Abstract:
A method for profiling an infusion of a medicament into the wall of an artery involves inserting an intravascular ultrasound device into the artery and advancing it to the location of the infusion. A pullback device withdraws the intravascular ultrasound device from the artery, pausing at predetermined axial sites along the location of the infiltrated medicament to image the infusion profile at each site. A computer then compiles the individual site profiles to produce three dimensional images indicating the extent of infiltration of the medicament into the tissue surrounding the artery.

Description:
FIELD OF THE INVENTION 
     The present invention relates generally to imaging procedures. More specifically, the present invention relates to methods and systems for imaging tissues surrounding arteries. The present invention is particularly, though not exclusively, useful for using intravascular ultrasound to profile an infiltration of a medicament into the tissue surrounding an artery. 
     BACKGROUND OF THE INVENTION 
     Angioplasty is a widely used procedure for treating a stenosis within a body vessel such as a human artery. Although the angioplasty procedure is generally successful in dilating the lumen of the vessel, and thereby allowing increased blood flow through the vessel, often times a restenosis occurs soon after the angioplasty procedure. It is widely recognized that the body&#39;s response (inflammation). to the tissue damage that occurs during an angioplasty procedure contributes to the occurrence of a restenosis. Several medicaments, however, are known to be efficacious for the prevention of a restenosis if properly delivered near the site of the inflammation. To that end, devices that are capable of penetrating the wall of a vessel with a dispenser and releasing a medicament into the vessel wall have been developed. For example, U.S. Pat. No. 5,713,863 which issued to Vigil et al. for an invention entitled “Catheter With Fluid Medication Injectors,” and which is assigned to the same assignee as the present invention, discloses such a device. It is the case, however, that these intravascular infusion devices can be used to deliver medicaments for prevention of restenosis as well as for other treatment and diagnostic purposes. 
     There are various forms of tissue injury that can result from an intravascular procedure, any one of which will trigger an inflammation response. As indicated above, such an inflammation response is widely recognized to contribute to the restenosis of the vessel. It is also known that this inflammation response will cause localized changes near the injured tissue including increased permeability and increased blood flow. This localized increase in blood flow and permeability will generally increase the dispersion rate of medicaments released near an injury in a vessel wall. 
     For a medicament to be effective in preventing a restenosis it must be delivered to a prescribed area and in a prescribed dosage. To do this efficiently, the size, shape and location of the prescribed treatment area must be determined, and this will depend on the amount and location of tissue injury. Also, the dispersion rate of the medicament will be affected by the amount of inflammation, the type of medicament, and the amount of medicament released. Due to the many variables involved, it would obviously be helpful to know exactly where the medicament has dispersed into tissue after it has been administered. 
     It happens that results of an intravascular infusion procedure are not the same from patient to patient. This may be due to a variety of reasons. One possible reason is the anatomical differences between patients. The differing results can also be due to different degrees of inflammation of the tissues, as discussed above. In any event, the actual distribution of the medicament has been a matter of estimate, based on clinical results. Heretofore, there has been no reliable in-vivo method to ascertain the success of an intravascular infusion procedure. Thus, it can be appreciated that it would be beneficial to know whether the medicament actually reached the target tissue. It would also be desirable to know whether the infused medicament is uniformly distributed in the target area. Of further interest to a clinician would be the concentration of the infused medicament in the tissues surrounding the arterial wall. 
     Information regarding the condition of tissues inside a patient can be obtained using diagnostic radiology. In particular, diagnostic ultrasound techniques can give information about tissue condition by differentiating between tissues at their anatomic boundaries inside the patient. Specifically, this happens as transmitted ultrasound waves reflect back to the transducer from these boundaries. The amplitude of the reflected ultrasound waves is then displayed as different shades of gray. Thus, anatomic structures with different acoustic density will be portrayed with different brightness. The introduction of a medicament into a tissue, however, changes its videodensitometry. Importantly, an ultrasonic image can show this difference. 
     Ultrasound technology is now available which will produce an inside view of an artery. Specifically, intravascular ultrasound, or IVUS, incorporates an ultrasound head within: a balloon catheter which can be used to obtain a cross sectional image of an artery. This image will also include the tissue that is surrounding the artery. An example of the use of IVUS can be found in the detection of plaque inside artery walls. Another example is the use of IVUS to determine the position and orientation of a probe during a procedure, using perivascular structures as landmarks. 
     In light of the above, it is an object of the present invention to provide a reliable method for profiling an infiltration of a medicament into the tissue surrounding an artery. Another object of the present invention is to provide a method and a system to determine the extent of the infiltration of the medicament into an arterial wall of a patient. A further object is to provide a system for quantitatively evaluating the distribution of the medicament in the tissue surrounding the artery. Yet another object of the present invention is to provide a method for profiling the infiltration of a medicament into the tissue surrounding the artery that is easy to perform, is safe, and is comparatively cost effective. 
     SUMMARY OF THE PREFERRED EMBODIMENTS 
     The present invention is directed to a method for determining the extent of an infiltration of a medicament into an arterial wall of a patient. Essentially, this is a two-step process. First, the medication is administered. Second, the extent of medication infiltration is determined. In accordance with the present method, a balloon catheter infusion device containing the fluid medicament is positioned in the artery of the patient at the treatment site. Upon being so positioned, the device then injects the medicament from inside the lumen of the artery into the wall of the artery. As the medicament is released, it infiltrates into the tissue surrounding the artery. It is anticipated that this procedure can be accomplished either at only one treatment site or repeated at a number of locations along the wall of the artery. This, of course depends on the pathology of the artery. In detail, when multiple infusions are to be performed, the infusion device is first advanced to a position in the artery that is most distal from the point of entry for the device. The device is then gradually pulled back through the artery, and the medicament is injected into selected sites along the arterial wall. When the infusion process is completed, the balloon catheter housing the infusion device is withdrawn from the artery. 
     In accordance with the present invention, after the infusion device has been withdrawn, another catheter is inserted into the lumen of the artery. This second catheter houses an intravascular ultrasound device (IVUS) of a type well known in the pertinent art. The IVUS is then advanced to the location of the infusion that is most distal from the point of entry of the device. The ultrasound is activated, and it begins imaging the arterial wall at a start point. 
     From this start point, the device is incrementally withdrawn, through the artery. This is preferably done using a motorized pullback device which will stabilize the IVUS in an axial orientation as it takes images of the artery between its incremental movements through the artery. 
     As the IVUS is thus pulled back along the axis of the artery, it creates a series of images at predetermined or preselected positions in the artery. 
     Each image, thus created, will represent the extent of medicament perfusion at a specific axial position in the artery. Once the ultrasound has created a profile of the tissue surrounding the artery, at the various axial positions in the artery, the IVUS is removed from the artery. It is known that IVUS, in general, provides a cross sectional view of the inside of an artery and the tissues immediately surrounding the artery. Thus, these images that are created at the series of specific axial sites in the artery, will each include a radial and an azimuthal dimension. The present invention envisions a computer/ultrasound interface that is capable of combining all of these images to produce a three dimensional image of the tissue surrounding the artery. 
     In operation, the specific sites for creating images with the IVUS are based on the location of the infusion. As indicated above, it is contemplated that multiple images will be created at a given infusion site. It then follows that, if a medicament has been infused at more than one site, each infusion site will be imaged a number of times. Further, at each infusion site it is desirable to know the boundaries of the perfusion or infiltration of a medicament. For diagnostic purposes, these boundaries will include a first end, the radial extent of the perfusion through an azimuthal range, and a second end. These measurements will then represent the extent of penetration of the medicament into the tissue surrounding the artery. Preferably, a minimum of three sites along the arterial wall at each infusion site will be selected for imaging with the IVUS. This determination will be repeated for each infiltration that has been performed. 
     In detail, and taking into account that IVUS generates images from specific axial positions in the artery, radial and azimuthal dimensions can be ascertained for each position. These dimensions correspond to the boundaries of the perfusion at each position. Beginning at a first position, the start point, a first image is created by the IVUS in a manner known in the art. When a clinician determines that this image represents the distal point of the perfusion of the medicament, at least two other axial positions are selected for imaging the perfusion. Accordingly, the pullback device incrementally withdraws the IVUS and pauses at a second position, a predetermined distance from the position of the first image. A second image is created at this second position. Once again, the pullback device is activated, and the IVUS is withdrawn to a third location along the artery. The imaging procedure is repeated, creating a third image. It can be appreciated that the clinician could select a greater number of sites depending on the specificity of the information desired. For instance, if images are created at increments of one to three millimeters along the artery at a given perfusion site, more than three images will be needed to observe the entire perfusion in detail. Consequently, the profile generated from the combined images will be more detailed than a corresponding profile generated from three images. In any event, the clinician can determine the number of images to be made based on observations of the image created at the first position. When the desired number of images has been made at the first infusion site, the IVUS is pulled back along the axis of the, artery. Accordingly, if additional infusions were made, a series of images is created at each infusion site. Upon the completion of the desired number of images at each location of perfusion, the IVUS is withdrawn from the artery. 
     In addition to creating images at specific sites along the inside of the artery, the present invention envisions using these images to quantify the results of the infusion. An important aspect of the present invention is an analysis of the profile created by the ultrasound. It is known that tissues with varying characteristics react differently to ultrasound radiation to produce images showing this variation. As noted above, the addition of a medicament to tissues changes the characteristics of the tissues containing the medicament for the purpose of creating an ultrasound image. Consequently, the tissues that contain the medicament will have a profile that differs from the profile of those tissues that do not contain the medicament. Based on this understanding, a quantitative analysis of the images can be performed to determine the relative amount of the medicament that has infiltrated into selected areas of tissue. Specifically, to accomplish this, data from the series of images is combined at an ultrasound/computer interface. It is known that each of the combined images-includes a radial and an azimuthal dimension of the perfusion. Accordingly, the composite of these images will yield a three dimensional image of each perfusion. Supported by these composite, three dimensional images, and the quantitative analysis of these images, a clinician can evaluate the pattern and the extent of the infiltration of the medicament. 
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS 
     The novel features of this invention, as well as the invention itself, both as to its structure and its operation, will be best understood from the accompanying drawings, taken in conjunction with the accompanying description, in which similar reference characters refer to similar parts, and in which: 
     FIG. 1 is a perspective view of a patient with an IVUS positioned in an artery in accordance with the present invention; 
     FIG. 2 is a cross sectional representation of an artery after an infusion, showing an intravascular ultrasound device positioned in the artery; 
     FIGS. 3A-3E are respective cross sectional views of the infusion of a medicament as would be seen at locations in an artery respectively indicated by lines  3 A— 3 A,  3 B— 3 B,  3 C— 3 C,  3 D— 3 D, and  3 E— 3 E in FIG. 2; and 
     FIG. 4 is a perspective view of a computer/ultrasound interface in accordance with the present invention. 
    
    
     DESCRIPTION OF THE PREFERRED EMBODIMENT 
     Referring initially to FIG. 1, a system for determining the extent of an infiltration of an administered medicament is shown and generally designated  10 . In accordance with the present invention, after an infusion procedure has been completed, a balloon catheter  12  housing an intravascular ultrasound device (IVUS)  14  is inserted into an artery  16  of a patient. The IVUS  14  is then advanced to an infusion site  18 . 
     As shown in FIG. 2, the infused medicament  20  infiltrates into a tissue  22  surrounding an artery  16 . The intravascular ultrasound device (IVUS)  14  is housed in a balloon catheter  12  in a manner well known in the art. It is also known that IVUS  14  images the tissue  22  surrounding the artery  16  from a position inside the artery  16 . Upon insertion of the IVUS  14  into the lumen  24  of the artery  16 , the IVUS  14  is advanced to a start point  26  therein. It is important to note that this start point  26  is distal to a first infusion site  18 . When the clinician determines that this start point  26  is distal to the infusion site  18  that will be imaged, the IVUS  14  is activated. The IVUS  14  is then pulled back incrementally along the axis  28  of the artery  16 , preferably using a motorized pullback device  30 , in a manner well known in the art. Accordingly, the pullback device  30  incrementally withdraws the IVUS  14  and pauses at a position  32   a , a predetermined distance from the start point  26 . The IVUS  14  is activated at this position  32   a , imaging the tissue  22  surrounding the artery  16 . Once again the IVUS  14  is incrementally withdrawn and stopped at a third position  32   b , whereupon it is activated to image the tissue  22  from this third axial position in the artery  16 . As the IVUS  14  is thus pulled back along the axis  28  of the artery.  16 , it is stopped and activated at preselected positions, for example  32   b, c, d , and  e.    
     It can be appreciated that it is desirable to know the boundaries of each perfusion of the medicament  20 . These boundaries include a first end  34 , a radius  36 , and a second end  38 . The radius  36  of the perfusion represents the depth of penetration of the medicament  20  into the tissue  22  surrounding the artery  16 . In order to ascertain the boundaries of a perfusion, a number of axial positions  32  can be selected for imaging with the IVUS  14  at the infusion site  18 . Inasmuch as the images created by IVUS  14  are formed at positions  32  along the axis  28  inside the artery  16 , these boundaries will be represented by a radial and an azimuthal dimension. When the length of the infusion site  18  has been traversed, IVUS  14  reaches a stop position  40  for that infusion site  18 . It follows that these determinations can be repeated for each infiltration that has been performed. Further, the IVUS  14  can be pulled back along the inside of the artery  16  and activated at a number of preselected positions  32   a-e  for each infusion site  18  to image each infiltration. 
     As shown in FIGS. 3A-3E, it is contemplated that a number of images  42   a-e  will be created at a given infusion site  18 . It follows that, if a medicament  20  has been infused at more than one infusion site  18 , each infusion site  18  will be imaged a number of times. Accordingly, the number of images  42  required at each infusion site  18  can be determined depending on the specificity of the information desired. For instance, if images  42  are created at increments of one to three millimeters along the artery  16  at a given infusion site  18 , several images  42  will be needed to observe the entire perfusion in detail. Consequently, the profile generated from these combined images  42  will be more detailed than a corresponding profile generated from a minimal three images  42 . In any event, the clinician can select the number of images to be made based on observations of the image  42  created at the first position  32   a , and on the specificity of the information desired. It can be appreciated that each image  42  thus created will represent the extent of the medicament  20  which has infiltrated the tissue  22  surrounding the artery  16  at each specific position, for example  32   a-e . FIGS. 3A,  3 B,  3 C,  3 D, and  3 E correspond to images  42   a-e . These images  42   a-e , in turn, are cross sectional views, created by IVUS  14  at positions  32   a-e  along the axis  28  of the artery  16 . For example, FIG. 3A shows image  42   a , as would be seen along the line  3 A— 3 A in FIG.  2 . It follows that FIG. 3B shows image  42   b  as would be seen along the line  3 B— 3 B. Thus, each image  42  represents a cross sectional view as imaged by IVUS  14  from a specific position  32  along the axis  28  of the artery  16 . Each image  42  that is created at each position  32  along the axis  28  will show a first end  34 , a radius  36 , and a second end  38 . Further, these cross sectional images  42  will each include an azimuthal dimension. When the desired number of images  42  has been made at the first infusion site  18 , the IVUS  14  is pulled back along the axis  28  of the artery  16 . Accordingly, if additional infusions have been performed, the IVUS  14  pauses at a second infusion site  18  to create a second series of images  42  in the same manner as the first series of images  42  was made. It follows that a series of images  42  can be created at each infusion site  18 . Upon the completion of the desired number of images  42  at each infusion site  18 , the IVUS  14  is withdrawn from the artery  16 . 
     FIG. 4 shows a computer/ultrasound interface  44 . In addition to creating images  42  at specific positions  32  for each infusion site  18  along the artery  16 , the present invention envisions using these images  42  to quantify the results of the infusion. To that end, the present invention contemplates integrating data from IVUS  14  at this interface  44 . The computer  46  at this interface  44  combines the images  42 , created by IVUS  14  at each infusion site  18  to create three dimensional images  48  of each infusion site  18 , indicating a profile of the infiltration of the medicament  20  at that infusion site  18 . Each image  42  is formed by the IVUS  14  at a specific axial position  32 . Since it is known that each of the images  42  includes a radial and an azimuthal dimension of the perfusion, it follows that the composite of these images  42  for each infusion site  18  will yield a three dimensional image  48  of each perfusion. 
     Another important aspect of the present invention is a quantitative analysis of the profile created by the IVUS  14 . This analysis can be performed by the computer  46  at the computer/ultrasound interface  44  to provide further details of the extent of the infiltration of the medicament  20  into the tissue  22  surrounding the artery  16 . As discussed above, the addition of a medicament  20  to tissues  22  changes the characteristics of the tissues  22  containing the medicament  20  for the purpose of creating an ultrasound image  42 . Consequently, the tissues  22  that contain the medicament  20  will have a profile that differs from the profile of those tissues  22  that do not contain the medicament  20 . Based on this understanding, a quantitative analysis of the images  42  can be performed to determine the relative amount of the medicament  20  that has infiltrated into selected areas of the tissue  22 . Supported by the composite, three dimensional images  48 , and the quantitative analysis of these composite images  48 , a clinician can evaluate the pattern and the extent of the infiltration of the medicament  20 . 
     While the particular methods and systems for ultrasonically profiling the infiltration of an administered medicament into the arterial wall of a patient as herein shown and disclosed in detail are fully capable of obtaining the objects and providing the advantages herein before stated, it is to be understood that it is merely illustrative of the presently preferred embodiments of the invention and that no limitations are intended to the details of construction or design herein shown other than as described in the appended claims.