Blood-Brain Barrier (BBB) can be opened locally, noninvasively and reversibly by low frequency focused ultra-sound (FUS) in the presence of microbubbles. In this study, Evans blue (EB) dye extravasation across BBB was enhanced by 1 MHz FUS at acoustic pressure of 0.35 MPa in the presence of microbubbles at clinically comparable dosage. The spatial distribution of EB extravasation was visualized using fluorescence imaging method. The center region of BBB disruption area showed more enhanced fluorescence signal than the surrounding region in general. However, EB dye deposition was heterogeneous in the center region. The findings in this study indicated potential use of fluorescence imaging to evaluate large molecules delivery across BBB.
Currently, placental maturity staging is mainly based on subjective observation of the physician. To address this issue, a new method is proposed for automatic staging of placental maturity based on B-mode ultrasound images. Due to small variations in the placental images, dense descriptor is utilized in place of the sparse descriptor to boost performance. Dense sampled DAISY descriptor is investigated for the demonstrated scale and translation invariant properties. Moreover, the extracted dense features are encoded by vector locally aggregated descriptor (VLAD) for performance boosting. The experimental results demonstrate an accuracy of 0.874, a sensitivity of 0.996 and a specificity of 0.874 for placental maturity staging. The experimental results also show that the dense features outperform the sparse features.
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.
The shear stress exerted on the cell membrane is an important factor in sonoporation. However, almost all previous calculations of shear stress were based on the Rooney's assumption, which is not applicable for the sonoporation experiments. In the article, to construct the microstreaming-shear stress model in sonoporation, it theoretically analyzed the microstreaming-shear stress exerted on the cell membrane generated by oscillating microbubble based on Nyborg's acoustic streaming theory. And the response of the model was compared with that of the sonoporation experiment. Cells were exposed by 1MHz 150 kPa ultrasound in the presence of SonoVue® microbubbles. The sonoporated cells were labeled by fluorescent markers and detected by fluorescence microscopy and flow cytometry. The theoretically analyzed microstreaming-shear stress was in accordance with the cell experimental result. Although some minor factors are ignored when building the model to calculate the microstreaming-shear stress, the model was still reasonable.
This paper describes a new method for shear wave velocity estimation that is capable of extruding outliers automatically without preset threshold. The proposed method is an adaptive random sample consensus (ARANDSAC) and the metric used here is finding the certain percentage of inliers according to the closest distance criterion. To evaluate the method, the simulation and phantom experiment results were compared using linear regression with all points (LRWAP) and radon sum transform (RS) method. The assessment reveals that the relative biases of mean estimation are 20.00%, 4.67% and 5.33% for LRWAP, ARANDSAC and RS respectively for simulation, 23.53%, 4.08% and 1.08% for phantom experiment. The results suggested that the proposed ARANDSAC algorithm is accurate in shear wave speed estimation.
Ultrasonic elastography, a non-invasive technique for assessing the elasticity properties of tissues, has shown promising results for disease diagnosis. However, biological soft tissues are viscoelastic in nature. Shearwave dispersion ultrasound vibrometry (SDUV) can simultaneously measure the elasticity and viscosity of tissue using shear wave propagation speeds at different frequencies. In this paper, the viscoelasticity of rat livers was measured quantitatively by SDUV for normal (stage F0) and fibrotic livers (stage F2). Meanwhile, an independent validation study was presented in which SDUV results were compared with those derived from dynamic mechanical analysis (DMA), which is the only mechanical test that simultaneously assesses the viscoelastic properties of tissue. Shear wave speeds were measured at frequencies of 100, 200, 300 and 400Hz with SDUV and the storage moduli and loss moduli were measured at the frequency range of 1-40Hz with DMA. The Voigt viscoelastic model was used in the two methods. The mean elasticity and viscosity obtained by SDUV ranged from 0.84±0.13kPa (F0) to 1.85±0.30kPa (F2) and from 1.12±0.11Pas (F0) to 1.70±0.31Pas (F2), respectively. The mean elasticity and viscosity derived from DMA ranged from 0.62±0.09kPa (F0) to 1.70±0.84kPa (F2) and from 3.38±0.32Pas (F0) to 4.63±1.30Pas (F2), respectively. Both SDUV and DMA demonstrated that the elasticity of rat livers increased from stage F0 to F2, a finding which was consistent with previous literature. However, the elasticity measurements obtained by SDUV had smaller differences than those obtained by DMA, whereas the viscosities obtained by the two methods were obviously different. We suggest that the difference could be related to factors such as tissue microstructure, the frequency range, sample size and the rheological model employed. For future work we propose some improvements in the comparative tests between SDUV and DMA, such as enlarging the harmonic frequency range of the shear wave to highlight the role of viscosity, finding an appropriate rheological model to improve the accuracy of tissue viscoelasticity estimations.
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.
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.
Experimental MS(n) mass spectral libraries currently do not adequately cover chemical space. This limits the robust annotation of metabolites in metabolomics studies of complex biological samples. In-silico fragmentation libraries would improve the identification of compounds from experimental multi-stage fragmentation data when experimental reference data is unavailable. Here we present a freely-available software package to automatically control Mass Frontier software to construct in-silico mass spectral libraries, and to perform spectral matching. Based on two case studies we have demonstrated that HAMMER allows researchers to generate in-silico mass spectral libraries in an automated and high-throughput fashion with little or no human intervention required.
Purpose: Methods for quantification of breast density on MRI using semiautomatic approaches are commonly used. In this study, the authors report on a fully automatic chest template-based method.Methods: Nonfat-suppressed breast MR images from 31 healthy women were analyzed. Among them, one case was randomly selected and used as the template, and the remaining 30 cases were used for testing. Unlike most model-based breast segmentation methods that use the breast region as the template, the chest body region on a middle slice was used as the template. Within the chest template, three body landmarks (thoracic spine and bilateral boundary of the pectoral muscle) were identified for performing the initial V-shape cut to determine the posterior lateral boundary of the breast. The chest template was mapped to each subjects image space to obtain a subject-specific chest model for exclusion. On the remaining image, the chest wall muscle was identified and excluded to obtain clean breast segmentation. The chest and muscle boundaries determined on the middle slice were used as the reference for the segmentation of adjacent slices, and the process continued superiorly and inferiorly until all 3D slices were segmented. The segmentation results were evaluated by an experienced radiologist to mark voxels that were wrongly included or excluded for error analysis.Results: The breast volumes measured by the proposed algorithm were very close to the radiologists corrected volumes, showing a % difference ranging from 0.01% to 3.04% in 30 tested subjects with a mean of 0.86% ± 0.72%. The total error was calculated by adding the inclusion and the exclusion errors (so they did not cancel each other out), which ranged from 0.05% to 6.75% with a mean of 3.05% ± 1.93%. The fibroglandular tissue segmented within the breast region determined by the algorithm and the radiologist were also very close, showing a % difference ranging from 0.02% to 2.52% with a mean of 1.03% ± 1.03%. The total error by adding the inclusion and exclusion errors ranged from 0.16% to 11.8%, with a mean of 2.89% ± 2.55%.Conclusions: The automatic chest template-based breast MRI segmentation method worked well for cases with different body and breast shapes and different density patterns. Compared to the radiologist-established truth, the mean difference in segmented breast volume was approximately 1%, and the total error by considering the additive inclusion and exclusion errors was approximately 3%. This method may provide a reliable tool for MRI-based segmentation of breast density.
New vibration pulses are developed for shear wave generation in a tissue region with preferred spectral distributions for ultrasound vibrometry applications. The primary objective of this work is to increase the frequency range of detectable harmonics of the shear wave. The secondary objective is to reduce the required peak intensity of transmitted pulses that induce the vibrations and shear waves. Unlike the periodic binary vibration pulses, the new vibration pulses have multiple pulses in one fundamental period of the vibration. The pulses are generated from an orthogonal-frequency wave composed of several sinusoidal signals, the amplitudes of which increase with frequency to compensate for higher loss at higher frequency in tissues. The new method has been evaluated by studying the shear wave propagation in in vitro chicken and swine liver. The experimental results show that the new vibration pulses significantly increase tissue vibration with a reduced peak ultrasound intensity, compared with the binary vibration pulses.
5?Fluorouracil (5?FU) is a commonly used anti?tumor chemotherapeutic drug for cervical carcinoma. However, increased drug resistance may occur following several cycles of 5?FU?based chemotherapy. Novel strategies of gene therapy for enhancing the sensitivity of cancer cells to 5?FU chemotherapy have been intensively explored. Human telomerase reverse transcriptase (hTERT)C27 is a newly constructed hTERT C?terminal polypeptide that is capable of promoting chromosome end?to?end fusion during anaphase and inducing telomere dysfunction. In the present study, the effects of hTERTC27 overexpression on 5?FU?induced proliferation inhibition and apoptosis were observed. HeLa cells were cultured and transfected with the constructed pcDNA3.1 or pcDNA3.1?hTERTC27 vectors. Expression of hTERTC27 was detected using western blot analysis and was assessed using MTT assays and flow cytometry. The results demonstrated that overexpressed hTERTC27 increased the sensitivity of the HeLa cells to 5?FU and significantly inhibited HeLa cell proliferation with 5?FU treatment. In addition, hTERTC27 overexpression evidently promoted the 5?FU?induced apoptosis by increasing the expression of activated caspase?3 and ?9 and by downregulating the expression of B?cell lymphoma 2. The results suggest that hTERTC27 overexpression is a potential clinical strategy for enhancing the antitumor effect of 5?FU chemotherapy in the treatment of cervical carcinoma.
Ultrasound is a very promising technology to mediated drug/gene transferring into cells. However the relations between cell experimental conditions and results have been still unknown. It seriously impeded the development of the technology. In the article, a transfer efficiency model for ultrasound mediated drug/gene transferring into cells in stable cavitation was constructed. To testify the model, the numerical results were compared with the cell experimental data from six literatures in the entirely different experimental conditions. The numerical results fit the cell experimental data well. Despite simplifications and limitations, the model for the first time established the relationship between the cell experimental results about transfer efficiency and the conditions including ultrasound, microbubble and cells in stable cavitation.
Muscle thickness is one of the most widely used parameters for quantifying muscle function. Ultrasonography is frequently used to estimate changes in muscle thickness in both static and dynamic contractions. Conventionally, most such measurements are conducted by manual analysis of ultrasound images. This manual approach is time consuming, subjective, susceptible to error and not suitable for measuring dynamic change. In this study, we developed an automated tracking method based on an optical flow algorithm using an affine motion model. The goal of the study was to evaluate the performance of the proposed method by comparing it with the manual approach and by determining its repeatability. Real-time B-mode ultrasound was used to examine the rectus femoris during voluntary contraction. The coefficient of multiple correlation (CMC) was used to quantify the level of agreement between the two methods and the repeatability of the proposed method. The two methods were also compared by linear regression and Bland-Altman analysis. The findings indicated that the results obtained using the proposed method were in good agreement with those obtained using the manual approach (CMC = 0.97 ± 0.02, difference = -0.06 ± 0.22 mm) and were highly repeatable (CMC = 0.91 ± 0.07). In conclusion, the automated method proposed here provides an accurate, highly repeatable and efficient approach to the estimation of muscle thickness during muscle contraction.
Muscle aspect ratio of cross-sectional area is one of the most widely used parameters for quantifying muscle function in both diagnosis and rehabilitation assessment. Ultrasound imaging has been frequently used to noninvasively study the characteristics of human muscles as a reliable method. However, the aspect ratio measurement is traditionally conducted by the manual digitization of reference points; thus, it is subjective, time-consuming, and prone to errors. In this paper, a novel method is proposed to continuously detect the muscle aspect ratio. Two keypoint pairs are manually digitized on the lateral and longitudinal borders at the first frame, and automatically tracked by an optical flow technique at the subsequent frames. The muscle aspect ratio is thereby obtained based on the estimated muscle width and thickness. Six ultrasound sequences from different subjects are used to evaluate this method, and the overall coefficient of multiple correlation of the results between manual and proposed methods is 0.97 ± 0.02. The linear regression shows that a good linear correlation between the results of the two methods is obtained (R(2) = 0.974), with difference -0.01 ± 0.16. The method proposed here provides an accurate, high repeatable, and efficient approach for estimating muscle aspect ratio during human motion, thus justifying its application in biological sciences.
Ultrasound elastography, based on shear wave propagation, enables the quantitative and non-invasive assessment of liver mechanical properties such as stiffness and has been found to be feasible for and useful in the diagnosis of hepatic fibrosis. Most ultrasound elastographic methods use a purely elastic model to describe liver mechanical properties. However, to describe tissue that is dispersive and to obtain an accurate measure of tissue elasticity, the viscoelasticity of the tissue should be examined. The objective of this study was to investigate the shear viscoelastic characteristics, as measured by ultrasound elastography, of liver fibrosis in a rat model and to evaluate the diagnostic accuracy of viscoelasticity for staging liver fibrosis. Liver fibrosis was induced in 37 rats using carbon tetrachloride (CCl4); 6 rats served as controls. Liver viscoelasticity was measured in vitro using shear waves induced by acoustic radiation force. The measured mean values of liver elasticity and viscosity ranged from 0.84 to 3.45 kPa and from 1.12 to 2.06 Pa·s for fibrosis stages F0-F4, respectively. Spearman correlation coefficients indicated that stage of fibrosis was well correlated with elasticity (0.88) and moderately correlated with viscosity (0.66). The areas under receiver operating characteristic curves were 0.97 (?F2), 0.91 (?F3) and 1.00 (F4) for elasticity and 0.91 (?F2), 0.79 (?F3) and 0.74 (F4) for viscosity, respectively. The results confirmed that shear wave velocity was dispersive in frequency, suggesting a viscoelastic model to describe liver fibrosis. The study finds that although viscosity is not as good as elasticity for staging fibrosis, it is important to consider viscosity to make an accurate estimation of elasticity; it may also provide other mechanical insights into liver tissues.
The purpose of ultrasound elastography is to identify lesions by reconstructing the hardness characteristics of tissue reconstructed from ultrasound data. Conventional quasi-static ultrasound elastography is easily applied to obtain axial strain components along the compression direction, with the results inverted to represent the distribution of tissue hardness under the assumption of constant internal stresses. However, previous works of quasi-static ultrasound elastography have found it difficult to obtain the lateral and shear strain components, due to the poor lateral resolution of conventional ultrasound probes. The physical nature of the strain field is a continuous vector field, which should be fully described by the axial, lateral, and shear strain components, and the clinical value of lateral and shear strain components of deformed tissue is gradually being recognized by both engineers and clinicians. Therefore, a biomechanical-model-constrained filtering framework is proposed here for recovering a full displacement field at a high spatial resolution from the noisy ultrasound data. In our implementation, after the biomechanical model constraint is integrated into the state-space equation, both the axial and lateral displacement components can be recovered at a high spatial resolution from the noisy displacement measurements using a robust H? filter, which only requires knowledge of the worst-case noise levels in the measurements. All of the strain components can then be calculated by applying a gradient operator to the recovered displacement field. Numerical experiments on synthetic data demonstrated the robustness and effectiveness of our approach, and experiments on phantom data and in-vivo clinical data also produced satisfying results.
The dynamic behaviour of a microbubble confined within a rigid micro-tube was studied using finite element method. The results indicated that the microbubble oscillation was limited when constrained within the micro-tube. Both the expansion ratio of its effective radius and natural frequency decreased with the decrease of the tube radius. Meanwhile, the deformation of the microbubble was non-spherical and became more significant when the ultrasound pressure amplitude increased. The dynamic behaviour in micro-tube was different from that in infinite liquid.
Low intensity ultrasonic therapy is always an important research area of ultrasonic medicine. This review concentrates on low intensity ultrasound enhancing bactericidal action of antibiotics against bacteria in vitro and in vivo, including planktonic bacteria, bacterial biofilms, Chlamydia, and bacteria in implants. These literatures show that low intensity ultrasound alone is not effective in killing bacteria, while the combination of low intensity ultrasound and antibiotics is promising. Low intensity ultrasound facilitating antibiotic treatment is still in its infancy, and still requires a great deal of research in order to develop the technology on medical treatment scale.
The article introduces the clinical testing method for the product of patient monitor, the definition of direct measurement and indirect measurement method, and the different testing methods. The clinical testing methods for none invasive blood pressure, pulse oxygen saturation and ECG analysis have significant value, which are important solutions to test the safety and effectiveness of medical devices by using the equivalent analysis method. These methods above are also provided as reference for other medical devices clinical testing.
Conventional interpolation algorithms for reconstructing freehand three-dimensional (3D) ultrasound data always contain speckle noises and artifacts. This paper describes a new algorithm for reconstructing regular voxel arrays with reduced speckles and preserved edges. To study speckle statistics properties including mean and variance in sequential B-mode images in 3D space, experiments were conducted on an ultrasound resolution phantom and real human tissues. In the volume reconstruction, the homogeneity of the neighborhood for each voxel was evaluated according to the local variance/mean of neighboring pixels. If a voxel was locating in a homogeneous region, its neighboring pixels were averaged as the interpolation output. Otherwise, the size of the voxel neighborhood was contracted and the ratio was re-calculated. If its neighborhood was deemed as an inhomogeneous region, the voxel value was calculated using an adaptive Gaussian distance weighted method with respect to the local statistics. A novel method was proposed to reconstruct volume data set with economical usage of memory. Preliminary results obtained from the phantom and a subjects forearm demonstrated that the proposed algorithm was able to well suppress speckles and preserve edges in 3D images. We expect that this study can provide a useful imaging tool for clinical applications using 3D ultrasound.
Based on LCD Module and Visual C++ development environment, this paper proposes a new method which can quickly develop the human-machine interface .We define a LCD module programming interface by designing Serial Communication Class(SCS). On this basis,we achieve the transplantation on an Embedded ARM Platform to fulfil the requirements of Medical Diagnostic Instruments (MDI). Experimental results show that this method has advantages of short development cycle and high level transplantation which has broad application prospects in the field of Medical Diagnosis Instrument.
The GP2 peptide is derived from the Human Epidermal growth factor Receptor 2 (HER2/nue), a marker protein for breast cancer present in saliva. In this paper we study the temperature dependent behavior of hydrated GP2 at terahertz frequencies and find that the peptide undergoes a dynamic transition between 200 and 220 K. By fitting suitable molecular models to the frequency response we determine the molecular processes involved above and below the transition temperature (T(D)). In particular, we show that below T(D) the dynamic transition is dominated by a simple harmonic vibration with a slow and temperature dependent relaxation time constant and that above T(D), the dynamic behavior is governed by two oscillators, one of which has a fast and temperature independent relaxation time constant and the other of which is a heavily damped oscillator with a slow and temperature dependent time constant. Furthermore a red shifting of the characteristic frequency of the damped oscillator was observed, confirming the presence of a non-harmonic vibration potential. Our measurements and modeling of GP2 highlight the unique capabilities of THz spectroscopy for protein characterization.
hTERTC27 is a newly constructed polypeptide that can induce telomere dysfunction. To study the synergistic antitumor effects of the hTERTC27 polypeptide driven by the early growth response protein-1 (Egr-1) promoter and chemotherapeutic 5-flurorouracil (5-FU) on nasopharyngeal carcinoma, a series of in vitro and in vivo experiments were performed. The results showed that hTERTC27 expression was significantly increased up to 7.21-folds by the 5-FU-activated Egr-1 promoter in C666-1 cells. Overexpressed hTERTC27 made the cells more sensitive to 5-FU, and additionally, inhibited cell proliferation about 20.41%. Combinational therapy of overexpressed hTERTC27 driven by the 5-FU-activated Egr-1 promoter and 5-FU synergistically inhibited cell proliferation and promoted apoptosis of C666-1 cells for about 4.75-fold and 1.76-fold in comparison with a sole therapy of hTERTC27 or 5-FU in vitro. In vivo experiments showed that overexpressed hTERTC27 driven by 5-FU-activated Egr-1 promoter and 5-FU synergistically reduced tumor volume, tumor weight, and local infiltration, which may be relative to tumor cell apoptosis. These results suggest that combinational therapy of overexpressed hTERTC27, which is driven by the 5-FU-activated Egr-1 promoter, and 5-FU may provide a novel approach to treat nasopharyngeal cancer.
The toxicity of QD has been extensively studied over the past decade. However, the potential toxicity of QDs impedes its use for clinical research. In this work, we established a preantral follicle in vitro culture system to investigate the effects of QD-Transferrin (QDs-Tf) bioconjugates on follicle development and oocyte maturation. The preantral follicles were cultured and exposed to CdTe/ZnTe QDs-Tf bioconjugates with various concentrations and the reproductive toxicity was assessed at different time points post-treatment. The invasion of QDs-Tf for oocytes was verified by laser scanning confocal microscope. Steroid production was evaluated by immunoassay. C-band Giemsa staining was performed to observe the chromosome abnormality of oocytes. The results showed that the QDs-Tf bioconjugates could permeate into granulosa cells and theca cells, but not into oocyte. There are no obvious changes of oocyte diameter, the mucification of cumulus-oocyte-complexes and the occurrence of aneulpoidy as compared with the control group. However, delay in the antrum formation and decrease in the ratio of oocytes with first polar body were observed in QDs-Tf-treated groups. The matured oocytes with first polar body decreased significantly by ~16% (from 79.6±10 % to 63±2.9 %) when the concentration of QDs-Tf bioconjugates exceeded 2.89 nmol·L(-1) (P < 0.05). Our results implied that the CdTe/ZnTe QDs-Tf bioconjugates were reproductive toxic for follicle development, and thus also revealed that this in vitro culture system of preantral follicle is a highly sensitive tool for study on the reproductive toxicity of nanoparticles.
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.
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