Search

Abstract This paper describes the design and initial proof-of-concept of a single pre-clinical transcranial focused ultrasound (FUS) system capable of performing histotripsy (mechanical ablation), hyperthermia, blood-brain barrier opening (BBBO), sonodynamic therapy, or neuromodulation in a murine brain. We have termed it the All-in-One FUS system for murine brain studies, which is the first FUS system of its kind. The 1.5 MHz ultrasound transducer was fabricated and driven using a custom electronic driver to produce 3-cycle pulses with a focal peak-negative pressure (P-) of up to 87 MPa at a low duty cycle (

Abstract Resonant Acoustic Rheometry (RAR), a newly developed ultrasound-based technique for non-contact characterization of soft viscoelastic materials, has shown promise for quantitative viscoelastic assessment of temporally changing soft biomaterials in real time, and may be used to monitor blood coagulation process. Here, we report the development of a novel, multichannel RAR (mRAR) system for simultaneous measurements of multiple temporally evolving samples and demonstration of its use for monitoring the coagulation of multiple small-volume plasma samples. The mRAR system was constructed using an array of 4 custom-designed ultrasound transducers at 5.0 MHz and a novel electronic driving system that controlled the generation of synchronized ultrasound pulses for real time assessment of multiple samples simultaneously. As a proof-of-concept of the operation of the mRAR system, we performed tests using pooled normal human plasma samples and anti-coagulated plasma samples from patients treated with warfarin with a range of International Normalized Ratio (INR) values as well-characterized samples with different coagulation kinetics. Our results show that simultaneous tracking of dynamic changes in 4 plasma samples triggered by either kaolin or tissue factor was achieved for the entire duration of coagulation. The mRAR system captured distinct changes in the samples and identified parameters including the clotting start time and parameters associated with the stiffness of the final clots that were consistent with INR levels. Data from this study demonstrate the feasibility of the mRAR system for efficient characterization of the kinetic coagulation processes of multiple plasma samples.

Cryptosporidium spp. are protozoan parasites of significant health importance found in environmental waters globally. Four commercially available Cryptosporidium-specific immunomagnetic separation (IMS) kits used in various water sample matrices were analysed and compared. Beads were characterised by flow cytometry and tested for the recovery efficiencies for oocysts spiked into different matrices: river water sediment, clay sample, and filter backwash sample. Results showed that Dynabeads™ Cryptosporidium and Waterborne Crypto-Grab™ kits contained immunoglobulin IgM antibody-coated beads. In contrast, the BioPoint CryptoBead and the TCS Isolate kits contained immunoglobulin IgG antibody-coated beads. BioPoint CryptoBead was significantly coated with more antibodies and were able to capture oocysts more rapidly compared to the other beads. Recovery efficiencies of Dynabeads™, TCS Isolate® beads, and BioPoint CryptoBead ranged from 55 to 93% when tested against different sample matrices, with BioPoint CryptoBead resulting in the highest at 93% in reagent-grade water and Dynabeads™ at 55%, the lowest against clay samples. The Waterborne beads did not perform well on any samples, with recovery efficiencies ranging from 0 to 8%. Fluorescence microscopy analyses showed that both the IMS method and the sample matrix processed affect the quality of the membranes, with the cleanest samples for microscopy examination observed from BioPoint CryptoBead. HIGHLIGHTS Antibody types on magnetic beads and IMS methods differ across commercially available IMS kits.; IgG-coated BioPoint beads had 75–93% recovery efficiencies across the different sample matrices and gave the cleanest slides for microscopy.; IMS recovery efficiency is influenced by both the method used and the matrix analysed, with the purity of the slides affecting the results.;

AbstractIn transabdominal histotripsy, ultrasound pulses are focused into the body to noninvasively destroy soft tissues via cavitation. However, the ability to focus is limited by phase aberration, or decorrelation of the ultrasound pulses due to spatial variation in the speed of sound throughout heterogeneous tissue. Phase aberration shifts, broadens, and weakens the focus, thereby reducing the safety and efficacy of histotripsy therapy. This paper reviews and discusses aberration effects in histotripsy and in related therapeutic ultrasound techniques (e.g., high intensity focused ultrasound), with an emphasis on aberration by soft tissues. Methods for aberration correction are reviewed and can be classified into two groups: model-based methods, which use segmented images of the tissue as input to an acoustic propagation model to predict and compensate phase differences, and signal-based methods, which use a receive-capable therapy array to detect phase differences by sensing acoustic signals backpropagating from the focus. The relative advantages and disadvantages of both groups of methods are discussed. Importantly, model-based methods can correct focal shift, while signal-based methods can restore substantial focal pressure, suggesting that both methods should be combined in a 2-step approach. Aberration correction will be critical to improving histotripsy treatments and expanding the histotripsy treatment envelope to enable non-invasive, non-thermal histotripsy therapy for more patients.

The future projected frequency of a specified baseline extreme sea level (ESL), often called the amplification factor (AF), is extensively used as a metric of evolving coastal flood hazard with sea level rise (SLR). The baseline ESL is typically analyzed using extreme value analysis, and the SLR is added to the resulting distribution. In the presence of SLR uncertainty, it is natural to analyze AFs probabilistically. I derive probability density functions (PDFs) of AF, given uncertainty distributions of SLR. If the ESL distribution is modeled as Gumbel and the SLR distribution as normal, then the AF distribution is log normal. However, in active tropical cyclone regions, ESL often has a longer tail than Gumbel, and a Frechet (Type-II) Generalized Extreme Value (GEV) is more appropriate. In this case, I show that the AF distribution has a divergent mean, preventing its use as a hazard metric. In addition, I show that for Frechet ESL, the AF cannot even be defined for SLR above a threshold $\left(\beta /\xi \right){f}_{0}^{-\xi },$ where f _0 is the specified baseline frequency (e.g., f _0 = 0.01 yr ^−1 for the 100-year exceedance), β is the GEV scale parameter and ξ the shape parameter. This SLR threshold can be as low as 0.5 m in the southeast US and Caribbean, within reach mid to late century. Above the threshold, ESL at all frequencies exceeds the baseline reference frequency, preventing the calculation of AF. The resulting probabilistic distribution of AF is insensitive to SLR above the threshold. These features detrimentally impact the utility of AF as a hazard metric. Frechet distributions are appropriate and commonly used for ESL in tropical cyclone regions, but AFs applied to such distributions must interpreted with caution. In such regions, coastal risk managers should consider other flood hazard metrics, such as probabilistic estimates of flood depth.

The Pongola Bush Nature Reserve lies in a narrow band along the escarpment between Mpumalanga and KwaZulu-Natal (KZN). Although referred to as ‘bush’, this vegetation type may be considered to fit into the intersection of two types of scarp forest: the Northern Afrotemperate Forest and the Southern Mistbelt Forest. The area was heavily logged in the early 1900s with the need for timber for the emerging gold mining industry in Barberton. The forest fragment is now protected but lacks formal tree diversity assessments, and this study sets out to establish its community composition and richness using a range of standard techniques. Distributed throughout the forest, 127 circular plots (each 80 m2) were surveyed. In these, 1152 stems were measured for species, height, and diameter at breast height (DBH). Four species contributed roughly 70% of the 70 Mg ha−1 above ground woody biomass. Stem size class distributions showed a high recruitment rate of small stemmed individuals and few large individuals. This pattern is consistent with the disturbance history of the site, with limited recruitment of certain species, mainly limited to early successional species. The Pongola Bush forest is particularly diverse in terms of tree species: 41 species were recorded, and it is estimated from the species area curve that there may be 70 tree species present. Conservation implications: This survey is the first formal tree diversity survey conducted on the Pongola Bush which may assist future research and conservation strategies.

NiMo (nickel-molybdenum) and NiMo with embedded CeO2 nanoparticles (NPs; 100 nm) were tested as antimicrobial coatings (~15 μm thickness) on titanium (Ti) surfaces using an electrochemical process for heat exchanger applications onboard marine vessels. Preliminary static biofouling and biocorrosion (also known as microbiologically influenced corrosion) assessments were carried out in glass bottles using pure-culture Desulfovibrio vulgaris, a sulfate-reducing bacterium (SRB), in deoxygenated ATCC 1249 medium at 37°C, and using an alga (Chlorella vulgaris) mixed with general heterotrophic bacteria (GHB) in enriched artificial seawater at 28°C. It was found that the coating containing NiMo/CeO2 NPs were much more effective than NiMo in preventing SRB biofilm formation with an efficacy of 99% reduction in D. vulgaris sessile cells after 21 day incubation. The coating also exhibited a 50% lower corrosion current density compared to the uncoated Ti against SRB corrosion. Both NiMo and NiMo/CeO2 NP coatings achieved 99% reduction in sessile algal cells. Confocal laser scanning microscopy (CLSM) biofilm images indicated a large reduction of sessile GHB cells. The CLSM images also confirmed the biocidal kill effects of the two coatings. Unlike polymer coatings, the “metallic” coatings are heat conductive. Thus, the corrosion resistant antifouling coatings are suitable for heat exchanger applications.

Histotripsy is the first noninvasive, non-ionizing, and non-thermal ablation technology guided by real-time imaging. Using focused ultrasound delivered from outside the body, histotripsy mechanically destroys tissue through cavitation, rendering the target into acellular debris. The material in the histotripsy ablation zone is absorbed by the body within 1–2 months, leaving a minimal remnant scar. Histotripsy has also been shown to stimulate an immune response and induce abscopal effects in animal models, which may have positive implications for future cancer treatment. Histotripsy has been investigated for a wide range of applications in preclinical studies, including the treatment of cancer, neurological diseases, and cardiovascular diseases. Three human clinical trials have been undertaken using histotripsy for the treatment of benign prostatic hyperplasia, liver cancer, and calcified valve stenosis. This review provides a comprehensive overview of histotripsy covering the origin, mechanism, bioeffects, parameters, instruments, and the latest results on preclinical and human studies.

Apoptosis is triggered in the developing mammalian brain by sedative, anesthetic or antiepileptic drugs during late gestation and early life. Whether human children are vulnerable to this toxicity mechanism remains unknown, as there are no imaging techniques to capture it. Apoptosis is characterized by distinct structural features, which affect the way damaged tissue scatters ultrasound compared to healthy tissue. We evaluated whether apoptosis, triggered by the anesthetic sevoflurane in the brains of neonatal rhesus macaques, can be detected using quantitative ultrasound (QUS).Neonatal (n = 15) rhesus macaques underwent 5 h of sevoflurane anesthesia. QUS images were obtained through the sagittal suture at 0.5 and 6 h. Brains were collected at 8 h and examined immunohistochemically to analyze apoptotic neuronal and oligodendroglial death.Significant apoptosis was detected in white and gray matter throughout the brain, including the thalamus. We measured a change in the effective scatterer size (ESS), a QUS biomarker derived from ultrasound echo signals obtained with clinical scanners, after sevoflurane-anesthesia in the thalamus. Although initial inclusion of all measurements did not reveal a significant correlation, when outliers were excluded, the change in the ESS between the pre- and post-anesthesia measurements correlated strongly and proportionally with the severity of apoptotic death.We report for the first time in vivo changes in QUS parameters, which may reflect severity of apoptosis in the brains of infant nonhuman primates. These findings suggest that QUS may enable in vivo studies of apoptosis in the brains of human infants following exposure to anesthetics, antiepileptics and other brain injury mechanisms.

Shear wave dispersion (variation of phase velocity with frequency) occurs in tissues with layered and anisotropic microstructure and viscous components, such as the uterine cervix. This phenomenon, mostly overlooked in previous applications of cervical Shear Wave Elasticity Imaging (SWEI) for preterm birth risk assessment, is expected to change drastically during pregnancy due to cervical remodeling. Here we demonstrate the potential of SWEI-based descriptors of dispersion as potential biomarkers for cervical remodeling during pregnancy. First, we performed a simulation-based pre-selection of two SWEI-based dispersion descriptors: the ratio R of group velocities computed with particle-velocity and particle-displacement, and the slope S of the phase velocity vs. frequency. The pre-selection consisted of comparing the contrast-to-noise ratio (CNR) of dispersion descriptors in materials with different degrees of dispersion with respect to a low-dispersive medium. Shear waves induced in these media by SWEI were simulated with a finite-element model of Zener viscoelastic solids. The pre-selection also considered two denoising strategies to improve CNR: a low-pass filter with automatic frequency cutoff determination, and singular value decomposition of shear wave displacements. After pre-selection, the descriptor-denoising combination that produced the largest CNR was applied to SWEI cervix data from 18 pregnant Rhesus macaques acquired at weeks 10 (mid-pregnancy stage) and 23 (late pregnancy stage) of the 24.5-weeks full pregnancy. A maximum likelihood linear mixed-effects model (LME) was used to evaluate the dependence of the dispersion descriptor on pregnancy stage, maternal age, parity and other experimental factors. The pre-selection study showed that descriptor S combined with singular value decomposition produced a CNR 11.6 times larger than the other descriptor and denoising strategy combinations. In the Non-Human Primates (NHP) study, the LME model showed that descriptor S significantly decreased from mid to late pregnancy (−0.37 ± 0.07 m/s-kHz per week, p< 0.00001) with respect to the base value of 15.5 ± 1.9 m/s-kHz. This change was more significant than changes in other SWEI features such as the group velocity previously reported. Also, S varied significantly between the anterior and posterior portions of the cervix (p= 0.02) and with maternal age (p= 0.008). Given the potential of shear wave dispersion to track cervical remodeling, we will extend its application to ongoing longitudinal human studies.

Objective and Impact Statement. This is the first longitudinal study investigating the effects of histotripsy on local tumor progression in an in vivo orthotopic, immunocompetent rat hepatocellular carcinoma (HCC) model. Introduction. Histotripsy is the first noninvasive, nonionizing, nonthermal, mechanical ablation technique using ultrasound to generate acoustic cavitation to liquefy the target tissue into acellular debris with millimeter accuracy. Previously, histotripsy has demonstrated in vivo ablation of noncancerous liver tissue. Methods. N1-S1 HCC tumors were generated in the livers of immunocompetent rats (n=6, control; n=15, treatment). Real-time ultrasound-guided histotripsy was applied to ablate either 100% tumor volume+up to 2 mm margin (n=9, complete treatment) or 50-75% tumor volume (n=6, partial treatment) by delivering 1-2 cycle histotripsy pulses at 100 Hz PRF (pulse repetition frequency) with p−≥30 MPa using a custom 1 MHz transducer. Rats were monitored weekly using MRI (magnetic resonance imaging) for 3 months or until tumors reached ~25 mm. Results. MRI revealed effective post-histotripsy reduction of tumor burden with near-complete resorption of the ablated tumor in 14/15 (93.3%) treated rats. Histopathology showed