Hemolysis Detection in Sub-Microliter Volumes of Blood Plasma.

OBJECTIVE: Hemolysis is one of the main reasons for blood sample rejection in clinical laboratories. The scope of this study is to develop a simple, sensitive, and cost-effective method for hemolysis detection in presence of interferants like bilirubin, and lipids in sub-microliter volumes of blood plasma. METHODS: Experimental samples were prepared in plasma extracted from whole blood. These samples were typically mixtures of hemoglobin, bilirubin, and lipids of varying concentrations. A multispectral optical setup was devised to probe these samples without any optical filters or moving parts. RESULTS: The hemoglobin content in the samples were measured within the range of 0 mg/dL to 400 mg/dL concentration using <1 µL of detection volume. Detection sensitivity of >90% accuracy and ∼10% coefficient of variation across 27 unknown samples. The optical attenuation path length used was merely ∼150 micrometers. The spectral interference due to overlapping absorption spectrum of bilirubin and scattering spectrum of lipids are resolved using linear matrix algebra algorithms. CONCLUSION: Hemolysis can lead to spurious measurements of key clinical parameters such as Potassium, Lactate Dehydrogenase, Aspartic Acid Transferase, and other diagnostic biomarkers. Commonly used visual inspection of blood plasma coloration is prone to variability. Description of the sample preparation, calibration and verification of the experimental setup and linear matrix algebra algorithm for analyte interference determination is reported here. SIGNIFICANCE: Owing to the sub-microliter detection volume and high sensitivity, the system has realistic potential to be implemented in point of care medical devices that demands such low volumes of clinical specimen.

Laplace-domain diffuse optical measurement.

Time-domain diffuse optical measurement systems determine depth-resolved absorption changes by using the time of flight distribution of the detected photons. It is well known that certain feature data, such as the Laplace transform of the temporal point spread function, is sufficient for image reconstruction and diffuse optical sensing. Conventional time-domain systems require the acquisition of full temporal profiles of diffusive photons and then numerically compute the feature dataset, for example, Laplace transformed intensities for imaging applications. We have proposed a novel method for directly obtaining the Laplace transform data. Our approach can significantly improve the data acquisition speed for time-domain diffuse optical imaging. We also demonstrated that the use of negative Laplace parameters can provide enhanced sensitivity to perturbations located in deep regions.

Ultrahigh-speed line-scan SD-OCT for four-dimensional in vivo imaging of small animal models.

We report an ultrahigh-speed and high-resolution line-scan spectral-domain optical coherence tomography (SD-OCT) system that integrates a number of mechanisms for improving image quality. The illumination uniformity is significantly improved by the use of a Powell lens; Phase stepping and differential reconstruction are combined to suppress autocorrelation artifacts; Nonlocal means (NLM) is employed to enhance the signal to noise ratio while minimizing motion artifacts. The system is capable of acquiring cross-sectional images at more than 3,500 B-scans per second with sensitivities between 70dB and 90dB. The high B-scan rate enables image post-processing with nonlocal means, an advanced noise reduction algorithm that affords enhanced morphological details and reduced motion artifacts. The achieved axial and lateral resolutions are 2.0 and 6.2 microns, respectively. We have used this system to acquire four-dimensional (three-dimensional space and one-dimensional time) imaging data from live chicken embryos at up to 40 volumes per second. Dynamic cardiac tissue deformation and blood flow could be clearly visualized at high temporal and spatial resolutions, providing valuable information for understanding the mechanical and fluid dynamic properties of the developing cardiac system.

Spread spectrum time-resolved diffuse optical measurement system for enhanced sensitivity in detecting human brain activity.

Diffuse optical spectroscopy (DOS) and imaging methods have been widely applied to noninvasive detection of brain activity. We have designed and implemented a low cost, portable, real-time one-channel time-resolved DOS system for neuroscience studies. Phantom experiments were carried out to test the performance of the system. We further conducted preliminary human experiments and demonstrated that enhanced sensitivity in detecting neural activity in the cortex could be achieved by the use of late arriving photons.

A method to study the hemodynamics of chicken embryo's aortic arches using optical coherence tomography.

Congenital cardiovascular defects are the leading cause of birth defect related death. It has been hypothesized that fluid mechanical forces of embryonic blood flow affect cardiovascular development and play a role in congenital malformations. Studies in small animal embryos can improve our understanding of congenital malformations and can lead to better treatment. We present a feasibility study in which high-resolution optical coherence tomography (OCT) and computational fluid dynamics (CFD) are combined to provide quantitative analysis of the embryonic flow mechanics and the associated anatomy in a small animal model.

Botulinum toxin type A for the treatment of head and neck chronic myofascial pain syndrome: A systematic review and meta-analysis.

BACKGROUND: The authors conducted a systematic review to study the efficacy of botulinum toxin type A (BoTN-A) in the treatment of myofascial pain syndrome. TYPES OF STUDIES REVIEWED: The authors identified randomized, double-masked, placebo-controlled studies on June 1, 2016, from PubMed, Web of Science, and the Cochrane Library. Three of the authors assessed the studies for risk of bias. Outcomes included pain reduction on a visual analog scale, the number of responders, and the posttreatment pain threshold to applied pressure using algometry. RESULTS: The initial search strategy yielded 253 unduplicated references, which the authors reduced to 13 relevant studies. The authors included 11 studies in the meta-analyses as the investigators of those studies had reported similar outcomes. Pooled results showed a nonsignificant improvement in the posttreatment intensity of pain in the BoTN-A group compared with the placebo group at 4 to 6 weeks (standardized difference in means [SDM], -0.110; 95% confidence interval [CI], -0.344 to 0.124; P = .356) and a significant improvement at 2 to 6 months (SDM, -0.360; 95% CI, -0.623 to -0.096; P = .008). The number of study participants who responded to treatment was not statistically significantly different between the groups (risk ratio, 1.346; 95% CI, 0.922-1.964; P = .123) nor was the increase of pain threshold to pressure (algometry) at 2 months (SDM, 0.131; 95% CI, -0.178 to 0.440; P = .405). The study investigators reported no major adverse events. CONCLUSIONS AND PRACTICAL IMPLICATIONS: Pain was reduced significantly in the group that received BoTN-A compared with the placebo group at 2 to 6 months but not at 4 to 6 weeks (with moderate quality of the evidence). Additional studies with larger numbers of participants are needed to confirm these results.

Imaging single chiral nanoparticles in turbid media using circular-polarization optical coherence microscopy.

Optical coherence tomography (OCT) is a widely used structural imaging method. However, it has limited use in molecular imaging due to the lack of an effective contrast mechanism. Gold nanoparticles have been widely used as molecular probes for optical microcopy based on Surface Plasmon Resonance (SPR). Unfortunately, the SPR enhanced backscattering from nanoparticles is still relatively weak compared with the background signal from microscopic structures in biological tissues when imaged with OCT. Consequently, it is extremely challenging to perform OCT imaging of conventional nanoparticles in thick tissues with sensitivity comparable to that of fluorescence imaging. We have discovered and demonstrated a novel approach towards remarkable contrast enhancement, which is achieved by the use of a circular-polarization optical coherence microscopy system and 3-dimensional chiral nanostructures as contrast agents. By detecting the circular intensity differential depolarization (CIDD), we successfully acquired high quality images of single chiral nanoparticles underneath a 1-mm-thick tissue -mimicking phantom.

Dark-field circular depolarization optical coherence microscopy.

Optical coherence microscopy (OCM) is a widely used structural imaging modality. To extend its application in molecular imaging, gold nanorods are widely used as contrast agents for OCM. However, they very often offer limited sensitivity as a result of poor signal to background ratio. Here we experimentally demonstrate that a novel OCM implementation based on dark-field circular depolarization detection can efficiently detect circularly depolarized signal from gold nanorods and at the same time efficiently suppress the background signals. This results into a significant improvement in signal to background ratio.

Plasmonic chiral contrast agents for optical coherence tomography: numerical study.

Optical coherence tomography (OCT) is a widely used morphological imaging modality. Various contrast agents, which change localized optical properties, are used to extend the applicability of OCT, where intrinsic contrast is not sufficient. In this paper we propose the use of a dual-rod gold nano-structure as a polarization sensitive contrast agent. Using numerical simulation, we demonstrated that the proposed structure has tunable chiral response. Enhanced cross-section due to Plasmon resonance in gold nanoparticles, along with the chiral behavior can provide enhanced detection sensitivity. The proposed contrast agents may extend the applicability of OCT to the problems that require the molecular contrast with enhanced sensitivity.