Development a low-cost electrical impedance tomography system for non-invasively detecting abnormal in breast tissue - Phantom study-

Electrical Impedance Tomography (EIT) is known as non-invasive method to detect and classify the abnormal breast tissues. Reimaging conductivity distribution within an area of the subject reveal abnormal tissues inside that area. In this work, we have created a very low-cost system with a simple 16-electrode phantom for doing research purposes. The EIT data were measured and reconstructed with EIDORS software.

Expanding the Horizons of Wireless Sensing

All interactions of objects, humans, and machines with the physical world are via contact forces. For instance, objects placed on a table exert their gravitational forces, and the contact interactions via our hands/feet are guided by the sense of contact force felt by our skin. Thus, the ability to sense the contact forces can allow us to measure all these ubiquitous interactions, enabling a myriad of applications. Furthermore, force sensors are a critical requirement for safer surgeries, which require measuring complex contact forces experienced as a surgical instrument interacts with the surrounding tissues during the surgical procedure. However, with currently available discrete point-force sensors, which require a battery to sense the forces and communicate the readings wirelessly, these ubiquitous sensing and surgical sensing applications are not practical. This motivates the development of new force sensors that can sense, and communicate wirelessly without consuming significant power to enable a battery-free design. In this magazine article, we present WiForce, a low-power wireless force sensor utilizing a joint sensing-communication paradigm. That is, instead of having separate sensing and communication blocks, WiForce directly transduces the force measurements onto variations in wireless signals reflecting WiForce from the sensor. This novel trans-duction mechanism also allows WiForce to generalize easily to a length continuum, where we can detect as well as localize forces acting on the continuum. We fabricate and test our sensor prototype in different scenarios, including testing beneath a tissue phantom, and obtain sub-N sensing and sub-mm localizing accuracies (0.34 N and 0.6 mm, respectively).

Interferometric imaging of thermal expansion for temperature control in retinal laser therapy

Precise control of the temperature rise is a prerequisite for proper photothermal therapy. In retinal laser therapy, the heat deposition is primarily governed by the melanin concentration, which can significantly vary across the retina and from patient to patient. In this work, we present a method for determining the optical and thermal properties of layered materials, directly applicable to the retina, using low-energy laser heating and phase-resolved optical coherence tomography (pOCT). The method is demonstrated on a polymer-based tissue phantom heated with a laser pulse focused onto an absorbing layer buried below the phantom's surface. Using a line-scan spectral-domain pOCT, optical path length changes induced by the thermal expansion were extracted from sequential B-scans. The material properties were then determined by matching the optical path length changes to a thermo-mechanical model developed for fast computation. This method determined the absorption coefficient with a precision of 2.5% and the temperature rise with a precision of about 0.2°C from a single laser exposure, while the peak did not exceed 8°C during 1 ms pulse, which is well within the tissue safety range and significantly more precise than other methods.

259 Injectable chitosan hydrogel for localized delivery of immune checkpoint inhibitors

BackgroundSystemic delivery of checkpoint inhibitors risks the development of immune-related adverse events (irAEs) in up to 85% of patients.1 Localized delivery methods with slow-release kinetics have the potential to avoid systemic exposure and reduce irAEs. Direct tumor injection is extremely difficult, as saline-based solutions are rapidly excluded from the high-pressure tumor environment. Utilizing hydrogels as a delivery medium and local depot can address this shortcoming. To this end, we developed an injectable chitosan-based hydrogel for intratumoral delivery of checkpoint antibodies.MethodsHydrogelLow-viscosity, 80% deacetylated chitosan (Heppe Medical Chitosan; Halle, Germany) was reacted with 1-ethyl-3-(-3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS) in the presence of β-glycerophosphate at room temperature for 48 hours. The mixture was then washed with ethanol and dried at 60°C. The resulting solid was dissolved in phosphate buffered saline (PBS) at concentrations from 35–70 mg/mL.In vitro release. 300 μg/mL bovine serum albumin (BSA) labeled with fluorescein-5-isothiocyanate (FITC) as a model protein drug was loaded into the hydrogel. The hydrogel was injected through a 28g needle and incubated with PBS. Samples were taken over a week period. Release kinetics were analyzed by fitting fluorescence data to zero-order, first-order, and Korsmeyer-Peppas models. To visualize retention after injection, dye-loaded hydrogels or dye in PBS alone were injected into a 0.6 wt% agar tissue phantom.In vivo imaging and tumor treatment. Flank MC38 tumors will be established in C57BL/6 mice. At tumor volumes of 50–100 mm3, 200 ug of fluorescently labeled aCTLA-4 and aPD-L1 included in the chitosan hydrogel will be delivered intratumorally. Images will be captured using an In Vivo Imaging System (IVIS). Antitumor activity will be assessed in a separate cohort using unlabeled antibodies.ResultsThe chitosan hydrogel was found to be injectable in needles as thin as 28g. After exiting the needle, the hydrogel reformed (figure 1A). Upon injection into the tissue phantom, dyed PBS immediately leaked out, primarily through the needle track, while the dyed hydrogel was retained (figure 1B). In vitro release studies demonstrated long-term, nearly zero-order, week-long sustained release (figure 1C). In vivo retention and tumor treatment studies are ongoing.Abstract 259 Figure 1Injectable chitosan hydrogel. (A) Re-formed BSA-FITC hydrogel in 1x PBS; (B) (i) Retained hydrogel in agar tissue phantom, (ii) Excluded 1x PBS in agar tissue phantom; (C) Release kinetics in 1x PBS.ConclusionsA novel injectable chitosan hydrogel was found to provide sustained release of a large model protein over a 1–2 week period with favorable in vitro kinetics. Importantly, this hydrogel can be engineered to provide faster or slower release as needed. Ongoing studies in vivo will quantify intratumoral retention, systemic dissemination, and antitumor activity.AcknowledgementsThis work is supported by the National Science Foundation Graduate Research Fellowship.ReferenceHommes J, Verheijden R, Suijkerbuijk K, Hamann D. Biomarkers of checkpoint inhibitor induced immune-related adverse events—a comprehensive review. Front Oncol 2021;10:1–16.Ethics ApprovalAnimal use was in compliance with the Public Health Service Policy on Human Care and Use of Laboratory Animals. All experiments involving laboratory animals were approved by the Institutional Animal Care and Use Committee at North Carolina State University (Protocol #19–795).

A novel algorithm of the digital nervous tissue phantom creation based on 3D Voronoi diagram application

The essential part of mathematical modelling of nutrients convectional reaction-diffusion is creation of a digital phantom of considered biological object. This process becomes an especial problem which needs to be solved before numerical calculations of the concentration gradients will be done. There are two principal ways to get the solution in this case. The first approach is the reconstruction of a digital phantom on the base of the experimental data directly. The second one is the creation of a virtual object according to the experimental evidence and the known principals de novo. The main advantage of the created phantom is a high adaptability to modelling demands and a physical problem formulation. In the present study a new algorithm of a digital phantom creation has been established. The principles of the claimed procedures are demonstrated by the example of a nervous tissue. Initially, one needs to create N 3D objects according to Voronoi diagrams. Each object has 144 edges and 69 boundaries on average. Having chosen M rear objects, a long 3D structure mimicking neurons axons is created according to a loft procedure from the start boundaries to the end ones. Then, the set of Boolean operations has been applied to form continuous smooth objects. The remain (N-(M+s)) objects are combined into several whole bodies using the loft procedures between the closet neighbours. The final structure has a good conformity with a nervous tissue architecture. Furthermore, the obtained phantom is correct to the mesh application and further numerical calculations.

In vitro CT visualization of the biopsy location by filling the core biopsy needle with contrast media

Background When performing computed tomography (CT)-guided biopsy procedures with non-disposable, automatic biopsy instruments, the actual course of the biopsy needle is not registered. Purpose To evaluate the ability to visualize the sampling location after CT-guided biopsy in vitro using a novel method, where the space between the inner needle and the outer cannula in a core biopsy needle is filled with contrast media; and to compare the grade of visibility for two different concentrations of contrast media. Material and Methods Core needle biopsies were performed in a tissue phantom using biopsy needles primed with two different iodine contrast media concentrations (140 mg I/mL and 400 mg I/mL). Commercially available needle-filling contraptions with sealing membranes were used to fill the needles. Each biopsy was imaged with CT, and the visibility was evaluated twice by three senior radiologists in a randomized order. Results The presence of traces was confirmed after biopsy, almost without exception for both concentrations. The visibility was sufficient to determine the biopsy location in all observations with the 400 mg I/mL filling, and in 7/10 observations with the 140 mg I/mL filling. The grade of visibility of the trace and the proportion of the biopsy needle course outlined were higher with the 400 mg I/mL filling. Conclusion With CT-guided biopsy in vitro, the sampling location can be visualized using a novel method of priming the biopsy needle with iodine contrast media, specifically highly concentrated contrast media.

Low-Cost and Easily Fabricated Ultrasound-Guided Breast Phantom for Breast Biopsy Training

We aimed to develop an inexpensive and easy-to-fabricate gelatin-based training phantom for improving the breast biopsy skill and confidence level of residents. Young’s modulus and acoustic properties of the gelatin tissue phantom and simulated tumors were investigated. Six residents were requested to evaluate the effectiveness of the breast phantom. The results showed that 83% (n = 5) of the participants agreed that the ultrasound image quality produced by the breast phantom was excellent or good. Only 17% (n = 1) of the participants claimed that there was room for improvement for the haptic feedback they received during the placement of the core needle into the breast phantom. The mean pre-instructional score was 17% (SD 17%) for all participants. The mean post-instructional score was 83% (SD 17%), giving an overall improvement of 67%. In conclusion, the mean needle biopsy skill and confidence levels of the participants substantially increased through simulation training on our breast phantom. The participants’ feedback showed the phantom is sufficiently realistic in terms of ultrasound imaging and haptic feedback during needle insertion; thus, the training outcome can be linked to the performance of residents when they perform a live biopsy.

Parameter Identification for Ultrasound Shear Wave Elastography Simulation

Elasticity of soft tissue is a valuable information to physicians in treatment and diagnosis of diseases. The elastic properties of tissue can be estimated with ultrasound (US) shear wave imaging (SWEI). In US-SWEI, a force push is applied inside the tissue and the resulting shear wave is detected by high-frequency imaging. The properties of the wave such as the shear wave velocity can be mapped to tissue elasticity. Commonly, wave features are extracted by tracking the peak of the shear wave, estimating the phase velocity or with machine learning methods. To tune and test these methods, often simulation data is employed since material properties and excitation can be accurately controlled. Subsequent validation on real US-SWEI data is in many cases performed on tissue phantoms such as gelatine. Clearly, validation performance of these procedures is dependent on the accuracy of the simulated tissue phantom and a thorough comparison of simulation and experimental data is needed. In this work, we estimate wave parameters from 400 US-SWEI data sets acquired in various homogeneous gelatine phantoms. We tune a linear material model to these parameters. We report an absolute percentage error for the shear wave velocity between simulation and phantom experiment of <2.5%. We validate our material model on unknown gelatine concentrations and estimate the shear wave velocity with an error <3.4% for in-range concentrations indicating that our material model is in good agreement with US-SWEI measurements.

A Technique for Mimicking Soft Tissue Manipulation from Experimental Data to a Wave Equation Model for a New Laparoscopic Virtual Reality Training System

Background: The difficulty of laparoscopic procedures and the specific psychomotor skills required support the need for a training system for intensive and repetitive practice to acquire the specific skills. The present VR training systems have some limitations with respect to the soft tissue models in the training system. This is associated with the need for a real-time simulation, which requires a balance between computational cost and accuracy. Objective: The primary objective of the study is to develop a two dimensional wave equation model that closely mimics the soft tissue manipulation in a laparoscopic procedure for a VR training system. Methods: A novel mathematical model based on the wave equation is prepared to represent the interaction between the laparoscopic tool and the soft tissue. The parameters within the model are determined through experimental analysis of a soft tissue phantom. The experimental setup involves a linear actuator applying force to the soft tissue phantom to generate deformation. Data acquisition is conducted through a camera and a robotic force acquisition system which measures force, displacement of the linear actuator and records a video. Through image processing, the displacements of the markers on the phantom’s x-y plane during its deformation are determined and these parameters are used to develop the model, which finally is validated through a comparative analysis. Results: The results from the developed model are observed and compared statistically as well as graphically with the finite element model based on deformation data. The results show that the deformation data between the developed model and the available model is significantly similar. Conclusion: This study demonstrates the adaptability of the wave equation to meet the needs of the specific surgical procedure through modification of the model based on the experimental data. Moreover, the comparative analysis further corroborates the relevance and validity of the model for the surgical training system.