Hari M. Varma

Speckle contrast optical tomography: A new method for deep tissue three-dimensional tomography of blood flow

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.

Mannose-Binding Lectin Promotes Local Microvascular Thrombosis After Transient Brain Ischemia in Mice

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.

Speckle contrast optical spectroscopy, a non-invasive, diffuse optical method for measuring microvascular blood flow in tissue

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.

High-speed multi-exposure laser speckle contrast imaging with a single-photon counting camera.

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.

Study of turbid media with light: Recovery of mechanical and optical properties from boundary measurement of intensity autocorrelation of light

We discuss the inverse problem associated with the propagation of the field autocorrelation of light through a highly scattering object like tissue. In the first part of the work, we reconstruct the optical absorption coefficient mu(a) and particle diffusion coefficient D(B) from simulated measurements which are integrals of a quantity computed from the measured intensity and intensity autocorrelation g(2)(tau) at the boundary. In the second part we recover the mean square displacement (MSD) distribution of particles in an inhomogeneous object from the sampled g(2)(tau) measured on the boundary. From the MSD, we compute the storage and loss moduli distributions in the object. We have devised computationally easy methods to construct the sensitivity matrices which are used in the iterative reconstruction algorithms for recovering these parameters from the measurements. The results of the reconstruction of mu(a), D(B), MSD and the viscoelastic parameters, which are presented, show reasonably good position and quantitative accuracy.

Convergence analysis of the Newton algorithm and a pseudo-time marching scheme for diffuse correlation tomography

We propose a self-regularized pseudo-time marching scheme to solve the ill-posed, nonlinear inverse problem associated with diffuse propagation of coherent light in a tissuelike object. In particular, in the context of diffuse correlation tomography (DCT), we consider the recovery of mechanical property distributions from partial and noisy boundary measurements of light intensity autocorrelation. We prove the existence of a minimizer for the Newton algorithm after establishing the existence of weak solutions for the forward equation of light amplitude autocorrelation and its Fréchet derivative and adjoint. The asymptotic stability of the solution of the ordinary differential equation obtained through the introduction of the pseudo-time is also analyzed. We show that the asymptotic solution obtained through the pseudo-time marching converges to that optimal solution provided the Hessian of the forward equation is positive definite in the neighborhood of optimal solution. The superior noise tolerance and regularization-insensitive nature of pseudo-dynamic strategy are proved through numerical simulations in the context of both DCT and diffuse optical tomography.

High-density speckle contrast optical tomography (SCOT) for three dimensional tomographic imaging of the small animal brain

Abstract 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. HighlightsHigh‐density speckle contrast optical tomography for in vivo imaging in small animals.Three‐dimensional reconstruction of reduced cerebral blood flow in mice with stroke.Reconstructed volume of blood flow compared to anatomical magnetic resonance image.

Multi-Distance and Multi-Exposure Speckle Contrast Spectroscopy for Measuring Blood Flow in Deep Tissues

A new method to measure blood flow using point sources and the diffusion model with speckle contrast is shown. Speckle contrast optical spectroscopy (SCOS) uses multi-distance or exposure to measure deep tissue blood flow.