Hemodynamic Oscillations Research Articles

A Noninvasive Method for Monitoring Intracranial Pressure During Postural Changes.

Intracranial hypertension (IH) is an important cause of secondary brain injury, and its association with poor outcomes has been extensively demonstrated. Pathological intracranial hypertension is defined as a persistent rise in intracranial pressure (ICP) to above 20-25mmHg, with symptoms such as headaches, loss of consciousness, seizures, and focal deficits, as well as ischemic damage. Therefore, monitoring of ICP is invaluable in the management of these symptoms. However, invasive measurements of ventricular pressure (requiring a surgical procedure) are considered the gold standard, thus limiting the practicality of ICP measurements. Vivonics, Inc., is developing a noninvasive optical device to assess ICP for use by emergency medical personnel, called IPASS: Intracranial Pressure Assessment and Screening System. IPASS uses four near-infrared sensors to measure hemodynamic oscillations at four different locations. Three sensors are used as reference signals and one sensor is used to detect cerebral blood volume oscillations. Pulse arrival delays between the measured cerebral blood volume oscillations and the blood volume oscillations measured at the three reference locations are calculated and correlated with estimated ICP changes, herein modulated by specific positional changes (in a head-down maneuver).

Functional near-infrared spectroscopy can detect low-frequency hemodynamic oscillations in the prefrontal cortex during steady-state visual evoked potential-inducing periodic facial expression stimuli presentation

Brain oscillations are vital to cognitive functions, while disrupted oscillatory activity is linked to various brain disorders. Although high-frequency neural oscillations (> 1 Hz) have been extensively studied in cognition, the neural mechanisms underlying low-frequency hemodynamic oscillations (LFHO) < 1 Hz have not yet been fully explored. One way to examine oscillatory neural dynamics is to use a facial expression (FE) paradigm to induce steady-state visual evoked potentials (SSVEPs), which has been used in electroencephalography studies of high-frequency brain oscillation activity. In this study, LFHO during SSVEP-inducing periodic flickering stimuli presentation were inspected using functional near-infrared spectroscopy (fNIRS), in which hemodynamic responses in the prefrontal cortex were recorded while participants were passively viewing dynamic FEs flickering at 0.2 Hz. The fast Fourier analysis results demonstrated that the power exhibited monochronic peaks at 0.2 Hz across all channels, indicating that the periodic events successfully elicited LFHO in the prefrontal cortex. More importantly, measurement of LFHO can effectively distinguish the brain activation difference between different cognitive conditions, with happy FE presentation showing greater LFHO power than neutral FE presentation. These results demonstrate that stimuli flashing at a given frequency can induce LFHO in the prefrontal cortex, which provides new insights into the cognitive mechanisms involved in slow oscillation.

Assessing Dynamic Cerebral Autoregulation in Patients with Sickle Cell Disease Using Near-Infrared Spectroscopy and Paced Breathing

Introduction. Sickle cell disease (SCD) is caused by hemoglobin S polymerization leading to vaso-occlusion, small vessel disease, and reduced tissue oxygen saturation. Noninvasive assessments and screening of small vessel disease and decreased oxygen saturation in select organs, like the brain, are poorly developed. Cerebral autoregulation, a mechanism that ensures cerebral blood flow (CBF) remains constant with changes in mean arterial pressure, is impaired with and is a marker of small vessel disease. Frequency-domain near-infrared spectroscopy (FD-NIRS) can be used as a noninvasive technique to measure cerebral autoregulation by recording cerebral microvascular changes in hemoglobin concentration that are related to cerebral blood flow. Transfer function analysis is a method to noninvasively quantify the relationship between measured physiologic signals, and can be used to estimate cerebral autoregulation. In this study, we hypothesized patients with SCD have impaired cerebral autoregulation and reduced tissue oxygen saturation, which we evaluated via FD-NIRS with transfer function analysis, as compared to healthy controls. Methods. All patients provided informed consent under an IRB protocol approved by the University of Pittsburgh and Carnegie Mellon University. Patients with SCD (n = 11) and healthy, race-matched controls (n =14) were enrolled. All participants sat upright in a chair with probes of a commercial multi-distance FD-NIRS apparatus applied to their forehead in a dark room (Fig. 1A). We used paced breathing to dynamically induce controlled changes in the microvascular tone at 0.1, 0.125, and 0.1667 Hz, spanning normal to more challenging breathing rates, with a visual metronome guiding each paced breathing session (Fig.1.B). To validate each breathing pace, we recorded the participants' respiratory rate via a belt placed around their chest, and their mean arterial pressure through a finger and arm cuff attached to a beat-to-beat finger plethysmographer (Fig.1.A). We used the modified Beer-Lambert law to calculate changes in oxy-hemoglobin (O), deoxy-hemoglobin (D), and total hemoglobin (T) concentrations. Data was bandpass-filtered around the paced breathing frequencies, and the Hilbert transform was applied to calculate the amplitude ratios, |D|/|O|, and phase latency, Arg(D)−Arg(O). The tissue oxygen saturation of hemoglobin, StO2 (mean ±SD), was computed based on an average baseline of two minutes. Results. Arg(D)−Arg(O) and |D|/|O| are shown for controls and patients at all paced breathing frequencies (Fig.1C-D) from the largest source-detector distance. A non-zero phase lag between D and O within both groups indicates influences of cerebral blood volume (CBV) and CBF changes. The phase differences of D and O are therefore related to cerebral autoregulation. We found a greater phase difference (mean range: -320° to -340°) in patients with SCD compared to controls (mean range: -200° to -240°), indicating the presence of vascular obstruction and impaired cerebral autoregulation. Higher amplitude ratios |D|/|O| may indicate slower blood transmit times. We found that patients with SCD had increased amplitude ratios for hemodynamic oscillations at lower paced breathing frequencies compared to healthy controls (Fig. 1D). Finally, we found a significantly reduced cerebral tissue oxygen saturation in patients with SCD (63.1 % ± 7.8 %) in comparison with controls (65.9 % ± 4.9 %, p&amp;lt;0.05, Fig.1E). Discussion. We provide preliminary evidence that FD-NIRS can be used to assess cerebral autoregulation in SCD. Our results confirm and extend those of a prior study by Reinhard et al, 2003, by using the phase latency, Arg(D)−Arg(O), and the amplitude ratios, |D|/|O|, to assess autoregulation. In addition, we detected a noticeable reduction in oxygen saturation in patients with SCD as compared to healthy controls. Further studies may extend our findings to additional frequencies in a larger sample size to more comprehensively assess the impact of mean arterial pressure on autoregulation. Noninvasive measurement of cerebral autoregulation and brain oxygenation in SCD by FD-NIRS may represent a novel biomarker of cerebral vasculopathy in SCD and may help monitor changes in cerebral oxygenation, particularly during treatment with drugs that modulate the hemoglobin oxygen affinity, such as the recently FDA-approved voxelotor. Figure 1 Disclosures No relevant conflicts of interest to declare.

Measuring the Frequency-Specific Functional Connectivity Using Wavelet Coherence Analysis in Stroke Rats Based on Intrinsic Signals

Optical intrinsic signal imaging (OISi) method is an optical technique to evaluate the functional connectivity (FC) of the cortex in animals. Already, using OISi, the FC of the cortex has been measured in time or frequency domain separately, and at frequencies below 0.08 Hz, which is not in the frequency range of hemodynamic oscillations which are able to track fast cortical events, including neurogenic, myogenic, cardiac and respiratory activities. In the current work, we calculated the wavelet coherence (WC) transform of the OISi time series to evaluate the cerebral response changes in the stroke rats. Utilizing WC, we measured FC at frequencies up to 4.5 Hz, and could monitor the time and frequency dependency of the FC simultaneously. The results showed that the WC of the brain diminished significantly in ischemic motor and somatosensory cortices. According to the statistical results, the signal amplitude, responsive area size, correlation, and wavelet coherence of the motor and the somatosensory cortices for stroke hemisphere were found to be significantly lower compared to the healthy hemisphere. The obtained results confirm that the OISi-based WC analysis is an efficient method to diagnose the relative severity of infarction and the size of the infarcted region after ischemic stroke.

Interactions between stimuli-evoked cortical activity and spontaneous low frequency oscillations measured with neuronal calcium

Spontaneous brain activity has been widely used to map brain connectivity. The interactions between task-evoked brain responses and the spontaneous cortical oscillations, especially within the low frequency range of ~0.1 ​Hz, are not fully understood. Trial-to-trial variabilities in brain’s response to sensory stimuli and the ability for brain to detect under noisy conditions suggest an appreciable impact of the brain state. Using a multimodality imaging platform, we simultaneously imaged neuronal Ca2+ and cerebral hemodynamics at baseline and in response to single-pulse forepaw stimuli in rat’s somatosensory cortex. The high sensitivity of this system enables detection of responses to very weak and strong stimuli and real time determination of low frequency oscillations without averaging. Results show that the ongoing neuronal oscillations inversely modulate Ca2+ transients evoked by sensory stimuli. High intensity stimuli reset the spontaneous neuronal oscillations to an unpreferable excitability following the stimulus. Cerebral hemodynamic responses also inversely interact with the spontaneous hemodynamic oscillations, correlating with the neuronal Ca2+ transient changes. The results reveal competing interactions between spontaneous oscillations and stimulation-evoked brain activities in somatosensory cortex and the resultant hemodynamics.

An Analysis of Phase Relationships between Oscillatory Processes in the Human Cardiovascular System

Abstract—The phase relationships between heart rate variability, respiration, forearm skin blood flow oscillations (according to laser Doppler flowmetry), and finger-pad tissue blood volume oscillations (according to photoplethysmography) were analyzed in relatively healthy volunteers at rest. The degree of synchronization between phases of analyzed signals was estimated based on the value of the phase wavelet coherence function. A significant phase synchronization was detected between forearm skin blood flow oscillations and finger-pad tissue blood volume oscillations in the low frequency region (0.0095–0.1 Hz) and at the frequency of heart rate of ~ 1 Hz. At a respiration rate of ~0.3 Hz, differences were detected in the phase synchronization of peripheral hemodynamic oscillations (blood volume and blood flow) with both heart rate variability and respiration. For finger-pad tissue blood volume oscillations, a high phase synchronization with both heart rate variability and respiratory rate was observed; for forearm blood flow oscillations, low phase synchronization occurred in both cases.

Slow hemodynamic oscillations during whole night recording and interactions with epileptic discharges: a simultaneous electroencephalography-near infrared spectroscopy case report study

Slow hemodynamic oscillations during whole night recording and interactions with epileptic discharges: a simultaneous electroencephalography-near infrared spectroscopy case report study

Phase dual-slopes in frequency-domain near-infrared spectroscopy for enhanced sensitivity to brain tissue: First applications to human subjects.

We present a first in vivo application of phase dual-slopes (DSϕ), measured with frequency-domain near-infrared spectroscopy on four healthy human subjects, to demonstrate their enhanced sensitivity to cerebral hemodynamics. During arterial blood pressure oscillations elicited at a frequency of 0.1 Hz, we compare three different ways to analyze either intensity (I) or phase (ϕ) data collected on the subject's forehead at multiple source-detector distances: Single-distance, single-slope and DS. Theoretical calculations based on diffusion theory show that the method with the deepest maximal sensitivity (at about 11 mm) is DSϕ. The in vivo results indicate a qualitative difference of phase data (especially DSϕ) and intensity data (especially single-distance intensity [SDI]), which we assign to stronger contributions from scalp hemodynamics to SDI and from cortical hemodynamics to DSϕ. Our findings suggest that scalp hemodynamic oscillations may be dominated by blood volume dynamics, whereas cortical hemodynamics may be dominated by blood flow velocity dynamics.

Responses of cerebral blood velocity and tissue oxygenation to low-frequency oscillations during simulated haemorrhagic stress in humans.

What is the central question of this study? Do low-frequency oscillations in arterial pressure and cerebral blood velocity protect cerebral blood velocity and oxygenation during central hypovolaemia? What is the main finding and its importance? Low-frequency oscillations in arterial pressure and cerebral blood velocity attenuate reductions in cerebral oxygen saturation but do not protect absolute cerebral blood velocity during central hypovolaemia. This finding indicates the potential importance of haemodynamic oscillations in maintaining cerebral oxygenation and therefore viability of tissues during challenges to cerebral blood flow and oxygen delivery. Tolerance to both real and simulated haemorrhage varies between individuals. Exaggerated low-frequency (∼0.1Hz) oscillations in mean arterial pressure and brain blood flow [indexed via middle cerebral artery velocity (MCAv)] have been associated with improved tolerance to reduced central blood volume. The mechanism for this association has not been explored. We hypothesized that inducing low-frequency oscillations in arterial pressure and cerebral blood velocity would attenuate reductions in cerebral blood velocity and oxygenation during simulated haemorrhage. Fourteen subjects (11men and three women) were exposed to oscillatory (0.1 and 0.05Hz) and non-oscillatory (0Hz) lower-body negative pressure profiles with an average chamber pressure of -60mmHg (randomized and counterbalanced order). Measurements included arterial pressure and stroke volume via finger photoplethysmography, MCAv via transcranial Doppler ultrasound, and cerebral oxygenation of the frontal lobe via near-infrared spectroscopy. Tolerance was higher during the two oscillatory profiles compared with the 0Hz profile (0.05Hz, P=0.04; 0.1Hz, P=0.09), accompanied by attenuated reductions in stroke volume (P<0.001) and cerebral oxygenation of the frontal lobe (P≤0.02). No differences were observed between profiles for reductions in mean arterial pressure (P=0.17) and MCAv (P=0.30). In partial support of our hypothesis, cerebral oxygenation, but not cerebral blood velocity, was protected during the oscillatory profiles. Interestingly, more subjects tolerated the oscillatory profiles compared with the static 0Hz profile, despite similar arterial pressure responses. These findings emphasize the potential importance of haemodynamic oscillations in maintaining perfusion and oxygenation of cerebral tissues during haemorrhagic stress.

Probing prefrontal cortex hemodynamic alterations during facial emotion recognition for major depression disorder through functional near-infrared spectroscopy

Objective. A serious issue in psychiatric practice is a lack of specific, objective biomarker to assist clinicians in establishing differential diagnosis and improving individualized treatment. Major depression disorder (MDD) is characterized by poorer ability in processing of facial emotional expressions. Approach. Applying a portable neuroimaging system using near-infrared spectroscopy, we investigated the prefrontal cortex hemodynamic activation changes during facial emotion recognition and rest periods for 27 MDD patients compared with 24 healthy controls (HC). Main results. The hemodynamic changes in the left prefrontal cortex for the MDD group showed significant differences in the median values and the Mayer wave power ratios of the oxygenated hemoglobin (oxy-Hb) and deoxygenated hemoglobin (deoxy-Hb) during the emotional face recognition compared with the HC subjects, indicating the abnormal oxidative metabolism and weaker local hemodynamic oscillations for the MDD. The mean cross wavelet coefficients and the average wavelet coherence coefficient between oxy-Hb and deoxy-Hb over the left prefrontal cortex, and also between the bilateral oxy-Hb in the MDD patients were significantly lower than the HC group, demonstrating abnormal locally functional connectivity over the left prefrontal cortex, and the inter-hemispheric connection between the bilateral prefrontal cortices. Significance. These results suggested that the hemodynamic changes over the left prefrontal cortex and between the bilateral prefrontal cortices detected by fNIRS could provide reliable predictors for the diagnosis of the depression in clinic, and also supported the rationale for use of transcranial magnetic stimulation over the left dorsolateral prefrontal cortex to restore excitability of prefrontal cortex that exhibits diminished regulation of emotion-generative systems in the MDD patients.

Frequency-resolved analysis of coherent oscillations of local cerebral blood volume, measured with near-infrared spectroscopy, and systemic arterial pressure in healthy human subjects.

We report a study on twenty-two healthy human subjects of the dynamic relationship between cerebral hemoglobin concentration ([HbT]), measured with near-infrared spectroscopy (NIRS) in the prefrontal cortex, and systemic arterial blood pressure (ABP), measured with finger plethysmography. [HbT] is a measure of local cerebral blood volume (CBV). We induced hemodynamic oscillations at discrete frequencies in the range 0.04–0.20 Hz with cyclic inflation and deflation of pneumatic cuffs wrapped around the subject’s thighs. We modeled the transfer function of ABP and [HbT] in terms of effective arterial (K(a)) and venous (K(v)) compliances, and a cerebral autoregulation time constant (τ(AR)). The mean values (± standard errors) of these parameters across the twenty-two subjects were K(a) = 0.01 ± 0.01 μM/mmHg, K(v) = 0.09 ± 0.05 μM/mmHg, and τ(AR) = 2.2 ± 1.3 s. Spatially resolved measurements in a subset of eight subjects reveal a spatial variability of these parameters that may exceed the inter-subject variability at a set location. This study sheds some light onto the role that ABP and cerebral blood flow (CBF) play in the dynamics of [HbT] measured with NIRS, and paves the way for new non-invasive optical studies of cerebral blood flow and cerebral autoregulation.

Multi-distance frequency-domain optical measurements of coherent cerebral hemodynamics.

We report non-invasive, bilateral optical measurements on the forehead of five healthy human subjects, of 0.1 Hz oscillatory hemodynamics elicited either by cyclic inflation of pneumatic thigh cuffs, or by paced breathing. Optical intensity and the phase of photon-density waves were collected with frequency-domain near-infrared spectroscopy at seven source-detector distances (11-40 mm). Coherent hemodynamic oscillations are represented by phasors of oxyhemoglobin (O) and deoxyhemoglobin (D) concentrations, and by the vector D/O that represents the amplitude ratio and phase difference of D and O. We found that, on average, the amplitude ratio (|D/O|) and the phase difference (∠(D/O)) obtained with single-distance intensity at 11-40 mm increase from 0.1 and −330°, to 0.2 and −200°, respectively. Single-distance phase and the intensity slope featured a weaker dependence on source-detector separation, and yielded |D/O| and ∠(D/O) values of about 0.5 and −200°, respectively, at distances greater than 20 mm. The key findings are: (1) single-distance phase and intensity slope are sensitive to deeper tissue compared to single-distance intensity; (2) deeper tissue hemodynamic oscillations, which more closely represent the brain, feature D and O phasors that are consistent with a greater relative flow-to-volume contributions in brain tissue compared to extracerebral, superficial tissue.

Low-frequency facial hemodynamic oscillations distinguish migraineurs from non-headache controls.

Surface imaging is a promising, noninvasive approach to assess regional perfusion in craniovascular disorders such as migraine. We used optical imaging to examine differences in facial blood volume at baseline and in response to ammonia inhalation (a noxious stimulus), as well as standardized measures of cardiovascular autonomic function, in healthy, non-headache controls (n = 43) and in interictal migraine subjects (n = 22). Resting facial cutaneous oscillation (FCO) frequency was significantly different in migraine compared to healthy controls. Following ammonia inhalation, healthy controls showed a significant increase in resting FCO frequency, whereas this response was not significant in the migraine group. Standardized autonomic reflex parameters did not differ significantly between study groups, and facial cutaneous activity did not correlate with standardized cardiovascular autonomic reflex parameters, suggesting potentially different regulation. This approach to the assessment of craniofacial hemodynamic function appears to exhibit differing mechanisms from previously available techniques, and represents a promising new physiological biomarker for the study of craniofacial vascular function in migraine and potentially other craniovascular disorders.

Depth dependence of coherent hemodynamics in the human head.

We report a near-infrared spectroscopy (NIRS) study of coherent hemodynamic oscillations measured on the human forehead at multiple source-detector distances (1 to 4cm). The physiological source of the coherent hemodynamics is arterial blood pressure oscillations at a frequency of 0.1Hz, induced by cyclic inflation (to a pressure of 200mmHg) and deflation of two thigh cuffs wrapped around the subject's thighs. To interpret our results, we use a recently developed hemodynamic model and a phasor representation of the oscillations of oxyhemoglobin, deoxyhemoglobin, and total hemoglobin concentrations in the tissue (phasors O, D, and T, respectively). The increase in the phase angle between D and O at larger source-detector separations is assigned to greater flow versus volume contributions and to a stronger blood flow autoregulation in deeper tissue (brain cortex) with respect to superficial tissue (scalp and skull). The relatively constant phase lag of T versus arterial blood pressure oscillations at all source-detector distances was assigned to competing effects from stronger autoregulation and smaller arterial-to-venous contributions in deeper tissue with respect to superficial tissue. We demonstrate the application of a hemodynamic model to interpret coherent hemodynamics measured with NIRS and to assess the different nature of shallow (extracerebral) versus deep (cerebral) tissue hemodynamics.

Hemodynamic instability during percutaneous ablation of extra-adrenal metastases of pheochromocytoma and paragangliomas: a case series

BackgroundSurgical manipulation of pheochromocytomas and paragangliomas (PPGLs) may induce large hemodynamic oscillations due to catecholamine release. Little is known regarding hemodynamic instability during percutaneous ablation of PPGLs. We examined intraprocedural hemodynamic variability and postoperative complications related to percutaneous ablation of extra-adrenal metastases of PPGL.MethodsFrom institutional PPGL registry we identified patients undergoing ablation of extra-adrenal PPGL metastases from January 1, 2000, through December 31, 2016. We reviewed medical records for clinical characteristics and hospital outcomes. Tumors were categorized as functional or nonfunctional based on preprocedural fractionated catecholamine and metanephrine profiles.ResultsTwenty-one patients (14 female [67%]) underwent 38 ablations. Twenty-four ablations were performed in patients with functional metastatic lesions, and 14 were in nonfunctional lesions. Intraprocedural use of potent vasodilators for hypertension was higher for patients with functional tumors (P = 0.02); use of vasopressors for hypotension was similar for functional and nonfunctional tumors (P = 0.74). Mean (±SD) intraprocedural blood pressure range (maximum–minimum blood pressure) during 38 procedures was greater for functional than nonfunctional tumors [systolic: 106 (±48) vs 64 (±30) mm Hg, P = 0.005; diastolic: 58 (±22) vs 35 (±14) mm Hg, P = 0.002; mean arterial: 84 (±43) vs 47 (±29) mm Hg, P = 0.007]. Complications included 5 unplanned intensive care unit admissions (3 for precautionary monitoring, 1 for recalcitrant hypotension, and 1 for hypertensive crisis), 1 case of postoperative bleeding, and 1 death.ConclusionsSubstantial hemodynamic instability may develop during ablation of functional and nonfunctional PPGL metastases. When anesthesia is provided for ablation of metastatic PPGLs in radiology suites, preparation for hemodynamic management should match standards used for surgical resection.

Slow oscillations of cerebral hemodynamics changes during low-level light therapy in the elderly with and without mild cognitive impairment: An fNIRS study

Low-level light therapy (LLLT) is used to stimulate cell function or reduce pain by applying light emitting diodes (LED) to the skin. LLLT is known to contribute to the neuronal recovery during the reconstruction of brain tissue for the treatment of degenerative disorders. This research aims to confirm the slow oscillations of cerebral hemodynamics changes when LLLT is applied to the elderly and patients with mild cognitive impairment (MCI). Eight patients with MCI and 7 healthy elderly participated in this study. They were randomly divided into four groups; carotid artery stimulation, vertebral artery stimulation, simultaneous carotid and vertebral artery stimulation, or sham stimulation. The subjects received LLLT using Color DNA ® (Color Seven Co.) with a LED light source for 30 minutes a day during 20 days. The hemodynamic responses were recorded by an fNIRS system (NIRScout ® ) with 74 channels at the first and the 20th intervention days, before, during, and after the LLLT. The spectral power density over the very low-frequency oscillations (VLFO) of cerebral hemodynamics was calculated using Welch technique. In both healthy and MCI patients, VLFO increased in the whole cerebral area during LLLT compared to the resting state, and these changes are more contrasting in the condition with simultaneous carotid and vertebral artery stimulation condition. These characteristics were observed in both the first and 20th intervention days however, VLFO in the 20th intervention day were more increased than the first day. Increase of very low frequency oscillations demonstrated increasing spontaneous activity of cerebrovascular tone and neuronal activation. These findings may suggest a possibility of modulating effect of LLLT on neuronal activity and blood vessel reconstruction.

Detailed view on slow sinusoidal, hemodynamic oscillations on the human brain cortex by Fourier transforming oxy/deoxy hyperspectral images.

Slow sinusoidal, hemodynamic oscillations (SSHOs) around 0.1 Hz are frequently seen in mammalian and human brains. In four patients undergoing epilepsy surgery, subtle but robust fluctuations in oxy‐ and deoxyhemoglobin were detected using hyperspectral imaging of the cortex. These SSHOs were stationary during the entire 4 to 10 min acquisition time. By Fourier filtering the oxy‐ and deoxyhemoglobin time signals with a small bandwidth, SSHOs became visible within localized regions of the brain, with distinctive frequencies and a continuous phase variation within that region. SSHOs of deoxyhemoglobin appeared to have an opposite phase and 11% smaller amplitude with respect to the oxyhemoglobin SSHOs. Although the origin of SSHOs remains unclear, we find indications that the observed SSHOs may embody a local propagating hemodynamic wave with velocities in line with capillary blood velocities, and conceivably related to vasomotion and maintenance of adequate tissue perfusion. Hyperspectral imaging of the human cortex during surgery allow in‐depth characterization of SSHOs, and may give further insight in the nature and potential (clinical) use of SSHOs.

Responses of cerebral blood flow and tissue oxygenation to low frequency oscillations during simulated hemorrhagic stress in humans

IntroductionHemorrhage is a leading cause of death from traumatic injury in both the military and civilian populations. Use of lower body negative pressure (LBNP) as a model of hemorrhage in humans has revealed that there is a spectrum of tolerance to this stress. Recent evidence from our laboratory suggests that low frequency (LF; ~0.1 Hz) oscillations in mean arterial pressure (MAP) and middle cerebral artery velocity (MCAv) play a role in this tolerance; high tolerant subjects exhibit greater LF power in MAP and MCAv when compared to low tolerant subjects. We hypothesize that exogenously inducing LF oscillations via oscillatory LBNP (OLBNP) will attenuate reductions in cerebral blood flow and oxygenation during simulated hemorrhagic stress.Methods11 young, healthy subjects (9M/2F) were exposed to two LBNP profiles with an average chamber pressure of −60 mmHg in a randomized and counterbalanced design: 1) static LBNP (0 Hz) and, 2) oscillatory LBNP (0.1 Hz). During both profiles, chamber pressure was gradually reduced to −60 mmHg over 1‐min after which pressure remained at −60 mmHg (0 Hz) for 9‐min or oscillated between −30 mmHg and −90 mmHg (0.1 Hz) for 9‐min. Profiles were separated by a 5‐min recovery. Physiological measurements included arterial pressure and stroke volume via finger photoplethysmography, MCAv via transcranial Doppler ultrasound, and regional cerebral oxygenation of the frontal lobe (ScO2) via near infrared spectroscopy. Hemodynamic data was analyzed using a paired t‐test. Tolerance was assessed with a Fischer's exact test.ResultsNo differences were observed between profiles for MAP (0 Hz, 79.8±2.5 mmHg vs. 0.1 Hz, 80.0±1.9 mmHg; P=0.93) and MCAv (0 Hz, 42.4±3.3 cm/s vs. 0.1 Hz, 43.5±3.7 cm/s P=0.43). The reduction in ScO2 was attenuated (P=0.05) during the 0.1 Hz profile (−4.1±1.2 %) compared to the 0 Hz profile (−6.1±1.1 %). A similar attenuation was observed in the stroke volume response (0 Hz, −42.6±2.5 % vs. 0.1 Hz, −30.6±2.5 %; P&lt;0.001). Importantly, 8/11 subjects completed the 0.1 Hz profile compared with just 5/11 subjects for the 0 Hz profile (P=0.048).DiscussionIn partial support of our hypothesis, cerebral oxygenation was protected during the 0.1 Hz OLBNP profile. While MCAv was similar between conditions, we propose that the oscillatory pattern of cerebral blood flow may elicit a shear‐stress induced vasodilation, so assessment of velocity may be masking an increase in flow. This possibility is further supported by the finding that stroke volume was also protected during the 0.1 Hz profile, which may reflect an increase in venous return during the upstroke period of the OLBNP profile. Importantly, more subjects were able to tolerate the 0.1 Hz profile compared to the static 0 Hz profile, despite similar arterial pressure responses. These findings emphasize the potential importance of hemodynamic oscillations in maintaining perfusion and oxygenation of cerebral tissue during a hemorrhagic stress.Support or Funding InformationUNTHSC ICMD Junior Faculty Seed GrantThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Long-term optical imaging of neurovascular coupling in mouse cortex using GCaMP6f and intrinsic hemodynamic signals

Cerebral hemodynamics are modulated in response to changes in neuronal activity, a process termed neurovascular coupling (NVC), which can be disrupted by neuropsychiatric diseases (e.g., stroke, Alzheimer's disease). Thus, there is growing interest to image long-term NVC dynamics with high spatiotemporal resolutions. Here, by combining the use of a genetically-encoded calcium indicator with optical techniques, we develop a longitudinal multimodal optical imaging platform (MIP) that enabled time-lapse tracking of NVC over a relatively large field of view in the mouse somatosensory cortex at single cell and single vessel resolutions. Specifically, GCaMP6f was used as marker of neuronal activity, which along with MIP allowed us to simultaneously measure the changes in neuronal [Ca2+]i fluorescence, cerebral blood flow velocity (CBFv) and hemodynamics longitudinally for more than eight weeks. We show that [Ca2+]i fluorescence was detectable one week post viral injection and the damage to local microvasculature and perfusion recovered two weeks after injection. By three weeks post viral injection, maximal neuronal and CBFv responses to hindpaw stimulations were observed. Moreover, single neuronal activation in response to hindpaw stimulation was consistently recorded, followed by ∼2 s delayed dilation of contiguous microvessels. Additionally, resting-state spontaneous neuronal and hemodynamic oscillations were detectable throughout the eight weeks of study. Our results demonstrate the capability of MIP for longitudinal investigation of the organization and plasticity of the neurovascular network during resting state and during stimulation-evoked neuronal activation at high spatiotemporal resolutions.

Perioperative hemodynamics and outcomes of patients on metyrosine undergoing resection of pheochromocytoma or paraganglioma

IntroductionTo describe outcomes of patients with metyrosine (MET) pretreatment for abdominal surgical resection of pheochromocytoma or paraganglioma (PCC/PGL) compared with patients who had phenoxybenzamine (PBZ) pretreatment. MethodsRetrospective review of perioperative outcomes for PCC/PGL patients treated with MET and propensity-matched comparison of MET and PBZ (MET + PBZ) with PBZ alone. ResultsMET preparation was given in 63 cases (26 laparoscopic and 37 open, of which 55 also received PBZ). All patients had wide perioperative hemodynamic oscillations. Patients with open procedures required more intravenous fluids and blood transfusions; 35% required postoperative vasopressor infusions for hypotension and 38% developed acute kidney injury. One laparoscopic procedure required postoperative vasopressor infusion, and 12% of patients developed acute kidney injury. Forty-five MET + PBZ patients were propensity-matched with PBZ-only patients. Intraoperatively, MET + PBZ patients had lower minimum systolic and diastolic blood pressures than PBZ-only patients (median systolic, 74 vs 80 mm Hg, P = 0.01; median diastolic, 42 vs 46 mm Hg, P = 0.005) and larger intraoperative blood pressure oscillations (median systolic range, 112 vs 93 mm Hg, P = 0.06; median diastolic range, 58 vs 51 mm Hg, P = 0.02). Postoperative vasopressor infusion use was similar between MET + PBZ and PBZ only (16% vs 11%, P = 0.76). Major outcomes were not different between regimens. ConclusionLarge hemodynamic oscillations were present in our PCC/PGL patients treated with MET + PBZ. These patients had a wider range of intraoperative blood pressure variations than PBZ-only patients. No differences in postoperative comorbid outcomes were found between MET + PBZ and PBZ-only groups.