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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 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.

We used diffuse correlation spectroscopy to assess cerebral autoregulation in acute ischemic stroke patients. Larger perfusion changes were observed in the infarcted hemisphere, and a novel relationship between perfusion and NIHSS was discovered.

We employ diffuse optics to measure spinal cord hemodynamics in response to pharmacologic and mechanical perturbations for the first time. Comparison of blood flow and blood pressure responses demonstrate robust spinal cord autoregulation.

We used diffuse correlation spectroscopy to continuously monitor cerebral blood flow changes in subarachnoid hemorrhage patients due to interventions in the clinic, and present a novel index for assessing cerebral autoregulation in these patients.

Localized tissue hypoxia is a consequence of vascular compromise or rapid cellular proliferation and is a potent inducer of compensatory angiogenesis. The oxygen-responsive transcriptional regulator hypoxia-inducible factor 2α (HIF-2α) is highly expressed in vascular ECs and, along with HIF-1α, activates expression of target genes whose products modulate vascular functions and angiogenesis. However, the mechanisms by which HIF-2α regulates EC function and tissue perfusion under physiological and pathological conditions are poorly understood. Using mice in which Hif2a was specifically deleted in ECs, we demonstrate here that HIF-2α expression is required for angiogenic responses during hindlimb ischemia and for the growth of autochthonous skin tumors. EC-specific Hif2a deletion resulted in increased vessel formation in both models; however, these vessels failed to undergo proper arteriogenesis, resulting in poor perfusion. Analysis of cultured HIF-2α-deficient ECs revealed cell-autonomous increases in migration, invasion, and morphogenetic activity, which correlated with HIF-2α-dependent expression of specific angiogenic factors, including delta-like ligand 4 (Dll4), a Notch ligand, and angiopoietin 2. By stimulating Dll4 signaling in cultured ECs or restoring Dll4 expression in ischemic muscle tissue, we rescued most of the HIF-2α-dependent EC phenotypes in vitro and in vivo, emphasizing the critical role of Dll4/Notch signaling as a downstream target of HIF-2α in ECs. These results indicate that HIF-1α and HIF-2α fulfill complementary, but largely nonoverlapping, essential functions in pathophysiological angiogenesis.

Blood flow in mice tumor models was measured with Diffuse Correlation Spectroscopy and compared to concurrent physiology monitoring. Positive correlations were (not) found between flow and heart (breath) rate during anesthesia periods.

f ICFO-Institut de Ciencies Fotoniques, Mediterranean Technology Park, 08860 Castelldefels (Barcelona), Spain Abstract. Weinvestigateandassesstheutilityofasimpleschemeforcontinuousabsolutebloodflowmonitoring based on diffuse correlation spectroscopy (DCS). The scheme calibrates DCS using venous-occlusion diffuse optical spectroscopy (VO-DOS) measurements of arm muscle tissue at a single time-point. A calibration coef- ficient(γ)forthearmisdetermined,permittingconversionofDCSbloodflowindicestoabsolutebloodflowunits, andastudyofhealthyadults(N ¼ 10)iscarriedouttoascertainthevariabilityof γ.TheaverageDCScalibration coefficient for the right (i.e., dominant) arm was γ ¼ð 1.24 � 0.15Þ × 10 8 ðmL · 100 mL −1 ·m in −1 Þ∕ðcm 2 ∕sÞ. However,variabilitycanbesignificantandisapparentinoursite-to-siteandday-to-dayrepeatedmeasurements. The peak hyperemic blood flow overshoot relative to baseline resting flow was also studied following arm-cuff ischemia; excellent agreement between VO-DOS and DCS was found (R 2 ¼ 0.95, slope ¼ 0.94 � 0.07, mean difference ¼ −0.10 � 0.45). Finally, we show that incorporation of subject-specific absolute optical prop- erties significantly improves blood flow calibration accuracy. © 2015 Society of Photo-Optical Instrumentation Engineers (SPIE)

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.