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ObjectivesTo investigate image-guided volumetric hyperthermia strategies using the ExAblate Body MR-guided focused ultrasound ablation system, involving mechanical transducer movement and sector-vortex beamforming.Materials and methodsAcoustic and thermal simulations were performed to investigate volumetric hyperthermia using mechanical transducer movement combined with sector-vortex beamforming, specifically for the ExAblate Body transducer. The system control in the ExAblate Body system was modified to achieve fast transducer movement and MR thermometry-based hyperthermia control, mechanical transducer movements and electronic sector-vortex beamforming were combined to optimize hyperthermia delivery. The experimental validation was performed using a tissue-mimicking phantom.ResultsThe developed simulation framework allowed for a parametric study with varying numbers of heating spots, sonication durations, and transducer movement times to evaluate the hyperthermia characteristics for mechanical transducer movement and sector-vortex beamforming. Hyperthermic patterns involving 2-4 sequential focal spots were analyzed. To demonstrate the feasibility of volumetric hyperthermia in the system, a tissue-mimicking phantom was sonicated with two distinct spots through mechanical transducer movement and sector-vortex beamforming. During hyperthermia, the average values of Tmax, T10, Tavg, T90, and Tmin over 200 s were measured within a circular ROI with a diameter of 10 pixels. These values were found to be 8.6, 7.9, 6.6, 5.2, and 4.5 °C, respectively, compared to the baseline temperature.ConclusionsThis study demonstrated the volumetric hyperthermia capabilities of the ExAblate Body system. The simulation framework developed in this study allowed for the evaluation of hyperthermia characteristics that could be implemented with the ExAblate MRgFUS system.

Introduction: The emergency department commonly evaluates eye pain and vision loss. Typically, these conditions can be managed outpatient; however, delays can lead to advanced pathology.Case Report: A 48-year-old homeless male presented with left-eye vision loss and pain. His exam revealed monocular decreased visual acuity, corneal ulcer, and hypopyon. The patient was diagnosed with bacterial keratitis and admitted for treatment but left against medical advice. He returned and was admitted for further treatment but was lost to follow-up thereafter.Conclusion: Our case features complicated bacterial keratitis with several treatment interruptions, demonstrating how healthcare disparities contribute to potentially preventable advanced pathology.

Despite the lasting aversion many hold towards rats and mice owing to historical associations with diseases such as the plague, there exists a growing consensus among researchers advocating for a reappraisal of these creatures. A noticeable trend is emerging in Western Europe, wherein rodents are increasingly viewed as urban neighbors, challenging the prevailing negative perceptions. To explain the ongoing shift, we use examples from medicine, popular culture, science, and exhibitions. The recognition of rats and mice as sentient and intelligent beings necessitates human stewardship in the context of urban coexistence. We conclude that understanding the ecology and behavior of rats and mice in urban environments, as well as human behavior change, is a prerequisite for achieving harmonious urban coexistence.

PURPOSE: To develop patient-specific 3D models using Finite-Difference Time-Domain (FDTD) simulations and pre-treatment planning tools for the selective thermal ablation of prostate cancer with interstitial ultrasound. This involves the integration with a FDA 510(k) cleared catheter-based ultrasound interstitial applicators and delivery system. METHODS: A 3D generalized prostate model was developed to generate temperature and thermal dose profiles for different applicator operating parameters and anticipated perfusion ranges. A priori planning, based upon these pre-calculated lethal thermal dose and iso-temperature clouds, was devised for iterative device selection and positioning. Full 3D patient-specific anatomic modeling of actual placement of single or multiple applicators to conformally ablate target regions can be applied, with optional integrated pilot-point temperature-based feedback control and urethral/rectum cooling. These numerical models were verified against previously reported ex-vivo experimental results obtained in soft tissues. RESULTS: For generic prostate tissue, 360 treatment schemes were simulated based on the number of transducers (1-4), applied power (8-20 W/cm2), heating time (5, 7.5, 10 min), and blood perfusion (0, 2.5, 5 kg/m3/s) using forward treatment modelling. Selectable ablation zones ranged from 0.8-3.0 cm and 0.8-5.3 cm in radial and axial directions, respectively. 3D patient-specific thermal treatment modeling for 12 Cases of T2/T3 prostate disease demonstrate applicability of workflow and technique for focal, quadrant and hemi-gland ablation. A temperature threshold (e.g., Tthres = 52 °C) at the treatment margin, emulating placement of invasive temperature sensing, can be applied for pilot-point feedback control to improve conformality of thermal ablation. Also, binary power control (e.g., Treg = 45 °C) can be applied which will regulate the applied power level to maintain the surrounding temperature to a safe limit or maximum threshold until the set heating time. CONCLUSIONS: Prostate-specific simulations of interstitial ultrasound applicators were used to generate a library of thermal-dose distributions to visually optimize and set applicator positioning and directivity during a priori treatment planning pre-procedure. Anatomic 3D forward treatment planning in patient-specific models, along with optional temperature-based feedback control, demonstrated single and multi-applicator implant strategies to effectively ablate focal disease while affording protection of normal tissues.

Apoptosis is a form of regulated cell death (RCD) that involves proteases of the caspase family. Pharmacological and genetic strategies that experimentally inhibit or delay apoptosis in mammalian systems have elucidated the key contribution of this process not only to (post-)embryonic development and adult tissue homeostasis, but also to the etiology of multiple human disorders. Consistent with this notion, while defects in the molecular machinery for apoptotic cell death impair organismal development and promote oncogenesis, the unwarranted activation of apoptosis promotes cell loss and tissue damage in the context of various neurological, cardiovascular, renal, hepatic, infectious, neoplastic and inflammatory conditions. Here, the Nomenclature Committee on Cell Death (NCCD) gathered to critically summarize an abundant pre-clinical literature mechanistically linking the core apoptotic apparatus to organismal homeostasis in the context of disease.

PurposeTo develop an effective and practical reconstruction pipeline to achieve motion-robust, multi-slice, real-time MR thermometry for monitoring thermal therapy in abdominal organs.MethodsThe application includes a fast spiral magnetic resonance imaging (MRI) pulse sequence and a real-time reconstruction pipeline based on multi-baseline proton resonance frequency shift (PRFS) method with visualization of temperature imaging. The pipeline supports multi-slice acquisition with minimal reconstruction lag. Simulations with a virtual motion phantom were performed to investigate the influence of the number of baselines and respiratory rate on the accuracy of temperature measurement. Phantom experiments with ultrasound heating were performed using a custom-made motion phantom to evaluate the performance of the pipeline. Lastly, experiments in healthy volunteers (N = 2) without heating were performed to evaluate the accuracy and stability of MR thermometry in abdominal organs (liver and kidney).ResultsThe multi-baseline approach with greater than 25 baselines resulted in minimal temperature errors in the simulation. Phantom experiments demonstrated a 713 ms update time for 3-slice acquisitions. Temperature maps with 30 baselines showed clear temperature distributions caused by ultrasound heating in the respiratory phantom. Finally, the pipeline was evaluated with physiologic motions in healthy volunteers without heating, which demonstrated the accuracy (root mean square error [RMSE]) of 1.23 ± 0.18 °C (liver) and 1.21 ± 0.17 °C (kidney) and precision of 1.13 ± 0.11 °C (liver) and 1.16 ± 0.15 °C (kidney) using 32 baselines.ConclusionsThe proposed real-time acquisition and reconstruction pipeline allows motion-robust, multi-slice, real-time temperature monitoring within the abdomen during free breathing.

BackgroundIn magnetic resonance (MR)-guided thermal therapy, respiratory motion can cause a significant temperature error in MR thermometry and reduce the efficiency of the treatment. A respiratory motion simulator is necessary for the development of new MR imaging (MRI) and motion compensation techniques.PurposeThe purpose of this study is to develop a low-cost and simple MR-compatible respiratory motion simulator to support proof-of-concept studies of MR monitoring approaches with respiratory-induced abdominal organ motion.MethodsThe phantom motion system integrates pneumatic control via an actuator subsystem located outside the MRI and coupled via plastic tubing to a compressible bag for distention and retraction within the MRI safe motion subsystem and phantom positioned within the MRI scanner. Performance of the respiratory motion simulator was evaluated with a real-time gradient echo MRI pulse sequence.ResultsThe motion simulator can produce respiratory rates in the range of 8-16 breaths/min. Our experiments showed the consistent periodic motion of the phantom during MRI acquisition in the range of 3.7-9 mm with 16 breaths/min. The operation of the simulator did not cause interference with MRI acquisition.ConclusionsIn this study, we have demonstrated the ability of the motion simulator to generate controlled respiratory motion of a phantom. The low-cost MR-compatible respiratory motion simulator can be easily constructed from off-the-shelf and 3D-printed parts based on open-source 3D models and instructions. This could lower the barriers to the development of new MRI techniques with motion compensation.

The identity and biological activity of most metabolites still remain unknown. A bottleneck in the exploration of metabolite structures and pharmaceutical activities is the compound purification needed for bioactivity assignments and downstream structure elucidation. To enable bioactivity-focused compound identification from complex mixtures, we develop a scalable native metabolomics approach that integrates non-targeted liquid chromatography tandem mass spectrometry and detection of protein binding via native mass spectrometry. A native metabolomics screen for protease inhibitors from an environmental cyanobacteria community reveals 30 chymotrypsin-binding cyclodepsipeptides. Guided by the native metabolomics results, we select and purify five of these compounds for full structure elucidation via tandem mass spectrometry, chemical derivatization, and nuclear magnetic resonance spectroscopy as well as evaluation of their biological activities. These results identify rivulariapeptolides as a family of serine protease inhibitors with nanomolar potency, highlighting native metabolomics as a promising approach for drug discovery, chemical ecology, and chemical biology studies.

ObjectiveChanges in ultrasound backscatter energy (CBE) imaging can monitor thermal therapy. Catheter-based ultrasound (CBUS) can treat deep tumors with precise spatial control of energy deposition and ablation zones, of which CBE estimation can be limited by low contrast and robustness due to small or inconsistent changes in ultrasound data. This study develops a multi-spatiotemporal compounding CBE (MST-CBE) imaging approach for monitoring specific to CBUS thermal therapy.MethodsEx vivo thermal ablations were performed with stereotactic positioning of a 180° directional CBUS applicator, temperature monitoring probes, endorectal US probe, and subsequent lesion sectioning and measurement. Five frames of raw radiofrequency data were acquired throughout in 15s intervals. Using window-by-window estimation methods, absolute and positive components of MST-CBE images at each point were obtained by the compounding ratio of squared envelope data within an increasing spatial size in each short-time window.ResultsCompared with conventional US, Nakagami, and CBE imaging, the detection contrast and robustness quantified by tissue-modification-ratio improved by 37.2 ± 4.7 (p < 0.001), 37.5 ± 5.2 (p < 0.001), and 6.4 ± 4.0 dB (p < 0.05) in the MST-CBE imaging, respectively. Correlation coefficient and bias between cross-sectional dimensions of the ablation zones measured in tissue sections and estimated from MST-CBE were up to 0.91 (p < 0.001) and -0.02 mm2, respectively.ConclusionThe MST-CBE approach can monitor the detailed changes within target tissues and effectively characterize the dimensions of the ablation zone during CBUS energy deposition.SignificanceThe MST-CBE approach could be practical for improved accuracy and contrast of monitoring and evaluation for CBUS thermal therapy.

PurposeThe ExAblate body MRgFUS system requires advanced beamforming strategies for volumetric hyperthermia. This study aims to develop and evaluate electronic beam steering, multi-focal patterns, and sector vortex beamforming approaches in conjunction with partial array activation using an acoustic and biothermal simulation framework along with phantom experiments.MethodsThe simulation framework was developed to calculate the 3D acoustic intensity and temperature distribution resulting from various beamforming and scanning strategies. A treatment cell electronically sweeping a single focus was implemented and evaluated in phantom experiments. The acoustic and thermal focal size of vortex beam propagation was quantified according to the vortex modes, number of active array elements, and focal depth.ResultsTurning off a percentage of the outer array to increase the f-number increased the focal size with a decrease in focal gain. 60% active elements allowed generating a sonication cell with an off-axis of 10 mm. The vortex mode number 4 with 60% active elements resulted in a larger heating volume than using the full array. Volumetric hyperthermia in the phantom was evaluated with the vortex mode 4 and respectively performed with 100% and 80% active elements. MR thermometry demonstrated that the volumes were found to be 18.8 and 29.7 cm3, respectively, with 80% array activation producing 1.58 times larger volume than the full array.ConclusionsThis study demonstrated that both electronic beam steering and sector vortex beamforming approaches in conjunction with partial array activation could generate large volume heating for HT delivery using the ExAblate body array.

The purpose of this study is to investigate the feasibility and performance of a stationary, non-focused dual-sectored tubular transurethral ultrasound applicator for thermal exposure of tissue regions adjacent to the urethra for treatment of stress urinary incontinence (SUI) through acoustic and biothermal simulations on 3D anatomical models. Parametric studies in a generalized tissue model over dual-sectored ultrasound applicator configurations (acoustic surface intensities, lateral active acoustic output sector angles, and durations) were performed. Selected configurations and delivery strategies were applied on 3D pelvic anatomical models. Temperature and thermal dose distributions on the target region and surrounding tissues were calculated. Endovaginal cooling was explored as a strategy to mitigate vaginal heating. The 75-90° dual-sectored transurethral tubular transducer (3.5 mm outer diameter (OD), 14 mm length, 6.5 MHz, 8.8-10.2 W/cm2) and 2-3-min sonication duration were selected from the parametric study for acoustic and biothermal simulations on anatomical models. The transurethral applicator with two opposing 75-90° active lateral tubular sectors can create two heated volumes for a total of up to 1.8 cm3 over 60 EM43 °C, with at least 10 mm radial penetration depth, 1.2 mm urethral sparing, and no lethal damage to the vagina and adjacent bone (