Calibration of diffuse correlation spectroscopy with a time-resolved near-infrared technique to yield absolute cerebral blood flow measurements: errata

Abstract: The authors provide corrections to tabular data and a figure, which do not alter the conclusions of the original paper [Biomed. Opt. Express 2, 2068 (2011)]

Using microscopic video data measures for driver behavior analysis during adverse winter weather: opportunities and challenges

ABSTRACT: This paper presents a driver behavior analysis using microscopic video data measures including vehicle speed, lane-changing ratio, and time to collision. An analytical framework was developed to evaluate the effect of adverse winter weather conditions on highway driving behavior based on automated (computer) and manual methods. The research was conducted through two case studies. The first case study was conducted to evaluate the feasibility of applying an automated approach to extracting driver behavior data based on 15 video recordings obtained in the winter 2013 at three different locations on the Don Valley Parkway in Toronto, Canada. A comparison was made between the automated approach and manual approach, and issues in collecting data using the automated approach under winter conditions were identified. The second case study was based on high quality data collected in the winter 2014, at a location on Highway 25 in Montreal, Canada. The results demonstrate the effectiveness of the automated analytical framework in analyzing driver behavior, as well as evaluating the impact of adverse winter weather conditions on driver behavior. This approach could be applied to evaluate winter maintenance strategies and crash risk on highways during adverse winter weather conditions

Quantitative measurement of cerebral blood flow in a juvenile porcine model by depth-resolved near-infrared spectroscopy

Nearly half a million children and young adults are affected by traumatic brain injury each year in the United States. Although adequate cerebral blood flow (CBF) is essential to recovery, complications that disrupt blood flow to the brain and exacerbate neurological injury often go undetected because no adequate bedside measure of CBF exists. In this study we validate a depth-resolved, near-infrared spectroscopy (NIRS) technique that provides quantitative CBF measurement despite significant signal contamination from skull and scalp tissue. The respiration rates of eight anesthetized pigs (weight: 16.2±0.5 kg, age: 1 to 2 months old) are modulated to achieve a range of CBF levels. Concomitant CBF measurements are performed with NIRS and CT perfusion. A significant correlation between CBF measurements from the two techniques is demonstrated (r 2=0.714, slope=0.92, p\u3c0.001), and the bias between the two techniques is -2.83 mL·min -1·100 g -1 (CI 0.95: -19.63 mL·min -1·100 g -1 -13.9 mL·min -1·100 g -1). This study demonstrates that accurate measurements of CBF can be achieved with depth-resolved NIRS despite significant signal contamination from scalp and skull. The ability to measure CBF at the bedside provides a means of detecting, and thereby preventing, secondary ischemia during neurointensive care. © 2010 Society of Photo-Optical Instrumentation Engineers

Assessing tumor physiology by dynamic contrast-enhanced near-infrared spectroscopy

The purpose of this study was to develop a dynamic contrast-enhanced (DCE) near-infrared spectroscopy (NIRS) technique to characterize tumor physiology. Dynamic data were acquired using two contrast agents of different molecular weights, indocyanine green (ICG) and IRDye 800CW carboxylate (IRDcxb). The DCE curves were analyzed using a kinetic model capable of extracting estimates of tumor blood flow (F), capillary transit time (t(c)) and the amount of dye that leaked into the extravascular space (EVS) - characterized by the extraction fraction (E). Data were acquired from five nude rats with tumor xenografts (\u3e10mm) implanted in the neck. Four DCE-NIR datasets (two from each contrast agent) were acquired for each rat. The dye concentration curve in arterial blood, which is required to quantify the model parameters, was measured non-invasively by dye densitometry. A modification to the kinetic model to characterize t(c) as a distribution of possible values, rather than finite, improved the fit of acquired tumor concentration curves, resulting in more reliable estimates. This modified kinetic model identified a difference between the extracted fraction of IRDcxb, 15 +/- 6 %, and ICG, 1.6 +/- 0.6 %, in the tumor, which can be explained by the difference in molecular weight: 67 kDa for ICG since it binds to albumin and 1.17 kDa for IRD. This study demonstrates the ability of DCE-NIRS to quantify tumor physiology. The next step is to adapt this approach with a dual-receptor approach

Comparison of time-resolved and continuous-wave near-infrared techniques for measuring cerebral blood flow in piglets

A primary focus of neurointensive care is monitoring the injured brain to detect harmful events that can impair cerebral blood flow (CBF), resulting in further injury. Since current noninvasive methods used in the clinic can only assess blood flow indirectly, the goal of this research is to develop an optical technique for measuring absolute CBF. A time-resolved near-infrared (TR-NIR) apparatus is built and CBF is determined by a bolus-tracking method using indocyanine green as an intravascular flow tracer. As a first step in the validation of this technique, CBF is measured in newborn piglets to avoid signal contamination from extracerebral tissue. Measurements are acquired under three conditions: normocapnia, hypercapnia, and following carotid occlusion. For comparison, CBF is concurrently measured by a previously developed continuous-wave NIR method. A strong correlation between CBF measurements from the two techniques is revealed with a slope of 0.79±0.06, an intercept of -2.2±2.5 ml/100 g/min, and an R 2 of 0.810±0.088. Results demonstrate that TR-NIR can measure CBF with reasonable accuracy and is sensitive to flow changes. The discrepancy between the two methods at higher CBF could be caused by differences in depth sensitivities between continuous-wave and time-resolved measurements. © 2010 Society of Photo-Optical Instrumentation Engineers

A simple and robust method for connecting small-molecule drugs using gene-expression signatures

Interaction of a drug or chemical with a biological system can result in a gene-expression profile or signature characteristic of the event. Using a suitably robust algorithm these signatures can potentially be used to connect molecules with similar pharmacological or toxicological properties. The Connectivity Map was a novel concept and innovative tool first introduced by Lamb et al to connect small molecules, genes, and diseases using genomic signatures [Lamb et al (2006), Science 313, 1929-1935]. However, the Connectivity Map had some limitations, particularly there was no effective safeguard against false connections if the observed connections were considered on an individual-by-individual basis. Further when several connections to the same small-molecule compound were viewed as a set, the implicit null hypothesis tested was not the most relevant one for the discovery of real connections. Here we propose a simple and robust method for constructing the reference gene-expression profiles and a new connection scoring scheme, which importantly allows the valuation of statistical significance of all the connections observed. We tested the new method with the two example gene-signatures (HDAC inhibitors and Estrogens) used by Lamb et al and also a new gene signature of immunosuppressive drugs. Our testing with this new method shows that it achieves a higher level of specificity and sensitivity than the original method. For example, our method successfully identified raloxifene and tamoxifen as having significant anti-estrogen effects, while Lamb et al's Connectivity Map failed to identify these. With these properties our new method has potential use in drug development for the recognition of pharmacological and toxicological properties in new drug candidates.Comment: 8 pages, 2 figures, and 2 tables; supplementary data supplied as a ZIP fil

Preservation of the metabolic rate of oxygen in preterm infants during indomethacin therapy for closure of the ductus arteriosus

Background:The aim of this study was to assess and quantify the effects of indomethacin on cerebral blood flow (CBF), oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen (CMRO 2) in preterm infants undergoing treatment for a patent ductus arteriosus (PDA).Methods:CBF and CMRO 2 were measured before and after the first dose of a 3-d course of indomethacin to close hemodynamically significant PDA in preterm neonates. Indocyanine-green (ICG) concentration curves were acquired before and after indomethacin injection to quantify CBF and CMRO 2.Results:Eight preterm neonates (gestational age, 27.6 ± 0.5 wk; birth weight, 992 ± 109 g; 6 males:2 females) were treated at a median age of 4.5 d (range, 4-21 d). Indomethacin resulted in an average CBF decrease of 18% (pre- and post-CBF = 12.9 ± 1.3 and 10.6 ± 0.8 ml/100 g/min, respectively) and an OEF increase of 11% (pre- and post-OEF = 0.38 ± 0.02 and 0.42 ± 0.02, respectively) but no significant change in CMRO 2 (pre- and post-CMRO 2 = 0.83 ± 0.07 and 0.76 ± 0.07 ml O 2 /100 g/min, respectively). Corresponding mean blood pressure (BP), arterial oxygen saturation (S a O 2), heart rate, and end-tidal carbon dioxide tension levels remained unchanged.Conclusion:Indomethacin resulted in significant reduction in CBF but did not alter CMRO 2 because of a compensatory increase in OEF. Copyright © 2013 International Pediatric Research Foundation, Inc

Quantification of joint blood flow by dynamic contrast-enhanced near-infrared spectroscopy: Application to monitoring disease activity in a rat model of rheumatoid arthritis

© The Authors. Published by SPIE under a Creative Commons Attribution 4.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI. Significance: Current guidelines for rheumatoid arthritis (RA) management recommend early treatment with disease modifying antirheumatic drugs (DMARDs). However, DMARD treatment fails in 30% of patients and current monitoring methods can only detect failure after 3 to 6 months of therapy. Aim: We investigated whether joint blood flow (BF), quantified using dynamic contrast-enhanced time-resolved near-infrared spectroscopy, can monitor disease activity and treatment response in a rat model of RA. Approach: Ankle joint BF was measured every 5 days in eight rats with adjuvant-induced arthritis (AIA) and four healthy controls. Arthritis was allowed to progress for 20 days before rats with AIA were treated with a DMARD once every 5 days until day 40. Results: Time and group had separate significant main effects on joint BF; however, there was no significant interaction between time and group despite a notable difference in average joint BF on day 5. Comparison of individual blood flow measures between rats with AIA and control group animals did not reveal a clear response to treatment. Conclusions: Joint BF time courses could not distinguish between rats with AIA and study controls. Heterogeneous disease response and low temporal frequency of BF measurements may have been important study limitations

The gains and losses of face in ongoing intercultural interaction: A case study of Chinese participant perspectives

Given the small number of existing studies of face in intercultural settings and the increasing attention given to participant perspectives in face research, this paper explores the gains and losses of face as perceived by Chinese government officials during a three-week delegation visit to the United States of America. These perspectives were obtained from the group’s spontaneous discussions during regular evening meetings when they reflected on the day’s events. Several key features emerged from the discussions. Firstly, face enhancement was a primary goal for the visit – enhancement of their own face as a delegation, of the face of the Ministry they belonged to, as well as the face of their American hosts. Secondly, the delegates attempted to manage these face goals strategically. Thirdly, they spoke of face as a volatile image that could rise and fall sharply and yet endured across incidents, days and weeks. The paper reports on and discusses these participant perspectives in the light of recent theorizing on face