Abstract:
A method and diagnostic apparatus for determining the condition of a patient&#39;s artery or arteries by the use of an ultrasound imaging system which operates in the triplex mode, with a B-mode image of a selected artery location, an A-mode perpendicular to the plane of the artery, at the selected location and a pulsed doppler, at the selected location at an angle to the plane of the artery, with the signals combined, the artery physically or chemical stimulated, the percent dilation of the artery is determined after stimulation, and therefore the condition of the artery is obtained.

Description:
BACKGROUND OF THE INVENTION 
       [0001]    1. Field of the Invention 
         [0002]    This invention relates to a method and diagnostic ultrasound apparatus for determining the condition of a person&#39;s artery or arteries, by using an ultrasound system which shares the PRF of its modes to provide a triplex mode, with a B-mode image displaying a selected artery location, an A-mode cursor perpendicular to the artery, and a pulsed doppler cursor at a 60-degree angle to the artery. 
         [0003]    2. Description of the Prior Art 
         [0004]    Cardiovascular disease causes more than 925,000 deaths annually in the United States alone. It has an economic burden of 128 billion dollars. This disease is highly prevalent and its progression may be preventable if detected and treated early in its onset. 
         [0005]    Cardiovascular disease begins to develop shortly after birth. Autopsies have shown that 50 to 75% of young men have coronary atherosclerosis with 5 to 10% having a high grade of stenosis. More than 75% of elderly individuals will have a high-grade stenosis. 
         [0006]    There are numerous causes of cardiovascular disease such as elevated serum Lipids, hypertension, diabetes mellitus, smoking, elevated homocysteine levels, decreased estrogen, renal failure and many other causes. Effective treatment of these disorders has been shown to reduce morbidity and mortality by 5 to 40%. The treatment of large populations as early as possible reduces the incident of cardiovascular death, however successful treatment of an individual is much less certain. At this time, we cannot tell if we have treated that individual for the right problems, or treated him or her sufficiently to ward off the progression of cardiovascular disease. The degree of control of cardiovascular disease in an individual is currently very difficult to measure. 
         [0007]    The wall of an artery is made up of three layers. The innermost layer touching the blood is called the intima. The next layer consists mostly of smooth muscle cells and is the media. The outermost layer is comprised of fibrous tissue, and is the adventitia. The intima has several parts. There is single layer of cells in contact with the blood called endothelial cells. Behind these cells is a thin layer of connective tissue (strands of fiber), possibly a few smooth muscle cells, and the basement membrane, which separates the intima from the media. 
         [0008]    Artherosclerosis develops between the endothelium and the basement membrane. Cholesterol and white cells from the blood stream penetrate the endothelial barrier, and then form plaque between the endothelium and the basement membrane. When these plaque deposits become large, they protrude into the artery and eventually close off the artery. 
         [0009]    Healthy endothelium is a very dynamic chemical factory. It can produce many substances, some of which keep plaque from forming. If the endothelium is depressed it reduces the production of and or stops making many of its beneficial chemicals, and may produce substance that can promote plaque formation. It is known that smoking, high blood pressure, etc. depresses endothelium function. 
         [0010]    Measuring the health of the endothelium gives us a measurement of the artherosclerosis process and the effectiveness of treatment. Healthy endothelium produces nitric oxide, depressed endothelium does not. Nitric oxide helps control the diameter of an artery. The more nitric oxide produced the larger the diameter of the artery. There are a number of factors that will cause healthy endothelium to produce more nitric oxide. One stimulus is to increase the blood flow in the artery, such as when a muscle is being used. The increased blood flow in the artery increases shear forces on the endothelium as it flows down the artery. The endothelium sense the higher flow, then secretes more nitric oxide and dilates the artery. When the flow returns to normal, the cells reduce nitric oxide secretion, and the artery decreases in diameter. 
         [0011]    If you place a blood pressure cuff around the forearm of an individual, and inflate it to greater than arterial pressure, blood flow will cease in the arm down stream from the cuff. The arm and hand below the cuff will develop an oxygen deficiency. When the cuff is released, the blood flow to the arm and hand is very high. When the oxygen is replaced, the blood flow returns to normal. 
         [0012]    The blood to the forearm is provided through the brachial artery on the inside of the upper arm, which is the artery of choice for monitoring by cardiologists. The diameter of the brachial artery can be measured using diagnostic ultrasound. When the blood flow is increased through the brachial artery, it dilates because of increased nitric oxide secretion, and this dilation is measured by using diagnostic ultrasound. If the endothelium is healthy, the artery can be made to dilate 10 to 20%. If the endothelium is depressed, the artery will dilate only 1 or 2%. By monitoring the artery dilation, we now have a measuring tool to determine the degree of success in treating artherosclerosis. 
         [0013]    Various treatment regimes for cardiovascular disease are used, many of which use various pharmaceuticals to lower cholesterol, to decrease the formation of plaque, and to increase blood flow in the artery being monitored. One of the problems with many of these pharmaceuticals is that it is difficult to measure the treatment progress or lack thereof, and visible results may take many months to be recognized. 
         [0014]    Thus one of the goals of cardiology is to be able to rapidly measure the progress of any given treatment regime. No one has been successful in terms of finding a technique to hasten measuring the results of treatment. Brachial artery studies have been conducted which look at the response of the endothelium to various drug regimes. It is common to measure the nitric oxide production of endothelium, and if it is increasing, you know that the outcome is progressing in a favorable fashion. How you improve the health of the endothelium so that the endothelium will produce more nitric oxide is important, since producing more nitric oxide will slow down, stabilize or actually reverse the artherosclerotic process. 
         [0015]    If you can measure nitric oxide, and if it goes up, you know that the artherosclerosis is abating, or if it goes down another treatment regime may be required. The health of the endothelium can be measured by checking arterial stiffness, such as checking reflected pressure waves in the arterial system. You can measure arterial stiffness by putting catheters inside arteries, or make a measurement by putting on an external device that will measure the pressure waves, and the reflected pressure waves in the arteries. 
         [0016]    The problem with these techniques is that you can only measure artherosclerosis after it has reached a very advanced state. You cannot deduce it early on and the above measuring techniques are insensitive to changes in arterial dilation. That is, it still takes six months to a year to see any kind of useful change in the patient&#39;s condition following the institution of the medical regimen. 
         [0017]    Imaging the brachial artery with an ultrasound system and obtaining the diameter of the artery is not a difficult process. The brachial artery is usually between 2.5 mm and 7 mm in diameter or ⅛ inch in size. Measurements can be made to an accuracy of 0.15-2 mm in the best case. This would give us an error of between 2 and 6%. Thus if we measured the dilatation of a brachial artery and found it to be 8% it is actually somewhere between 6 and 10% best case. This does not give us sufficient accuracy to evaluate an individual&#39;s treatment progress. 
         [0018]    A diagnostic apparatus was developed using ultrasound and a wall-tracking device that included A-mode (radio frequency) waves. This system only measured the diameter of an artery to within 0.15 mm. The unique feature of a wall tracking system is that it can lock onto the wall of the artery and track movement of the wall to within 0.001 mm. We do not need to know the absolute diameter of an artery but how much the diameter changes during the study. Using a wall tracking system, we now can measure changes in artery diameter to within 1%, and thus accurately determine the percent dilation of the artery, and the progress or lack of progress of a treatment regime. 
       SUMMARY OF THE INVENTION 
       [0019]    This invention relates to a diagnostic ultrasound apparatus which uses sharing of the PRF of all the modes to provide a triplex mode of B-mode imaging to locate an artery to be measured, an A-mode cursor perpendicular to the artery, and a pulsed doppler cursor at a 60-degree angle to the artery to measure the arterial diameter before and after chemical, or physical stimulation, and determine the percentage of arterial dilation of the artery and the progress or lack of progress of a treatment regime. 
         [0020]    The principal object of the invention is to provide a method and diagnostic ultrasound apparatus for determining the condition of a person&#39;s artery or arteries by using an ultrasound apparatus in the PRF shared triplex mode, with a B-mode for artery location, an A-mode cursor perpendicular to the artery, and a pulsed Doppler cursor at a 60-degree angle to the artery, which combination allows us to measure the percent dilation of the artery upon chemical or physical stimulation. 
         [0021]    A further object of the invention is to provide a method and apparatus of the character aforesaid which provides a high degree of accuracy. 
         [0022]    A further object of the invention is to provide a method and apparatus of the character aforesaid which is simple to use. 
         [0023]    A further object of the invention is to provide a method and apparatus of the character aforesaid which uses conventional ultrasound apparatus that has been modified to share the PRF of all modes so as to operate in the triplex mode. 
         [0024]    A further object of the invention is to provide a method and apparatus of the character aforesaid which is simple to construct but sturdy and reliable in operation. 
         [0025]    Other objects and advantageous features of the invention will be apparent from the description and claims. 
     
    
     
       DESCRIPTION OF THE DRAWINGS 
         [0026]    The mature and characteristic features of the invention will be more readily understood from the following description taken in connection with the accompanying drawings forming part hereof in which: 
           [0027]      FIG. 1  is a plan view of the apparatus of the invention; 
           [0028]      FIG. 2  is a perspective view of a typical brachial artery; 
           [0029]      FIG. 3  is a block diagram of the apparatus of the invention for artery diameter and blood flow; 
           [0030]      FIG. 4  is a typical display generated by the apparatus of the invention of an artery being measured; 
           [0031]      FIG. 5  is two graphs illustrating blood flow and artery diameter; 
           [0032]      FIG. 6  is a flow chart of the patient&#39;s wall tracker flow; 
           [0033]      FIG. 7  is a flow chart of the patient&#39;s process diameter section of the wall tracker. 
           [0034]      FIG. 8  is a flow chart of the patient&#39;s heartbeat level distension section of the wall tracker, and 
           [0035]      FIG. 9  is a flow chart of the patient&#39;s Doppler processing. 
       
    
    
       [0036]    It should, of course, be understood that the description and drawings herein are merely illustrative, and that various modifications and changes can be made in the method and apparatus disclosed without departing from the spirit of the invention. 
         [0037]    Like numerals refer to like parts throughout the several views. 
       DESCRIPTION OF THE PREFERRED EMBODIMENT 
       [0038]    When referring to the preferred embodiments, certain terminology will be utilized for the sake of clarity. Use of such terminology is intended to encompass not only the described embodiment, but also technical equivalents, which operate and function in substantially the same way to bring about the same result. 
         [0039]    Referring now more particularly to  FIG. 2  of the drawings, a perspective view of a typical brachial artery  10  is therein illustrated. The wall of artery  10  is made up of three layers, an innermost layer  11 , which is the intima, a center layer  12  which consists mostly of smooth muscle cell, and is the media, and an outermost layer  14  of fibrous tissue, which is the adventita. 
         [0040]    The intima  11  has a single layer  15 , of cells in contact with the blood (not shown) known as the endothelium, a thin layer  16  of connective tissue (fiber strands) and possibly a few muscle cells, and the basement membrane  20 , which separates the intima from the media. 
         [0041]    Plaque deposits (not shown) develop in the intima between the endothelium layer  15  and the basement membrane  20 . 
         [0042]    Referring additionally to  FIGS. 1 ,  3  a typical human arm  30  is therein illustrated, with an ultrasound system  31  to be described, which includes a standard well known transducer  32  extending therefrom, and adjacent to the forearm  33  of arm  30 . The drive of the transducer  32  is done by well-known programming, and the electronics of the ultrasound system  31 . 
         [0043]    In one embodiment, the standard transducer  32  includes an array of elements of 128 crystals, with the crystals that are fired determined by the control electronics in the ultrasound system  31 . If operating in the A-mode, one of those crystals is selected for transmission. If operating in a Doppler mode, you use just one crystal on transmit. Note that a number of crystals are used to listen to the reflected wave. Thus you use a single crystal to transmit and multiple crystals to receive. It will thus be appreciated that in the subject system a single transducer is used that is first operated in the A-mode and then in the Doppler mode. An inflatable cuff  34  of well known type is illustrated on forearm  33 , for controlling blood flow through arm  30 , to be described. The Ultrasound apparatus  31  can be any desired system, with a preferred system being the Tetrad 2300 Color flow system, available from W. L. Gore &amp; Associates, Inc., Denver, Colo., which includes a beamformer which has been modified to share the pulse repetition frequency (PRF) to provide a triplex mode. 
         [0044]    Referring additionally to  FIGS. 4 ,  5  an ultrasound display  40  is illustrated, which includes an artery  10 , preferably the brachial artery of arm  30 , which has an anterior wall  24  and a posterior wall  26 . An A-mode cursor  28  is superimposed on the display  40 , perpendicular to the longitudinal axis of artery  10 , which is at the position of acquisition of an A-mode signal. 
         [0045]    A Doppler cursor  50  is shown on display  40 , and is disposed at an angle with respect to A-mode cursor  28 , preferably 60 degrees. A Doppler pulse gate  52 , of the Doppler cursor  50  is positioned inside artery  10  by a track ball  51  as shown in  FIG. 3 , represented by lines  52  and  53 , and as described below. The track ball  51  positions the A-mode cursor for left to right (horizontal) motion in response to left to right track ball input. The Doppler gate  52  is positioned along the Doppler cursor  50 , between the anterior wall  24  and posterior wall  26  of artery  10  by using the up and down motion (vertical) of the track ball  51 . 
         [0046]    Measuring endothelium health using the brachial artery dilatation method consists of a few steps. The person whose artery is to be measured must be lying flat on an examining table in a relaxed position. The cuff  34  is placed on the arm  30 , which must extend outwardly, and be fixed in place so it cannot move during the study. The transducer  32  is placed adjacent the arm  30 , and the system  31  activated. The blood pressure cuff  34  is inflated to a pressure of 20 mmHg greater than systolic blood pressure. Approximately 5 minutes later the cuff  34  is released, and the blood flow and the artery diameter are measured by use of the transducer  32  for 3 to 5 minutes to be described. 
         [0047]    The blood flow measured in the brachial artery  10  is usually 10 to 15 cm/sec. When the blood pressure cuff  34  is inflated on the forearm  33 , the blood flow in the brachial artery  10  decreases. Upon release of the cuff  34 , the blood flow in the brachial artery  10  rises sharply to a maximum value. The time from cuff  34  release until maximal blood flow “a” is approximately 3 seconds. Point “c” is the point at which blood flow has fallen to half of its maximal value. The time from maximal flow to one-half maximal flow is time “b”. If the blood pressure cuff  34  is applied for 2 minutes, time “b” is very short, if the cuff  34  is applied for 10 minutes, time “b” is much longer. 
         [0048]    In  FIG. 5 , the bottom graph shows what happens to the diameter of the brachial artery  10  during the test. The normal brachial artery  10  diameter decreases when the cuff  34  is applied because brachial artery blood flow is decreased, and there is less nitric oxide production. Upon release of the cuff  34 , the higher blood flow now stimulates increased nitric oxide production and dilation of the artery  10 , but this is a slower process than the increase in blood flow. The endothelial cells  15  have to become aware of the higher blood flow and then generate nitric oxide. The nitric oxide diffuses from the cells  15  through the intima  11 , and into the smooth muscle cells of the media  12 . These muscle cells must relax and allow the artery  10  to dilate, which process is slow. The time to maximum artery  10  dilation is about 40 seconds in young healthy individuals. It may take 2 to 3 minutes to reach maximum artery dilation in people with depressed endothelium. 
         [0049]    The maximum diameter reached by the brachial artery  10  depends upon how strongly the nitric oxide machinery was turned on. This stimulus strength is measured by time “b” seen in the blood flow diagram. The longer it takes to reach point “c” the longer the time “b”, and the more the brachial artery  10  dilates in a normal individual. 
         [0050]    The triplex mode color flow ultrasound system  31 , as illustrated in detail in  FIG. 3  includes a display monitor  40 , a keyboard  41  for controlling the ultrasound system, and a transducer  32  for collecting patient data. By means of a local area network connection (LAN)  45 , digitized RF data is sent to a reader  44  for storage and analysis and is displayed on video display  48 . Doppler I and Q signals  46  from the system  31 , are inputted to the reader  44  audio input for Doppler spectrum analysis and display. SVHS video from system  31  is inputted to the reader&#39;s frame grabber input for storage and display on the video display  48 . 
         [0051]    Referring to  FIG. 4 , the B-mode display is used to place the A-mode cursor  28  over the center of the artery  10  in the longitudinal plane, with the anterior wall  24  and posterior wall  26  displayed as shown. 
         [0052]    Referring to  FIG. 6  of the flow charts, the digitized RF data is first band pass filtered  61  about the center frequency of the transducer  32 . The first A-line of RF data is stored as the reference line  62 . Markers  60  are then placed on the anterior and posterior walls  24  and  26 , on the inside of the artery  10  reference line. 
         [0053]    In  FIG. 7  the subsequent new lines are checked for missing packets  70 . If a missed packet is detected  71 , the missing line number is displayed  73 . The new line is band pass filtered  72 , about the center frequency of the transducer  32 . The new lines are then compared to the reference line by correlation  74 , to measure the anterior and posterior walls movement in digitizer sample clock cycles. The new position is checked for errors by comparing and reporting errors to the display  76 . 
         [0054]    Referring again to  FIG. 6 , the new position is used to update the markers  64 . Once all of the wall position data is stored, the diastolic minimum and maximum pressures are identified by the Heart Beat Level Distension  65 , and the percent dilation is calculated by the following formula: 
         [0000]      Percent dilatation=100×(diastolic maximum−diastolic minimum)/diastolic minimum. 
         [0055]    The percent dilatation result is sent to the display  66 . 
         [0056]    Referring to  FIG. 8 , the updated marks which contain all wall position information, is used to calculate the standard deviation  110  of the distension data to check that the data is within limits and to adapt to changing amount of dilation by setting a hysteresis value. 
         [0057]    The highest diastolic maximum at the beginning of the study is located  111 , and from there moved forward to the downward hysteresis point  112 . If there is more data  113 , the minimum and maximum index pointers are set  114 . Searching forward  115 , the systolic minimum and upward inflection point is located. If the upward inflection point is found  116 , the minimum and maximum index pointers are set again  117 , from there search forward for the diastolic maximum  118 , until the downward inflection point is found  119 . If found, the diastolic and systolic values for the current heartbeat are assigned  121 , and the global variables for the minimum and maximum are updated  122 . The heartbeat counter is incremented  123 . If at any time there is no more data to process  113  and  120 , or an abort occurs  124 , flow continues to find the maximum diastolic value  125 . 
         [0058]    Referring to  FIG. 9 , I and Q Doppler data from disk is inputted to switch  91 , with the user having the option to reverse spectrum direction  90 . 
         [0059]    The I and Q Doppler data is windowed  92 , by a Blackman Harris minimum 4 term. A 1024 point fast Fourier transformer, FFT  93 , returns Doppler spectrum data that is low pass filtered  94  to remove wall movement artifacts. 
         [0060]    The processed spectrum is stored in a first Gray scale buffer  95 , with the user having the option to shift baseline  98  to prevent wrap around of spectrum peaks. The baseline-shifted spectrum is stored in a second Gray scale buffer  96  and displayed  97 . The shifted spectrum has the peak envelope detected  99  and stored  100 . The peak and valley detector  101  locates the diastolic and systolic points. Using the diastolic points to mark the beginning of one heartbeat and the start of the next the T ½ calc  102 , calculates the time required for the flow to lower to ½ of its maximum value, and is displayed  103 . 
         [0061]    In one embodiment, the dilation percent is corrected by the diameter of the artery. The larger the artery, the less percent dilation you would expect to get in a normal individual. 
         [0062]    As to blood flow, blood flow is determined by the area under the curve of the blood flow. In other words, you measure how high the velocity goes and for how long over normal blood flow. This measurement corrects for the expected normal percent dilation. 
         [0063]    In other words, if a patient has a very high blood flow over a long period of time, you would expect a normal percent dilation to be somewhere around 15%. If the patient&#39;s artery only dilates 5%, then you know that their endothelium is very thick. You would then integrate the flow over time and that becomes a number, which you multiply times a constant. 
         [0064]    What this means is that a normal dilation for somebody with high blood flow might be 15%, but with somebody with low blood flow because of whatever reason, they might be perfectly healthy at 10%. 
         [0065]    It will thus be seen that a Method and Ultrasonic Diagnostic Apparatus have been described with which the objects of the invention are achieved.