microbubbles.

Imaging or therapeutic agents larger than the blood-brain barrier's (BBB) exclusion threshold of 400 Da could be delivered locally, non-invasively and reversibly by focused ultrasound (FUS) with circulating microbubbles. The size of agents is an important factor to the delivery outcome using this method. Liposomes are important drug carriers with controllable sizes in a range of nanometers. However, discrepancies among deliveries of intact liposomes with different sizes, especially those larger than 50 nm, across the BBB opened by FUS with microbubbles remain unexplored. In the present study, rhodamine-labeled long-circulating pegylated liposomes with diameters of 55 nm, 120 nm and 200 nm were delivered to mice brains after BBB disruption by pulsed FUS with microbubbles. Four groups of peak rarefactional pressure and microbubble dosages were used: 0.53 MPa with 0.1 µL/g (group 1), 0.53 MPa with 0.5 µL/g (group 2), 0.64 MPa with 0.1 µL/g (group 3) and 0.64 MPa with 0.5 µL/g (group 4). The delivery outcome was observed using fluorescence imaging of brain sections. It was found that the delivery of 55-nm liposomes showed higher success rates than 120-nm or 200-nm liposomes from groups 1-3. The result indicated that it may be more difficult to deliver larger liposomes (>120 nm) passively than 55-nm liposomes after BBB opening by FUS with microbubbles. The relative fluorescence area of 55-nm liposomes to the total area of the sonicated region was statistically larger than that of the 120-nm or 200-nm liposomes. Increasing peak rarefactional pressure amplitude or microbubble dose could induce more accumulation of liposomes in the brain using FUS with microbubbles. Moreover, the distribution pattern of delivered liposomes was heterogeneous and characterized by separated fluorescence spots with cloud-like periphery surrounding a bright center, indicating confined diffusion in the extracellular matrix after extravasation from the microvasculature. These findings are expected to provide useful information for developing FUS with microbubbles as an effective trans-BBB liposomal drug delivery strategy.

Optimising phase and amplitude modulation schemes for imaging microbubble contrast agents at low acoustic power.

A series of in vitro experiments were performed to determine the efficacy of generalised phase- and amplitude-modulated sequences for low-power nonlinear microbubble contrast imaging. The microbubble agent Definity (Dupont, Boston, MA) was exposed to sequences in which the phase and amplitude were changed from one pulse to the next. Echoes from these pulses were combined to suppress or enhance particular linear or nonlinear components. The results show that established two-pulse pulse-inversion and amplitude-modulation approaches perform similarly, providing 14 +/- 1 dB of enhancement, compared with the echoes from the linear scatterer. A two-pulse combined phase and amplitude sequence achieved an additional 4 +/- 1 dB of enhancement. This improvement is due to improved preservation of second and third order harmonic signals, while maintaining the suppression of the linear signals. These results were obtained at low power, below the threshold of microbubble destruction, and are applicable to real-time perfusion imaging.

Harmonic chirp imaging method for ultrasound contrast agent.

Coded excitation is currently used in medical ultrasound to increase signal-to-noise ratio (SNR) and penetration depth. We propose a chirp excitation method for contrast agents using the second harmonic component of the response. This method is based on a compression filter that selectively compresses and extracts the second harmonic component from the received echo signal. Simulations have shown a clear increase in response for chirp excitation over pulse excitation with the same peak amplitude. This was confirmed by two-dimensional (2-D) optical observations of bubble response with a fast framing camera. To evaluate the harmonic compression method, we applied it to simulated bubble echoes, to measured propagation harmonics, and to B-mode scans of a flow phantom and compared it to regular pulse excitation imaging. An increase of approximately 10 dB in SNR was found for chirp excitation. The compression method was found to perform well in terms of resolution. Axial resolution was in all cases within 10% of the axial resolution from pulse excitation. Range side-lobe levels were 30 dB below the main lobe for the simulated bubble echoes and measured propagation harmonics. However, side-lobes were visible in the B-mode contrast images.

Nonlinear coded excitation method for ultrasound contrast imaging.

Coded excitation with compression on receive is used in medical ultrasound (US) imaging to increase signal-to-noise ratio (SNR) and penetration depth. We performed a computer simulation study to investigate if chirped pulse excitation can be applied in US contrast agent imaging to increase SNR and contrast-to-tissue ratio (CTR) and, thus, reduce contrast agent destruction and tissue harmonics. A new nonlinear compression technique is proposed that selectively compresses the second harmonic component of the response. We compared a chirp of 9.4-micros duration, 2-MHz centre frequency, 45% relative bandwidth to a Gaussian pulse with equal centre frequency and bandwidth. For peak pressures between 50 and 300 kPa, we found for resonant bubbles an increase in response between 10 and 13 dB. Moreover, the axial resolution after compression was comparable to axial resolution of conventional imaging. This effect was relatively insensitive to peak excitation pressure and was largest for bubbles having resonance frequency around the centre frequency of the excitation.

Cytoplasm segmentation on cervical cell images using graph cut-based approach.

This paper proposes a method to segment the cytoplasm in cervical cell images using graph cut-based algorithm. First, the A* channel in CIE LAB color space is extracted for contrast enhancement. Then, in order to effectively extract cytoplasm boundaries when image histograms present non-bimodal distribution, Otsu multiple thresholding is performed on the contrast enhanced image to generate initial segments, based on which the segments are refined by the multi-way graph cut method. We use 21 cervical cell images with non-ideal imaging condition to evaluate cytoplasm segmentation performance. The proposed method achieved a 93% accuracy which outperformed state-of-the-art works.

Segmentation of cytoplasm and nuclei of abnormal cells in cervical cytology using global and local graph cuts.

Automation-assisted reading (AAR) techniques have the potential to reduce errors and increase productivity in cervical cancer screening. The sensitivity of AAR relies heavily on automated segmentation of abnormal cervical cells, which is handled poorly by current segmentation algorithms. In this paper, a global and local scheme based on graph cut approach is proposed to segment cervical cells in images with a mix of healthy and abnormal cells. For cytoplasm segmentation, the multi-way graph cut is performed globally on the a* channel enhanced image, which can be effective when the image histogram presents a non-bimodal distribution. For segmentation of nuclei, especially when they are abnormal, we propose to use graph cut adaptively and locally, which allows the combination of intensity, texture, boundary and region information. Two concave points-based approaches are integrated to split the touching-nuclei. As part of an ongoing clinical trial, preliminary validation results obtained from 21 cervical cell images with non-ideal imaging condition and pathology show that our segmentation method achieved 93% accuracy for cytoplasm, and 88.4% F-measure for abnormal nuclei, outperforming state of the art methods in terms of accuracy. Our method has the potential to improve the sensitivity of AAR in screening for cervical cancer.

Standard plane localization in ultrasound by radial component model and selective search.

Acquisition of the standard plane is crucial for medical ultrasound diagnosis. However, this process requires substantial experience and a thorough knowledge of human anatomy. Therefore it is very challenging for novices and even time consuming for experienced examiners. We proposed a hierarchical, supervised learning framework for automatically detecting the standard plane from consecutive 2-D ultrasound images. We tested this technique by developing a system that localizes the fetal abdominal standard plane from ultrasound video by detecting three key anatomical structures: the stomach bubble, umbilical vein and spine. We first proposed a novel radial component-based model to describe the geometric constraints of these key anatomical structures. We then introduced a novel selective search method which exploits the vessel probability algorithm to produce probable locations for the spine and umbilical vein. Next, using component classifiers trained by random forests, we detected the key anatomical structures at their probable locations within the regions constrained by the radial component-based model. Finally, a second-level classifier combined the results from the component detection to identify an ultrasound image as either a "fetal abdominal standard plane" or a "non- fetal abdominal standard plane." Experimental results on 223 fetal abdomen videos showed that the detection accuracy of our method was as high as 85.6% and significantly outperformed both the full abdomen and the separate anatomy detection methods without geometric constraints. The experimental results demonstrated that our system shows great promise for application to clinical practice.

Targeted ultrasound-mediated delivery of nanoparticles: on the development of a new HIFU-based therapy and imaging device.

Ultrasound-mediated delivery (USMD) is an active research topic, as researchers develop applications for therapeutic ultrasound in addition to thermal ablation. In USMD, ultrasound is used in conjunction with microbubbles and drugs, nanoparticles, siRNA, pDNA, stem cells, etc., to facilitate their cellular delivery and uptake using pressure and temperature-mediated mechanisms to bring about a desired therapeutic effect. To investigate the potential of targeted USMD of nanoparticles, pDNA, and stem cells for cardiovascular and other applications, a general-purpose preclinical research tool, therapy imaging probe system (TIPS) was designed. It consists of a wideband annular array, a small-animal acoustic coupler, a motorized positioning system, integrated control software for ultrasound image-guided treatment planning and execution, and triggering electronics that allow ECG and respiration-gated ultrasound exposures. TIPS was then used to enhance delivery of nanoparticles into the murine myocardium and heart vessel walls to demonstrate the feasibility of the technology, pave the way for additional basic research in cardiovascular USMD, and begin to explore the requirements that USMD devices will have to meet to be useful in a clinical setting.