Diagnostic imaging of lymph structures

Abstract

In accordance with the present invention, there are provided methods for identifying the sentinel lymph node in a drainage field for a tissue or organ in a subject. In select embodiments, the invention allows for the identification of the first or sentinel lymph node that drains the tissue or organ, particularly those tissues associated with neoplastic or infectious diseases and disorders, and within the pertinent lymph drainage basin. Once the drainage basin from the tissue or organ, i.e., the sentinel lymph node, is identified, a preoperative or intraoperative mapping of the affected lymphatic structure can be carried out with a contrast agent. Identification of the first or sentinel lymph node, on the most direct drainage pathway in the drainage field, can be accomplished by a variety of imaging techniques, including ultrasound, MRI, CT, nuclear and others. Moreover, once the lymphatic structure is identified as being associated with neoplastic or infectious diseases and disorders, the affected lymphatic structure can be removed surgically or by a suitable minimally invasive procedure to allow pathological analysis to be performed to determine whether certain diseases or disorders exist, without resort to more radical lymphadenectomy. Further, the agent can be made to carry diagnostic or therapeutic probes to be activated and/or delivered to the injection site or any part of the lymphatic pathway downstream from the injection site.

That which is claimed is:  
     
         1 . A method for identifying, diagnosing, or treating one or more lymph structures in a subject, said method comprising: 
 administering to said subject a diagnostically effective amount of a particulate contrast agent, said contrast agent having a mean particle size in the range of about 1 micron up to about 10 microns in diameter wherein at least a portion of said contrast agent associates with said lymph structure; and    imaging said subject whereby said lymph structure is detected.    
     
     
         2 . A method according to  claim 1 , wherein said lymph structure comprises a lymph vessel or lymph node.  
     
     
         3 . A method according to  claim 2 , wherein said agent is percutaneously administered to said subject to localize to a lymph vessel.  
     
     
         4 . A method according to  claim 3 , wherein said method further comprises massaging the injection site or stimulating the injection site by exercise.  
     
     
         5 . A method according to  claim 1 , wherein said lymph structure is the sentinel lymph node.  
     
     
         6 . A method according to  claim 1 , wherein said particulate contrast agent comprises a microbubble preparation having dispersed therein a plurality of microbubbles.  
     
     
         7 . A method according to  claim 6 , wherein said microbubbles comprise a fluorocarbon gas or gas precursor.  
     
     
         8 . A method according to  claim 1 , wherein said imaging comprises a technique selected from the group consisting of X-ray imaging, magnetic resonance (MR) imaging, computed tomography (CT) imaging, ultrasound (US) imaging and optical imaging.  
     
     
         9 . A method according to  claim 1 , wherein said imaging comprises ultrasound imaging.  
     
     
         10 . A method according to  claim 9 , wherein said ultrasound imaging comprises harmonic ultrasound imaging.  
     
     
         11 . A method according to  claim 1 , wherein said contrast agent further comprises a dye.  
     
     
         12 . A method according to  claim 1 , wherein said contrast agent carries diagnostic probes that are released at any site from the point of injection to any portion of the lymphatic chain.  
     
     
         13 . A method according to  claim 1 , wherein said contrast agent carries a therapeutic substance to treat or infect the target tissue at the site of injection or anywhere along the lymphatic pathway.  
     
     
         14 . A method for identifying a sentinel lymph node in a subject comprising the steps of: 
 administering to said subject a diagnostically effective amount of a contrast agent comprising a plurality of microbubbles, wherein at least a portion of said contrast agent associates with said sentinel lymph node; and    imaging said subject whereby said sentinel lymph node is detected.    
     
     
         15 . A method according to  claim 14 , wherein said microbubbles comprise a fluorocarbon gas or gas precursor.  
     
     
         16 . A method according to  claim 14 , wherein said imaging comprises a technique selected from the group consisting of X-ray imaging, magnetic resonance (MR) imaging, computed tomography (CT) imaging, ultrasound (US) imaging and optical imaging.  
     
     
         17 . A method according to  claim 14 , wherein said imaging comprises ultrasound imaging.  
     
     
         18 . A method according to  claim 14 , wherein said sentinel lymph node is downstream from tissue that is neoplastic or suspected to be neoplastic.  
     
     
         19 . A method for identifying, diagnosing, or treating one or more lymph structures in a subject, said method comprising: 
 administering to said subject a diagnostically effective amount of microbubble contrast agent, wherein at least a portion of said contrast agent associates with said lymph structure; and    imaging said subject whereby said lymph structure is detected.    
     
     
         20 . A method according to  claim 16 , wherein said agent is modified to promote macrophage uptake.