Kimberly Gannon

Fast blood flow monitoring in deep tissues with real-time software correlators

We introduce, validate and demonstrate a new software correlator for high-speed measurement of blood flow in deep tissues based on diffuse correlation spectroscopy (DCS). The software correlator scheme employs standard PC-based data acquisition boards to measure temporal intensity autocorrelation functions continuously at 50 - 100 Hz, the fastest blood flow measurements reported with DCS to date. The data streams, obtained in vivo for typical source-detector separations of 2.5 cm, easily resolve pulsatile heart-beat fluctuations in blood flow which were previously considered to be noise. We employ the device to separate tissue blood flow from tissue absorption/scattering dynamics and thereby show that the origin of the pulsatile DCS signal is primarily flow, and we monitor cerebral autoregulation dynamics in healthy volunteers more accurately than with traditional instrumentation as a result of increased data acquisition rates. Finally, we characterize measurement signal-to-noise ratio and identify count rate and averaging parameters needed for optimal performance.

Dynamic autoregulation of cerebral blood flow measured non-invasively with fast diffuse correlation spectroscopy:

Cerebral autoregulation (CA) maintains cerebral blood flow (CBF) in the presence of systemic blood pressure changes. Brain injury can cause loss of CA and resulting dysregulation of CBF, and the degree of CA impairment is a functional indicator of cerebral tissue health. Here, we demonstrate a new approach to noninvasively estimate cerebral autoregulation in healthy adult volunteers. The approach employs pulsatile CBF measurements obtained using high-speed diffuse correlation spectroscopy (DCS). Rapid thigh-cuff deflation initiates a chain of responses that permits estimation of rates of dynamic autoregulation in the cerebral microvasculature. The regulation rate estimated with DCS in the microvasculature (median: 0.26 s−1, inter quartile range: 0.19 s−1) agrees well (R = 0.81, slope = 0.9) with regulation rates measured by transcranial Doppler ultrasound (TCD) in the proximal vasculature (median: 0.28 s−1, inter quartile range: 0.10 s−1). We also obtained an index of systemic autoregulation in concurrently measured scalp microvasculature. Systemic autoregulation begins later than cerebral autoregulation and exhibited a different rate (0.55 s−1, inter quartile range: 0.72 s−1). Our work demonstrates the potential of diffuse correlation spectroscopy for bedside monitoring of cerebral autoregulation in the microvasculature of patients with brain injury.

Non-Invasive Respiratory Impedance Enhances Cerebral Perfusion in Healthy Adults

Optimization of cerebral blood flow (CBF) is the cornerstone of clinical management in a number of neurologic diseases, most notably ischemic stroke. Intrathoracic pressure influences cardiac output and has the potential to impact CBF. Here, we aim to quantify cerebral hemodynamic changes in response to increased respiratory impedance (RI) using a non-invasive respiratory device. We measured cerebral perfusion under varying levels of RI (6 cm H2O, 9 cm H2O, and 12 cm H2O) in 20 healthy volunteers. Simultaneous measurements of microvascular CBF and middle cerebral artery mean flow velocity (MFV), respectively, were performed with optical diffuse correlation spectroscopy and transcranial Doppler ultrasound. At a high level of RI, MFV increased by 6.4% compared to baseline (p = 0.004), but changes in cortical CBF were non-significant. In a multivariable linear regression model accounting for end-tidal CO2, RI was associated with increases in both MFV (coefficient: 0.49, p < 0.001) and cortical CBF (coefficient: 0.13, p < 0.001), although the magnitude of the effect was small. Manipulating intrathoracic pressure via non-invasive RI was well tolerated and produced a small but measurable increase in cerebral perfusion in healthy individuals. Future studies in acute ischemic stroke patients with impaired cerebral autoregulation are warranted in order to assess whether RI is feasible as a novel non-invasive therapy for stroke.

Noninvasive optical monitoring of critical closing pressure and arteriole compliance in human subjects

The critical closing pressure (CrCP) of the cerebral circulation depends on both tissue intracranial pressure and vasomotor tone. CrCP defines the arterial blood pressure (ABP) at which cerebral blood flow approaches zero, and their difference (ABP − CrCP) is an accurate estimate of cerebral perfusion pressure. Here we demonstrate a novel non-invasive technique for continuous monitoring of CrCP at the bedside. The methodology combines optical diffuse correlation spectroscopy (DCS) measurements of pulsatile cerebral blood flow in arterioles with concurrent ABP data during the cardiac cycle. Together, the two waveforms permit calculation of CrCP via the two-compartment Windkessel model for flow in the cerebral arterioles. Measurements of CrCP by optics (DCS) and transcranial Doppler ultrasound (TCD) were carried out in 18 healthy adults; they demonstrated good agreement (R = 0.66, slope = 1.14 ± 0.23) with means of 11.1 ± 5.0 and 13.0 ± 7.5 mmHg, respectively. Additionally, a potentially useful and rarely measured arteriole compliance parameter was derived from the phase difference between ABP and DCS arteriole blood flow waveforms. The measurements provide evidence that DCS signals originate predominantly from arteriole blood flow and are well suited for long-term continuous monitoring of CrCP and assessment of arteriole compliance in the clinic.

Internal Carotid Artery and Sphenoidal Emissary (Vesalian) Vein Fistula Mimicking a Carotid–Cavernous Sinus Fistula

A 53-year-old woman presented to an outpatient appointment with one month of pulsatile tinnitus and progressive orbital swelling. Clinical examination revealed left pulsatile exophthalmos, chemosis, and an orbital bruit. Magnetic resonance angiography (MRA) demonstrated enlargement and high flow through the cavernous sinus on the left (Figure 1A). Clinical presentation was thought to be 1 Department of Neurology, University of Pennsylvania, Philadelphia, PA, USA 2 Department of Neurosurgery, University of Pennsylvania, Philadelphia, PA, USA 3 Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA 4 Department of Internal Medicine, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA, USA

Clinical applications of high-speed blood flow measurements with diffuse correlation spectroscopy

Diffuse Correlation Spectroscopy (DCS) is an increasingly popular non-invasive optical technique to clinically measure deep tissue blood flow, albeit at slow measurement rates of 0.5-1 Hz. We recently reported the development of a new ‘fast’ DCS instrument that continuously measures blood flow at 50-100 Hz (simultaneously from 8 channels), using conventional DCS sources/detectors, and optimized software computations. A particularly interesting result was our ability to optically record pulsatile micro-vascular blood flow waveforms, and therein readily identify high frequency features such as the dicrotic notch. Here, we showcase the utility and potential of high-speed measurements of blood flow (and arterial blood pressure) in a few clinical applications. First, we employ the fast-DCS instrumentation to measure cerebral autoregulation (CVAR) dynamics. Cerebral autoregulation refers to the mechanism by which cerebral blood flow (CBF) is maintained during fluctuations in blood pressure; CVAR is impaired in the injured brain. We derive an index of autoregulation by measuring the rates of decrease (and recovery) of blood flow and blood pressure following a sudden, induced change in systemic blood pressure (e.g., bilateral thigh cuff deflation). Our pilot experiments in healthy volunteers show that DCS measured rates of micro-vascular regulation are comparable to conventional large vessel regulatory metrics (e.g., measured with transcranial Doppler ultrasound). Second, we utilized pulsatile blood flow oscillations in cerebral arteries to estimate the critical closing pressure (CrCP), i.e., the arterial blood pressure at which CBF approaches zero. Pilot experiments in healthy subjects show good agreement between CrCP measured with DCS and transcranial Doppler ultrasound.

Functional monitoring of blood flow dynamics in brain with photon correlation techniques

We introduce a new software correlator approach for continuous high-speed (up to 100 Hz) monitoring of blood flow dynamics with Diffuse Correlation Spectroscopy. The functionality of the high-speed software correlator is demonstrated with measurements of baseline blood flow dynamics. The utility of high-data-rate blood flow monitoring is demonstrated with measurements of cerebral autoregulation dynamics.