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Spreading depolarizations (SD) refer to the near-complete depolarization of neurons that is associated with brain injuries such as ischemic stroke. The present gold standard for SD monitoring in humans is invasive electrocorticography (ECoG). A promising non-invasive alternative to ECoG is diffuse optical monitoring of SD-related flow and hemoglobin transients. To investigate the clinical utility of flow and hemoglobin transients, we analyzed their association with infarction in rat focal brain ischemia. Optical images of flow, oxy-hemoglobin, and deoxy-hemoglobin were continuously acquired with Laser Speckle and Optical Intrinsic Signal imaging for 2 h after photochemically induced distal middle cerebral artery occlusion in Sprague-Dawley rats (n = 10). Imaging was performed through a 6 × 6 mm window centered 3 mm posterior and 4 mm lateral to Bregma. Rats were sacrificed after 24 h, and the brain slices were stained for assessment of infarction. We mapped the infarcted area onto the imaging data and used nine circular regions of interest (ROI) to distinguish infarcted from non-infarcted tissue. Transients propagating through each ROI were characterized with six parameters (negative, positive, and total amplitude; negative and positive slope; duration). Transients were also classified into three morphology types (positive monophasic, biphasic, negative monophasic). Flow transient morphology, positive amplitude, positive slope, and total amplitude were all strongly associated with infarction (p 0.001). Associations with infarction were also observed for oxy-hemoglobin morphology, oxy-hemoglobin positive amplitude and slope, and deoxy-hemoglobin positive slope and duration (all p 0.01). These results suggest that flow and hemoglobin transients accompanying SD have value for detecting infarction.

Cardiac arrest often results in severe neurologic injury. Improving care for these patients is difficult as few noninvasive biomarkers exist that allow physicians to monitor neurologic health. The amount of low-frequency power (LFP, 0.01-0.1 Hz) in cerebral haemodynamics has been used in functional magnetic resonance imaging as a marker of neuronal activity. Our hypothesis was that increased LFP in cerebral blood flow (CBF) would be correlated with improvements in invasive measures of neurologic health.We adapted the use of LFP for to monitoring of CBF with diffuse correlation spectroscopy. We asked whether LFP (or other optical biomarkers) correlated with invasive microdialysis biomarkers (lactate-pyruvate ratio - LPR - and glycerol concentration) of neuronal injury in the 4 h after return of spontaneous circulation in a swine model of paediatric cardiac arrest (Sus scrofa domestica, 8-11 kg, 51% female). Associations were tested using a mixed linear effects model.We found that higher LFP was associated with higher LPR and higher glycerol concentration. No other biomarkers were associated with LPR; cerebral haemoglobin concentration, oxygen extraction fraction, and one EEG metric were associated with glycerol concentration.Contrary to expectations, higher LFP in CBF was correlated with worse invasive biomarkers. Higher LFP may represent higher neurologic activity, or disruptions in neurovascular coupling. Either effect may be harmful in the acute period after cardiac arrest. Thus, these results suggest our methodology holds promise for development of new, clinically relevant biomarkers than can guide resuscitation and post-resuscitation care. Institutional protocol number: 19-001327.

Direct assessment of blood oxygenation in the human placenta can provide information about placental function. However, the monitoring of placental oxygenation involves invasive sampling or imaging techniques that are poorly suited for bedside use. Here we show that placental oxygen haemodynamics can be non-invasively probed, in real time, up to 4.2 cm below the body surface via concurrent frequency-domain diffuse optical spectroscopy and ultrasound imaging. We developed the multimodal instrument to facilitate assessment of anterior placental properties by leveraging image-reconstruction algorithms that integrate ultrasound information about the morphology of tissue layers with optical information on haemodynamics. In a pilot investigation involving pregnancies in the third trimester, we studied women with normal (15) or some type of abnormal (9) placental function. We found no significant differences in baseline haemoglobin properties, but we found statistically significant differences in the placental haemodynamic responses to maternal hyperoxia. The results suggest that non-invasive monitoring of placental oxygenation may aid the early detection of placenta-related adverse pregnancy outcomes and maternal vascular malperfusion.

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The prospective multicenter ACRIN 6691 trial was designed to evaluate whether changes from baseline to mid-therapy in a diffuse optical spectroscopic imaging (DOSI)–derived imaging endpoint, the tissue optical index (TOI), predict pathologic complete response (pCR) in women undergoing breast cancer neoadjuvant chemotherapy (NAC). DOSI instruments were constructed at the University of California, Irvine (Irvine, CA), and delivered to six institutions where 60 subjects with newly diagnosed breast tumors (at least 2 cm in the longest dimension) were enrolled over a 2-year period. Bedside DOSI images of the tissue concentrations of deoxy-hemoglobin (ctHHb), oxy-hemoglobin (ctHbO2), water (ctH2O), lipid, and TOI (ctHHb × ctH2O/lipid) were acquired on both breasts up to four times during NAC treatment: baseline, 1-week, mid-point, and completion. Of the 34 subjects (mean age 48.4 ± 10.7 years) with complete, evaluable data from both normal and tumor-containing breast, 10 (29%) achieved pCR as determined by central pathology review. The percent change in tumor-to-normal TOI ratio (%TOITN) from baseline to mid-therapy ranged from −82% to 321%, with a median of −36%. Using pCR as the reference standard and ROC curve methodology, %TOITN AUC was 0.60 (95% CI, 0.39–0.81). In the cohort of 17 patients with baseline tumor oxygen saturation (%StO2) greater than the 77% population median, %TOITN AUC improved to 0.83 (95% CI, 0.63–1.00). We conclude that the combination of baseline functional properties and dynamic optical response shows promise for clinical outcome prediction. Cancer Res; 76(20); 5933–44. ©2016 AACR.

List of Chemotherapy regimens used in this study.

In lyotropic chromonic liquid crystals (LCLCs), twist distortion of the nematic director costs much less energy than splay or bend distortion. This feature leads to novel mirror-symmetry breaking director configurations when the LCLCs are confined by interfaces or contain suspended particles. Spherical colloids in an aligned LCLC nematic phase, for example, induce chiral director perturbations (“twisted tails”). The asymmetry of rod-like particles in an aligned LCLC offer a richer set of possibilities due to their aspect ratio (α) and mean orientation angle (〈θ〉) between their long axis and the uniform far-field director. Here we report on the director configuration, equilibrium orientation, and angular diffusion of rod-like particles with planar anchoring suspended in an aligned LCLC. Video microscopy reveals, counterintuitively, that two-thirds of the rods have an angled equilibrium orientation (〈θ〉 ≠ 0) that decreases with increasing α, while only one-third of the rods are aligned (〈θ〉 = 0). Polarized optical video-microscopy and Landau–de Gennes numerical modeling demonstrate that the angled and aligned rods are accompanied by distinct chiral director configurations. Angled rods have a longitudinal mirror plane (LMP) parallel to their long axis and approximately parallel to the substrate walls. Aligned rods have a transverse and longitudinal mirror plane (TLMP), where the transverse mirror plane is perpendicular to the rod's long axis. Effectively, the small twist elastic constant of LCLCs promotes chiral director configurations that modify the natural tendency of rods to orient along the far-field director. Additional diffusion experiments confirm that rods are angularly confined with strength that depends on α.

OBJECTIVE: Cardiac surgery utilizing circulatory arrest is most commonly performed under deep hypothermia (~18°C) to suppress tissue oxygen demand and provide neuroprotection during operative circulatory arrest. Studies investigating the effects of deep hypothermic circulatory arrest (DHCA) on neurodevelopmental outcomes of patients with congenital heart disease give conflicting results. Here, we address these issues by quantifying changes in cerebral oxygen saturation, blood flow, and oxygen metabolism in neonates during DHCA and investigating the association of these changes with post-operative brain injury. METHODS: Neonates with critical congenital heart disease undergoing DHCA were recruited for continuous intraoperative monitoring of cerebral oxygen saturation (ScO(2)) and an index of cerebral blood flow (CBF(i)) using two non-invasive optical techniques, diffuse optical spectroscopy (DOS) and diffuse correlation spectroscopy (DCS). Pre- and post-operative brain magnetic resonance imaging (MRI) was performed to detect white matter injury (WMI). RESULTS: Fifteen neonates were studied, and 11/15 underwent brain MRI. During DHCA, ScO(2) decreased exponentially in time with a median decay rate of −0.04 min(−1). This decay rate was highly variable between subjects. Subjects who had larger decreases in ScO(2) during DHCA were more likely to have post-operative WMI (p=0.02). CONCLUSIONS: Cerebral oxygen extraction persists during DHCA and varies widely from patient-to-patient. Patients with a higher degree of oxygen extraction during DHCA were more likely to show new WMI in post-operative MRI. These findings suggest cerebral oxygen extraction should be monitored during DHCA to identify patients at risk for hypoxic-ischemic injury, and that current commercial cerebral oximeters may underestimate cerebral oxygen extraction.

Cerebral metabolic rate of oxygen (We aim to develop a minimally invasive optical technique for real-time measurement ofWe used a pair of macromolecular phosphorescent probes with nonoverlapping optical spectra, which were localized in the intra- and extravascular compartments of the brain tissue, thus providing a readout of oxygen gradients between these two compartments. In parallel, we measured CBF using laser speckle contrast imaging.The method enables computation and tracking ofThe independent records of intravascular and extravascular partial pressures of oxygen, CBF, and

New exogenous probes are needed for both imaging diagnostics and therapeutics. Here, we introduce a novel nanocomposite near-infrared (NIR) fluorescent imaging probe and test its potency as a photosensitizing agent for photodynamic therapy (PDT) against triple-negative breast cancer cells. The active component in the nanocomposite is a small molecule, pyropheophorbide a-phosphatidylethanolamine-QSY21 (Pyro-PtdEtn-QSY), which is imbedded into lipid nanoparticles for transport in the body. The probe targets abnormal choline metabolism in cancer cells; specifically, the overexpression of phosphatidylcholine-specific phospholipase C (PC-PLC) in breast, prostate, and ovarian cancers. Pyro-PtdEtn-QSY consists of a NIR fluorophore and a quencher, attached to a PtdEtn moiety. It is selectively activated by PC-PLC resulting in enhanced fluorescence in cancer cells compared to normal cells. In our in vitro investigation, four breast cancer cell lines showed higher probe activation levels than noncancerous control cells, immortalized human mammary gland cells, and normal human T cells. Moreover, the ability of this nanocomposite to function as a sensitizer in PDT experiments on MDA-MB-231 cells suggests that the probe is promising as a theranostic agent.

Rapid estimation of the depth and margins of fluorescence targets buried below the tissue surface could improve upon current image-guided surgery techniques for tumor resection.We describe algorithms and instrumentation that permit rapid estimation of the depth and transverse margins of fluorescence target(s) in turbid media; the work aims to introduce, experimentally demonstrate, and characterize the methodology.Spatial frequency domain fluorescence diffuse optical tomography (SFD-FDOT) technique is adapted for rapid and computationally inexpensive estimation of fluorophore target depth and lateral margins. The algorithm utilizes the variation of diffuse fluorescence intensity with respect to spatial-modulation-frequency to compute target depth. The lateral margins are determined via analytical inversion of the data using depth information obtained from the first step. We characterize method performance using fluorescent contrast targets embedded in tissue-simulating phantoms.Single and multiple targets with significant lateral size were imaged at varying depths as deep as 1 cm. Phantom data analysis showed good depth-sensitivity, and the reconstructed transverse margins were mostly within ∼30 % error from true margins.The study suggests that the rapid SFD-FDOT approach could be useful in resection surgery and, more broadly, as a first step in more rigorous SFD-FDOT reconstructions. The experiments permit evaluation of current limitations.

In this study, we used diffuse optics to address the need for non-invasive, continuous monitoring of cerebral physiology following traumatic brain injury (TBI). We combined frequency-domain and broadband diffuse optical spectroscopy with diffuse correlation spectroscopy to monitor cerebral oxygen metabolism, cerebral blood volume, and cerebral water content in an established adult swine-model of impact TBI. Cerebral physiology was monitored before and after TBI (up to 14 days post injury). Overall, our results suggest that non-invasive optical monitoring can assess cerebral physiologic impairments post-TBI, including an initial reduction in oxygen metabolism, development of cerebral hemorrhage/hematoma, and brain swelling.

Neurologic injury is a leading cause of morbidity and mortality following pediatric cardiac arrest. In this study, we assess the feasibility of quantitative, non-invasive, frequency-domain diffuse optical spectroscopy (FD-DOS) neuromonitoring during cardiopulmonary resuscitation (CPR), and its predictive utility for return of spontaneous circulation (ROSC) in an established pediatric swine model of cardiac arrest. Cerebral tissue optical properties, oxy- and deoxy-hemoglobin concentration ([HbO2], [Hb]), oxygen saturation (StO2) and total hemoglobin concentration (THC) were measured by a FD-DOS probe placed on the forehead in 1-month-old swine (8–11 kg; n = 52) during seven minutes of asphyxiation followed by twenty minutes of CPR. ROSC prediction and time-dependent performance of prediction throughout early CPR (w, w = 0.1) with tenfold cross-validation. FD-DOS CPR data was successfully acquired in 48/52 animals; 37/48 achieved ROSC. Changes in scattering coefficient (785 nm), [HbO2], StO2 and THC from baseline were significantly different in ROSC versus No-ROSC subjects (p 2] of + 1.3 µmol/L from 1-min of CPR achieved the highest weighted Youden index (0.96) for ROSC prediction. We demonstrate feasibility of quantitative, non-invasive FD-DOS neuromonitoring, and stable, specific, early ROSC prediction from the third minute of CPR.

Optimal surgical management of spine trauma will restore blood flow to the ischemic spinal cord. However, spine stabilization may also further exacerbate injury by inducing ischemia. Current electrophysiological technology is not capable of detecting acute changes in spinal cord blood flow or localizing ischemia. Further, alerts are delayed and unreliable. We developed an epidural optical device capable of directly measuring and immediately detecting changes in spinal cord blood flow using diffuse correlation spectroscopy (DCS). Herein we test the hypothesis that our device can continuously monitor blood flow during spine distraction. Additionally, we demonstrate the ability of our device to monitor multiple sites along the spinal cord and axially resolve changes in spinal cord blood flow. DCS-measured blood flow in the spinal cord was monitored at up to three spatial locations (cranial to, at, and caudal to the distraction site) during surgical distraction in a sheep model. Distraction was halted at 50% of baseline blood flow at the distraction site. We were able to monitor blood flow with DCS in multiple regions of the spinal cord simultaneously at ∼1 Hz. The distraction site had a greater decrement in flow than sites cranial to the injury (median −40 vs. −7%,). This pilot study demonstrated high temporal resolution and the capacity to axially resolve changes in spinal cord blood flow at and remote from the site of distraction. These early results suggest that this technology may assist in the surgical management of spine trauma and in corrective surgery of the spine.

Background Extra-corporeal membrane oxygenation (ECMO) is a life-saving intervention for severe respiratory and cardiac diseases. However, 50% of survivors have abnormal neurologic exams. Current ECMO management is guided by systemic metrics, which may poorly predict cerebral perfusion. Continuous optical monitoring of cerebral hemodynamics during ECMO holds potential to detect risk factors of brain injury such as impaired cerebrovascular autoregulation (CA). Methods We conducted daily measurements of microvascular cerebral blood flow (CBF), oxygen saturation, and total hemoglobin concentration using diffuse correlation spectroscopy (DCS) and frequency-domain diffuse optical spectroscopy in nine neonates. We characterize CA utilizing the correlation coefficient (DCSx) between CBF and mean arterial blood pressure (MAP) during ECMO pump flow changes. Results Average MAP and pump flow levels were weakly correlated with CBF and were not correlated with cerebral oxygen saturation. CA integrity varied between individuals and with time. Systemic measurements of MAP, pulse pressure, and left cardiac dysfunction were not predictive of impaired CA. Conclusions Our pilot results suggest that systemic measures alone cannot distinguish impaired CA from intact CA during ECMO. Furthermore, optical neuromonitoring could help determine patient-specific ECMO pump flows for optimal CA integrity, thereby reducing risk of secondary brain injury. Impact Cerebral blood flow and oxygenation are not well predicted by systemic proxies such as ECMO pump flow or blood pressure. Continuous, quantitative, bedside monitoring of cerebral blood flow and oxygenation with optical tools enables new insight into the adequacy of cerebral perfusion during ECMO. A demonstration of hybrid diffuse optical and correlation spectroscopies to continuously measure cerebral blood oxygen saturation and flow in patients on ECMO, enabling assessment of cerebral autoregulation. An observation of poor correlation of cerebral blood flow and oxygenation with systemic mean arterial pressure and ECMO pump flow, suggesting that clinical decision making guided by target values for these surrogates may not be neuroprotective. ~50% of ECMO survivors have long-term neurological deficiencies; continuous monitoring of brain health throughout therapy may reduce these tragically common sequelae through brain-focused adjustment of ECMO parameters.

International audience; Conductive and transparent coatings consisting of silver nanowires (AgNWs) are promising candidates for emerging flexible electronics applications. Coatings of aligned AgNWs offer unusual electronic and optical anisotropies, with potential for use in micro-circuits, antennas, and polarization sensors. Here we explore a microfluidics setup and flow-induced alignment mechanisms to create centimeter-scale highly conductive coatings of aligned AgNWs with order parameters reaching 0.84, leading to large electrical and optical anisotropies. By varying flow rates, we establish the relationship between the shear rate and the alignment and investigate possible alignment mechanisms. The angle-dependent sheet resistance of the aligned AgNW networks exhibits an electronic transport anisotropy of ∼10× while maintaining low resistivity (

This report is the second part of a comprehensive two-part series aimed at reviewing an extensive and diverse toolkit of novel methods to explore brain health and function. While the first report focused on neurophotonic tools mostly applicable to animal studies, here, we highlight optical spectroscopy and imaging methods relevant to noninvasive human brain studies. We outline current state-of-the-art technologies and software advances, explore the most recent impact of these technologies on neuroscience and clinical applications, identify the areas where innovation is needed, and provide an outlook for the future directions.

Dynamic cerebral autoregulation (dCA) can be derived from spontaneous oscillations in arterial blood pressure (ABP) and cerebral blood flow (CBF). Transcranial Doppler (TCD) measures CBF-velocity and is commonly used to assess dCA. Diffuse correlation spectroscopy (DCS) is a promising optical technique for non-invasive CBF monitoring, so here we aimed to validate DCS as a tool for quantifying dCA. In 33 healthy adults and 17 acute ischemic stroke patients, resting-state hemodynamic were monitored simultaneously with high-speed (20 Hz) DCS and TCD. dCA parameters were calcaulated by a transfer function analysis using a Fourier decomposition of ABP and CBF (or CBF-velocity). Strong correlation was found between DCS and TCD measured gain (magnitude of regulation) in healthy volunteers (r = 0.73, p

With few exceptions1-3, polydispersity or molecular heterogeneity in matter tends to impede self-assembly and state transformation. For example, shape transformations of liquid droplets with monodisperse ingredients have been reported in equilibrium4-7 and non-equilibrium studies8,9, and these transition phenomena were understood on the basis of homogeneous material responses. Here, by contrast, we study equilibrium suspensions of drops composed of polydisperse nematic liquid crystal oligomers (NLCOs). Surprisingly, molecular heterogeneity in the polydisperse drops promotes reversible shape transitions to a rich variety of non-spherical morphologies with unique internal structure. We find that variation of oligomer chain length distribution, temperature, and surfactant concentration alters the balance between NLCO elastic energy and interfacial energy, and drives formation of nematic structures that range from roughened spheres to 'flower' shapes to branched filamentous networks with controllable diameters. The branched structures with confined liquid crystal director fields can be produced reversibly over areas of at least one square centimetre and can be converted into liquid crystal elastomers by ultraviolet curing. Observations and modelling reveal that chain length polydispersity plays a crucial role in driving these morphogenic phenomena, via spatial segregation. This insight suggests new routes for encoding network structure and function in soft materials.

Exercise training can mitigate symptoms of claudication (walking-induced muscle pain) in patients with peripheral artery disease (PAD). One adaptive response enabling this improvement is enhanced muscle oxygen metabolism. To explore this issue, we used arterial-occlusion diffuse optical spectroscopy (AO-DOS) to measure the effects of exercise training on the metabolic rate of oxygen (MRO2) in resting calf muscle. Additionally, venous-occlusion DOS (VO-DOS) and frequency-domain DOS (FD-DOS) were used to measure muscle blood flow (F) and tissue oxygen saturation (StO2), and resting calf muscle oxygen extraction fraction (OEF) was calculated from MRO2, F, and blood hemoglobin. Lastly, the venous/arterial ratio (γ) of blood monitored by FD-DOS was calculated from OEF and StO2. PAD patients who experience claudication (n = 28) were randomly assigned to exercise and control groups. Patients in the exercise group received 3 months of supervised exercise training. Optical measurements were obtained at baseline and at 3 months in both groups. Resting MRO2, OEF, and F, respectively, increased by 30% (12%, 44%) (p < 0.001), 17% (6%, 45%) (p = 0.003), and 7% (0%, 16%) (p = 0.11), after exercise training (median (interquartile range)). The pre-exercise γ was 0.76 (0.61, 0.89); it decreased by 12% (35%, 6%) after exercise training (p = 0.011). Improvement in exercise performance was associated with a correlative increase in resting OEF (R = 0.45, p = 0.02).

We investigate the short-time vibrational properties and structure of two-dimensional, bidisperse, colloidal glasses and supercooled liquids in the vicinity of the re-entrant glass transition, as a function of interparticle depletion attraction strength. The long-time spatiotemporal dynamics of the samples are measured to be non-monotonic, confirming that the suspensions evolve from repulsive glass to supercooled liquid to attractive glass with increasing depletion attraction. Here, we search for vibrational signatures of the re-entrant behavior in the short-time spatiotemporal dynamics, i.e., dynamics associated with particle motion inside its nearest-neighbor cage. Interestingly, we observe that the anharmonicity of these in-cage vibrations varies non-monotonically with increasing attraction strength, consistent with the non-monotonic long-time structural relaxation dynamics of the re-entrant glass. We also extract effective spring constants between neighboring particles; we find that spring stiffness involving small particles also varies non-monotonically with increasing attraction strength, while stiffness between large particles increases monotonically. Last, from study of depletion-dependent local structure and vibration participation fractions, we gain microscopic insight into the particle-size-dependent contributions to short-time vibrational modes in the glass and supercooled liquid states.

INTRODUCTION: Mechanical thrombectomy is revolutionizing treatment of acute stroke due to large vessel occlusion (LVO). Unfortunately, use of the modified Thrombolysis in Cerebral Infarction score (mTICI) to characterize recanalization of the cerebral vasculature does not address microvascular perfusion of the distal parenchyma, nor provide more than a vascular “snapshot”. Thus, little is known about tissue-level hemodynamic consequences of LVO recanalization. Diffuse correlation spectroscopy (DCS) and diffuse optical spectroscopy (DOS) are promising methods for continuous, non-invasive, contrast-free transcranial monitoring of cerebral microvasculature. METHODS: Here we use a combined DCS/DOS system to monitor frontal lobe hemodynamic changes during endovascular treatment of two patients with ischemic stroke due to cervical internal carotid artery (ICA) occlusions. RESULTS AND DISCUSSION: The monitoring instrument identified a recanalization-induced increase in ipsilateral cerebral blood flow (CBF) with little or no concurrent change in contralateral CBF and extracerebral blood flow. The results suggest that diffuse optical monitoring is sensitive to intracerebral hemodynamics in patients with cervical ICA occlusion and can measure microvascular responses to mechanical thrombectomy.

A fundamental challenge for disordered solids is predicting macroscopic yield from the microscopic arrangements of constituent particles. Yield is accompanied by a sudden and large increase in energy dissipation due to the onset of plastic rearrangements. This suggests that one path to understanding bulk rheology is to map particle configurations to their mode of deformation. Here, we perform laboratory experiments and numerical simulations that are designed to do just that: 2D dense colloidal systems are subjected to oscillatory shear, and particle trajectories and bulk rheology are measured. We quantify particle microstructure using excess entropy. Results reveal a direct relation between excess entropy and energy dissipation, that is insensitive to the nature of interactions among particles. We use this relation to build a physically-informed model that connects rheology to microstructure. Our findings suggest a framework for tailoring the rheological response of disordered materials by tuning microstructural properties.

Autorregulació cerebral; Malaltia cerebrovascular; Òptica difusa Autorregulación cerebral; Enfermedad cerebrovascular; Óptica difusa Cerebral autoregulation; Cerebrovascular disease; Diffuse optics Background The cortical microvascular cerebral blood flow response (CBF) to different changes in head-of-bed (HOB) position has been shown to be altered in acute ischemic stroke (AIS) by diffuse correlation spectroscopy (DCS) technique. However, the relationship between these relative ΔCBF changes and associated systemic blood pressure changes has not been studied, even though blood pressure is a major driver of cerebral blood flow. Methods Transcranial DCS data from four studies measuring bilateral frontal microvascular cerebral blood flow in healthy controls (n = 15), patients with asymptomatic severe internal carotid artery stenosis (ICA, n = 27), and patients with acute ischemic stroke (AIS, n = 72) were aggregated. DCS-measured CBF was measured in response to a short head-of-bed (HOB) position manipulation protocol (supine/elevated/supine, 5 min at each position). In a sub-group (AIS, n = 26; ICA, n = 14; control, n = 15), mean arterial pressure (MAP) was measured dynamically during the protocol. Results After elevated positioning, DCS CBF returned to baseline supine values in controls (p = 0.890) but not in patients with AIS (9.6% [6.0,13.3], mean 95% CI, p

Hydrocephalus is a disorder of cerebral spinal fluid (CSF) physiology that results in increased intracranial pressure (ICP). It is commonly treated via surgical placement of a shunt in the ventricles to divert CSF. Diffuse optical measurements of cerebral perfusion and oxygen extraction were acquired before and after surgical shunt placement in neonates with hydrocephalus. An invasive ICP measurement was made at the time of shunt placement. Shunting increased cerebral perfusion and decreased oxygen extraction only in infants with elevated ICP. This suggests abnormally low perfusion in patients with elevated ICP, and normal perfusion in patients without elevated ICP.

Monitoring critical closing pressure (CrCP) can be a useful and noninvasive measure of intracranial pressure (ICP), especially in patients with high risk factors for brain injury. We monitored five patients undergoing cardiac ablation procedures using diffuse correlation spectroscopy (DCS). We utilized the prolonged diastolic events that occur during this procedure to validate non-invasive measurements of CrCP with DCS. to estimate the gold standard CrCP during long diastolic events induced during the procedure and compared them to estimations from normal pressure and flow waveforms prior to each event.

Extracorporeal membrane oxygenation (ECMO) is an important therapy for critically ill children but survivors have neurodevelopmental impairments. Cerebral inflammatory response resulting in brain edema is observed on ECMO. This pathologic response may adversely impact the quantitative accuracy of diffuse optical spectroscopy (DOS) neuromonitoring (including commercial NIRS) which commonly assumes a 75% water fraction. Using fresh brain tissue desiccation, we directly quantified the severity of cerebral edema in pediatric swine following cardiac arrest, CPR and 22-24 hours of ECMO therapy. The fractional error in DOS quantification of cerebral hemodynamics from assuming 75% water fraction was determined to be

We examine the correlation of non-invasive, frequency-domain diffuse optical spectroscopy (FD-DOS) and diffuse correlation spectroscopy (DCS) measurements of cerebral tissue oxygen extraction fraction (OEF) and relative cerebral blood flow (rCBF) with invasive cerebral microdialysis measurement of the cerebral lactate-pyruvate ratio (LPR), a biomarker of metabolic stress, during extracorporeal membrane oxygenation (ECMO) in a pediatric swine model of ECMO assisted cardiopulmonary resuscitation (n=15). During 22-24 hours of ECMO, non-invasive FD-DOS/DCS neuromonitoring of OEF and rCBF demonstrated significant correlations with cerebral LPR. Non-invasive detection of critical neurometabolic stress at the bedside may facilitate brain-targeted ECMO management after cardiac arrest.

Currently, no bedside tool measures placental hemoglobin properties. Thus, we developed a hybrid optical/ultrasound (US) system to measure and study placental oxygen dynamics noninvasively. The system combines a Frequency-Domain Diffuse Optical Spectroscopy (FD-DOS) instrument that is capable of probing tissue as deep as 5 cm below the surface, with a commercial US device to provide synchronized tissue morphological information. Multi-layer models of photon diffusion are then utilized to reconstruct placental hemoglobin properties from FD-DOS data with morphological constraints from US. Phantom experiments, simulations, and studies in human subjects demonstrate that this instrument quantifies in vivo placental hemodynamics non-invasively.

Mild hypothermic cardiopulmonary bypass (CPB) is used during neonatal cardiac surgery. To elucidate potential risk factors for brain injury, diffuse optical spectroscopy, diffuse correlation spectroscopy, and cerebral microdialysis techniques were employed to monitor cerebral hemodynamics during mild hypothermic CPB in a swine model. Optical metrics were further compared with microdialysis metrics. Stable microdialysis metabolite levels, a significant decrease in CMRO2, and trending (but not significant) decreases in CBF and increases in OEF were observed. This suggests that the optical metrics may be more sensitive to neurologic injury during CPB than microdialysis.

We present a novel method for real-time measurement of the oxygen (pO2) gradients between intra- and extra-vascular compartments in rat brain cortex during functional activation. This information, obtained in parallel with measurements of cerebral blood flow (CBF), permits determination of absolute cerebral metabolic rate of oxygen (CMRO2). The timing of pO2, CBF, and CMRO2 responses is captured with high temporal resolution (~7 Hz). We discuss these results in the context of physiological models that connect oxidative metabolism to neuronal activation.