Abstract:
An intraluminal sensor designs for multifunctional characterization of injured, stunned, infarcted myocardium, atherosclerotic plagues and tumors are disclosed. Various embodiments of the present invention comprise the sensor tips for a catheter. The tips comprises differential sensor arrangements, and use built-in electromagnet assemblies for a single or multiple axis sensing of various parameters of local magnetic field.

Description:
RELATED APPLICATIONS 
       [0001]    This application claims priority to priority to PCT Patent Application Ser. No. PCT/US06/18128, filed 11 May 2006 (May 11, 2006); WO06/122202; PD: 16 Nov. 2006 (Nov. 16, 2006), which claims priority to U.S. Provisional Patent Application Ser. No. 60/679940, filed 11 May 2005 (May 11, 2005 or May 5, 2005). 
     
    
     BACKGROUND OF THE INVENTION 
       [0002]    1. Field of the Invention 
         [0003]    The present invention relates to an intraluminal sensor design for multifunctional characterization of injured, stunned, infarcted myocardium, atherosclerotic plagues and tumors. 
         [0004]    More particularly, the present invention relates to an intraluminal sensor design for multifunctional characterization of injured, stunned, infarcted myocardium, atherosclerotic plagues and tumors, where the sensor includes 
         [0005]    2. Description of the Related Art 
         [0006]    U.S. Pat. No. 5,735,279 to Klavenes, et al. discloses the use of a magneto sensor magnetometer to detect magnetic changes in vivo. U.S. Pat. No. 6,027,946 to Weiteschies, et al. discloses the use of a magneto sensor detector to measure the spacial distribution of relaxing magnetic markers in vivo. U.S. Pat. No. 5,594,849 to Kuc, et al. discloses the use of magneto sensor magnetometers for measuring magnetic field intensity. U.S. Pat. No. 6,123,902 to Koch, et al. discloses the use of a magneto sensor detector to detect small amounts of bound analytes in a solution. U.S. Pat. No. 6,048,515 to Kresse, et al. discloses the use of nanoparticles comprising an iron containing core and a targeting polymer coating to determine the biological behavior of the nanoparticles. 
         [0007]    However, there is still a need in the art for intraluminal sensors for multifunctional characterization of injured, stunned, infarcted myocardium, atherosclerotic plagues and tumors. 
       SUMMARY OF THE INVENTION 
       [0008]    The present invention provides an intraluminal sensor design for multifunctional characterization of injured, stunned, infarcted myocardium, atherosclerotic plagues and tumors. The intraluminal sensor includes a sensing element attached to a distal end of a catheter and includes differential sensing element arrangements. The sensors includes a built-in electromagnet assembly. The sensing elements can be disposed along a single axis or plane or along multiple axes or planes. The sensor is adapted to sense various parameters of a local magnetic field or a magnetic field distribution of an area of interest adjacent an artery, vein or other bodily structure subject to catheter deployment. The sensor of this invention may also include auxiliary sensors or groups of auxiliary sensors simultaneously or sequentially for measuring local physiological parameters in the vicinity of the sensor such as temperature, pressure, pH, chemical composition, and blood assay. 
         [0009]    The present invention provides a magnetic detection system including a catheter having a sensor of this invention mounted on its distal end. The sensor is adapted to measure magnetic fields and/or magnetic field distribution associated with locations in an area of interest in an animal, including an human, body. The area of interest is generally accessible via a artery or a vein or other duct or channel that can accommodate a catheter. 
         [0010]    The present invention provides a magnetic detection system including a catheter having a sensor of this invention and a ultrasonic transmitter mounted on its distal. The sensor is adapted to measure magnetic fields and/or magnetic field distribution associated with locations in an area of interest in an animal, including an human, body. The ultrasonic transmitter, which can be a dual beam ultrasonic transmitter, is adapted to introduce a mechanical vibration to locations with in the area of interest. 
         [0011]    The present invention provides a magnetic detection system including a catheter having a magneto sensor, a ultrasonic transmitter, a coil mounted on its distal and a magnetically active agent introduction conduit having an orifice disposed at or near the distal end of the catheter. The sensor is adapted to measure magnetic fields and/or magnetic field distribution associated with locations in an area of interest in an animal, including an human, body. The ultrasonic transmitter, which can be a dual beam ultrasonic transmitter, is adapted to introduce a mechanical vibration to the locations with in the area of interest. The coil is adapted to introduce a modulation to the locations with in the area of interest. The conduit is designed to introduce a magnetically active agent into the area of interest. 
         [0012]    The present invention also provides a method for measuring magnetic fields, magnetic field distributions and/or changes therein, where the method includes inserting a catheter of this invention into an artery, vein or other suitable structure in an animal, including an human and positioning a distal end of the catheter adjacent an area of interest of the animal. The method also includes the step of measuring a magnetic field distribution of the area of interest. The method may also include the step of making a series of magnetic field distribution measurements as the catheter is moved within the artery or vein to acquire a distribution along the artery or vein. The method also includes the step of administering a magnetically active agent to the animal before and/or after measuring the magnetic field distribution. The method may also include the step of making a second series of magnetic field distribution measurements as the catheter is moved within the artery or vein to acquire a distribution along the artery or vein after administration of the magnetically active agent. The method can also include applying a controlled external magnetic field to the area of interest to produce a controlled modulation of any magnetically active agent within loci within the area of interest. The method can also include applying an ultrasonic beam to the area of interest to induce mechanical vibrations of magnetically active agents accumulated in loci within the area of interest. The method may includes the step of comparing different distribution or field data to obtain data before and after administration, modulation or mechanical vibration. The method also includes analyzing the data to identify locations within the area of interest that evidence an accumulation of magnetically active agents. The analyzing step can also use imaging data such as ultrasonic data to register the magnetic data, where registration means that the magnetic data is made to conform to physical locations within the area of interest. The method can also include the step of measuring a physical and/or chemical property in, near or surrounding the area of interest. The method of the present invention may be employed for various medical diagnostic purposes, such as locating vulnerable plaque in a patient&#39;s body. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS  
         [0013]    The invention can be better understood with reference to the following detailed description together with the appended illustrative drawings in which like elements are numbered the same: 
           [0014]      FIG. 1A-C  depict an isometric view, a side view and a top view of an embodiment of an intraluminal sensor of the present invention; 
           [0015]      FIG. 2A-C  depict a side view and a top view of an embodiment of an intraluminal sensor of the present invention and a view of the two field EM layer; 
           [0016]      FIG. 3A-C  depict a side view and a top view of an embodiment of an intraluminal sensor of the present invention and a view of the two field EM layer; 
           [0017]      FIG. 4  depicts an isometric view of a diagram of the method of operation of a multi-element sensor of this invention; 
           [0018]      FIG. 5A-B  depicts an isometric view and a front view of another embodiment of a multi-element sensor of this invention; 
           [0019]      FIG. 6  depicts a front view of another embodiment of a multi-element sensor of this invention; 
           [0020]      FIG. 7  depicts a front view of another embodiment of a multi-element sensor of this invention; 
           [0021]      FIG. 8  depicts a front view of another embodiment of a multi-element sensor of this invention; 
           [0022]      FIG. 9  depicts an isometric view of another embodiment of a multi-element sensor of this invention; and 
           [0023]      FIG. 10  depicts an isometric view of another embodiment of a multi-element sensor of this invention. 
       
    
    
     DETAILED DESCRIPTION OF THE INVENTION  
       [0024]    The inventors have found that new magneto sensor apparatuses for attachment to a distal end of a catheter can be construction including a plurality of sensing elements or arrays thereof, where the sensing elements include magnetic or magneto sensors, temperature sensors, pH sensors, chemical sensors, ion specific sensors, or a combination thereof. The apparatus include a built-in electromagnet for the application of external magnetic field to augment a measured magnetic field in an area of interest proximate the sensor apparatus via catheter insertion into an animal, including an human. 
         [0000]    Catheter Sensor Tips of this Invention 
         [0025]    Referring now to  FIGS. 1A-C , three views of an embodiment of an intravascular magneto sensor apparatus of the present invention, generally  100 , are shown, where the apparatus is adapted to be attached to, affixed to or connected to a distal ent of a catheter which can be inserted into a body and directed to adjacent an area of interest accessible from an artery, vein or other bodily structure amenable to catheter insertion. Looking at  FIG. 1A , the apparatus  100  includes a hemi-spherically shaped base  102 . On the flat surface  104  of the base  102  is disposed a multi-layered sensor assembly  106 . The assembly  106  includes an electromagnet (EM) construct  108  including an electromagnetic (EM) layer  110  sandwiched between two support and protective layers  112  and  114 . The assembly  106  also includes a sensor construct  116  disposed on top of the EM construct  108 . The sensor construct  116  includes a sensor support layer  118  and a four magneto-sensing elements S 1 , S 2 , S 3  and S 4  disposed on a top surface  120  of the layer  118 . The elements S 1 , S 2 , S 3  and S 4  are connected to a contact  122  via conducting elements C 1 , C 2 , C 3  and C 4 , respectively. The contact  122  is in electrical communication with a sensor cable  124 . The assembly  106  also includes a tab  126  adapted to be inserted into a catheter attaching the assembly  106  to the catheter and to connect the EM layer  110  and the sensor cable  122  to electrical conduits extending through the catheter to a power source for supply power to the EM layer  110  and an receiver for receiving sensing data from the sensors S 1 , S 2 , S 3  and S 4 . A head portion  128  of the assembly  106  has a length L and a width W. 
         [0026]    Referring now to  FIGS. 2A-C , three views of another embodiment of a multi-layered sensor assembly, generally  200 , of an intravascular magneto sensor apparatus of the present invention are shown, which is split-electromagnet design (EM-1 and EM-2). Looking at  FIG. 2A , the assembly  200  includes an electromagnet (EM) construct  202  including a first and second electromagnetic (EM) layers  204   a  and  204   b  sandwiched between two support and protective layers  206   a  &amp;  b  and  208   a  &amp;  b.  The EM construct  202  also includes a connecting member  210  forming notches  212  in the construct  202 . The assembly  206  also includes a sensor construct  214  disposed on top of the EM construct  202 . The sensor construct  214  includes a sensor support layer  216  and a eight magneto-sensing elements S 11 , S 12 , S 13  and S 14  and S 21 , S 22 , S 23  and S 24  disposed on a top surface  218  of the layer  216  so that the elements S 11 , S 12 , S 13  and S 14  are disposed above the EM layer  204   a,  while the elements S 21 , S 22 , S 23  and S 24  are disposed above the EM layer  204   b.  The elements S 11 , S 12 , S 13  and S 14  are connected to a contact  220   a  via conducting elements C 11 , C 12 , C 13  and C 14 , respectively; while the S 21 , S 22 , S 23  and S 24  are connected to a contact  220   b  via conducting elements C 21 , C 22 , C 23  and C 24 , respectively. The contacts  220   a  &amp;  b  are in electrical communication with sensor cables  222   a  &amp;  b,  respectively. The assembly  206  also includes a tab  224  adapted to be inserted into a catheter attaching the assembly  206  to the catheter and to connect the EM layers  204   a  &amp;  b  and the sensor cables  222   a  &amp;  b  to electrical conduits extending through the catheter to a power source for supply power to the EM layers  204   a  &amp;  b  and an receiver for receiving sensing data from the sensors S 1 , S 2 , S 3  and S 4 . The EM layer  204   a  &amp;  b  have length L 1  and L 2 , respectively, and width W 1  and W 2 , respectively, where the lengths can be the same or different and the widths can be the same of different. Moreover, the material comprising in the EM layer can be the same or different. By changing the EM layer material, its length and width, each sensor array can sense magnetic field distribution in the presence of different applied magnetic field. 
         [0027]    Referring now to  FIGS. 3A-C , three views of another embodiment of a multi-layered sensor assembly, generally  300 , of an intravascular magneto sensor apparatus of the present invention are shown, which is a triple split-electromagnet design (EM-1, EM-2 and EM-3). Looking at  FIG. 3A , the assembly  300  includes an electromagnet (EM) construct  302  including a first and second electromagnetic (EM) layers  304   a - c  sandwiched between two support and protective layers  306   a - c  and  308   a - c.  The EM construct  302  also includes a connecting member  310   a - b  forming notches  312   a - b  in the construct  302 . The assembly  306  also includes a sensor construct  314  disposed on top of the EM construct  302 . The sensor construct  314  includes a sensor support layer  316  and a eight magneto-sensing elements S 11 , S 12 , S 13  and S 14  and S 21 , S 22 , S 23  and S 24  and S 31 , S 32 , S 33  and S 34  disposed on a top surface  318  of the layer  316  so that the elements S 11 , S 12 , S 13  and S 14  are disposed above the EM layer  304   a;  the elements S 21 , S 22 , S 23  and S 24  are disposed above the EM layer  304   b;  while the elements S 31 , S 32 , S 33  and S 34  are disposed above the EM layer  304   c.  The elements S 11 , S 12 , S 13  and S 14  are connected to a contact  320   a  via conducting elements C 11 , C 12 , C 13  and C 14 , respectively; the S 21 , S 22 , S 23  and S 24  are connected to a contact  320   b  via conducting elements C 21 , C 22 , C 23  and C 24 , respectively; while the S 31 , S 32 , S 33  and S 34  are connected to a contact  320   c  via conducting elements C 31 , C 32 , C 33  and C 34 , respectively. The contacts  320   a - c  are in electrical communication with sensor cables  322   a - c,  respectively. The assembly  306  also includes a tab  324  adapted to be inserted into a catheter attaching the assembly  306  to the catheter and to connect the EM layers  304   a - c  and the sensor cables  322   a - c  to electrical conduits extending through the catheter to a power source for supply power to the EM layers  304   a - c  and an receiver for receiving sensing data from the sensors S 1 , S 2 , S 3  and S 4 . The EM layer  304   a - c  have length L 1 , L 2  and L 3 , respectively, and width W 1 , W 2  and W 3 , respectively, where the lengths can be the same or different and the widths can be the same of different. Moreover, the material comprising in the EM layer can be the same or different. By changing the EM layer material, its length and width, each sensor array can sense magnetic field distribution in the presence of different applied magnetic field. 
         [0028]    These embodiments are directed to an intraluminal multifunction sensor of a planar design with differential sensor arrangement. The planar sensor arrangement or sensing layer comprises microfabricated magnetosensors. An example of the magnetosensor is microfabricated magnetoresistive sensor. The sensors can be based on the giant magnetoresistive (GMR) sensors, colossal magnetoresistive (CMR), extraordinary magnetoresistive (EMR), ballastic magnetoresistive (BMR), or other magnetoresistive sensors or mixtures or combinations thereof. By constructing catheter tips having multiple sensing element arrays covering a fairly long span, the tips can be used to magnetically image a long span of an artery such as the coronary arteries without having to move the catheter along the artery. 
         [0029]    Referring now to  FIG. 4 , the built-in electromagnet (EM) produces an excitation magnetic field H z , typically not exceeding a saturation field of the sensing layer. Individual microfabricated magnetosensors S 1 -S 4  sense field components other than excitation field. The sensed fields are in the plane containing each magnetosensors S 1 -S 4  as shown by circulating field associated with an area of interest AOI. Thus, each magnetosensors S 1 -S 4  senses as slightly different magnetic field associated with the AOI. One can be use differential analysis techniques to gain information about the magnetic field distributions associated with the AOI both before and after the administration of a magnetically active agent to the AOI. The AOI can be a location in an animal, including an human. 
         [0030]    Referring now to  FIGS. 5A-B , two views of an embodiment of a 3-axis intravascular magneto sensor apparatus the invention, generally  500 , are shown, where the apparatus is adapted to simultaneously sensing along three independent axes. The apparatus  500  includes the same basic structure as the embodiments of  FIGS. 1A-C ,  2 A-C and  3 A-C, but the assembly  502  is in the form or a hollow triangular solid. The assembly  502  includes three sides  504   a - c.  The surface  504   a  includes four sensing elements S 11 , S 12 , S 13  and S 14 . The surface  504   b  includes four sensing elements S 21 , S 22 , S 23  and S 24 . And, the surface  504   c  includes four sensing elements S 31 , S 32 , S 33  and S 34 . This embodiment is directed to an intraluminal multifunction sensor of non-planar design with differential, multiple axis sensor arrangement. 
         [0031]    Referring now to  FIG. 6 , an embodiment of a 5-axis intravascular magneto sensor apparatus the invention, generally  600 , are shown, where the apparatus is adapted to simultaneously sensing along five independent axes. The apparatus  600  includes the same basic structure as the embodiments of  FIGS. 1A-C ,  2 A-C and  3 A-C, but the assembly  602  is in the form or a hollow pentagonal solid. The assembly  602  includes five sides  604   a - e.  The surface  604   a  includes four sensing elements S 11 , S 12 , S 13  and S 14 . The surface  604   b  includes four sensing elements S 21 , S 22 , S 23  and S 24 . The surface  604   c  includes four sensing elements S 31 , S 32 , S 33  and S 34 . The surface  604   d  includes four sensing elements S 41 , S 42 , S 43  and S 44 . And, the surface  604   e  includes four sensing elements S 51 , S 52 , S 53  and S 54 . This embodiment is directed to an intraluminal multifunction sensor of non-planar design with differential, multiple axis sensor arrangement. 
         [0032]    Referring now to  FIG. 7 , an embodiment of a 6-axis intravascular magneto sensor apparatus the invention, generally  700 , are shown, where the apparatus is adapted to simultaneously sensing along six independent axes. The apparatus  700  includes the same basic structure as the embodiments of  FIGS. 1A-C ,  2 A-C and  3 A-C, but the assembly  702  is in the form or a hollow hexagonal solid. The assembly  502  includes six sides  704   a - f.  The surface  704   a  includes four sensing elements S 11 , S 12 , S 13  and S 14 . The surface  704   b  includes four sensing elements S 21 , S 22 , S 23  and S 24 . The surface  704   c  includes four sensing elements S 31 , S 32 , S 33  and S 34 . The surface  704   d  includes four sensing elements S 41 , S 42 , S 43  and S 44 . The surface  704   e  includes four sensing elements S 51 , S 52 , S 53  and S 54 . And, the surface  704   f  includes four sensing elements S 61 , S 62 , S 63  and S 64 . This embodiment is directed to an intraluminal multifunction sensor of non-planar design with differential, multiple axis sensor arrangement. 
         [0033]    Referring now to  FIG. 8 , another embodiment of a cylindrical intravascular magneto sensor apparatus the invention, generally  800 , are shown, where the apparatus is adapted to simultaneously sensing along three independent axes. The apparatus  800  includes the same basic structure as the embodiments of  FIGS. 1A-C ,  2 A-C and  3 A-C, but the assembly  802  is in the form or a hollow cylindrical solid. The cylinder  802  includes a first set of four sensing elements S 11 , S 12 , S 13  and S 14  disposed on the outer surface of the cylinder  802 . The cylinder  802  includes a second set of four sensing elements S 21 , S 22 , S 23  and S 24 . The cylinder  802  includes a third set of four sensing elements S 31 , S 32 , S 33  and S 34 . The cylinder  802  includes a fourth set of four sensing elements S 41 , S 42 , S 43  and S 44 . And, the cylinder  802  includes a fifth set of four sensing elements S 51 , S 52 , S 53  and S 54 . This embodiment is directed to an intraluminal multifunction sensor of non-planar design with differential, multiple axis sensor arrangement. The cylinder  802  also includes five set of auxiliary sensors T 1 -T 11 , where only the odd sensors are shown. 
         [0034]    It should be recognized that the multi-axes embodiments of this invention can be of any regular or irregular polygonal shaped solid. Although planar, triangular, pentagonal, hexagonal and cylindrical were shown, an ordinary artisan would clearly recognize that other polygonal solids such as square, rectangular, heptagonal, octagonal, nonagonal, decagonal, etc. can be used as well. 
         [0035]    Referring now to  FIG. 9 , another embodiment of a intravascular magneto sensor apparatus the invention of  FIG. 1A , including auxiliary sensing elements T 1  and T 2  for simultaneous or subsequent differential measurements locally of physiological parameters such as a temperature sensor, a blood pressure sensor, an pH sensor, a chemical composition sensor, an ion specific sensor, and a blood assay sensor, or a combination thereof. 
         [0036]    A first method embodiment of the present invention is shown in  FIG. 10 . This embodiment is directed toward a method for identifying loci in a target body that accumulates magnetic substances. The differential sensor base L is chosen to be larger than an area of interest (AOI) to be detected. The differential sensor base L is typically chosen to be long enough to electronically subtract background noise locally present due to environment or from surrounding electrically active tissues. Examples of areas of local characterization may be injured, stunned, and infarcted myocardium, atherosclerotic plaque, benign and tumor lesions. 
         [0037]    All references cited herein are incorporated by reference. Although the invention has been disclosed with reference to its preferred embodiments, from reading this description those of skill in the art may appreciate changes and modification that may be made which do not depart from the scope and spirit of the invention as described above and claimed hereafter.