In this study, the feasibility of visualization of human joints using photoacoustic tomography (PAT) is investigated. To verify this idea, the system of integrated optical fiber bundles and a custom-made flexible transducer is established, both of which give the advantage of morphological adaptation; therefore, the coupling section can be worn on human limbs. The imaging capacity of the flexible-transducer-based PAT system is validated by mapping the structures of the finger and the wrist joint. To the best of our knowledge, it is the first time to achieve photoacoustic imaging of such large human wrist joints. The cross-sectional photoacoustic images of a healthy joint clearly exhibit the main internal structures, including the phalanx, tendons, and blood vessels, which are comparable with the corresponding images by 3.0 T magnetic resonance imaging. The experimental results demonstrate that the proposed system holds promise for early diagnosis of joint disorders.

A spectrophotometer with an LED as the light source for uric acid detection is proposed in this work. The mechanism of uric acid detection is based on energy absorbed by sodium urate, which is a chemical product of uric acid and sodium hydroxide solution. For the performance validation, comparison between the spectrophotometer with an LED and halogen lamp is carried out. Measurement results suggest that the spectrophotometer system with LED light has better sensitivity than that with halogen light. At a 460 nm wavelength, the sensitivity for the spectrophotometer with an LED is 0.0046 dL/mg, which is 73% higher than that with halogen light that records 0.0012 dL/mg. This enhanced sensitivity is attributed to the higher luminous efficacy of the LED light beam. As a result, a larger amount of flux interacts with the sample, leading to the sensitivity enhancement. The spectrophotometer with an LED is also applied for the detection of uric acid in a real human urine sample. Based on the experimental data at a 460 nm wavelength, the method manages to achieve the sensitivity of 0.0016 dL/mg, accuracy of 96.01%, limit of detection of 4.79 mg/dL, and limit of quantification of 14.52 mg/dL. These findings show that the use of LED as the input light source is promising for the spectrophotometer.

Based on natural protein materials, a series of lenses with different heights and focal lengths were assembled on glass substrates by femtosecond laser non-contact, masking, and cold processing. This lens array itself possesses unique and characteristic optical performance in three-dimensional parallel imaging and bending imaging. What is more profound is that by using equilibrium swelling of protein-hydrogel, once the lens array was placed in a liquid environment, with the change of ion concentration (e.g., pH), the refractive index and curvature of the protein-hydrogel would change, which leads to the flex of the focal plane of the lens, finally realizing the dynamical tunability of a protein microlens. These smart stress devices may have great potential in optical biosensing and microfluidic chip integration fields.

The changes of mechanical properties and biological activities of monomeric erythrocytes are studied using optical tweezers micromanipulation technology. Firstly, the mechanical properties of irradiated erythrocyte membranes are obtained. Weaker power laser irradiation can delay the decay of the mechanical properties of erythrocytes and promote the biological activity of erythrocytes, while higher power laser irradiation damages erythrocytes. The stronger the laser irradiation is, the more obvious and rapid the damage will be. The temperature of the cell surface will be changed by regulating the laser power and irradiation time, so the biological functions of erythrocyte can be controlled. Secondly, the finite element simulation of the temperature change on the cell surface under the condition of laser irradiation is carried out using simulation software, and the precise temperature of the cell surface irradiated cumulatively by a laser with different powers is obtained. Finally, the processes of abscission, unfolding, and denaturation of hemoglobins in erythrocytes at different temperatures due to the photothermal effect are analyzed using the model. The mechanism of laser irradiation on the elasticity of erythrocyte membranes is also obtained.

Echinococcosis—a parasitic disease caused by Echinococcus granulosus or Echinococcus multilocularis larvae—occurs in many regions in the world. This disease can pose a serious threat to public health and thus requires a convenient and cost-effective method for early detection. So, we developed a novel method based on visual saliency and scale-invariant features that detects the tapeworm parasites. This method improves upon existing bottom-up computational saliency models by introducing a visual attention mechanism. The results indicated that the proposed method offers a higher level of both accuracy and computational efficiency when detecting Echinococcus granulosus protoscoleces, which in turn could improve early detection of echinococcosis.

This Letter tackles the issue of non-contact detection of ultrasonic fields by utilizing a novel optical method based on the parametric indirect microscopic imaging (PIMI) technique. A general theoretical model describing the three-dimensional anisotropic photoelastic effect in solid was developed. The mechanism of polarization status variations of light passing through the stress and strain fields was analyzed. Non-contact measurements of the ultrasonic field propagating in an isotropic quartz glass have been fulfilled by the PIMI technique under different ultrasonic excitation conditions. PIMI parameters such as sin δ, Φ, and the Stokes parameters have been found to be sensitive to ultrasonic fields.

We demonstrated a method for measurement of central corneal thickness (CCT) with a sub-micrometer sensitivity using a spectral domain optical coherence tomography system without needing a super broad bandwidth light source. By combining the frequency and phase components of Fourier transform, the method is capable of measurement of a large dynamic range with a high sensitivity. Absolute phases are retrieved by comparing the correlations between the detected and simulated interference fringes. The phase unwrapping ability of the present method was quantitatively tested by measuring the displacement of a piezo linear stage. The human CCTs of six volunteers were measured to verify its clinical application. It provides a potential tool for clinical diagnosis and research applications in ophthalmology.

We propose a fast and accurate automated algorithm to segment retinal pigment epithelium and internal limiting membrane layers from spectral domain optical coherence tomography (SDOCT) B-scan images. A hybrid algorithm, which combines intensity thresholding and graph-based algorithms, was used to process and analyze SDOCT radial scans (120 B scans) images obtained from twenty patients. The relative difference in position of the layers segmented by the proposed hybrid algorithm and by the clinical expert was 1.49% ± 0.01%. The processing time of the hybrid algorithm was 9.3 s for six B scans. Dice’s coefficient of the hybrid algorithm was 96.7% ± 1.6%. The proposed hybrid algorithm for the segmentation of SDOCT images had good agreement with manual segmentation and reduced processing time.

Photoacoustic (PA) microscopy comes with high potential for human skin imaging, since it allows noninvasively high-resolution imaging of the natural hemoglobin at depths of several millimeters. Here, we developed a PA microscopy to achieve high-resolution, high-contrast, and large field of view imaging of skin. A three-dimensional (3D) depth-coding technology was used to encode the depth information in PA images, which is very intuitive for identifying the depth of blood vessels in a two-dimensional image, and the vascular structure can be analyzed at different depths. Imaging results demonstrate that the 3D depth-coded PA microscopy should be translated from the bench to the bedside.

Blood oxygenation and flow are both important parameters in a living body. In this Letter, we introduce a simple configuration to simultaneously measure blood flow and oxygenation using an off-the-shelf spectrometer. With the integration time of 10 ms, flow phantom measurements, a liquid blood phantom test, and an arm cuff occlusion paradigm were performed to validate the feasibility of the system. We expect this proof-of-concept study would be widely adopted by other researchers for acquiring both blood flow and oxygenation changes due to its straightforward configuration and the possibility of multimodal measurement.

Photoacoustic imaging (PAI) has been used to characterize the spatial and quantitative features of lipid-rich atherosclerotic plaques with high sensitivity and specificity. In this Letter, we first validate that the ultra-low temperature and formaldehyde treatment have no effect on photoacoustic characteristics of the artery samples. Comparative experiments between the PAI and histological results demonstrate that the ultra-low temperature or formaldehyde treatment has few effects on the PAI of the lipid-rich atherosclerotic plaques; the lipid relative concentration and the lipid percentage by PAI hold high correlation with histology.

We demonstrate a system for measuring the ocular axial length (AL) with high sensitivity and high speed using spectral-domain low-coherence interferometry (SD-LCI). To address the limit in measuring such a large range by using SD-LCI, we propose a full-range method to recognize the positive and negative depths. The reference arm length is changed synchronously with the shift of the focal point of the probing beam. The system provides a composite depth range that is sufficient to cover the whole eye. We demonstrate the performance of the presented system by measuring the ALs of five volunteers. This system can provide the A-scan ocular biometric assessment of the corneal thickness and AL in 0.1 s.

Photoacoustic (PA) tomography (PAT) breaks the barrier for high-resolution optical imaging in a strong light-scattering medium, having a great potential for both clinical implementation and small animal studies. However, many organs and tissues lack enough PA contrast or even hinder the propagation of PA waves. Therefore, it is challenging to interpret pure PAT images, especially three-dimensional (3D) PA images for deep tissues, without enough structural information. To overcome this limitation, in this study, we integrated PAT with X-ray computed tomography (CT) in a standalone system. PAT provides optical contrast and CT gives anatomical information. We performed agar, tissue phantom, and animal studies, and the results demonstrated that PAT/CT imaging systems can provide accurate spatial registration of important complementary contrasts.

An endoscopic imaging system using a plenoptic technique to reconstruct 3-D information is demonstrated and analyzed in this Letter. The proposed setup integrates a clinical surgical endoscope with a plenoptic camera to achieve a depth accuracy error of about 1 mm and a precision error of about 2 mm, within a 25 mm×25 mm field of view, operating at 11 frames per second.

We experimentally demonstrate a metamaterials (MMs)-based terahertz (THz) sensor to quickly distinguish the cancer tissues from normal tissues. The MMs-based THz sensor has two strong resonance absorption peaks at about 0.706 and 1.14 THz, respectively. When the sensor is covered with cancer tissues, the redshifts at about 0.706 and 1.14 THz are 31 and 19 GHz, respectively. However, if normal tissue is attached to the surface of the sensor, the corresponding redshifts are only 15 and 12 GHz, respectively. This study proposes a new method for quick diagnosis of early lung cancer and other cancers.

We develop an improved global reconstruction method for Fourier ptychographic microscopy, a newly reported technique for wide-field and high-resolution microscopic observation. The gradational strategy and graphic processing unit computing are applied to accelerate the conventional global reconstruction method. Both simulations and experiments are carried out to evaluate the performance of our method, and the results show that this method offers a much faster convergence speed and maintains a good reconstruction quality.

Photoacoustic tomography is a noninvasive and nonionized biomedical imaging modality but it cannot reveal the inner structure and sideward boundary information of blood vessels in the linear array detection mode. In contrast, Monte Carlo (MC) light transport could provide the optical fluence distribution around the entire vascular area. This research explores the combination of linear array transducer-based photoacoustic tomography and MC light transport in the blood vessel quantification. Simulation, phantom, and in vivo experiments are in good correlation with the ultrasound imaging, validating this approach can clearly visualize the internal region of blood vessels from background tissue.

As a high-resulotion biological imaging technology, photoacoustic microscopy (PAM) is difficult to use in real-time imaging due to the long data acquisition time. Herein, a fast data acquisition and image recovery method named sparse PAM based on a low-rank matrix approximation is proposed. Specifically, the process to recover the final image from incomplete data is formulated into a low-rank matrix completion framework, and the “Go Decomposition” algorithm is utilized to solve the problem. Finally, both simulated and real PAM experiments are conducted to verify the performance of the proposed method and demonstrate clinical potential for many biological diseases.

Brain regenerative studies require precise visualization of the morphological structures. However, few imaging methods can effectively detect the adult zebrafish brain in real time with high resolution and good penetration depth. Long-term in vivo monitoring of brain injuries and brain regeneration on adult zebrafish is achieved in this study by using 1325 nm spectral-domain optical coherence tomography (SD-OCT). The SD-OCT is able to noninvasively visualize the skull injury and brain lesion of adult zebrafish. Valuable phenomenon such as the fractured skull, swollen brain tissues, and part of the brain regeneration process can be conducted based on the SD-OCT images at different time points during a period of 43 days.

This work proposes a method to concurrently calibrate multiple acoustic speeds in different mediums with a photoacoustic (PA) and ultrasound (US) dual-modality imaging system. First, physical infrastructure information of the target is acquired through a US image. Then, we repeatedly build PA images around a special target to yield the best focused result by dynamically updating the acoustic speeds in a different medium of the target. With these correct acoustic propagation velocities in the according mediums, we can effectively optimize the PA image quality as the experiments proved, which might benefit future research in biomedical imaging science.

A reconstruction method guided by early-photon fluorescence yield tomography is proposed for time-domain fluorescence lifetime tomography (FLT) in this study. The method employs the early-arriving photons to reconstruct a fluorescence yield map, which is utilized as a priori information to reconstruct the FLT via all the photons along the temporal-point spread functions. Phantom experiments demonstrate that, compared with the method using all the photons for reconstruction of fluorescence yield and lifetime maps, the proposed method can achieve higher spatial resolution and reduced crosstalk between different targets without sacrificing the quantification accuracy of lifetime and contrast between heterogeneous targets.

Simplified spherical harmonics approximation (SPN) equations are widely used in modeling light propagation in biological tissues. However, with the increase of order N, its computational burden will severely aggravate. We propose a graphics processing unit (GPU) accelerated framework for SPN equations. Compared with the conventional central processing unit implementation, an increased performance of the GPU framework is obtained with an increase in mesh size, with the best speed-up ratio of 25 among the studied cases. The influence of thread distribution on the performance of the GPU framework is also investigated.

Since significant ocular differences in both anatomical structure and optical properties exist between rodents and humans, clinical imaging devices for human use are not suitable for use on rodents. In this study, we develop a contact probe with a flexible surface that can closely fit the rodent cornea for fundus imaging with a confocal scanning laser ophthalmoscope. Both Zemax simulation and in vivo fundus imaging demonstrate that this contact probe can significantly improve both the imaging quality and the operational convenience.

The goal of this work is to evaluate the compositional and morphological changes of human dentin after erbium, chromium:yttrium–scandium–gallium–garnet (Er,Cr:YSGG) laser irradiation by Raman spectroscopy. The dentin surface of human molars are irradiated with an Er,Cr:YSGG laser at the output power of 3 and 3.5 W. Raman spectra before and after treatments are measured and analyzed. The results show that Raman spectroscopy can efficiently monitor the compositional changes of human dentin induced by an Er,Cr:YSGG laser. Although no new bands, band shifts, or disappearance of bands occurred, the intensities of the organic peaks associated with Amide I and CH2 are reduced significantly.

We build up a common-path optical coherence tomography (OCT) system using reflected light of sample surface as reference light. As the zero path length reference point has nothing to do with the distance between probe and organ, it can be utilized in endoscopic system. Besides, an optical delay stair is used in this common-path OCT to reconstruct the exact morphology of tissue surface, diminishing the distortion caused by sample surface reference.

The appearance of blood vessels is an important biomarker to distinguish diseased from healthy tissues in several fields of medical applications. Photoacoustic microangiography has the advantage of directly visualizing blood vessel networks within microcirculatory tissue. Usually these images are interpreted qualitatively. However, a quantitative analysis is needed to better describe the characteristics of the blood vessels. This Letter addresses this problem by leveraging an efficient multiscale Hessian filter-based segmentation method, and four measurement parameters are acquired. The feasibility of our approach is demonstrated on experimental data and we expect the proposed method to be beneficial for several microcirculatory disease studies.

We develop a prototype endoscope system that can perform high-dynamic-range structure imaging and hyperspectral imaging. The system is used to successfully acquire the oxyhemoglobin spectrum of blood capillaries and obtain in vivo images of the various vascular pattern structures of the underside of the human tongue with high intrinsic contrast and high dynamic range. The dynamic range of the acquired high-dynamic-range mucosa image is 116.5 dB, which is 68.2 dB higher than that of the mucosa images acquired by a normal low-dynamic-range CCD. Our results demonstrate the system’s tremendous potential for the clinical diagnosis of gastrointestinal diseases.

In this work two different fluorochromes (Alexa 594 and Alexa 680) are conjugated to the same monoclonal antibody (Cetuximab) for obtaining a characteristic M-shaped dual-peak spectrum. Dual-labeling of Cetuximab by mixing both fluorochromes before the conjugation step gives spectral results similar to those of mixing of fluorochrome-labeled Cetuximab after the conjugation step (P>0.05). In conclusion, both methods may be used equivalently for producing a dual-labeled single-antibody probe. Future studies may test whether the M-shaped spectrum may increase the diagnostic confidence in tumor-targeted multispectral optical imaging.

In this Letter, we discuss Raman–Nath acousto-optic diffraction, and a new model of Raman–Nath acousto-optic diffraction is presented. The model is based on the individual and simultaneous occurrences of phase-grating diffraction and the Doppler effect and optical phase modulation and photon–phonon scattering. We find that the optical phase modulation can cause temporal and spatial fluctuations of the diffracted light power escaping from the acoustic field.

It is highly necessary to study the phenomenon of photon migration in the knee joint for the non-invasive near-infrared optical early diagnosis of the osteoarthritis of the knee. We investigate the migration trace and distribution rule of the photons in knee layered structure, which are simulated by the Monte-Carlo modeling. The proportion of photons which collide with bone tissue then migrate out of the muscle tissue and photons directly migrate out of muscle tissue is calculated. For analyzing the signal-to-noise ratio to determine the accurate position of the detector, we perform quantitative evaluations of distribution of photons, as well as qualitative assessments of the distribution of photons.

A tunable pulsed laser induced photoacoustic (PA) measurement set-up is established in the forward mode to monitor in vitro glucose concentration. A series of experiments are investigated to verify the feasibility of this set-up and scheme. Peak-to-peak values (PPVs) of several glucose aqueous solutions are recorded and averaged 512 times at each wavelength. Experimental results demonstrate that the time-resolved PA profile of glucose solutions has a good agreement with the PA theories. The characteristic wavelengths of glucose solution are determined via differential method. The root-mean-square error (RMSE) of predicted concentration reaches 3.15 mg/dl at the optimum wavelength of 1 510 nm via least square (LS) fitting algorithm.

Activating mutants in rat sarcoma (RAS) and B-rapid accelerated fibrosarcoma (BRAF) are found in at least a third of cases of human tumors and melanoma; hence, numerous therapeutic treatments target this pathway. In this letter, we study the adhesion force of RAS-coated beads with BRAF-coated beads, BRAF (A246P) mutant–coated beads, and GST-coated beads using optical tweezers. One full and two fractional RAS–BRAF specific binding modes are identified using the rupture force distribution. The koff (0) of the full binding mode in RAS–BRAF is 3.71×10-4/s and 1.16×10-4s-1 in RAS–BRAF (A246P), whereas the xb is around 3 \times 10-10 m in both groups.

We carry out in situ single-molecule measurements of the specific interaction between apolipoprotein A-I (apoA-I) and ATP binding cassette transporter A1 (ABCA1) on THP-1 cells. Single-molecule force spectroscopy shows that similar to normal apoA-I, the dysfunctional apoA-I from diabetes patients interacts with ABCA1 via two different binding sites on the cells. The strength of dysfunctional apoA-I binding to a high-capacity binding site is 26.5+(-)4.9 pN. The minor direct apoA-I/ABCA1 binding strength is 56.7+(-)4.1 pN. These results facilitate a pathological understanding of the mechanisms that underlie the specific interaction of apoA-I and ABCA1 at the single-molecule level.

Determination of NO concentration in live cells is essential to evaluate its related cellular functions. In this letter, the concentration of NO in HeLa cells and rat dorsal root ganglion (DRG) neurons are studied by confocal laser scanning microscopy using DAF-2 DA as a fluorescence probe. The results show the fluorescence intensity of NO in HeLa cells is higher than that in DRG neurons, which indicats that the former exhibits higher NO concentration. Furthermore, the experimental conditions for low photobleaching and phototoxicity are optimized.

Monte Carlo (MC) method is a statistical method for simulating photon propagation in media in the optical molecular imaging field. However, obtaining an accurate result using the method is quite time-consuming, especially because the boundary of the media is complex. A voxel classification method is proposed to reduce the computation cost. All the voxels generated by dividing the media are classified into three types (outside, boundary, and inside) according to the position of the voxel. The classified information is used to determine the relative position of the photon and the intersection between photon path and media boundary in the MC method. The influencing factors and effectiveness of the proposed method are analyzed and validated by simulation experiments.