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Circulation. 1995;91:1036-1043

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(Circulation. 1995;91:1036-1043.)
© 1995 American Heart Association, Inc.

Articles

Sensitive Detection of Abnormal Aortic Architecture in Marfan Syndrome With High-Frequency Ultrasonic Tissue Characterization

Dino Recchia, MD; Angela M. Sharkey, MD; Matthew S. Bosner, MD; Nicholas T. Kouchoukos, MD; Samuel A. Wickline, MD

From Washington University School of Medicine, St Louis, Mo.


*    Abstract
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 *Abstract
down arrowIntroduction
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down arrowResults
down arrowDiscussion
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Background Aneurysmal dilation of the aorta with subsequent rupture or dissection occurs frequently in patients with Marfan syndrome and is the primary cause of morbidity. These complications are related to the altered composition and disorganized structure of the aortic media. Our goal was to use high-frequency ultrasonic tissue characterization to identify these structural changes in abnormal aorta from patients with Marfan syndrome. We measured integrated backscatter and anisotropy of backscatter of ultrasound from specimens of aorta from patients with Marfan syndrome undergoing aortic root replacement and compared these values with those from aortic specimens of patients without clinical aortic pathology.

Methods and Results Aortic tissue was obtained at the time of surgery from 11 patients with Marfan syndrome undergoing repair of an aortic aneurysm or dissection. Normal tissue was obtained at the time of autopsy from 8 patients without evidence of aortic disease. Acoustic microscopy at 50 MHz was performed to measure integrated backscatter from each specimen. The magnitude of ultrasonic anisotropy of backscatter for each tissue type was determined as an index of the three-dimensional (3D) organization of the vessel matrix. The collagen content of each specimen was determined with a hydroxyproline assay. Marfan aortas exhibited less backscatter than did normal aortas (-40.9±2.9 versus -32.6±2.2 dB for patients with Marfan syndrome and healthy subjects, respectively, P<.0001). No significant difference in collagen concentrations was observed between normal and Marfan aorta (262.7±52.7 versus 282.4±41.8 mg/g tissue for normal and Marfan aortas, respectively, P=.42), despite the large difference in backscatter. Histological analysis revealed striking differences in both the amount and organization of the elastin in the aortic aneurysm segments from patients with Marfan syndrome compared with normal aorta. Normal aorta was characterized by well-formed elastin fibers arranged in a lamellar pattern. The media from aneurysms in Marfan aorta exhibited a profound decrease in elastin content that was associated with loss of the highly aligned and ordered lamellar arrangement. The directional dependence of scattering, or ultrasonic anisotropy, also differed dramatically between the two tissue types. Backscatter from normal aorta decreased substantially when the media was insonified parallel compared with perpendicular to the principal axis of the elastin fibers. Marfan aorta exhibited a much smaller directional dependence of scattering. Normal aortas manifested a 14-fold greater ultrasonic anisotropy than did Marfan aortas (24.1±3.7 versus 12.4±3.3 dB for normal and Marfan aortas, P<.0001), which is indicative of the profound extent of matrix disorganization in Marfan syndrome.

Conclusions These data show that high-frequency ultrasonic tissue characterization sensitively detects changes in vessel wall composition and organization that occur in the aorta of patients with Marfan syndrome. Aortic segments from these patients manifested a significant decrease in integrated backscatter compared with normal aorta (approximately 8 dB, or greater than a 6-fold decrease in scattering). A 15-fold reduction in the ultrasonic anisotropy of Marfan tissue was observed, which suggests a marked disorganization of the 3D architecture of these aortas. These data support the hypothesis that high-frequency ultrasonic tissue characterization may be useful for identifying abnormalities of vessel wall composition, architecture, and material properties.


Key Words: ultrasonics • Marfan syndrome • aneurysm


*    Introduction
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 up arrowAbstract
 *Introduction
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down arrowResults
down arrowDiscussion
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Marfan syndrome is a heritable disorder of connective tissue structure and function with manifestations in the ocular, skeletal, and cardiovascular systems.1 Recent data suggest that Marfan syndrome is related to abnormalities in the production of the molecule fibrillin, which is a microfibril that forms the scaffolding on which elastin fibers are assembled.2 3 4 The elastin fibers in this disorder are abnormal in both structure and organization, which leads to altered material properties that characterize affected tissues. Aneurysmal dilatation of the aorta with subsequent rupture and/or dissection occurs frequently in patients with Marfan syndrome and is the major cause of significant morbidity and mortality.5 6 These cardiovascular complications are related directly to the altered composition and disorganized structure of the aortic media. We hypothesize that sensitive detection of time-dependent changes in the arterial matrix at the cellular level could be useful for monitoring disease progression and perhaps for determining the appropriate timing of both medical and surgical intervention.

Ultrasonic tissue characterization provides a method for defining the physical properties of soft tissue based on measurements of scattered ultrasound. The interaction of ultrasound with biological tissues depends in part on the specific biochemical composition of the tissue and its underlying three-dimensional (3D) architecture.7 8 Quantitative tissue characterization with low-frequency ultrasound (2.5 to 5.0 MHz) has been applied for identifying selected pathological states in myocardium that include ischemia, infarction, and cardiomyopathy.9

The 3D organization of soft tissue also can be quantified with acoustic tissue characterization methods. Our laboratory previously showed that tissues with a high degree of organization and alignment of component parts, such as myocardium and tendon, manifest considerable directional dependence of ultrasonic properties, or ultrasonic anisotropy.10 11 12 13 14 15 16 Both the ultrasonic energy backscattered from these highly aligned tissues and the attenuation suffered by the ultrasonic waves propagating through tissue are highly dependent on the angle of insonification with respect to the predominant fiber axis of the tissue. The magnitude of ultrasonic anisotropy can be quantified to provide a measure of the 3D organization of the tissue.

A principal biophysical abnormality in aortas of patients with Marfan syndrome is due to alterations in the amount and structure of elastin fibers.17 Preliminary data from our laboratory showed that the scattering of high-frequency ultrasound by normal vascular tissue depends in part on the amount of both collagen and elastin in the arterial wall.18 The goal of the present work was to use ultrasonic tissue characterization to identify these structural changes at the cellular level in the abnormal aorta from patients with Marfan syndrome. Accordingly, we measured integrated backscatter and anisotropy of backscatter of ultrasound from excised specimens of aorta from patients with Marfan syndrome undergoing aortic root replacement and compared these values with those from aortic specimens of patients without clinical aortic pathology. Our data indicate that ultrasonic tissue characterization provides a sensitive method for elucidating abnormal matrix architecture in aortas of patients with Marfan syndrome.


*    Methods
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 up arrowAbstract
 up arrowIntroduction
 *Methods
down arrowResults
down arrowDiscussion
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Preparation of Aortic Tissues
Aortic tissue was obtained at the time of surgery from patients with Marfan syndrome undergoing repair of an aortic aneurysm or dissection. All patients met established diagnostic criteria for Marfan syndrome.1 19 Segments of aortic tissue (approximately 2x2 cm) were excised at surgery from the center of the aneurysmal zone and marked so that their original orientation could be identified to permit insonification from either perpendicular or parallel directions with respect to circumferential fiber orientations. Normal tissue was obtained at the time of autopsy from patients without evidence of aortic disease. All tissues in both affected and normal patients were obtained from the ascending aorta and were free of any significant atherosclerosis. The tissue was fixed in 10% buffered formalin and scanned within 48 hours. A total of 20 sections of aorta were studied, 8 from normal individuals and 11 from patients with Marfan syndrome. The sections were mounted in a specially designed tissue holder for acoustic microscopy.

Acquisition of Ultrasonic Data
A high-resolution, high-frequency acoustic microscope was used to acquire backscattered radio frequency (RF) data from each specimen. A 50-MHz (nominal frequency), broadband, focused, piezoelectric delay-line transducer (1/4-in diameter, 1/2-in focal length, model V390, Panametrics Co) was operated in the pulse-echo mode with custom-designed electronics (General Electric Co). The motion of the transducer over the tissue specimen was controlled by an Aerotech Unidex 12 motion controller with servomotors that permitted motion of the transducer along the x, y, and z axes with step resolution as fine as 1 µm. Ultrasonic RF data were collected with a Tektronix DSA 601 digitizing oscilloscope at 500 megasamples per second with 8-bit resolution. The entire system was controlled by a Macintosh IIfx computer with a GPIB interface bus. The excitatory RF pulse envelope incorporated approximately 1.5 cycles with a duration of about 30 nanoseconds.20 The transducer was positioned so that its focal zone was in the middle of the specimen.

Each specimen of aorta was cut open longitudinally along the direction of blood flow and placed flat on a special tissue holder with its luminal side up in a water tank filled with degassed saline at 21°C. This position ensured that the initial direction of insonification was perpendicular to the major fiber axis of the vessel (see Fig 1Down). To measure ultrasonic anisotropy, a 1-mm-thick section was then taken from the same specimen at the edge of the previously cut surface and mounted in the tissue holder with the cut surface facing the transducer. This position ensured a direction of insonification that was orthogonal to the previous one and parallel to the circumferential orientation of the major fiber axis of the vessel (Fig 1Down).



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  		Figure 1. Schematic showing orientation of the ultrasound beam in relation to the major fiber axis of the arterial wall. The area outlined by the square represents the sample of arterial wall removed for insonification. Elastin fibers are oriented circumferentially around the vessel wall orthogonal to the direction of blood flow. Each tissue section was insonified both perpendicular and parallel to the major fiber axis, as illustrated in the lower panel.

Aortic tissue was imaged first in a low-resolution mode to define the lateral boundaries of the specimens by moving the transducer in the x-y plane in 100-µm translational steps over the entire surface of the tissue and recording gated, peak-detected values for backscattered RF from tissue segments just below the surface. The low-resolution scan was used as a guide for additional scanning in a higher-resolution B-scan mode to depict the internal structure of each specimen. For the B scans, approximately 200 independent RF lines were recorded at 100-µm intervals. At each independent site, RF lines were averaged 256 times to improve the signal-to-noise ratio. A total of 800 to 1000 independent RF lines were obtained for each specimen. The envelope of RF lines at each site was determined by computing the "analytic signal," by use of the Hilbert transform, according to methods previously described.21 The envelope-detected B scan could then be displayed on the Macintosh screen. The RF data were stored on a 44-megabyte hard disk (Peripheral Land Inc) for later analysis off-line. Each of the tissue specimens was scanned identically.

Analysis of Ultrasonic Data
Segments of RF lines (350 nanoseconds long) were gated from within the arterial media for each tissue section. The gated data were multiplied by a Hamming window, and power spectra were determined by fast Fourier transformation. The power spectrum from each specimen was referenced to the power spectrum backscattered from a near-perfect (steel plate) reflector to compute the frequency-dependent backscatter transfer function according to methods previously described.22 23 Integrated backscatter was computed from the average of the frequency-dependent backscatter transfer function over the useful bandwidth of the transducer (30 to 55 MHz) and was expressed in decibels relative to scattering from the steel plate. No compensation was applied for ultrasonic attenuation.

Histological and Biochemical Analyses
After ultrasonic data had been obtained, the tissue was divided in half. One half was used for determination of collagen concentration as described below. The other half was embedded in paraffin and sectioned for histological analysis. The tissue sections for histology and collagen content corresponded to the areas from which ultrasonic data were acquired. Each section was stained for elastin with van Gieson stain, collagen with Masson's trichrome, and mucopolysaccharides with alcian blue. The intimal and medial thicknesses of each specimen were determined from the van Gieson stained specimen by use of an optical micrometer.

The collagen in formalin-fixed vessels was assessed after removal of all loose adventitial tissue with hydroxyproline assays based on standard colorimetric techniques previously described.24 25 26 Although formalin is known to react with and precipitate various proteins, the measurement of hydroxyproline concentration is not affected by this method of fixation.27 28 All studies were performed in triplicate, and the results were expressed as micrograms of hydroxyproline per milligram of dry weight of aortic tissue. Collagen concentration was calculated by multiplying the hydroxyproline concentration by 7.41.28 29 30 31

Statistical Analysis
Histological, biochemical, and ultrasonic measurements from normal and Marfan aortas were compared by use of commercially available statistical software (STATVIEW 4.0, Abacus Concepts). Nonpaired two-tailed Student's t tests were used to test the significance of differences, and statistical significance was attributed at the level of P<.05. SD values are reported.


*    Results
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*Results
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Patients with Marfan syndrome were younger than the healthy patients, but this difference was not statistically significant (33±5 versus 42±20 years for Marfan and healthy subjects, respectively, P=.14). There was no diffference in sex distribution between the two groups. The TableDown lists the clinical features of the patients with Marfan syndrome. All patients demonstrated cardiovascular and musculoskeletal manifestations of the syndrome. Ophthalmic involvement was present in approximately one half the patients. Three patients had coexisting abdominal aortic aneurysms, but none were large enough to require surgery. The indication for surgery in all patients with Marfan syndrome was ascending aortic aneurysm without dissection. Concomitant procedures included coronary artery bypass grafting in one patient found to have significant coronary artery disease and mitral valve replacement in another because of severe mitral regurgitation.


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  		Table 1. Clinical Manifestations in Patients With Marfan Syndrome

Gross and microscopic examination of both the normal and Marfan aortas revealed little to no overlying atherosclerosis in any specimen. There was no evidence of dissecting hematoma in any of the Marfan patients. The wall thickness (excluding adventitia) was 1.56 mm for Marfan aortas compared with 1.0 mm for normal aortas, which represented a statistically significant difference (P=.0005). The majority of this difference was due to increased medial thickness (1470±351 versus 972±157 mm for Marfan and normal aortas, respectively, P=.002), with no significant difference in the intimal thicknesses (34±33 versus 86±80 mm for normal and Marfan aortas, respectively, P=.14).

Histological analysis revealed striking differences in both the amount and organization of the elastin in the aneurysms from patients with Marfan syndrome compared with normal aorta. Fig 2Down shows representative sections from both normal and Marfan aortas stained for elastin and mucopolysaccharides. Normal aorta was characterized histologically by well-formed elastin fibers arranged in a lamellar pattern. Staining of the normal aorta for mucopolysaccharides revealed little to be present. The media from aneurysms in Marfan aorta, on the other hand, exhibited a profound decrease in the amount of elastin present and loss of the highly aligned and ordered lamellar arrangement. Extensive deposits of mucopolysaccharides were present throughout the media, and these changes were relatively uniform throughout the specimens.



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  		Figure 2. Top, Examples of the histological structure of normal aorta from a patient without Marfan syndrome (A) and aneurysmal aorta from a Marfan patient (B). Note the well-formed elastin fibers and their lamellar arrangement in the normal aorta. The Marfan aorta exhibits a profound decrease in the amount of elastin present and loss of the highly aligned and ordered lamellar arrangement (van Gieson stain for elastin, x160). Bottom, Examples of both normal (C) and Marfan (D) aorta stained with alcian blue. Note the large areas of mucopolysaccharide deposition (stained blue) in the Marfan tissue (alcian blue stain, x160).

Fig 3Down shows an example of the histological structure of normal aorta and its corresponding unprocessed RF data compared with matched data from an aneurysm in a patient with Marfan syndrome. Inspection of the unprocessed RF data revealed that normal aorta produces a large specular echo at the intima interface, followed by relatively high ultrasonic scattering throughout the media and less scattering from the adventitia. The RF data from Marfan aorta also differed markedly from those of normal patients. A large specular echo appeared at the intima interface, as in normal aorta, but reduced backscatter was observed throughout the remainder of the vessel wall.



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  		Figure 3. Examples of the histological structure and the corresponding unprocessed radiofrequency (RF) data of normal aorta from a patient without Marfan syndrome (left) and aneurysmal aorta from a Marfan patient (right). Normal tissue exhibits well-formed elastin fibers arranged in a lamellar fashion. RF data from the normal aorta reveal a large specular echo at the water-intima interface followed by relatively high ultrasonic scattering throughout the media. The Marfan aorta exhibits a profound decrease in the amount of elastin present and loss of the highly aligned and ordered lamellar arrangement. RF data from the abnormal Marfan aorta also exhibit a large specular echo at the water-intima interface, but the ultrasonic scattering throughout the media is greatly reduced (van Gieson stain for elastin, x250).

Fig 4Down depicts quantitative differences in integrated backscatter from the aortic media in patients with Marfan syndrome compared with normal aortas. There was significantly less backscatter from the Marfan aortas compared with normal aortas (-40.9±2.9 versus -32.6±2.2 dB for Marfan and normal aortas, respectively, P<.0001). Hydroxyproline measurements revealed no significant difference in collagen content between normal and Marfan aortas (262.7±52.7 versus 282.4±41.8 mg/g tissue for normal and Marfan aortas, respectively, P=.42) despite the large difference in backscatter.



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  		Figure 4. Scatterplot depicting the quantitative differences in integrated backscatter from the aortic media in patients with Marfan syndrome compared with healthy subjects. There was significantly less backscatter from the Marfan aortas compared with normal aortas (-40.9±2.9 vs -32.6±2.2 dB for Marfan and normal aortas, respectively, P<.0001).

The directional dependence of scattering also differed dramatically between the two tissue types. Fig 5Down shows the changes in the unprocessed RF data when the aorta is insonified from orthogonal directions for both normal and Marfan tissue. Backscatter from normal aorta decreased substantially when the media was insonified parallel compared with perpendicular to the principal axis of the elastin fibers. Marfan aorta, on the other hand, exhibited a much smaller directional dependence of scattering. Fig 6Down shows the magnitude of ultrasonic anisotropy (difference in integrated backscatter between perpendicular and parallel directions of insonification) between the tissue types. Normal aortas manifested a 15-fold greater ultrasonic anisotropy than did Marfan aortas (24.1±3.7 versus 12.4±3.3 dB for normal and Marfan aortas, respectively, P<.0001).



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  		Figure 5. Graph showing changes in the unprocessed radiofrequency data when the aorta is insonified from mutually orthogonal directions for both normal and Marfan tissue. The asterisk denotes the specular echo at the water-intima interface. Backscatter from normal aorta decreased substantially when the media was insonified parallel compared with perpendicular to the principal axis of the elastin fibers. Marfan aorta, on the other hand, exhibited a significantly smaller directional dependence of scattering.



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  		Figure 6. Bar graph showing the magnitude of ultrasonic anisotropy (difference in integrated backscatter between perpendicular and parallel directions of insonification) between tissue types. Normal aortas manifested a 15-fold greater ultrasonic anisotropy than did Marfan aortas (P<.0001).


*    Discussion
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 up arrowAbstract
 up arrowIntroduction
 up arrowMethods
up arrowResults
*Discussion
down arrowReferences
 
We have shown that ultrasonic tissue characterization with high-frequency ultrasound sensitively detects changes in vessel wall composition and organization in aortas from patients with Marfan syndrome. Aortic segments from these patients manifested a significant decrease in integrated backscatter compared with normal aorta (approximately 8 dB, or greater than a 6-fold decrease in scattering). A 15-fold reduction in the ultrasonic anisotropy of Marfan tissue was observed, which suggests a marked disorganization of the 3D architecture of these aortas. These data support the hypothesis that high-frequency ultrasonic tissue characterization may be potentially useful for identifying abnormalities of vessel wall composition, architecture, and material properties.

Previous observational studies by other laboratories showed that normal muscular and elastic arteries exhibit a wide range of scattering behavior when imaged with intravascular ultrasound.32 33 Recent data from our laboratory demonstrated the important role played by both collagen and elastin in the scattering of high-frequency ultrasound by normal arterial tissue.18 Systematic interrogation of normal elastic, transitional, and muscular arteries from pigs revealed linear correlations between integrated backscatter and both elastin and collagen. The presence of smooth muscle cells was inversely correlated with backscatter.

In the present study, aneurysmal aortic specimens from patients with Marfan syndrome demonstrated significantly less backscatter and anisotropy than did normal aortic specimens, despite a similar relative concentration of collagen in the vessel wall. However, the fibrous tissue that constituted the matrix of Marfan aortas did not appear well organized or aligned at the light microscopic level. We also observed that the aortic elastin content differed markedly in patients with Marfan syndrome (see Fig 2Up). Thus, the observed decrease in integrated backscatter may be due, at least in part, to a decrease in the elastin content of the Marfan tissue. In addition, structural disorganization of fibrous matrix elements, such as collagen and elastin, also may contribute to the decreased backscatter observed in Marfan aortas.

Changes in the aortic media of patients with Marfan syndrome comprise not only alterations in the amount and structure of elastin fibers but also changes in the amount and composition of other extracellular matrix elements.34 The progressive development of cystic changes in the aortic media is associated with the deposition of mucopolysaccharides. The tissue from the patients with Marfan syndrome in our study displayed areas of cystic change and extensive pools of mucopolysaccharides that stained with alcian blue (Fig 2Up). It is likely that this homogeneous matrix material scatters little ultrasound and is responsible in part for the decreased backscatter seen in the Marfan aortas. The Young's moduli for collagen and elastin are on the order of 109 and 106 dynes/cm2, respectively, whereas other viscoelastic materials deposited in the matrix exhibit substantially smaller elastic moduli.35 36 For example, hyaluronic acid exhibits a dynamic storage modulus of approximately 102 dynes/cm2.36 Because ultrasonic scattering is determined in part by elastic stiffness and mass density,37 these local variations in elastic properties may exert a profound influence on scattering behavior from Marfan aorta. The interaction of ultrasound with glycoprotein and mucopolysaccharide matrix components requires further delineation with respect to differences in their viscoelastic properties compared with those of collagen and elastin.

The decreased ultrasonic anisotropy in Marfan aorta implies an alteration of both structural organization and mechanical behavior. The mechanical properties of aortic tissue depend on both the amount and organization of collagen and elastin within the vessel wall.36 In normal aorta, these fibers are laid down primarily along stress lines in a circumferential pattern.36 We hypothesize that the highly ordered and aligned nature of these medial components is important for providing the elastic stiffness required to resist the hemodynamic load imposed on the aorta. Because abnormalities in tissue organization are likely to influence the biomechanical properties of the aorta, it is plausible that detection of the extent of matrix disorganization would be useful for monitoring disease progression.

Other studies have shown that cystic medial degeneration with elastin fiber fragmentation occurs in aortic aneurysms from causes other than Marfan syndrome.38 39 40 41 Normal aging can produce similar changes in aortic structure, which may represent vessel wall remodeling secondary to repeated hemodynamic trauma.39 42 We anticipate that changes in ultrasonic backscatter and anisotropy would accompany any pathological process that produces similar ultrastructural changes in the vessel wall. Preliminary results from our laboratory suggest that the changes in ultrasonic scattering from non-Marfan aneurysmal tissues are qualitatively similar to those observed in Marfan patients (D.R., unpublished data). This concordance of findings in different types of aneurysms lends support to the hypothesis that specific composition and organization of matrix elements represent principal determinants of ultrasonic scattering from vessels.

Potential Limitations
Several potential limitations of this study merit discussion. The tissue used in this study was from patients with enough aneurysmal dilation to warrant surgical intervention; therefore, these data may represent a worst-case scenario. It is not known whether similar changes in scattering would be present in patients with lesser degrees of aortic involvment. We did not have access to tissue from patients with less severe aortic dilation and could not test this hypothesis.

The nominal frequency used in our study was 50 MHz, which is somewhat higher than that currently used for clinical intravascular imaging (20 to 40 MHz). Recently, Lockwood et al32 successfully implemented an intravascular imaging system operating at 45 MHz, suggesting that this frequency has potential clinical utility. It is unlikely that frequencies much higher than 50 MHz will be clinically useful, however, because of the significant attenuation of ultrasound in this frequency range. The scattering effects of blood itself may be important at these higher frequencies and appear as excess attenuation that could influence clinical interpretation of backscatter from vascular tissue.43 The effects of cardiac cycle–dependent variations of scattering from blood may also require compensation.

Patients with Marfan syndrome were modestly younger than the healthy patients in the study, which raises the possibility that the difference in age contributed to the observed differences in scattering. However, the physiological significance of the 10-year difference in age is not clear. Previous pathological studies suggested that aging may cause degeneration of the aortic media.39 42 One would hypothesize, therefore, that the samples from the healthy older patients would scatter less ultrasound than samples from younger patients based on age alone, and this might make the difference between Marfan and normal aortas less apparent. However, we documented the converse (ie, sixfold less scattering from the Marfan aortas), making the age difference an implausible explanation for the observed decreased scattering.

The effects of formalin fixation on the backscatter from vascular tissue have not been firmly established. Several reports indicate that fixation with formalin does not appreciably alter the scattering properties of most tissues.44 45 Potkin et al46 recently reported that the apparent scattering behavior of arterial tissue was not significantly altered by formalin fixation. We also have observed no significant change in integrated backscatter after formalin fixation, but we have observed a modest increase in attenuation (unpublished observation). Thus, these data should provide an accurate representation of the scattering behavior from the tissues examined.

The method for measuring the magnitude of ultrasonic anisotropy entailed insonification from orthogonal views. This procedure may not be feasible in vivo because imaging parallel to the circumference of the vessel cannot be achieved. However, imaging from angles other than perpendicular frequently occurs in clinical intravascular imaging. Previous studies by de Kroon et al47 48 showed that the angle dependence of scattering is different for different vessel types, which suggests that the angle dependence of scattering may serve as a useful index of underlying tissue architecture.

Clinical Implications
Our data suggest that high-frequency tissue characterization may be useful for detecting pathological changes in the aortas of patients with Marfan syndrome. At present, methods such as transthoracic and transesophageal echocardiography, computed tomography, and magnetic resonance imaging provide data only on changes in the luminal dimension and the presence or absence of dissection. These modalities provide no direct data on the intrinsic structure and material properties of the aortic wall itself. Tissue characterization may play a complementary role to these other modalities by providing a novel quantitative assessment of the altered biophysical properties of affected tissue. We speculate that this technique may be applicable longitudinally to permit detection of early changes in aortic wall composition and structure. Vascular tissue characterization may also be useful for evaluating other types of aortic aneurysms and may serve an adjunctive role in monitoring the temporal progression of selected degenerative aortic diseases.


*    Acknowledgments
 
This work was supported in part by grant HL-42950 from the National Institutes of Health, an Established Investigator Award from the American Heart Association (S.A.W.), and an Affiliate Fellowship Award from the Missouri Affiliate of the American Heart Association (D.R.). We acknowledge the technical assistance of Michael Scott in performing the hydroxyproline assays. We are also indebted to Dr James Miller for helpful discussions.


*    Footnotes
 
Reprint requests to Samuel A. Wickline, MD, Jewish Hospital at Washington University School of Medicine, Division of Cardiology, 216 S Kingshighway, St Louis, MO 63178.

Received June 17, 1994; accepted August 9, 1994.


*    References
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up arrowResults
up arrowDiscussion
*References
 

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