In this study we evaluate the influences of optical property assumptions on near-infrared diffuse correlation spectroscopy (DCS) flow index measurements. The optical properties, absorption coefficient (µa) and reduced scattering coefficient (µs′), are independently varied using liquid phantoms and measured concurrently with the flow index using a hybrid optical system combining a dual-wavelength DCS flow device with a commercial frequency-domain tissue-oximeter. DCS flow indices are calculated at two wavelengths (785 and 830 nm) using measured µa and µs′ or assumed constant µa and µs′. Inaccurate µs′ assumptions resulted in much greater flow index errors than inaccurate µa. Underestimated/overestimated µs′ from −35%/+175% lead to flow index errors of +110%/−80%, whereas underestimated/overestimated µa from −40%/+150% lead to −20%/+40%, regardless of the wavelengths used. Examination of a clinical study involving human head and neck tumors indicates up to +280% flow index errors resulted from inter-patient optical property variations. These findings suggest that studies involving significant µa and µs′ changes should concurrently measure flow index and optical properties for accurate extraction of blood flow information.

A portable diffuse correlation spectroscopy (DCS) flowmeter has been extended to measure both tissue blood flow and oxygenation (namely, DCS flow oximeter). For validation purposes, calf muscle blood oxygenation during cuff inflation and deflation was measured concurrently using the DCS flow oximeter and a commercial tissue oximeter. The oxygenation traces from the two measurements exhibited similar dynamic responses, and data were highly correlated (r(mean)>0.9, P<10(-5), n=10). The portable, inexpensive, and easy-to-use DCS flow oximeter holds promise for bedside monitoring of tissue blood flow and oxygenation in clinics.

Airway remodeling, caused by inflammation and fibrosis, is a major component of chronic obstructive pulmonary disease (COPD) and currently has no effective treatment. Transforming growth factor–β (TGF-β) has been widely implicated in the pathogenesis of airway remodeling in COPD. TGF-β is expressed in a latent form that requires activation. The integrin αvβ8 (encoded by the itgb8 gene) is a receptor for latent TGF-β and is essential for its activation. Expression of integrin αvβ8 is increased in airway fibroblasts in COPD and thus is an attractive therapeutic target for the treatment of airway remodeling in COPD. We demonstrate that an engineered optimized antibody to human αvβ8 (B5) inhibited TGF-β activation in transgenic mice expressing only human and not mouse ITGB8. The B5 engineered antibody blocked fibroinflammatory responses induced by tobacco smoke, cytokines, and allergens by inhibiting TGF-β activation. To clarify the mechanism of action of B5, we used hydrodynamic, mutational, and electron microscopic methods to demonstrate that αvβ8 predominantly adopts a constitutively active, extended-closed headpiece conformation. Epitope mapping and functional characterization of B5 revealed an allosteric mechanism of action due to locking-in of a low-affinity αvβ8 conformation. Collectively, these data demonstrate a new model for integrin function and present a strategy to selectively target the TGF-β pathway to treat fibroinflammatory airway diseases.

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Intraoperative monitoring of cerebral hemodynamics during carotid endarterectomy (CEA) provides essential information for detecting cerebral hypoperfusion induced by temporary internal carotid artery (ICA) clamping and post-CEA hyperperfusion syndrome. This study tests the feasibility and sensitivity of a novel dual-wavelength near-infrared diffuse correlation spectroscopy technique in detecting cerebral blood flow (CBF) and cerebral oxygenation in patients undergoing CEA. Two fiber-optic probes were taped on both sides of the forehead for cerebral hemodynamic measurements, and the instantaneous decreases in CBF and electroencephalogram (EEG) alpha-band power during ICA clamping were compared to test the measurement sensitivities of the two techniques. The ICA clamps resulted in significant CBF decreases (-24.7 ± 7.3%) accompanied with cerebral deoxygenation at the surgical sides (n = 12). The post-CEA CBF were significantly higher (+43.2 ± 16.9%) than the pre-CEA CBF. The CBF responses to ICA clamping were significantly faster, larger and more sensitive than EEG responses. Simultaneous monitoring of CBF, cerebral oxygenation and EEG power provides a comprehensive evaluation of cerebral physiological status, thus showing potential for the adoption of acute interventions (e.g., shunting, medications) during CEA to reduce the risks of severe cerebral ischemia and cerebral hyperperfusion syndrome.