Non-interferometric photoacoustic remote sensing (ni-pars)

Abstract

A photoacoustic remote sensing system (NI-PARS) for imaging a subsurface structure in a sample, has an excitation beam configured to generate ultrasonic signals in the sample at an excitation location; an interrogation beam incident on the sample at the excitation location, a portion of the interrogation beam returning from the sample that is indicative of the generated ultrasonic signals; an optical system that focuses at least one of the excitation beam and the interrogation beam with a focal point that is below the surface of the sample; and a detector that detects the returning portion of the interrogation beam.

1 - 16 . (canceled) 
     
     
         17 . A method of imaging a sample, comprising:
 receiving, at one or more processors, information relating to a non-interferometrically detected portion of an interrogation beam, wherein the detected portion of the interrogation beam was detected using a non-interferometric detector, wherein the detected portion of the beam returned from a sample interrogated with the interrogation beam and excited with an excitation beam to generate signals in the sample at an excitation location, wherein the interrogation beam was directed to the sample at or adjacent to the excitation location, and wherein at least one of the excitation beam or the interrogation beam were focused below a surface of the sample; and   generating or calculating, by the one or more processors, an image of the sample based on the received information.   
     
     
         18 . The method of  claim 17 , wherein generating or calculating the image is based on a detected intensity modulation of the detected portion of the interrogation beam, wherein the non-interferometric detector is configured to preclude phase-modulation sensitivity to enable detection of intensity variations. 
     
     
         19 . The method of  claim 17 , wherein the interrogation beam or the excitation beam are focused within 1 mm of the surface of the sample. 
     
     
         20 . The method of  claim 17 , wherein at least one of the interrogation beam or the excitation beam is focused at a depth greater than 1 µm below the surface of the sample. 
     
     
         21 . The method of  claim 17 , wherein the interrogation beam is focused at a first focal point or the excitation beam is focused at a second focal point, the first or second focal points being below the surface of the sample. 
     
     
         22 . The method of  claim 21 , wherein at least one of the first or second focal points are spaced below the surface of the sample at a depth that is greater than a focal zone of a respective at least one of the interrogation beam or the excitation beam. 
     
     
         23 . The method of  claim 17 , wherein the interrogation beam and the excitation beam have a separation of less than 1 mm within the sample. 
     
     
         24 . The method of  claim 17 , wherein the excitation beam has a focal point that is within a focal zone of the interrogation beam; or the interrogation beam has a focal point that is within a focal zone of the excitation beam. 
     
     
         25 . The method of  claim 17 , wherein the excitation beam is scanned through the sample while the interrogation beam is stationary. 
     
     
         26 . The method of  claim 17 , wherein the interrogation beam is scanned through the sample while the excitation beam is stationary. 
     
     
         27 . The method of  claim 17 , wherein both the interrogation beam and the excitation beam are scanned through the sample concurrently. 
     
     
         28 . The method of  claim 17 , wherein at least one of the interrogation beam or the excitation beam has a focal diameter of less than 30 µm. 
     
     
         29 . The method of  claim 17 , wherein the method is used for estimating blood flow in vessels flowing into and out of a region of tissue. 
     
     
         30 . The method of  claim 17 , wherein the method is used for estimating oxygen saturation in the sample. 
     
     
         31 . The method of  claim 17 , wherein the method is used in one or more of the following applications:
 imaging angiogenesis for pre-clinical tumor models;   estimating oxygen saturation using multi-wavelength photoacoustic excitation;   estimating venous oxygen saturation where pulse oximetry cannot be used;   estimating cerebrovenous oxygen saturation and/or central venous oxygen saturation;   estimating oxygen flux and/or oxygen consumption;   clinical imaging of micro- and macro-circulation and pigmented cells;   imaging of the eye;   augmenting or replacing fluorescein angiography;   imaging dermatological lesions;   imaging melanoma;   imaging basal cell carcinoma;   imaging hemangioma;   imaging psoriasis;   imaging eczema;   imaging dermatitis;   imaging Mohs surgery;   imaging to verify tumor margin resections;   imaging peripheral vascular disease;   imaging diabetic and/or pressure ulcers   burn imaging;   plastic surgery;   microsurgery;   imaging of circulating tumor cells;   imaging melanoma cells;   imaging lymph node angiogenesis;   imaging response to photodynamic therapies;   imaging response to photodynamic therapies having vascular ablative mechanisms;   imaging response to chemotherapeutics;   imaging response to anti-angiogenic drugs;   imaging response to radiotherapy;   imaging histology;   imaging pathology specimen;   imaging vascular beds and depth of invasion in Barrett’s esophagus and/or colorectal cancers;   functional imaging during brain surgery;   assessment of internal bleeding and/or cauterization verification;   imaging perfusion sufficiency of organs and/or organ transplants;   imaging angiogenesis around islet transplants;   imaging of skin-grafts;   imaging of tissue scaffolds and/or biomaterials to evaluate vascularization and/or immune rejection;   imaging to aid microsurgery;   guidance to avoid cutting blood vessels and/or nerves;   imaging of contrast agents in clinical or pre-clinical applications;   identification of sentinel lymph nodes;   non- or minimally-invasive identification of tumors in lymph nodes;   imaging of genetically-encoded reporters, wherein the genetically-encoded reporters include tyrosinase, chromoproteins, and/or fluorescent proteins for pre-clinical or clinical molecular imaging applications;   imaging actively or passively targeted optically absorbing nanoparticles for molecular imaging;   imaging of blood clots; or   staging an age of blood clots.   
     
     
         32 . The method of  claim 17 , wherein the non-interferometric detector is configured to sense a pressure-induced refractive-index modulation or a temperature-induced refractive-index modulation. 
     
     
         33 . The method of  claim 17 , wherein the non-interferometric detector is not sensitive to scattered probe beam phase modulations associated with motion of scatterers, and is not sensitive to subsurface and surface oscillations. 
     
     
         34 . The method of  claim 17 , further comprising amplifying an existing refractive index where absorption is present to detect change in intensity reflectivity. 
     
     
         35 . A non-interferometric photoacoustic remote sensing system (NI-PARS) for imaging a subsurface structure in a sample, comprising:
 a processor configured to calculate an image of a sample based on a detected intensity modulation of a returning portion of an interrogation beam from below a surface of the sample, wherein:
 the sample was excited using an excitation beam configured to generate signals in the sample at an excitation location; 
 the sample was interrogated using the interrogation beam incident on the sample at the excitation location, wherein the returning portion of the interrogation beam is indicative of the generated signals; 
 the excitation beam and the interrogation beam were focused below a surface of the sample; and 
 the returning portion of the interrogation beam was detected using a non-interferometric detector configured for non-interferometric . 
   
     
     
         36 . A method of imaging a sample, comprising:
 calculating an image of a sample based on a detected intensity modulation of a returning portion of an interrogation beam from below a surface of the sample, wherein:
 the returning portion of the interrogation beam was non-interferometrically detected using a using a non-interferometric detector configured for non-interferometric sensing, 
 the sample was excited using an excitation beam configured to generate signals in the sample at an excitation location; 
 the sample was interrogated using the interrogation beam, wherein the returning portion of the interrogation beam is indicative of the generated signals; and 
 at least one of the excitation beam or the interrogation beam were focused below a surface of the sample.