Tissue-like Material Research Articles

Imaging aspects of tympanokeratoma in dog

Tympanokeratoma is an otic affliction, frequently known as cholesteatoma or epidermoid cyst, being characterized as an non-neoplastic mass formation at the level of the middle ear. This mass is compose of keratin debris covered with keratinizing squamous epithelium, with multiple layers. It presents a continuous growth and determines the destruction of the tympanic bulla wall. Imaging examination reveals the presence of a soft tissue-like material in the middle ear and with different grades of affliction of the tympanic bulla wall integrity. The imaging examination helps to identify the tympanokeratoma, but the final diagnosis is establish by histopathological examination.

Implementing a simulation-based curriculum for hybrid intracavitary/interstitial brachytherapy using a new, commercially available, US/MR/CT-compatible gynecologic phantom

To establish a simulation-based workshop for teaching hybrid intracavitary/interstitial (IC/IS) brachytherapy skills using a new, commercially available US/CT/MRI-compatible gynecologic phantom prototype. The VIOMERSE gynecological trainer phantom consisted of tissue-like colloid material and was US, CT, and MRI-compatible. We designed a hands-on workshop incorporating the phantom prototype to teach skills for hybrid IC/IS brachytherapy including pre-implant planning, procedural steps of implant placement, and post-implant evaluation. The workshop impact was evaluated with pre- and post-workshop surveys and responses were analyzed with Wilcoxon matched-pairs signed-rank test. Thirteen residents, divided into small groups, attended one of three separate 1-h workshop sessions held during the gynecologic education block. Workshop steps included IC applicator placement, tumor mapping and pre-planning desired location and depth of needles for hybrid IC/IS application, IS needle labelling and insertion, image review of needle placements, comparison of IC-alone versus IC/IS brachytherapy plans. Responses to questions ascertaining knowledge, confidence, and ability in planning and executing hybrid IC/IS procedures all demonstrated significant improvement from pre- to post-workshop. In response to whether the session was an effective learning experience, all residents rated the workshop with a score of 9 (n = 1) or 10 (n = 12) out of 10, with a score of 10 indicating "strongly agree." Implementation of a hybrid IC/IS brachytherapy workshop utilizing a new, commercially-available phantom prototype was successful, with clear, subjective benefit for the residents in our program. This experience may inform continued efforts towards standardizing brachytherapy curricula across programs and increasing trainee exposure to interstitial procedures.

GPP07 Presentation Time: 9:40 AM: Investigating the Efficacy of Simulation-Based Education for Interstitial Gynecologic Brachytherapy Using a Novel US/MR/CT-Compatible Gynecologic Phantom

<h3>Purpose</h3> Brachytherapy is an essential component of curative treatment for cervical cancer. Simulation-based education using models is an effective method for teaching intracavitary (IC) brachytherapy skills. While the use of interstitial (including hybrid) applications is increasing among physicians, simulation training for gynecologic interstitial brachytherapy has been unsatisfactory. This is in part due to the limitations of current simulation models, including unsuitable material for needle placement and incompatibility with ultrasound (US), CT and/or MRI imaging. We present here the results from a simulation-based hybrid brachytherapy workshop held in March 2022, in which we seek to validate a novel, commercially available US/CT/MRI-compatible gynecologic phantom for its use in gynecologic brachytherapy training. <h3>Materials and Methods</h3> The SIM (Simulated Inanimate Models, Pittsford, NY) gynecological trainer phantom modeled a uterus, cervix, and vaginal canal within a block of tissue-like colloid material. The model also contained a gel-filled bladder and air-filled rectum. The phantom was US, CT, and MRI-compatible with realistic visualization of the pelvic organs, pubic bones, and sacral bones on imaging due to variable physical and hydrogen densities. We CT simulated the phantom with a tandem-and-ovoid applicator with 20 mm ovoids and a 30-degree curved tandem in place. We segmented the bladder and rectum and created a cervical HR-CTV with dimensions of 35 × 35 × 40 mm³. We then simulated the model again with 2 free-hand interstitial needles alongside the tandem-and-ovoids to improve geographic coverage of the HR-CTV. We designed a workshop incorporating the phantom and simulated datasets, during which trainees performed the following elements: 1- IC placement; 2- review of the IC-alone optimized plan treatment planning system; 3- schematic mapping on 3D diagrams of the HR-CTV in axial, coronal, and sagittal orientations; 4- pre-planning of location and depth of desired interstitial needles; 5- interstitial needle labeling and placement; 6- evaluation and modification of needle placement with imaging; 7- plan review and DVH comparison of HR-CTC coverage and organ-at-risk limits with and without the supplemental needles. Pre- and post-workshop surveys with Likert-style questions were administered. A Wilcoxon matched-pairs signed-rank test was used to assess statistical differences between pre- and post-workshop responses. <h3>Results</h3> Thirteen residents (PGY 2-5) participated in the workshops over the course of 3 separate 1-hour sessions. Seven residents reported performing 2 or more intracavitary procedures, and 6 reported performing 2 or more interstitial gynecologic procedures prior to workshop participation. All eligible residents completed each component of the workshop. Responses to questions ascertaining knowledge, preparedness, comfort, confidence, and ability in planning and executing IC and hybrid interstitial brachytherapy procedures all demonstrated significant improvement from pre- to post-workshop (Figure 1). In response to whether the session was an effective learning experience, all 13 residents rated the workshop with a score of 9 (n=1) or 10 (n=12) out of 10, with a score of 10 indicating ‘strongly agree.' Suggested improvements to the model included increasing dimensions of the vagina, angling of the cervix/uterus, and adding a visible/palpable tumor. <h3>Conclusions</h3> The novel gynecologic phantom simulates live tissue, permits needle placement, is US/CT/MR-compatible, and is commercially available. The improvements seen in trainee knowledge, skills, and confidence validate the novel gynecologic phantom for interstitial brachytherapy skills training. Based on responses from the workshop, improvements to the model are currently in progress, with modified model expected by the ABS annual meeting.

PO17: Assessment of a Prototype Gynecologic US/MR/CT Phantom for Utilization in Interstitial Brachytherapy Training

<h3>Purpose</h3> Simulation-based education has been previously demonstrated to be efficacious for teaching intracavitary (IC) brachytherapy. In principle, the success of this "hands-on" approach could be extended to interstitial (IS) and/or hybrid IC/IS brachytherapy. Yet, this education technique has not been adopted and one reason may be the shortcomings of current simulation models. Highly-desirable features which were not available in current simulation models included: non-stylized realistic anatomical representation, compatibility with image-guidance (ultrasound, CT, and/or MRI), practical material for needle placement, and commercial availability. Our work presents results from our evaluation of the physical, radiographic, and imaging characteristics of a new commercial prototype phantom designed for simulation-based education. <h3>Materials and Methods</h3> The SIM (Simulated Inanimate Models, Pittsford, NY) gynecological trainer prototype phantom was constructed based on a representative female pelvis CT imageset to provide physically realistic anatomy within a block of tissue-like material. The original CT imageset was truncated to a region of interest with dimensions of 160 × 160 × 220 mm. To provide a planning imageset, the phantom was imaged using CT with 1 mm slice reconstruction and using an axial T2 MRI sequence with 1.5 mm slice reconstruction. We assessed the anatomic dimensions of the model, physical compatibility with different hybrid applicators, and the quality of the radiographic model on imaging. After the implant was approved, a planning CT was taken, an HR-CTV was drawn, and the plan quality was evaluated. After clinical assessment, feedback was provided to the manufacturer for consideration in future designs. <h3>Results</h3> The phantom consisted of a 15 mm introitus which preceded a cylindrical air cavity with length of 75 mm and average diameter of 20 mm with irregular ridges intended to represent a vaginal canal which was capped by a pliable opening of 3 mm intended to represent an intact cervical os. Near the cervical region, the cylindrical air cavity widened from 20 to 28 mm. Proximal to the cervical os, there was a conical air cavity 80 mm in length which represented an intrauterine canal. In addition to the air cavities and tissue, the phantom was composed of three other distinct materials designed to represent bones, bladder, and rectum - each of which was distinguishable on US-, CT- and MR-based imaging. Within the phantom, an experienced physician was able to place a tandem-and-ovoid (TO) applicator with a 30 degree curved tandem, but was restricted to ovoid sizes ≤ 20 mm. To supplement the TO, the physician was able to place three IS needles to produce a realistic hybrid IC/IS implant intended to cover a hypothetical 35 × 35 × 40 mm³ HR-CTV. Coronal and sagittal views of the phantom post-implant planning CT imageset with <i>in situ</i> hybrid IC/IS equipment are shown in Figure 1. Figure 1 also contains the final plan with HR-CTV D_90% = 102% with the purple HR-CTV contour and red 100% isodose line. The primary clinical feedback provided to the manufacturer on this prototype phantom included: enlarging the vaginal canal dimensions to physically accommodate larger IC applicators; adding a visual/palpable cervical tumor to provide a target and recreate the needle-placement decision-making process. <h3>Conclusions</h3> We report the basic characteristics of a novel gynecologic phantom prototype which intended for simulation-based training. This phantom provided an anatomically-realistic "hand-on" tool composed of various materials which were each distinguishable on three modalities: US, CT, MR. Clinical feedback was provided to the manufacturer for consideration in the next generation of this phantom.

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.

Image-Guided Surgical Simulation in Minimally Invasive Liver Procedures: Development of a Liver Tumor Porcine Model Using a Multimodality Imaging Assessment.

Background: Image-guided liver surgery and interventions are growing as part of the current trend to translate liver procedures into minimally invasive approaches. Hands-on surgical training in such techniques is required. Consequently, a meaningful and realistic liver tumor model using multi-imaging modalities, such as ultrasound (US), computed tomography (CT), magnetic resonance (MR), cone beam-CT (CBCT), is mandatory. The first aim of this study is to develop a novel tumor-mimic model and assess it with multi-imaging modalities. The second aim is to evaluate the usefulness of the model during image-guided liver procedures. Materials and Methods: The tumor-mimic model is made of a composition of hydrogel, smashed muscle, and gadolinium contrast solution. Five ex vivo livers and three pigs were included in the study. Procedures were performed in an experimental hybrid operating room. Under general anesthesia, US guidance was required to inject the biotumor formula into the pig's liver. US, CT, CBCT, and MR acquisitions were then performed after the initial injection. In vivo models were then used to perform liver procedures, including US-guided biopsy, radiofrequency ablation, and laparoscopic resection. Results: The formula developed is easily injected generating a tissue-like material. Visualization using multi-imaging modalities was appropriate, thereby allowing to perform image-guided techniques. Conclusion: A novel design of an in vivo and ex vivo tissue-like tumor liver model is presented. Due to the multimodality imaging appraisal, it may provide a realistic and meaningful model allowing to perform image-guided liver procedures.

Estimation of Rabbit Pancreas Dispersion Between 400 and 1000 nm

Current biophotonics methods cover the entire optical spectrum from the deep ultraviolet to the terahertz. To optimize such methods for diagnostic and therapeutic applications, the need to obtain the wideband dispersion of tissues is high. The pancreas is a very important organ in the human body, since it produces insulin and its malfunction may induce diabetes. A reduced number of biophotonics publications regarding the pancreas is available, meaning that studies to determine its optical properties and their variation during optical clearing treatments are necessary. Considering this fact, we used the total internal reflection method to measure the refractive index of the rabbit pancreas for wavelengths between 400 and 850 nm. The experimental results allowed to calculate the pancreas dispersion with the Cauchy, Conrady and Cornu equations. It was observed that all those equations provided good data fitting in the spectral range of the measurements, but differences were observed outside these limits. Considering the wavelength of 633 nm, the mean value from the three dispersions was 1.3521, while the one published for porcine pancreas is 1.3517. The dispersion calculated with the Conrady equation does not present a fast decreasing behavior for shorter wavelengths as the ones calculated with the Cauchy and Cornu equations, but comparing these curves with a dispersion for a tissue-like material, all seem to have good agreement.

Tunable plant-based materials via in vitro cell culture using a Zinnia elegans model

Abstract Current systems for plant-based biomaterial production are inefficient and place unsustainable demands on environmental resources. This work proposes a novel solution to these shortcomings based on selective cultivation of tunable plant tissues using scalable, land-free techniques unconstrained by seasonality, climate, or local resource availability. By limiting biomass cultivation to only desirable plant tissues, ex planta farming promises to improve yields while reducing plant waste and competition for arable land. Employing a Zinnia elegans model system, this work provides the first proof-of-concept demonstration of isolated, tissue-like plant material production in vitro by way of gel-mediated cell culture. Parameters governing cell development and morphology including hormone concentrations, medium pH, and initial cell density are optimized and implemented to demonstrate the tunability of cultured biomaterials at cellular and macroscopic scales. Targeted deposition of cell-doped, nutrient-rich gel scaffolds via casting and 3D bioprinting enable biomaterial growth in near-final form, reducing downstream processing requirements. These investigations demonstrate the implementation of plant cell culture in a new application space, propose novel methods for quantification and evaluation of cell development, and characterize morphological developments in response to critical culture parameters—illustrating the feasibility and potential of the proposed techniques.

Shock-induced bubble collapse near a tissue-like material

In this study, we numerically investigate the shock-induced bubble collapse phenomenon near a tissue-like material. Here, a sharp-interface model is applied to represent a 3-material system containing the liquid, the air and the gelatin. We present the results of the complex interface dynamics and compare them with the experimental data. The goal of this study is to understand the mechanism of the shock wave–bubble interaction near tissues in a more accurate manner with advanced numerical methods.

Using a look-up table technique and finite element calculations for quick detection of stiff inclusions in silicone rubber

PurposeThe aim of the study was to show that a new method, using a look-up table technique, can be used to detect the presence and position of an inclusion embedded in a tissue-like material. Due to the time-consuming nature of the finite element (FE) method or FEM, real-time applications involving FEM as part of a control loop, are traditionally limited to slowly varying systems. By using a simplified two-dimensional FE model and a look-up table, we show by simulations and experiments that it is possible to achieve reasonable computational times in a tactile resonance sensor application.Design/methodology/approachA piezoelectric disk was placed in the center of a silicone rubber disk (SRD) with viscoelastic properties, where it acted as both sensor and actuator and dissipated radial acoustic waves into the silicone. The look-up table was constructed by calculating the radial Lamb wave transition frequencies in the impedance frequency response of the sensor while varying the position of an inclusion. A position-matching algorithm was developed that matched measured and calculated Lamb wave transitions and thereby identified the presence and position of an inclusion.FindingsIn an experiment, the position of a hard inclusion was determined by measuring the Lamb transition frequencies of the first radial resonance in two SRDs. The result of the matching algorithm for Disk 1 was that the matched position was less than 3% from the expected value. For Disk 2, the matching algorithm erroneously reported two false positions before reporting a position that was less than 5% from the expected value. An explanation for this discrepancy is presented. In a verifying experiment, the algorithm identified the condition with no inclusion present.Originality/valueThe approach outlined in this work, adds to the prospect of developing time-sensitive diagnostic instruments. This approach has the potential to provide a powerful technique to quickly present spatial information on detected tumors.

Clinical analysis and nonsurgical management of 11 dogs with aural cholesteatoma.

Aural cholesteatomas, also called tympanokeratomas, are destructive and expansile growths of keratinizing epithelium that develop in the middle ear. They have been reported sporadically in dogs, and surgery is usually the recommended treatment. To describe the common clinical, radiological and histological findings of cholesteatoma; to report on the outcome of conservative management. Eleven dogs (13 ears) with cholesteatomas. Medical records were reviewed for dogs diagnosed with cholesteatoma between 2012 and 2018. All dogs had computed tomography (CT) and/or magnetic resonance imaging (MRI) followed by trans-canal endoscopic procedure (TEP) for removal and biopsy of middle ear lesions. Dogs were then treated with in-clinic flushing initially weekly tapered to monthly, as well as at-home ear cleaning and application of topical otic steroid medication, initially daily then tapered to once or twice weekly. Nine dogs had a history of chronic otitis externa; head tilt or facial paralysis was present in seven and four cases, respectively. Otic examination identified a protruding nodule in seven ears. CT demonstrated soft tissue-like material in 12 bullae and expansion in seven bullae. MRI revealed minimally contrast-enhancing bulla contents in 12 ears. Post-TEP and with maintenance medical treatment, nine ears had no further signs of middle ear disease during a mean follow-up of 27.9months. The results suggest that otitis externa may not necessarily precede cholesteatoma in all dogs. MRI appears to be more sensitive than CT for identifying cholesteatomas. Conservative treatment of cholesteatomas could be useful before or as an alternative to surgery.

Underwater Contact Behavior of Alginate and Catechol-Conjugated Alginate Hydrogel Beads.

Modifying hydrogels with catechol functionality is a promising approach for improving their mechanical and interfacial properties in water, particularly in biological environments. However, the effects of this modification on hydrogels' contact behavior with soft tissues are not well-studied due to the complexity of hydrogels and lack of suitable techniques to probe this behavior. In addition, modification can alter the mechanical properties of hydrogels, resulting in consequences for adhesive strength as well. In this work, we report an investigation of the contact behavior of alginate hydrogels with and without conjugation of catechol functionality, aiming to elucidate the role of catechol modification on wet adhesion of alginates to a model tissue-like material, gelatin. To directly characterize this soft-on-soft contact, which has commonly been a challenge, we developed an indentation-based contact adhesion measurement using alginate hydrogel beads as the testing probe. We found that <3% conjugation of catechol can significantly improve the adhesion of alginate to gelatin by half an order of magnitude, with this adhesion depending heavily on contact time and pH. In contrast, the reduced elastic modulus from modification resulted in lower adhesive strength on rigid substrates. These findings provide valuable insight into the effects of catechol modification of hydrogels, especially in their interaction with tissue-like soft substrates, as well as a simple method for the direct measurement of time- and pH-dependent hydrogel adhesion behavior underwater.

The relative biological effectiveness of antiprotons

Background and purposeAside from the enhancement of physical dose deposited by antiprotons annihilating in tissue-like material compared to protons of the same range a further increase of biological effective dose has been demonstrated. This enhancement can be expressed in an increase of the relative biological effectiveness (RBE) of antiprotons near the end of range. We have performed the first-ever direct measurement of the RBE of antiprotons both at rest and in flight. Materials and methodsExperimental data were generated on the RBE of an antiproton beam entering a tissue-like target consisting of V79 cells embedded in gelatin with an energy providing a range of approximately 10cm. ResultsThe RBE in the entrance channel (the “plateau”) is only slightly above the value for a comparable proton beam, and remains low until the proximal edge of the spread-out Bragg peak (SOBP). A steep increase of RBE is seen starting from the onset of the SOBP. ConclusionsThis paper reports the final results of the experiment AD-4/ACE at CERN on the first-ever direct measurement of RBE of antiprotons and constitutes the first step toward developing treatment plans.

Shape-Shifting Droplet Networks.

We consider a three-dimensional network of aqueous droplets joined by single lipid bilayers to form a cohesive, tissuelike material. The droplets in these networks can be programed to have distinct osmolarities so that osmotic gradients generate internal stresses via local fluid flows to cause the network to change shape. We discover, using molecular dynamics simulations, a reversible folding-unfolding process by adding an osmotic interaction with the surrounding environment which necessarily evolves dynamically as the shape of the network changes. This discovery is the next important step towards osmotic robotics in this system. We also explore analytically and numerically how the networks become faceted via buckling and how quasi-one-dimensional networks become three dimensional.

Bullous Bleeding: Esophagitis Dissecans Superficialis in a Patient With Bullous Pemphigoid

Introduction: Esophagitis Dissecans Superficialis (EDS), characterized by sloughing of the esophageal epithelial lining, is a rare endoscopic finding. Causes include medications, hot beverages, celiac disease, collagen vascular diseases, idiopathy, and autoimmune bullous dermatoses (ABDs), such as Bullous Pemphigoid (BP) and Pemphigus Vulgaris (PV). Symptoms include dysphagia, odynophagia, and heartburn; vomiting of mucosal casts and hematemesis rarely occurs. We present a patient with BP and EDS with upper gastrointestinal bleeding (UGIB). Case: A 54 year-old female with a medical history of end stage renal disease, due to hypertension, status post renal allograft transplant, with graft failure on hemodialysis, presented to the emergency department (ED) with hematemesis. For 2 weeks she had worsening oral ulcerations and hematuria and 6 hours prior, she had severe nausea, burning chest pain, and 4-5 episodes of bright red vomitus. With 1 episode, she saw a “½ foot” long grayish-white soft tissue-like material. In the ED, she was hypertensive and tachycardic, with cutaneous blisters at various stages of healing. Hemoglobin was 7.1 g/dL, from 8.1 g/dL 2 weeks prior. An urgent EGD revealed mucosal sloughing involving the entire esophagus and posterior oro-pharynx, with associated clots and bleeding. Biopsy was deferred. Further history indicated she had a 4 month history of skin blisters and oral ulcerations, occurring after her transplant immunosuppresants were withdrawn, and was diagnosed with BP. Workup revealed a BP180 IgG > 150 units (normal < 9) and skin biopsy showed linear basement membrane pattern staining for IgG and C3 antibody. Her esophageal findings were attributed to her underlying BP. With PPI therapy, high-dose methylprednisolone, and mycophenolate mofetil she had significant improvement with resolution of hematemesis. A repeat endoscopic evaluation was declined. Discussion: Hematemesis with vomiting of esophageal mucosal casts is a rarely reported presentation of EDS. EDS has many potential causes, and recently, the pathophysiology and relationship between EDS and ABDs such as BP and PV have been increasingly acknowledged in the literature. Conclusion: EDS should be considered in patients who present with hematemesis and/or report of vomiting esophageal mucosal casts; endoscopic findings of exfoliative esophagitis support the diagnosis. These clinical findings should lead to consideration of ABDs as an etiology, to guide appropriate management decisions.

Activated Schwann Cell-Like Cells on Aligned Fibrin-Poly(Lactic-Co-Glycolic Acid) Structures: A Novel Construct for Application in Peripheral Nerve Regeneration

Tissue engineering approaches in nerve regeneration search for ways to support gold standard therapy (autologous nerve grafts) and to improve results by bridging nerve defects with different kinds of conduits. In this study, we describe electrospinning of aligned fibrin-poly(lactic-co-glycolic acid) (PLGA) fibers in an attempt to create a biomimicking tissue-like material seeded with Schwann cell-like cells (SCLs) in vitro for potential use as an in vivo scaffold. Rat adipose-derived stem cells (rASCs) were differentiated into SCLs and evaluated with flow cytometry concerning their differentiation and activation status [S100b, P75, myelin-associated glycoprotein (MAG), and protein 0 (P0)]. After receiving the proliferation stimulus forskolin, SCLs expressed S100b and P75; comparable to native, activated Schwann cells, while cultured without forskolin, cells switched to a promyelinating phenotype and expressed S100b, MAG, and P0. Human fibrinogen and thrombin, blended with PLGA, were electrospun and the alignment and homogeneity of the fibers were proven by scanning electron microscopy. Electrospun scaffolds were seeded with SCLs and the formation of Büngner-like structures in SCLs was evaluated with phalloidin/propidium iodide staining. Carrier fibrin gels containing rASCs acted as a self-shaping matrix to form a tubular structure. In this study, we could show that rASCs can be differentiated into activated, proliferating SCLs and that these cells react to minimal changes in stimulus, switching to a promyelinating phenotype. Aligned electrospun fibrin-PLGA fibers promoted the formation of Büngner-like structures in SCLs, which also rolled the fibrin-PLGA matrix into a tubular scaffold. These in vitro findings favor further in vivo testing.

Biotransformation of soybean oil to a self-healing biopolymer

Soybean oil in the presence of mineral salts, peptone, carbohydrates, lipase, and lipopeptide transformed to a soft tissue-like material after 10-day incubation at 37°C with shaking at 200 rpm. When damaged, the resultant soft tissue self-healed in an aqueous medium. Analysis revealed that during the self-assembly process, components present in the aqueous medium were entangled in the soft tissue; upon damage, release of these components accelerated healing. Superficial damage resulted in smooth healing, whereas deep damage gave uneven healing similar to deep skin wounds.

A Novel 3D Label-Free Monitoring System of hES-Derived Cardiomyocyte Clusters: A Step Forward to In Vitro Cardiotoxicity Testing

Unexpected adverse effects on the cardiovascular system remain a major challenge in the development of novel active pharmaceutical ingredients (API). To overcome the current limitations of animal-based in vitro and in vivo test systems, stem cell derived human cardiomyocyte clusters (hCMC) offer the opportunity for highly predictable pre-clinical testing. The three-dimensional structure of hCMC appears more representative of tissue milieu than traditional monolayer cell culture. However, there is a lack of long-term, real time monitoring systems for tissue-like cardiac material. To address this issue, we have developed a microcavity array (MCA)-based label-free monitoring system that eliminates the need for critical hCMC adhesion and outgrowth steps. In contrast, feasible field potential derived action potential recording is possible immediately after positioning within the microcavity. Moreover, this approach allows extended observation of adverse effects on hCMC. For the first time, we describe herein the monitoring of hCMC over 35 days while preserving the hCMC structure and electrophysiological characteristics. Furthermore, we demonstrated the sensitive detection and quantification of adverse API effects using E4031, doxorubicin, and noradrenaline directly on unaltered 3D cultures. The MCA system provides multi-parameter analysis capabilities incorporating field potential recording, impedance spectroscopy, and optical read-outs on individual clusters giving a comprehensive insight into induced cellular alterations within a complex cardiac culture over days or even weeks.

Photon counting spectral breast CT: Effect of adaptive filtration on CT numbers, noise, and contrast to noise ratio

Photon counting spectral (PCS) computed tomography (CT) shows promise for breast imaging. An issue with current photon-counting detectors is low count rate capabilities, artifacts resulting from nonuniform count rate across the field of view, and suboptimal spectral information. These issues are addressed in part by using tissue-equivalent adaptive filtration of the x-ray beam. The purpose of the study was to investigate the effect of adaptive filtration on different aspects of PCS breast CT. The theoretical formulation for the filter shape was derived for different filter materials and evaluated by simulation and an experimental prototype of the filter was fabricated from a tissue-like material (acrylic). The PCS CT images of a glandular breast phantom with adipose and iodine contrast elements were simulated at 40, 60, 90, and 120 kVp tube voltages, with and without adaptive filter. The CT numbers, CT noise, and contrast-to-noise ratio (CNR) were compared for spectral CT images acquired with and without adaptive filters. Similar comparison was made for material-decomposed PCS CT images. The adaptive filter improved the uniformity of CT numbers, CT noise, and CNR in both ordinary and material decomposed PCS CT images. At the same tube output the average CT noise with adaptive filter, although uniform, was higher than the average noise without adaptive filter due to x-ray absorption by the filter. Increasing tube output, so that average skin exposure with the adaptive filter was same as without filter, made the noise with adaptive filter comparable to or lower than that without adaptive filter. Similar effects were observed when energy weighting was applied, and when material decompositions were performed using energy selective CT data. An adaptive filter decreases count rate requirements to the photon counting detectors which enables PCS breast CT based on commercially available detector technologies. Adaptive filter also improves image quality in PCS breast CT by decreasing beam hardening artifacts and by eliminating spatial nonuniformities of CT numbers, noise, and CNR.

Investigation of fragment doses produced by heavy ions in tissue-like material

In this paper, the distribution of fragments produced by 55 MeV/n ⁴⁰Ar¹⁷⁺ ions in tissue-equivalent material is reported as a function angles relative to the incident particle direction. The relative fragment doses at different angles and the total dose due to the primary beam have been estimated. The results show that the fragments produced by primary beam were concentrated at very small angles, so the fraction of particle fluence diverging from the primary beam was very small. Even though the diverging fluence is a small fraction of the total, it should still be taken into account because biological systems are very sensitive to low doses of heavy ion irradiation.