Theoretical investigation of transgastric and intraductal approaches for ultrasound-based thermal therapy of the pancreas.

BackgroundThe goal of this study was to theoretically investigate the feasibility of intraductal and transgastric approaches to ultrasound-based thermal therapy of pancreatic tumors, and to evaluate possible treatment strategies.MethodsThis study considered ultrasound applicators with 1.2 mm outer diameter tubular transducers, which are inserted into the tissue to be treated by an endoscopic approach, either via insertion through the gastric wall (transgastric) or within the pancreatic duct lumen (intraductal). 8 patient-specific, 3D, transient, biothermal and acoustic finite element models were generated to model hyperthermia (n = 2) and ablation (n = 6), using sectored (210°-270°, n = 4) and 360° (n = 4) transducers for treatment of 3.3-17.0 cm3 tumors in the head (n = 5), body (n = 2), and tail (n = 1) of the pancreas. A parametric study was performed to determine appropriate treatment parameters as a function of tissue attenuation, blood perfusion rates, and distance to sensitive anatomy.ResultsParametric studies indicated that pancreatic tumors up to 2.5 or 2.7 cm diameter can be ablated within 10 min with the transgastric and intraductal approaches, respectively. Patient-specific simulations demonstrated that 67.1-83.3% of the volumes of four sample 3.3-11.4 cm3 tumors could be ablated within 3-10 min using transgastric or intraductal approaches. 55.3-60.0% of the volume of a large 17.0 cm3 tumor could be ablated using multiple applicator positions within 20-30 min with either transgastric or intraductal approaches. 89.9-94.7% of the volume of two 4.4-11.4 cm3 tumors could be treated with intraductal hyperthermia. Sectored applicators are effective in directing acoustic output away from and preserving sensitive structures. When acoustic energy is directed towards sensitive structures, applicators should be placed at least 13.9-14.8 mm from major vessels like the aorta, 9.4-12.0 mm from other vessels, depending on the vessel size and flow rate, and 14 mm from the duodenum.ConclusionsThis study demonstrated the feasibility of generating shaped or conformal ablative or hyperthermic temperature distributions within pancreatic tumors using transgastric or intraductal ultrasound

Effect of practical layered dielectric loads on SAR patterns from dual concentric conductor microstrip antennas

Radiation patterns of 2 and 4cm square Dual Concentric Conductor (DCC) microstrip antennas were studied theoretically with Finite Difference Time Domain (FDTD) analysis and compared with experimental measurements of power deposition (SAR) in layered lossy dielectric loads. Single and array configurations were investigated with 915 MHz excitation applied across either one, two or four sides, or four corners of the square apertures. FDTD simulations were carried out for realistic models of a muscle tissue load coupled to the DCC antennas with a 5 mm thick bolus of either distilled water or low loss Silicone Oil. This study characterizes the effect on SAR of adding three additional thin dielectric layers which are necessary for clinical use of the applicator. These layers consist of a 0.1 mm thick dielectric coating on the array surface to provide electrical isolation of DCC apertures, and 0.15 mm thick plastic layers above and below the bolus to contain the liquid. Experimental measurements of SAR in a plane 1 cm deep in muscle phantom agree well with theoretical FDTD simulations in the multi-layered tissue models. These studies reveal significant changes in SAR for applicator configurations involving low dielectric constant (Er) layers on either side of a high Er water bolus layer. Prominent changes include a broadening and centring of the SAR under each aperture as well as increased SAR penetration in muscle. No significant differences are noted between the simple and complete load configurations for the low Er Silicone Oil bolus. Both theoretical and measured data demonstrate relatively uniform SAR distributions with50% of maximum SAR extending to the perimeter of single and multi-aperture array configurations of DCC applicators when using a thin 5 mm water or Silicone Oil bolus

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

A Glycoprotein in Shells of Conspecifics Induces Larval Settlement of the Pacific Oyster Crassostrea gigas

Settlement of larvae of Crassostrea gigas on shell chips (SC) prepared from shells of 11 different species of mollusks was investigated. Furthermore, the settlement inducing compound in the shell of C. gigas was extracted and subjected to various treatments to characterize the chemical cue. C. gigas larvae settled on SC of all species tested except on Patinopecten yessoensis and Atrina pinnata. In SC of species that induced C. gigas larvae to settle, settlement was proportionate to the amount of SC supplied to the larvae. When compared to C. gigas SC, all species except Crassostrea nippona showed lower settlement inducing activities, suggesting that the cue may be more abundant or in a more available form to the larvae in shells of conspecific and C. nippona than in other species. The settlement inducing activity of C. gigas SC remained intact after antibiotic treatment. Extraction of C. gigas SC with diethyl ether (Et2O-ex), ethanol (EtOH-ex), and water (Aq-ex) did not induce larval settlement of C. gigas larvae. However, extraction of C. gigas SC with 2N of hydrochloric acid (HCl-ex) induced larval settlement that was at the same level as the SC. The settlement inducing compound in the HCl-ex was stable at 100°C but was destroyed or degraded after pepsin, trypsin, PNGase F and trifluoromethanesulfonic acid treatments. This chemical cue eluted between the molecular mass range of 45 and 150 kDa after gel filtration and revealed a major band at 55 kDa on the SDS-PAGE gel after staining with Stains-all. Thus, a 55 kDa glycoprotein component in the organic matrix of C. gigas shells is hypothesized to be the chemical basis of larval settlement on conspecifics

Low Intensity Pulsed Ultrasound (LIPUS) for the Treatment of Spinal Disc Degeneration

Low intensity pulsed ultrasound (LIPUS)can induce cellular and bulk tissue effects that can be exploited for therapeutic purposes. In contrast to HIFU ablation, these acoustic exposures are minimal, and at most generate low temperature elevation. In order to facilitate clinical studies of image-guided therapeutic ultrasound for intervertebral disc regeneration and treatment of back pain, we plan to: (i) implement studies in proven animal models in vivo to demonstrate potential of ultrasound to increase cellularity, reduce inflammation, and improve remodeling to acute or degenerative disc-related back injury; and (ii) to demonstrate through experiments that a MRg-HIFU system is one possible vehicle for therapeutic delivery

Deployable cylindrical phased-array applicator mimicking a concentric-ring configuration for minimally-invasive delivery of therapeutic ultrasound

A novel design for a deployable catheter-based ultrasound applicator for endoluminal and laparoscopic intervention is introduced. By combining a 1D cylindrical ring phased array with an expandable paraboloid or conical-shaped balloon-based reflector, the applicator can be controllably collapsed for compact delivery and deployed to mimic a forward-firing larger diameter concentric ring array with tight focusing and electronic steering capabilities in depth. Comprehensive acoustic and biothermal parametric studies were employed to characterize the capabilities of the applicator design as a function of transducer dimensions, phased array configuration, and balloon reflector geometry. Modeling results indicate that practical balloon sizes (43-57 mm expanded diameter), transducer array configurations (e.g. 1.5 MHz, 10 mm OD  ×  20 mm length, 8 or 16 array elements), and sonication durations (30 s) are capable of producing spatially-localized acoustic intensity focal patterns and ablative thermal lesions (width: 2.8-4.8 mm; length: 5.3-40.1 mm) in generalized soft tissue across a 5-100 mm depth range. Larger focal intensity gain magnitudes and narrower focal dimensions are attainable using paraboloid-shaped balloon reflectors with natural geometric focal depths of 25-55 mm, whereas conical-shaped reflectors (angled 45-55°) produce broader foci and extend electronic steering range in depth. A proof-of-concept phased array applicator assembly was fabricated and characterized using hydrophone and radiation force balance measurements and demonstrated good agreement with simulation. The results of this study suggest that combining small diameter cylindrical phased arrays with expandable balloon reflectors can enhance minimally invasive ultrasound-based intervention by augmenting achievable focal gains and penetration depths with dynamic adjustment of treatment depth

Catheter-based ultrasound technology for image-guided thermal therapy: Current technology and applications

Catheter-based ultrasound (CBUS) is applied to deliver minimally invasive thermal therapy to solid cancer tumours, benign tissue growth, vascular disease, and tissue remodelling. Compared to other energy modalities used in catheter-based surgical interventions, unique features of ultrasound result in conformable and precise energy delivery with high selectivity, fast treatment times, and larger treatment volumes. We present a concise review of CBUS technology being currently utilized in animal and clinical studies or being developed for future applications. CBUS devices have been categorised into interstitial, endoluminal and endovascular/cardiac applications. Basic applicator designs, site-specific evaluations and possible treatment applications have been discussed in brief. Particular emphasis has been given to ablation studies that incorporate image guidance for applicator placement, therapy monitoring, feedback control, and post-procedure assessment. Examples of devices included here span the entire spectrum of the development cycle from preliminary simulation-based design studies to implementation in clinical investigations. The use of CBUS under image guidance has the potential for significantly improving precision and applicability of thermal therapy delivery

Transurethral high-intensity ultrasound for treatment of stress urinary incontinence (SUI): simulation studies with patient-specific models

BackgroundStress urinary incontinence (SUI) is prevalent in adult women, attributed to weakened endopelvic supporting tissues, and typically treated using drugs and invasive surgical procedures. The objective of this in silico study is to explore transurethral high-intensity ultrasound for delivery of precise thermal therapy to the endopelvic tissues adjacent to the mid-urethra, to induce thermal remodeling as a potential minimally invasive treatment alternative.Methods3D acoustic (Rayleigh-Sommerfeld) and biothermal (Pennes bioheat) models of the ultrasound applicator and surrounding tissues were devised. Parametric studies over transducer configuration [frequency, radius-of-curvature (ROC)] and treatment settings (power, duration) were performed, and select cases on patient-specific models were used for further evaluation. Transient temperature and thermal dose distributions were calculated, and temperature and dose metrics reported.ResultsConfigurations using a 5-MHz curvilinear transducer (3.5 × 10 mm, 28 mm ROC) with single 90 s sonication can create heated zones with 11 mm penetration (>50 °C) while sparing the inner 1.8 mm (<45 °C) radial depth of the urethral mucosa. Sequential and discrete applicator rotations can sweep out bilateral coagulation volumes (1.4 W power, 15° rotations, 600 s total time), produce large volumetric (1124 mm³ above 60 EM43 °C) and wide angular (∼50.5° per lateral sweep) coverage, with up to 15.6 mm thermal penetration and at least 1.6 mm radial urethral protection (<5 EM43 °C).ConclusionTransurethral applicators with curvilinear ultrasound transducers can deliver spatially selective temperature elevations to lateral mid-urethral targets as a possible means to tighten the endopelvic fascia and adjacent tissues