Device for inducing vascular injury and/or blockage in an animal model

Abstract

Ultrashort laser pulses are used to induce photodisruptive breakdown in vasculature in an animal to controllably produce hemorrhage, thrombosis or breach of blood-brain barrier in individual, specifically targeted blood vessels. Damage is limited to the targeted vessels such that neighboring vessels exhibit no signs of vascular damage, including vessels directly above or below the targeted vessel. Ultrashort laser pulses of lower energy are also used to observe and quantify the baseline and altered states of blood flow. Observation and measurement may be performed (1) by TPLSM, OCT or other known techniques, providing a real-time, in vivo model for the dynamics and effects of vascular injury.

1 .- 48 . (canceled)  
     
     
         49 . A device for producing spatially-localized injury to vasculature in an animal, comprising: 
 an animal mount for holding the animal in a fixed position;    an optical source for producing a photodisruption beam, wherein the photodisruption beam comprises a plurality of ultrashort pulses adapted for driving a nonlinear interaction within the target vasculature; and    a microscope objective for focusing the photodisruption beam onto target vasculature in the animal; wherein the animal has a window formed therein for providing optical access to the target vasculature.    
     
     
         50 . The device of  claim 49 , wherein the optical source comprises an optical oscillator and an optical pump.  
     
     
         51 . The device of  claim 49 , wherein the optical source further comprises an optical amplifier.  
     
     
         52 . The device of  claim 49 , further comprising detectors for detecting light produced in the animal by the ultrashort pulses.  
     
     
         53 . The device of  claim 49 , wherein an imaging beam is directed through the microscope objective for imaging the animal.  
     
     
         54 . The device of  claim 49 , wherein the microscope objective is part of a two photon laser scanning microscope.  
     
     
         55 . The device of  claim 49 , wherein the microscope objective is part of an optical coherence tomography microscope.  
     
     
         56 . The device of  claim 49 , wherein the animal mount comprises a kinematic mount for the removal and repositioning of the animal.  
     
     
         57 . The device of  claim 49 , further comprising a measurement device for observing blood flow in the animal.  
     
     
         58 . The device of  claim 49 , wherein the ultrashort pulses have pulsewidths in a range from 10 femtoseconds to 100 picoseconds.  
     
     
         59 . A device for producing spatially-localized injury to vasculature in a live animal, wherein the animal has an optically transparent window disposed over an area comprising target vasculature, the device comprising: 
 an optical source for producing a photodisruption beam, wherein the photodisruption beam comprises a plurality of ultrashort pulses adapted for driving a nonlinear interaction within the target vasculature; and    a microscope objective for focusing the photodisruption beam onto the target vasculature in the animal; and    an animal mount for stabilizing the animal within an optical path of the photodisruption beam.    
     
     
         60 . The device of  claim 59 , wherein the optical source comprises an optical oscillator and an optical pump.  
     
     
         61 . The device of  claim 59 , wherein the optical source further comprises an optical amplifier.  
     
     
         62 . The device of  claim 59 , further comprising detectors for detecting light produced in the animal by the ultrashort pulses.  
     
     
         63 . The device of  claim 59 , wherein an imaging beam is directed through the microscope objective for imaging the animal.  
     
     
         64 . The device of  claim 59 , wherein the microscope objective is part of a two photon laser scanning microscope.  
     
     
         65 . The device of  claim 59 , wherein the microscope objective is part of an optical coherence tomography microscope.  
     
     
         66 . The device of  claim 59 , wherein the animal mount comprises a kinematic mount for the removal and repositioning of the animal.  
     
     
         67 . The device of  claim 59 , further comprising a measurement device for observing blood flow in the animal.  
     
     
         68 . The device of  claim 59 , wherein the ultrashort pulses have pulsewidths in a range from 10 femtoseconds to 100 picroseconds.