Tissue-mimicking Phantom Studies Research Articles

Diffuse reflectance spectroscopy for optical characterizations of orthotopic head and neck cancer models in vivo.

We demonstrated an easy-to-build, portable diffuse reflectance spectroscopy device along with a Monte Carlo inverse model to quantify tissue absorption and scattering-based parameters of orthotopic head and neck cancer models in vivo. Both tissue-mimicking phantom studies and animal studies were conducted to verify the optical spectroscopy system and Monte Carlo inverse model for the accurate extraction of tissue optical properties. For the first time, we reported the tissue absorption and scattering coefficients of mouse normal tongue tissues and tongue tumor tissues. Our in vivo animal studies showed reduced total hemoglobin concentration, lower tissue vascular oxygen saturation, and increased tissue scattering in the orthotopic tongue tumors compared to the normal tongue tissues. Our data also showed that mice tongue tumors with different sizes may have significantly different tissue absorption and scattering-based parameters. Small tongue tumors (volume was ∼60 mm3) had increased absorption coefficients, decreased reduced-scattering coefficients, and increased total hemoglobin concentrations compared to tiny tongue tumors (volume was ∼18 mm3). These results demonstrated the potential of diffuse reflectance spectroscopy to noninvasively evaluate tumor biology using orthotopic tongue cancer models for future head and neck cancer research.

Non-contact optical spectroscopy for tumor-sensitive diffuse reflectance and fluorescence measurements on murine subcutaneous tissue models: Monte Carlo modeling and experimental validations.

Fiber-optic probes are commonly used in biomedical optical spectroscopy platforms for light delivery and collection. At the same time, it was reported that the inconsistent probe-sample contact could induce significant distortions in measured optical signals, which consequently cause large analysis errors. To address this challenge, non-contact optical spectroscopy has been explored for tissue characterizations. However, existing non-contact optical spectroscopy platforms primarily focused on diffuse reflectance measurements and may still use a fiber probe in which the probe was imaged onto the tissue surface using a lens, which serves as a non-contact probe for the measurements. Here, we report a fiber-probe-free, dark-field-based, non-contact optical spectroscopy for both diffuse reflectance and fluorescence measurements on turbid medium and tissues. To optimize the system design, we developed a novel Monte Carlo method to simulate such a non-contact setup for both diffuse reflectance and fluorescence measurements on murine subcutaneous tissue models with a spherical tumor-like target. We performed Monte Carlo simulations to identify the most tumor-sensitive configurations, from which we found that both the depth of the light focal point in tissue and the lens numerical aperture would dramatically affect the system's tumor detection sensitivity. We then conducted tissue-mimicking phantom studies to solidify these findings. Our reported Monte Carlo technique can be a useful computational tool for designing non-contact optical spectroscopy systems. Our non-contact optical setup and experimental findings will potentially offer a new approach for sensitive optical monitoring of tumor physiology in biological models using a non-contact optical spectroscopy platform to advance cancer research.

A novel tissue mechanics-based method for improved motion tracking in quasi-static ultrasound elastography.

Most cancers are associated with biological and structural changes that lead to tissue stiffening. Therefore, imaging tissue stiffness using quasi-static ultrasound elastography (USE) can potentially be effective in cancer diagnosis. USE techniques developed for stiffness image reconstruction use noisy displacement data to obtain the stiffness images. In this study, we propose a technique to substantially improve the accuracy of the displacement data computed through ultrasound tissue motion tracking techniques, especially in the lateral direction. The proposed technique uses mathematical constraints derived from fundamental tissue mechanics principles to regularize displacement and strain fields obtained using Global Ultrasound Elastography (GLUE) and Second-Order Ultrasound Elastography (SOUL) methods. The principles include a novel technique to enforce (1) tissue incompressibility using 3D Boussinesq model and (2) deformation compatibility using the compatibility differential equation. The technique was validated thoroughly using metrics pertaining to Signal-to-Noise-Ratio (SNR), Contrast-to-Noise-Ratio (CNR) and Normalized Cross Correlation (NCC) for four tissue-mimicking phantom models and two clinical breast ultrasound elastography cases. The results show substantial improvement in the displacement and strain images generated using the proposed technique. The tissue-mimicking phantom study results indicate that the proposed method is superior in improving image quality compared to the GLUE and SOUL techniques as it shows an average axial strain SNR and CNR improvement of 44% and 63%, and lateral strain SNR and CNR improvement of 130% and 435%, respectively. The results of the phantom study also indicate higher accuracy of displacement images obtained using the proposed technique, including improvement ranges of 7-84% and 26-140% for axial and lateral displacement images, respectively. For the clinical cases, the results indicate average improvement of 48% and 64% in SNR and CNR, respectively, in the axial strain images, and average improvement of 40% and 41% in SNR and CNR, respectively, in the lateral strain images. The proposed method is very effective in producing improved estimate of tissue displacement and strain images, especially with the lateral displacement and strain where the improvement is highly remarkable. While the method shows promise for clinical applications, further investigation is necessary for rigorous assessment of the method's performance in the clinic.

Empirical method for rapid quantification of intrinsic fluorescence signals of key metabolic probes from optical spectra measured on tissue-mimicking turbid medium.

.Significance: Optical fluorescence spectroscopy technique has been explored extensively to quantify both glucose uptake and mitochondrial metabolism with proper fluorescent probes in small tumor models in vivo. However, it remains a great challenge to rapidly quantify the intrinsic metabolic fluorophores from the optically measured fluorescence spectra that contain significant distortions due to tissue absorption and scattering.Aim: To enable rapid spectral data processing and quantify the in vivo metabolic parameters in real-time, we present an empirical ratio-metric method for rapid fluorescence spectra attenuation correction with high accuracy.Approach: A first-order approximation of intrinsic fluorescence spectra can be obtained by dividing the fluorescence spectra by diffuse reflectance spectra with some variable powers. We further developed this approximation for rapid extraction of intrinsic key metabolic probes (2-NBDG for glucose uptake and TMRE for mitochondrial function) by dividing the distorted fluorescence spectra by diffuse reflectance intensities recorded at excitation and emission peak with a pair of system-dependent powers. Tissue-mimicking phantom studies were conducted to evaluate the method.Results: The tissue-mimicking phantom studies demonstrated that our empirical method could quantify the key intrinsic metabolic probes in near real-time with an average percent error of .Conclusions: An empirical method was demonstrated for rapid quantification of key metabolic probes from fluorescence spectra measured on a tissue-mimicking turbid medium. The proposed method will potentially facilitate real-time monitoring of key metabolic parameters of tumor models in vivo using optical spectroscopy, which will significantly advance translational cancer research.

Fast Acoustic Steering Via Tilting Electromechanical Reflectors (FASTER): A Novel Method for High Volume Rate 3-D Ultrasound Imaging.

The 3-D ultrasound imaging is essential for a wide range of clinical applications in diagnostic and interventional cardiology, radiology, and obstetrics for prenatal imaging. 3-D ultrasound imaging is also pivotal for advancing technical developments of emerging imaging technologies, such as elastography, blood flow imaging, functional ultrasound (fUS), and super-resolution microvessel imaging. At present, however, existing 3-D ultrasound imaging methods suffer from low imaging volume rate, suboptimal imaging quality, and high costs associated with 2-D ultrasound transducers. Here, we report a novel 3-D ultrasound imaging technique, fast acoustic steering via tilting electromechanical reflectors (FASTER), which provides both high imaging quality and fast imaging speed while at low cost. Capitalizing upon unique water immersible and fast-tilting microfabricated mirror to scan ultrafast plane waves in the elevational direction, FASTER is capable of high volume rate, large field-of-view (FOV) 3-D imaging with conventional 1-D transducers. In this article, we introduce the fundamental concepts of FASTER and present a series of calibration and validation studies for FASTER 3-D imaging. In a wire phantom and tissue-mimicking phantom study, we demonstrated that FASTER was capable of providing spatially accurate 3-D images with a 500-Hz imaging volume rate and an imaging FOV with a range of 48° (20 mm at 25-mm depth) in the elevational direction. We also showed that FASTER had comparable imaging quality with conventional mechanical translation-based 3-D imaging. The principles and results presented in this study establish the technical foundation for the new paradigm of high volume rate 3-D ultrasound imaging based on ultrafast plane waves and fast-tilting, water-immersible microfabricated mirrors.

Analytical Estimation of Out-of-plane Strain in Ultrasound Elastography to Improve Axial and Lateral Displacement Fields.

Many types of cancers are associated with changes in tissue mechanical properties. This has led to the development of elastography as a clinically viable method where tissue mechanical properties are mapped and visualized for cancer detection and staging. In quasi-static ultrasound elastography, a mechanical stimulation is applied to the tissue using ultrasound probe. Using ultrasound radiofrequency (RF) data acquired before and after the stimulation, the tissue displacement field can be estimated. Elasticity image reconstruction algorithms use this displacement data to generate images of the tissue elasticity properties. The accuracy of the generated elasticity images depends highly on the accuracy of the tissue displacement estimation. Tissue incompressibility can be used as a constraint to improve the estimation of axial and, more importantly, the lateral displacements in 2D ultrasound elastography. Especially in clinical applications, this requires accurate estimation of the out-of-plane strain. Here, we propose a method for providing an accurate estimate of the out-of-plane strain which is incorporated in the incompressibility equation to improve the axial and lateral displacements estimation before elastography image reconstruction. The method was validated using in silico and tissue mimicking phantom studies, leading to significant improvement in the estimated displacement.

A dynamic generalized coherence factor for side lobe suppression in ultrasound imaging

Coherence-based weighting techniques have been widely studied to weight beamsummed data to improve image quality in ultrasound imaging. Although generalized coherence factor (GCF) enhances the robustness of coherence factor (CF) with preserved speckle pattern by including some incoherent components, the side lobe suppression performance is insufficient due to constant cut-off frequency M0. To address this problem, we introduced in this paper a dynamic GCF method, referred to as DGCF-C, based on the amplitude standard deviation and the convolution output of aperture data. The cut-off frequency is adaptively selected for GCF at each imaging point using the amplitude standard deviation of aperture data. Moreover, the convolution output of aperture data is used to calculate the dynamic GCF. The proposed method is evaluated in simulation and tissue-mimicking phantom studies. The image quality was analyzed in terms of resolution, contrast ratio (CR), generalized contrast-to-noise ratio (GCNR), speckle signal-to-noise ratio (sSNR), and signal-to-noise ratio (SNR). The results demonstrate that DGCF-C (Mmax=2) achieves mean resolution improvements of 35.1% in simulation, and 32.6% in experiment, compared with GCF (M0=1). Moreover, DGCF-C (Mmax=4) outperforms GCF (M0=2) with an average GCNR improvement of 13.5% and an average sSNR improvement of 15.2%, which indicates the better-preservation of speckle.

Light-Emitting-Diode-Based Multispectral Photoacoustic Computed Tomography System.

Photoacoustic computed tomography (PACT) has been widely explored for non-ionizing functional and molecular imaging of humans and small animals. In order for light to penetrate deep inside tissue, a bulky and high-cost tunable laser is typically used. Light-emitting diodes (LEDs) have recently emerged as cost-effective and portable alternative illumination sources for photoacoustic imaging. In this study, we have developed a portable, low-cost, five-dimensional (x, y, z, t, PACT system using multi-wavelength LED excitation to enable similar functional and molecular imaging capabilities as standard tunable lasers. Four LED arrays and a linear ultrasound transducer detector array are housed in a hollow cylindrical geometry that rotates 360 degrees to allow multiple projections through the subject of interest placed inside the cylinder. The structural, functional, and molecular imaging capabilities of the LED–PACT system are validated using various tissue-mimicking phantom studies. The axial, lateral, and elevational resolutions of the system at 2.3 cm depth are estimated as 0.12 mm, 0.3 mm, and 2.1 mm, respectively. Spectrally unmixed photoacoustic contrasts from tubes filled with oxy- and deoxy-hemoglobin, indocyanine green, methylene blue, and melanin molecules demonstrate the multispectral molecular imaging capabilities of the system. Human-finger-mimicking phantoms made of a bone and blood tubes show structural and functional oxygen saturation imaging capabilities. Together, these results demonstrate the potential of the proposed LED-based, low-cost, portable PACT system for pre-clinical and clinical applications.

Magnetically Actuated Forward-Looking Interventional Ultrasound Imaging: Feasibility Studies.

Interventional ultrasound imaging is a prerequisite for guiding implants and treatment within the hearts and blood vessels. Due to limitations on the catheter's diameter, interventional ultrasonic transducers have side-looking structures although forward-looking imaging may provide more intuitive and real time guidance in treating diseased sites ahead of catheters. To address the issue, a magnetically actuated forward-looking interventional ultrasound imaging device is implemented for the first time. A forward-looking catheter containing a 1mm ring type focused 35MHz ultrasound transducer and a micro magnet, was fabricated. For imaging, the transducer was placed at the center of four electromagnetic coils positioned on four sides of a squared acrylic housing. By modifying the magnetic field, the catheter tip could be remotely translated for sector scanning. The scanning angle could reach up to 3° in 1Hz with 15mT, while wider angles of 5° could be achieved with a higher magnetic field of 25mT for ex-vivo imaging. The position of the transducer could be detected by monitoring the motion with a CCD camera, mimicking clinical X-ray imaging. In the wire target and tissue mimicking phantom studies, the measured hole size, spatial resolution and distance between wires by the proposed system were comparable with the values from a linear scanner. Multi-frame real time data acquisition was demonstrated via ex-vivo imaging on a pig's coronary artery. The feasibility of magnetically actuated forward-looking interventional ultrasound imaging was demonstrated. The remote-controlled scanning method may allow to simplify the structures of forward-looking interventional ultrasound imaging catheters.

Scattering-independent glucose absorption measurement using a spectrally resolved reflectance setup with specialized variable source-detector separations.

We report a novel approach for the accurate measurement of glucose absorption in turbid media using a spectrally resolved reflectance setup. Our proposed reflectance setup with specialized variable source-detector separations enables scattering-independent absorption measurement, which is critical to in vivo long-term glucose concentration monitoring. Starting from the first-order approximation of the radiative transfer equation (RTE), we developed a scattering-independent glucose absorption measurement method and then evaluated this approach by Monte Carlo simulations as well as tissue-mimicking phantom studies in which glucose concentration was accurately measured. Our study demonstrates the potential of our proposed scattering-independent absorption measurement technique as an effective tool to quantify glucose levels in turbid media, which is an important step towards future in vivo long-term glucose concentration monitoring in human subjects.

Breast Ultrasound Elastography Using Full Inversion-Based Elastic Modulus Reconstruction

Several cancer types, including breast cancer, are associated with tissue structural changes that yield tissue stiffening. Clinical breast examination (CBE) is a physical examination of the breast to find palpable breast tumors. This test lacks accuracy necessary for effective assessment and diagnosis of breast cancer. To develop an effective breast cancer diagnostic technique, an imaging method is proposed that maps the distribution of breast tissue relative elasticity modulus. Unlike CBE, this technique is quantitative; hence, it is expected that its accuracy is independent of the physician's experience. The proposed technique is a quasi-static elastography technique which uses radiofrequency data acquired through ultrasound imaging to determine both axial and lateral tissue displacements resulting from tissue mechanical stimulation. These displacements serve as input data for elastography image reconstruction. The reconstruction technique is developed using a full inversion framework where elastic tissue deformation equations are inverted using an iterative process. Each iteration in this process involves stress computation using finite-element analysis followed by updating elastic modulus until convergence is achieved. The proposed technique was validated by two tissue mimicking phantom studies before it was successfully applied to a clinical case. The two independent phantom studies demonstrated the robustness of the proposed method demonstrated by reconstruction errors of less than 12%. Elastic modulus images of the clinical case were compared to corresponding B-modes images where cancerous areas were identified as hypo-echoic areas. This comparison indicated marked tissue stiffening in those areas. Results obtained from the phantom and patient studies conducted in this study indicate that the proposed method is reasonably accurate; hence, the technique can be potentially used for quantitative assessment of breast cancer. The elasticity reconstruction algorithm developed in this work can be easily implemented on clinical ultrasound systems with no requirement to any additional hardware attachment for mechanical stimulation or data acquisition. As such, it can be applied as a low cost and potentially widely available technology for breast cancer diagnosis.

Quantitative Differentiation of Pneumonia from Normal Lungs: Diagnostic Assessment Using Photoacoustic Spectral Response.

Pneumonia is an acute lung infection that takes life of many young children in developing countries. Early stage (red hepatization) detection of pneumonia would be pragmatic to control mortality rate. Detection of this disease at early stages demands the knowledge of pathology, making it difficult to screen noninvasively. We propose photoacoustic spectral response (PASR), a noninvasive elasticity-dependent technique for early stage pneumonia detection. We report the quantitative red hepatization detection of pneumonia through median frequency, spectral energy, and variance. Significant contrast in spectral parameters due to change in sample elasticity is found. The tissue-mimicking phantom study illustrates a 39% increase in median frequency for 1.5 times the change in density. On applying to formalin-fixed pneumonia-affected goat lungs, it provides a distinct change in spectral parameters between pneumonia affected areas and normal lungs. The obtained PASR results were found to be highly correlating to standard histopathology. The proposed technique therefore has potential to be a regular diagnostic tool for early pneumonia detection.

Astaxanthin conjugated polypyrrole nanoparticles as a multimodal agent for photo-based therapy and imaging

Polymeric nanoparticles are emerging as promising candidates for photo-based therapy and imaging due to their versatile chemical properties and easy fabrication and functionalization. In the present study we synthesized polypyrrole nanoparticles by stabilization with astaxanthin conjugated bovine serum albumin polymer (PPy@BSA-Astx). The synthesized nanoparticles were biocompatible with MBA-MD-231 and HEK-293 cells. Interestingly, the fabricated nanoparticles produced reactive oxygen species under 808-nm laser exposure and exerted a hyperthermic effect when the power density of the laser was increased. The photodynamic efficiency of PPy@BSA-Astx was measured by DPBF assay, and it was found to generate sufficient amount of reactive radicals to kill the cells at a power density of 0.3W/cm2. In photothermal aspect, the temperature level was reached to 57°C within 5min at 1W/cm2 power density, at the concentration of 50μg/mL. The in vitro cell toxicity studies showed concentration dependent photothermal and photodynamic toxicity. Fluorescence microscopic investigation explored the cell death and intra-cellular organ destruction by photodynamic treatment. In addition, we observed a strong photoacoustic signal from a tissue mimicking phantom study of nanoparticle treated MBA-MD-231 cells. In conclusion, the fabricated PPy@BSA-Astx nanoparticles can be used as photoacoustic imaging based prognostic agents for photothermal or photodynamic treatment.

A coupled subsample displacement estimation method for ultrasound-based strain elastography

Obtaining accurate displacement estimates along both axial (parallel to the acoustic beam) and lateral (perpendicular to the beam) directions is an important task for several clinical applications such as shear strain imaging, modulus reconstruction and temperature imaging, where a full description of the two or three-dimensional (2D/3D) deformation field is required. In this study we propose an improved speckle tracking algorithm where axial and lateral motion estimations are simultaneously performed to enhance motion tracking accuracy. More specifically, using conventional ultrasound echo data, this algorithm first finds an iso-contour in the vicinity of the peak correlation between two segments of the pre- and post-deformation ultrasound radiofrequency echo data. The algorithm then attempts to find the center of the iso-contour of the correlation function that corresponds to the unknown (sub-sample) motion vector between these two segments of echo data.This algorithm has been tested using computer-simulated data, studies with a tissue-mimicking phantom, and in vivo breast lesion data. Computer simulation results show that the method improves the accuracy of both lateral and axial tracking. Such improvements are more significant when the deformation is small or along the lateral direction. Results from the tissue-mimicking phantom study are consistent with findings observed in computer simulations. Using in vivo breast lesion data we found that, compared to the 2D quadratic subsample displacement estimation methods, higher quality axial strain and shear strain images (e.g. 18.6% improvement in contrast-to-noise ratio for shear strain images) can be obtained for large deformations (up to 5% frame-to-frame and 15% local strains) in a multi-compression technique. Our initial results demonstrated that this conceptually and computationally simple method could improve the image quality of ultrasound-based strain elastography with current clinical equipment.

A novel shape-similarity-based elastography technique for prostate cancer assessment.

Association between tissue stiffness alteration and pathology is well known. This has formed the basis for prostate elastography imaging techniques where images of prostate tissue mechanical properties are reconstructed. In this paper, the authors present a novel prostate elastography technique which, unlike other techniques, relies on magnitude image data only. This proposed technique works in conjunction with ultrasound or magnetic resonance imaging (MRI) imaging modalities and it requires the prostate's pre- and postdeformation images as input. It uses a constrained reconstruction method where the elastic moduli of the prostate's normal and pathological tissues are determined based on an essential subset of the tissue deformation provided by the images data. The elasticity reconstruction technique uses optimization where similarity between calculated and observed shape features of the postcompression prostate image is maximized. The method was validated with an in silico phantom study followed by studies using ultrasound and MR with tissue-mimicking phantoms. Using the proposed methods, it was observed that the maximum uncertainties of the reconstructed Young's modulus ratios of tumor to normal tissue were 15.6% and 9.7%, which were obtained from the transrectal ultrasound (TRUS) and MR tissue-mimicking phantom studies, respectively. This novel prostate elastography technique relies on prostate TRUS or MRI images that can be routinely acquired without additional imaging hardware. The phantom studies provided evidence that the proposed technique has a good potential to reconstruct prostate stiffness maps noninvasively particularly when applied in conjunction with MRI. Further studies are necessary to evaluate the technique's merits for clinical use.

Towards clinical prostate ultrasound elastography using full inversion approach

Various types of cancers including prostate cancer are known to be associated with biological changes that lead to tissue stiffening. Digital rectal examination is based on manually palpating the prostate tissue via the rectum. This test lacks sufficient accuracy required for early diagnosis which is necessary for effective management of prostate cancer. To develop an effective prostate cancer diagnostic technique, the authors propose an imaging technique that maps the distribution of the relative prostate tissue's elasticity modulus. Unlike digital rectal examination, this technique is quantitative, capable of accurately detecting small prostate lesions that cannot be sensed by manual palpation, and its accuracy is independent of the physician's experience. The proposed technique is a quasistatic elastography technique which uses ultrasound imaging to acquire tissue displacements resulting from transrectal ultrasound mechanical stimulation. The system involves a standard ultrasound imaging unit with accessibility to its radiofrequency data. The displacements are used as data for the tissue elasticity reconstruction. This reconstruction does not require tissue segmentation and is based on physics governing tissue mechanics. It is formulated using an inverse problem framework where elastic tissue deformation equations are fully inverted using an iterative scheme where each iteration involves stress calculation followed by elastic modulus updating until convergence is achieved.In silico and tissue mimicking phantom studies were conducted to validate the proposed technique, followed by a clinical pilot study involving two prostate cancer patients with whole-mount histopathology analysis on prostatectomy specimens to confirm a cancer location. The phantom studies demonstrated robustness and reasonably high accuracy of the proposed method. Obtained Young's modulus ratios indicated reconstruction errors of less than 12%. Reconstructed elastic modulus images of the two clinical cases were compared to whole-mount histopathology slides where cancerous areas were identified. This comparison indicated marked tissue stiffening in the cancer area with reasonably accurate consistency observed between cancerous lesions identified by histopathology and high stiffness areas of the elastography images. Results obtained from the phantom and patient studies indicate that the proposed method is reasonably accurate for detecting cancerous lesions. The proposed system does not require any additional hardware attachment for mechanical stimulation or data acquisition while the elasticity reconstruction algorithm can be easily implemented, leading to a low cost system that can be potentially utilized as an effective clinical tool for prostate cancer diagnosis.

A novel fast full inversion based breast ultrasound elastography technique

Cancer detection and classification have been the focus of many imaging and therapeutic research studies. Elastography is a non-invasive technique to visualize suspicious soft tissue areas where tissue stiffness is used as image contrast mechanism. In this study, a breast ultrasound elastography system including software and hardware is proposed. Unlike current elastography systems that image the tissue strain and present it as an approximation to relative tissue stiffness, this system is capable of imaging the breast absolute Young’s modulus in fast fashion. To improve the quality of elastography images, a novel system consisting of two load cells has been attached to the ultrasound probe. The load cells measure the breast surface forces to be used for calculating the tissue stress distribution throughout the breast. To facilitate fast imaging, this stress calculation is conducted by an accelerated finite element method. Acquired tissue displacements and surface force data are used as input to the proposed Young’s modulus reconstruction technique. Numerical and tissue mimicking phantom studies were conducted for validating the proposed system. These studies indicated that fast imaging of breast tissue absolute Young’s modulus using the proposed ultrasound elastography system is feasible. The tissue mimicking phantom study indicated that the system is capable of providing reliable absolute Young’s modulus values for both normal tissue and tumour as the maximum Young’s modulus reconstruction error was less than 6%. This demonstrates that the proposed system has a good potential to be used for clinical breast cancer assessment.

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.