We introduce a new, non-invasive, diffuse optical technique, speckle contrast optical spectroscopy (SCOS), for probing deep tissue blood flow using the statistical properties of laser speckle contrast and the photon diffusion model for a point source. The feasibility of the method is tested using liquid phantoms which demonstrate that SCOS is capable of measuring the dynamic properties of turbid media non-invasively. We further present an in vivo measurement in a human forearm muscle using SCOS in two modalities: one with the dependence of the speckle contrast on the source-detector separation and another on the exposure time. In doing so, we also introduce crucial corrections to the speckle contrast that account for the variance of the shot and sensor dark noises.

Abstract:A novel tomographic method based on the laser speckle contrast, speckle contrast optical tomography (SCOT) is introduced that allows us to reconstruct three dimensional distribution of blood flow in deep tissues. This method is analogous to the diffuse optical tomography (DOT) but for deep tissue blood flow. We develop a reconstruction algorithm based on first Born approximation to generate three dimensional distribution of flow using the experimental data obtained from tissue simulating phantoms.

Laser speckle contrast imaging (LSCI) has emerged as a valuable tool for cerebral blood flow (CBF) imaging. We present a multi-exposure laser speckle imaging (MESI) method which uses a high-frame rate acquisition with a negligible inter-frame dead time to mimic multiple exposures in a single-shot acquisition series. Our approach takes advantage of the noise-free readout and high-sensitivity of a complementary metal-oxide-semiconductor (CMOS) single-photon avalanche diode (SPAD) array to provide real-time speckle contrast measurement with high temporal resolution and accuracy. To demonstrate its feasibility, we provide comparisons between in vivo measurements with both the standard and the new approach performed on a mouse brain, in identical conditions.

High-density speckle contrast optical tomography (SCOT) utilizing tens of thousands of source-detector pairs, was developed for in vivo imaging of blood flow in small animals. The reduction in cerebral blood flow (CBF) due to local ischemic stroke in a mouse brain was transcanially imaged and reconstructed in three dimensions. The reconstructed volume was then compared with corresponding magnetic resonance images demonstrating that the volume of reduced CBF agrees with the infarct zone at twenty-four hours.

Background and Purpose-Several lines of evidence support the involvement of mannose-binding lectin (MBL) in stroke brain damage. The lectin pathway of the complement system facilitates thrombin activation and clot formation under certain experimental conditions. In the present study, we examine whether MBL promotes thrombosis after ischemia/ reperfusion and influences the course and prognosis of ischemic stroke. Methods-Middle cerebral artery occlusion/reperfusion was performed in MBL-deficient (n=85) and wild-type (WT; n=83) mice, and the brain lesion was assessed by MRI at days 1 and 7. Relative cerebral blood flow was monitored up to 6 hours after middle cerebral artery occlusion with laser speckle contrast imaging. Fibrin(ogen) was analyzed in the brain vasculature and plasma, and the effects of thrombin inhibitor argatroban were evaluated to assess the role of MBL in thrombin activation. Results-Infarct volumes and neurological deficits were smaller in MBL knockout mice than in WT mice. Relative cerebral blood flow values during middle cerebral artery occlusion and at reperfusion were similar in both groups, but decreased during the next 6 hours in the WT group only. Also, the WT mice showed more fibrin(ogen) in brain vessels and a better outcome after argatroban treatment. In contrast, argatroban did not improve the outcome in MBL knockout mice. Conclusions-MBL promotes brain damage and functional impairment after brain ischemia/reperfusion in mice. These effects are secondary to intravascular thrombosis and impaired relative cerebral blood flow during reperfusion. Argatroban protects WT mice, but not MBL knockout mice, emphasizing a role of MBL in local thrombus formation in acute ischemia/reperfusion. (Stroke. 2014;45:1453-1459.)Key Words: brain ◼ complement pathway, mannose-binding lectin ◼ complement system proteins ◼ infarction, middle cerebral artery ◼ reperfusion Mannose-Binding Lectin Promotes Local Microvascular Thrombosis After Transient Brain Ischemia in MiceXavier de la Rosa, MS; Alvaro Cervera, MD, PhD; Anna K. Kristoffersen, PhD; Claudia P. Valdés, MS; Hari M. Varma, MS; Carles Justicia, PhD; Turgut Durduran, PhD;Ángel Chamorro, MD, PhD; Anna M. Planas, PhD Received November 11, 2013; final revision received February 26, 2014; accepted February 28, 2014. MethodsAn extended version of methods can be found in the online-only Data Supplement. Animal WorkAnimal work was undertaken with approval of the Ethical Committee of the University of Barcelona and in compliance with the Spanish law. Adult (3-4-month-old), male wild-type (WT) and MBL KO mice 31 in the C57BL/6J background were used. 17 Brain Ischemia/ReperfusionIschemia was produced by intraluminal 90-minute occlusion of the right middle cerebral artery (MCAO) in WT (n=83) and MBL KO (n=85) mice. Cerebral perfusion was assessed with laser Doppler flowmetry (Perimed AB, Järfälla, Sweden). A neurological score ranging from 0 (no deficit) to 20 (maximal deficit) was performed at days 1 and 7 after MCAO. MRI StudiesMRI was performed in a 7.0-T ...