Spectral analysis of ultrasound backscatter for non-invasive measurement of plaque composition.

Carotid atherosclerotic plaque composition may be an important indication of patient risk for future cerebrovascular events. Ultrasound spectral analysis has the potential to provide a robust measure of plaque composition in vivo if the backscatter transfer function can be sufficiently isolated from the effects of attenuation from overlying tissue, receive and transmit transfer functions from the ultrasound system and transducer, and diffraction. This study examines the usefulness of the nonlinearly generated second harmonic portion of the backscatter signal and the effects of a variety of attenuation compensation techniques for noninvasively characterizing human carotid plaque using spectral analysis and machine learning. Post-beamformed ultrasound backscatter radiofrequency (RF) data were acquired from 6 normal subjects and 119 carotid endarterectomy patients prior to surgery. Plaque obtained following surgery was histologically processed, and regions of interest (ROI) corresponding to homogenous tissue types (fibrous/fibro-lipidic, hemorrhagic and/or necrotic core and calcified) were selected from RF data. Both the harmonic and fundamental power spectra for each ROI was obtained and normalized by data from a uniform phantom (0.5 dB/cm-MHz slope of attenuation). Additional attenuation compensation approaches were compared to simply using the reference phantom: (1) optimum power spectral shift estimation, (2) one-step adventitial, or (3) two-step adventitial. Spectral parameters extracted from both the fundamental and harmonic estimates of the backscatter transfer function of 363 ROI's from 152 plaque specimens were used to train and test random forest and support vector machine classification models. The best results came from using spectral parameters derived from both the fundamental and second harmonic bands with a predictive accuracy of 65-68%, kappa statistic of 0.49-0.54, and accuracies of 84% for fibrous, 68-74% for hemorrhagic and/or necrotic core, and 78-81% for calcified ROI's. The result indicated that the nonlinearly generated second harmonic portion of backscatter is useful for carotid plaque tissue characterization and that a reference phantom approach with a 0.5 dB/cm-MHz slope of attenuation works as well as more complicated approaches.

Cyclic Variation of Spectral Parameters for the Differentiation of Atrial Myocardium Before and Immediately Following Radiofrequency Ablation.

Radiofrequency ablation (RFA) is a common treatment of atrial fibrillation. However, current treatment is associated with a greater than 20% recurrence rate, in part due to inadequate monitoring of tissue viability during ablation. Spectral parameters, in particular cyclic variation of integrated backscatter (CVIB), have shown promise as early indicators of myocardial recovery from ischemia. Our aim was to demonstrate the use of spectral parameters to differentiate atrial myocardium before and after radiofrequency ablation. An AcuNav 10 F catheter was used to collect radiofrequency signals from the posterior wall of the left atrium of patients before and immediately after RFA for AF. The normalized power spectrum was obtained and three spectral parameters (integrated backscatter [IB], slope, and intercept) were extracted across two continuous heart cycles. Parameters were gated for ventricular end-diastole and compared before and after ablation. Additionally, the cyclic variation of each of these three parameters was generated as an average of the variation across the two recorded heart cycles. Data from 14 patients before and after ablation demonstrated a significant difference in the magnitude of the cyclic variation of integrated backscatter (9.0 vs. 6.0 dB, p < .001) and cyclic variation of the intercept (14.0 vs. 11.5 dB, p = .04). No significant difference was noted in the magnitude of the cyclic variation of the slope. Among spectral parameters gated for end-diastole, significant differences were noted in the slope (-4.39 vs. -3.73 dB/MHz, p = .002) and intercept (16.8 vs. 11.9 dB, p = .002). No significant difference was noted in the integrated backscatter. Spectral parameters are able to differentiate atrial myocardium before and immediately following ablation and may be useful in monitoring atrial ablations.

Artificial Intelligence in Intracoronary Imaging.

PURPOSE OF REVIEW: This paper investigates present uses and future potential of artificial intelligence (AI) applied to intracoronary imaging technologies. RECENT FINDINGS: Advances in data analytics and digitized medical imaging have enabled clinical application of AI to improve patient outcomes and reduce costs through better diagnosis and enhanced workflow. Applications of AI to IVUS and IVOCT have produced improvements in image segmentation, plaque analysis, and stent evaluation. Machine learning algorithms are able to predict future coronary events through the use of imaging results, clinical evaluations, laboratory tests, and demographics. The application of AI to intracoronary imaging holds significant promise for improved understanding and treatment of coronary heart disease. Even in these early stages, AI has demonstrated the ability to improve the prediction of cardiac events. Large curated data sets and databases are needed to speed the development of AI and enable testing and comparison among algorithms.

Tissue classification in intercostal and paravertebral ultrasound using spectral analysis of radiofrequency backscatter.

Paravertebral and intercostal nerve blocks have experienced a resurgence in popularity. Ultrasound has become the gold standard for visualization of the needle during injection of the analgesic, but the intercostal artery and vein can be difficult to visualize. We investigated the use of spectral analysis of raw radiofrequency (RF) ultrasound signals for identification of the intercostal vessels and six other tissue types in the intercostal and paravertebral spaces. Features derived from the one-dimensional spectrum, two-dimensional spectrum, and cepstrum were used to train four different machine learning algorithms. In addition, the use of the average normalized spectrum as the feature set was compared with the derived feature set. Compared to a support vector machine (SVM) (74.2%), an artificial neural network (ANN) (68.2%), and multinomial analysis (64.1%), a random forest (84.9%) resulted in the most accurate classification. The accuracy using a random forest trained with the first 15 principal components of the average normalized spectrum was 87.0%. These results demonstrate that using a machine learning algorithm with spectral analysis of raw RF ultrasound signals has the potential to provide tissue characterization in intercostal and paravertebral ultrasound.

Spectral Analysis of Ultrasound Radiofrequency Backscatter for the Detection of Intercostal Blood Vessels.

Spectral analysis of ultrasound radiofrequency backscatter has the potential to identify intercostal blood vessels during ultrasound-guided placement of paravertebral nerve blocks and intercostal nerve blocks. Autoregressive models were used for spectral estimation, and bandwidth, autoregressive order and region-of-interest size were evaluated. Eight spectral parameters were calculated and used to create random forests. An autoregressive order of 10, bandwidth of 6 dB and region-of-interest size of 1.0 mm resulted in the minimum out-of-bag error. An additional random forest, using these chosen values, was created from 70% of the data and evaluated independently from the remaining 30% of data. The random forest achieved a predictive accuracy of 92% and Youden's index of 0.85. These results suggest that spectral analysis of ultrasound radiofrequency backscatter has the potential to identify intercostal blood vessels. (jokling@siue.edu) © 2018 World Federation for Ultrasound in Medicine and Biology.

Ex vivo validation of 45 MHz intravascular ultrasound backscatter tissue characterization.

AIMS: The objectives of the present study are to describe the algorithm for VH(®) IVUS using the 45-MHz rotational IVUS catheter and the associated ex vivo validation in comparison to the gold standard histology. METHODS AND RESULTS: The first phase of the present study was to construct the 45 MHz VH IVUS algorithm by using a total of 55 human coronary artery specimens [111 independent coronary lesions and 510 homogenous regions of interest (ROIs)], obtained at autopsy. Regions were selected from histology and matched with their corresponding IVUS data to build the plaque classification system using spectral analysis and statistical random forests. In the second phase, the ex vivo validation of the VH IVUS algorithm assessed a total of 1060 ROIs (120 lesions from 60 coronary arteries) in comparison with histology. In an independent manner, two interventional cardiologists also classified a randomly selected subset of the ROIs for assessment of inter- and intra-observer reproducibility of VH IVUS image interpretation.When including all ROIs, the predictive accuracies were 90.8% for fibrous tissue, 85.8% for fibro fatty tissue, 88.3% for necrotic core, and 88.0% for dense calcium. The exclusion of ROIs in the acoustically attenuated areas improved the predictive accuracies, ranging from 91.9 to 96.8%. The independent analysis of randomly selected 253 ROIs showed substantial agreement for inter-observer (k = 0.66) and intra-observer (k = 0.88) reproducibility. CONCLUSION: Tissue classification by 45 MHz VH IVUS technology, when not influenced by calcium-induced acoustic attenuation, provided combined tissue accuracy >88% to identify tissue types compared with the gold standard histologic assessment, with high inter- and intra-observer reproducibility.

Reproducibility of intravascular ultrasound radiofrequency data analysis (virtual histology) with a 45-MHz rotational imaging catheter in ex vivo human coronary arteries.

BACKGROUND: Despite the frequent use of spectral analysis of intravascular ultrasound radiofrequency data (VH(®) IVUS) in clinical studies, the assessment for reproducibility using this with high frequency IVUS remains unexplored. PURPOSE: The aim of this study was to examine the reproducibility of VH IVUS using 45-MHz rotational IVUS in ex vivo human coronary arteries. METHODS: Data were collected using 45-MHz VH IVUS (Revolution(®), Volcano Corporation, San Diego, CA, USA) via a series of pullbacks from eight human coronary artery specimens. Imaging data were analyzed by two independent observers. Intraobserver and interobserver reproducibility were assessed using five pullbacks from five vessels. The intercatheter reproducibility was assessed using three different catheters in each of the five vessels. The intracatheter reproducibility was assessed between the two sequential pullbacks from each of the 15 catheters used in the intercatheter assessment. RESULTS: Geometrical measurements consistently showed low variability (relative difference <10%) and excellent intraclass correlation coefficients (ICCs), ranging from 0.88 to 1.00. With respect to the compositional measurements, the relative differences were predominantly higher than those of geometrical measurements. In particular, fibrous-fatty area showed a higher relative difference (17.5% in intercatheter assessment) compared to fibrous, necrotic core, and dense calcium areas (6.5%, 8.4%, and 6.4%, respectively). However, each compositional measurement also showed acceptable reproducibility (ICCs ranging from 0.82 to 1.00). CONCLUSIONS: The 45-MHz rotational VH IVUS technology had acceptable reproducibility with respect to geometrical and compositional assessments in ex vivo human coronary arteries. These data are crucial when designing future longitudinal studies addressing geometrical measurements and plaque characterization by 45-MHz VH IVUS.

Layer-dependent variation in the anisotropy of apparent integrated backscatter from human coronary arteries.

Clinical imaging of the coronary arteries in the cardiac catheterization laboratory using intravascular ultrasound (IVUS) is known to display a three-layered appearance, corresponding to the intima/plaque, media and adventitia. It is not known whether ultrasonic anisotropy arising from these tissues may alter this pattern in future IVUS systems that insonify in the forward direction or obliquely. In anticipation of such devices, the current study was carried out by imaging fresh human coronary arteries in two orthogonal directions in vitro. Twenty-six sites from 12 arteries were imaged with a side-looking IVUS system, and with an acoustic microscope both radially and axially. Side-looking IVUS and radial acoustic microscopy scans demonstrated the typical "bright-dark-bright" pattern of the backscatter, with the media being significantly darker than the other two layers. Images obtained in the axial orientation exhibited a markedly different pattern, with the relative brightness of the media significantly larger than that of the intima/plaque.

Phase I/II trial of high intensity focused ultrasound for the treatment of previously untreated localized prostate cancer.

PURPOSE: We examined the safety and potential efficacy of transrectally delivered high intensity focused ultrasound for the full gland ablation of previously untreated localized prostate cancer. MATERIALS AND METHODS: A total of 20 patients with localized prostate cancer underwent 1 to 3 high intensity focused ultrasound treatments of the prostate. The primary outcome was safety and the secondary outcomes were prostate specific antigen, prostate biopsy and quality of life measures. RESULTS: A total of 19 patients had complete followup. Serious adverse events related to treatment were limited with the most common adverse event being transient urinary retention more than 30 days in duration in only 10% of patients. Rectal injury occurred in 1 patient. With 1 to 3 treatments 42% of the patients achieved prostate specific antigen less than 0.5 ng/ml and a negative prostate biopsy. CONCLUSIONS: High intensity focused ultrasound in patients with previously untreated prostate cancer is generally well tolerated and it has the potential to completely ablate the prostate gland. With further refinement of the optimal treatment dose and technique this technology has the potential to be an effective form of therapy for localized prostate cancer.

A ring transducer system for medical ultrasound research.

An ultrasonic ring transducer system has been developed for experimental studies of scattering and imaging. The transducer consists of 2048 rectangular elements with a 2.5-MHz center frequency, a 67% -6 dB bandwidth, and a 0.23-mm pitch arranged in a 150-mm-diameter ring with a 25-mm elevation. At the center frequency, the element size is 0.30lambda x 42lambda and the pitch is 0.38lambda. The system has 128 parallel transmit channels, 16 parallel receive channels, a 2048:128 transmit multiplexer, a 2048:16 receive multiplexer, independently programmable transmit waveforms with 8-bit resolution, and receive amplifiers with time variable gain independently programmable over a 40-dB range. Receive signals are sampled at 20 MHz with 12-bit resolution. Arbitrary transmit and receive apertures can be synthesized. Calibration software minimizes system nonidealities caused by noncircularity of the ring and element-to-element response differences. Application software enables the system to be used by specification of high-level parameters in control files from which low-level hardware-dependent parameters are derived by specialized code. Use of the system is illustrated by producing focused and steered beams, synthesizing a spatially limited plane wave, measuring angular scattering, and forming b-scan images.

Impact of propagation through an aberrating medium on the linear effective apodization of a nonlinearly generated second harmonic field.

Techniques based on the nonlinearly generated second harmonic signal (tissue harmonic imaging) have rapidly supplanted linear (fundamental) imaging methods as the standard in two-dimensional echocardiography. Enhancements to the compactness of the nonlinearly generated second harmonic (2f) field component with respect to the fundamental (1f) field component are widely considered to be among the factors contributing to the observed image quality improvements. The objective of this study was to measure the impact of phase and amplitude aberrations resulting from propagation through an inhomogeneous tissue, on the beamwidths associated with: the fundamental (1f); the nonlinearly generated second harmonic (2f); and the linearly propagated, effective apodization signal at the same (21) frequency. Modifications to the transmit characteristics of a phased-array imaging system were validated with hydrophone measurements. Results demonstrate that the characteristics of the diffraction pattern associated with the linear-propagation effective apodization transmit case were found to be in good agreement with the detailed spatial characteristics of the nonlinearly generated second harmonic field. The effects of the abdominal wall tissue aberrators are apparent for all three of the beam profiles studied. Consistent with the improved image quality associated with harmonic imaging, the aberrated nonlinearly generated second harmonic beam was shown to remain more compact than the corresponding aberrated fundamental beam patterns in the presence of the interposed aberrator.

On the stability of the effective apodization of the nonlinearly generated second harmonic with respect to range.

The concept of an effective apodization was introduced to describe the field pattern for the nonlinearly generated second harmonic (2f) within the focal zone using a linear propagation model. Our objective in this study was to investigate the validity of the concept of an effective apodization at 2f as an approach to approximating the field of the second harmonic over a wide range of depths. Two experimental setups were employed: a vascular imaging array with a water path and an adult cardiac imaging array with an attenuating liver path. In both cases the spatial dependencies of the ultrasonic fields were mapped by scanning a point-like hydrophone within a series of planes orthogonal to the propagation direction. The sampling distances were located before, within, and beyond the focal zone. The signals were Fourier transformed and the complex values at 2f were linearly backpropagated to the transmit plane in order to obtain an effective apodization. The measured results demonstrated a relatively constant effective apodization at 2f as a function of propagation distance. Finite amplitude computer simulations were found to be in agreement with these measurements. Thus the measure of the effective apodization at 2f provides an approximation to the second harmonic field outside the focal zone.

Spatial coherence of backscatter for the nonlinearly produced second harmonic for specific transmit apodizations.

To be successful, correlation-based, phase-aberration correction requires a high correlation among backscattered signals. For harmonic imaging, the spatial coherence of backscatter for the second harmonic component is different than the spatial coherence of backscatter for the fundamental component. The purpose of this work was to determine the effect of changing the transmit apodization on the spatial coherence of backscatter for the nonlinearly generated second harmonic. Our approach was to determine the effective apodizations for the fundamental and second harmonic using both experimental measurements and simulations. Two-dimensional measurements of the transverse cross sections of the finite-amplitude ultrasonic fields generated by rectangular and circular apertures were acquired with a hydrophone. Three different one-dimensional transmit apodization functions were investigated: uniform, Riesz, and trapezoidal. An effective apodization was obtained for each transmit apodization by backpropagating the values measured from within the transmit focal zone using a linear angular spectrum approach. Predictions of the spatial coherence of backscatter were obtained using the pulse-echo Van Cittert-Zernike theorem. In all cases the effective apodization at 2f was narrower than the transmit apodization. We demonstrate that certain transmit apodizations result in a greater spatial coherence of backscatter at the second harmonic than at the fundamental.

Spatial coherence of the nonlinearly generated second harmonic portion of backscatter for a clinical imaging system.

Correlation-based approaches to phase aberration correction rely on the spatial coherence of backscattered signals. The spatial coherence of backscatter from speckle-producing targets is predicted by the auto correlation of the transmit apodization (Van Cittert-Zernike theorem). Work by others indicates that the second harmonic beam has a wider mainlobe with lower sidelobes than a beam transmitted at 2f. The purpose of this paper is to demonstrate that the spatial coherence of backscatter for the second harmonic is different from that of the fundamental, as would be anticipated from applying the Van Cittert-Zernike theorem to the reported measurements of the second harmonic field. Another objective of this work is to introduce the concept of the effective apodization and to verify that the effective apodization of the second harmonic is narrower than the transmit apodization. The spatial coherence of backscatter was measured using three clinical arrays with a modified clinical imaging system. The spatial coherence results were verified using a pseudo-array scan in a transverse plane of the transmitted field with a hydrophone. An effective apodization was determined by backpropagating these values using a linear angular spectrum approach. The spatial coherence for the harmonic portion of backscatter differed systematically and significantly from the auto correlation of the transmit apodization.