CA1138575A - Image averaging for angiography by registration and combination of serial images - Google Patents

Abstract

Docket No. 1920-123 Inventors: Samuel H. Brooks, Robert H. Selzer Donald W. Crawford and David H. Blankenhorn Title: IMAGE AVERAGING FOR ANGIOGRAPHY BY REGISTRATION AND COMBINATION OF SERIAL IMAGES A method and apparatus for angiography in which information contained within multiple serial images of contrast medium flowing through a blood vessel is combined to form a single image having improved vessel edge delineation. More specifically, a method is disclosed whereby a contrast medium opaque to X-rays is injected into a blood vessel distant from an artery section of interest, preferably injected into a vein, whereby the contrast medium is mixed with blood prior to its passing through the artery section. Multiple X-ray images are obtained as the contrast medium and blood mixture flows through the artery section. These multiple images are registered with respect to each other according to a landmark contained within the patient, the landmark having a predetermined relationship to the vessel of interest. The landmark could be a bone, catheter or any other material opaque to X-rays. Density measurements are made with respect to each corresponding image segment or element of the multiple images and are combined to synthesize a composite image. The synthesized image has an edge uncertainty equal to that of one of the individual images divided by the square root of the total number of images utilized.

Description

The field of art to which the invention pertains 6 includes apparatus and methods for arterial angiography in 7 which a single composite image is constructed from information 8 contained in multiple, serially obtained images.
lP BACKGROUND AND SUMMARY OF THE INVENTION
11 Arterial angiography as commonly practiced 12 involves an arterial injection of a contrast medium opaque 13 to X-rays and subsequent X-ray photography of the artery 14 section of interest distal to the injection. A single picture or series of pictures of the artery section is taken 16 as the contrast medium flows therethrough. A large amount 17 of contrast medium is required in order to provide sufficient 1 contrast to highlight the artery edge profile in each 19 picture. Injection of this large amount of contrast medium

2 poses a significant risk of trauma or fatality. As an 21 example, coronary angiography has a fatality risk of the 2 order of 0.01 to 0.001. On the other hand, if the contrast 2 medium is injected in a vein, there is much lower risk of 2 adverse consequences of the order of 0.0001. However, the 2 resulting X-ray image has low contrast because of mixture, 2 thereby dilution, of the contrast medium with substantial , . ,,, ~

113~575 1 amounts of blood by the time it reaches the artery of 2 interest. This low contrast makes it difficult to precisely

3 define the artery edge, thereby making it difficult for a skilled person to determine whether corrective therapy is appropriate.
6 The present invention discloses a method and 7 apparatus which eliminates the above-described disadvantages 8 of current angiography, angiography being defined as any 9 method for visualizing a blood vessel, the edge or lumen usually being of interest. Specifically, one aspect of the 11 invention utilizes venous injection of the contrast medium 12 while still providing an image which has a contrast equal to 13 or better than that of an image obtained after direct 14 arterial injection of the contrast medium. The method according to the invention includes the steps of injecting a 16 contrast medium so that it will mix with blood to flow 17 through a vessel or artery section of interest, obtaining 18 multiple images of the vessel section as the blood/contrast 19 medium mixture flows therethrough, and synthesizing a single composite image of the vessel section from information 21 contained in the multiple images. In specific embodiments 22 of the invention, a contrast medium opaque to X-rays is 23 utilized. The vessel is irradiated by an X-ray source, the 24 rays passing therethrough forming an image on an appropriately positioned X-ray sensitive film/screen combination. The 26 synthesizing step includes registering the multiple im~ges 113~575 1 from landmarks that are contained within the patient 2 and that have a relationship to the vessel of interest, 3 and identifying density indices of corresponding segments of

4 the registered images. A single image having corresponding ~ indices either averaged or cumulatively added is formed from 6 the identified density indices. In one embodiment, when the 7 vessel does not move, the synthesizing step can include 8 manually overlapping and registering transparent image 9 negatives so that one may look through the registered negatives to observe the artery edge. This embodiment can 11 be utilized for only a limited number of negatives because 1 their cumulative opasueness will soon mask the detail 1 required for vessel resolution. In a preferred embodiment, 1 computer technology is utilized whereby each image segment 1 or element is assigned a digital representation according to 1 its average density, a synthesized image being formed by the 1 computer based upon the density information of each corres-1 ponding image segment.
1 One may utilize an X-ray sensitive phosphor 2 in lieu of the X-ray sensitive film/screen combination, the 2 phosphor being electronically scanned and the resultant 2 signal being used to drive a video display tube or converted 2 to a digital format for computer storage and subsequent 2 processing.
2 If the vessel is moving during the time interval 2 ~uring which the images are obtained, a method of synthesizing .~
.

~ a co osite image includes the steps of defining anticipated 2 image profiles based upon average vessel edge profiles of 3 healthy vessels. The anticipated profile for the vessel at 4 rest, called a base profile, is defined. An anticipated S profile for each of the subsequent images is then derived 6 with respect to the base profile. For example, an image 7 taken 1/6th of a second after the image corresponding to the 8 base profile would have a profile which represents the anticipated position of the vessel edge 1/6th of a second after that of the vessel edge corresponding to the base ~1 profile. Each image segment associated wi~h the second ~2 image is then corrected by an amount equal to the offset 13 between the base profile and the anticipated vessel edge 14 profile for that picture, the correction being made so as to 51 ascertain the position of the vessel edge at the time of the 16 base profile position. This process is repeated for each of 17 the subsequent images, thereby providing images in which all 18 of the vessel edges are corrected so that they correspond to 19 the time of the base profile. This offsetting can be most efficiently accomplished by a computer. Once the corrected 21 images are developed, a synthesized image can be obtained ~2 as explained above.
23 Although in the preferred embodiment multiple 24 images are obtained using X-ray photography, other techniques for obtaining vessel edge profiles could also be utilized.
26 According to another aspect of the invention, the images .. 1~3~S7S

1 could be obtained by the use of ultrasonic diagnostic 2 instruments which are capable of distinguishing one type of 3 tissue characteristic from another, thereby eliminating any 4 need for injection of a contrast medium. When sound travels through 60ft tissue it suffers attenuation which increases 6 with frequency. The greater the attenuation, the higher the 7 relative reduction in the high frequency components. Means for developing a pictorial representation of the attenuation 9 and reduction in high frequency components are well known in 1 the art and can provide an alternative method of obtaining 1 multiple images of the vessel, the images obtained being 12 ¦ processed in the same manner as the X-ray images described 13 ¦ above.

15 l 16 ¦ BRIEF DESCRIPTION OF THE DRAWINGS
17 ¦ Fi~ure 1 is a perspective view showing the 1~ ¦ apparatus used in the present invention;
19 Figures 2A-2D are diagramatic representations 20 ¦ showing development of a composite angiogram from a series 21 ¦ of X-ray images;
22 l 23 ¦ Figure 3 is a diagramatic representation showing 24 ~ an embodiment utilizing a digital system to synthesize a 25 ~ composite image;

Figure 4 illustrates a second embodiment of the invention in which images are formed on an X-ray responsive phosphor, the pattern of each phosphor image being electron-ically recorded, processed and displayed;
Figures 5A and 5B are diagramatic representations showing a method of synthesizing a composite image of a vessel whose profile is changing as multiple X-ray images are being obtained; and Figure 6 illustrates a third embodiment of the invention in which images are formed from reflected ultrasonic waves.
DETAILED DESCRIPTION
The invention provides an apparatus for and a method of arterial angiography in which a contrast medium is injected at a point distant from an artery or vessel of interest, the medium being mixed with blood prior to flowing through the vessel of interest. Multiple images are obtained of the vessel as the mixture of medium and blood flows therethrough. The multiple images are registered so that density image information from each can be combined into a single composite image having a vessel edge much more clearly defined than that of any of the multiple images.
This more clearly defined vessel edge allows a skilled person to more accurately decide as to the advisability of corrective therapy.
7.

' ~138575 `I

1¦ Referring to Figure 1, the basic apparatus 21 necessary to practice the teachings of the invention are 31 shown. An X-ray source 10 is directed at a patient 12 ~¦ resting on a table 14. Located directly beneath the patient

5 ¦ is a medium sensitive to X-ray irradiation which in this

6 ¦ first embodiment is an X-ray sensitive film/screen combin-

7 ¦ ation appropriately positioned within a camera 16. The

8 ¦ camera 16 is adapted to take multiple images at a rate of

9 ¦ approximately 6 frames per second although higher or lower lO ¦ rates can be utilized. Images obtained from the camera 16 11 ¦ are processed in a manner to be explained belcw by a processing 12 ¦ means 18, the output of which is a single synthesized 13 ¦ composite image 20 derived from all of the images obtained 14 ¦ by the camera 16. Again it is emphasized that since the 15 ¦ contrast medium has been injectea at a point distant from to 16 ¦ the vessel of interest, for reasons as explained above, any 1~ ¦ single image of the vessel having the contrast medium 18 passing therethrough would have insufficient resolution to 19 accurately determine location of a vessel edge. However, 2Q multiple images of the vessel obtained while it contains a 21 diluted contrast medium, and thus a contrast medium concen-22 tration less likely to cause harm to the patient, can be 23, combined to provide a composite image which will have the 24 same or superior resolution with respect to images obtained from a more concentrated mixture of blood and contrast 26 medium.

1 In one embodiment of the invention, image regis-2 tration is effected by physically aligning each image 3 according to a landmark or landmarks within the patient such 4 as a bone, catheter, or any other item somewhat opaque to X-rays. The thus registered images will constitute a ~ composite image having a resolution greater than that of any 7 single image. This embodiment is limited to only a few images because the cumulative opaqueness of a large number 9 of images will mask the detail necessary for proper vessel

10 resolution .

11¦ Referring to Figures 2A-2D, a series of X-ray

12¦ images Il, I2 ... In is obtained by the camera 16, the

13¦ letter n representing the total number of images. It is

14¦ important that each X-ray image have at least one registration

15¦ landmark as above explained, the landmark having a predeter-

16¦ mined relationship to the vessel section of interest so that

17 slight movements by the patient and vessel which result in

18 misregistration of the various images with respect to the

19 vessel can be corrected. Referring to the first image Il, two such means are shown, the first being a catheter 30 21 located within the patient's body and the second being a 22 bone segment 32. Also shown is a somewhat indistinct vessel 23 section 34, the edges of which are to be defined. Upon 24 registration of the images Il through In~ a co~posite 2~ image is derived as shown at Ic.
26 ___ ~13~3575 1 The composite image Ic can be synthesized by 2 many methods, all of which are diagramatically represented 3 as the processing means 18 shown in Figure 1. One method 4 which can be used when the vessel is immoble is to manually overlap and register the transparent images Il through 6 In as previously described then view the composite image 7 Ic formed ~y the thus registered individual images. The 8 viewing can be accomplished by back lighting the image 9 array. To understand this method, and subsequent methods to be explained below, assume that each image Il through In 11 consists of a series of image segments or elements, one 12 segment of which would be Sl in image Il, S2 in image 13 ¦ I2 and Sn in image In. Each segment Sl through SN
14 ¦ has a predetermined relationship to the landmarks, i.e. to 15 ¦ the catheter 30 or the bone segment 32. The segment Sc 16 ¦ for the composite image Ic has a density egual to the 17 ¦ combined densities of its corresponding segments S
18 ¦ through SN of the series of images Il through In.
19 ¦ Another processing means 18 which can be employed

20 ¦ is shown diagrammatically in Figure 3 and consists of 2i ¦ digitizing a density index associated with each image 22 ¦ segment, and then combining the density indices of each 23 corresponding image segment of each of the images Il 24 through In to develop a composite image Ic. Equipment to accomplish the above is well known in the digital processing 26 art. Briefly, the system consists of a light source 36, the ~ ~3B575 l output of which is projected through one of the X-ray images 2 Il through In~ indicated at 37. A film digitizer 38, an ~ example of which is a D57 digitizer made by Dicomed Corporation, 4 converts the image into a series of digital words, each word corresponding to the density index of an image segment. The 6 digitizer 38 consists of an electronic image disector camera 7 40, deflection and control circuits 42 and an analog to 8 digital converter 44. The deflection and control circuits 9 42 control operation of both the image disector camera 40 and the analog to digital converter 44. The digital output ll of the film digitizer 38 is provided to a digital computer ~2 46 and stored for subsequent processing. A computer which 13 could be used for this purpose is the Digital E~uipment 14 Corporation PDP ll-45 although many other commercially l~ available computers could also be utilized. After subsequent 16 images I2 through In are digitized and stored in the 17 computer 46, the computer can combine the corresponding 18 image segment density information in any desired way, such 19 as by addition or averaging, to derive a new density index for each picture segment. The output of the computer 46,

21 which consists of these derived density indicies, is provided

22 to a picture recorder 48 which in turn outputs a composite

23 image Ic based on the derived density indices. As one can

24 appreciate, the system above describd can provide a composite image Ic having each image segment corresponding to the average density of that segment in the preceding images I

,. 11.

1 ~ thr ugh In~ ~>r a composite image having each image segment 2 ¦ corresponding to a summation of the density information of 31 that segment in the preceding image Il through In. All 41 of the above described individual image processing method 5 1 steps and apparatus components are well known in the 6 ¦ digital processing art for other and diverse purposes.
7 ¦ A further embodiment of the invention, shown in 8 ¦ Figure 4, utilizes the same X-ray source lO of the first 9 ¦ embodiment to irradiate a patient 12 laying on a table 14.
lO ¦ However instead of the camera 16, the X-rays, after having ll ¦ passed through the patient 12, irradiate an X-ray sensitive 12 ¦ phosphor contained within an image intensifier tube/scanner 13 ¦ combination 58. If the vessel being X-rayed is relatively 14 ¦ motionless, the output of the image intensifier tube~scanner 15 ¦ combination 58 can be displayed by a video display unit 60 16 ¦ of the type that holds successive scans up to at least 30, 17 ¦ thereby allowing a composite image Ic to be developed as l~ ¦ each subsequent image I2 through In is provided to the ~9 1 display unit 60. One example of such a video display unit i5 a ~lodel 639 Scan Converter manufactured by Hughes Aircraft 21 ¦ Company. Alternatively, the output of the image intensifier 22 ¦ tube/scanner 58 can be provided to an analog to digital 23 converter 61, the output of which is provided to a digital 24 ¦ computer 62 which can process information from the various 2~ ¦ images Il through In as previously described to form a 26 ¦ composite image Ic. The composite image can be displayed 11395~5 1 in many ways, one example of which would be by a standard 2 television monitor 64.
3 Movement of the blood vessel during the image 4 taking interval makes registration more difficult. One method of effecting registration, diagramatically illustrated 6 in Figure 5, comprises establishing a base line position for 7 the vessel edge, the base line Bl corresponding to an 8 anticipated vessel edge profile in the first image Il.
9 The base line Bl can be manually defined by a skilled person. From this base line position Bl, an anticipated vessel edge position B2 through Bn for each of the 12 subsequent images I2 through In is defined based upon 13 knowledge as to the movement of an averase vessel during the 14 time interval between each image. Having established the anticipated profiles Bl through Bn~ one can derive an 16 anticipated offset for the vessel edge of each image I2 17 through In with respect to the base profile Bl. Vessel 18 edge profiles Bl through Bn wh,ch correspond to images 19 Il through In are shown in a vessel edge correction chart 65. Using the second image I2 as an example, each 21 segment of the image I2 is offset by an amount equal to 223 the anticipated offset B2_gl Of its vessel edge with respect to the base line profile Bl Thus a first image 24 segment 68 of the second image I2 located along the abscissa at xl, would be offset towards the base line B
26 by a first ~ffset distance 70 equal ~o the value of B2-B

i 113~3575 1 ¦ at Xl. Similarly, a second image segment 72 located along 2 ¦ the abscissa at X2 would be offset towards the base line 31 Bl by a second offset distance 74 equal to the value of 41 B2-Bl at x2. After each of the images I2 through 5 ¦ In are corrected in accordance with the above, a composite image Ic shown at 76 and a composite vessel edge 77 are 7 ¦ synthesized as previously explained. However, by using 8 ¦ high-speed X-ray camera eauipment currently available, 9 ¦ movement of the vessel during the time interval over which lO ¦ the images are obtained will be small with respect to the 11 ¦ allowable uncertainty in vessel edge location, thereby 12 ¦ making the somewhat elaborate method described above 13 ¦ unnecessary.
14 ¦ Utilizing the present invention, the estimated 1~ ¦ vessel edge finding error is q~ite low. This can be 16 ¦ illustrated by an example in which 100 cc of Hypaque 75 17 ¦ Mr(385 mg iodine/ml) is venously injected in the arm 18 ¦ whereas the X-ray site is in the femoral artery. The 19 estimated blood volume between the injection sight and the 20 ¦ X-ray site is 1500 ml. For an injection duration of 4 21 ¦ seconds and an injection rate of 25 ml per second, it is 22 ¦ estimated that peak concentration in the femoral artery to 23 ¦ be X-rayed is 23.1 mg of iodine per ml of fluid present in 24 I the vessel. A concentration greater than 80% of the peak 2~ ¦ concentration, or 18.5 milligrams of iodine, will be present 26 ¦ in the artery for five seconds. Thus 30 images of the Il ~13~575 ~
I

1 ¦ artery can be taken utilizing a frame rate of 6 frames/second.
2 ¦ The standard deviation of a vessel edge in a low-contrast 3 ¦ image from which a skilled person can locate the artery 41 edge is estimated to be 400 microns, whereas the standard ~¦ deviation for 30 images combined as above-described is ~¦ estimated to be 73 microns (400 divided by the square root 7 ¦ of thirty). Thus one can appreciate that the invention 8 ¦ teaches a method for obtaining a more precise definition of 9 ¦ the artery edge without the high concentration contrast 10 ¦ medium which would be required if the medium were injected 11 ¦ directly into the artery of interest.
12 ¦ A second example utilizes a coronary artery as 13 ¦ the X-ray site and as an injection site a distant pulmonary 14 ¦ artery selected so that approximately 500 ml blood is 15 ¦ contained between the injection site and the X-ray site.
16 ¦ An injection of 100 cc's of Hypague 75 Mr during a 4 17 ¦ second interval results in a peak concentration in the 18 ¦ coronary artery of 56.4 mg of iodine per ml of fluid.
19 Concentrations exceeding 80 percent of this peak concentration 20 ¦ will occur for 2.5 seconds, thereby allowing at a rate of 21 6 images per second 15 i~ages to be obtained. The standard ~2 deviation of a single image in this instance would be 170 23 microns and the standard deviation of the 15 images when 24 combined according to the principles of the invention ~5 will be 43.9 microns.
26 ___ 1~385'7S
., ~

1 ¦ A third embodiment of the invention utili7es 2 ¦ ultrasonic imaging as a non-invasive alternative to the 3 injection of a con.rast medium into a patient, although a 4 contrast medium could be utilized in conjunction with ultrasonic imaging. It is theorized that this method is ~ most useful when the artery sec~ion of interest is within a 7 few centimeters of the skin and is not obscured by bone or 8 gaseous-containing structures. The carotid artery meets the 9 above requirements and is medically significant because of the frequent build-up of atherosclerotic plaque. Instrument-11 ation currently available is capable of producing an image 12 ¦ of calcified plaGue having a resolution of approximately 1 mm.
13 ¦ Referring to Figure 6, a patient 90 is shown 14 ¦ on a supporting table 92. An ultrasonic wave transmitter 15 ¦ and receiver 94 is positioned so that radiating ultrasonic 1~ ¦ waves 96 will intersect an artery section of interest 98.
17 ¦ The ultrasonic transmitter is chosen to radiate in the 1~ ¦ frequency range between 1 MHz and 10 MHz, although both 19 ¦ higher and lower frequencies could also be utilized consistent 2~ ¦ with patient safety. The ultrasonic waves 100 reflected 21 ¦ from the artery section of interest 98 are converted to an 22 ¦ image by an the ultrasonic transmitter and receiver 94, many 23 ¦ types of which are commercially available. Multiple images 24 ¦ of the artery section are obtained and processed by a

25 ¦ processing means 104 as previously described, the output

26 being a composite image 106. A bone 108 or catheter 110 can 113~575 1 be used for registration of the multiple images. Alternatively, 2 a separate ultrasonic receiver 112 could be positioned below 3 the patient 90 for conversion of the waves 114 passing 4 through the patient 90 to an image to be supplied to the sl processing means 104.

Claims (3)

The embodiments of the invention in which an exclusive property or privilege is claimed are defined as follows:

1. In a method of arterial angiography in which an image of an artery section edge is obtained along a fixed direction with respect to said section, the steps comprising:
injecting a contrast medium distant from an artery section of interest to mix with blood to flow through said artery section;
thereafter sequentially obtaining multiple images of said artery section;
obtaining anticipated time-position profiles of said artery section edges, one position profile being designated a base line profile, each subsequent position profile corres-ponding to a time of one of said multiple images;
matching each of said multiple images to its corres-ponding anticipated artery edge profile;
developing a second artery edge profile for each of said images, said second profile being offset from said anticipated profile by the offset between said anticipated profile and said base profile; and constructing a composite image of said artery edge from said second artery edge profiles.

2. The method of claim 1 in which said developing step comprises:
registering each of said multiple images according to at least one landmark internal to a patient;
dividing each of said multiple images into a plurality of image segments; and offsetting each image segment by an amount equal to the distance between its anticipated position and said base line profile, all of the offset image segments comprising an image having an artery edge profile corrected for the antici-pated movement of the artery edge in the time interval occuring between the base line profile and the time the image was attained.

3. The method of claim 1 in which said images are obtained from a single exposure source.