Animal studies and preliminary results in humans suggest that lower extremity and myocardial ischemia can be attenuated by treatment with angiogenic cytokines. The resident population of endothelial cells that is competent to respond to an available level of angiogenic growth factors, however, may potentially limit the extent to which cytokine supplementation enhances tissue neovascularization. Accordingly, we transplanted human endothelial progenitor cells (hEPCs) to athymic nude mice with hindlimb ischemia. Blood flow recovery and capillary density in the ischemic hindlimb were markedly improved, and the rate of limb loss was significantly reduced. Ex vivo expanded hEPCs may thus have utility as a “supply-side” strategy for therapeutic neovascularization.

https://www.pnas.org/content/pnas/97/7/3422.full.pdf

Transplantation of ex vivo expanded endothelial progenitor cells for therapeutic neovascularization.

The healing process in acute wounds has been extensively studied and the knowledge derived from these studies has often been extrapolated to the care of chronic wounds, on the assumption that nonhealing chronic wounds were simply aberrations of the normal tissue repair process. However, this approach is less than satisfactory, as the chronic wound healing process differs in many important respects from that seen in acute wounds. In chronic wounds, the orderly sequence of events seen in acute wounds becomes disrupted or “stuck” at one or more of the different stages of wound healing. For the normal repair process to resume, the barrier to healing must be identified and removed through application of the correct techniques. It is important, therefore, to understand the molecular events that are involved in the wound healing process in order to select the most appropriate intervention. Wound bed preparation is the management of a wound in order to accelerate endogenous healing or to facilitate the effectiveness of other therapeutic measures. Experts in wound management consider that wound bed preparation is an important concept with significant potential as an educational tool in wound management.

This article was developed after a meeting of wound healing experts in June 2002 and is intended to provide an overview of the current status, role, and key elements of wound bed preparation. Readers will be able to examine the following issues;

• the current status of wound bed preparation;

• an analysis of the acute and chronic wound environments;

• how wound healing can take place in these environments;

• the role of wound bed preparation in the clinic;

• the clinical and cellular components of the wound bed preparation concept;

• a detailed analysis of the components of wound bed preparation.

(WOUND REP REG 2003;11:1–28)

Wound bed preparation: a systematic approach to wound management.

First introduced in the 1980s, laser speckle contrast imaging is a powerful tool for full-field imaging of blood flow. Recently laser speckle contrast imaging has gained increased attention, in part due to its rapid adoption for blood flow studies in the brain. We review the underlying physics of speckle contrast imaging and discuss recent developments to improve the quantitative accuracy of blood flow measures. We also review applications of laser speckle contrast imaging in neuroscience, dermatology and ophthalmology.

/pdf/laser-speckle-contrast-imaging-in-biomedical-optics-1lk5nj5vp2.pdf

Laser speckle contrast imaging in biomedical optics

A method for dynamic, high-resolution cerebral blood flow (CBF) imaging is presented in this article. By illuminating the cortex with laser light and imaging the resulting speckle pattern, relative CBF images with tens of microns spatial and millisecond temporal resolution are obtained. The regional CBF changes measured with the speckle technique are validated through direct comparison with conventional laser-Doppler measurements. Using this method, dynamic images of the relative CBF changes during focal cerebral ischemia and cortical spreading depression were obtained along with electrophysiologic recordings. Upon middle cerebral artery (MCA) occlusion, the speckle technique yielded high-resolution images of the residual CBF gradient encompassing the ischemic core, penumbra, oligemic, and normally perfused tissues over a 6 × 4 mm cortical area. Successive speckle images demonstrated a further decrease in residual CBF indicating an expansion of the ischemic zone with finely delineated borders. Dynamic CBF...

https://journals.sagepub.com/doi/pdf/10.1097/00004647-200103000-00002

Dynamic Imaging of Cerebral Blood Flow Using Laser Speckle

Laser Doppler velocimetry uses the frequency shift produced by the Doppler effect to measure velocity. It can be used to monitor blood flow or other tissue movement in the body. Laser speckle is a random interference effect that gives a grainy appearance to objects illuminated by laser light. If the object consists of individual moving scatterers (such as blood cells), the speckle pattern fluctuates. These fluctuations provide information about the velocity distribution of the scatterers. It can be shown that the speckle and Doppler approaches are different ways of looking at the same phenomenon. Both these techniques measure at a single point. If a map of the velocity distribution is required, some form of scanning must be introduced. This has been done for both time-varying speckle and laser Doppler. However, with the speckle technique it is also possible to devise a full-field technique that gives an instantaneous map of velocities in real time. This review article presents the theory and practice of these techniques using a tutorial approach and compares the relative merits of the scanning and full-field approaches to velocity map imaging. The article concludes with a review of reported applications of these techniques to blood perfusion mapping and imaging.

/pdf/laser-doppler-speckle-and-related-techniques-for-blood-2tg3to9jwf.pdf

Laser Doppler, speckle and related techniques for blood perfusion mapping and imaging

A laser Doppler perfusion imaging technique based on dynamic light scattering in tissue is reported. When a laser beam sequentially scans the tissue (maximal area approximately 12 cm*12 cm), moving blood cells generate Doppler components in the backscattered light. A fraction of this light is detected by a remote photodiode and converted into an electrical signal. In the signal processor, a signal proportional to the tissue perfusion at each measurement point is calculated and stored. When the scanning procedure is completed, the system generates a color-coded perfusion image on a monitor. A perfusion image is typically built up of data from 4096 measurement sites, recorded during a time period of 4 min. This image has a spatial resolution of about 2 mm. A theory for the system inherent amplification factor dependence on the distance between individual measurement points and detector is proposed and correction measures are presented. Performance results for the laser Doppler perfusion imager obtained with a flow simulator are presented. The advantages of the method are discussed. >

Laser Doppler perfusion imaging by dynamic light scattering

Monte Carlo simulation of photon migration in tissue was used to assess the sampling depth, measuring depth and photon pathlength in laser Doppler flowmetry. The median sampling depth and photon pathlength in skin, liver and brain tissue were calculated for different probe geometries. The shallowest median sampling depth found was 68 μm for a 120 μm diameter single fibre probe applied to a one-layered skin tissue model. By using separate transmitting and receiving fibres, the median sampling depth, which amounted to 146 μm for a 250 μm fibre centre separation, by be successively increased to 233 μm when the fibres' centres are separated by 700 μm. Total photon pathlength and thereby the number of multiple Doppler shifts increase with fibre separation, thus favouring the choice of a probe with a small fibre separation when linearity is more important than a large sampling depth. Owing mainly to differences in the tissue g-value and scattering coefficient, the median sampling depth is shallower for liver and deeper for brain, in comparison with skin tissue. For skin tissue, the influence on the sampling depth of a homogeneously distributed blood volume was found to be limited to about 1 per cent per percentage increase in tissue blood content, and may, therefore, be disregarded in most practical situations. Simulations show that the median measuring depth is strongly dependent on the perfusion profile.

Prediction of sampling depth and photon pathlength in laser Doppler flowmetry

Quasielastic scattering of coherent light in tissue can be utilized to probe the superficial blood flow of the skin and other organs. This fundamental principle has been employed in the construction of laser Doppler tissue perfusion monitors and imagers, intended for experimental and clinical investigations of tissue blood flow. In this paper, the theory of laser Doppler equipment is discussed. The measuring depth can be estimated by Monte Carlo simulation, while the dynamic light scattering (light scattering including Doppler effects) can be modeled by autocorrelation techniques. Based on these techniques estimators for tissue perfusion and tissue blood cell concentration are derived. The operating principle of the laser Doppler monitor is described in detail, with special reference to the design of probes. This monitor is useful for tracking temporal changes in tissue perfusion at a single point. The principle of a recently developed laser Doppler perfusion imager is reviewed. This imager is useful in mapping the spatial variations in tissue perfusion. Different ways of evaluating the performances of the monitor and imager in both mechanical flow simulators and in-vivo studies are discussed. Finally a brief overview is made of some fields of application in which the laser Doppler technique for measurement of tissue perfusion has been successfully used.© (1992) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

Tissue perfusion monitoring and imaging by coherent light scattering

A tissue perfusion imager is presented, the characteristics of which combine the advantages of laser Doppler flowmetry with a facility for displaying spatial information on microvascular perfusion. A preliminary evaluation of the system was performed at a scanning rate of four positions/s. The evaluation shows that an arrested skin blood flow distal to finger occlusion is readily and clearly revealed by the perfusion imager as is the extension of the hyperemia surrounding an experimental burn. The perfuser imager is noninvasive, allowing the recording of tissue blood flow without touching the object. >

Imaging of tissue blood flow by coherent light scattering

Mapping of blood perfusion over a welldefined tissue area has been performed by an imaging technique based on the scattering of coherent light in tissue. When a laser beam sequentially scans the tissue, Doppler components in the backscattered light are generated by the moving red blood cells. A fraction of this backscattered light is detected by a photodetector, and signals proportional to the tissue perfusion in each measurement point are calculated and stored in a computer. When the scanning procedure is terminated, a color-coded perfusion image is generated and presented on a monitor, in order to give the operator an informative overview of the perfusion status of the tissue under study

https://ieeexplore.ieee.org/iel4/499/4080/00691653.pdf

A. Jakobsson

Papers

Laser Doppler perfusion imaging by dynamic light scattering

Prediction of sampling depth and photon pathlength in laser Doppler flowmetry

Tissue perfusion monitoring and imaging by coherent light scattering

Imaging of tissue blood flow by coherent light scattering

Two-dimensional Microvascular Blood Flow Mapping