Assessment of microvascular circulation

Abstract

Methods and compositions are disclosed to quantitatively measure in vivo blood vessel diameter, blood velocity, and other flow dynamics. Such methods and compositions can optimize therapeutic interventions designed to prevent or reduce the risk of cardiovascular and blood disorders. In one aspect, the methods and apparatus involve calculating blood vessel characteristics from a two dimensional image of a blood vessel in the conjunctiva of a subject's eye. In another aspect, a series of temporal images of a blood vessel are obtained to determine blood flow properties. The apparatus can include, for example, a biomicroscope, an illuminating light source and a high speed camera to acquire the series of temporal images with the data then analyzed by a programmed processor.

What is claimed is: 
     
         1 . A method for determining blood velocity in a target tissue comprising:
 acquiring a series of temporal frames with registered images of at least one vessel in the target tissue, the series of temporal frames being acquired relying on mono static beam geometry;   identifying at least one blood cell present in each of a plurality of frames; and   calculating blood velocity within the vessel based on a distance traveled by the blood cell in the vessel between frames.   
     
     
         2 . The method of  claim 1 , wherein the target tissue is a conjunctiva of an eye. 
     
     
         3 . The method of  claim 2  wherein the method further comprises compensating for target movement by tracking eye movements. 
     
     
         4 . The method of  claim 2 , wherein the series of temporal frames are acquired without dilating the eye. 
     
     
         5 . The method of  claim 1 , wherein the step of acquiring the images further comprises illuminating the target tissue with light having a wavelength in a range of about 500 nm to 560 nm. 
     
     
         6 . The method of  claim 1  further comprising determining blood flow in the blood vessel by:
 obtaining a two-dimensional image of the vessel in the target tissue; 
 determining dimensions of the vessel from the two-dimensional image; and 
 calculating blood flow within the vessel based on blood cell velocity and blood vessel dimensions. 
 
     
     
         7 . A noninvasive method for predicting or detecting blood flow abnormalities in a subject comprising:
 obtaining blood flow properties within at least one conjunctival vessel in a first eye of a subject;   obtaining blood flow properties within at least one conjunctival vessel in a second eye of a subject; and   comparing the measurements from the first and second eyes, wherein a difference in blood flow dynamics between the two eyes is an indicator of blood flow abnormalities.   
     
     
         8 . A hemodynamics measurement apparatus comprising:
 a light source configured to project radiation onto a target tissue optics configured to image at least one vessel in the tissue;   a detector to capture a series of temporal images of the vessel; and   a processor to calculate blood flow dynamics in the vessel from the series of images,   wherein radiation from the light source that is projected onto the target tissue is in the form of light, and the light passes through a same location in space between the light source and the optics proximate to the target tissue as light collected in reflection from the target tissue by the detector.   
     
     
         9 . The apparatus of  claim 8 , wherein the apparatus further comprises a biomicroscope. 
     
     
         10 . The apparatus of  claim 8 , wherein the light source generates light of at least one wavelength in the range of about 450 to 600 nm. 
     
     
         11 . The apparatus of  claim 10 , wherein the light source generates light at a wavelength in a range from about 500 nm to about 560 nm. 
     
     
         12 . The apparatus of  claim 8 , wherein the apparatus is configured to image at least one blood vessel in the conjunctiva of a subject's eye. 
     
     
         13 . The apparatus of  claim 12 , wherein the apparatus further comprises an eye tracking mechanism compensates for movement of the eye from one temporal image to another. 
     
     
         14 . The apparatus of  claim 13  wherein the eye tracking mechanism is configured to detect changes in pupil position. 
     
     
         15 . The apparatus of  claim 12 , wherein the apparatus is configured to image at least one blood vessel in the conjunctiva of a subject's eye when the eye is not dilated. 
     
     
         16 . The apparatus of  claim 8  wherein the detector comprises a camera. 
     
     
         17 . The apparatus of  claim 16 , wherein the camera is a charge-coupled device (CCD) 
     
     
         18 . The apparatus of  claim 16  further comprises a camera controller configured to acquire a plurality of images over a time interval. 
     
     
         19 . The apparatus of  claim 18  wherein the camera controller is configured to acquire images at least 40 Hz. 
     
     
         20 . The apparatus of  claim 8 , wherein the apparatus is a handheld apparatus.