Tissue Phantoms Research Articles

Design of eye phantom for optical coherence tomography angiography study.

Tissue phantoms play an important role in validating biomedical imaging techniques. For optical imaging systems such as optical coherence tomography, creating layers of phantoms with different refractive indices is important. This paper explored various phantom materials to create eye-mimicking phantoms. The phantom also included microfluidic channels to mimic vasculature. To verify the optical properties of the created phantom, the transmission and reflection spectroscopy was performed using a photoluminescent spectrometer studying the complete visible and near infrared spectrum. We created a 3D model to house multiple layers that mimicked the retina at one end and the contact lens at the other, representing the anterior segment of the eye. A realistic retinal layer-mimicking, which, among other things, may pave the way for new combined imaging modalities.

Mueller matrix analysis of a biologically sourced engineered tissue construct as polarimetric phantom.

The polarimetric properties of biological tissues are often difficult to ascertain independent of their complex structural and organizational features. Conventional polarimetric tissue phantoms have well-characterized optical properties but are overly simplified. We demonstrate that an innovative, biologically sourced, engineered tissue construct better recapitulates the desired structural and polarimetric properties of native collagenous tissues, with the added benefit of potential tunability of the polarimetric response. We bridge the gap between non-biological polarimetric phantoms and native tissues. We aim to evaluate a synthesized tissue construct for its effectiveness as a phantom that mimics the polarimetric properties in typical collagenous tissues. We use a fibroblast-derived, ring-shaped engineered tissue construct as an innovative tissue phantom for polarimetric imaging. We perform polarimetry measurements and subsequent analysis using the Mueller matrix decomposition and Mueller matrix transformation methods. Scalar polarimetric parameters of the engineered tissue are analyzed at different time points for both a control group and for those treated with the transforming growth factor . Second-harmonic generation (SHG) imaging and three-dimensional collagen fiber organization analysis are also applied. We identify linear retardance and circular depolarization as the parameters that are most sensitive to the tissue culture time and the addition of . Aside from a statistically significant increase over time, the behavior of linear retardance and circular depolarization indicates that the addition of accelerates the growth of the engineered tissue, which is consistent with expectations. We also find through SHG images that collagen fiber organization becomes more aligned over time but is not susceptible to the addition of . The engineered tissue construct exhibits changes in polarimetric properties, especially linear retardance and circular depolarization, over culture time and under treatments. This tissue construct has the potential to act as a controlled modular optical phantom for polarimetric-based methods.

A software tool for fabricating phantoms mimicking human tissues with designated dielectric properties and frequency.

Dielectric materials play a crucial role in assessing and refining the measurement performance of dielectric properties for specific tasks. The availability ofviable and standardized dielectric materials could greatly enhance medical applications related to dielectric properties. However, obtaining reliable phantoms with designated dielectric properties across a specified frequency range remains challenging. In this study, we propose software to easily determine the components of dielectric materials in the frequency range of 16 MHz to 3 GHz. A total of 184 phantoms were fabricated and measured using open-ended coaxial probe method. The relationship among dielectric properties, frequency, and thecomponents of dielectric materials was fitted through feedforward neural networks. Software was developed to quickly calculate the composition of dielectric materials. We performed validation experiments including blood, muscle, skin, and lung tissue phantoms at 128 MHz, 298 MHz, 915 MHz, and 2.45 GHz. Compared with literature values, the relative errors of dielectric properties are less than 15 %. This study establishes a reliable method for fabricating dielectric materials with designated dielectric properties and frequency through the development of the software. This research holds significant importance in enhancing medical research and applications that rely on tissue simulation using dielectric phantoms.

Magneto-Thermal Hydrogel Swarms for Targeted Lesion Sealing.

Magnetic microswarms capable of performing navigation to targeted lesions show great potential for in vivo medical applications. However, using the swarms for lesion cavity filling encounters challenges from precise delivery and sealing. Herein, this work develops a magneto-thermal hydrogel swarm consisting of magnetic hydrogel particles, which can perform phase transition induced by temperature change. The particles are prepared using a temperature-responsive hydrogel matrix, tissue adhesive monomers, and magnetic microparticles. The swarms can be remolded to various shapes, and it can be used to seal perforation in phantom and gastric tissue. The swarms can also serve as drug carriers, and their drug release profiles induced by temperature changes are characterized. Finally, the targeted delivery, adaptive filling, and sealing of a gastric ulcer using the swarms are achieved in ex vivo and in vivo environments.

A 3D wideband electromagnetic horn antenna applicator for biomedical applications

Abstract This paper proposes a new, compact, wideband 3D horn antenna for biomedical wireless applications such as cancer and tumor detection. In order to achieve the best penetration level, the antenna has been built and tuned to work in the low frequency range of 0.48–1.24 GHz, which can exhibit a high-resolution detection result. The proposed applicator is a double ridge horn antenna (DRHA). The layout and operation of the key needed components to assemble a wideband hyperthermia system are provided in this study. We assume a cylindrical human tissue phantom with wideband dispersive tissue properties, and simulation results are given. The resulting field maps are displayed in several planes to illustrate the energy localization process. The findings indicate that, in contrast to traditional narrowband systems, wideband operation may improve energy localization in deep tumor locations while eliminating hot spots. The suggested antenna was built and measured to verify the result.

Corked Microcapsules Enabling Controlled Ultrasound-Mediated Protein Delivery.

While ultrasound represents a facile, portable, and noninvasive trigger for drug delivery vehicles, most reported ultrasound-triggered drug delivery vehicles predominately present "burst" release profiles that are hard to control after the initial activation stimulus. Herein, we report a submerged electrospraying technique to fabricate protein-loaded microcapsules in which silica "corks" are embedded within the microcapsule shell. Upon the application of an ultrasound trigger, the corks can be perturbed within the shell, allowing for the release of the protein payload through a phantom tissue mimic to a degree proportional to the number/time of pulses applied. Specifically, multiple ultrasound pulses were shown to enable a 15- to 23-fold increase in the rate of release of the model bovine serum albumin protein payload relative to no ultrasound being applied, with release returning to a lower level when the ultrasound stimulus was removed. Coupled with the low cytotoxicity of the vehicle components, the corked microcapsules show promise for expanding the potential to use ultrasound to facilitate both on-demand and pulsatile release profiles.

Limitations of effective medium models for tissue phantoms in the THz frequency range

The absorption of terahertz (THz) radiation by water molecules facilitates its application to several biomedical applications such as cancer detection. Therefore, it is critical for the THz technologies to be characterised with water content in a sample. In this paper, we analyse gelatine phantoms in the THz frequency range, with continuously varying hydration levels as they dry over time. Water molecules in close proximity to the protein molecule, termed ‘bound water’, feature properties different from the ‘free water’ molecules at larger distances. We find that a common model for predicting electromagnetic properties of phantoms and tissue samples, which assumes that only the free water varies with hydration while the bound water remains constant, does not agree well with measured results. To gain insight into this behaviour, we simultaneously measured the phantom in Raman spectroscopy, which shows a continuously varying concentration of bound water with hydration level. It follows from this investigation, that the permittivity contributions of neither the biomolecules nor water are expected to be linear with water density. This means that the often used, simple effective medium model will not be accurate for many biological tissues or phantoms.

Morphological Characterization of Tissue Destruction According to the Distance Between Holmium:YAG Laser Tip and Tissue Surface.

Little is known about the soft tissue destruction by holmium laser clinically used for holmium laser enucleation of the prostate (HoLEP), subject to the distance between the laser fiber tip and the tissue surface. We aimed to investigate the impact of the distance between the laser fiber tip and the phantom surface (DLP) on a soft tissue phantom (STP) in relation to the surgical modes of HoLEP. STP responses to the laser pulses produced by a commercial holmium:yttrium aluminum garnet (Holmium:YAG) laser at an output setting 2 J were observed at different values of the DLP (0, 1, 2, 3, and 4 mm) to look at (1) the single laser pulse-induced cavitation bubble and its penetration into the STP, (2) the STP destruction by a single pulse, (3) the STP destruction by 60 pulses repeated at 12 Hz, and (4) the thermal effect by the multiple pulses visualized on a thermosensitive bovine serum albumin (BSA) STP. We observed that the laser pulse produced a heated gas bubble in water centered at the laser fiber tip. The bubble shape depended on the DLP. The bubble completely penetrated into the STP at the DLP of 0 mm and the penetration decreased with the DLP. The size of the destruction of the STP by the laser pulses was shown to decrease as the DLP increased. Test with the BSA STP showed that, at the DLP of 3 mm, the destruction became insignificant while the thermal effects were still effective. We illustrated that soft tissue destruction by the Holmium:YAG laser is associated with cavitation effects. We provide for the first time experimental evidence for various surgical modes in HoLEP such as incision and hemostasis in relation to the DLP.

Sensor-Embedded Tissue Phantom for Magnetic Resonance Elastography Mechanical Failure Testing

Abstract Magnetic Resonance Elastography (MRE) is an imaging technique capable of quantifying the stiffness of in vivo tissue by applying and imaging shear waves produced by an MRE actuator. Poor image acquisition may result from the MRE procedure if there is insufficient contact between the MRE actuator and the patient. An experimental test setup outside of the clinic will aid in reducing the number of failed acquisitions by enabling the development of advanced actuators and actuator systems. This work presents the development and testing of a sensor-embedded tissue phantom setup paired with a support vector machine (SVM) classifier to automate the MRE actuator testing process. MRE actuation of soft tissue is simulated by utilizing a voice coil positioning stage that interfaces with a phantom. To capture the resulting vibrations, accelerometers are embedded inside the phantom. Subsequent characterization experiments verify the functionality of the developed phantoms to capture wave propagation. A secondary investigation was performed by utilizing the developed setup to collect acceleration measurements at varying contact distances. We provide an overview of feature analysis and selection to develop SVM models for contact detection. Multiple SVM models are reported, and the best-performing model displayed almost perfect validation (94.53%) and test (90.91%) accuracy. The pairing of sensor-embedded phantom with an SVM for detection demonstrates potential improvements to the MRE actuator developmental process by automatically assessing contact-related issues prior to clinical testing.

A Breast Tumor Monitoring Vest with Flexible UWB Antennas-A Proof-of-Concept Study Using Realistic Breast Phantoms.

Breast cancers can appear and progress rapidly, necessitating more frequent monitoring outside of hospital settings to significantly reduce mortality rates. Recently, there has been considerable interest in developing techniques for portable, user-friendly, and low-cost breast tumor monitoring applications, enabling frequent and cost-efficient examinations. Microwave technique-based breast cancer detection, which is based on differential dielectric properties of malignant and healthy tissues, is regarded as a promising solution for cost-effective breast tumor monitoring. This paper presents the development process of the first proof-of-concept of a breast tumor monitoring vest which is based on the microwave technique. Two unique vests are designed and evaluated on realistic 3D human tissue phantoms having different breast density types. Additionally, the measured results are verified using simulations carried out on anatomically realistic voxel models of the electromagnetic simulations. The radio channel characteristics are evaluated and analyzed between the antennas embedded in the vest in tumor cases and reference cases. Both measurements and simulation results show that the proposed vest can detect tumors even if only 1 cm in diameter. Additionally, simulation results show detectability with 0.5 cm tumors. It is observed that the detectability of breast tumors depends on the frequency, antenna selection, size of the tumors, and breast types, causing differences of 0.5-30 dB in channel responses between the tumorous and reference cases. Due to simplicity and cost-efficiency, the proposed channel analysis-based breast monitoring vests can be used for breast health checks in smaller healthcare centers and for user-friendly home monitoring which can prove beneficial in rural areas and developing countries.

Design a metamaterial based applicator for hyperthermia cancer treatment

This research describes a metamaterial-based applicator with and without water bolus for cancer treatment. The metamaterial based applicator consists of a double spiral antenna and a slotted square shape artificial magnetic conductor (SSA) structure. The antenna is designed on a low-cost FR4 substrate with dimensions of 32 × 32 × 3.27 mm3, and the SSA unit cell which behaves as a metamaterial, is designed on an RT-duroid substrate with dimensions of 15 × 15 × 0.76 mm3 (size of the unit cell). The 4 × 4 unit cells of the SSA structure are optimized to direct the maximum field toward the cancer tissue. The proposed applicator (antenna + SSA structure) is tested for hyperthermia treatment using a heterogeneous phantom (skin, fat, and muscle layers) and the human-mimicked model with an air medium and a water bolus layer. The applicator’s performance is evaluated in terms of specific absorption rate (SAR), penetration depth (PD), and effective field size (EFS). Further, thermal analysis is performed, with 1.5 W of input power at the antenna port, and the maximum temperature rise of 44 0C is obtained. The cancer tissue (tumor) temperature ranges between 41 °C to 45 °C, sufficient for effective hyperthermia therapy. Finally, the suggested metamaterial based applicator is built and tested in the presence of a phantom and head tissue simulating liquid.

Interstitial dual-mode ultrasound with a 3-mm MR-compatible catheter for image-guided HIFU and directional in-vitro tissue ablations.

Current interstitial techniques of tumor ablation face challenges that ultrasound technologies could meet. The ablation radius and directionality of the ultrasound beam could improve the efficiency and precision. Here, a 9-gauge MR-compatible dual-mode ultrasound catheter prototype was experimentally evaluated for Ultrasound Image-guided High Intensity Focused Ultrasound (USgHIFU) conformal ablations. The prototype consisted of 64 piezocomposite linear array elements and was driven by an open research programmable dual-mode ultrasound platform. After verifying the US-image guidance capabilities of the prototype, the HIFU output performances (dynamic focusing and HIFU intensities) were quantitatively characterized, together with the associated 3D HIFU-induced thermal heating in tissue phantoms (using MR thermometry). Finally, the ability to produce robustly HIFU-induced thermal ablations in in-vitro liver was studied experimentally and compared to numerical modeling. Investigations of several HIFU dynamic focusing allowed overcoming the challenges of miniaturizing the device: mono-focal focusing maximized deep energy deposition, while multi-focal strategies eliminated grating lobes. The linear-array design of the prototype made it possible to produce interstitial ultrasound images of tissue and tumor mimics in situ. Multi-focal pressure fields were generated without grating lobes and transducer surface intensities reached up to Isapa = 14 W·cm-2. Seventeen elementary thermal ablations were performed in vitro. Rotation of the catheter proved the directionality of ablation, sparing non-targeted tissue. This experimental proof of concept demonstrates the feasibility of treating volumes comparable to those of primary solid tumors with a miniaturized USgHIFU catheter whose dimensions are close to those of tools traditionally used in interventional radiology, while offering new functionalities.

Enhancing photoacoustic imaging for lung diagnostics and BCI communication: simulation of cavity structures artifact generation and evaluation of noise reduction techniques.

Pandemics like COVID-19 have highlighted the potential of Photoacoustic imaging (PAI) for Brain-Computer Interface (BCI) communication and lung diagnostics. However, PAI struggles with the clear imaging of blood vessels in areas like the lungs and brain due to their cavity structures. This paper presents a simulation model to analyze the generation and propagation mechanism within phantom tissues of PAI artifacts, focusing on the evaluation of both Anisotropic diffusion filtering (ADF) and Non-local mean (NLM) filtering, which significantly reduce noise and eliminate artifacts and signify a pivotal point for selecting artifact-removal algorithms under varying conditions of light distribution. Experimental validation demonstrated the efficacy of our technique, elucidating the effect of light source uniformity on artifact-removal performance. The NLM filtering simulation and ADF experimental validation increased the peak signal-to-noise ratio by 11.33% and 18.1%, respectively. The proposed technique adds a promising dimension for BCI and is an accurate imaging solution for diagnosing lung diseases.

Microwave Technique for Linear Skull Fracture Detection-Simulation and Experimental Study Using Realistic Human Head Models.

Microwave (MW) sensing is regarded as a promising technique for various medical monitoring and diagnostic applications due to its numerous advantages and the potential to be developed into a portable device for use outside hospital settings. The detection of skull fractures and the monitoring of their healing process would greatly benefit from a rapidly and frequently usable application that can be employed outside the hospital. This paper presents a simulation- and experiment-based study on skull fracture detection with the MW technique using realistic models for the first time. It also presents assessments on the most promising frequency ranges for skull fracture detection within the Industrial, Scientific and Medical (ISM) and ultrawideband (UWB) ranges. Evaluations are carried out with electromagnetic simulations using different head tissue layer models corresponding to different locations in the human head, as well as an anatomically realistic human head simulation model. The measurements are conducted with a real human skull combined with tissue phantoms developed in our laboratory. The comprehensive evaluations show that fractures cause clear differences in antenna and channel parameters (S11 and S21). The difference in S11 is 0.1-20 dB and in S21 is 0.1-30 dB, depending on the fracture width and location. Skull fractures with a less than 1 mm width can be detected with microwaves at different fracture locations. The detectability is frequency dependent. Power flow representations illustrate how fractures impact on the signal propagation at different frequencies. MW-based detection of skull fractures provides the possibility to (1) detect fractures using a safe and low-cost portable device, (2) monitor the healing-process of fractures, and (3) bring essential information for emerging portable MW-based diagnostic applications that can detect, e.g., strokes.

Line-field confocal optical coherence tomography based on tandem interferometry with a focus-tunable lens.

This article introduces an innovative line-field confocal optical coherence tomography (LC-OCT) system based on tandem interferometry, featuring a focus-tunable lens for dynamic focusing. The principle of tandem interferometry is first recalled, and an analytical expression of the interferometric signal detected is established in order to identify the influence of key experimental parameters. The LC-OCT system is based on a Linnik-type imaging interferometer with a focus-tunable lens for focus scanning, coupled to a Michelson-type compensating interferometer using a piezoelectric linear translation stage for coherence plane scanning. The system achieves axial and lateral image resolutions of approximately 1 µm over the entire imaging depth (400 µm), in line with conventional LC-OCT. Vertical section images (B-scans) of skin acquired at 14.3 fps reveal distinguishable structures within the epidermis and dermis. Using refocusing and stitching, images of a tissue phantom were obtained with an imaging depth superior to 1.4 mm. The system holds promise for LC-OCT miniaturization, along with enhanced imaging speed and extended imaging depth.

Effect of orientation angle for needle-free jet injection

In this paper, we report on the delivery efficiency of needle-free jet injections using injectors with typical jet speed vj≈140m/s, orifice diameter do=157μm, and volume V=0.1 mL. The target substrates were either hydrogel tissue phantoms or porcine tissues combined with excised human skin. The novelty of this study is two-fold: First, we investigate the influence of injection angle relative to the skin surface, and second, we also study the influence of the jet path relative to the orientation of muscle fibers. While most commercial jet injectors employ a fitting that would render the device normal to the skin surface, recent studies have proposed oblique injections, which may be beneficial for intradermal or subcutaneous tissue injection. Furthermore, for deeper intramuscular injections, we propose that an angled jet path taking the muscle fiber orientation into account may result in a bolus or dispersion zone that is conducive to increased cellular uptake of the drug.

Fabrication and Characterization of Brain Tissue Phantoms Using Agarose Gels for Ultraviolet Vision Systems.

Recreating cerebral tissue using a tissue-mimicking phantom is valuable because it provides a tool for studying physiological and biological processes related to tissues without the necessity of performing the study directly in the tissue or even in a patient. The reproduction of the optical properties allows investigation in areas such as imaging, optics, and ultrasound, among others. This paper presents a methodology for manufacturing agarose-based phantoms that mimic the optical characteristics of brain tissue using scattering and absorbing agents and proposes combinations of these agents to recreate the healthy brain tissue optical coefficients within the wavelength range of 350 to 500 nm. The results of the characterization of the manufactured phantoms propose ideal combinations of the used materials for their use in controlled environment experiments in the UV range, following a cost-effective methodology.

Active Surface-Enhanced Raman Spectroscopy (SERS): A Novel Concept for Enhancing Signal Contrast in Complex Matrices Using External Perturbation.

Noninvasive detection of surface-enhanced Raman spectroscopy (SERS) signals from deep within tissue represents a common challenge in many biological and clinical applications including disease diagnosis and therapy monitoring. Such signals are typically weak and not readily discernible from often much larger Raman and fluorescence background signals (e.g., from surrounding tissue). Consequently, suboptimal sensitivity in the detection of SERS signals is often achieved in these situations. Similar issues can arise in SERS measurements in other diffusely scattering samples and complex matrices. Here, we propose a novel concept, active SERS, for the efficient retrieval of SERS signals from deep within complex matrices such as biological tissues that mitigates these issues. It relies on applying an external perturbation to the sample to alter the SERS signal from nanoparticles (NPs) deep inside the matrix. A measurement with and without, or before and after, such perturbation then can provide powerful contrasting data enabling an effective elimination of the matrix signals to reveal more clearly the desired SERS signal without the interfering background and associated artifacts. The concept is demonstrated using ultrasound (US) as an external source of perturbation and SERS NPs inserted deep within a heterogeneous tissue phantom mimicking a cluster of NPs accumulated within a small target lesion. The overall SERS signal intensity induced by the applied US perturbation decreased by ∼21% and the SERS signal contrast was considerably improved by eliminating subtraction artifacts present in a conventional measurement performed at a neighboring spatial location in a heterogeneous tissue sample. Although the technique was demonstrated with SERS gold NPs with a standard Raman label, it is envisaged that active SERS NPs (both the nanoscale metal geometry and Raman label) could be specifically designed to deliver an augmented response to the external stimulus to further enhance the achievable SERS signal contrast and yield even greater improvement in detection sensitivity. The method was demonstrated using transmission Raman spectroscopy; however, it is also applicable to other Raman implementations including spatially offset Raman spectroscopy and conventional Raman spectroscopy performed both at depth and at surfaces of complex matrices.

Validation of conductivity tensor imaging against diffusion tensor magnetic resonance electrical impedance tomography

Diffusion tensor magnetic resonance electrical impedance tomography (DT-MREIT) and electrodeless conductivity tensor imaging (CTI) are two emerging modalities that can quantify low-frequency tissue anisotropic conductivity properties by assuming similar properties underlie ionic mobility and water diffusion. While both methods have potential applications to estimating neuro-modulation fields or formulating forward models used for electrical source imaging, a direct comparison of the two modalities has not yet been performed in-vitro or in-vivo. Therefore, the aim of this study was to test the equivalence of these two modalities. We scanned a tissue phantom and the head of human subject using DT-MREIT and CTI protocols and reconstructed conductivity tensor and effective low frequency conductivities. We found both gray and white matter conductivities recovered by each technique were equivalent within 0.05 S/m. Both DT-MREIT and CTI require multiple processing steps, and we further assess the effects of each factor on reconstructions and evaluate the extent to which different measurement mechanisms potentially cause discrepancies between the two methods. Finally, we discuss the implications for spectral models of measuring conductivity using these techniques. The study further establishes the credibility of CTI as an electrodeless non-invasive method of measuring low frequency conductivity properties.

Fast Segmentation of Convex Cyst-like Structures in Gelatin Soft Tissue Phantoms under Ultrasound Imaging with Artifacts and Limited Training Samples

Fast Segmentation of Convex Cyst-like Structures in Gelatin Soft Tissue Phantoms under Ultrasound Imaging with Artifacts and Limited Training Samples