Photoacoustic mesoscopy:pushing toward the depth limit in the high-resolution optical imaging for biomedical applications and clinical potentials

Photoacoustic mesoscopy(PAMe) offers high-sensitivity in vivo imaging based on the rich optical contrast in biological tissues,with sub-100-micron resolutions at a few millimeters depth. By benefiting from low ultrasonic scattering,this emerging technology has pushed the penetration depth beyond the optical diffuse limit unprecedented for high-resolution optical methods.Here,we review ed the state-of-art implementations of PAMe and their achievements in biological and primary clinical applications. With the high-frequency focused ultrasonic detector,the high-resolution optical visualization can be achieved by utilizing various PAMe systems. These capabilities of PAMe have made it well applicable for understanding the biological mechanisms,exploring the pathological features and analyzing the characteristics of human skin. Future improvements and prospects of PAMe are also mentioned,suggesting its great potential tow ards the corresponding emerging biomedical and clinical applications.

Time-Frequency Analysis of EEG Signals Evoked by Voluntary, Stimulated and Imaginary Motions

In order to investigate the characteristics of sensorimotor cortex during motor execution(ME), voluntary, stimulated and imaginary finger flexions were performed by ten volunteer subjects. Electroencephalogram(EEG) data were recorded according to the modified 10-20 International EEG System. The patterns were compared by the analysis of the motion-evoked EEG signals focusing on the contralateral(C3) and ipsilateral(C4) channels for hemispheric differences. The EEG energy distributions at alpha(8—13 Hz), beta(14—30 Hz) and gamma(30—50 Hz) bands were computed by wavelet transform(WT) and compared by the analysis of variance(ANOVA). The timefrequency(TF) analysis indicated that there existed a contralateral dominance of alpha post-movement event-related synchronization(ERS) pattern during the voluntary task, and that the energy of alpha band increased in the ipsilateral area during the stimulated(median nerve of wrist) task. Besides, the contralateral alpha and beta event-related desynchronization(ERD) patterns were observed in both stimulated and imaginary tasks. Another significant difference was found in the mean power values of gamma band(p<0.01)between the imaginary and other tasks. The results show that significant hemispheric differences such as alpha and beta band EEG energy distributions and TF changing phenomena(ERS/ERD) were found between C3 and C4 areas during all of the three patterns. The largest energy distribution was always at the alpha band for each task.

Effects of Low-Intensity Ultrasound on Cell Proliferation and Reproductivity

Ultrasound has been widely used in clinics. Cellular responses to low-intensity ultrasound are parameter-dependent. Proper parameter setting is vital to its exact use. To get guidelines for parameter setting, lowintensity ultrasound stimulation on the proliferation and reproductivity of Hep G2 and 3T3 cells in vitro was examined with a 1.06 MHz-generator by changing the parameters(including intensity, pulse repetition frequency and duty cycle)in a wide range. Cell viability and reproductivity at different time after sonication were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)and colony formation assay to indicate timerelated proliferation. The results illustrate that ultrasound irradiation at 0.4—0.8 W/cm^2 and high pulse repetition frequency(100 Hz)can facilitate cell proliferation, while above 0.8 W/cm^2 would resist it. The extent of resistance closely correlated with duty cycle and pulse repetition frequency. Resistance effect at low pulse repetition frequency(1 Hz)is greater than that at high pulse repetition frequency(100 Hz)and not time-related. The influence of high pulse repetition frequency is time-accumulated, indicating cellular process involved. These findings would provide valuable guidelines for the application of low-intensity ultrasound in stem cell transformation and tissue engineering.

Norcantharidin combined with ABT-737 for hepatocellular carcinoma: Therapeutic effects and molecular mechanisms

AIM: To study the therapeutic effect of norcantharidin(NCTD) combined with ABT-737 on hepatocellular carcinoma cells and the molecular mechanism. METHODS: Two hepatocellular carcinoma(HCC) cell lines, Hep G2 and SMMC-7721, were selected. ABT-737 and NCTD were allocated into groups to be used alone or in combination. Hep G2 and SMMC-7721 cells were cultured in vitro. Liver cancer cells in the logarithmic phase of growth were vaccinated and cultured to the cell wall stage; these cells were treated for 48 h with different concentrations of NCTD, or ABT-737, or NCTD combined with ABT-737. The cell proliferation inhibition rate was detected by methyl thiazolyl tetrazolium. The expression of Mcl in HCC cells was detected by Western Blotting, and the cells in each group after treatment had apoptosis detected by flow cytometry. The proliferation inhibition rate, the expression of Mcl-1 in cells and the apoptosis inducing effect of treatment were observed in each group, and the effect of NCTD on ABT-737 in the treatment of HCC and its mechanism of action were analyzed.RESULTS: As the concentration of NCTD increased, the cell proliferation inhibition rate gradually decreased; and the treatment effect of ABT-737 1-3 μm combined with NCTD on cell proliferation inhibition was stronger than that of ABT-737 alone. The difference was statistically significant(P < 0.05). In observing the expression of Mcl-1 in cells after the treatment of different concentrations of NCTD, this was partiallyinhibited after treatment with NCTD 15 μm, and the expression of Mcl-1 was almost undetectable after treatment with NCTD 30 μm and 60 μm. The effect on inducing apoptosis with the treatment of ABT-737 or NCTD alone for 48 h was lower than that of the control group. The difference was not statistically significant(P > 0.05). The effect on inducing apoptosis in Hep G2 and SMMC-7721 cells with the treatment of ABT-737 combined with NCTD for 48 h was greater than that of ABT-737 or NCTD alone. The difference was statistically significant(P < 0.05). CONCLUSION: NCTD combined with ABT-737 has a positive role in the treatment of HCC, and it has great value in clinical research.

Monte Carlo simulation based thinning and calculating method for noninvasive blood glucose sensing by near-infrared spectroscopy

Previous results show that the floating reference theory(FRT)is an effective tool to reduce the infuence of interference factors on noninvasive blood glucose sensing by near infrared spectros-copy(NIRS).It is the key to measure the floating reference point(FRP)precisely for the application of FRT.Monte Carlo(MC)simulation has been introduced to quantitatively in-vestigate the effects of positioning errors and light source drifts on measuring FRP.In this article,thinning and calculating method(TCM)is proposed to quantify the positioning error.Mean-while,the normalization process(NP)is developed to significantly reduce the error induced by light source drift.The results according to TCM show that 7 purm deviations in positioning can generate about 10.63%relative error in FRP.It is more noticeable that 1%fluctuation in light source intensity may lead to 12.21%relative errors.Gratifyingly,the proposed NP model can effectively reduce the error caused by light source drift.Therefore,the measurement system for FRPs must meet that the positioning error is less than 7 purm,and the light source drift is kept within 1%.Furthermore,an improvement for measurement system is proposed in order to take advantage of the NP model.

Three-dimensional quantication of protoporphyrin IX in photodynamic therapy using SFDI/DFT:A pilot experimental validation

Photodynamic therapy(PDT)dosimetry,induding light dose,photosensitizer dose and tissue oxygen,has been a research focus in PDT.In this work,we present a three-dimensional(3D)quantification of protoporphyrin X(PpIX)using combined spatial frequency domain imaging(SFDI)and diffuse fuorescence tomography(DFT).The SFDI maps both the distributions of tissue absorption and scattering properties at three wavelengths and accordingly provides the optical background for DFT and extracts the tissue oxygenation for assessing the therapeutic outcomes,while DFT dynamically monitors the 3D distribution of PpEX dose from measured fluorescence signals for the procedure optimization.A pilot in vrivo application in tumor nude models showed that the proposed SFDI/DFT is able to dynamically trace changes in the PpX concentration and tissue oaxygen during the treatment,rendering it a potentially powerful tool for PDT to improve clinical eficacy.

Editorial:special issue on medical detection technology

Medical detection technology-from biochemical analysis to medical imaging has witnessed tremendous progress in the past decades,driven by the breakthrough of biomedical and scientific theories,the innovation of engineering techniques,as well as the discovery of new contrast mechanisms.These substantial progresses have significantly promoted

sEMG Feature Analysis on Forearm Muscle Fatigue During Isometric Contractions

In order to detect and assess the muscle fatigue state with the surface electromyography(sEMG) characteristic parameters,this paper carried out a series of isometric contraction experiments to induce the fatigue on the forearm muscles from four subjects,and recorded the sEMG signals of the flexor carpi ulnaris.sEMG's median frequency(MDF) and mean frequency(MF) were extracted by short term Fourier transform(STFT),and the root mean square(RMS) of wavelet coefficients in the frequency band of 5—45 Hz was obtained by continuous wavelet transform(CWT).The results demonstrate that both MDF and MF show downward trends within 1 min; however,RMS shows an upward trend within the same time.The three parameters are closely correlated with absolute values of mean correlation coefficients greater than 0.8.It is suggested that the three parameters above can be used as reliable indicators to evaluate the level of muscle fatigue during isometric contractions.

Electric Wheelchair Control System Using Brain-Computer Interface Based on Alpha-Wave Blocking

A brain-computer interface(BCI)-based electric wheelchair control system was developed, which enables the users to move the wheelchair forward or backward, and turn left or right without any pre-learning. This control system makes use of the amplitude enhancement of alpha-wave blocking in electroencephalogram(EEG) when eyes close for more than 1 s to constitute a BCI for the switch control of wheelchair movements. The system was formed by BCI control panel, data acquisition, signal processing unit and interface control circuit. Eight volunteers participated in the wheelchair control experiments according to the preset routes. The experimental results show that the mean success control rate of all the subjects was 81.3%, with the highest reaching 93.7%. When one subject's triggering time was 2.8 s, i.e., the flashing time of each cycle light was 2.8 s, the average information transfer rate was 8.10 bit/min, with the highest reaching 12.54 bit/min.

A Rubik’s microfluidic cube

A Rubik’s cube as a reconfigurable microfluidic system is presented in this work.Composed of physically interlocking microfluidic blocks,the microfluidic cube enables the on-site design and configuration of custom microfluidics by twisting the faces of the cube.The reconfiguration of the microfluidics could be done by solving an ordinary Rubik’s cube with the help of Rubik’s cube algorithms and computer programs.An O-ring-aided strategy is used to enable self-sealing and the automatic alignment of the microfluidic cube blocks.Owing to the interlocking mechanics of cube blocks,the proposed microfluidic cube exhibits good reconfigurability and robustness in versatile applications and proves to be a promising candidate for the rapid deployment of microfluidic systems in resource-limited settings.

Simultaneous determination of ternary cephalosporin solutions by Raman spectroscopy

Cephalosporins are widely used as veterinary and human antibiotics. However, cephalosporin abuse is harmful to human health and causes allergic reactions or antibiotic resistance. We investigate a method fea- turing Raman spectroscopy and chemometrics to quantify mixture solutions of three typical cephalosporins, namely, ceftriaxone, cefotaxime sodium, and cefazolin sodium. Partial least-squares regression models are built on spectral data that are preprocessed by various methods. With prediction relative errors within 5% and high correlation coefficients of 0.998, we demonstrate that Raman spectroscopy combined with multivariate analysis is feasible for use in the quantitative determination of cephalosporin solutions. OCIS codes： 300.6450. 070.4340. 070.4790.

Region stepwise reconstruction method based on two source–detector-separation groups for reconstructing background optical properties of two-layered slab sample

The accuracy of the background optical properties has a considerable effect on the quality of reconstructed images in near-infrared functional brain imaging based on continuous wave diffuse optical tomography（CW-DOT）. We propose a region stepwise reconstruction method in CW-DOT scheme for reconstructing the background absorption and reduced scattering coefficients of the two-layered slab sample with the known geometric information. According to the relation between the thickness of the top layer and source– detector separation, the conventional measurement data are divided into two groups and are employed to reconstruct the top and bottom background optical properties, respectively. The numerical simulation results demonstrate that the proposed method can reconstruct the background optical properties of two-layered slab sample effectively. The region-of-interest reconstruction results are better than those of the conventional simultaneous reconstruction method.

Image reconstruction method for laminar optical tomography with only a single Monte-Carlo simulation

Laminar optical tomography （LOT） is a new mesoscopic functional optical imaging technique. Currently, the forward problem of LOT image reconstruction is generally solved on the basis of Monte-Carlo （MC） methods. However, considering the nonlinear nature of the image reconstruction in LOT with the increasing number of source positions, methods based on MC take too much computation time. This letter develops a fast image reconstruction algorithm based on perturbation MC （pMC） for reconstructing the absorption or scattering image of a slab medium, which is suitable for LOT or other functional optical tomography system with narrow source-detector separation and dense sampling. To calculate the pMC parameters, i.e., the path length passed by a photon and the collision numbers experienced in each voxel with only one baseline MC simulation, we propose a scheme named as the trajectory translation and target voxel regression （TT＆TVR） based on the reciprocity principle. To further speed up the image reconstruction procedure, the weighted average of the pMC parameters for all survival photons is adopted and the region of interest （ROI） is extracted from the raw data to save as the prior information of the image reconstruction. The method is applied to the absorption reconstruction of the layered inhomogeneous media. Results demonstrate that the reconstructing time is less than 20 s with the X - Y section of the sample subdivided into 50 × 50 voxels, and the target size quantitativeness ratio can be obtained in a satisfying accuracy in the source-detector separations of 0.4 and 1.25 mm, respectively.

An experimental investigation on two-dimensional shape-based diffuse optical tomography

A two-dimensional （2D） shape-based approach of image reconstruction using a boundary element method is developed for diffuse optical tomography （DOT）. The experimental validation uses a four-channel time- correlated single photon counting （TCSPC） system for detection and an intensity data-type for image reconstruction. The optical and geometric parameters are simultaneously recovered using a difference imaging scheme. Results demonstrate that the proposed DOT modality is a promising methodology of in vivo reconstruction of the optical structures of tissues.