Direct measurement of tissue blood flow and metabolism with diffuse optics

Department of Physics and Astronomy, University of Pennsylvania, Philadelphia, PA 19104, USA.
Philosophical Transactions of The Royal Society A Mathematical Physical and Engineering Sciences (Impact Factor: 2.15). 11/2011; 369(1955):4390-406. DOI: 10.1098/rsta.2011.0232
Source: PubMed


Diffuse optics has proven useful for quantitative assessment of tissue oxy- and deoxyhaemoglobin concentrations and, more recently, for measurement of microvascular blood flow. In this paper, we focus on the flow monitoring technique: diffuse correlation spectroscopy (DCS). Representative clinical and pre-clinical studies from our laboratory illustrate the potential of DCS. Validation of DCS blood flow indices in human brain and muscle is presented. Comparison of DCS with arterial spin-labelled MRI, xenon-CT and Doppler ultrasound shows good agreement (0.50<r<0.95) over a wide range of tissue types and source detector distances, corroborating the potential of the method to measure perfusion non-invasively and in vivo at the microvasculature level. All-optical measurements of cerebral oxygen metabolism in both rat brain, following middle cerebral artery occlusion, and human brain, during functional activation, are also described. In both situations, the use of combined DCS and diffuse optical spectroscopy/near-infrared spectroscopy to monitor changes in oxygen consumption by the tissue is demonstrated. Finally, recent results spanning from gene expression-induced angiogenic response to stroke care and cancer treatment monitoring are discussed. Collectively, the research illustrates the capability of DCS to quantitatively monitor perfusion from bench to bedside, providing results that match up both with literature findings and with similar experiments performed with other techniques.

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Available from: Rickson Mesquita, Dec 26, 2013
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    • "Tissue blood flowmetry based on non-invasive optical techniques, such as laser-Doppler flowmetry (LDF) at large interoptode spacings [1–5] or diffuse correlation spectroscopy (DCS) [6–8], is a unique tool allowing investigating particular physiological phenomena in humans that are not accessible with other known techniques (see note [9]). In fact, optical flowmeters have the advantage of: 1) being non-invasive; 2) allowing long acquisition times with fast repeated measurements; 3) not inducing psychological stress in the subjects (that may influence the regulatory processes of the investigated vascular system); 4) allowing to work in special environmental conditions (e.g. in water); 5) being capable to work with particular tissues such as the bone, where optical techniques remains the only solution for some specific investigative protocols [5]. "
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    ABSTRACT: A bone tissue phantom prototype allowing to test, in general, optical flowmeters at large interoptode spacings, such as laser-Doppler flowmetry or diffuse correlation spectroscopy, has been developed by 3D-stereolithography technique. It has been demonstrated that complex tissue vascular systems of any geometrical shape can be conceived. Absorption coefficient, reduced scattering coefficient and refractive index of the optical phantom have been measured to ensure that the optical parameters reasonably reproduce real human bone tissue in vivo. An experimental demonstration of a possible use of the optical phantom, utilizing a laser-Doppler flowmeter, is also presented.
    Biomedical Optics Express 08/2014; 5(8). DOI:10.1364/BOE.5.002715 · 3.65 Impact Factor
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    • "Measures of spinal cord blood flow were estimated from DCS data by fitting the measured intensity autocorrelation function to the solution of the photon correlation diffusion equation in the semi-infinite geometry with extrapolated zero boundary conditions [41,46]. The Brownian motion model was used to approximate the mean-square particle displacement of the moving scatterers in the tissue, and thus to derive a spinal cord blood flow index (BFI) [41]. Relative changes in blood flow (ΔBF) were calculated from ΔBF(t) = ΔBFI(t) = BFI(t)/BFI(t0) – 1, where t0 denotes the baseline period and baseline data are derived from two-minute averages of BFI before the interventions. "
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    ABSTRACT: Spinal cord ischemia can lead to paralysis or paraparesis, but if detected early it may be amenable to treatment. Current methods use evoked potentials for detection of spinal cord ischemia, a decades old technology whose warning signs are indirect and significantly delayed from the onset of ischemia. Here we introduce and demonstrate a prototype fiber optic device that directly measures spinal cord blood flow and oxygenation. This technical advance in neurological monitoring promises a new standard of care for detection of spinal cord ischemia and the opportunity for early intervention. We demonstrate the probe in an adult Dorset sheep model. Both open and percutaneous approaches were evaluated during pharmacologic, physiological, and mechanical interventions designed to induce variations in spinal cord blood flow and oxygenation. The induced variations were rapidly and reproducibly detected, demonstrating direct measurement of spinal cord ischemia in real-time. In the future, this form of hemodynamic spinal cord diagnosis could significantly improve monitoring and management in a broad range of patients, including those undergoing thoracic and abdominal aortic revascularization, spine stabilization procedures for scoliosis and trauma, spinal cord tumor resection, and those requiring management of spinal cord injury in intensive care settings.
    PLoS ONE 12/2013; 8(12):e83370. DOI:10.1371/journal.pone.0083370 · 3.23 Impact Factor
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    • "The DCS instrumentation and techniques have been described in detail in previous publications [2,12,14,21]. Briefly, the DCS measurements were performed with an instrument consisting of two continuous-wave, long coherence-length (i.e., >20 m), 785 nm lasers (CrystaLaser Inc., Reno, NV), and two arrays of four avalanche photodiodes (PerkinElmer, Canada). "
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    ABSTRACT: A pilot study explores relative contributions of extra-cerebral (scalp/skull) versus brain (cerebral) tissues to the blood flow index determined by diffuse correlation spectroscopy (DCS). Microvascular DCS flow measurements were made on the head during baseline and breath-holding/hyperventilation tasks, both with and without pressure. Baseline (resting) data enabled estimation of extra-cerebral flow signals and their pressure dependencies. A simple two-component model was used to derive baseline and activated cerebral blood flow (CBF) signals, and the DCS flow indices were also cross-correlated with concurrent Transcranial Doppler Ultrasound (TCD) blood velocity measurements. The study suggests new pressure-dependent experimental paradigms for elucidation of blood flow contributions from extra-cerebral and cerebral tissues.
    Biomedical Optics Express 07/2013; 4(7):978-994. DOI:10.1364/BOE.4.000978 · 3.65 Impact Factor
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