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.

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.

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.

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.

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.

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.