Ultrasound tissue characterization with measurement of backscatter has been employed in numerous experimental and clinical studies of cardiac pathology, yet the cellular components responsible for scattering from cardiac tissues have not been unequivocally identified. This laboratory has proposed a mathematical model for myocardial backscatter that postulates the fibrous extracellular matrix (ECM) as a significant determinant of backscatter. To demonstrate the importance of ECM, this group sought to determine whether measurements of backscatter from the isolated ECM could reproduce the known directional dependence, or anisotropy of backscatter, from intact cardiac tissues in vitro. Segments of left ventricular free wall from ten formalin fixed porcine hearts were insonified at 50 MHz, traversing the heart wall from endo- to epicardium to measure the anisotropy of myocardial backscatter, defined as the difference between peak (perpendicular to fibers) and trough (parallel to fibers) backscatter amplitude. The tissue segments were then treated with 10% NaOH to dissolve all of the cellular components, leaving only the intact ECM. Scanning electron micrographs (SEM) were obtained of tissue sections to reveal complete digestion of the cellular elements. The dimensions of the residual voids resulting from cell digestion were approximately the diameter of the intact myocytes (10–30 μm). These samples were reinsonified after seven days of treatment to compare the anisotropy of integrated backscatter. The magnitude of anisotropy of backscatter changed from to for intact as compared with digested specimens. Because digestion of the myocardium leaves only extracellular sources of ultrasonic scattering, and because the isolated ECM exhibits similar ultrasonic anisotropy as does the intact myocardium, it is concluded that there is a direct association between the ECM and the anisotropy of backscatter within intact tissue. Thus, it is suggested that ultrasonic tissue characterization represents a potentially clinically applicable method for delineating the structure and function of the ECM.
REFERENCES
1.
K. T.
Weber
, “Cardiac intersitium in health and disease: The fibrillar collagen network
,” J. Am. Coll. Cardiol.
13
, 1637
–1652
(1989
).2.
S. L.-Y.
Woo
, P. O.
Newton
, D. A.
MacKenna
, and R. M.
Lyon
, “A comparative evaluation of the mechanical properties of the rabbit medial collateral and anterior cruciate ligaments
,” J. Biomech.
25
, 377
–386
(1992
).3.
J. B.
Caulfield
and T. K.
Borg
, “The collagen network of the heart
,” Lab. Invest.
40
, 364
–372
(1979
).4.
D. A.
MacKenna
, S. M.
Vaplon
, and A. D.
McCulloch
, “Microstructural model of perimysial collagen fibers for resting myocardial mechanics during ventricular filling
,” Am. J. Physiol.
273
, H1576
–1586
(1997
).5.
D. A.
MacKenna
, J. H.
Omens
, and J. W.
Covell
, “Perimysial collagen fibers uncoil rather than stretch during diastolic filling
,” Basic Res. Cardiol.
91
, 112
–122
(1996
).6.
C. S.
Hall
, E. D.
Verdonk
, S. A.
Wickline
, J. E.
Perez
, and J. G.
Miller
, “Anisotropy of the apparent frequency dependence of backscatter in formalin fixed human myocardium
,” J. Acoust. Soc. Am.
101
, 563
–568
(1997
).7.
E. D.
Verdonk
, B. K.
Hoffmeister
, S. A.
Wickline
, and J. G.
Miller
, “Anisotropy of the slope of ultrasonic attenuation in formalin fixed human myocardium
,” J. Acoust. Soc. Am.
99
, 3837
–3843
(1996
).8.
J. G.
Mottley
and J. G.
Miller
, “Anisotropy of the ultrasonic backscatter of myocardial tissue: I. Theory and measurements in vitro
,” J. Acoust. Soc. Am.
83
, 755
–761
(1988
).9.
D.
Recchia
, C. S.
Hall
, R. K.
Shepherd
, J. G.
Miller
, and S. A.
Wickline
, “Mechanisms of the view-dependence of ultrasonic backscatter from normal myocardium
,” IEEE Trans. Ultrason. Ferroelectr. Freq.
42
, 91
–98
(1995
).10.
J.
Naito
et al., “Myocardial integrated ultrasonic backscatter in patients with old myocardial infarction: Comparison with radionuclide evaluation
,” Am. Heart J.
132
, 54
–60
(1996
).11.
E. D.
Verdonk
, S. A.
Wickline
, and J. G.
Miller
, “Anisotropy of ultrasonic velocity and elastic properties in normal human myocardium
,” J. Acoust. Soc. Am.
92
, 3039
–3050
(1992
).12.
B. K.
Hoffmeister
, S. M.
Handley
, S. A.
Wickline
, and J. G.
Miller
, “Ultrasonic determination of the anisotropy of Young’s modulus of fixed tendon and fixed myocardium
,” J. Acoust. Soc. Am.
100
, 3933
–3940
(1996
).13.
D.
Recchia
, J. G.
Miller
, and S. A.
Wickline
, “Quantification of ultrasonic anisotropy in normal myocardium with lateral gain compensation of two-dimensional integrated backscatter images
,” Ultrasound Med. Biol.
19
, 497
–505
(1993
).14.
A. E.
Finch-Johnston
, H. M.
Gussak
, J.
Mobley
, M. R.
Holland
, O.
Petrovic
, J. E.
Perez
, and J. G.
Miller
, “Effect of time delay on the apparent magnitude of cyclic variation of myocardial ultrasonic backscatter in standard echocardiographic views
,” Ultrason. Imaging
17
, 77
(1995
).15.
D. A.
Lythall
, R. B.
Logan-Sinclair
, C. J.
Ilsley
, S. S.
Kushwaha
, M. H.
Yacoub
, and D. G.
Gibson
, “Relation between cyclic variation in echo amplitude and segmental contraction in normal and abnormal hearts
,” Br. Heart J.
66
, 268
–276
(1991
).16.
M. R.
Milunski
, K. A.
Wear
, J. E.
Perez
, B. E.
Sobel
, J. G.
Miller
, and S. A.
Wickline
, “The effect of frequency on the magnitude of cyclic variation of backscatter in dogs and its implications for prompt detection of the immediate consequences of myocardial ischemia
,” Circulation
80
, II
-565
(1989
).17.
A. F. v. d.
Steen
, H.
Rijsterborgh
, C. T.
Lancee
, F.
Mastik
, R.
Krams
, P. D.
Verdouw
, J. R.
Roelandt
, and N.
Bom
, “Influence of data processing on cyclic variation of integrated backscatter and wall thickness in stunned porcine myocardium
,” Ultrasound Med. Biol.
23
, 405
–414
(1997
).18.
B. F.
Vandenberg
, L.
Rath
, T. A.
Shoup
, R. E.
Kerber
, S. M.
Collins
, and D. J.
Skorton
, “Cyclic variation in normal myocardium is view dependent: Clinical studies with a real time backscatter imaging system
,” J. Am. Soc. Echocardiogr
2
, 308
–314
(1989
).19.
K. A.
Wear
, M. R.
Milunski
, S. A.
Wickline
, J. E.
Perez
, B. E.
Sobel
, and J. G.
Miller
, “The effect of frequency on the magnitude of cyclic variation of backscatter in dogs and implications for prompt detection of acute myocardial ischemia
,” IEEE Trans. Ultrason. Ferroelectr. Freq.
38
, 498
–502
(1991
).20.
M. R.
Milunski
, G. A.
Mohr
, K. A.
Wear
, B. E.
Sobel
, J. G.
Miller
, and S. A.
Wickline
, “Early identification with integrated backscatter of viable but stunned myocardium in dogs
,” J. Am. Coll. Cardiol.
14
, 462
–471
(1989
).21.
S. A.
Wickline
, L. J.
Thomas
, J. G.
Miller
, B. E.
Sobel
, and J. E.
Perez
, “Sensitive detection of the effects of reperfusion on myocardium by ultrasonic tissue characterization with integrated backscatter
,” Circulation
74
, 389
–400
(1986
).22.
J. E.
Perez
, J. B.
McGill
, J. V.
Santiago
, K. B.
Schechtman
, A. D.
Waggoner
, J. G.
Miller
, and B. E.
Sobel
, “Abnormal myocardial acoustic properties in diabetic patients and their correlation with the severity of disease
,” J. Am. Coll. Cardiol.
19
, 1154
–1162
(1992
).23.
S.
Takiuchi
, H.
Ito
, K.
Iwakura
, Y.
Taniyama
, N.
Nishikawa
, T.
Masuyama
, M.
Hori
, Y.
Higashino
, K.
Fujii
, and T.
Minamino
, “Ultrasonic tissue characterization predicts myocardial viability in early stage of reperfused acute myocardial infarction
,” Circulation
97
, 356
–362
(1998
).24.
J. H.
Rose
, M. R.
Kaufmann
, S. A.
Wickline
, C. S.
Hall
, and J. G.
Miller
, “A proposed microscopic elastic wave theory for ultrasonic backscatter from myocardial tissue
,” J. Acoust. Soc. Am.
97
, 656
–668
(1994
).25.
S. A.
Wickline
, E. D.
Verdonk
, and J. G.
Miller
, “Three-dimensional characterization of human ventricular myofiber architecture by ultrasonic backscatter
,” J. Clin. Invest.
88
, 438
–446
(1991
).26.
K. N.
Kumar
and J. G.
Mottley
, “Quantitative modeling of the anisotropy of ultrasonic backscatter from canine myocardium
,” IEEE Trans. Ultrason. Ferroelectr. Freq.
41
, 441
(1994
).27.
L.
Landini
and M. F.
Santarelli
, “A regression model of ultrasound reflectivity from normal myocardium
,” Med. Eng. Phys.
17
, 141
–144
(1995
).28.
M. F.
Santarelli
and L.
Landini
, “A model of ultrasound backscatter for the assessment of myocardial tissue structure and architecture
,” IEEE Trans. Biomed. Eng.
43
, 901
–911
(1996
).29.
D. T.
Linker
, B. A. J.
Angelsen
, and R. L.
Popp
, “Autocorrelation length of normal and myopathic human myocardium measured by acoustic microscopy: Implications for clinical ultrasonic tissue characterization
,” Ultrasound Med. Biol.
16
, 793
–799
(1990
).30.
O.
Ohtani
, T.
Ushiki
, T.
Taguchi
, and A.
Kikuta
, “Collagen fibrillar networks as skeletal frameworks: A demonstration by cell-maceration/scanning electron microscope method
,” Arch. Histol. Cytol.
51
, 249
–261
(1988
).31.
S. A.
Wickline
, L. J.
Thomas
III, J. G.
Miller
, B. E.
Sobel
, and J. E.
Perez
, “A relationship between ultrasonic integrated backscatter and myocardial contractile function
,” J. Clin. Invest.
76
, 2151
–2160
(1985
).32.
E. L.
Madsen
, M. F.
Insana
, and J. A.
Zagzebski
, “Method of data reduction for accurate determination of acoustic backscatter coefficients
,” J. Acoust. Soc. Am.
76
, 913
–923
(1984
).33.
F. G.
Spinale
, J. L.
Zellner
, W. S.
Johnson
, D. M.
Eble
, and P. D.
Munyer
, “Cellular and extracellular remodeling with the development and recovery from tachycardia-induced cardiomyopathy—changes in fibrillar collagen, myocyte adhesion capacity and proteoglycans
,” J. Mol. Cell. Cardiol.
28
, 1591
–1608
(1996
).34.
M.
Zhao
, H.
Zhang
, T. F.
Robinson
, S. M.
Factor
, E. H.
Sonnenblick
, and C.
Eng
, “Profound structural alterations of the extracellular collagen matrix in postischemic dysfunctional (“stunned”) but viable myocardium
,” J. Am. Coll. Cardiol.
10
, 1322
–1334
(1987
).35.
S. A.
Wickline
, E. D.
Verdonk
, A. K.
Wong
, R. K.
Shepard
, and J. G.
Miller
, “Structural remodeling of human myocardial tissue after infarction
,” Circulation
85
, 259
–268
(1992
).36.
E. D.
Schleicher
, E.
Wagner
, and A. G.
Nerlich
, “Increased accumulation of the glycoxidation product N-epsilon (carboxymethyl) lysine in human tissues in diabetes and aging
,” J. Clin. Invest.
99
, 457
–468
(1997
).37.
D. R.
Sell
, M. A.
Lane
, W. A.
Johnson
, E. J.
Masoro
, O. B.
Mock
, K. M.
Reiser
, J. F.
Fogarty
, R. G.
Cutler
, D. K.
Ingram
, G. S.
Roth
, and V. M.
Monnier
, “Longevity and the genetic determination of collagen glycoxidation kinetics in mammalian senescence
,” Proc. Natl. Acad. Sci. USA
93
, 485
–490
(1996
).38.
T. F.
Robinson
, L.
Cohen-Gould
, R. M.
Remily
, J. M.
Capasso
, and S. M.
Factor
, “Extracellular structures in heart muscle
,” Adv. Myocardiol
5
, 243
–255
(1985
).39.
G. G.
Ahumada
and J. E.
Saffitz
, “Fibronectin in rat heart: A link between cardiac myocytes and collagen
,” J. Histochem. Cytochem.
32
, 383
–388
(1984
).40.
E.
Schwartz
, S.
Goldfischer
, B.
Coltoff-Schiller
, and O. O.
Blumenfeld
, “Extracellular matrix microfibrils are composed of core proteins coated with fibronectin
,” J. Histochem. Cytochem.
33
, 268
–274
(1985
).41.
T. F.
Robinson
, S. M.
Factor
, J. M.
Capasso
, B. A.
Wittenberg
, O. O.
Blumenfeld
, and S.
Seifter
, “Morphology, composition, and function of struts between cardiac myocytes of rate and hamster
,” Cell Tissue Res.
249
, 247
–255
(1987
).
This content is only available via PDF.
© 2000 Acoustical Society of America.
2000
Acoustical Society of America
You do not currently have access to this content.
