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

Abstract

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. 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. 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.