Ultrasound contrast agents containing microbubbles of perfluoracarbon gasses

Abstract

Disclosed herein are agents for enhancing the contrast in an ultrasound image. These agents are extremely small bubbles, or “microbubbles,” comprised of specially selected gases. The microbubbles described herein exhibit long life spans in solution and may be produced at a size small enough to traverse the lungs, thus enabling improved ultrasound imaging of the cardiovascular system and other vital organs. Also disclosed herein is a method for selecting gases from which contrast agents may be produced. The method is based on calculations using inherent physical properties of gases and describes a means to associate the properties of a gas with the time for dissolution of microbubbles comprised of the gas.

I claim:  
     
         1 . Contrast media for ultrasound image-enhancement comprising microbubbles of a biocompatible gas having a Q coefficient greater than 5 where  
         Q= 4.0×10 −7   ×ρ/C   s   D    
       and ρ is the density of the gas (Kgm −3 ), C s  is the water solubility of the gas (M) and D is the diffusivity of the gas in solution (cm 3 sec −1 )  
     
     
         2 . Contrast media of  claim 1  comprising a suspension of gas bubbles smaller than 8 microns in a biocompatible aqueous liquid vehicle.  
     
     
         3 . Contrast media of  claim 1  wherein the gas is sulfur hexafluoride.  
     
     
         4 . Contrast media of  claim 1  wherein the gas is hexafluoropropylene.  
     
     
         5 . Contrast media of  claim 1  wherein the gas is octafluoropropane.  
     
     
         6 . Contrast media of  claim 1  wherein the gas is hexafluoroethane.  
     
     
         7 . Contrast media of  claim 1  wherein the gas is octafluoro-2-butene.  
     
     
         8 . Contrast media of  claim 1  wherein the gas is hexafluoro-2-butyne.  
     
     
         9 . Contrast media of  claim 1  wherein the gas is hexafluorobuta-1,3-diene.  
     
     
         10 . Contrast media of  claim 1  wherein the gas is octafluorocyclobutane.  
     
     
         11 . Contrast media of  claim 1  wherein the gas is decafluorobutane.  
     
     
         12 . Contrast media of  claim 1  where the gas is dodecafluoropentane.  
     
     
         13 . A method for selecting a gas for use as an ultrasound image-enhancement agent comprising the steps of 
 determining the solubility, C s , of the gas in a solution;    determining the density, ρ, of the gas;    determining the diffusivity, D, of the gas in the solution;    calculating a Q coefficient where      Q= 4.0×10 −7   ×ρ/C   s   D      and selecting a gas having a Q coefficient of greater than 5.    
     
     
         14 . The method of  claim 1  wherein the diffusivity, D, is determined from the molar volume, Vm, of a gas by the formula  
         D= 13.26×10 −5 ·η −1.14   ·V   m   −0.589    
       where η is the solution viscosity (cP).