METHODS
Real-Time
Intravascular Ultrasound in Humans
Imaging
Natesa G. Pandian, MD, Andreas Kreis, MD, Andrew Weintraub, MD, Amir Motarjeme, MD, Mark Desnoyers, MD, Jeffrey M. Isner, MD, Marvin Konstam, MD, Deeb N. Salem, MD, and Vie Millen, MD
The capabtiity of obtaining cross-sectional, high resokWn images of arteries with the use of uttrasound catheters has recently been demonstrated in animal studies. in this study the in vivo foasibiiii of intravascular ultrasound imaging in humans was evaluated. in 26 patients who had undergone diagnostic cardiic catheterization or iiiofemorai arteriography, 1 of 3 different modets of 20-MHz uitrasound catheteri was advanced retrograde, into the iliac arteries and aorta or anterograde into the femoral artertes and real-time cross-sectional images of the arteries were obtained in ail. In 10, the iliac arteries were normal and appeared chcutar and putsatik with a t-layered wail and crisply defined lumens. in 7 patients with nonobstructive plaques, the plaque was easily identified in the ultrasound image as a linear, bright, adynamic echo-dense structure. in 4 with obstructive disease in the iliac artery, ths arterial lumen appeared irregular, bordered by a thiikened, nonpuisatiie wail. Variabte grades of atheromatous abnormalities in the wail could be visuatized. In ail 5 patients with arteriographic evidence of obstructive disease of the femoral artery, intravascular ultrasound displayed reduced lumens and irregular borders with protruding high-intensity echoes in the wail. in ail patients, the arterial lumen and the normal or abnormal wail were well visualized in the ultrasound images. There were no complications. This study thus demonstrates the feasibitii of intravascular ultrasound imaghtg of arterial chwtation in humans. With further improvements in catheter design and image quatity, this imaging approach is likely to have a number of potential appikzations in the assessment of peripheral and coronary arterial diseases and in guiding interventional therapeutic procedures. (Am J Cardid 1990;65:1392-1396)
From the Departments of Medicine, Radiology and Pathology, Tufts University School of Medicine and New England Medical Center Hcspitals, Boston, Massachusetts, and Good Samaritan Hospital, Downers Grove, Illinois. Manuscript received July 17, 1989; revised manuscript received and accepted January 24, 1990. Address for reprints: Natesa G. Pandian, MD, Tufts-New England Medical Center, 750 Washington Street, Box 32, Boston, Massachusetts02111.
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elective arteriography, the standard method to evaluate coronary and peripheral arterial atherosclerosis, has limitations in providing precise assessment of obstructive arterial lesions.1-3 Increased understanding of the diagnostic and prognostic importance of atherosclerotic lesions, and problems such as perforations and dissections encountered during catheter-based interventional procedures have emphasized the need for a technique that could delineate better the cross-sectional morphology of obstructive atherosclerotic arteries, particularly in the coronary arterial system.4-12 Among alternate attempts to derive this information, fiberoptic angioscopy has been found to be useful in yielding glimpses of the luminal surface of arteries, protruding atheromas, intravascular thrombi and intimal flaps8 This technique, however, is cumbersome and does not allow precise assessment of the cross-sectional area, the size and composition of an atheroma or the thickness of the wall. Currently, considerable interest is focused on examining the potential of intravascular ultrasound catheters to obtain cross-sectional images of arteries and detect atheromas.13-23 The capability of intravascular ultrasound imaging to yield real-time 2dimensional images of peripheral, pulmonary and coronary arteries has been demonstrated in animals.13J8-23 This study explores the in vivo feasibility of intravascular high frequency ultrasound imaging of the arterial system in conscious humans.
S
METHODS intravascular ultrasound imaging devkus: We used
3 different models of intravascular ultrasound imaging catheters. In all models, the probe is designed to be inserted into an artery via an introducer sheath. In 13 patients, a prototype intravascular imaging instrument (Summit Technology) was used, the details of which have been described previously.i3 This device is 120 cm long and consists of an outer 6Fr probe sheath and an inner moving probe core with a single 20-MHz ultrasound transducer tip. During operation the probe core and transducer are rotated mechanically at 1,800 revolutions/min within the stationary sheath. The image, transmitted to a calibrated display system in real-time, has a resolution of 0.25 mm. In 12 patients, we used a commercially available, intravascular ultrasound probe (Sonicath, Boston Scientific Corp.). This device is a 6Fr disposable catheter enclosing a mechanically rotating driveshaft with a 20-MHz ultrasound crystal at its tip. The catheter is used with an imaging console adapted for 20-MHz use and 3,600 scans (Diasonics). The cath-
eter has tracts for guidewires, a proximal tract at the distal end of the catheter and a distal tract protruding beyond the catheter tip. In 1 patient, we used another commercially available ultrasound catheter, containing a 20-MHz fixed crystal and a rotating mirror (Cardicvascular Imaging Systems). ’ 4 Intravascular ultraround imaging: We studied 26 patients after obtaining informed consent and with the approval of the institutional human investigation review committee. Intravascular imaging of the abdominal aorta and iliac arteries was performed in 19 patients after clinically indicated diagnostic cardiac catheterization for coronary artery disease. The presence and location of atherosclerotic lesions was evaluated by angiography as well. In 7 patients who underwent iliofemoral arteriography for peripheral vascular disease, intravascular imaging of the iliac arteries was performed in 2 and of the femoral arteries in 5. After the diagnostic procedure in each group, a 7Fr introducer sheath was placed in the femoral artery. Then, under fluoroscopy, the ultrasound catheter was advanced retrograde into the iliac artery to the level of abdominal aorta, or anterograde into the femoral artery (Figure 1). From the time of introduction of the ultrasound catheter, ultrasound images were continuously recorded on videotape. Whenever the ultrasound images appeared to show abnormalities, the intravascular location of the catheter was noted by fluoroscopy. After imaging was completed, the ultrasound catheter and the sheath were removed and hemostasis achieved. RESULTS
Among the 26 patients, contrast angiography showed normal iliac arteries in 10, nonobstructive plaques with or without calcification in the right iliac
artery in 7, moderately obstructive disease in the right iliac artery in 2, severe obstructive disease in both iliac arteries in 2 and severe to mild degrees of obstructive disease in the femoral arteries in 5. In all 26 patients, intravascular ultrasound yielded dynamic cross-sectional images of the arteries in realtime (Figures 1 to 5). Perfectly circular and pulsatile images of the normal iliac arteries were obtained in 8 of the 10 patients who evidenced no abnormalities in the contrast angiogram (Figures 2 and 3). The catheter tended often to align with one area of the wall but it could be manipulated to the center of the vessel for brief periods. Except during imaging of the abdominal aorta, the whole circumference of which was beyond the range of ultrasound depth resolution in some, we were able to obtain circular images in all circumstances. The pulsatile nature and the changing caliber of the vessel could be easily appreciated as the catheter was advanced in various arteries. In the patients in whom we used the prototype device, we could not visualize the arterial wall thickness clearly in most. In the images obtained with the refined ultrasound catheters used in later patients, the wall definition and resolution were superior. Normal iliac and femoral arteries appeared with a 3-layered appearance of the wall consisting of a thin inner echogenic layer, a middle hypoechoic layer and an outer echobright layer (Figures 3,4A). Even when the outer layer blended with the signals arising from adjacent structures, the pulsatile nature of the vessel and optimum adjustment of the technical controls allowed recognition of the outer boundary of the wall. Two patients with normal angiographic anatomy exhibited increased focal thickening of the inner layer in the ultrasound images (Figure 4B). In patients with calcific plaques, an intense echodensity was noted at 1 or multiple segments of the
FIGURE 1. v images showing theuttrawuadWandintravaecdar ultraseundiInageeebtaked *av=totypecathebr. TopkR,ldtraeelmdcalheterinUnerightGacawtenyafapatknt. -cauwterinthe Topmfdfb fenwrd~ef~patknt. Tau, dgh~fmordd#ldgr~efthe~palientdepidngnveredenede.noitem kft,uitrruoundbnageracordcdataetenotkdteinihefenwdarteryfromthe paikntwheeederiegrambslmvn.llle kman(L)eixebemdmdthewd(W)exmiteilTegdarandiighhtensity edwee. Bottom tight, dbaeamd image efadkeaeediIacartetyfmmamether
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dlrasound FIGURE 2. Intravasadar alidem-wtslths~paUents.The wh/tehwmpmsmts llnssmamctirdes(arrow,top/eR)sesninrideuwarteftal lumens(L)arecahetardngsignak.The~appearcirculrwithaisplydsftnedhmle!ns.lllecanwtert~toaligll t01shk!ofthewan(w).
tients with moderately obstructive iliac disease seen on angiography, the ultrasound image revealed a smaller lumen with an irregular, nonpulsatile wall (Figures 1 and 4). In one, a linear free-edged structure, consistent with an intimal flap, was seen oscillating within the lumen (Figure 4D). In the 2 patients with severe obstructive disease of the iliac arteries, striking reductions in the area and marked alterations in the shape of the lumen were noted at various segments (Figure 5). The inner layer of the vessel wall was markedly thick, filled with both soft echo signals and focally bright areas. The degree of inner layer thickness was highly variable at different radii of the cross-sectional image and at different levels of the vessel. The middle layer appeared thinner or indistinct at sites of severe disease. In all the 5 patients who manifested disease in the femoral arteriogram, the intravascular ultrasound images were abnormal. The lumens were irregularly shaped, bordered fre quently by high intensity bright echo signals (Figure 1). There were no complications related to intravascular ultrasound imaging or the diagnostic procedure in any of the patients. The patients did not feel any unusual sensation or discomfort with intravascular ultrasound imaging. The catheter demonstrated no clots or damage after removal.
images
of normal iliac devke,fmn4 aS=mmcsdibrationmark.
vessel (Figure 5). This echodensity exhibited no pulsation while the other portions of the artery at the same cross-sectional level were dynamic. While the arterial wall could be seen for the most part at this site, the wall segment outlying calcific plaques was not visualized owing to signal attenuation by the calcium. In the 2 pa-
DISCUSSION Our experience indicates that in vivo intravascular ultrasound imaging of arterial circulation is feasible in humans and that it has the ability to differentiate diseased arteries from normal vessels. The ability to image
FIGURE 3. Intravasadm 8g8S(Obt8hSdWith~Nl8W~~~~ tdbammdcaUwter~a20-MHz l-OtdlDgCry~),OfthO-~ (top), and n&c artdes -~md@fwB~
dtrasotmd
(bottom)
V8SSSlS.ThSdStMCObStW8SllthOClSS8St
caubrauonmarksisSmm.C=cclthaar ~L=hmnsn;W=wan.
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im-
tronl3
FIGURE 5 Medogrm drasemdhuges(~wRha20Mllz iixed-uyetd/rt3tdbg eftheleRlIacmWyfremapatkmtwRh sigdkmt--.The 4?m8wspeinttethedtesef-bneging.Thehanens&e~tethe allg&@kMWOWhg.TllOVaIyblghlmlndshapekweIevident.lbeeuterparthlOfthOWdbllOtSOOll~dtOSOfCddficalhbecauweefriorul~.The cEetmcebelweenthedesestmmksislmm.c=-~ca= ~~w$~~-~~ 1
md
~vasadar mimw
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;-.
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a pulsatile artery in its cross-section in real-time provides a unique strength to the diagnostic and therapeutic approach for arterial diseases. The importance of the cross-sectional anatomy of an atherosclerotic vesselthe luminal shape and size, the morphology of an atheroma and the thickness of the arterial wall-is being increasingly recognized in assessing the clinical significance of an arterial steno&* and when attempting catheter-based interventional procedures.9-12 The tendency of interventional catheter devices to slip away from fibrocalcific atheromas and engage the points of least resistance often result both in incomplete removal of obstructions, and in complications such as perforations and arterial dissections. Adequate visualization of the lumen, obstructive atheroma and the vessel wall thickness during interventional procedures could aid in directing the interventional device to the precise target site, and in deciding when to quit and when to persist. Intravascular ultrasound imaging appears to have the potential to provide needed guidance.17-23 Ability to measure lumen area and wall thickness by intravascular ultrasound and to detect atheromas, arterial dissections and intraluminal thrombi has been demonstrated in vitro.15-*l In vivo studies in animals and preliminary experience in humans point to the capability of obtaining real-time images of various blood vessels, including coronary arteries, and of identifying intimal flaps and intravascular thrombi.*3J4J8-23 Our study extends the previous in vitro and in vivo animal work to humans. Since our attempt was only to assess the feasibility, we did not perform systematic quantitative comparisons between intravascular ultrasound and arteriography. Our experience also points out certain problems that need to be addressed before this type of catheter-based ultrasound imaging is extended to make routine diagnostic or therapeutic decisions. While in vitro experiments have yielded high resolution images of the wall, such definition of the arterial wall appears to be difficult to obtain consistently in vivo. Since the catheter often tends to align to one side of the wall, constant fine manipulation appears to be necessary to get circular images with good resolution. How well the catheter can be negotiated in tortuous vessels and in highly mobile coronary arteries remains to be examined. While the lumen is depicted well in general, the presence of tibrocalcific plaques appears to attenuate the ultrasound signal strength, making it difficult to recognize the wall outlying a plaque. With future improvements in catheter design and image processing, these problems are likely to be solved. Further refinements in instrumentation, and systematic in vivo human investigations, are necessary to verify the ability of intravascular ultrasound in quantitating the size and composition of an atheroma, in guiding interventional procedures, in assessing the effects of interventions and in defining the practical utility in coronary circulation.23 Ackmwledgment: We thank Robert Arcangeli, Robert Crowley, Patrick von Behren and Susan Mattozzi for the technical assistance in the use of the Bos-
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ton Scientific/Diasonics intravascular ultrasound probe. We are grateful to Richard Caro, Alex Sacharoff and Ed Boleza for the technical assistance with the Summit Technology prototype probe. We thank Carol Sykes for help during the use of the Cardiovascular Imaging Systems intravascular ultrasound system. We appreciate the help of Sarah Katz and Linda Wing in the preparation of the manuscript. REFERENCES 1. Marcus ML, Skorton DJ, Johnson MR, Collins SM, Harrison DJ, Kerber RE. Visual estimates of percent diameter coronary stenosis: “a battered gold standard.” JACC 1988;11:882-885. 2. Gould KL. Percent coronary stenosis: battered gold standard, pernicious relic or clinical practicality? JACC 1988:f 1~886-888. 3. White CW, Wright CB, Doty DB, Hiratzka LF, Eastham C, Harrison DC, Marcus ML. Does visual interpretation of the coronary arteriogram predict the physiologic importance of a coronary stenosis? N Engl J Med 1984;310;819-824. 4. Roberts WC. Coronary arteries in fatal acute myccardial infarction. Circulation 1972:45:215-220. 5. Wailer BF. Coronary luminal shape and the arc of disease free wall: morphologic observations and clinical relevance. JACC 1985,6;1100-1101. 6. Ambrose JA. Coronary arteriographic analysis and angiographic morphology. JACC 1989;13:1492-1493. 7. Harrison D, White C, Hiratzka L, Doty D, Eastham C, Marcus M. The value of lesion cross-sectional area determined by quantitative coronary angiography in assessing the physiologic significance of left anterior descending coronary stenosis. Circulation 1984,69:1 I1 l-l I1 9. 6. Forrester JS, Litvak F, Grundfest W, Hickey A. A perspective of coronary artery disease seen through the arteries of living man. Circulation 1987;75:505513. 9. Isner JM, Donaldson RF, Funai JT, Deckelbaum Ll, Pandian NG, Clarke RH, Konstam MA, Salem DN, Bernstein JS. Factors contributing to perforations resulting from laser coronary angioplasty: observations in an intact human postmortem preparation of intraoperative coronary angioplasty. Circulation 1985; 72(suppl ll):II-191-11-199. 10. Wailer BF. Crackers, breakers, stretchers, drillers, scrapers, shavers, burners, welders and melters:-the future treatment of atherosclerotic coronary artery disease? A clinical-pathologic assessment. JACC 1989;13:969-987. 11. Black AJR, Namay DL, Neiderman AL, Lembo NJ, Roubin GS, Douglas JS, King SB. Tear or dissection after coronary angioplasty: morphologic correlates of an ischemic complication. Circulation 1989;79:1035-1042. 12. Meier B, Gruentzig A, Hollman J, Ischinger T, Bradford J. Does length or eccentricity of coronary stenosis influence the outcome of transluminal dilatation? Circulation 1983x57:497-499. 13. Pandian NG, Kreis A, Brockway B, lsner JM, Sacharoff A, Boleza E. Caro R, Muller D. Ultrasound angioscopy: real-time, two-dimensional, intraluminal ultrasound imaging of blood vessels. Am J Cardiol 1988,62;493-494. 14. Yock PG, Johnson EI, Linker DT. Intravascular ultrasound: development and clinical potential. Am J Cardiac imaging 1988;2:185-193. 15. Gussenhoven EJ, Essed CE, Lancee CT, Mastik F, Frietman P, Van Egmond FC, Reibcr J, Bosch H, Van Urk H, Roelandt J, Born N. Arterial wall characteristics determined by intravascular ultrasound imaging: an in vitro study. JACC 1989;4:947-952. 16. Pandian NG, Kreis A, Brockway B, Isner J, Salem D, Sacharoff A, Boleza E, Caro R. Ultrasound angicscopy: feasibility and potential. Echocardiography 1989,6:1-7. 17. Tobis J. Mallery J, Gessert J, Griffith J, Mahon D, Bessen M, Moriuchi M, Macleay L, McRae M, Henry WL. Intravascular ultrasound cross-sectional arterial imaging before and after balloon angioplasty in vitro. Circulation 1989:80:873-882. 16. Hodgson J, Graham SP, Savakus AD, Dame SG, Stephens DN, Dhillon D, Brands D, Sheehan H, Eberle MJ. Clinical percutaneous imaging of coronary anatomy using an over-thewire ultrasound catheter system. fnt J Cardiac Imaging 1989;4:187-193. 19. Pandian NG, Kreis A, O’Donnell T. Intravascular ultrasound estimation of arterial stenosis. J Am Sot Echocardiography 1989;2:390-397. 20. Pandian NG, Kreis A, Brockway B. Detection of intraarterial thrombus by intravascular high frequency two-dimensional ultrasound imaging. In vitro and in viva studies. Am J Cardiol 1990x55:1 280-1283. 21. Pandian NG, Kreis A, Brockway, Sacharoff A, Caro R. intravascular high frequency twc-dimensional ultrasound detection of arterial dissection and intimal flaps. Am J Cardiol 1990,65:1278-1280. 22. Born N, Roelandt J. Intravascular ultrasound. Techniques, developments, clinical perspectives. Dordrecht: Kluwer Academic Publishers, 1989. 23. Pandian NG. Intravascular and intracardiac echocardiography: an old concept, now on the road to reality. Circulation 1989;80:1091-1094.
Real-Time
Intravascular Ultrasound in Humans
Imaging
Natesa G. Pandian, MD, Andreas Kreis, MD, Andrew Weintraub, MD, Amir Motarjeme, MD, Mark Desnoyers, MD, Jeffrey M. Isner, MD, Marvin Konstam, MD, Deeb N. Salem, MD, and Vie Millen, MD
The capabtiity of obtaining cross-sectional, high resokWn images of arteries with the use of uttrasound catheters has recently been demonstrated in animal studies. in this study the in vivo foasibiiii of intravascular ultrasound imaging in humans was evaluated. in 26 patients who had undergone diagnostic cardiic catheterization or iiiofemorai arteriography, 1 of 3 different modets of 20-MHz uitrasound catheteri was advanced retrograde, into the iliac arteries and aorta or anterograde into the femoral artertes and real-time cross-sectional images of the arteries were obtained in ail. In 10, the iliac arteries were normal and appeared chcutar and putsatik with a t-layered wail and crisply defined lumens. in 7 patients with nonobstructive plaques, the plaque was easily identified in the ultrasound image as a linear, bright, adynamic echo-dense structure. in 4 with obstructive disease in the iliac artery, ths arterial lumen appeared irregular, bordered by a thiikened, nonpuisatiie wail. Variabte grades of atheromatous abnormalities in the wail could be visuatized. In ail 5 patients with arteriographic evidence of obstructive disease of the femoral artery, intravascular ultrasound displayed reduced lumens and irregular borders with protruding high-intensity echoes in the wail. in ail patients, the arterial lumen and the normal or abnormal wail were well visualized in the ultrasound images. There were no complications. This study thus demonstrates the feasibitii of intravascular ultrasound imaghtg of arterial chwtation in humans. With further improvements in catheter design and image quatity, this imaging approach is likely to have a number of potential appikzations in the assessment of peripheral and coronary arterial diseases and in guiding interventional therapeutic procedures. (Am J Cardid 1990;65:1392-1396)
From the Departments of Medicine, Radiology and Pathology, Tufts University School of Medicine and New England Medical Center Hcspitals, Boston, Massachusetts, and Good Samaritan Hospital, Downers Grove, Illinois. Manuscript received July 17, 1989; revised manuscript received and accepted January 24, 1990. Address for reprints: Natesa G. Pandian, MD, Tufts-New England Medical Center, 750 Washington Street, Box 32, Boston, Massachusetts02111.
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elective arteriography, the standard method to evaluate coronary and peripheral arterial atherosclerosis, has limitations in providing precise assessment of obstructive arterial lesions.1-3 Increased understanding of the diagnostic and prognostic importance of atherosclerotic lesions, and problems such as perforations and dissections encountered during catheter-based interventional procedures have emphasized the need for a technique that could delineate better the cross-sectional morphology of obstructive atherosclerotic arteries, particularly in the coronary arterial system.4-12 Among alternate attempts to derive this information, fiberoptic angioscopy has been found to be useful in yielding glimpses of the luminal surface of arteries, protruding atheromas, intravascular thrombi and intimal flaps8 This technique, however, is cumbersome and does not allow precise assessment of the cross-sectional area, the size and composition of an atheroma or the thickness of the wall. Currently, considerable interest is focused on examining the potential of intravascular ultrasound catheters to obtain cross-sectional images of arteries and detect atheromas.13-23 The capability of intravascular ultrasound imaging to yield real-time 2dimensional images of peripheral, pulmonary and coronary arteries has been demonstrated in animals.13J8-23 This study explores the in vivo feasibility of intravascular high frequency ultrasound imaging of the arterial system in conscious humans.
S
METHODS intravascular ultrasound imaging devkus: We used
3 different models of intravascular ultrasound imaging catheters. In all models, the probe is designed to be inserted into an artery via an introducer sheath. In 13 patients, a prototype intravascular imaging instrument (Summit Technology) was used, the details of which have been described previously.i3 This device is 120 cm long and consists of an outer 6Fr probe sheath and an inner moving probe core with a single 20-MHz ultrasound transducer tip. During operation the probe core and transducer are rotated mechanically at 1,800 revolutions/min within the stationary sheath. The image, transmitted to a calibrated display system in real-time, has a resolution of 0.25 mm. In 12 patients, we used a commercially available, intravascular ultrasound probe (Sonicath, Boston Scientific Corp.). This device is a 6Fr disposable catheter enclosing a mechanically rotating driveshaft with a 20-MHz ultrasound crystal at its tip. The catheter is used with an imaging console adapted for 20-MHz use and 3,600 scans (Diasonics). The cath-
eter has tracts for guidewires, a proximal tract at the distal end of the catheter and a distal tract protruding beyond the catheter tip. In 1 patient, we used another commercially available ultrasound catheter, containing a 20-MHz fixed crystal and a rotating mirror (Cardicvascular Imaging Systems). ’ 4 Intravascular ultraround imaging: We studied 26 patients after obtaining informed consent and with the approval of the institutional human investigation review committee. Intravascular imaging of the abdominal aorta and iliac arteries was performed in 19 patients after clinically indicated diagnostic cardiac catheterization for coronary artery disease. The presence and location of atherosclerotic lesions was evaluated by angiography as well. In 7 patients who underwent iliofemoral arteriography for peripheral vascular disease, intravascular imaging of the iliac arteries was performed in 2 and of the femoral arteries in 5. After the diagnostic procedure in each group, a 7Fr introducer sheath was placed in the femoral artery. Then, under fluoroscopy, the ultrasound catheter was advanced retrograde into the iliac artery to the level of abdominal aorta, or anterograde into the femoral artery (Figure 1). From the time of introduction of the ultrasound catheter, ultrasound images were continuously recorded on videotape. Whenever the ultrasound images appeared to show abnormalities, the intravascular location of the catheter was noted by fluoroscopy. After imaging was completed, the ultrasound catheter and the sheath were removed and hemostasis achieved. RESULTS
Among the 26 patients, contrast angiography showed normal iliac arteries in 10, nonobstructive plaques with or without calcification in the right iliac
artery in 7, moderately obstructive disease in the right iliac artery in 2, severe obstructive disease in both iliac arteries in 2 and severe to mild degrees of obstructive disease in the femoral arteries in 5. In all 26 patients, intravascular ultrasound yielded dynamic cross-sectional images of the arteries in realtime (Figures 1 to 5). Perfectly circular and pulsatile images of the normal iliac arteries were obtained in 8 of the 10 patients who evidenced no abnormalities in the contrast angiogram (Figures 2 and 3). The catheter tended often to align with one area of the wall but it could be manipulated to the center of the vessel for brief periods. Except during imaging of the abdominal aorta, the whole circumference of which was beyond the range of ultrasound depth resolution in some, we were able to obtain circular images in all circumstances. The pulsatile nature and the changing caliber of the vessel could be easily appreciated as the catheter was advanced in various arteries. In the patients in whom we used the prototype device, we could not visualize the arterial wall thickness clearly in most. In the images obtained with the refined ultrasound catheters used in later patients, the wall definition and resolution were superior. Normal iliac and femoral arteries appeared with a 3-layered appearance of the wall consisting of a thin inner echogenic layer, a middle hypoechoic layer and an outer echobright layer (Figures 3,4A). Even when the outer layer blended with the signals arising from adjacent structures, the pulsatile nature of the vessel and optimum adjustment of the technical controls allowed recognition of the outer boundary of the wall. Two patients with normal angiographic anatomy exhibited increased focal thickening of the inner layer in the ultrasound images (Figure 4B). In patients with calcific plaques, an intense echodensity was noted at 1 or multiple segments of the
FIGURE 1. v images showing theuttrawuadWandintravaecdar ultraseundiInageeebtaked *av=totypecathebr. TopkR,ldtraeelmdcalheterinUnerightGacawtenyafapatknt. -cauwterinthe Topmfdfb fenwrd~ef~patknt. Tau, dgh~fmordd#ldgr~efthe~palientdepidngnveredenede.noitem kft,uitrruoundbnageracordcdataetenotkdteinihefenwdarteryfromthe paikntwheeederiegrambslmvn.llle kman(L)eixebemdmdthewd(W)exmiteilTegdarandiighhtensity edwee. Bottom tight, dbaeamd image efadkeaeediIacartetyfmmamether
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dlrasound FIGURE 2. Intravasadar alidem-wtslths~paUents.The wh/tehwmpmsmts llnssmamctirdes(arrow,top/eR)sesninrideuwarteftal lumens(L)arecahetardngsignak.The~appearcirculrwithaisplydsftnedhmle!ns.lllecanwtert~toaligll t01shk!ofthewan(w).
tients with moderately obstructive iliac disease seen on angiography, the ultrasound image revealed a smaller lumen with an irregular, nonpulsatile wall (Figures 1 and 4). In one, a linear free-edged structure, consistent with an intimal flap, was seen oscillating within the lumen (Figure 4D). In the 2 patients with severe obstructive disease of the iliac arteries, striking reductions in the area and marked alterations in the shape of the lumen were noted at various segments (Figure 5). The inner layer of the vessel wall was markedly thick, filled with both soft echo signals and focally bright areas. The degree of inner layer thickness was highly variable at different radii of the cross-sectional image and at different levels of the vessel. The middle layer appeared thinner or indistinct at sites of severe disease. In all the 5 patients who manifested disease in the femoral arteriogram, the intravascular ultrasound images were abnormal. The lumens were irregularly shaped, bordered fre quently by high intensity bright echo signals (Figure 1). There were no complications related to intravascular ultrasound imaging or the diagnostic procedure in any of the patients. The patients did not feel any unusual sensation or discomfort with intravascular ultrasound imaging. The catheter demonstrated no clots or damage after removal.
images
of normal iliac devke,fmn4 aS=mmcsdibrationmark.
vessel (Figure 5). This echodensity exhibited no pulsation while the other portions of the artery at the same cross-sectional level were dynamic. While the arterial wall could be seen for the most part at this site, the wall segment outlying calcific plaques was not visualized owing to signal attenuation by the calcium. In the 2 pa-
DISCUSSION Our experience indicates that in vivo intravascular ultrasound imaging of arterial circulation is feasible in humans and that it has the ability to differentiate diseased arteries from normal vessels. The ability to image
FIGURE 3. Intravasadm 8g8S(Obt8hSdWith~Nl8W~~~~ tdbammdcaUwter~a20-MHz l-OtdlDgCry~),OfthO-~ (top), and n&c artdes -~md@fwB~
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(bottom)
V8SSSlS.ThSdStMCObStW8SllthOClSS8St
caubrauonmarksisSmm.C=cclthaar ~L=hmnsn;W=wan.
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im-
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FIGURE 5 Medogrm drasemdhuges(~wRha20Mllz iixed-uyetd/rt3tdbg eftheleRlIacmWyfremapatkmtwRh sigdkmt--.The 4?m8wspeinttethedtesef-bneging.Thehanens&e~tethe allg&@kMWOWhg.TllOVaIyblghlmlndshapekweIevident.lbeeuterparthlOfthOWdbllOtSOOll~dtOSOfCddficalhbecauweefriorul~.The cEetmcebelweenthedesestmmksislmm.c=-~ca= ~~w$~~-~~ 1
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;-.
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a pulsatile artery in its cross-section in real-time provides a unique strength to the diagnostic and therapeutic approach for arterial diseases. The importance of the cross-sectional anatomy of an atherosclerotic vesselthe luminal shape and size, the morphology of an atheroma and the thickness of the arterial wall-is being increasingly recognized in assessing the clinical significance of an arterial steno&* and when attempting catheter-based interventional procedures.9-12 The tendency of interventional catheter devices to slip away from fibrocalcific atheromas and engage the points of least resistance often result both in incomplete removal of obstructions, and in complications such as perforations and arterial dissections. Adequate visualization of the lumen, obstructive atheroma and the vessel wall thickness during interventional procedures could aid in directing the interventional device to the precise target site, and in deciding when to quit and when to persist. Intravascular ultrasound imaging appears to have the potential to provide needed guidance.17-23 Ability to measure lumen area and wall thickness by intravascular ultrasound and to detect atheromas, arterial dissections and intraluminal thrombi has been demonstrated in vitro.15-*l In vivo studies in animals and preliminary experience in humans point to the capability of obtaining real-time images of various blood vessels, including coronary arteries, and of identifying intimal flaps and intravascular thrombi.*3J4J8-23 Our study extends the previous in vitro and in vivo animal work to humans. Since our attempt was only to assess the feasibility, we did not perform systematic quantitative comparisons between intravascular ultrasound and arteriography. Our experience also points out certain problems that need to be addressed before this type of catheter-based ultrasound imaging is extended to make routine diagnostic or therapeutic decisions. While in vitro experiments have yielded high resolution images of the wall, such definition of the arterial wall appears to be difficult to obtain consistently in vivo. Since the catheter often tends to align to one side of the wall, constant fine manipulation appears to be necessary to get circular images with good resolution. How well the catheter can be negotiated in tortuous vessels and in highly mobile coronary arteries remains to be examined. While the lumen is depicted well in general, the presence of tibrocalcific plaques appears to attenuate the ultrasound signal strength, making it difficult to recognize the wall outlying a plaque. With future improvements in catheter design and image processing, these problems are likely to be solved. Further refinements in instrumentation, and systematic in vivo human investigations, are necessary to verify the ability of intravascular ultrasound in quantitating the size and composition of an atheroma, in guiding interventional procedures, in assessing the effects of interventions and in defining the practical utility in coronary circulation.23 Ackmwledgment: We thank Robert Arcangeli, Robert Crowley, Patrick von Behren and Susan Mattozzi for the technical assistance in the use of the Bos-
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ton Scientific/Diasonics intravascular ultrasound probe. We are grateful to Richard Caro, Alex Sacharoff and Ed Boleza for the technical assistance with the Summit Technology prototype probe. We thank Carol Sykes for help during the use of the Cardiovascular Imaging Systems intravascular ultrasound system. We appreciate the help of Sarah Katz and Linda Wing in the preparation of the manuscript. REFERENCES 1. Marcus ML, Skorton DJ, Johnson MR, Collins SM, Harrison DJ, Kerber RE. Visual estimates of percent diameter coronary stenosis: “a battered gold standard.” JACC 1988;11:882-885. 2. Gould KL. Percent coronary stenosis: battered gold standard, pernicious relic or clinical practicality? JACC 1988:f 1~886-888. 3. White CW, Wright CB, Doty DB, Hiratzka LF, Eastham C, Harrison DC, Marcus ML. Does visual interpretation of the coronary arteriogram predict the physiologic importance of a coronary stenosis? N Engl J Med 1984;310;819-824. 4. Roberts WC. Coronary arteries in fatal acute myccardial infarction. Circulation 1972:45:215-220. 5. Wailer BF. Coronary luminal shape and the arc of disease free wall: morphologic observations and clinical relevance. JACC 1985,6;1100-1101. 6. Ambrose JA. Coronary arteriographic analysis and angiographic morphology. JACC 1989;13:1492-1493. 7. Harrison D, White C, Hiratzka L, Doty D, Eastham C, Marcus M. The value of lesion cross-sectional area determined by quantitative coronary angiography in assessing the physiologic significance of left anterior descending coronary stenosis. Circulation 1984,69:1 I1 l-l I1 9. 6. Forrester JS, Litvak F, Grundfest W, Hickey A. A perspective of coronary artery disease seen through the arteries of living man. Circulation 1987;75:505513. 9. Isner JM, Donaldson RF, Funai JT, Deckelbaum Ll, Pandian NG, Clarke RH, Konstam MA, Salem DN, Bernstein JS. Factors contributing to perforations resulting from laser coronary angioplasty: observations in an intact human postmortem preparation of intraoperative coronary angioplasty. Circulation 1985; 72(suppl ll):II-191-11-199. 10. Wailer BF. Crackers, breakers, stretchers, drillers, scrapers, shavers, burners, welders and melters:-the future treatment of atherosclerotic coronary artery disease? A clinical-pathologic assessment. JACC 1989;13:969-987. 11. Black AJR, Namay DL, Neiderman AL, Lembo NJ, Roubin GS, Douglas JS, King SB. Tear or dissection after coronary angioplasty: morphologic correlates of an ischemic complication. Circulation 1989;79:1035-1042. 12. Meier B, Gruentzig A, Hollman J, Ischinger T, Bradford J. Does length or eccentricity of coronary stenosis influence the outcome of transluminal dilatation? Circulation 1983x57:497-499. 13. Pandian NG, Kreis A, Brockway B, lsner JM, Sacharoff A, Boleza E. Caro R, Muller D. Ultrasound angioscopy: real-time, two-dimensional, intraluminal ultrasound imaging of blood vessels. Am J Cardiol 1988,62;493-494. 14. Yock PG, Johnson EI, Linker DT. Intravascular ultrasound: development and clinical potential. Am J Cardiac imaging 1988;2:185-193. 15. Gussenhoven EJ, Essed CE, Lancee CT, Mastik F, Frietman P, Van Egmond FC, Reibcr J, Bosch H, Van Urk H, Roelandt J, Born N. Arterial wall characteristics determined by intravascular ultrasound imaging: an in vitro study. JACC 1989;4:947-952. 16. Pandian NG, Kreis A, Brockway B, Isner J, Salem D, Sacharoff A, Boleza E, Caro R. Ultrasound angicscopy: feasibility and potential. Echocardiography 1989,6:1-7. 17. Tobis J. Mallery J, Gessert J, Griffith J, Mahon D, Bessen M, Moriuchi M, Macleay L, McRae M, Henry WL. Intravascular ultrasound cross-sectional arterial imaging before and after balloon angioplasty in vitro. Circulation 1989:80:873-882. 16. Hodgson J, Graham SP, Savakus AD, Dame SG, Stephens DN, Dhillon D, Brands D, Sheehan H, Eberle MJ. Clinical percutaneous imaging of coronary anatomy using an over-thewire ultrasound catheter system. fnt J Cardiac Imaging 1989;4:187-193. 19. Pandian NG, Kreis A, O’Donnell T. Intravascular ultrasound estimation of arterial stenosis. J Am Sot Echocardiography 1989;2:390-397. 20. Pandian NG, Kreis A, Brockway B. Detection of intraarterial thrombus by intravascular high frequency two-dimensional ultrasound imaging. In vitro and in viva studies. Am J Cardiol 1990x55:1 280-1283. 21. Pandian NG, Kreis A, Brockway, Sacharoff A, Caro R. intravascular high frequency twc-dimensional ultrasound detection of arterial dissection and intimal flaps. Am J Cardiol 1990,65:1278-1280. 22. Born N, Roelandt J. Intravascular ultrasound. Techniques, developments, clinical perspectives. Dordrecht: Kluwer Academic Publishers, 1989. 23. Pandian NG. Intravascular and intracardiac echocardiography: an old concept, now on the road to reality. Circulation 1989;80:1091-1094.
