Midband Fit Research Articles

Implementation and validation of an ultrasonic tissue characterization technique for quantitative assessment of normal‐tissue toxicity in radiation therapy

The goal of this study was to implement and validate a noninvasive, quantitative ultrasonic technique for accurate and reproducible measurement of normal-tissue toxicity in radiation therapy. The authors adapted an existing ultrasonic tissue characterization (UTC) technique that used a calibrated 1D spectrum based on region-of-interest analysis. They modified the calibration procedure by using a reference phantom instead of a planar reflector. This UTC method utilized ultrasonic radiofrequency echo signals to generate spectral parameters related to the physical properties (e.g., size, shape, and relative acoustic impedance) of tissue microstructures. Three spectral parameters were investigated for quantification of normal-tissue injury: Spectral slope, intercept, and midband fit. They conducted a tissue-mimicking phantom study to verify the reproducibility of UTC measurements and initiated a clinical study of radiation-induced breast-tissue toxicity. Spectral parameter values from measurements on two phantoms were reproducible within 1% of each other. Eleven postradiation breast-cancer patients were studied and significant differences between the irradiated and untreated (contralateral) breasts were observed for spectral intercept (p = 0.003) and midband fit (p < 0.001) but not for slope (p = 0.14). In comparison to the untreated breast, the average difference in the spectral intercept was 2.99 +/- 0.75 dB and the average difference in the midband fit was 3.99 +/- 0.65 dB. The preliminary clinical study demonstrated the feasibility of using the quantitative ultrasonic method to evaluate normal-tissue toxicity in radiation therapy.

Automated and Objective Assessments of Radiation-induced Fibrosis using Advanced Ultrasound Imaging in Breast Cancer Radiation Therapy

We have recently reported that ultrasound imaging together with ultrasound tissue characterization (UTC) can provide quantitative assessment of radiation-induced tissue toxicity (ASTRO and RSNA 2007). Specifically, an UTC parameter, midband-fit (MBF), correlates with the presence of soft-tissue fibrosis. We now report an automated-tissue-toxicity-assessment (ATTA) program to evaluate radiation-induced fibrosis in the clinic. This study evaluates the performance of our ATTA program.

Challenges in Atherosclerotic Plaque Characterization With Intravascular Ultrasound (IVUS): From Data Collection to Classification

In vivo plaque characterization is an important research field in interventional cardiology. We will study the realistic challenges to this goal by deploying 40 MHz single-element, mechanically rotating transducers. The intrinsic variability among the transducers' spectral parameters as well as tissue signals will be demonstrated. Subsequently, we will show that global data normalization is not suited for data calibration, due to the aforementioned variations as well as the stringent characteristics of spectral features. We will describe the sensitivity of an existing feature extraction algorithm based on eight spectral signatures (integrated backscatter coefficient, slope, midband-fit (MBF), intercept, and maximum and minimum powers and their relative frequencies) to a number of factors, such as the window size and order of the autoregressive (AR) model. It will be further demonstrated that the variations in the transducer's spectral parameters (i.e., center frequency and bandwidth) cause inconsistencies among extracted features. In this paper, two fundamental questions are addressed: 1) what is the best reliable way to extract the most informative features? and 2) which classification algorithm is the most appropriate for this problem? We will present a full-spectrum analysis as an alternative to the eight-feature approach. For the first time, different classification algorithms, such as k-nearest neighbors (k-NN) and linear Fisher, will be employed and their performances quantified. Finally, we will explore the reliability of the training dataset and the complexity of the recognition algorithm and illustrate that these two aspects can highly impact the accuracy of the end result, which has not been considered until now.

High Frequency Ultrasound Tissue Characterization and Acoustic Microscopy of Intracellular Changes

The objective of this work is to investigate changes in the acoustic properties of cells when exposed to chemotherapy for monitoring treatment response. High frequency ultrasound spectroscopy (10-60 MHz) and scanning acoustic microscopy (0.9 GHz) were performed on HeLa cells ( Ackermann et al. 1954, Masters 2002) that were exposed to the chemotherapeutic agent cisplatin. Ultrasonic radio-frequency data were acquired from pellets containing HeLa cells after exposure to cisplatin to induce apoptosis. Scanning acoustic and laser fluorescence microscopy images were recorded from single HeLa cells exposed to the same drug. Data acquisition in both cases was performed at several time points throughout the chemotherapeutic treatment for up to 27 h. In the high frequency ultrasound investigation, normalized power spectra were calculated within a region-of-interest. A 20 MHz transducer (f-number 2.35) and a 40 MHz transducer (f-number 3) were used for the data collection in the high frequency ultrasound experiments. The backscatter coefficients, integrated backscatter coefficients, mid-band fit and spectral slope were computed as a function of treatment time to monitor acoustical property changes during apoptosis. Acoustic attenuation was measured using the spectral substitution technique at all time points. Spectral parameter changes were detected after 12 h of exposure and coincided with the initiation of cell damage as assessed by optical microscopy. Integrated backscatter coefficients increased by over 100% between 0 h and 24 h of treatment, with small changes in the associated attenuation (∼0.1 dB/[MHz cm]). Acoustic microscopy was performed at 0.9 GHz frequency. The cell structure was imaged using staining in laser fluorescence microscopy. All cells showed excellent correspondence between the locations of apoptotic nuclear condensation observed in optical imaging and changes in attenuation contrast in acoustic microscopy images. The time after drug exposure at which such changes occurred in the optical images were coincident with the time of changes detected in the acoustic microscopy images and the high frequency ultrasound experiments. (E-mail: Sebastian.Brand@gmail.com)

EUS spectrum analysis for in vivo characterization of pancreatic and lymph node tissue: a pilot study

EUS is limited by variability in the examiner's subjective interpretation of B-scan images to differentiate among normal, inflammatory, and malignant tissue. By using information otherwise discarded by conventional EUS systems, quantitative spectral analysis of the raw radiofrequency (RF) signals underlying EUS images enables tissue to be characterized more objectively. Our purpose was to determine the feasibility of using spectral analysis of EUS data for characterization of pancreatic tissue and lymph nodes. A pilot study of eligible patients was conducted to analyze the RF data obtained during EUS by using spectral parameters. Twenty-one subjects who underwent EUS of the esophagus, stomach, pancreas, and surrounding intra-abdominal and mediastinal lymph nodes. Linear regression parameters of calibrated power spectra of the RF signals were tested to differentiate normal pancreas from chronic pancreatitis and from pancreatic cancer as well as benign from malignant-appearing lymph nodes. The mean intercept, slope, and midband fit of the spectra differed significantly among normal pancreas, adenocarcinoma, and chronic pancreatitis when all were compared with each other (P < .01). On direct comparison, mean midband fit for adenocarcinoma differed significantly from that for chronic pancreatitis (P < .05). For lymph nodes, mean midband fit and intercept differed significantly between benign- and malignant-appearing lymph nodes (P < .01 and P < .05, respectively). Small sample population and spatial averaging inherent to this technique. Mean spectral parameters in EUS imaging can provide a noninvasive method to discriminate normal from diseased pancreas and lymph nodes.

Quantitative Assessment of Radiation Therapy Associated Breast Tissue Toxicity

To investigate the use of ultrasound tissue characterization (UTC) imaging to quantitatively evaluate normal tissue toxicity in breast cancer radiation treatment. For women with early stage breast cancer, breast-conservation surgery in combination with radiation therapy is an effective treatment. However, efficacy of radiation therapy is limited by radiation injury to normal tissue. There is currently no objective means of measuring breast tissue injury/toxicity in the clinic. We investigated the use of UTC to examine skin and subcutaneous tissue of the breast. Twenty two breast cancer patients were enrolled. All patients received a standard course of radiation: the whole breast received 50–50.4 Gy followed by an electron boost of 10–16 Gy at the lumpectomy site. Follow up time was 6 to 94 months with a median of 22 months. Patients were scanned with a clinical Ultrasonix® scanner in a supine position. Radio-frequency echo signals were acquired from the treated and the contra-lateral breast. Our UTC technique analyzes the RF signals and extracts spectral features that are associated with properties of tissue microstructures. Four UTC parameters were computed to quantitatively measure toxicity: skin thickness, UTC slope, intercept and midband fit (MBF). Statistical analysis was performed to correlate the UTC findings with clinical assessments (RTOG clinical toxicity scale). UTC measurements for the treated breast were compared with the contra-lateral (untreated) breast for quantitative assessment of normal tissue radiation toxicity. Two breast images are shown in the Figure: (a) treated right breast and (b) untreated left breast. The skin thickening (arrows) and hyper-echogenecity of the fat were observed. The plot on the right is the UTC 1-D power spectra. For all patients, the average thickness of the treated breast skin is 2.50 ± 0.82 mm while untreated skin is 1.68 ± 0.62 mm. For the underlying tissue, there are significant changes for the treated breast in the UTC intercept (p = 0.017) and midband fit (p = 0.002), except slope (p = 0.077). Changes in midband fit were primarily related to soft tissue stiffness, which correlates the presence of fibrosis. The UTC evaluations were consistent with the clinical breast toxicity assessments. Ultrasound tissue characterization provides an objective quantitative method of assessing radiation damage to the skin and the underlying breast tissue. This tool will become increasingly valuable as we evaluate new strategies for breast cancer radiation therapy.

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.

Improved visualization of high-intensity focused ultrasound lesions

Spectral parameter imaging in both the fundamental and harmonic of backscattered radio-frequency (RF) data were used for immediate visualization of high-intensity focused ultrasound (HIFU) lesion sites. A focused 5-MHz HIFU transducer with a coaxial 9-MHz focused single-element diagnostic transducer was used to create and scan lesions in chicken breast and freshly excised rabbit liver. B-mode images derived from the backscattered RF signal envelope were compared with midband fit (MBF) spectral parameter images in the fundamental (9-MHz) and harmonic (18-MHz) bands of the diagnostic probe. Images of HIFU-induced lesions derived from the MBF to the calibrated spectrum showed improved contrast (∼ 3 dB) of tumor margins versus surround compared with images produced from the conventional signal envelope. MBF parameter images produced from the harmonic band showed higher contrast in attenuated structures (core, shadow) compared with either the conventional envelope (3.3 dB core; 11.6 dB shadow) or MBF images of the fundamental band (4.4 dB core; 7.4 dB shadow). The gradient between the lesion and surround was 3.4 dB/mm, 6.9 dB/mm and 17.2 dB/mm for B-mode, MBF-fundamental mode and MBF-harmonic mode, respectively. Images of threshold and “popcorn” lesions produced in freshly excised rabbit liver were most easily visualized and boundaries best-defined using MBF-harmonic mode. (E-mail: rsilverman@rrinyc.org

On the statistics of ultrasonic spectral parameters

Several factors affect the accuracy and precision of ultrasonic spectrum analysis, which is used for characterization of normal and diseased tissue in a variety of organs. For example, averaging procedures and the sequence of operations affect the accuracy and precision of spectrum analysis. Averaging procedures and logarithmic conversion ( i.e., conversion to dB) introduce a constant bias that affects spectral amplitudes and the values of intercept and midband fit; the bias depends on the sequencing of the log conversion and averaging as well as the number of independent spectra or spectral parameters that are averaged. We derive expressions that permit correction of such biases. Furthermore, we show that standard deviations for slope and midband-fit estimation can be minimized by averaging spectra before dB conversion and before computing spectral parameters by linear regression. Experimental results using phantoms agree remarkably with theoretical predictions for the data window functions studied in this article, Hamming and rectangular. (E-mail: kalam@rrinyc.org; kaisar.alam@ieee.org)

75 MHz Ultrasound Biomicroscopy of Anterior Segment of Eye

Very high frequency ultrasound (35-50 MHz) has had a significant impact upon clinical imaging of the anterior segment of the eye, offering an axial resolution as small as 30 microm. Higher frequencies, while potentially offering even finer resolution, are more affected by absorption in ocular tissues and even in the fluid coupling medium. Our aim was to develop and apply improved transducer technology utilizing frequencies beyond those routinely used for ultrasound biomicroscopy of the eye. A 75-MHz lithium niobate transducer with 2 mm aperture and 6 mm focal length was fabricated. We scanned the ciliary body and cornea of a human eye six years post-LASIK. Spectral parameter images were produced from the midband fit to local calibrated power spectra. Images were compared with those produced using a 35 MHz lithium niobate transducer of similar fractional bandwidth and focal ratio. The 75-MHz transducer was found to have a fractional bandwidth (-6 dB) of 61%. Images of the post-LASIK cornea showed higher stromal backscatter at 75 MHz than at 35 MHz. The improved lateral resolution resulted in better visualization of discontinuities in Bowman's layer, indicative of microfolds or breaks occurring at the time of surgery. The LASIK surface was evident as a discontinuity in stromal backscatter between the stromal component of the flap and the residual stroma. The iris and ciliary body were visualized despite attenuation by the overlying sclera. Very high frequency ultrasound imaging of the anterior segment of the eye has been restricted to the 35-50 MHz band for over a decade. We showed that higher frequencies can be used in vivo to image the cornea and anterior segment. This improvement in resolution and high sensitivity to backscatter from the corneal stroma will provide benefits in clinical diagnostic imaging of the anterior segment.

Spectral parameter imaging of the corneal stroma

Frederic L. Lizzi was a pioneer in the fields of high‐frequency ultrasound and tissue characterization. This report details use of spectral parameter imaging of very‐high‐frequency radio frequency data for characterization of the cornea. The corneal stroma consists of broad 1–2‐micron‐thick belts (lamellae) embedded in a proteoglycan matrix. The lamellae consist of collagen fibrils 30 nm in diameter with center‐to‐center spacing of about 60 nm. Any disturbance to this orderly arrangement will result in loss of optical transparency. Parameter images representing the slope, intercept, and midband fit to the calibrated power spectrum were generated by post‐processing of radio frequency data of 35‐ and 70‐MHz scans of the cornea. Stromal backscatter was significantly higher at 70 MHz than at 35 MHz. In an uncomplicated LASIK‐treated cornea examined 6 years postsurgery, significant differences in backscatter between the stroma anterior versus posterior to the LASIK interface were observed. This may relate to alteration in lamellar organization, even in the absence of loss of optical transparency. Frequencies beyond 50 MHz offer a probe of tissue microstructure that could be employed in evaluation of stromal organization. [Work supported by NIH Grant EB000238 and Research to Prevent Blindness.]

Ultrasonic spectral parameter characterization of apoptosis

Ultrasound (US) spectral analysis methods are used to analyze the radiofrequency (RF) data collected from cell pellets exposed to chemotherapeutics that induce apoptosis and other chemicals that induce nuclear transformations. Calibrated backscatter spectra from regions-of-interest (ROI) were analyzed using linear regression techniques to calculate the spectral slope and midband fit. Two f/2 transducers, with operating frequencies of 30 and 34 MHz (relative bandwidths of 93% and 78%, respectively) were used with a custom-made imaging system that enabled the collection of the raw RF data. For apoptotic cells, the spectral slope increased from 0.37 dB/MHz before drug exposure to 0.57 dB/MHz 24 h after, corresponding to a change in effective scatterer radius from 8.7 to 3.2 μm. The midband fit increased in a time-dependent fashion, peaking at 13dB 24 h after exposure. The statistical deviation of the spectral parameters was in close agreement with theoretical predictions. The results provide a framework for using spectral parameter methods to monitor apoptosis in in vitro and in in vivo systems and are being used to guide the design of system and signal analysis parameters. (E-mail: mkolios@ryerson.ca)

Assessing spectral algorithms to predict atherosclerotic plaque composition with normalized and raw intravascular ultrasound data

Spectral analysis of backscattered intravascular ultrasound (IVUS) data has demonstrated the ability to characterize plaque. We compared the ability of spectral parameters (e.g., slope, midband fit and y-intercept), computed via classic Fourier transform (CPSD), Welch power spectrum (WPSD) and autoregressive (MPSD) models, to classify plaque composition. Data were collected ex vivo from 32 human left anterior descending coronary arteries. Regions-of-interest (ROIs), selected from histology, comprised 64 collagen-rich, 24 fibrolipidic, 23 calcified and 37 calcified-necrotic regions. A novel quantitative method was used to correlate IVUS data with corresponding histologic sections. Periodograms of IVUS samples, identified for each ROI, were used to calculate spectral parameters. Statistical classification trees (CT) were computed with 75% of the data for plaque characterization. The remaining data were used to assess the accuracy of the CTs. The overall accuracies for normalized spectra with CPSD, WPSD and MPSD were, respectively, 84.7%, 85.6% and 81.1% (training data) and 54.1%, 64.9% and 37.8% (test data). These numbers were improved to 89.2%, 91.9% and 89.2% (training) and 62.2%, 73% and 59.5% (test) when the calcified and calcified-necrotic regions were combined for analysis. Most CTs misclassified a few fibrolipidic regions as collagen, which is histologically acceptable, and the unnormalized and normalized spectra results were similar. (E-mail: vince@bme.ri.ccf.org)

Statistics of ultrasonic spectral parameters for prostate and liver examinations

A theoretical analysis was performed to describe statistical characteristics of calibrated spectral parameters used for ultrasonic tissue evaluation in the prostate and liver. The analysis assumes that radiofrequency (rf) echo signals exhibit Gaussian statistics. It derives the probability density function (pdf) of spectral parameters that are computed using sliding-window analysis techniques. The analysis relates the standard deviations of linear-regression spectral-parameter estimates to system and analysis parameters including bandwidth, center frequency, and the length of the sliding analysis window. The analysis also derives the pdf for mid-band fit parameter images. Theoretical results are found to agree well with clinical data from homogeneous segments in liver and prostate. The results offer a basis for evaluating spectral-estimator precision and for conducting future studies of lesion detectability based on spectral features.

Statistical framework for ultrasonic spectral parameter imaging

This study examines the statistics of ultrasonic spectral parameter images that are being used to evaluate tissue microstructure in several organs. The parameters are derived from sliding-window spectrum analysis of radiofrequency echo signals. Calibrated spectra are expressed in dB and analyzed with linear regression procedures to compute spectral slope, intercept and midband fit, which is directly related to integrated backscatter. Local values of each parameter are quantitatively depicted in gray-scale cross-sectional images to determine tissue type, response to therapy and physical scatterer properties. In this report, we treat the statistics of each type of parameter image for statistically homogeneous scatterers. Probability density functions are derived for each parameter, and theoretical results are compared with corresponding histograms clinically measured in homogeneous tissue segments in the liver and prostate. Excellent agreement was found between theoretical density functions and data histograms for homogeneous tissue segments. Departures from theory are observed in heterogeneous tissue segments. The results demonstrate how the statistics of each spectral parameter and integrated backscatter are related to system and analysis parameters. These results are now being used to guide the design of system and analysis parameters, to improve assays of tissue heterogeneity and to evaluate the precision of estimating features associated with effective scatterer sizes and concentrations.

Experimental assessment of spectrum analysis of ultrasonic echoes as a method for estimating scatterer properties

In vitro experiments using weak scatterers ranging in size from mean longest diameter of 26.9 to 83.0 μm were performed to test the validity of theoretical predictions for scatterer size and concentration derived from normalized power spectrum parameters of ultrasonic backscatterer echoes. Scatterers consisting of cell clusters were suspended in collagen gel and scanned by a 10 MHz transducer system. Optical measurements validated theoretical predictions that (1) slope value is a function solely of scatterer size; (2) intercept value is a function of scatterer size and concentration; and (3) midband fit value increases as scatterer concentration increases, and, to a lesser extent, as size increases. These results were obtained under relatively ideal conditions of minimal attenuation and scatterer spacing (not closer than two scatterer diameters) and were consistent with the assumptions underlying the scattering theory.