The new Editor-in-Chief, Brian Pogue, gives an overview of the biomedical optics community.

JBO thanks everyone who served as a reviewer in 2017.

Normal development of the visual system in infants relies on clear images being projected onto the retina, which can be disrupted by lens opacity caused by congenital cataract. This disruption, if uncorrected in early life, results in amblyopia (permanently decreased vision even after removal of the cataract). Doctors are able to prevent amblyopia by removing the cataract during the first several weeks of life, but this surgery risks a host of complications, which can be equally visually disabling. Here, we investigated the feasibility of focusing light noninvasively through highly scattering cataractous lenses to stimulate the retina, thereby preventing amblyopia. This approach would allow the cataractous lens removal surgery to be delayed and hence greatly reduce the risk of complications from early surgery. Employing a wavefront shaping technique named time-reversed ultrasonically encoded optical focusing in reflection mode, we focused 532-nm light through a highly scattering ex vivo adult human cataractous lens. This work demonstrates a potential clinical application of wavefront shaping techniques.

A two-frequency laser scanning confocal fluorescence microscope (TF-LSCFM) based on intensity modulated fluorescence signal detection was proposed. The specimen-induced spherical aberration and scattering effect were suppressed intrinsically, and high image contrast was presented due to heterodyne interference. An improved axial point spread function in a TF-LSCFM compared with a conventional laser scanning confocal fluorescence microscope was demonstrated and discussed.

Noninvasive photobiomodulation therapy (PBMT) of spinal cord disease remains speculative due to the lack of evidence for whether photobiomodulatory irradiances can be transcutaneously delivered to the spinal cord under a clinically acceptable PBMT surface irradiation protocol. We developed a flexible nine-channel photodetection probe for deployment within the spinal canal of a cadaver dog after hemilaminectomy to measure transcutaneously transmitted PBMT irradiance at nine sites over an eight-cm spinal canal length. The probe was built upon a 6.325-mm tubular stem, to the surface of which nine photodiodes were epoxied at approximately 1 cm apart. The photodiode has a form factor of 4.80  mm×2.10  mm×1.15  mm (length×width×height). Each photodiode was individually calibrated to deliver 1 V per 7.58  μW/cm2 continuous irradiance at 850 nm. The outputs of eight photodiodes were logged concurrently using a data acquisition module interfacing eight channels of differential analog signals, while the output of the ninth photodiode was measured by a precision multimeter. This flexible probe rendered simultaneous intraspinal (nine-site) measurements of transcutaneous PBMT irradiations at 980 nm in a pilot cadaver dog model. At a surface continuous irradiance of 3.14  W/cm2 applied off-contact between L1 and L2, intraspinal irradiances picked up by nine photodiodes had a maximum of 327.48  μW/cm2 without the skin and 5.68  μW/cm2 with the skin.

We present a highly scalable Monte Carlo (MC) three-dimensional photon transport simulation platform designed for heterogeneous computing systems. Through the development of a massively parallel MC algorithm using the Open Computing Language framework, this research extends our existing graphics processing unit (GPU)-accelerated MC technique to a highly scalable vendor-independent heterogeneous computing environment, achieving significantly improved performance and software portability. A number of parallel computing techniques are investigated to achieve portable performance over a wide range of computing hardware. Furthermore, multiple thread-level and device-level load-balancing strategies are developed to obtain efficient simulations using multiple central processing units and GPUs.

An important step in establishing the diagnostic potential for emerging optical imaging techniques is accurate registration between imaging data and the corresponding tissue histopathology typically used as gold standard in clinical diagnostics. We present a method to precisely register data acquired with a point-scanning spectroscopic imaging technique from fresh surgical tissue specimen blocks with corresponding histological sections. Using a visible aiming beam to augment point-scanning multispectral time-resolved fluorescence spectroscopy on video images, we evaluate two different markers for the registration with histology: fiducial markers using a 405-nm CW laser and the tissue block’s outer shape characteristics. We compare the registration performance with benchmark methods using either the fiducial markers or the outer shape characteristics alone to a hybrid method using both feature types. The hybrid method was found to perform best reaching an average error of 0.78±0.67  mm. This method provides a profound framework to validate diagnostical abilities of optical fiber-based techniques and furthermore enables the application of supervised machine learning techniques to automate tissue characterization.

Presbyopia correction involves different types of studies such as lens design, clinical study, and the development of objective metrics, such as the visual Strehl ratio. Different contact lens designs have been proposed for presbyopia correction, but performance depends on pupil diameter. We will analyze the potential use of a nonsymmetrical element, a cubic phase mask (CPM) solution, to develop a contact or intraocular lens whose performance is nearly insensitive to changes in pupil diameter. We will show the through focus optical transfer function of the proposed element for different pupil diameters ranging from 3 to 7 mm. Additionally, we will show the images obtained through computation and experiment for a group of eye charts with different visual acuities. Our results show that a CPM shaped as 7.07  μm*(Z33−Z3−3)−0.9  μmZ20 is a good solution for a range of clear vision with a visual acuity of at least 0.1 logMar from 0.4 to 6 m for pupil diameters in the 3- to 7-mm range. Our results appear to be a good starting point for further development and study of this kind of CPM solution for presbyopia.

The study aimed to determine whether the red fluorescence (RF) of a dental microcosm biofilm as measured with quantitative light-induced fluorescence (QLF) technology is useful for assessing the efficacy of antimicrobials. Dental microcosm biofilms were formed on bovine enamel discs and grown under 0.3% sucrose challenge and treated with chlorhexidine (CHX) solutions at different concentrations (0.05%, 0.1%, and 0.5%) plus a negative control [sterile distilled water (DW)] twice daily for 7 days. The biofilms were photographed using a QLF-digital system to evaluate the RF by calculating the red/green ratio, and pH values of the medium were measured daily. After 7 days, the bacterial viability of the biofilm was assessed by measuring the counts of viable total bacteria and aciduric bacteria, and the percentage surface microhardness changes (%SHC) was evaluated. The RF and cariogenic properties were compared for the different concentrations of CHX, and their correlations were examined. The RF and its increase rate were much lower for CHX-treated biofilms than for DW-treated biofilms. The RF after 7 days of maturation decreased significantly with increasing CHX concentrations ( p<0.001) and was from 31% (for 0.05% CHX) to 46% (for 0.5% CHX) lower than that of the DW group. Strong correlations were reported between the RF of the 7-day-maturation biofilms and cariogenic properties, such as the number of total bacteria ( r=0.93), number of aciduric bacteria ( r=0.97), supernatant pH ( r=0.43), and %SHC ( r=0.98). In conclusion, the RF of dental biofilms as measured with QLF technology can be used to nondestructively assess and monitor the effect of antimicrobials against biofilm.

Intravascular imaging techniques provide detailed specification about plaque appearance and morphology, but cannot deliver information about the biochemical composition of atherosclerotic plaques. As the biochemical composition is related to the plaque type, important aspects such as the risk of a plaque rupture and treatment are still difficult to assess. Currently, various spectroscopic techniques are tested for potential applications for the chemical analysis of plaque depositions. Here, we employ Raman spectroscopy in combination with optical coherence tomography (OCT) for the characterization of plaques on rabbits in vivo. Experiments were carried out on New Zealand white rabbits treated with a fat- and cholesterol-enriched diet, using a Raman probe setup with a 785-nm multimode laser as an excitation source. Subsequently, OCT images were acquired with a swept source at 1305±55  nm at 22.6 mW. Raman spectra were recorded from normal regions and regions with early plaque formations. The probe positioning was monitored by x-ray angiography. The spectral information identified plaque depositions consisting of lipids, with triglycerides as the major component. Afterward, OCT images of the spectroscopically investigated areas were obtained. The spectral information correlates well with the observed intravascular morphology and is in good agreement with histology. Raman spectroscopy can provide detailed biochemical specification of atherosclerotic plaques.

An in-house fabricated portable device has been tested to detect cervical precancer through the intrinsic fluorescence from human cervix of the whole uterus in a clinical setting. A previously validated technique based on simultaneously acquired polarized fluorescence and polarized elastic scattering spectra from a turbid medium is used to extract the intrinsic fluorescence. Using a diode laser at 405 nm, intrinsic fluorescence of flavin adenine dinucleotide, which is the dominant fluorophore and other contributing fluorophores in the epithelium of cervical tissue, has been extracted. Different grades of cervical precancer (cervical intraepithelial neoplasia; CIN) have been discriminated using principal component analysis-based Mahalanobis distance and linear discriminant analysis. Normal, CIN I and CIN II samples have been discriminated from one another with high sensitivity and specificity at 95% confidence level. This ex vivo study with cervix of whole uterus samples immediately after hysterectomy in a clinical environment indicates that the in-house fabricated portable device has the potential to be used as a screening tool for in vivo precancer detection using intrinsic fluorescence.

Manifestation of Čerenkov radiation as a contaminating signal is a significant issue in radiation therapy dose measurement by fiber-coupled scintillator dosimeters. To enhance the scintillation signal transmission while minimizing Čerenkov radiation contamination, we designed a fiber probe using a silver-only coated hollow waveguide (HWG). The HWG with scintillator inserted in its tip, embedded in tissue-mimicking phantoms, was irradiated with clinical electron and photon beams generated by a medical linear accelerator. Optical spectra of the irradiated tip were taken using a fiber spectrometer, and the signal was deconvolved with a linear fitting algorithm. The resultant decomposed spectra of the scintillator with and without Čerenkov correction were in agreement with measurements performed by a standard electron diode and ion chamber for electron and photon beam dosimetry, respectively, indicating the minimal effect of Čerenkov contamination in the HWG-based dosimeter. Furthermore, compared with a silver/dielectric-coated HWG fiber dosimeter design, we observed higher signal transmission in the design based on the use of silver-only HWG.

The purpose of the study was to compare muscle oxygenation as measured by two portable, wireless near-infrared spectroscopy (NIRS) devices under resting and dynamic conditions. A recently developed low-cost NIRS device (MOXY) was compared against an established PortaMon system that makes use of the spatially resolved spectroscopy algorithm. The influence of increasing external pressure on tissue oxygen saturation index (TSI) indicated that both devices are stable between 2 and 20 mmHg. However, above this pressure, MOXY reports declining TSI values. Analysis of adipose tissue thickness (ATT) and TSI shows a significant, nonlinear difference between devices at rest. The devices report similar TSI (%) values at a low ATT ( <7  mm) (PortaMon minus MOXY difference is +1.1±2.8%) with the major subsequent change between the devices occurring between 7 and 10 mm; at ATT values >10  mm the difference remains constant ( −14.7±2.8%). The most likely explanation for this difference is the small source–detector separation (2.5 cm) in the MOXY resulting in lower tissue penetration into muscle in subjects with higher ATT. Interday test–retest reliability of resting TSI was evaluated on five separate occasions, with the PortaMon reporting a lower coefficient of variation (1.8% to 2.5% versus 5.7% to 6.2%). In studies on male subjects with low ATT, decreases in the TSI were strongly correlated during isometric exercise, arterial occlusion, and incremental arm crank exercise. However, the MOXY reports a greater dynamic range, particularly during ischemia induced by isometric contraction or occlusion ( Δ74.3% versus Δ43.7%; hyperemia MAX—occlusion MIN). This study shows that in this subject group both MOXY and PortaMon produce physiologically credible TSI measures during rest and exercise. However, the absolute values obtained during exercise are generally not comparable between devices unless corrected by physiological calibration following an arterial occlusion.

Water loss is an early onset indicator of osteoarthritis. Although Raman spectroscopy (RS) holds the potential for measurement of cartilage hydration, the knowledge of Raman OH-stretch bands of biological tissue is very limited. We assesed here the sensitivity of RS to identify and classify water types in the cartilage. Raman spectrum measurements over the high wavenumber range were employed to identify different water fractions in articular cartilage. Raman spectra were collected from wet and sequentially dehydrated cartilage along with pure collagen type II and chondroitin sulfate standards. OH-stretch band of cartilage is dominated by mobile water, up to 95% of total intensities. We identified six peaks in cartilage spectrum using second-derivative analysis: peaks at 3200 and 3650  cm−1 are associated with organic matrix (both collagen and proteglycan) and matrix-bound water molecules. Peaks at 3250, 3453, and 3630  cm−1 are associated with collagen and collagen-related water molecules, whereas the peak at 3520  cm−1 is associated with proteoglycan (PG) and PG-related water molecules. The current work is the first thorough analysis of the Raman OH-stretch band of the cartilage and with the knowledge generated by this study, it may now be possible to study on cartilage hydration by RS.

Here, we compared the hemodynamic response observed during swallowing of water or saliva using near-infrared spectroscopy (NIRS). Sixteen healthy adults swallowed water or saliva in a randomized order. Relative concentration changes in oxygenated and deoxygenated hemoglobin during swallowing were assessed. Both swallowing tasks led to the strongest NIRS signal change over the bilateral inferior frontal gyrus. Water swallowing led to a stronger activation over the right hemisphere while the activation focus for saliva swallowing was stronger left lateralized. The NIRS time course also differed between both swallowing tasks especially at the beginning of the tasks, which might be a sign of differences in task effort. Our results show that NIRS is a sensitive measure to reveal differences in the topographical distribution and time course of the hemodynamic response between distinct swallowing tasks and might be therefore an adequate diagnostic and therapy tool for swallowing difficulties.

We study the effectiveness of several low-cost oblique illumination filters to improve overall image quality, in comparison with standard bright field imaging. For this purpose, a dataset composed of 3360 diatom images belonging to 21 taxa was acquired. Subjective and objective image quality assessments were done. The subjective evaluation was performed by a group of diatom experts by psychophysical test where resolution, focus, and contrast were assessed. Moreover, some objective nonreference image quality metrics were applied to the same image dataset to complete the study, together with the calculation of several texture features to analyze the effect of these filters in terms of textural properties. Both image quality evaluation methods, subjective and objective, showed better results for images acquired using these illumination filters in comparison with the no filtered image. These promising results confirm that this kind of illumination filters can be a practical way to improve the image quality, thanks to the simple and low cost of the design and manufacturing process.

Photoacoustic tomography (PAT) is a hybrid imaging modality where we intend to reconstruct optical properties of heterogeneous media from measured ultrasound signals generated by the photoacoustic effect. In recent years, there have been considerable interests in using PAT to image two-photon absorption, in addition to the usual single-photon absorption, inside diffusive media. We present a mathematical model for quantitative image reconstruction in two-photon photoacoustic tomography (TP-PAT). We propose a computational strategy for the reconstruction of the optical absorption coefficients and provide some numerical evidences based on synthetic photoacoustic acoustic data to demonstrate the feasibility of quantitative reconstructions in TP-PAT.

Observation of temperature-mediated phase transitions between lipid components of the adipose tissues has been performed by combined use of the Abbe refractometry and optical coherence tomography. The phase transitions of the lipid components were clearly observed in the range of temperatures from 24°C to 60°C, and assessed by quantitatively monitoring the changes of the refractive index of 1- to 2-mm-thick porcine fat tissue slices. The developed approach has a great potential as an alternative method for obtaining accurate information on the processes occurring during thermal lipolysis.

We present a method for the correction of motion artifacts present in two- and three-dimensional in vivo endoscopic images produced by rotary-pullback catheters. This method can correct for cardiac/breathing-based motion artifacts and catheter-based motion artifacts such as nonuniform rotational distortion (NURD). This method assumes that en face tissue imaging contains slowly varying structures that are roughly parallel to the pullback axis. The method reduces motion artifacts using a dynamic time warping solution through a cost matrix that measures similarities between adjacent frames in en face images. We optimize and demonstrate the suitability of this method using a real and simulated NURD phantom and in vivo endoscopic pulmonary optical coherence tomography and autofluorescence images. Qualitative and quantitative evaluations of the method show an enhancement of the image quality.

Pulmonary metastasectomy for osteosarcoma provides a select group of patients an opportunity for long-term survival and possible cure. Unfortunately, a complete metastasectomy is challenging due an inability to accurately identify lesions that lay below the threshold of preoperative imaging or intraoperative visual and tactile inspection. Growing evidence suggests that osteosarcomas express a number of unique molecular markers, including the folate receptor alpha. In this case report, we describe the application of a folate receptor-targeted, near-infrared optical contrast agent (OTL38) to improve osteosarcoma localization during minimally invasive pulmonary resection. In addition to localizing preoperatively identified lesions, this technology helped identify additional disease that was undetected on preoperative imaging or with traditional intraoperative techniques. This report marks the first successful utilization of a molecular imaging probe useful for osteosarcomas. This technology may provide a unique approach to improve pulmonary metastasectomy of osteosarcomas.

Based on our recently developed quantitative fluorescence resonance energy transfer (FRET) measurement method using simultaneous spectral unmixing of excitation and emission spectra (ExEm-spFRET), we here set up an improved spectrometer-microscope (SM) for implementing modified ExEm-spFRET (mExEm-spFRET), in which a system correction factor ( fsc) is introduced. Our SM system is very stable for at least six months. Implementation of mExEm-spFRET with four or two excitation wavelengths on SM for single living cells expressing different FRET constructs obtained consistent FRET efficiency ( E) and acceptor–donor concentration ratio ( Rc) values. We also performed mExEm-spFRET measurement for single living cells coexpressing cyan fluorescent protein (CFP)-Bax and yellow fluorescent protein (YFP)-Bax and found that the E values between CFP-Bax and YFP-Bax were very low (2.2%) and independent of Rc for control cells, indicating that Bax did not exist as homooligomer in healthy cells, but positively proportional to Rc in the case of Rc<1 and kept constant value (25%) when Rc>1 for staurosporine (STS)-treated cells, demonstrating that all Bax formed homooligomer after STS treatment for 6 h.

We have developed a polarization microscope based on a commercial transmission microscope. We replace the halogen light source by a collimated LED light source module of six different colors. We use achromatic polarized optical elements that can cover the six different wavelength ranges in the polarization state generator (PSG) and polarization state analyzer (PSA) modules. The dual-rotating wave plate method is used to measure the Mueller matrix of samples, which requires the simultaneous rotation of the two quarter-wave plates in both PSG and PSA at certain angular steps. A scientific CCD detector is used as the image receiving module. A LabView-based software is developed to control the rotation angels of the wave plates and the exposure time of the detector to allow the system to run fully automatically in preprogrammed schedules. Standard samples, such as air, polarizers, and quarter-wave plates, are used to calibrate the intrinsic Mueller matrix of optical components, such as the objectives, using the eigenvalue calibration method. Errors due to the images walk-off in the PSA are studied. Errors in the Mueller matrices are below 0.01 using air and polarizer as standard samples. Data analysis based on Mueller matrix transformation and Mueller matrix polarization decomposition is used to demonstrate the potential application of this microscope in pathological diagnosis.

An automated serial histology setup combining optical coherence tomography (OCT) imaging with vibratome sectioning was used to image eight wild type mouse brains. The datasets resulted in thousands of volumetric tiles resolved at a voxel size of (4.9×4.9×6.5)  μm3 stitched back together to give a three-dimensional map of the brain from which a template OCT brain was obtained. To assess deformation caused by tissue sectioning, reconstruction algorithms, and fixation, OCT datasets were compared to both in vivo and ex vivo magnetic resonance imaging (MRI) imaging. The OCT brain template yielded a highly detailed map of the brain structure, with a high contrast in white matter fiber bundles and was highly resemblant to the in vivo MRI template. Brain labeling using the Allen brain framework showed little variation in regional brain volume among imaging modalities with no statistical differences. The high correspondence between the OCT template brain and its in vivo counterpart demonstrates the potential of whole brain histology to validate in vivo imaging.

The metabolic rate of oxygen consumption is an important metric of tissue oxygen metabolism and is especially critical in the brain, yet few methods are available for measuring it. We use a custom combined photoacoustic-microultrasound system and demonstrate cerebral oxygen consumption estimation in vivo. In particular, the cerebral metabolic rate of oxygen consumption was estimated in a murine model during variation of inhaled oxygen from hypoxia to hyperoxia. The hypothesis of brain autoregulation was confirmed with our method even though oxygen saturation and flow in vessels changed.

Tissue perfusion is essential for transporting blood oxygen and nutrients. Measurement of tissue perfusion rate would have a significant impact in clinical and preclinical arenas. However, there are few techniques to image this important parameter and they typically require contrast agents. A label-free methodology based on tissue compression and imaging with a high-frequency photoacoustic-ultrasound system is introduced for estimating and visualizing tissue perfusion rates. Experiments demonstrate statistically significant differences in depth-resolved perfusion rates in a human subject with various temperature exposure conditions.

Whole thoracic irradiation (WTI) is known to cause deterioration in cardiac function. Whether irradiation predisposes the heart to further ischemia and reperfusion (IR) injury is not well known. The aim of this study is to examine the susceptibility of rat hearts to IR injury following a single fraction of 15 Gy WTI and to investigate the role of mitochondrial metabolism in the differential susceptibility to IR injury. After day 35 of irradiation, ex vivo hearts from irradiated and nonirradiated rats (controls) were exposed to 25-min global ischemia followed by 60-min IR, or hearts were perfused without IR for the same protocol duration [time controls (TC)]. Online fluorometry of metabolic indices [redox state: reduced nicotinamide adenine dinucleotide (NADH), oxidized flavin adenine dinucleotide (FAD), and NADH/FAD redox ratio] and functional variables [systolic left ventricular pressure (LVP), diastolic LVP (diaLVP), coronary flow (CF), and heart rate were recorded in the beating heart; developed LVP (dLVP) and rate pressure product (RPP)] were derived. At the end of each experimental protocol, hearts were immediately snap frozen in liquid N2 for later three-dimensional imaging of the mitochondrial redox state using optical cryoimaging. Irradiation caused a delay in recovery of dLVP and RPP after IR when compared to nonirradiated hearts but recovered to the same level at the end of reperfusion. CF in the irradiated hearts recovered better than the control hearts after IR injury. Both fluorometry and 3-D cryoimaging showed that in WTI and control hearts, the redox ratio increased during ischemia (reduced) and decreased on reperfusion (oxidized) when compared to their respective TCs; however, there was no significant difference in the redox state between WTI and controls. In conclusion, our results show that although irradiation of rat hearts compromised baseline cardiovascular function, it did not alter cardiac mitochondrial redox state and induce greater susceptibility of these hearts to IR injury.

Stroke due to hypoperfusion or emboli is a devastating adverse event of cardiac surgery, but early detection and treatment could protect patients from an unfavorable postoperative course. Hypoperfusion and emboli can be detected with transcranial Doppler of the middle cerebral artery (MCA). The measured blood flow velocity correlates with cerebral oxygenation determined clinically by near-infrared spectroscopy (NIRS) of the frontal cortex. We tested the potential advantage of a spatially extended NIRS in detecting critical events in three cardiac surgery patients with a whole-head fiber holder of the FOIRE-3000 continuous-wave NIRS system. Principle components analysis was performed to differentiate between global and localized hypoperfusion or ischemic territories of the middle and anterior cerebral arteries. In one patient, we detected a critical hypoperfusion of the right MCA, which was not apparent in the frontal channels but was accompanied by intra- and postoperative neurological correlates of ischemia. We conclude that spatially extended NIRS of temporal and parietal vascular territories could improve the detection of critically low cerebral perfusion. Even in severe hemispheric stroke, NIRS of the frontal lobe may remain normal because the anterior cerebral artery can be supplied by the contralateral side directly or via the anterior communicating artery.

Optical coherence tomography (OCT) is a prevalent, interferometric, high-resolution imaging method with broad biomedical applications. Nonetheless, OCT images suffer from an artifact called speckle, which degrades the image quality. Digital filters offer an opportunity for image improvement in clinical OCT devices, where hardware modification to enhance images is expensive. To reduce speckle, a wide variety of digital filters have been proposed; selecting the most appropriate filter for an OCT image/image set is a challenging decision, especially in dermatology applications of OCT where a different variety of tissues are imaged. To tackle this challenge, we propose an expandable learnable despeckling framework, we call LDF. LDF decides which speckle reduction algorithm is most effective on a given image by learning a figure of merit (FOM) as a single quantitative image assessment measure. LDF is learnable, which means when implemented on an OCT machine, each given image/image set is retrained and its performance is improved. Also, LDF is expandable, meaning that any despeckling algorithm can easily be added to it. The architecture of LDF includes two main parts: (i) an autoencoder neural network and (ii) filter classifier. The autoencoder learns the FOM based on several quality assessment measures obtained from the OCT image including signal-to-noise ratio, contrast-to-noise ratio, equivalent number of looks, edge preservation index, and mean structural similarity index. Subsequently, the filter classifier identifies the most efficient filter from the following categories: (a) sliding window filters including median, mean, and symmetric nearest neighborhood, (b) adaptive statistical-based filters including Wiener, homomorphic Lee, and Kuwahara, and (c) edge preserved patch or pixel correlation-based filters including nonlocal mean, total variation, and block matching three-dimensional filtering.

Temperature mapping during thermotherapy can help precisely control the heating process, both temporally and spatially, to efficiently kill the tumor cells and prevent the healthy tissues from heating damage. Photoacoustic tomography (PAT) has been used for noninvasive temperature mapping with high sensitivity, based on the linear correlation between the tissue’s Grüneisen parameter and temperature. However, limited by the tissue’s unknown optical properties and thus the optical fluence at depths beyond the optical diffusion limit, the reported PAT thermometry usually takes a ratiometric measurement at different temperatures and thus cannot provide absolute measurements. Moreover, ratiometric measurement over time at different temperatures has to assume that the tissue’s optical properties do not change with temperatures, which is usually not valid due to the temperature-induced hemodynamic changes. We propose an optical-diffusion-model-enhanced PAT temperature mapping that can obtain the absolute temperature distribution in deep tissue, without the need of multiple measurements at different temperatures. Based on the initial acoustic pressure reconstructed from multi-illumination photoacoustic signals, both the local optical fluence and the optical parameters including absorption and scattering coefficients are first estimated by the optical-diffusion model, then the temperature distribution is obtained from the reconstructed Grüneisen parameters. We have developed a mathematic model for the multi-illumination PAT of absolute temperatures, and our two-dimensional numerical simulations have shown the feasibility of this new method. The proposed absolute temperature mapping method may set the technical foundation for better temperature control in deep tissue in thermotherapy.

Iterative phase retrieval (IPR) has developed into a feasible and simple computational method to retrieve a complex-valued sample. Due to coherent illumination, the reconstructed image quality is degraded by speckle noise arising from a laser. Accordingly, partially coherent illumination has been introduced to alleviate this restriction. We apply weighted feedback modality into multidistance and multiwavelength phase retrieval to realize high-contrast and fast imaging. In simulation, it is proved that IPR based on weighted feedback accelerates the convergence in partially coherent illumination and speckle illumination. In experiment, the resolution chart and biological specimen are reconstructed in lensless and lens-based systems, which also demonstrate the performance of weighted feedback. This work provides a simple and high-contrast imaging modality for IPR. Also, it facilitates compact and flexible experimental implementation for label-free imaging.

We report the design, fabrication, and characterization of an optical fiber sensor based on the surface plasmon resonance (SPR) technique for the simultaneous determination of lead (Pb) and copper (Cu) metal ions in aqueous samples. Two cascade channels over a single optical fiber are fabricated by removing cladding from two well-separated regions of the fiber. SPR working as a transducing mechanism for the sensor is realized by coating thin films of copper and silver over unclad cores of channel I and channel II, respectively. Ion-imprinted nanoparticles for both ions are separately synthesized and coated over the metal-coated unclad cores of the fiber as the recognition layers for sensor fabrication. A first channel having layer of Pb(II) ion-imprinted nanoparticles detects Pb(II) ions and a second channel having layer of Cu(II) ion-imprinted nanoparticles are used for the detection of Cu(II) ions. Both channels are characterized using the wavelength interrogation method. The sensor operates in the range between 0 to 1000  μg/L and 0 to 1000  mg/L for Pb(II) and Cu(II) ions, respectively. These ranges cover water resources and the human body for these ions. The sensitivities of channel I and channel II are found to be 8.19×104  nm/(μg/L) and 4.07×105  nm/(mg/L) near the lowest concentration of Pb(II) and Cu(II) ions, respectively. The sensor can detect concentrations of Pb(II) and Cu(II) ions as low as 4.06 × 10⁻¹² g/L and 8.18 × 10⁻¹⁰ g/L, respectively, which are the least among the reported values in the literature. Further, the probe is simple, cost effective, highly selective, and applicable for online monitoring and remote sensing.

DNA-functionalized nanoparticles, when paired with surface-enhanced Raman spectroscopy (SERS), can rapidly detect microRNA. However, widespread use of this approach is hindered by drawbacks associated with large and expensive benchtop Raman microscopes. MicroRNA-17 (miRNA-17) has emerged as a potential epigenetic indicator of preeclampsia, a condition that occurs during pregnancy. Biomarker detection using an SERS point-of-care device could enable prompt diagnosis and prevention as early as the first trimester. Recently, strides have been made in developing portable Raman systems for field applications. An SERS assay for miRNA-17 was assessed and translated from traditional benchtop Raman microscopes to a handheld system. Three different photoactive molecules were compared as potential Raman reporter molecules: a chromophore, malachite green isothiocyanate (MGITC), a fluorophore, tetramethylrhodamine isothiocyanate, and a polarizable small molecule 5,5-dithio-bis-(2-nitrobenzoic acid) (DTNB). For the benchtop Raman microscope, the DTNB-labeled assay yielded the greatest sensitivity under 532-nm laser excitation, but the MGITC-labeled assay prevailed at 785 nm. Conversely, DTNB was preferable for the miniaturized 785-nm Raman system. This comparison showed significant SERS enhancement variation in response to 1-nM miRNA-17, implying that the sensitivity of the assay may be more heavily dependent on the excitation wavelength, instrumentation, and Raman reporter chosen than on the plasmonic coupling from DNA/miRNA-mediated nanoparticle assemblies.

The objective of this work was to compare the accuracy of analyte concentration estimation when using transmission versus diffuse reflectance spectroscopy of a scattering medium. Monte Carlo ray tracing of light through the medium was used in conjunction with pure component absorption spectra and Beer–Lambert absorption along each ray’s pathlength to generate matched sets of pseudoabsorbance spectra, containing water and six analytes present in skin. PLS regression models revealed an improvement in accuracy when using transmission compared to reflectance for a range of medium thicknesses and instrument noise levels. An analytical expression revealed the source of the accuracy degradation with reflectance was due both to the reduced collection efficiency for a fixed instrument etendue and to the broad pathlength distribution that detected light travels in the medium before exiting from the incident side.