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The purpose of this study was to assess the accuracy of absolute cerebral blood flow (CBF) measurements obtained by dynamic contrast-enhanced (DCE) near-infrared spectroscopy (NIRS) using indocyanine green as a perfusion contrast agent. For validation, CBF was measured independently using the MRI perfusion method arterial spin labeling (ASL). Data were acquired at two sites and under two flow conditions (normocapnia and hypercapnia). Depth sensitivity was enhanced using time-resolved detection, which was demonstrated in a separate set of experiments using a tourniquet to temporally impede scalp blood flow. A strong correlation between CBF measurements from ASL and DCE-NIRS was observed (slope = 0.99 ± 0.08, y-intercept = −1.7 ± 7.4 mL/100 g/min, and R2 = 0.88). Mean difference between the two techniques was 1.9 mL/100 g/min (95% confidence interval ranged from −15 to 19 mL/100g/min and the mean ASL CBF was 75.4 mL/100 g/min). Error analysis showed that structural information and baseline absorption coefficient were needed for optimal CBF reconstruction with DCE-NIRS. This study demonstrated that DCE-NIRS is sensitive to blood flow in the adult brain and can provide accurate CBF measurements with the appropriate modeling techniques.

Resting-state functional connectivity analysis using optical neuroimaging holds the potential to be a powerful bridge between mouse models of disease and clinical neurologic monitoring. However, analysis techniques specific to optical methods are rudimentary, and algorithms from magnetic resonance imaging are not always applicable to optics. We have developed visual processing tools to increase data quality, improve brain segmentation, and average across sessions with better field-of-view. We demonstrate improved performance using resting-state optical intrinsic signal from normal mice. The proposed methods increase the amount of usable data from neuroimaging studies, improve image fidelity, and should be translatable to human optical neuroimaging systems.

We present pilot results on the validation of non-invasive assessment of elevated intracranial pressure with optical measurement of critical closing pressure. A strong correlation (r=0.85) between optical measurements of critical closing pressure and invasive measurements of intracranial pressure was observed in 5 infants with hydrocephalus, and 1 adult patient with diffuse hypoxic ischemic brain injury. By facilitating timely detection of intracranial hypertension, this approach has potential to reduce risk of brain damage in hydrocephalus and other vulnerable patient populations.

Speech comprehension relies on highly distributed, dynamically interconnected neuroanatomical loci. Accordingly, performance on complex speech processing tasks such as dichotic listening can be used to assess the integrity and health of many functional and structural aspects of the brain. Despite the potential merits as a clinical assessment tool, however, the neural substrates activated during dichotic listening remain relatively opaque at higher processing levels. Ultimately, this knowledge gap limits diagnostic use of the task. At the level of the prefrontal cortex, dichotic listening induces an asymmetric response wherein regions on the right hemisphere exhibit a higher functional activation than on the left. Superficially, this finding is counterintuitive given the left hemisphere’s dominance for speech and language. To obtain a more in-depth perspective on the potentially distinct roles of the right and left prefrontal cortex, we optically monitored cerebral blood flow in the dorsolateral prefrontal cortex (DLPFC) during dichotic listening tasks in human subjects. The method permitted us to avoid systematic experimental confounds that functional magnetic resonance imaging (fMRI) measurements suffer from, namely the influence of scanner noise. In addition to reproducing the documented larger activation amplitude in the right hemisphere, we also found that repeated listening task blocks were associated with altered kinetics of blood flow in the right, but not the left DLPFC. Interestingly, subjects with the most prominent regional blood flow changes in the right hemisphere also displayed large distortion product otoacoustic emissions (DPOAEs) in the left ear, possibly signaling a correlation between prefrontal activity and top-down listening control infrastructure through medial olivocochlear efferent projections to the inner ear. Overall, our results suggest that the right prefrontal cortical regions play an active role in optimizing task performance.

Intrathoracic pressure influences cardiac output and may affect cerebral blood flow (CBF). We aimed to quantify the cerebral hemodynamic response to intrathoracic pressure reduction in patients with acute ischemic stroke using a noninvasive respiratory impedance (RI) device. We assessed low-level (6 cm H(2)O) and high-level (12 cm H(2)O) RI in 17 spontaneously breathing patients within 72 h of anterior circulation acute ischemic stroke. Average age was 65 years, and 35% were female. Frontal lobe tissue perfusion and middle cerebral artery velocity (MCAv) were continuously monitored with optical diffuse correlation spectroscopy (DCS) and transcranial Doppler ultrasound, respectively. High-level RI resulted in a 7% increase in MCAv (p = 0.004). MCAv varied across all studied levels (baseline vs low-level vs high-level, p = 0.006), with a significant test of trend (p = 0.002). Changes were not seen in DCS measured tissue perfusion by nonparametric pairwise comparison. Mixed effects regression analysis identified a small increase in both MCAv (low-level RI: β 2.1, p

The dynamics in supercooled liquids slow enormously upon approaching the glass transition, albeit without significant change of liquid structure. This empirical observation has stimulated development of many theoretical models which attempt to elucidate microscopic mechanisms in glasses and glass precursors. Here, quasi-two-dimensional colloidal supercooled liquids and glasses are employed to experimentally test predictions of widely used models: mode coupling theory (MCT) and its important extension, inhomogeneous MCT (IMCT). We measure two-point dynamic correlation functions in the glass forming liquids to determine structural relaxation times, τα, and mode coupling exponents, a, b, and γ; these parameters are then used to extract the mode coupling dynamic crossover packing area-fraction, ϕ c. This information, along with our measurements of supercooled liquid spatiotemporal dynamics, permits characterization of dynamic heterogeneities in the samples and facilitates direct experimental tests of the scaling predictions of IMCT. The time scales at which dynamic heterogeneities are largest, and their spatial sizes, exhibit power law growth on approaching ϕ c. Within experimental error, the exponents of the measured power laws are close to the predictions of IMCT.

Rapid detection of ischemic conditions at the bedside can improve treatment of acute brain injury. In this observational study of 11 critically ill brain-injured adults, we employed a monitoring approach that interleaves time-resolved near-infrared spectroscopy (TR-NIRS) measurements of cerebral oxygen saturation and oxygen extraction fraction (OEF) with diffuse correlation spectroscopy (DCS) measurement of cerebral blood flow (CBF). Using this approach, we demonstrate the clinical promise of non-invasive, continuous optical monitoring of changes in CBF and cerebral metabolic rate of oxygen (CMRO2). In addition, the optical CBF and CMRO2 measures were compared to invasive brain tissue oxygen tension (PbtO2), thermal diffusion flowmetry CBF, and cerebral microdialysis measures obtained concurrently. The optical CBF and CMRO2 information successfully distinguished between ischemic, hypermetabolic, and hyperemic conditions that arose spontaneously during patient care. Moreover, CBF monitoring during pressor-induced changes of mean arterial blood pressure enabled assessment of cerebral autoregulation. In total, the findings suggest that this hybrid non-invasive neurometabolic optical monitor (NNOM) can facilitate clinical detection of adverse physiological changes in brain injured patients that are otherwise difficult to measure with conventional bedside monitoring techniques.

Liquid structure and dynamics are experimentally investigated in colloidal suspensions with short-range depletion attraction. The colloidal fluid samples consist of hard-sphere colloidal particles suspended along with rodlike depletants based on surfactant micelles. The spheres have a range of surface chemistries, diameters, and packing fractions, and the rodlike micelle length depends on the temperature. Thus, the combination of hard-spheres and depletants generates a sample wherein short-range interparticle attraction can be temperature-tuned in situ. Video optical microscopy and particle tracking techniques are employed to measure particle trajectories from which structural and dynamical quantities are derived, including the particle pair correlation function [g(r)], mean square displacement, long-time diffusion coefficient, and the sample two-body excess entropy (S2). The samples with stronger short-range attractions exhibit more order, as characterized by g(r) and S2. The stronger short-range attractions are also observed to lead to slower long-time diffusion and more heterogeneous dynamics at intermediate time scales. Finally, the excess entropy scaling law prediction, i.e., the exponential relationship between two-body excess entropy and long-time diffusivity, is observed across the full range of samples.

Physical review / D 88(4), 042004 (2013). doi:10.1103/PhysRevD.88.042004, We report on the measurement of the all-particle cosmic ray energy spectrum with the IceTop air shower array in the energy range from 1.58 PeV to 1.26 EeV. The IceTop air shower array is the surface component of the IceCube Neutrino Observatory at the geographical South Pole. The analysis was performed using only information from IceTop. The data used in this work were taken from June 1, 2010 to May 13, 2011. During that period the IceTop array consisted of 73 stations, compared to 81 in its final configuration. The measured spectrum exhibits a clear deviation from a single power law above the knee around 4 PeV and below 1 EeV. We observe spectral hardening around 18 PeV and steepening around 130 PeV., Published by Soc., [S.l.]

Spinal cord ischemia leads to iatrogenic injury in multiple surgical fields, and the ability to immediately identify onset and anatomic origin of ischemia is critical to its management. Current clinical monitoring, however, does not directly measure spinal cord blood flow, resulting in poor sensitivity/specificity, delayed alerts, and delayed intervention. We have developed an epidural device employing diffuse correlation spectroscopy (DCS) to monitor spinal cord ischemia continuously at multiple positions. We investigate the ability of this device to localize spinal cord ischemia in a porcine model and validate DCS versus Laser Doppler Flowmetry (LDF). Specifically, we demonstrate continuous (>0.1Hz) spatially resolved (3 locations) monitoring of spinal cord blood flow in a purely ischemic model with an epidural DCS probe. Changes in blood flow measured by DCS and LDF were highly correlated (r = 0.83). Spinal cord blood flow measured by DCS caudal to aortic occlusion decreased 62%. This monitor demonstrated a sensitivity of 0.87 and specificity of 0.91 for detection of a 25% decrease in flow. This technology may enable early identification and critically important localization of spinal cord ischemia.

Thin films that exhibit spatially heterogeneous swelling often buckle into the third dimension to minimize stress. These effects, in turn, offer a promising strategy to fabricate complex three-dimensional structures from two-dimensional sheets. Here we employ surface topography as a new means to guide buckling of swollen polymer bilayer films and thereby control the morphology of resulting three-dimensional objects. Topographic patterns are created on poly(dimethylsiloxane) (PDMS) films selectively coated with a thin layer of non-swelling parylene on different sides of the patterned films. After swelling in an organic solvent, various structures are formed, including half-pipes, helical tubules, and ribbons. We demonstrate these effects and introduce a simple geometric model that qualitatively captures the relationship between surface topography and the resulting swollen film morphologies. The model's limitations are also examined.

The dynamic manipulation of colloidal particle shape offers a novel design mechanism for the creation of advanced responsive materials. To this end, we introduce a versatile new strategy for shape control of anisotropic polymeric colloidal particles. The concept utilizes temperature-sensitive absorption of a suitable solvent from a binary mixture. Specifically, increasing the temperature in the vicinity of the demixing transition of a binary mixture causes more solvent to be absorbed into the polymeric colloidal particle, which, in turn, lowers the glass transition temperature of the polymer inside the particle, with a concomitant decrease in viscosity. The balance between the internal viscosity and surface tension of the particle is thus disrupted, and the anisotropic shape of the particle shifts to become more spherical. Subsequent rapid temperature quenching can halt the process, leaving the particle with an intermediate anisotropy. The resultant shape anisotropy control provides new routes for studies of the phase transitions of anisotropic colloids and enables the fabrication of unique particles for materials applications.

Purpose: The authors introduce a state-of-the-art all-optical clinical diffuse optical tomography (DOT) imaging instrument which collects spatially dense, multispectral, frequency-domain breast data in the parallel-plate geometry. Methods: The instrument utilizes a CCD-based heterodyne detection scheme that permits massively parallel detection of diffuse photon density wave amplitude and phase for a large number of source–detector pairs (106). The stand-alone clinical DOT instrument thus offers high spatial resolution with reduced crosstalk between absorption and scattering. Other novel features include a fringe profilometry system for breast boundary segmentation, real-time data normalization, and a patient bed design which permits both axial and sagittal breast measurements. Results: The authors validated the instrument using tissue simulating phantoms with two different chromophore-containing targets and one scattering target. The authors also demonstrated the instrument in a case study breast cancer patient; the reconstructed 3D image of endogenous chromophores and scattering gave tumor localization in agreement with MRI. Conclusions: Imaging with a novel parallel-plate DOT breast imager that employs highly parallel, high-resolution CCD detection in the frequency-domain was demonstrated.

To compare neuroimaging data between subjects, images from individual sessions need to be aligned to a common reference or “atlas.” Atlas registration of optical intrinsic signal imaging of mice, for example, is commonly performed using affine transforms with parameters determined by manual selection of canonical skull landmarks. Errors introduced by such procedures have not previously been investigated. We quantify the variability that arises from this process and consequent errors from misalignment that affect interpretation of functional neuroimaging data. We propose an improved method, using separately acquired high-resolution images and demonstrate improvements in variability and alignment using this method.

Background: Diffuse correlation spectroscopy (DCS) noninvasively permits continuous, quantitative, bedside measurements of cerebral blood flow (CBF). To test whether optical monitoring (OM) can detect decrements in CBF producing cerebral hypoxia, we applied the OM technique continuously to probe brain-injured patients who also had invasive brain tissue oxygen (PbO 2 ) monitors. Methods: Comatose patients with a Glasgow Coma Score (GCS) < 8) were enrolled in an IRB-approved protocol after obtaining informed consent from the legally authorized representative. Patients underwent 6–8 h of daily monitoring. Brain PbO 2 was measured with a Clark electrode. Absolute CBF was monitored with DCS, calibrated by perfusion measurements based on intravenous indocyanine green bolus administration. Variation of optical CBF and mean arterial pressure (MAP) from baseline was measured during periods of brain hypoxia (defined as a drop in PbO 2 below 19 mmHg for more than 6 min from baseline (PbO 2 > 21 mmHg). In a secondary analysis, we compared optical CBF and MAP during randomly selected 12-min periods of “normal” (> 21 mmHg) and “low” (< 19 mmHg) PbO 2 . Receiver operator characteristic (ROC) and logistic regression analysis were employed to assess the utility of optical CBF, MAP, and the two-variable combination, for discrimination of brain hypoxia from normal brain oxygen tension. Results: Seven patients were enrolled and monitored for a total of 17 days. Baseline-normalized MAP and CBF significantly decreased during brain hypoxia events (p < 0.05). Through use of randomly selected, temporally sparse windows of low and high PbO 2 , we observed that both MAP and optical CBF discriminated between periods of brain hypoxia and normal brain oxygen tension (ROC AUC 0.761, 0.762, respectively). Further, combining these variables using logistic regression analysis markedly improved the ability to distinguish low- and high-PbO 2 epochs (AUC 0.876). Conclusions: The data suggest optical techniques may be able to provide continuous individualized CBF measurement to indicate occurrence of brain hypoxia and guide brain-directed therapy.

The European physical journal / C Particles and fields C 79(3), 214 (2019). doi:10.1140/epjc/s10052-019-6702-y, Published by Springer24928, Heidelberg

Introduction: We have shown that during CPR, novel non-invasive monitoring of cerebral tissue oxygenation (StO 2 , %) and total hemoglobin concentration (THC, μmol/L) by frequency-domain diffuse optical spectroscopy (FD-DOS) is associated with ROSC in a swine model of pediatric cardiac arrest. Our objective is to find the optimal non-invasive predictor for ROSC and assess feasibility of a stable critical threshold over time in early CPR. Hypothesis: Stable critical thresholds with high sensitivity or specificity for ROSC may be established in early CPR (2 and THC measurements initiated at CPR start. Methods: One-month-old swine (n=31) underwent 7 minutes of asphyxia, induction of ventricular fibrillation, and up to 20 minutes of CPR till ROSC or death (no ROSC). Absolute StO 2 and THC and absolute and relative change from 1 minute into CPR (time for chest molding and FD-DOS placement) were evaluated as ROSC predictors over time. For each variable, an ROC curve and two critical thresholds, maximizing specificity (=1) or sensitivity (=1), were determined at 1-min intervals from 2-10 minutes of CPR using univariate logistic regression. Optimal predictor was selected by highest mean AUC. A stable specificity or sensitivity threshold was feasible if the mean threshold had a specificity or sensitivity >0.9 over all intervals, respectively. Results: Absolute change in StO 2 (ΔStO 2 ) had the highest mean (SD) AUC of 0.90 (0.07). Consistently >0.8, the AUC exceeded 0.9 after 7 minutes of CPR ( see Fig. ). The mean specificity threshold (ΔStO 2 = +5.1%) and sensitivity threshold (ΔStO 2 = +1.4%) achieved an overall specificity of 0.93 and sensitivity of 0.98, respectively. Conclusions: Non-invasive monitoring of absolute change in StO 2 was most predictive of ROSC and stable critical thresholds with high specificity or sensitivity were established in early CPR. Future work will independently validate this promising tool for CPR optimization.

Management of deep hypothermic (DH) cardiopulmonary bypass (CPB), a critical neuroprotective strategy, currently relies on non-invasive temperature to guide cerebral metabolic suppression during complex cardiac surgery in neonates. Considerable inter-subject variability in temperature response and residual metabolism may contribute to the persisting risk for postoperative neurological injury. To characterize and mitigate this variability, we assess the sufficiency of conventional nasopharyngeal temperature (NPT) guidance, and in the process, validate combined non-invasive frequency-domain diffuse optical spectroscopy (FD-DOS) and diffuse correlation spectroscopy (DCS) for direct measurement of cerebral metabolic rate of oxygen ( CMRO2). During CPB, n = 8 neonatal swine underwent cooling from normothermia to 18℃, sustained DH perfusion for 40 min, and then rewarming to simulate cardiac surgery. Continuous non-invasive and invasive measurements of intracranial temperature (ICT) and CMRO2 were acquired. Significant hysteresis ( p 2 relationships were found. Resolution of this hysteresis in the ICT versus CMRO2 relationship identified a crucial insufficiency of conventional NPT guidance. Non-invasive CMRO2 temperature coefficients with respect to NPT ( Q10 = 2.0) and ICT ( Q10 = 2.5) are consistent with previous reports and provide further validation of FD-DOS/DCS CMRO2 monitoring during DH CPB to optimize management.

© The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License 2017. We investigate a scheme for noninvasive continuous monitoring of absolute cerebral blood flow (CBF) in adult human patients based on a combination of time-resolved dynamic contrast-enhanced near-infrared spectroscopy (DCE-NIRS) and diffuse correlation spectroscopy (DCS) with semi-infinite head model of photon propogation. Continuous CBF is obtained via calibration of the DCS blood flow index (BFI) with absolute CBF obtained by intermittent intravenous injections of the optical contrast agent indocyanine green. A calibration coefficient (?) for the CBF is thus determined, permitting conversion of DCS BFI to absolute blood flow units at all other times. A study of patients with acute brain injury (N 7) is carried out to ascertain the stability of ?. The patientaveraged DCS calibration coefficient across multiple monitoring days and multiple patients was determined, and good agreement between the two calibration coefficients measured at different times during single monitoring days was found. The patient-averaged calibration coefficient of 1.24 × 109 omL/100 g/ min/ocm2/sp was applied to previously measured DCS BFI from similar brain-injured patients; in this case, absolute CBF was underestimated compared with XeCT, an effect we show is primarily due to use of semi-infinite homogeneous models of the head.

High-energy neutrino emission has been predicted for several short-lived astrophysical transients including gamma-ray bursts (GRBs), core-collapse supernovae with choked jets, and neutron star mergers. IceCube's optical and x-ray follow-up program searches for such transient sources by looking for two or more muon neutrino candidates in directional coincidence and arriving within 100 s. The measured rate of neutrino alerts is consistent with the expected rate of chance coincidences of atmospheric background events and no likely electromagnetic counterparts have been identified in Swift follow-up observations. Here, we calculate generic bounds on the neutrino flux of short-lived transient sources. Assuming an E-2.5 neutrino spectrum, we find that the neutrino flux of rare sources, like long gamma-ray bursts, is constrained to, 0, SCOPUS: ar.j, info:eu-repo/semantics/published

SS 433 is a binary system containing a supergiant star that is overflowing its Roche lobe with matter accreting onto a compact object (either a black hole or neutron star)

We prepare two-dimensional crystalline packings of colloidal particles on surfaces of the nematic liquid crystal (NLC) 5CB, and we investigate the diffusion and vibrational phonon modes of these particles using video microscopy. Short-time particle diffusion at the air-NLC interface is well described by a Stokes-Einstein model with viscosity similar to that of 5CB. Crystal phonon modes, measured by particle displacement covariance techniques, are demonstrated to depend on the elastic constants of 5CB through interparticle forces produced by LC defects that extend from the interface into the underlying bulk material. The displacement correlations permit characterization of transverse and longitudinal sound velocities of the crystal packings, as well as the particle interactions produced by the LC defects. All behaviors are studied in the nematic phase as a function of increasing temperature up to the nematic-isotropic transition.

Background Spinal cord ischemia occurs frequently during thoracic aneurysm repair. Current methods based on electrophysiology techniques to detect ischemia are indirect, non-specific, and temporally slow. In this article, the authors report the testing of a spinal cord blood flow and oxygenation monitor, based on diffuse correlation and optical spectroscopies, during aortic occlusion in a sheep model. Methods Testing was carried out in 16 Dorset sheep. Sensitivity in detecting spinal cord blood flow and oxygenation changes during aortic occlusion, pharmacologically induced hypotension and hypertension, and physiologically induced hypoxia/hypercarbia was assessed. Accuracy of the diffuse correlation spectroscopy measurements was determined via comparison with microsphere blood flow measurements. Precision was assessed through repeated measurements in response to pharmacologic interventions. Results The fiber-optic probe can be placed percutaneously and is capable of continuously measuring spinal cord blood flow and oxygenation preoperatively, intraoperatively, and postoperatively. The device is sensitive to spinal cord blood flow and oxygenation changes associated with aortic occlusion, immediately detecting a decrease in blood flow (−65 ± 32%; n = 32) and blood oxygenation (−17 ± 13%, n = 11) in 100% of trials. Comparison of spinal cord blood flow measurements by the device with microsphere measurements led to a correlation of R2 = 0.49, P < 0.01, and the within-sheep coefficient of variation was 9.69%. Finally, diffuse correlation spectroscopy is temporally more sensitive to ischemic interventions than motor-evoked potentials. Conclusion The first-generation spinal fiber-optic monitoring device offers a novel and potentially important step forward in the monitoring of spinal cord ischemia.

We demonstrate real-time quantitative phase imaging as a new optical approach for measuring the evaporation dynamics of sessile microdroplets. Quantitative phase images of various droplets were captured during evaporation. The images enabled us to generate time-resolved three-dimensional topographic profiles of droplet shape with nanometer accuracy and, without any assumptions about droplet geometry, to directly measure important physical parameters that characterize surface wetting processes. Specifically, the time-dependent variation of the droplet height, volume, contact radius, contact angle distribution along the droplet's perimeter, and mass flux density for two different surface preparations are reported. The studies clearly demonstrate three phases of evaporation reported previously: pinned, depinned, and drying modes; the studies also reveal instances of partial pinning. Finally, the apparatus is employed to investigate the cooperative evaporation of the sprayed droplets. We observe and explain the neighbor-induced reduction in evaporation rate, that is, as compared to predictions for isolated droplets. In the future, the new experimental methods should stimulate the exploration of colloidal particle dynamics on the gas-liquid-solid interface.

Various helicases and single stranded DNA (ssDNA) binding proteins unfold G-quadruplex (GQ) structures. However, the underlying mechanisms of this activity have only recently come to focus. We report kinetic studies on Bloom (BLM) helicase and human telomeric GQ interactions using single-molecule Forster resonance energy transfer (smFRET). Using partial duplex DNA (pdDNA) constructs with different 5' ssDNA overhangs, we show that BLM localizes in the vicinity of ssDNA/double-stranded DNA (dsDNA) junction and reels in the ssDNA overhang in an ATP-dependent manner. A comparison of DNA constructs with or without GQ in the overhang shows that GQ unfolding is achieved in 50-70% of reeling attempts under physiological salt and pH conditions. The unsuccessful attempts often result in dissociation of BLM from DNA which slows down the overall BLM activity. BLM-mediated GQ unfolding is typically followed by refolding of the GQ, a pattern that is repeated several times before BLM dissociates from DNA. BLM is significantly less processive compared to the highly efficient GQ destabilizer Pif1 that can repeat GQ unfolding activity hundreds of times before dissociating from DNA. Despite the variations in processivity, our studies point to possible common patterns used by different helicases in minimizing the duration of stable GQ formation.

SummaryDynamics of the nucleosome and exposure of nucleosomal DNA play key roles in many nuclear processes, but local dynamics of the nucleosome and its modulation by DNA sequence are poorly understood. Using single-molecule assays, we observed that the nucleosome can unwrap asymmetrically and directionally under force. The relative DNA flexibility of the inner quarters of nucleosomal DNA controls the unwrapping direction such that the nucleosome unwraps from the stiffer side. If the DNA flexibility is similar on two sides, it stochastically unwraps from either side. The two ends of the nucleosome are orchestrated such that the opening of one end helps to stabilize the other end, providing a mechanism to amplify even small differences in flexibility to a large asymmetry in nucleosome stability. Our discovery of DNA flexibility as a critical factor for nucleosome dynamics and mechanical stability suggests a novel mechanism of gene regulation by DNA sequence and modifications.

The deposition process at the edge of evaporating colloidal drops varies with the shape of suspended particles. Experiments with prolate ellipsoidal particles suggest that the spatiotemporal properties of the deposit depend strongly on particle aspect ratio. As the aspect ratio increases, the particles form less densely-packed deposits and the statistical behavior of the deposit interface crosses over from the Kardar-Parisi-Zhang (KPZ) universality class to another universality class which was suggested to be consistent with the KPZ plus quenched disorder. Here, we numerically study the effect of particle interaction anisotropy on deposit growth. In essence, we model the ellipsoids, at the interface, as disk-like particles with two types of interaction patches that correspond to specific features at the poles and equator of the ellipsoid. The numerical results corroborate experimental observations and further suggest that the deposition transition can stem from interparticle interaction anisotropy. Possible extensions of our model to other systems are also discussed.

Introduction: Optimization of cerebral blood flow is a cornerstone of clinical management in a number of neurologic diseases, most notably acute ischemic stroke. Intra-thoracic pressure influences cardiac output and has the potential to impact cerebral blood flow (CBF). We aimed to quantify cerebral hemodynamic changes in acute ischemic stroke patients during increased respiratory impedance using a non-invasive oral device. Methods: Cerebral perfusion was measured during low (6cm H 2 0) and high (12cm H 2 0) levels of respiratory impedance in 20 patients within 72 hours of acute ischemic stroke. Microvascular CBF was measured by optical diffuse correlation spectroscopy, and middle cerebral artery mean flow velocity (MFV) was assessed by transcranial Doppler ultrasound. Results: High level respiratory impedance resulted in a 10% increase in MFV. Low level respiratory impedance resulted in a smaller (4%) non-significant change in MFV. Changes in cortical CBF were non-significant (figure). MFV varied across all studied levels (baseline vs low vs high, p=0.0017) with a significant test of trend (p=0.001), but this was not seen with microvascular CBF (p=0.33). Heart rate, cardiac output, and end tidal CO 2 remained stable during all levels of respiratory impedance. There was a small increase in mean arterial blood pressure at the low and high level of respiratory impedance, 4% (p=0.013) and 6% (p=0.017) respectively. All patients completed the protocol in its entirety, and the respiratory impedance exercise was well tolerated. Conclusions: Manipulating intrathoracic pressure via non-invasive respiratory impedance was safe and produced a small but measurable increase in cerebral blood flow in acute stroke patients. Future studies are warranted to assess whether respiratory impedance is feasible during hyperacute stroke management, and to determine the effect of volume status on the hemodynamic response to respiratory impedance.

Introduction: Optimizing cerebral blood flow (CBF) is a cornerstone of clinical management for a number of neurologic disease states, most notably acute ischemic stroke. Transdermal nitric oxide donors are being investigated for acute stroke, though the effect of inhaled nitric oxide (iNO) on CBF remains largely unknown. Here we aim to quantify the cerebral hemodynamic response to iNO in healthy volunteers. Methods: Cerebral perfusion was measured during three doses of iNO (5ppm, 10ppm, and 20ppm) using the iNOMAX system (Mallinckrodt Pharmaceuticals) in 20 healthy volunteers. Continuous measurements of microvascular CBF were made with diffuse correlation spectroscopy (DCS), while middle cerebral artery mean flow velocity (MFV) was measured with transcranial Doppler. Cardiopulmonary status and nitric oxide toxicity (i.e. NO 2 ) were continuously monitored for safety. Results: Overall, iNO was safe and well tolerated. All subjects completed the protocol in its entirety. All 3 doses of iNO resulted in a small but statistically significant increase in microvascular CBF as compared to baseline (figure). No significant changes in MFV were identified (figure). During administration of iNO, there was no detrimental effect on blood pressure, nor was there any significant accumulation of toxic metabolites. Conclusions: iNO was safe and produced a small but significant increase in microvascular CBF in healthy volunteers. Future studies are warranted to determine the optimal dose of iNO and to explore the effect in acute ischemic stroke patients.

We calibrated the DCS blood flow index against contrast-enhanced time-resolved NIRS for absolute cerebral blood flow. Absolute calibration was stable across single days. A “best” calibration coefficient was obtained from the study population.

Near-infrared spectroscopy and diffuse correlation spectroscopy were applied to measure oxygen saturation and blood flow changes in skeletal muscle. Comparison results between healthy subjects and peripheral artery disease patients were given in this study.

An optics-MRI perfusion validation study investigated whether time-resolved contrast-enhanced NIRS can measure cerebral blood flow changes induced by altering arterial PCO2. Strong correlation between flow estimates from MRI and contrast-enhanced NIRS was found.

Non-hypoxic levels of tumor oxygen saturation within 10 days of the first dose of therapy predict pathologic complete response to breast cancer neoadjuvant chemotherapy in a 33-subject clinical trial.

Spinal cord ischemia is a tragic and devastating complication of surgery and trauma. We have developed a catheter-based optical tool to continuously monitor spinal cord hemodynamics and oxygen saturation at multiple sites along the spine.

We studied rat somatosensory cortex in vivo responses to functional activation based on real-time measurements of intravascular and extravascular oxygen tension using two-color phosphorescence lifetime spectroscopy and cerebral blood flow using laser speckle contrast imaging.

Surgery and trauma commonly cause spinal cord ischemia. We have developed a catheter-based optical tool to continuously monitor spinal cord blood flow intraoperatively in a ovine model of spinal surgery.

We discovered a limitation of SVD-based analytic inversion algorithm for spatial frequency domain fluorescence diffuse optical tomography. We illustrate the issue and introduce an algorithm to overcome this challenge.

We demonstrate a noninvasive system for real-time monitoring of tumor blood flow and automatic adjustment of treatment light fluence-rate to conserve tumor perfusion during PDT. Improved efficacy was observed using blood-flow informed light delivery.

The aim of this tutorial is to teach the roots of diffuse optics and then show how this qualitatively different approach to “optics” is finding application in medicine. A long introduction will offer a coherent discussion about light transport in tissue-like turbid media. In particular, we will move quickly from traditional absorption and scattering phenomena in optically thin media to the transport equation and then to the diffusion models for light, including boundary conditions, spectroscopy, and basics of tomography. Transport of both light fluence rate and light correlations will be described. Many excellent primary papers and reviews have been written about this subject matter, and I will cite them in my tutorial, but my introduction is largely based on materials in references [1]–[7].

Fluorescence-guided surgery (FGS) and other interventions are rapidly evolving as a class of technologically driven interventional approaches in which many surgical specialties visualize fluorescent molecular tracers or biomarkers through associated cameras or oculars to guide clinical decisions on pathological lesion detection and excision/ablation. The technology has been commercialized for some specific applications, but also presents technical challenges unique to optical imaging that could confound the utility of some interventional procedures where real-time decisions must be made. Accordingly, the AAPM has initiated the publication of this Blue Paper of The Emerging Technology Working Group (TETAWG) and the creation of a Task Group from the Therapy Physics Committee within the Treatment Delivery Subcommittee. In describing the relevant issues, this document outlines the key parameters, stakeholders, impacts, and outcomes of clinical FGS technology and its applications. The presentation is not intended to be conclusive, but rather to inform the field of medical physics and stimulate the discussions needed in the field with respect to a seemingly low-risk imaging technology that has high potential for significant therapeutic impact. This AAPM Task Group is working toward consensus around guidelines and standards for advancing the field safely and effectively.

We built a heterodyne frequency-domain near-infrared spectroscopy (NIRS) instrument integrated with ultrasound for investigation of placenta physiology. The instrument was characterized and first measurements quantified placenta vascular oxygenation in healthy human subjects.

Deformation of a fluid interface caused by the presence of objects at the interface can lead to large lateral forces between objects. We explore these fluid-mediated attractive force between partially submerged vertical cylinders. Forces are experimentally measured by slowly separating cylinder pairs and cylinder triplets after capillary rise is initially established for cylinders in contact. For cylinder pairs, numerical computations and a theoretical model are found to be in good agreement with measurements. The model provides insight into the relative importance of the contributions to the total force. For small separations, the lateral force is dominated by the fluid pressure acting over the wetted cylinder surfaces. At large separations, the surface tension acting along the contact line dominates the lateral force. A crossover between the two regimes occurs at a separation of around half of a capillary length. The experimentally measured forces between cylinder triplets are also in good agreement with numerical computations, and we show that pairwise contributions account for nearly all of the attractive force between triplets. For cylinders with an equilibrium capillary rise height greater than the height of the cylinder, we find that the attractive force depends on the height of the cylinders above the submersion level, which provides a means to create precisely controlled tunable cohesive forces between objects deforming a fluid interface.

The ARIANNA experiment seeks to observe the diffuse flux of neutrinos in the 10^8 - 10^10 GeV energy range using a grid of radio detectors at the surface of the Ross Ice Shelf of Antarctica. The detector measures the coherent Cherenkov radiation produced at radio frequencies, from about 100 MHz to 1 GHz, by charged particle showers generated by neutrino interactions in the ice. The ARIANNA Hexagonal Radio Array (HRA) is being constructed as a prototype for the full array. During the 2013-14 austral summer, three HRA stations collected radio data which was wirelessly transmitted off site in nearly real-time. The performance of these stations is described and a simple analysis to search for neutrino signals is presented. The analysis employs a set of three cuts that reject background triggers while preserving 90% of simulated cosmogenic neutrino triggers. No neutrino candidates are found in the data and a model-independent 90% confidence level Neyman upper limit is placed on the all flavor neutrino+antineutrino flux in a sliding decade-wide energy bin. The limit reaches a minimum of 1.9x10^-23 GeV^-1 cm^-2 s^-1 sr^-1 in the 10^8.5 - 10^9.5 GeV energy bin. Simulations of the performance of the full detector are also described. The sensitivity of the full ARIANNA experiment is presented and compared with current neutrino flux models., 22 pages, 22 figures. Published in Astroparticle Physics