SENSITIVE DETECTION OF ABNORMAL AORTIC ARCHITECTURE IN MARFAN-SYNDROME WITH HIGH-FREQUENCY ULTRASONIC TISSUE CHARACTERIZATION

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. O ur goal was to use high-frequency ultrasonic tissue characterization t o identify these structural changes in abnormal aorta from patients wi th Marfan syndrome. We measured integrated backscatter and anisotropy of backscatter of ultrasound from specimens of aorta from patients wit h Marfan syndrome undergoing aortic root replacement and compared thes e values with those from aortic specimens of patients without clinical aortic pathology. Methods and Results Aortic tissue was obtained at t he time of surgery from 11 patients with Marfan syndrome undergoing re pair of an aortic aneurysm or dissection. Normal tissue was obtained a t the time of autopsy from 8 patients without evidence of aortic disea se. 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 collage n 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 he althy subjects, respectively, P<.0001). No significant difference in c ollagen concentrations was observed between normal and Marfan aorta (2 62.7+/-52.7 versus 282.4+/-41.8 mg/g tissue for normal and Marfan aort as, respectively, P=.42), despite the large difference in backscatter. Histological analysis revealed striking differences in both the amoun t and organization of the elastin in the aortic aneurysm segments from patients with Marfan syndrome compared with normal aorta. Normal aort a was characterized by well-formed elastin fibers arranged in a lamell ar pattern. The media from aneurysms in Marfan aorta exhibited a profo und decrease in elastin content that was associated with loss of the h ighly aligned and ordered lamellar arrangement. The directional depend ence of scattering, or ultrasonic anisotropy, also differed dramatical ly between the two tissue types. Backscatter from normal aorta decreas ed substantially when the media was insonified parallel compared with perpendicular to the principal axis of the elastin fibers. Marfan aort a exhibited a much smaller directional dependence of scattering. Norma l aortas manifested a 14-fold greater ultrasonic anisotropy than did M arfan aortas (24.1+/-3.7 versus 12.4+/-3.3 dB for normal and Marfan ao rtas, P<.0001), which is indicative of the profound extent of matrix d isorganization in Marfan syndrome. Conclusions These data show that hi gh-frequency ultrasonic tissue characterization sensitively detects ch anges in vessel wall composition and organization that occur in the ao rta of patients with Marfan syndrome. Aortic segments from these patie nts manifested a significant decrease in integrated backscatter compar ed with normal aorta (approximately 8 dB, or greater than a B-fold dec rease in scattering). A 15-fold reduction in the ultrasonic anisotropy of Marfan tissue was observed, which suggests a marked disorganizatio n of the 3D architecture of these aortas. These data support the hypot hesis that high-frequency ultrasonic tissue characterization may be us eful for identifying abnormalities of vessel wall composition, archite cture, and material properties.