© 2003 by European Society of Cardiology
Copyright © 2003, The European Society of Cardiology
Myocardial Tissue Characterization in Echocardiography with Videodensitometry: Evaluation of a New Semi-automatic Software Applied on a Population of Hypertensive Patients
1Hôpital Saint-André, Bordeaux, France
2IôDP, 36 rue du chemin vert, 75011 Paris, France
Received 30 September 2002; received in revised form 12 February 2003; .
| Abstract |
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Background: The interactions between ultrasound and cardiac muscle can be exploited to characterize abnormalities of myocardial structure in echocardiography. Two different methods permit an objective assessment of myocardial tissue characterization: analysis of the radiofrequency signal and videodensitometry. We conducted a videodensitometric study using a new practical semi-automatic software applied on digital signal to evaluate gray level cyclic variations of myocardial walls. The aim was to determine parameters differentiating healthy and hypertrophic myocardium in hypertensive patients.
Methods and results: Echocardiographic examinations were performed on 30 hypertensives vs 30 healthy controls using second harmonic imaging. Dynamic 2D sequences were recorded in digital form and transferred on computer. Region of interest (ROI) was selected on interventricular septum (IVS) and the software automatically analyzed its systolo-diastolic displacements. ROI echo intensity and its cyclic variations were computed. Values were normalized with blood backscatter. The hypertensives had a smaller amplitude of gray level cyclic variation than did the controls (22±6 vs 27±11; P=0.02), and this parameter was correlated in multivariate analysis with left ventricle fractional shortening (P=0.032) and diastolic pressure(P=0.014).
Conclusions: Magnitude of gray level cyclic variation of IVS can be studied easily with this new semi-automatic software, is altered in hypertensives and correlated with parameters of systolic function.
Keywords: Tissue characterization; echocardiography; videodensitometry; arterial hypertension; acoustic reflectivity; left ventricular hypertrophy
| Introduction |
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A new perspective for echocardiographic examination has emerged over the last 15 years due to advances in digital signal processing, namely the ability to examine the structure of the myocardium from the acoustic properties of sound-reflecting tissues. The tissue reflectivity of the myocardial walls, which is closely linked to its histological structure, can now be determined in an operator-independent manner[1–6]. Two different techniques are currently available:
- 1. The gold standard but still within the domain of research: direct analysis of the raw radiofrequency signal from the transducer.
- 2. Videodensitometric analysis that exploits methods of statistical quantification of the normal echocardiographic images to determine mean gray levels of a selected region of interest (ROI).
- 2. Videodensitometric analysis that exploits methods of statistical quantification of the normal echocardiographic images to determine mean gray levels of a selected region of interest (ROI).
Both methods have been applied with encouraging results to various pathological states, in particular to ischemic[7,8], dilated[9–11], and hypertrophic cardiomyopathy[12–15]. We studied here myocardial tissue characterization with a modern videodensitometric method applied in a population of hypertensives patients:
- Echocardiographic 2D sequences were recorded for the first time with second harmonic imaging mode.
- Sequences were recorded in digital form (on magneto-optical disks) directly from the echocardiograph prior to the analog conversion that produces the final image.
- The digital signals were then processed using a new prototype software that automatically analyzed myocardial wall systolo-diastolic displacements and measured gray levels of a ROI following its movements during the whole cardiac cycle.
- Sequences were recorded in digital form (on magneto-optical disks) directly from the echocardiograph prior to the analog conversion that produces the final image.
The objectives of this study were to evaluate the feasibility and the reproducibility of the measurements, and to determine parameters of acoustic reflectivity that could be employed to discriminate between healthy and hypertrophic myocardium in patients with high blood pressure (BP).
| Methods |
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General Protocol
Thirty consecutive patients (17 men, 13 women, mean age 56±17 years), referred for investigation of hypertension were included in group A (hypertension group). Some of them were treated with calcium antagonists or
-blockers. None received β-blockers, diuretics, or ACE inhibitors. Group B consisted of 30 healthy volunteers (19 men, 11 women, mean age 53±13 years) without any cardiovascular medication. Diabetics, patients with renal failure, heart disease (whether dilated, ischemic, or with primary hypertrophy or valve disorders), atrial fibrillation were excluded.
Echographic Procedures
All examinations were conducted by the same operator on a Acuson echocardiograph (Sequoia) operating in second harmonic mode, with an emission frequency of 1.75 MHz and reception tuned to 3.5 MHz. The dynamic range was fixed at 85 dB. Emission power, focal plane, filters, and overall gain were adjusted to minimize noise on the image. To avoid bias in the analysis of the results, the manual adjustment for the depth gain compensation was kept at zero (linear curve).
The operator recorded an M-mode tracing (100 mm/s) in parasternal short axis view enabling measurement of ventricular diameter and wall thickness. Only patients with good recordings were included. According to the recommendations of the ASE, we measured the interventricular septum thickness (IVS), posterior wall thickness (PW), end diastolic diameter (EDD) and end systolic diameter (ESD) of the left ventricle. We calculated the fractional shortening (FS), the thickening of the IVS (IVS Th) and of the PW (PW Th), the left ventricular mass (LVM) indexed for body surface area (LVM-I) according to the recommendations of Devereux[16,17]. Left ventricular hypertrophy (LVH) was defined as LVM-I above 134 g/m2 in men and 110 g/m2 in women.
Tissue Characterization
For tissue characterization, the operator zoomed in on a parasternal short axis view: this function concentrates all lines of the image on a smaller area, thereby increasing resolution. The gamma curve was identical for all patients. A 4 s 2D sequence was recorded on the hard disk (at 25 images/s, in DICOM format with a 20-fold JPEG compression), then transferred to a Power Mac PC running the purpose-designed software developed by IôDP (Paris, France).
After calibrating the image, the operator manually positioned a rectangular ROI of 10 mm width and variable length to cover the entire left ventricle (Fig. 1). The software analyzed the echogenicity of the ROI line by line, image by image, over the entire sequence, and then displayed a time-motion (TM) representation of the mean gray levels using a scale from 0 to 256. The image resolution was 4 pixels/mm.
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On this TM image, the software (Fig. 2) carried out a semi-automatic detection of endocardial displacements, then followed the boundaries of the IVS by two parallel curves (Fig. 3). Within this interval, gray level values of the whole pixels were used to establish automatically the temporal cyclic variation in gray levels. We verified that the curves did not include specular reflections from the endocardium. A sample positioned in the left ventricular cavity near the IVS analyzed gray levels of blood. We thus obtained a sinusoidal curve of the variations in gray levels (Fig. 4). Data were transferred to an Excel spreadsheet.
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Parameters of Levels of Gray
Two types of parameters were analyzed from the sinusoidal curves collected from the IVS:
- Three parameters of levels of gray were computed: the median gray level of the curve, the peak gray level (mean of five highest values), the minimal gray level (mean of five lowest values). Values were normalized by subtracting the level of gray of blood recorded close to the IVS.
- The cyclic variation in amplitude of gray levels represented by the difference between the peak and the minimal value of the curve. This index being that of a change is thus independent of the gain of the scanner.
- The cyclic variation in amplitude of gray levels represented by the difference between the peak and the minimal value of the curve. This index being that of a change is thus independent of the gain of the scanner.
Statistics
Data were analyzed using SPSS software. General details of the two groups are expressed as means and standard deviations. Means were compared using Student's t-test. For the parameters of tissue characterization exhibiting significant differences between the two groups, we conducted a multivariate analysis of the influence of sex, age, weight, height, BP, wall thickness and LVM-I, and parameters of overall and regional systolic function.
The reliability of the videodensitometric software was evaluated from the intra-observer reproducibility on a sample of 20 patients taken at random. In each patient, two sequences were recorded and then processed by the software. We calculated the coefficient of correlation, the mean differences, and especially the standard deviation of the difference and the coefficient of variation.
Finally, we compared on a control group of 10 patients, values of echogenicity from sequences recorded successively in second harmonic imaging and fundamental frequency with identical echographic settings.
| Results |
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Main data of patients from the two groups are listed in Table 1. The patients in group A had significantly higher BP, thicker myocardial walls, and higher LVM than did the controls (76% of the hypertensives (23/30) had LVH).
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The values of echogenicity of walls and blood are shown in Table 2. The raw echogenicity of IVS did not differ between the two groups. The maximal values and medians of the corrected values were higher in the control group (P=0.021 and P=0.029, respectively). The amplitude of variation in gray levels from the IVS was greater in controls than in the hypertensives (P=0.02).
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In the multivariate regression analysis, the amplitude of variation in levels of gray of the IVS or IVS delta was correlated positively with FS (P=0.032, correlation coefficient R=0.24) and negatively with diastolic BP (P=0.014; R=0.43) (Fig. 5).
The second harmonic mode sequences produced higher values of raw and corrected echogenicity from the IVS than the fundamental frequency (Table 3; P<0.001). The same was found for the echogenicity of blood. However, the amplitude of variation in gray levels did not differ significantly between the two modes.
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The reliability of the software was evaluated by calculating the reproducibility of the measurements on two separate occasions in 20 patients (Table 4) for the following parameters:
- Median corrected echogenicity of the IVS,
- Amplitude of variation of the IVS.
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For the median echogenicity, linear regression produced a correlation coefficient of 0.99 for the IVS. The mean difference was 0.8±1.9. For the amplitude of variation, the correlation coefficient was 0.91 with mean differences of 1.2±2.5.
| Discussion |
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The reflected ultrasonic signal comes from the structural components of cardiac muscle. This analog signal is then analyzed by the processing systems in the echocardiographs. One of the ambitions of echocardiography is to exploit this signal for a structural analysis of the myocardium. The first studies in videodensitometry were based on the analysis of 2D echo sequences recorded on S-VHS tapes and then digitized on computers before gray level analysis. This method suffers from the digital analog conversion phase. Here we conducted a study on an echocardiograph in which we could collect digital signal directly on magneto-optical disks upstream to the scan converter.
We focused on IVS because as many authors we consider that it represents the reference wall for tissue characterization being close to the probe and perpendicular to US beam. Ultrasonic waves interact with constituents of the myocardium by Rayleigh scattering if they are close to or shorter than the emission wavelength. O'Brien et al.[4] compared acoustic reflectivity with the histological structure of the myocardium in autopsied dogs. He concluded that myocardial reflectivity stemmed from small reflecting structures on the ultra-structural scale: elements of myofibrils and connective tissue. Studies conducted on pathological myocardium, both in animals[1,18] and humans[6,19–21] have demonstrated an increase in reflectivity of the ischemic[8], hypertrophic[5], or dilated myocardium[3,9]. This hyper-reflectivity is related in a proportional manner to the increased amount of collagen. Echographic tissue characterization thus provides an indirect evaluation of the extent of myocardial fibrosis. In primary hypertrophic cardiomyopathies[5,14], a disorder of myocardial muscle fibers may also enhance reflectivity.
Various pathologies[14] or physiological states (athlete's heart)[13,22] can induce LVH. Numerous studies have been devoted to characterization of myocardial tissues in such conditions by analysis of backscatter (IBS) or videodensitometry. The largest post-hypertensive LVH series to date is that of Lucarini et al.[23] who found a weak correlation between LVM-I and the IBS of the IVS in 88 hypertensive patients. Moreover, in the group with marked hypertrophy, values of IBS were significantly higher than in the hypertensive patients without hypertrophy (P<0.0001) or in those with slight to moderate hypertrophy (P<0.02). Other studies[12,24,25] have failed to find any differences in reflectivity between healthy controls and hypertensives probably because the latter only had a slight to moderate hypertension. In agreement with literature reports, we observed that the raw echogenicity of the IVS did not differ between hypertensives and controls.
Many authors[15,24,26,27] have noted a systolo-diastolic cyclic variation (CV-IBS) in myocardial reflectivity over the cardiac cycle with a zenith at the end of diastole and a nadir at the end of systole[28,29]. This appears to be of multi-factorial origin, related to both the functional and structural properties of the myocardium. Several authors[24,26,29] have shown that the cyclic variations in the healthy heart are greater than in those with LVH. Cyclic variations have also been linked to parameters of systolic function[27,30,31]. In the present study, the multivariate analysis showed that the FS was positively correlated with the amplitude of variation in gray level of IVS and that this amplitude was altered in hypertensives. In agreement with other authors, we did not find any difference on the PW analysis.
The position and the size of the ROI are two important considerations. The ROI must be placed over the myocardium and not overlap the adjacent endocardium or pericardium. A major problem for CV-IBS analysis is that it is necessary to reposition the ROI manually in most echocardiographs as done in most recent studies. Our new software is able to determine automatically myocardial displacements and then to analyze myocardial walls echogenicity at each time of the cardiac cycle, on each frame of the sequence without manual reposition of the ROI. It is important to define a ROI that provides the maximum amount of information which depend not only on size but more particularly on the definition of the image. The width of the ROI we used is similar to what was reported by others, but with a better definition (4 pixels/mm2) thanks to the zoom function of the Acuson Sequoia that concentrates all pixels over a smaller region.
The attenuation of the ultrasound varies from patient to patient. Schwartz et al.[32] observed a higher attenuation at higher emission frequencies, the further away the structure was from the collector. Lattanzi et al.[13,14] has proposed correcting the value of the IBS by multiplying it by a factor representing the product of the coefficient of attenuation and the thickness of tissues through which the beam passes. Other authors suggest normalizing the echogenicity of walls compared to reference structures. Some have employed the pericardium[3,13,23], but this reference presents several potential drawbacks: (1) in videodensitometry, the operator cannot control the automatic amplification in depth applied in some machines, so the pericardium positioned far from IVS is submitted to a higher amplification; (2) the pericardium is a very narrow structure, and it is difficult to position a small ROI without including neighboring structures; (3) finally, the gray level of the pericardium is frequently near the maximal value of 256. Therefore, if the gain is increased, this value reaches a ceiling of 256, while the echogenicity of the myocardium continues to increase.
Blood represents a second reference structure available[24] with many advantages. First, it is easier to position a larger ROI in the left ventricular cavity than on the pericardium. Second, it is also convenient, as we did, to position the ROI just near the wall under study. This limits the influence of automatic depth gain compensation often performed by echocardiographs. And finally, it also takes account of the attenuation of echoes, which will tend to be similar for the tissues and neighboring blood.
We employed for the first time second harmonic mode for tissue characterization. This mode has been shown to be superior to fundamental mode using contrast agents and for the determination of ventricular volumes. We compared sequences recorded from 10 patients in both fundamental and second harmonic modes. The raw second harmonic signal from the IVS was stronger than the fundamental one. Although this was only obtained from a small sample, the difference was highly significant (P<0.001). There was also a difference between the two modes for the corrected values which confirms for the first time with numeric parameters that the contrast between blood and myocardial walls is better with second harmonic imaging. However, this mode did not appear to influence the amplitude of variation in gray level of walls.
The limitation of the study stems essentially from the small size of the population, and so some of the findings lack statistical power. Moreover all the hypertensives had been taking BP lowering agents for some time, agents which may have an influence on LVM and on systolic function and so may influence results of gray level cyclic variations. However, we noticed no statistical differences between the two groups for regional systolic function parameters.
| Conclusions |
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Videodensitometry applied to the echographic images has encountered a number of difficulties in the processing of the analog signal. The development of digital echocardiographic machines has now paved the way for modern videodensitometric analysis of a high quality image. We have demonstrated in this study, in agreement with other authors, that the cyclic variation in amplitude of gray levels of the myocardium is correlated with systolic function and is attenuated in hypertensives. We employed for this a new semi-automatic computer program able to evaluate myocardial wall displacements, and analyze gray level cyclic variations on the whole cardiac cycle. This software could be applied to analyze raw data now available on new echocardiographs.
| Acknowledgements |
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This work was possible thanks to a grant from the Société Française d'hypertension artérielle.
| References |
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- O'Donnel M, Mimbs J.W, Miller J.G, et al. Relationship between collagen and ultrasonic backscatter in myocardial tissue. J Acoust Soc Am (1981) 62:580–588.
- Shaw T.R, Logan-sinclair R.B, Surin C, et al. Relation between regional echo intensity and myocardial connective tissue in chronic left ventricular disease. Br Heart J (1984) 51:46–53.
[Abstract/Free Full Text] - Picano E, Pelosi G, Marzilli M, et al. In vivo quantitative evaluation of myocardial fibrosis in humans. Circulation (1990) 81:58–64.
[Abstract/Free Full Text] - O'Brien P, O'Brien W, Rhyne T, et al. Relation of ultrasonic backscatter and acoustic propagation properties to myofibrillar length and myocardial thickness. Circulation (1995) 91:171–175.
[Abstract/Free Full Text] - Ciulla M, Paliotti R, Hess D.B, et al. Echocardiographic patterns of myocardial fibrosis in hypertensive patients: endomyocardial biopsy versus ultrasonic tissue characterization. J Am Soc Echocardiogr (1997) 10(6):657–664.[CrossRef][Web of Science][Medline]
- Hoyt R, Collins S, Skorton D, et al. Assessment of fibrosis in infarcted human hearts by analysis of ultrasonic backscatter. Circulation (1985) 71:740–744.
[Abstract/Free Full Text] - Mimbs J.W, Bauwens D, Cohen R.D, et al. Effects of myocardial ischemia on quantitative ultrasonic backscatter and identification of responsible determinants. Circ Res (1981) 49:89–96.
[Abstract/Free Full Text] - Rasmussen S, Lovelace D.E, Knobel S.B, et al. Echocardiographic detection of ischemic and infarcted myocardium. J Am Coll Cardiol (1984) 3:733–743.[Abstract]
- Vered Z, Barzilai B, Mohr G.A, et al. Quantitative ultrasonic tissue characterization with real-time integrated backscatter imaging in normal subjects and in patients with dilated cardiomyopathy. Circulation (1987) 5:1067–1073.
- Bouki K.P, Lange A, Palka P, et al. Regional variations of ultrasonic integrated backscatter in normal and myopathic left ventricles. Eur Heart J (1996) 17:1747–1755.
[Abstract/Free Full Text] - Ferdeghini E.M, Pinamonti B, Picano E. Quantitative texture analysis in echocardiography: application to the diagnosis of myocarditis. J Clin Ultrasound (1991) 19(5):263–270.[Web of Science][Medline]
- Chandrasekaran K, Aylward P.E, Feagle S.R, et al. Feasibility of identifying amyloid and hypertrophic cardiomyopathy with the use of computerized quantitative texture analysis of clinical echocardiographic data. J Am Coll Cardiol (1989) 13:832–840.[Abstract]
- Lattanzi F, Di Bello V, Picano E, et al. Normal ultrasonic myocardial reflectivity in athletes with increased ventricular mass. A tissue characterization study. Circulation (1992) 85:1828–1834.
[Abstract/Free Full Text] - Lattanzi F, Spirito P, Picano E, et al. Quantitative assessment of ultrasonic myocardial reflectivity in hypertrophic cardiomyopathy. J Am Coll Cardiol (1991) 17:1085–1090.[Abstract]
- Naito J, Masuyama T, Tanouchi J, et al. Analysis of transmural trend of myocardial integrated ultrasound backscatter for differentiation of hypertrophic cardiomyopathy and ventricular hypertrophy due to hypertension. J Am Coll Cardiol (1994) 24:517–524.[Abstract]
- Devereux R.B, Reichek N, et al. Echocardiographic determination of left ventricular mass in man. Anatomic validation of the method. Circulation (1977) 55:613–618.
[Abstract/Free Full Text] - Devereux R.B. Detection of left ventricular hypertrophy by M-mode echocardiography. Anatomic validation, standardization, and comparison to other methods. Hypertension (1987) 9(Suppl):II19–II26.[Medline]
- Mimbs J.W, O'Donnel M, Bauwens D, et al. The dependence of ultrasonic attenuation and backscatter on collagen content in dog and rabbit hearts. Circ Res (1980) 47:49–51.
[Free Full Text] - Perez J.E, Barzilai B, Madaras E.I, et al. Applicability of ultrasonic tissue characterization for longitudinal assessment and differentiation of calcification and fibrosis in cardiomyopathy. J Am Coll Cardiol (1984) 4:88–95.[Abstract]
- Skorton D.J, Chivers R.C, Collins S.M, et al. Ultrasonic tissue characterization in cardiology. Am J Noninvasive Cardiol (1987) 1:88–97.
- Hoyt R.M, Skorton D.J, Collins S.M, et al. Ultrasonic backscatter and collagen in normal ventricular myocardium. Circulation (1984) 69:775–782.
[Abstract/Free Full Text] - Hickson R.C, Hammons G.T, Holloszy J.O, et al. Development and regression of exercise-induced cardiac hypertrophy in rats. Am J Physiol (1979) 236:H268–H272.[Web of Science][Medline]
- Lucarini A.R, Talarico L, Di Bello V, et al. Increased myocardial ultrasonic reflectivity is associated with extreme hypertensive left ventricular hypertrophy: a tissue characterization study in humans. Am J Hypertension (1998) 11:1442–1449.[CrossRef][Web of Science][Medline]
- Zoni A, Regolisti G, Aschieri D, et al. Myocardial ultrasonic tissue characterization in patients with different types of left ventricular hypertrophy: a videodensitometric approach. J Am Soc Echocardiogr (1997) 10:74–82.[CrossRef][Web of Science][Medline]
- Gigli G, Lattanzi A, Picano E, et al. Normal ultrasonic myocardial reflectivity in hypertensive patients. A tissue characterization study. Hypertension (1993) 21(3):329–334.
[Abstract/Free Full Text] - Masuyama T, Frederick G, St Goar F.G, et al. Ultrasonic tissue characterization on human hypertrophied hearts in vivo with cardiac cycle-dependent variation in integrated backscatter. Circulation (1989) 80:925–934.
[Abstract/Free Full Text] - Wickline S.A, Thomas L.J, Miller J.G, et al. A relationship between integrated backscatter and myocardial contractile function. J Clin Invest (1988) 76:2151–2160.[CrossRef]
- Marini C, Picano E, Varga A, et al. Cyclic variation in myocardial gray level as a marker of viability in man. A videodensitometric study. Eur Heart J (1996) 17:472–479.
[Abstract/Free Full Text] - Bombardini T, Galli R, Paterni M, et al. A videodensitometric study of transmural heterogeneity of cyclic echo amplitude variation in human myocardium. Am J Cardiol (1996) 78:212–216.[Web of Science][Medline]
- Eaton M.H, Lappas D, Waggoner A.D, et al. Ultrasonic myocardial tissue characterization in the operating room: initial results using transoesophageal echocardiography. J Am Soc Echocardiogr (1991) 4(6):541–546.[Medline]
- Iliceto S, Galiuto L, Colonna P, et al. Effects of atrial pacing stress test on ultrasonic integrated backscatter cyclic variations in normal subjects and in patients with coronary artery disease. Eur Heart J (1997) 18(10):1590–1598.
[Abstract/Free Full Text] - Schwartz K.Q, Chen X, Steinmetz S, et al. Methods for quantifying ultrasound backscatter and two-dimensional video intensity: implications for contrast-enhanced sonography. J Am Soc Echocardiogr (1998) 11(2):155–167.[CrossRef][Web of Science][Medline]
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