Three-dimensional characterization of human ventricular myofiber architecture by ultrasonic backscatter.

Normal human left ventricular architecture comprises a highly aligned array of cardiac myofibers whose orientation depends on transmural location. This study was designed to determine whether measurement of integrated backscatter could be used detect the progressive transmural shift of myofiber alignment that occurs from epicardium to endocardium in human ventricular wall segments. Integrated backscatter was measured at 32 transmural levels in seven cylindrical biopsy specimens (1.4 cm diam) sampled from normal regions of six explanted fixed human hearts by insonification of samples at 180 independent angles in 2 degrees steps around their entire circumference with a 5-MHz broadband piezoelectric transducer. Histologic analysis was performed to determine fiber orientation. Integrated backscatter varied approximately as a sinusoidal function of the angle of insonification at each transmural level. Greater integrated backscatter was observed for insonification perpendicular as compared with parallel to fibers (difference = 14.5 +/- 0.6 dB). Ultrasonic analysis revealed a progressive transmural shift in fiber orientation of approximately 9.2 +/- 0.7 degrees/mm of tissue. Histologic analysis revealed a concordant shift in fiber orientation of 7.9 +/- 0.8 degrees/mm of tissue. Thus, human myocardium manifests anisotropy of ultrasonic scattering that may be useful for characterization of the intramural fiber alignment and overall three-dimensional organization of cardiac myofibers.     

Characterization of anisotropic myocardial backscatter using spectral slope, intercept and midband fit parameters

The specific myocardial structural components that contribute to the observed level of backscatter from the heart and its dependence on the angle of insonification have not been completely identified: The objectives of this study were to measure the anisotropy of backscatter from myocardium using the approach first introduced by Lizzi et al. [J Acoust Soc Am 73, 1366-1373 (1983)] and to use the extracted spectral parameters (spectral slope, intercept and midband fit) to characterize changes in the apparent scatterer size, spatial concentration and acoustic impedance properties as functions of the angle of insonification. Backscatter measurements were performed in vitro on eight cylindrical formalin-fixed lamb myocardial specimens using a 5 MHz focused transducer. The backscattered spectral data as a function of angle of insonification relative to the myocardial fiber direction were analyzed over the frequency range of 4 to 6 MHz. The spectral parameters describing features of backscatter were determined by applying a linear fit to attenuation-compensated normalized spectra. Results show that values of the spectral slope do not exhibit a significant dependence on the angle of insonification within uncertainties; however, the zero-frequency intercept showed clear anisotropy and was found to be a maximum for insonification perpendicular to the predominant myofiber orientation and a minimum for parallel insonification. A comparison of midband fit values at 5 MHz with attenuation-compensated integrated backscatter values showed excellent agreement for all angles of insonification. These data suggest that measurements of spectral slope, intercept, and midband fit can provide insights regarding aspects of tissue microstructure underlying the observed anisotropy of myocardial scattering properties. Measurements of the slope parameter suggest a very modest change in effective scatterer size with angle of insonification. However, the observed anisotropy in intercept and midband fit and apparent absence of anisotropy in the spectral slope suggests an angle of insonification dependence of acoustic concentration, the combination of effective spatial scatterer concentration and acoustic impedance properties, without a significant contribution from changes in effective scatterer size.     

Anisotropy of apparent backscatter in the short-axis view of mouse hearts

The goals of this investigation were to measure the anisotropy of backscattered ultrasound observed in the short-axis view of mouse hearts in systole and diastole and to compare these measurements with predictions from a computer simulation. Measurements of midmyocardial apparent backscatter were obtained from analyses of the hearts of seven wild-type mice using a clinical imaging system utilizing a linear array with a nominal center frequency of 13 MHz. A computer model simulating the short-axis view was implemented based on previous measurements of the angle of insonification dependence of myocardial backscatter and attenuation. Results demonstrate that the measured backscatter was largest for those myocardial regions corresponding to approximately perpendicular insonification relative to the myofibers and the smallest for regions of approximately parallel insonification, with the minimum to maximum values of apparent backscatter differing by approximately 10 dB. The measured anisotropy of backscatter was similar for end-systole and end-diastole and was in good agreement with the predicted anisotropy obtained from the computer simulations. (E-mail: mrh@wuphys.wustl.edu)     

Regional variation in the measured apparent ultrasonic backscatter of mid-gestational fetal pig hearts

The goal of this study was to characterize and compare regional backscatter properties of fetal hearts through measurements of the apparent integrated backscatter. Sixteen excised, formalin-fixed fetal pig hearts, representing an estimated 53 to 63 days of gestation, were investigated. Spatially localized measurements of integrated backscatter from these specimens were acquired using a 50 MHz single-element transducer. The apparent integrated backscatter measurements demonstrate different patterns of backscatter from the myocardium of the right ventricle compared with that of the left ventricle. These backscatter measurements appear to be consistent with the anisotropy of the fiber orientation observed in histologic assessment of the same specimens. For each of the 16 hearts, the apparent integrated backscatter from the right ventricular myocardium was larger than that from the left ventricular myocardium, exhibiting mean apparent backscatter values of –35.9 ± 2.0 dB and –40.1 ± 1.9 dB (mean ± standard deviation; n = 16; p < 0.001), respectively. This study suggests that the intrinsic ultrasonic properties of the left and right ventricular myocardium are distinct in fetal pig hearts at mid-gestation. (E-mail: mrh@wuphys.wustl.edu)     

Quantitative comparison of myocardial fiber structure between mice,rabbit, and sheep using diffusion tensor cardiovascular magnetic resonance

Background

Accurate interpretations of cardiac functions require precise structural models of the myocardium, but the latter is not available always and for all species. Although scaling or substitution of myocardial fiber information from alternate species has been used in cardiac functional modeling, the validity of such practice has not been tested.

Methods

Fixed mouse (n = 10), rabbit (n = 6), and sheep (n = 5) hearts underwent diffusion tensor imaging (DTI). The myocardial structures in terms of the left ventricular fiber orientation helix angle index were quantitatively compared between the mouse rabbit and sheep hearts.

Results

The results show that significant fiber structural differences exist between any two of the three species. Specifically, the subepicardial fiber orientation, and the transmural range and linearity of fiber helix angles are significantly different between the mouse and either rabbit or sheep. Additionally, a significant difference was found between the transmural helix angle range between the rabbit and sheep. Across different circumferential regions of the heart, the fiber orientation was not found to be significantly different.

Conclusions

The current study indicates that myocardial structural differences exist between different size hearts. An immediate implication of the present findings for myocardial structural or functional modeling studies is that caution must be exercised when extrapolating myocardial structures from one species to another.     

Measurements of ultrasonic attenuation properties of midgestational fetal pig hearts

The objectives of this study were to measure the relative attenuation properties of the left and right ventricles in fetal pig hearts and to compare the spatial variation in attenuation measurements with those observed in previously published backscatter measurements. Approximately 1.0-mm-thick, short-axis slices of excised, formalin-fixed heart were examined from 15 midgestational fetal pigs using a 50-MHz single-element transducer. Measurements of the attenuation properties demonstrate regional differences in the left and right ventricular myocardium that appear consistent with the previously reported regional differences in apparent integrated backscatter measurements of the same fetal pig hearts. For regions of perpendicular insonification relative to the myofiber orientation, the right ventricular free wall showed larger values for the slope of the attenuation coefficient from 30-60 MHz (1.48 +/- 0.22 dB/(cm x MHz) (mean +/- SD) and attenuation coefficient at 45 MHz (46.3 +/- 7.3 dB/cm [mean +/- SD]) than the left ventricular free wall (1.18 +/- 0.24 dB/(cm x MHz) and 37.0 +/- 7.9 dB/cm (mean +/- SD) for slope of attenuation coefficient and attenuation coefficient at 45 MHz, respectively). This attenuation study supports the hypothesis that intrinsic differences in the myocardium of the left and right ventricles exist in fetal pig hearts at midgestation.     

Anisotropy of high-frequency integrated backscatter from aortic valve cusps

The biaxial anisotropy of integrated backscatter from aortic valve cusps was characterized ex vivo as an initial assessment of the suitability of high-frequency ultrasound for nondestructive evaluation of fiber alignment in tissue-engineered heart valves. Apparent integrated backscatter (AIB) from eight fresh, intact porcine cusps was measured over an 80 degrees range of insonification angles using a 40-MHz ultrasound system. Angular dependence of backscatter was characterized by fitting a sinusoid to plots of AIB versus insonification angle for data acquired while rotating the transducer about the cusps in the circumferential and radial directions. Angular variations in backscatter were detected along both directions in individual specimens, although the mean amplitude of the fitted sinusoid was significantly greater for the circumferential data (12.1 +/- 2.6 dB) than the radial data (3.5 +/- 3.1 dB, p = 0.002). The higher angular variation of backscatter in the circumferential direction implies that collagen fibers in the fibrosa layer are the most prominent source of high-frequency scattering from porcine aortic valve cusps. The ability to characterize anisotropic backscattering from individual specimens demonstrates that high-frequency ultrasound can be used for nondestructive evaluation of fiber alignment in heart valve biomaterials. (E-mail: jlacefield@eng.uwo.ca).     

血流对组织背向散射强度的影响

目的　探讨心脏灌注压、血液浓度和血流速度对组织背向散射强度的影响。方法　以 0～ 2 0 0mmHg 的压力用全血和代血浆分别灌注 40只中国本兔的离体心脏 ,测定心肌背向散射积分值。检测 3 0例正常人左右颈总动脉和颈内静脉腔内的背向散射积分 ,并与血流速度进行相关分析。结果　全血和代血浆灌注离体心脏 ,心肌背向散射积分的测值均随着灌注压的升高而逐渐增大 ,在较低压力阶段 (0～ 60mmHg)心肌背向散射积分随灌注压升高而明显增大 ,但在较高的压力阶段增高的趋势逐渐减小。在各种不同的压力下 ,用全血灌注时心肌背向散射积分均高于用代血浆灌注时的测值。颈总动脉和颈内静脉血流的平均背向散射积分相近[(9.5± 1.8)dBvs (9.9± 1.5 )dB ,P =0 .3 5 ] ,和血流速度无关 (相关系数为 0 .0 71)。结论　血液浓度和灌注压对心肌的背向散射积分值有一定的影响 ,但血流速度对组织背向散射强度无明显的影响。     

Alterations in ultrasonic backscatter during intra-aortic balloon counterpulsation support in patients with acute myocardial infarction

Alterations of ultrasonic backscatter parameters have been evident in humans with myocardial infarction or ischemia. The backscatter variability could be restored in ischemic or stunned myocardium after reperfusion. The aims of this study were to determinate changes in regional myocardial ultrasonic backscatter during intra-aortic balloon counterpulsation (IABP) support in patients with acute myocardial infarction (AMI), and to evaluate whether backscatter imaging could be a functional guide of IABP support. A total of 9 patients with AMI were investigated during IABP support with a two-dimensional (2-D) ultrasonic backscatter imaging approach for parasternal short-axis view. Coronary angiography was performed in 6 of the 9 patients. A total of 21 vessel territories were studied in different modes of IABP support: 1:1, 1:2 and standby. Restoration of cyclic variation of backscatter after IABP support was demonstrated in 10 vessel territories. Failure of restoration of cyclic variation of backscatter after IABP support was noted in 6 vessel territories with severe coronary lesions (total or nearly total occlusion) or scar tissue. No changes of the ultrasonic backscatter were found in nonischemic vessel territories with patent coronary arteries or TIMI III coronary flow. In addition, the wall motion score did not change significantly with different IABP support. These results suggest that IABP could restore the cyclic variation of backscatter in ischemic myocardium. Myocardial anisotropy may play an influential role in the alterations of ultrasonic backscatter. We propose that ultrasonic backscatter could be a noninvasively functional guide of IABP use in patients with AMI.     

Backscatter tensor imaging and 3D speckle tracking for simultaneous ex vivo structure and deformation measurement of myocardium

Objective: Biaxial mechanical testing is a common method for elucidation of mechanical properties of excised ventricular myocardium, especially in the context of structural remodeling that accompanies heart disease. Current imaging strategies in biaxial testing are based on optical camera imaging of the tissue surface, thus providing no information about the tissue microstructure and limiting strain measurements to two dimensions. Here, these limitations are overcome by replacing the camera with ultrasound imaging in order to measure both transmural fiber orientation and 3D tissue deformation during biaxial testing. Methods: Quasi-static biaxial mechanical testing is applied to four samples of excised porcine ventricular myocardium (two left- and two right-ventricular tissues). During testing, a rotational scan of an ultrasound linear array provides data for both backscatter tensor imaging and 3D speckle tracking, from which transmural fiber orientation and tissue deformation are computed, respectively. Ultrasound-derived fiber orientation and tissue strain are validated against histology and camera surface imaging, respectively. Discussion: Ultrasound-derived fiber angle and tissue strain exhibit good accuracy, with root-mean-square errors of 9.9° and 1.2% strain, respectively. Further investigation into the optimization of backscatter tensor imaging is warranted. Replacing the rotational scan of a linear array with volume imaging with a matrix array will improve the technique. Conclusion: Ultrasound imaging can replace the optical camera measurement during biaxial mechanical testing of ventricular myocardium in order to accurately provide measurements of transmural fiber orientation and tissue strain. In situ knowledge of transmural fiber structure and tissue deformation can enhance the inverse problem used to determine tissue mechanical properties from biaxial testing.     

Estimating myocardial attenuation from M-mode ultrasonic backscatter

The objective of this investigation was to determine whether measurements of myocardial attenuation can be obtained from analyses of M-mode images. We exploited the inherent anisotropy of myocardial properties as a means of systematically varying the attenuation to evaluate this M-mode image-based method for myocardial tissue characterization. A commercially available ultrasonic imaging system was used to acquire M-mode images of 24 excised cylindrical specimens from six formalin-fixed sheep hearts that were analyzed using video signal analysis. Data were compensated for the presence of bright intramural myocardial echoes, a potentially significant contributor to uncertainty in measurements of attenuation from backscattered ultrasound. The estimated attenuation coefficient in dB/cm at an effective center frequency of 2.75 MHz as a function of angle of insonification for measurements obtained from analyses of M-mode images is presented. Given a linear frequency-dependence of attenuation in myocardial tissue over frequencies ranging from 1.5 MHz to 8 MHz, as has been previously reported, M-mode image-based analyses were used to estimate the slope of attenuation. Results showed slopes of attenuation (over a -10 dB transmit bandwidth of 1.875 MHz to 3.75 MHz) ranging from 1.00 +/- 0.07 to 1.81 +/- 0.08 dB/(cm.MHz) for perpendicular and parallel insonification, respectively. These values were in good agreement with contemporaneously measured values (0.99 +/- 0.02 to 1.77 +/- 0.04 dB/(cm.MHz)) obtained over a frequency bandwidth of 4 MHz to 7 MHz using a through-transmission radio-frequency-based approach. These data suggest that robust measurements of myocardial attenuation can be obtained from analyses of M-mode images and that this method may be diagnostically feasible in the clinical setting.     

Echocardiographic-based assessment of myocardial fiber structure in individual, excised hearts

The objective of this study was to assess the feasibility of using echocardiographic imaging as an approach for determining the myocardial fiber structure of intact, individual hearts. Seven formalin-fixed, ex vivo sheep hearts were imaged using a commercially available echocardiographic imaging system, and the intrinsic fiber structure for the reconstructed short-axis cross section was determined for a specific distance from the apex of each heart. Diffusion tensor magnetic resonance (DT-MR) images of each heart were acquired and fiber maps were created for comparison with the fiber structure obtained from the corresponding reconstructed echocardiographic images. These two methods of obtaining the fiber structure showed relatively good agreement, suggesting that measurements of fiber orientation for individual hearts can be derived from echocardiographic images. Further development of this method may provide a clinically useful approach for mapping the fiber orientation in individual patients over the heart cycle.     

The frequency dependence of ultrasonic velocity and the anisotropy of dispersion in both freshly excised and formalin-fixed myocardium

The objectives of this study were to measure the frequency dependence of the ultrasonic velocity in myocardium and to quantify the frequency dependence of phase velocity as a function of the insonification angle relative to the predominant direction of the myofibers. Broadband phase spectroscopy data were acquired, spanning a frequency range of 3 to 8 MHz. Measurements were made on 36 tissue specimens cored from 12 freshly excised lamb hearts and were repeated after fixation with formalin. Measured phase velocities were found to be well characterized by a logarithmic fit. For freshly excised myocardium, the dispersion over the 3 to 8 MHz bandwidth was dependent on the direction of insonification, ranging from 1.2 m/s change for perpendicular insonification (across the myofibers) to 3.7 m/s for parallel insonification (along the myofibers). The effects of formalin-fixation resulted in a significant increase in dispersion for perpendicular insonification, but did not appreciably alter the dispersion for parallel insonification.     

Diffusion MR tractography of the heart

Histological studies have shown that the myocardium consists of an array of crossing helical fiber tracts. Changes in myocardial fiber architecture occur in ischemic heart disease and heart failure, and can be imaged non-destructively with diffusion-encoded MR. Several diffusion-encoding schemes have been developed, ranging from scalar measurements of mean diffusivity to a 6-dimensional imaging technique known as diffusion spectrum imaging or DSI. The properties of DSI make it particularly suited to the generation of 3-dimensional tractograms of myofiber architecture. In this article we review the physical basis of diffusion-tractography in the myocardium and the attributes of the available techniques, placing particular emphasis on DSI. The application of DSI in ischemic heart disease is reviewed, and the requisites for widespread clinical translation of diffusion MR tractography in the heart are discussed.     

Cardiovascular magnetic resonance in carotid atherosclerotic disease

Histological studies have shown that the myocardium consists of an array of crossing helical fiber tracts. Changes in myocardial fiber architecture occur in ischemic heart disease and heart failure, and can be imaged non-destructively with diffusion-encoded MR. Several diffusion-encoding schemes have been developed, ranging from scalar measurements of mean diffusivity to a 6-dimensional imaging technique known as diffusion spectrum imaging or DSI. The properties of DSI make it particularly suited to the generation of 3-dimensional tractograms of myofiber architecture. In this article we review the physical basis of diffusion-tractography in the myocardium and the attributes of the available techniques, placing particular emphasis on DSI. The application of DSI in ischemic heart disease is reviewed, and the requisites for widespread clinical translation of diffusion MR tractography in the heart are discussed.     

Transmural variation of myocardial attenuation and its potential effect on contrast-mediated estimates of regional myocardial perfusion.

Promising technical developments suggest that it may be feasible to use contrast echocardiography to estimate regional myocardial perfusion. Although the optimal approach has not yet been determined, the use of a nonlinear (harmonic) response of the contrast agent is common to several recent advances. The purpose of this article is to delineate the relation between the anisotropic (angle-dependent) ultrasonic attenuation of the myocardium through which the sound wave has propagated and the regional, nonlinear response of the contrast agent. Apparent perfusion will be modulated by this regionally varying, path-dependent attenuation, which is determined by the local angle between the propagating sound wave and the myofiber orientation. We illustrate the potential magnitude of the effect of myocardial anisotropy for the apical 4-chamber view by examining propagation along the septum and the lateral wall. We present experimentally measured values of the attenuation of excised sheep myocardium, showing statistically significant differences in the attenuation in the mid wall compared with that in symmetrical zones to the left and right of the mid wall, reflecting the well-known myofiber orientations in these 3 regions. The nonlinear (harmonic) response of a contrast agent depends on the local pressure amplitude, which for a given mechanical index is determined by the attenuation accumulated along the path to the point where the regional perfusion is estimated.     

背向散射积分技术评价PTCA术前后左室肌回声与收缩功能

目的：用超声背向散射积分(IBS)评价经皮冠状动脉成形术(PTCA)前后左室肌回声及收缩功能变化。方法：对33例择期行PTCA 支架术的冠心病患者用HP 5500型超声诊断仪，于PTCA术前及术后3天、1～3个月对胸骨旁乳头肌短轴切面的前间壁、下壁、后壁、侧壁行二维超声心动图(2DE)检测各节段的室壁运动情况、声学密度一背向散射积分(AD-IBS)检测心肌背向散射积分平均值及其标化值，心肌整层及心内外膜下心肌层的周期变化幅度并计算跨壁梯度指数。结果：左室存活心肌背向散射积分参数值于术后3天就有了改善，与术前相比有统计学意义；术后1～3个月检测，左室存活心肌回声及收缩功能均有明显改善。结论：PTCA能够有效地挽救存活心肌，背向散射积分技术能够为早期检测存活心肌及早期评价或预测PTCA疗效提供敏感指标。     

Magnetic susceptibility anisotropy of myocardium imaged by cardiovascular magnetic resonance reflects the anisotropy of myocardial filament α-helix polypeptide bonds

Background

A key component of evaluating myocardial tissue function is the assessment of myofiber organization and structure. Studies suggest that striated muscle fibers are magnetically anisotropic, which, if measurable in the heart, may provide a tool to assess myocardial microstructure and function.

Methods

To determine whether this weak anisotropy is observable and spatially quantifiable with cardiovascular magnetic resonance (CMR), both gradient-echo and diffusion-weighted data were collected from intact mouse heart specimens at 9.4 Tesla. Susceptibility anisotropy was experimentally calculated using a voxelwise analysis of myocardial tissue susceptibility as a function of myofiber angle. A myocardial tissue simulation was developed to evaluate the role of the known diamagnetic anisotropy of the peptide bond in the observed susceptibility contrast.

Results

The CMR data revealed that myocardial tissue fibers that were parallel and perpendicular to the magnetic field direction appeared relatively paramagnetic and diamagnetic, respectively. A linear relationship was found between the magnetic susceptibility of the myocardial tissue and the squared sine of the myofiber angle with respect to the field direction. The multi-filament model simulation yielded susceptibility anisotropy values that reflected those found in the experimental data, and were consistent that this anisotropy decreased as the echo time increased.

Conclusions

Though other sources of susceptibility anisotropy in myocardium may exist, the arrangement of peptide bonds in the myofilaments is a significant, and likely the most dominant source of susceptibility anisotropy. This anisotropy can be further exploited to probe the integrity and organization of myofibers in both healthy and diseased heart tissue.     

Modelling and correcting azimuthal anisotropy in Sentinel-1 backscatter data

Sentinel-1 backscatter data – acquired in dual-polarized (VV/VH) Interferometric Wide (IW) swath mode – show an azimuth angle dependency. The orientation of the tangential plane of the surface observed can alter the backscatter differently depending on the azimuth angle of the viewing geometry. In this study, two years of Sentinel-1 backscatter data over Western Europe have been investigated to show that the azimuthal anisotropy of backscatter is mainly caused by the orientation of the topography’s slope. The SRTM-3 digital elevation model (DEM) is used to describe the azimuthal anisotropy in the Tyrolean Alps and in addition, an algorithm is presented to take into account the azimuthal dependency by calculating correction parameters for each relative orbit of Sentinel-1.     

Transmural variation of myocardial attenuation measured with a clinical imager

The objective of this study was to quantify the transmural variation in attenuation for the septal and lateral walls of the heart. Our approach was to utilize a commercially available ultrasonic imaging system to acquire images of excised sections of eight sheep hearts with an orientation similar to that encountered in the apical four-chamber view. The measured values (mean ± SE) of the slope of attenuation for the transmural regions of the septum are: 1.40 ± 0.11, 0.99 ± 0.09, and 1.85 ± 0.16 (dB/cm/MHz) for the left subendocardial, midmyocardial, and right subendocardial zones, respectively. The analogous data from the lateral wall are: 1.42 ± 0.11, 0.83 ± 0.07, and 1.20 ± 0.16 (dB/cm/MHz) for the subendocardial, midmyocardial, and subepicardial zones, respectively. These data demonstrate that ultrasonic attenuation associated with the septum and the lateral wall, when imaged in a manner similar to that of the apical four-chamber view, is anisotropic. (E-mail: jgm@howdy.wustl.edu)