Ring artifacts removal in X-ray-induced acoustic computed tomography

X-ray-induced acoustic computed tomography(XACT)is a hybrid imaging modality for detecting X-ray absorption distribution via ultrasound emission.It facilitates imaging from a single projection X-ray illumination,thus reducing the radiation exposure and improving imaging speed.Nonuniform detector response caused by the interference between multichannel data acquisition for ring array transducers and amplifier systems yields ring artifacts in the reconstructed XACT images,which compromises the image quality.We propose model-based algorithms for ring artifacts corrected XACT imaging and demonstrate their effcacy on numerical and experimental measurements.The corrected reconstructions indicate significantly reduced ring artifacts as compared to their conventional counterparts.

Multimodal intravascular imaging technology for characterization of atherosclerosis

Early detection of vulnerable plaques is the critical step in the prevention of acute coronary events.Morphology,composition,and mechanical property of a coronary artery have been demonstrated to be the key characteristics for the identification of vulnerable plaques.Several intravascular multimodal imaging technologies providing co-registered simultaneous images have been developed and applied in clinical studies to improve the characterization of atherosclerosis.In this paper,the authors review the present system and probe designs of representative intra-vascular multimodal techniques.In addition,the scientific innovations,potential limitations,and future directions of these technologies are also discussed.

PROBING THE IMPACT OF GAMMA-IRRADIATION ON THE METABOLIC STATE OF NEURAL STEM AND PRECURSOR CELLS USING DUAL-WAVELENGTH INTRINSIC SIGNAL TWO-PHOTON EXCITED FLUORESCENCE

Two-photon excitedfluorescence(TPEF)spectroscopy and imaging were used to investigate the effects of gamma-irradiation on neural stem and precursor cells(NSPCs).While the observed signal from reduced nicotinamide adenine dinucleotide(NADH)was localized to the mitochondria,the signal typically associated with oxidizedflavoproteins(Fp)was distributed diffusely throughout the cell.The measured TPEF emission and excitation spectra were similar to the established spectra of NAD(P)H and Fp.Fpfluorescence intensity was markedly increased by addition of the electron transport chain(ETC)modulator menadione to the medium,along with a concomitant decrease in the NAD(P)H signal.Three-dimensional(3D)neurospheres were imaged to obtain the cellular metabolic index(CMI),calculated as the ratio of Fp to NAD(P)Hfluorescence intensity.Radiation effects were found to differ between low-dose(
50 cGy)and high-dose(50 cGy)exposures.Low-dose irradiation caused a marked drop in CMI values accompanied by increased cellular proliferation.At higher doses,both NAD(P)H and Fp signals increased,leading to an overall elevation in CMI values.Thesefindings underscore the complex relationship between radiation dose,metabolic state,and proliferation status in NSPCs and highlight the ability of TPEF spectroscopy and imaging to characterize metabolism in 3D spheroids.

NON-INVASIVE MEASUREMENT OF DEEP TISSUE TEMPERATURE CHANGES CAUSED BY APOPTOSIS DURING BREAST CANCER NEOADJUVANT CHEMOTHERAPY:A CASE STUDY

Treatment-induced apoptosis of cancer cells is one goal of cancer therapy.Interestingly,more heat is generated by mitochondria during apoptosis,especially the uncoupled apoptotic state,^(1,2) compared to the resting state.In this case study,we explore these thermal effects by longitudinally measuring temperature variations in a breast lesion of a pathological complete responder during neoadjuvant chemotherapy(NAC).Diffuse Optical Spectroscopic Imaging(DOSI)was employed to derive absolute deep tissue temperature using subtle spectral features of the water peak at 975 nm.^(3)A significant temperature increase was observed in time windows during the anthracycline and cyclophosphamide(AC)regimen but not in the paclitaxel and bevacizumab regimen.Hemoglobin concentration changes generally did not follow temperature,suggesting the measured temperature increases were likely due to mitochondrial uncoupling rather than a direct vascular effect.A simultaneous increase of tissue oxygen saturation with temperature was observed,suggesting that oxidative stress also contributes to apoptosis.Although preliminary,this study indicates longitudinal DOSI tissue temperature monitoring provides information that can improve our understanding of the mechanisms of tissue response during NAC.

Anti-Helicobacter pylori effect of CaG-NANA, a new sialic acid derivative

AIM To investigate the bactericidal effects of calcium chelated N-acetylneuraminic acid-glycomacropeptide(CaG-NANA) against Helicobacter pylori(H.pylori).METHODS For manufacture of Ca G-NANA,calcium(Ca) was combined with glycomacropeptide(GMP) by chelating,and N-acetylneuraminic acid(NANA) was produced with Ca-GMP substrate by an enzymatic method.The final concentration of each component was 5% Ca,7% NANA,85% GMP,and 3% water.For in vitro study,various concentrations of CaG-NANA were investigated under the minimal inhibitory concentration(MIC).For in vivo study,Ca G-NANA was administered orally for 3 wk after H.pylori infection.The levels of inflamma-tory cytokines in blood were analyzed by enzyme-linked immunosorbent assay and eradication of H.pylori was assessed by histological observation.RESULTS The time-kill curves showed a persistent decrease in cellnumbers,which depended on the dose of CaG-NANA,and MIC of Ca G-NANA against H.pylori was 0.5% in vitro.Histopathologic observation revealed no obvious inflammation or pathologic changes in the gastric mucosa in the CaG-NANA treatment group in vivo.The colonization of H.pylori was reduced after CaG-NANA treatment.The levels of interleukin(IL)-6,IL-1β,tumor necrosis factor-α,and IL-10 were also decreased by CaG-NANA.CONCLUSION Ca G-NANA demonstrates effective anti-bactericidal activity against H.pylori both in vitro and in vivo.

ENHANCED FLUORESCENCE IMAGING WITH DMSO-MEDIATED OPTICAL CLEARING

Recent studies have demonstrated that topical application of glycerol on intact skin does not affect its optical scattering properties.Investigators from our research group recently revisited the use of dimethyl sulfoxide(DMSO)as an agent with optical clearing potential.We address the use of optical clearing to enhance quantitation of subsurface fluorescence emission.We employed both in vitro and in vivo model systems to study the effect of topical DMSO application on fluorescence emission.Our in vitro experiments performed on a tissue-simulating phantom suggest that DMSO-mediated optical clearing enables enhanced characterization of subsurface fluorophores.With topical DMSO application,a marked increase in fluorescence emission was observed.After 30 min,the fluorescence signal at the DMSO-treated site was 9×greater than the contralateral saline-treated site.This ratio increased to 13×at 105 min after agent application.In summary,DMSO is an effective optical clearing agent for improved fluorescence emission quantitation and warrants further study in preclinical in vivo studies.Based on outcomes from previous clinical studies on the toxicity profile of DMSO,we postulate that clinical application of DMSO as an optical clearing agent,can be performed safely,although further study is warranted.

Applications of a new In vivo tumor spheroid based shell-less chorioallantoic membrane 3-D model in bioengineering research

The chicken chorioallantoic membrane (CAM) is a classical in vivo biological model in studies of angiogenesis. Combined with the right tumor system and experimental configuration this classical model can offer new approaches to investigating tumor processes. The increase in development of biotechnolo- gical devices for cancer diagnosis and treatment, calls for more sophisticated tumor models that can easily adapt to the technology, and provide a more accurate, stable and consistent platform for rapid quantitative and qualitative analysis. As we discuss a variety of applications of this novel in vivo tumor spheroid based shell-less CAM model in biomedical engineering research, we will show that it is extremely versatile and easily adaptable to an array of biomedical applications. The model is particularly useful in quantitative studies of the progression of avascular tumors into vascularized tumors in the CAM. Its environment is more stable, flat and has a large working area and wider field of view excellent for imaging and longitudinal studies. Finally, rapid data acquisition, screening and validation of biomedical devices and therapeutics are possible with the short experimental window.

Enhance the delivery of light energy ultra-deep into turbid medium by controlling multiple scattering photons to travel in open channels

Multiple light scattering is considered as the major limitation for deep imaging and focusing in turbid media.In this paper,we present an innovative method to overcome this limitation and enhance the delivery of light energy ultradeep into turbid media with significant improvement in focusing.Our method is based on a wide-field reflection matrix optical coherence tomography(RM-OCT).The time-reversal decomposition of the RM is calibrated with the Tikhonov regularization parameter in order to get more accurate reversal results deep inside the scattering sample.We propose a concept named model energy matrix,which provides a direct mapping of light energy distribution inside the scattering sample.To the best of our knowledge,it is the first time that a method to measure and quantify the distribution of beam intensity inside a scattering sample is demonstrated.By employing the inversion of RM to find the matched wavefront and shaping with a phase-only spatial light modulator,we succeeded in both focusing a beam deep(~9.6 times of scattering mean free path,SMFP)inside the sample and increasing the delivery of light energy by an order of magnitude at an ultra-deep(~14.4 SMFP)position.This technique provides a powerful tool to understand the propagation of photon in a scattering medium and opens a new way to focus light inside biological tissues.

Photodynamic therapy mediated immune therapy of brain tumors

Photodynamic therapy of tumors requires the topical, systemic or oral administration of a photosensitizing compound,illumination of the tumor area by light of a specific wavelength and the presence of oxygen. Light activation of the photosensitizer transfers energy to molecular oxygen creating singlet oxygen, a highly reactive and toxic species that rapidly reacts with cellular components causing oxidative damage, ultimately leading to cell death. Tumor destruction caused by photodynamic therapy is not only a result of direct tumor cell toxicity via the generation of reactive oxygen species but there is also an immunological and vascular component involved. The immune response to photodynamic therapy has been demonstrated to significantly enhance its efficacy. Depending on a number of factors, including type of photosensitizer, light dose and dose rate, photodynamic therapy has been shown to induce cell death via apoptosis, necrosis, autophagy and in particular immunogenic cell death. It is the purpose of this review to focus mainly on the role photodynamic therapy could play in the generation of specific anti-tumor immunity and vaccines for the treatment of brain tumors.

Ultrahigh-sensitive optical coherence elastography

The phase stability of an optical coherence elastography(OCE)system is the key determining factor for achieving a precise elasticity measurement,and it can be affected by the signal-to-noise ratio(SNR),timing jitters in the signal acquisition process,and fluctuations in the optical path difference(OPD)between the sample and reference arms.In this study,we developed an OCE system based on swept-source optical coherence tomography(SS-OCT)with a common-path configuration(SS-OCECP).Our system has a phase stability of 4.2 mrad without external stabilization or extensive post-processing,such as averaging.This phase stability allows us to detect a displacement as small as~300 pm.A common-path interferometer was incorporated by integrating a 3-mm wedged window into the SS-OCT system to provide intrinsic compensation for polarization and dispersion mismatch,as well as to minimize phase fluctuations caused by the OPD variation.The wedged window generates two reference signals that produce two OCT images,allowing for averaging to improve the SNR.Furthermore,the electrical components are optimized to minimize the timing jitters and prevent edge collisions by adjusting the delays between the trigger,k-clock,and signal,utilizing a high-speed waveform digitizer,and incorporating a high-bandwidth balanced photodetector.We validated the SSOCECP performance in a tissue-mimicking phantom and an in vivo rabbit model,and the results demonstrated a significantly improved phase stability compared to that of the conventional SS-OCE.To the best of our knowledge,we demonstrated the first SS-OCECP system,which possesses high-phase stability and can be utilized to significantly improve the sensitivity of elastography.

Interfacing photonic crystal fiber with a metallic nanoantenna for enhanced light nanofocusing

The direct interfacing of photonic crystal fiber to a metallic nanoantenna has widespread application in nanoscale imaging, optical lithography, nanoscale lasers, quantum communication, in vivo sensing, and medical surgery.We report on the fabrication of a needle-shaped plasmonic nanoantenna on the end facet of a photonic crystal fiber using electron-beam-induced evaporation of platinum. We demonstrate the coupling of light from the fiber waveguide mode to the subwavelength nanoantenna plasmonic mode focusing down to the apex of the plasmonic needle using a polarization-resolved far-field side-scatter imaging technique. Our work provides an important step toward widespread application of optical fibers in nearfield spectroscopic techniques such as tip-enhanced Raman and fluorescence microscopy, single-photon excitation and quantum sensors, nanoscale optical lithography, and lab-on-fiber devices.

Advances in Doppler OCT

We review the principle and some recent applications of Doppler optical coherence tomography （OCT）. The advances of the phase-resolved Doppler OCT method are described. Functional OCT algorithms which are based on an extension of the phase-resolved scheme are also introduced. Recent applications of Doppler OCT for quantification of flow, imaging of microvasculature and vocal fold vibration, and optical coherence elastography are briefly discussed.

A miniaturized system for measurement of the refractive index of sub-microliter liquid

This study introduced the research and development of a portable and miniaturized system for the measurement of the refractive index of sub-microliter liquid based on a microfluidic chip. A technical method of double-beam interference, was proposed for use in the measurement. Based on this, by using a laser diode as a light source,changes in the refractive index were calculated by utilizing a complementary metal–oxide–semiconductor to detect the movement of interference fringes of the liquid. Firstly, this study simulated the effects of influencing factors on the interference infringes of two Gaussian beams, such as their spot sizes, distance between two beam spots, and detection range. Secondly, this research introduced the system design and construction of the doublebeam interference method and analyzed the results of refractive index tests on sub-microliter aqueous glucose solutions with different concentrations. The measurement accuracy reached 10^(-4) refractive index units. This system has a compact structure and is rendered portable by using batteries for its power supply. The entire system is designed to be a double Z-shaped structure with a length of about 15 cm, a width of 5 cm, and a height of about 10 cm. It can be used to measure changes in the refractive index of sub-microliter to nanoliter liquids based on the use of a microfluidic chip.