Tissue-mimicking Material Research Articles

Detection and differentiation of semi-transparent materials simulating biological structures using optical coherence tomography: a phantom study.

.SignificanceLymphatic and peripheral nervous system imaging is of prime importance for monitoring various important pathologic processes including cancer development and metastasis, and response to therapy.AimOptical coherence tomography (OCT) is a promising approach for this imaging task but is challenged by the near-transparent nature of these structures. Our aim is to detect and differentiate semi-transparent materials using OCT texture analysis, toward label-free neurography and lymphography.ApproachWe have recently demonstrated an innovative OCT texture analysis-based approach that used speckle statistics to image lymphatics and nerves in-vivo that does not rely on negative contrast. However, these two near-transparent structures could not be easily differentiated from each other in the texture analysis parameter space. Here, we perform a rigorous follow-up study to improve upon this differentiation in controlled phantoms mimicking the optical properties of these tissues.ResultsThe results of the three-parameter Rayleigh distribution fit to the OCT images of six types of tissue-mimicking materials varying in transparency and biophysical properties demonstrate clear differences between them, suggesting routes for improved lymphatics-nerves differentiation.ConclusionsWe demonstrate a novel OCT texture analysis-based lymphatics-nerves differentiation methodology in tissue-simulating phantoms. Future work will focus on longitudinal in-vivo lymphangiography and neurography in response to cancer therapeutics toward adaptive personalized medicine.

My contributions to ultrasound metrology

My work in ultrasound metrology has centered around developing pre-clinical testing methods for therapeutic ultrasound devices. These test methods include radiation force balance systems and methods specifically for high-intensity therapeutic ultrasound, time-delay spectrometry methods for measuring hydrophone sensitivity, acoustic characterization of tissue-mimicking material that has been approved as a medical device development tool and a comparison protocol of computational and experimental acoustic characterization for therapeutic ultrasound devices. The purpose of this work at the FDA is to develop bench testing methods to ensure proper review of medical ultrasound devices to evaluate device safety and performance. The test instruments and methods developed have helped promote the development and recognition of voluntary consensus standards, as well as FDA industry guidance, that can provide the basis for least-burdensome data collection requirements by manufacturers and allow the FDA to assess device safety and effectiveness in a more consistent, methodical and scientifically rigorous manner.

A Comparison of the Sensitivity of Contrast-Specific Imaging Modes on Clinical and Preclinical Ultrasound Scanners.

Ultrasonic contrast agents are used routinely to aid clinical diagnosis. All premium- and mid-range scanners utilise contrast-specific imaging techniques to preferentially isolate and display the nonlinear signals generated from the microbubbles when insonated with a series of ultrasound pulses. In this manuscript the abilities of four premium ultrasound scanners to detect and display the ultrasound signal from two commercially available contrast agents—SonoVue and DEFINITY®—are compared. A flow phantom was built using tubes with internal diameters of 1.6 mm and 3.2 mm, suspended at depths of 1, 5 and 8 cm and embedded in tissue-mimicking material. Dilute solutions of SonoVue and DEFINITY® were pumped through the phantom at 0.25 mL/s and 1.5 mL/s. Four transducers were used to scan the tubes—a GE Logiq E9 (C2-9) curvilinear probe, a Philips iU22 L9-3 linear array probe, an Esaote MyLab Twice linear array LA523 (4–13 MHz) and a Fujifilm VisualSonics Vevo3100 MX250 (15–30 MHz) linear array probe. We defined a new parameter to compare the ability of the ultrasound scanners to display the contrast enhancement. This was defined as the ratio of grey-scale intensity ratio in contrast-specific imaging mode relative to the B-mode intensity from the same region-of-interest within the corresponding B-mode image. The study demonstrated that the flow rates used in this study had no effect on the contrast-specific imaging mode to B-mode (CSIM-BM) ratio for the three clinical scanners studied, with SonoVue demonstrating broadly similar CSIM-BM ratios across all 3 clinical scanners. DEFINITY® also displayed similar results to SonoVue except when insonated with the Esaote MyLab Twice LA523 transducer, where it demonstrated significantly higher CSIM-BM ratios at superficial depths.

A Multimodality Myocardial Perfusion Phantom: Initial Quantitative Imaging Results.

This proof-of-concept study explores the multimodal application of a dedicated cardiac flow phantom for ground truth contrast measurements in dynamic myocardial perfusion imaging with CT, PET/CT, and MRI. A 3D-printed cardiac flow phantom and flow circuit mimics the shape of the left ventricular cavity (LVC) and three myocardial regions. The regions are filled with tissue-mimicking materials and the flow circuit regulates and measures contrast flow through LVC and myocardial regions. Normal tissue perfusion and perfusion deficits were simulated. Phantom measurements in PET/CT, CT, and MRI were evaluated with clinically used hardware and software. The reference arterial input flow was 4.0 L/min and myocardial flow 80 mL/min, corresponding to myocardial blood flow (MBF) of 1.6 mL/g/min. The phantom demonstrated successful completion of all processes involved in quantitative, multimodal myocardial perfusion imaging (MPI) applications. Contrast kinetics in time intensity curves were in line with expectations for a mimicked perfusion deficit (38 s vs. 32 s in normal tissue). Derived MBF in PET/CT and CT led to under- and overestimation of reference flow of 0.9 mL/g/min and 4.5 mL/g/min, respectively. Simulated perfusion deficit (0.8 mL/g/min) in CT resulted in MBF of 2.8 mL/g/min. We successfully performed initial, quantitative perfusion measurements with a dedicated phantom setup utilizing clinical hardware and software. These results showcase the multimodal phantom’s potential.

A Multilayered, Lesion-Embedded Ultrasound Breast Phantom with Realistic Visual and Haptic Feedback for Needle Biopsy.

Anthropomorphic phantoms have been used to provide residents with training in ultrasound-guided breast biopsy. However, different individuals differ in terms of the acoustic properties and stiffness of their breast tissues. The individual differences should be reflected in the training breast phantoms. This study aimed to develop a breast tissue-mimicking phantom that offers realistic haptic feedback and ultrasound imaging during needle insertion. We investigated the tunability of the mechanical and acoustic properties of breast tissue-mimicking materials (TMMs) to emulate fat, glandular and tumor tissues. The Design of experiments (DOE) methods and physician's feedback were used to reveal the effect of component concentration on Young's modulus and acoustic properties of breast TMMs. Furthermore, the relative backscatter power of the TMM was studied to adjust the contrast between the simulated tumor and background glandular tissue. The results indicated that Young's moduli of TMMs could be altered by adjusting the concentrations of glycerol, agar and olive oil. Changing the concentration of silicon carbide in a TMM could enhance the contrast between the target and the background materials in an ultrasound image. Finally, a series of TMMs were suggested for fat, glandular, benign tumor and malignant tumor tissues. A breast phantom with a tunability appropriately reflecting the individual differences of breast tissues was developed.

Identification of Material Viscoelastic Properties using the Motion of a Rigid Sphere Located at Tissue-Mimicking Material Interface in Response to a Dynamic Force

The motion of a rigid sphere located at tissue-mimicking material interface in response to a dynamic force of short duration for the purpose of the determination of material viscoelastic properties was investigated in this study. The experiments were performed using a rigid sphere located at tissue-like material (gelatin phantom) interfaces. An electromagnet was used to apply the desired dynamic force to the sphere and a high-speed camera was used to track the movement of the sphere. Using the experimentally measured response of the sphere and the dynamic response of the sphere predicted by a sophisticated analytical model of the sphere located at a medium interface, the shear modulus, density and damping of the tissue-mimicking material were determined. The procedure followed in this study successfully produced the shear modulus, density and viscous damping ratio of the 20% (and 30%) gelation phantom as 1320 Pa, 1040 kg/m3 and 0.12 (and 2580 Pa, 1180 kg/m3 and 0.2), respectively. As the sophisticated theoretical model that is valid for small and large sphere displacements includes many parameters for the system such as the mass and size of the sphere, the inertia force of the medium involved in motion and the radiation damping due to shear waves and the experimental setup is very straightforward, it is believed that the procedure proposed in this study can be widely exploited to identify accurate material viscoelastic properties in practice.

Fabrication and Characterization of Tissue-Mimicking Phantoms for Ultrasound-Guided Cannulation Training.

Tissue-mimicking materials (TMMs) have been investigated and used for decades as imaging phantoms in various medical applications. They are designed and fabricated to replicate certain biological tissue characteristics, a process often dictated by the target application. Moreover, TMMs have been utilized in some medical procedural training requiring the use of imaging modalities. One potential application for TMMs is ultrasound-guided cannulation training. Cannulation is a procedure that requires a level of dexterity to gain vascular access using ultrasound guidance while avoiding complications like vessel laceration and bleeding. However, an ideal phantom for this application is yet to be developed. This work investigates the development and characterization of high-fidelity phantoms for cannulation training. The mechanical (shore hardness, elastic modulus, and needle-interaction forces) and acoustic (B-mode ultrasound scans) properties of candidate materials were quantitatively compared with biological tissue. The evaluated materials included ballistic gel, plasticized polyvinyl chloride (PVC), silicone, gelatin, agar, and polyvinyl alcohol (PVA)- cryogel. Mechanical testing demonstrated that each material could replicate the Shore hardness and elasticity characteristics of different biological tissues (skin, fat, and muscle), with PVA and PVC showing tunability by varying composition or fabrication processes. Shore hardness (OO-range) for PVA ranged between 6.3 ± 1.0 to 59.3 ± 2.6 and PVC from 4.8 ± 0.7 to 14.6 ± 0.8. Ultrasound scans of PVA were the closest to human scans, both qualitatively (based on experts' opinion) and quantitatively (based on pixel intensity measurements). Modified mixtures of PVA are found to best serve as high-fidelity cannulation phantoms. Alternatively, PVC can be used to avoid troublesome fabrication processes of PVA.

Characterization of Acoustic, Cavitation, and Thermal Properties of Poly(vinyl alcohol) Hydrogels for Use as Therapeutic Ultrasound Tissue Mimics.

The thermal and mechanical effects induced in tissue by ultrasound can be exploited for therapeutic applications. Tissue-mimicking materials (TMMs), reflecting different soft tissue properties, are required for experimental evaluation of therapeutic potential. In the study described here, poly(vinyl alcohol) (PVA) hydrogels were characterized. Hydrogels prepared using different concentrations (5%-20% w/w) and molecular weights of PVA ± cellulose scatterers (2.5%-10% w/w) were characterized acoustically (sound speed, attenuation) as a function of temperature (25°C-45°C), thermally (thermal conductivity, specific heat capacity) and in terms of their cavitation thresholds. Results were compared with measurements in fresh sheep tissue (kidney, liver, spleen). Sound speed depended most strongly on PVA concentration, and attenuation, on cellulose content. For the range of formulations investigated, the PVA gel acoustic properties (sound speed: 1532 ± 17 to 1590 ± 9 m/s, attenuation coefficient: 0.08 ± 0.01 to 0.37 ± 0.02 dB/cm) fell within those measured in fresh tissue. Cavitation thresholds for 10% PVA hydrogels (50% occurrence: 4.1-5.4 MPa, 75% occurrence: 5.4-8.2 MPa) decreased with increasing cellulose content. In summary, PVA cellulose composite hydrogels may be suitable mimics of acoustic, cavitation and thermal properties of soft tissue for a number of therapeutic ultrasound applications.

Skin Phantoms for Microwave Breast Cancer Detection: A Comparative Study

The advancement of microwave radar prototypes for breast cancer detection purposes requires stable tissue-mimicking materials (phantoms) that dielectrically represent the breast tissues and allow for repeated experiments in controlled laboratory environment. In this study, we compare the dielectric properties of three different skin phantoms in to assess their suitability for prototype testing in the frequency range of 0.5 10 GHz. First, we verify the properties of two polyurethane-based fat-mimicking phantoms. Then, we evaluate the skin phantoms in larger blocks and as 2-mm thin layers. Finally, we conduct two separate experiments with the 2-mm skin phantoms layered over the two different fat phantoms. All the results are compared to dielectric properties of excised human skin tissue reported in the literature.

The comparison of noninvasive assessments of shear modulus using quantitative T2 magnetic resonance imaging and rheology of agarose hydrogel

Nondestructive and noninvasive assessments of the mechanical properties of biological tissues in vivo are essential in tissue engineering studies, for example, for designing scaffolds and monitoring tissue growth and degeneration. Agarose is widely used in biomaterial and tissue engineering studies to develop phantoms and tissue-mimicking materials because of its high biocompatibility, high stability, and low toxicity. This study aimed to provide an alternate method for nondestructive and noninvasive assessment of mechanical properties of agarose hydrogels by employing the more basic method without additional instruments compared to the standard method used in magnetic resonance imaging (MRI) measurements. In this study, the mechanical properties of agarose hydrogels of various concentrations were assessed noninvasively using quantitative T2 MRI to obtain the relaxation rate r2, and their results were compared to those from rheological measurements using the amplitude sweep method to obtain the shear modulus. The comparisons showed that the shear modulus and r2 increased exponentially with agarose concentration; however, agarose with concentrations lower than 2% had a different exponential factor than those at higher concentrations, supporting the previous cascade model theory that suggested the concentration limit for forming percolating networks in agarose hydrogels and agarose–solvent interactions. The results of this study show that the shear modulus can be assessed noninvasively by quantitative T2 MRI measurements; both methods characterize hydrogen bonding of the agarose. However, the factors related to agarose–water interactions and agarose network chains that contribute to the modulus must be considered, especially at agarose of low concentrations.

A method for determining elastic constants and boundary conditions of three-dimensional hyperelastic materials

Although there have been many studies on the identification of elastic constants and boundary conditions, it is still challenging to simultaneously estimate the unknown elastic constants and boundary conditions of a three-dimensional hyperelastic material under locally observed boundary conditions with noise. In this paper, a novel inverse method based on two different objective functions is proposed. The first objective function is constructed by a “dual fields” construction method, which utilizes redundant Cauchy boundary conditions (displacement boundary conditions and force boundary conditions) on the observable boundary. The second objective function is based on the gap between measured and calculated displacements of the observable boundary. The inverse analysis is conducted by an adjoint method and a linear approximation method based on the theories of continuum mechanics and finite element method to obtain the Jacobian matrices of the objective functions with respect to different variables. An alternating iterative algorithm based on Gauss–Newton method is proposed to minimize the objective functions. The proposed inverse algorithm is tested using nearly incompressible Neo-Hookean and nearly incompressible Mooney–Rivlin hyperelastic model in numerical experiments and physical experiments with a silicone-based tissue-mimicking material. The results of both numerical and physical experiments show the feasibility and accuracy of the proposed method.

Nonlinear Viscoelastic Properties of 3D-Printed Tissue Mimicking Materials and Metrics to Determine the Best Printed Material Match to Tissue Mechanical Behavior

3D-printed biomaterials have become ubiquitous for clinical applications including tissue-mimicking surgical/procedure planning models and implantable tissue engineering scaffolds. In each case, a fundamental hypothesis is that printed material mechanical properties should match those of the tissue being replaced or modeled as closely as possible. Evaluating these hypotheses requires 1) consistent nonlinear elastic/viscoelastic constitutive model fits of 3D-printed biomaterials and tissues and 2) metrics to determine how well 3D-printed biomaterial mechanical properties match a corresponding tissue. Here we utilize inverse finite element modeling to fit nonlinear viscoelastic models with Neo-Hookean kernels to 29 Polyjet 3D-printed tissue-mimicking materials. We demonstrate that the viscoelastic models fit well with R2 > 0.95. We also introduce three metrics ( least-squares difference, Kolmogorov–Smirnov statistics, and the area under stress/strain or load/displacement curve) to compare printed material properties to tissue properties. All metrics showed lower values for better matches between 3D-printed materials and tissues. These results provide a template for comparing 3D-printed material mechanical properties to tissue mechanical properties, and therefore, a basis for testing the fundamental hypotheses of 3D-printed tissue-mimicking materials.

Development and characterization of polyurethane-based tissue and blood mimicking materials for high intensity therapeutic ultrasound.

A polyurethane-based tissue mimicking material (TMM) and blood mimicking material (BMM) for the acoustic and thermal characterization of high intensity therapeutic ultrasound (HITU) devices has been developed. Urethane powder and other chemicals were dispersed into either a high temperature hydrogel matrix (gellan gum) or degassed water to form the TMM and BMM, respectively. The ultrasonic properties of both TMM and BMM, including attenuation coefficient, speed of sound, acoustical impedance, and backscatter coefficient, were characterized at room temperature. The thermal conductivity and diffusivity, BMM viscosity, and TMM Young's modulus were also measured. Importantly, the attenuation coefficient has a nearly linear frequency dependence, as is the case for most soft tissues and blood at 37 °C. Their mean values are 0.61f1.2 dB cm-1 (TMM) and 0.2f1.1 dB cm-1 (BMM) based on measurements from 1 to 8 MHz using a time delay spectrometry (TDS) system. Most of the other relevant physical parameters are also close to the reported values of soft tissues and blood. These polyurethane-based TMM and BMM are appropriate for developing standardized dosimetry techniques, validating numerical models, and determining the safety and efficacy of HITU devices.

A Non-invasive Method to Estimate the Stress-Strain Curve of Soft Tissue Using Ultrasound Elastography.

Ultrasound elastography performed under small strain conditions has been intensively studied. However, small deformations may be not sufficiently large to differentiate some abnormal tissues. By combining quasi-static and shear wave elastography, we developed a non-invasive method to estimate the localized stress- strain curve of materials. This method exerts progressive multistep uniaxial compression on the materials, and shear wave measurements were performed at every compression step. This method estimates the 2-D displacements between steps via a 2-D region growing motion tracking method and accumulates these displacements to obtain the large material displacements with respect to the initial configuration. At each step, the shear modulus and stress were calculated according to linear elastic theory. The proposed method was tested on custom-made tissue-mimicking phantoms. Mechanical compression testing was conducted on the samples made of the same material as the phantoms and taken as the reference. The stress-strain curves for the same material from the proposed method and from mechanical testing are in good agreement. The root mean square error (RMSE) and area percentage error (APE) of the stress-strain curve between ultrasound measurement and mechanical testing for soft materials ranged from 0.18 to 0.26 kPa and from 5.6% to 7.8%, respectively. The RMSE and APE for stiff materials ranged from 0.56 to 1.17 kPa and 8.0% to 17.9%. Therefore, our method was able to provide good estimates of the stress-strain curve for tissue-mimicking materials.

3D Printing of Noncytotoxic High-Resolution Microchannels in Bisphenol-A Ethoxylate Dimethacrylate Tissue-Mimicking Materials.

The ability to create cell-laden fluidic models that mimic the geometries and physical properties of vascularized tissue would be extremely beneficial to the study of disease etiologies and future therapies, including in the case of cancer where there is increasing interest in studying alterations to the microvasculature. Engineered systems can present significant advantages over animal studies, alleviating challenges associated with variable complexity and control. Three-dimensional (3D)-printable tissue-mimicking hydrogels can offer an alternative, where control of the biophysical properties of the materials can be achieved. Hydrogel-based systems that can recreate complex 3D structures and channels with diameters <500 μm are challenging to produce. We present a noncytotoxic photo-responsive hydrogel that supports 3D printing of complex 3D structures with microchannels down to 150 μm in diameter. Fine tuning of the 3D-printing process has allowed the production of complex structures, where for demonstration purposes we present a helical channel with diameters between 250 and 370 μm around a central channel of 150 μm in diameter in materials with mechanical and acoustic properties that closely replicate those of tissue. The ability to control and accurately reproduce the complex features of the microvasculature has value across a wide range of biomedical applications, especially when the materials involved accurately mimic the physical properties of tissue. An approach that is additionally cell compatible provides a unique setup that can be exploited to study aspects of biomedical research with an unprecedented level of accuracy.

Buildup Factor Computation and Percentage Depth Dose Simulation of Tissue Mimicking Materials for an External Photon Beam (0.15–15 MeV)

Nowadays, the use of tissue mimicking material (TMM) is widespread in both diagnostic and therapeutic medicine, as well as for quality assurance and control. For example, patient exposure evaluation during therapeutic tests has been commonly measured using TMMs. However, only a few materials have been developed for research use at the megavoltage photon energy encountered in medical radiology. In this paper, we extended our previous work to cover the photon energy range of 0.15–15 MeV for five human tissues (adipose, cortical bone, fat, lung and muscle). As a selection criterion for TMM, other than the attenuation coefficient, we introduced the computation of the buildup factor (BUF) for a given couple of energy and depth based on the geometric progression fitting method. Hence, we developed a C++ program able to compute BUF for depths up to 40 mean free path. Moreover, we simulated the percentage depth dose (PDD) of a 6 MV photon beam through each tissue and their equivalent materials using the Geant4 Monte Carlo toolkit (version 10.5). After the comparison of a set of parameters (mass attenuation and mass energy absorption coefficients, BUF, equivalent and effective atomic numbers, electron density, superficial and maximal dose and dose at 10 and 20 cm depths), we found that SB3 (a mixture of epoxy and calcium carbonate) and MS15 (a mixture of epoxy, phenol, polyethylene and aluminum oxide) accurately imitate cortical bone and muscle tissues, respectively. AP6 (a mixture of epoxy, phenol, polyethylene and teflon), glycerol trioleate and LN1 (a mixture of polyurethane and aluminum oxide) are also suitable TMMs for adipose, fat and lung tissues, respectively. Therefore, this work can be useful to physician researchers in dosimetry and radiological diagnosis.

Design and validation of a phantom for transcranial ultrasonography.

Commercial medical ultrasound phantoms are highly specific as they simulate particular clinical scenarios. This makes them expensive to use in multi-target research and training. General approaches to human tissue and organ modeling are described in the manufacturing methodology, access to which is restricted by the manufacturer's trade secret. Our aim is to propose a reproducible methodology to design a head phantom for transcranial ultrasound training and research from widely available materials and to validate its applicability. To create an anthropomorphic phantom, we used data from real patients obtained by CT and MRI scans. We combined FDM and LCD 3D printing to achieve the desired acoustic performance and ergonomics of the phantom. We fabricated the phantom using polyvinyl chloride plastisol, photopolymer, and PLA to simulate brain tissue, temporal acoustic windows, and acoustically opaque parts of the skull, respectively. Notably, the phantom fabrication method uses only readily available materials and is easy to reproduce. We developed a basic one and anatomical one versions of the head phantom. The basic version contains a simplified brain: tissue-mimicking material is poured into the skull with needles inserted, which specific pattern is easy to recognize in B-mode images. The anatomical version has an anatomically correct brain dummy extracted from MRI data and contains multiple randomly distributed small metal, plastic, and bony objects ranging in size from 1 to 3mm each. The proposed methodology allows producing head phantoms for transcranial ultrasound training and research. The anatomical accuracy of the model is proved by ultrasonography and CT studies. Both versions of the phantom comprise the skull and the brain and are intended for ultrasound imaging through the temporal bone acoustic window. Needles and small objects serve as navigation targets during the training procedure. The basic version helps learning basic navigation skills, while the anatomical one provides a realistic setting to perform the diagnostic procedure.

A patient-specific multi-modality abdominal aortic aneurysm imaging phantom

PurposeMultimodality imaging of the vascular system is a rapidly growing area of innovation and research, which is increasing with awareness of the dangers of ionizing radiation. Phantom models that are applicable across multiple imaging modalities facilitate testing and comparisons in pre-clinical studies of new devices. Additionally, phantom models are of benefit to surgical trainees for gaining experience with new techniques. We propose a temperature-stable, high-fidelity method for creating complex abdominal aortic aneurysm phantoms that are compatible with both radiation-based, and ultrasound-based imaging modalities, using low cost materials.MethodsVolumetric CT data of an abdominal aortic aneurysm were acquired. Regions of interest were segmented to form a model compatible with 3D printing. The novel phantom fabrication method comprised a hybrid approach of using 3D printing of water-soluble materials to create wall-less, patient-derived vascular structures embedded within tailored tissue-mimicking materials to create realistic surrounding tissues. A non-soluble 3-D printed spine was included to provide a radiological landmark.ResultsThe phantom was found to provide realistic appearances with intravascular ultrasound, computed tomography and transcutaneous ultrasound. Furthermore, the utility of this phantom as a training model was demonstrated during a simulated endovascular aneurysm repair procedure with image fusion.ConclusionWith the hybrid fabrication method demonstrated here, complex multimodality imaging patient-derived vascular phantoms can be successfully fabricated. These have potential roles in the benchtop development of emerging imaging technologies, refinement of novel minimally invasive surgical techniques and as clinical training tools.

Tissue-mimicking phantom materials with tunable optical properties suitable for assessment of diffuse reflectance spectroscopy during electrosurgery.

Emerging intraoperative tumor margin assessment techniques require the development of more complex and reliable organ phantoms to assess the performance of the technique before its translation into the clinic. In this work, electrically conductive tissue-mimicking materials (TMMs) based on fat, water and agar/gelatin were produced with tunable optical properties. The composition of the phantoms allowed for the assessment of tumor margins using diffuse reflectance spectroscopy, as the fat/water ratio served as a discriminating factor between the healthy and malignant tissue. Moreover, the possibility of using polyvinyl alcohol (PVA) or transglutaminase in combination with fat, water and gelatin for developing TMMs was studied. The diffuse spectral response of the developed phantom materials had a good match with the spectral response of porcine muscle and adipose tissue, as well as in vitro human breast tissue. Using the developed recipe, anatomically relevant heterogeneous breast phantoms representing the optical properties of different layers of the human breast were fabricated using 3D-printed molds. These TMMs can be used for further development of phantoms applicable for simulating the realistic breast conserving surgery workflow in order to evaluate the intraoperative optical-based tumor margin assessment techniques during electrosurgery.

Photoacoustic imaging phantoms for assessment of object detectability and boundary buildup artifacts

Standardized phantoms and test methods are needed to accelerate clinical translation of emerging photoacoustic imaging (PAI) devices. Evaluating object detectability in PAI is challenging due to variations in target morphology and artifacts including boundary buildup. Here we introduce breast fat and parenchyma tissue-mimicking materials based on emulsions of silicone oil and ethylene glycol in polyacrylamide hydrogel. 3D-printed molds were used to fabricate solid target inclusions that produced more filled-in appearance than traditional PAI phantoms. Phantoms were used to assess understudied image quality characteristics (IQCs) of three PAI systems. Object detectability was characterized vs. target diameter, absorption coefficient, and depth. Boundary buildup was quantified by target core/boundary ratio, which was higher in transducers with lower center frequency. Target diameter measurement accuracy was also size-dependent and improved with increasing transducer frequency. These phantoms enable evaluation of multiple key IQCs and may support development of comprehensive standardized test methods for PAI devices.