Description, Feasibility, and Histological Assessment of the Vsling, a Novel Transcatheter Ventricular Repair Device.

Background: Reshaping the dilated left ventricle using a surgically implanted papillary muscle sling has been shown to provide long-term improvement in cardiac function compared to annuloplasty alone in patients with systolic heart failure. A papillary muscle sling which can be implanted via a transcatheter approach has the potential to make this treatment more widely available to patients. Methods: The Vsling transcatheter papillary muscle sling device was evaluated in a chronic animal model (sacrificed at 30 and 90 days), in a simulator, and in a human cadaver. Results: The Vsling device was successfully implanted in 10 pigs, 6 simulator procedures, and 1 human cadaver. Procedure complexity and device usability were rated as reasonable or better by 6 interventional cardiologists. Gross and histological analysis in chronic pigs through 90 days demonstrated near-complete endothelial coverage with mild inflammation and small hematoma formation but without adverse tissue reactions, thrombi, or embolization. Conclusions: Preliminary feasibility and safety of the Vsling implant and implantation procedure have been demonstrated. Human trials are planned to begin in the summer of 2022.

Sutureless energy-based wound closure: a step in the quest for trocar site hernia prevention.

OBJECTIVE: Easy and safe methods of fascia closure are needed in order to reduce the risk for trocar site hernias without affecting procedure time significantly. Here we present a method for port site closure using heat induced collagen denaturation. MATERIAL AND METHODS: Controlled heat-induced collagen denaturation was applied to laparoscopic trocar sites in living porcine animal models. These were compared to control trocar sites which were left open. Port sites were evaluated visually at days 14 and 28 after the procedure, and both visually and pathologically at post-procedural day 42. RESULTS: A total of 12 port sites were evaluated in three pigs. No incisional hernias were noted at any of the trocar sites in both groups. Histological evaluation revealed that one of the six control ports appeared to have a complete transfascial defect, whereas none of the study group trocars showed this finding. Furthermore, the study port sites showed a more robust scarring pattern. CONCLUSIONS: Heat-induced collagen denaturation in this preliminary study was found to be safe and allowed better scarring of the healing port sites. We believe that this technology may offer a safe and efficient closure of laparoscopic trocar sites. More studies are needed to further evaluate the true effectiveness of this technology.

Soft-surface grasping: radular opening in Aplysia californica.

Grasping soft, irregular material is challenging both for animals and robots. The feeding systems of many animals have adapted to this challenge. In particular, the feeding system of the marine mollusk Aplysia californica, a generalist herbivore, allows it to grasp and ingest seaweeds of varying shape, texture and toughness. On the surface of the grasper of A. californica is a structure known as the radula, a thin flexible cartilaginous sheet with fine teeth. Previous in vitro studies suggested that intrinsic muscles, I7, are responsible for opening the radula. Lesioning I7 in vivo does not prevent animals from grasping and ingesting food. New in vitro studies demonstrate that a set of fine muscle fibers on the ventral surface of the radula - the sub-radular fibers (SRFs) - mediate opening movements even if the I7 muscles are absent. Both in vitro and in vivo lesions demonstrate that removing the SRFs leads to profound deficits in radular opening, and significantly reduces feeding efficiency. A theoretical biomechanical analysis of the actions of the SRFs suggests that they induce the radular surface to open around a central crease in the radular surface and to arch the radular surface, allowing it to softly conform to irregular material. A three-dimensional model of the radular surface, based on in vivo observations and magnetic resonance imaging of intact animals, provides support for the biomechanical analysis. These results suggest how a soft grasper can work during feeding, and suggest novel designs for artificial soft graspers.

Patient positioning based on a radioactive tracer implanted in patients with localized prostate cancer: a performance and safety evaluation.

PURPOSE: To evaluate the performance and safety of a radiation therapy positioning system (RealEye) based on tracking a radioactive marker (Tracer) implanted in patients with localized prostate cancer. METHODS AND MATERIALS: We performed a single-arm multi-institutional trial in 20 patients. The iridium-192 ((192)Ir)-containing Tracer was implanted in the patient together with 4 standard gold seed fiducials. Patient prostate-related symptoms were evaluated with the International Prostate Symptom Score (IPSS) questionnaire. Computed tomography (CT) was performed for treatment planning, during treatment, and after treatment to evaluate the migration stability of the Tracer. At 5 treatment sessions, cone beam CT was performed to test the positioning accuracy of the RealEye. RESULTS: The Tracer was successfully implanted in all patients. No device or procedure-related adverse events occurred. Changes in IPSS scores were limited. The difference between the mean change in Tracer-fiducial distance and the mean change in fiducial-fiducial distance was -0.39 mm (95% confidence interval [CI] upper boundary, -0.22 mm). The adjusted mean difference between Tracer position according to RealEye and the Tracer position on the CBCT for all patients was 1.34 mm (95% CI upper boundary, 1.41 mm). CONCLUSIONS: Implantation of the Tracer is feasible and safe. Migration stability of the Tracer is good. Prostate patients can be positioned and monitored accurately by using RealEye.

Tracking accuracy of a real-time fiducial tracking system for patient positioning and monitoring in radiation therapy.

PURPOSE: In radiation therapy there is a need to accurately know the location of the target in real time. A novel radioactive tracking technology has been developed to answer this need. The technology consists of a radioactive implanted fiducial marker designed to minimize migration and a linac mounted tracking device. This study measured the static and dynamic accuracy of the new tracking technology in a clinical radiation therapy environment. METHODS AND MATERIALS: The tracking device was installed on the linac gantry. The radioactive marker was located in a tissue equivalent phantom. Marker location was measured simultaneously by the radioactive tracking system and by a Microscribe G2 coordinate measuring machine (certified spatial accuracy of 0.38 mm). Localization consistency throughout a volume and absolute accuracy in the Fixed coordinate system were measured at multiple gantry angles over volumes of at least 10 cm in diameter centered at isocenter. Dynamic accuracy was measured with the marker located inside a breathing phantom. RESULTS: The mean consistency for the static source was 0.58 mm throughout the tested region at all measured gantry angles. The mean absolute position error in the Fixed coordinate system for all gantry angles was 0.97 mm. The mean real-time tracking error for the dynamic source within the breathing phantom was less than 1 mm. CONCLUSIONS: This novel radioactive tracking technology has the potential to be useful in accurate target localization and real-time monitoring for radiation therapy.

Analysis of dose to patient, spouse/caretaker, and staff, from an implanted trackable radioactive fiducial for use in the radiation treatment of prostate cancer.

PURPOSE: A fiducial tracking system based on a novel radioactive tracking technology is being developed for real-time target tracking in radiation therapy. In this study, the authors calculate the radiation dose to the patient, the spouse/caretaker, and the medical staff that would result from a 100 microCi Ir192 radioactive fiducial marker permanently implanted in the prostate of a radiation therapy patient. METHODS: Local tissue dose was calculated by Monte Carlo simulation. The patient's whole body effective dose equivalent was calculated by summing the doses to the sensitive organs. Exposure of the spouse/caretaker was calculated from the NRC guidelines. Exposure of the medical staff was based on estimates of proximity to and time spent with the patient. RESULTS: The local dose is below 40 Gy at 5 mm from the marker and below 10 Gy at 10 mm from the marker. The whole body effective dose equivalent to the patient is 64 mSv. The dose to the spouse/caretaker is 0.25 mSv. The annual exposures of the medical staff are 0.2 mSv for a doctor performing implantations and 0.34 mSv for a radiation therapist positioning patients for therapy. CONCLUSIONS: The local dose is not expected to have any clinically significant effect on the surrounding tissue which is irradiated during therapy. The dose to the patient is small in comparison to the whole body dose received from the therapy itself. The exposure of all other people is well below the recommended limits. The authors conclude that there is no radiation exposure related contraindication for use of this technology in the radiation treatment of prostate cancer.

Stability, visibility, and histologic analysis of a new implanted fiducial for use as a kilovoltage radiographic or radioactive marker for patient positioning and monitoring in radiotherapy.

PURPOSE: To analyze the stability, visibility, and histology of a novel implantable soft-tissue marker (nonradioactive and radioactive) implanted in dog prostate and rabbit liver. METHODS AND MATERIALS: A total of 34 nonradioactive and 35 radioactive markers were implanted in 1 dog and 16 rabbits. Stability was assessed by measuring intermarker distance (IMD) variation relative to IMDs at implantation. The IMDs were measured weekly for 4 months in the dog and biweekly for 2-4 weeks in the rabbits. Ultrasound and X-ray imaging were performed on all subjects. Computed tomography and MRI were performed on the dog. Histologic analysis was performed on the rabbits after 2 or 4 months. RESULTS: A total of 139 measurements had a mean (+/- SD) absolute IMD variation of 1.1 +/- 1.1 mm. These IMD variations are consistent with those reported in the literature as due to random organ deformation. The markers were visible, identifiable, and induced minimal or no image artifacts in all tested imaging modalities. Histologic analysis revealed that all pathologic changes were highly localized and not expected to be clinically significant. CONCLUSIONS: The markers were stable from the time of implantation. The markers were found to be compatible with all common medical imaging modalities. The markers caused no significant histologic effects. With respect to marker stability, visibility, and histologic analysis these implanted fiducials are appropriate for soft-tissue target positioning in radiotherapy.

The kinematics of multifunctionality: comparisons of biting and swallowing in Aplysia californica.

What are the mechanisms of multifunctionality, i.e. the use of the same peripheral structures for multiple behaviors? We studied this question using the multifunctional feeding apparatus of the marine mollusk Aplysia californica, in which the same muscles mediate biting (an attempt to grasp food) and swallowing (ingestion of food). Biting and swallowing responses were compared using magnetic resonance imaging of intact, behaving animals and a three-dimensional kinematic model. Biting is associated with larger amplitude protractions of the grasper (radula/odontophore) than swallowing, and smaller retractions. Larger biting protractions than in swallowing appear to be due to a more anterior position of the grasper as the behavior begins, a larger amplitude contraction of protractor muscle I2, and contraction of the posterior portion of the I1/I3/jaw complex. The posterior I1/I3/jaw complex may be context-dependent, i.e. its mechanical context changes the direction of the force it exerts. Thus, the posterior of I1/I3 may aid protraction near the peak of biting, whereas the entire I1/I3/jaw complex acts as a retractor during swallowing. In addition, larger amplitude closure of the grasper during swallowing allows an animal to exert more force as it ingests food. These results demonstrate that differential deployment of the periphery can mediate multifunctionality.

Mechanical reconfiguration mediates swallowing and rejection in Aplysia californica.

Muscular hydrostats, such as tongues, trunks or tentacles, have fewer constraints on their degrees of freedom than musculoskeletal systems, so changes in a structure's shape may alter the positions and lengths of other components (i.e., induce mechanical reconfiguration). We studied mechanical reconfiguration during rejection and swallowing in the marine mollusk Aplysia californica. During rejection, inedible material is pushed out of an animal's buccal cavity. The grasper (radula/odontophore) closes on inedible material, and then a posterior muscle, I2, pushes the grasper toward the jaws (protracts it). After the material is released, an anterior muscle complex (the I1/I3/jaw complex) pushes the grasper toward the esophagus (retracts it). During swallowing, the grasper is protracted open, and then retracts closed, pulling in food. Grasper closure changes its shape. Magnetic resonance images show that grasper closure lengthens I2. A kinetic model quantified the changes in the ability of I2 and I1/I3 to exert force as grasper shape changed. Grasper closure increases I2's ability to protract during rejection, and increases I1/I3's ability to retract during swallowing. Motor neurons controlling radular closure may therefore affect the behavioral outputs of I2's and I1/I3's motor neurons. Thus, motor neurons may modulate the outputs of other motor neurons through mechanical reconfiguration.

Neural control exploits changing mechanical advantage and context dependence to generate different feeding responses in Aplysia.

How does neural control reflect changes in mechanical advantage and muscle function? In the Aplysia feeding system a protractor muscle's mechanical advantage decreases as it moves the structure that grasps food (the radula/odontophore) in an anterior direction. In contrast, as the radula/odontophore is moved forward, the jaw musculature's mechanical advantage shifts so that it may act to assist forward movement of the radula/odontophore instead of pushing it posteriorly. To test whether the jaw musculature's context-dependent function can compensate for the falling mechanical advantage of the protractor muscle, we created a kinetic model of Aplysia's feeding apparatus. During biting, the model predicts that the reduction of the force in the protractor muscle I2 will prevent it from overcoming passive forces that resist the large anterior radula/odontophore displacements observed during biting. To produce protractions of the magnitude observed during biting behaviors, the nervous system could increase I2's contractile strength by neuromodulating I2, or it could recruit the I1/I3 jaw muscle complex. Driving the kinetic model with in vivo EMG and ENG predicts that, during biting, early activation of the context-dependent jaw muscle I1/I3 may assist in moving the radula/odontophore anteriorly during the final phase of protraction. In contrast, during swallowing, later activation of I1/I3 causes it to act purely as a retractor. Shifting the timing of onset of I1/I3 activation allows the nervous system to use a mechanical equilibrium point that allows I1/I3 to act as a protractor rather than an equilibrium point that allows I1/I3 to act as a retractor. This use of equilibrium points may be similar to that proposed for vertebrate control of movement.

Imaging freely moving subjects using continuous interleaved orthogonal magnetic resonance imaging.

Magnetic resonance imaging has shown increasing clinical utility for the diagnosis of abnormalities in fetal development. MRI is not yet as effective for fetal imaging as ultrasound because of the difficulty of imaging freely moving subjects. We describe a design approach to overcome this difficulty. By interleaving orthogonal images of a subject, it is possible to rapidly and interactively localize the scan plane in a moving subject and confirm image plane orientation relative to the subject. We derive the equations necessary to optimize the tip angles for the acquisition of the orthogonal images so as to minimize artifact in the main image despite the long T1 of a fluid environment (e.g., amniotic fluid). To fully utilize the orthogonal images for rapid localization, it is critical to minimize the delay between acquisition and display, and to avoid segmented reconstruction techniques that are commonly used in high frame rate imaging. We demonstrate that this approach can be used to perform interactive scan plane localization on a moving subject and can obtain high temporal resolution images while confirming the image plane orientation relative to the subject.

A kinematic model of swallowing in Aplysia californica based on radula/odontophore kinematics and in vivo magnetic resonance images.

A kinematic model of the buccal mass of Aplysia californica during swallowing has been developed that incorporates the kinematics of the odontophore, the muscular structure that underlies the pincer-like grasping structure, the radula. The model is based on real-time magnetic resonance images (MRIs) of the mid-sagittal cross section of the buccal mass during swallowing. Using kinematic relationships derived from isolated odontophores induced to perform feeding-like movements, the model generates predictions about movement of the buccal mass in the medio-lateral dimension during the feeding cycle that are well-matched to corresponding coronal MRIs of the buccal mass during swallowing. The model successfully reproduces changes in the lengths of the intrinsic (I) buccal muscles I2 and I3 measured experimentally. The model predicts changes in the length of the radular opener muscle I7 throughout the swallowing cycle, generates hypotheses about the muscular basis of radular opening prior to the onset of forward rotation during swallowing and suggests possible context-dependent functions for the I7 muscle, the radular stalk and the I5 (ARC) muscle during radular opening and closing.

Radula-centric and odontophore-centric kinematic models of swallowing in Aplysia californica.

Two kinematic models of the radula/odontophore of the marine mollusc Aplysia californica were created to characterize the movement of structures inside the buccal mass during the feeding cycle in vivo. Both models produce a continuous range of three-dimensional shape changes in the radula/odontophore, but they are fundamentally different in construction. The radulacentric model treats the radular halves as rigid bodies that can pitch, yaw and roll relative to a fixed radular stalk, thus creating a three-dimensional shape. The odontophore-centric model creates a globally convex solid representation of the radula/odontophore directly, which then constrains the positions and shapes of internal structures. Both radula/odontophore models are placed into a pre-existing kinematic model of the I1/I3 and I2 muscles to generate three-dimensional representations of the entire buccal mass. High-temporal-resolution, mid-sagittal magnetic resonance (MR) images of swallowing adults in vivo are used to provide non-invasive, artifact-free shape and position parameter inputs for the models. These images allow structures inside the buccal mass to be visualized directly, including the radula, radular stalk and lumen of the I1/I3 cavity. Both radula-centric and odontophore-centric models were able to reproduce two-dimensional, mid-sagittal radula/odontophore and buccal mass kinematics, but the odontophore-centric model's predictions of I1/I3, I2 and I7 muscle dimensions more accurately matched data from MR-imaged adults and transilluminated juveniles.

Kinematics of the buccal mass during swallowing based on magnetic resonance imaging in intact, behaving Aplysia californica.

A novel magnetic resonance imaging interface has been developed that makes it possible to image movements in intact, freely moving subjects. We have used this interface to image the internal structures of the feeding apparatus (i.e. the buccal mass) of the marine mollusc Aplysia californica. The temporal and spatial resolution of the resulting images is sufficient to describe the kinematics of specific muscles of the buccal mass and the internal movements of the main structures responsible for grasping food, the radula and the odontophore. These observations suggest that a previously undescribed feature on the anterior margin of the odontophore, a fluid-filled structure that we term the prow, may aid in opening the jaw lumen early in protraction. Radular closing during swallowing occurs near the peak of protraction as the radular stalk is pushed rapidly out of the odontophore. Retraction of the odontophore is enhanced by the closure of the lumen of the jaws on the elongated odontophore, causing the odontophore to rotate rapidly towards the esophagus. Radular opening occurs after the peak of retraction and without the active contraction of the protractor muscle 12 and is due, in part, to the movement of the radular stalk into the odontophore. The large variability between responses also suggests that the great flexibility of swallowing responses may be due to variability in neural control and in the biomechanics of the ingested food and to the inherent flexibility of the buccal mass.