Pilot ex vivo study on non-thermal ablation of human prostate adenocarcinoma tissue using boiling histotripsy.

Focused ultrasound technologies are of growing interest for noninvasive ablation of localized prostate cancer (PCa). Here we present the results of the first case study evaluating the feasibility of non-thermal mechanical ablation of human prostate adenocarcinoma tissue using the boiling histotripsy (BH) method on ex vivo tissue. High intensity focused ultrasound field was generated using a 1.5-MHz custom-made transducer with nominal F#=0.75. A sonication protocol of 734 W acoustic power, 10-ms long BH-pulses, 30 pulses per focal spot, 1 % duty cycle, and 1 mm distance between single foci was tested in an ex vivo human prostate tissue sample containing PCa. The protocol used here has been successfully applied in the previous BH studies for mechanical disintegration of ex vivo prostatic human tissue with benign hyperplasia. BH treatment was monitored using B-mode ultrasound. Post-treatment histologic analysis demonstrated BH produced liquefaction of the targeted tissue volume. BH treated benign prostate parenchyma and PCa had similar tissue fractionation into subcellular fragments. The results of the study demonstrated that PCa tumor tissue can be mechanically ablated using the BH method. Further studies will aim on optimizing protocol parameters to accelerate treatment while maintaining complete destruction of the targeted tissue volume into subcellular debris.

[A novel method for non-invasive mechanical ablation of prostate tumors using pulsed focused ultrasound].

AIM: of the study: demonstrate the feasibility of non-invasive mechanical disintegration of human prostate tissue using pulsed high-intensity focused ultrasound (pHIFU), a method termed boiling histotripsy. MATERIALS AND METHODS: An ultrasound experimental system was developed for producing localized mechanical lesions in ex vivo biological tissue samples under ultrasound guidance. A series of experiments was carried out to create small single-focus lesions (volume < 2 mm3) and one large lesion (volume > 50 mm3) in ex vivo prostate tissue samples. After irradiation, two samples were bisected to visualize the region of destruction; the other tissue samples were examined histologically. RESULTS: During pHIFU irradiation under B-mode ultrasound guidance, a region of increased echogenicity caused by formation of vapor-gas bubbles was visualized in the target region. After exposure, small and large lesions filled with a suspension of liquefied tissue were observed. Histological examination confirmed that the prostate tissue in the focal region was disintegrated into subcellular fragments. CONCLUSION: A pilot study showed the feasibility of using boiling histotripsy as a non-invasive method for treating prostate diseases.

Marination and cooking performance of portioned broiler breast fillets with the wooden breast condition.

The wooden breast (WB) condition in broiler breast meat negatively influences technological meat quality. However, it is unknown if the WB effects are uniform throughout the Pectoralis major. The objective of this study was to determine the effects of WB on the marination and cooking performance of the dorsal and ventral portions of broiler breast fillets. Sixty butterfly breast fillets were collected from the deboning line of a commercial plant and sorted into normal (no WB) and severe WB categories. Each fillet was horizontally portioned into dorsal and ventral halves. Portions from one side of each butterfly were used as non-marinated controls, while portions from the other side were vacuum-tumble marinated (16 rpm, -0.6 atm, 4°C, 20 min) with 20% (wt/wt) marinade to meat ratio. Marinade was formulated to target a final concentration of 0.75% salt and 0.45% sodium tripolyphosphate in the final product. Samples were cooked to 78°C in a combination oven. Marinade uptake and retention were lower (P < 0.001) in both the ventral and dorsal portions of the WB fillets. The dorsal portions had greater (P < 0.001) marinade uptake and retention than the ventral portions in both normal and WB fillets. For non-marinated samples, cook loss was greater (P < 0.05) in both the ventral and dorsal portions of WB fillets. In marinated samples, however, cook loss was similar between the dorsal portions of normal and WB fillets. Final cooked product yield was calculated based on pre-marination and post-cook weights. Non-marinated WB samples exhibited lower (P < 0.001) cooked product yields than normal samples in both portions. For marinated samples, cooked product yields were greater (P < 0.001) in the dorsal portions. Data demonstrated that the dorsal portion of the Pectoralis major more readily absorbs and retains marinade during vacuum tumbling and storage than the ventral portion. Although the WB condition negatively influenced marination and cooking performance in both fillet portions, the effects were less severe in the dorsal portion.

Descriptive sensory analysis of marinated and non-marinated wooden breast fillet portions.

The wooden breast (WB) myopathy influences muscle composition and texture characteristics in broiler breast meat. It is unknown if marination reduces the negative influence of WB on meat sensory quality or if WB effects are uniform throughout the Pectoralis major. The objective of this study was to determine the effects of marination on the sensory attributes and instrumental shear force measurements of the ventral (skin-side) and dorsal (bone-side) portions of normal and severe WB meat. Sixty butterfly fillets (30 normal and 30 severe WB) were selected from the deboning line of a commercial processing plant. Individual fillets were portioned into ventral and dorsal halves. Portions from one side of each butterfly were used as non-marinated controls, and portions from the other side were vacuum-tumble marinated (16 rpm, -0.6 atm, 4°C, 20 min) with 20% (wt/wt) marinade to meat ratio. Marinade was formulated to target a concentration of 0.75% (w/v) salt and 0.45% (w/v) sodium tripolyphosphate in the final product. Descriptive sensory analysis (9 trained panelists) was conducted to evaluate visual, texture, and flavor attributes (0-15 point scale) of breast portions along with Warner-Bratzler shear force. Significant interaction effects between WB and marination were not observed for the sensory attributes. Greater springiness, cohesiveness, hardness, fibrousness, and chewiness scores were observed in WB samples (P < 0.001). Marination decreased cohesiveness, hardness, and chewiness (P < 0.05) and increased juiciness (P = 0.002). The effects of WB on sensory texture attributes were more apparent in the ventral portions of the breast fillets. Flavor attributes (salty and brothy) increased (P < 0.001) with marination. In non-marinated samples, shear force was similar between normal and WB samples. In marinated samples, however, shear force was greater (P < 0.001) in WB samples. Data suggest that the WB effect on meat sensory quality is not uniform throughout the Pectoralis major and that WB-related differences in cooked meat sensory texture attributes are lessened but not eliminated by vacuum-tumbling marination.

Impact of stone characteristics on cavitation in burst wave lithotripsy.

Non-invasive kidney stone treatments such as shock wave lithotripsy (SWL) and burst wave lithotripsy (BWL) rely on the delivery of pressure waves through tissue to the stone. In both SWL and BWL, the potential to hinder comminution by exciting cavitation proximal to the stone has been reported. To elucidate how different stones alter prefocal cavitation in BWL, different natural and synthetic stones were treated in vitro using a therapy transducer operating at 350 kHz (peak negative pressure 7 MPa, pulse length 20 cycles, pulse repetition frequency 10 Hz). Stones were held in a confined volume of water designed to mimic the geometry of a kidney calyx, with the water filtered and degassed to maintain conditions for which the cavitation threshold (in the absence of a stone) matches that from in vivo observations. Stone targeting and cavitation monitoring were performed via ultrasound imaging using a diagnostic probe aligned coaxially with the therapy transducer. Quantitative differences in the extent and location of cavitation activity were observed for different stone types-e.g., "softer" stones (natural and synthetic) that disintegrate into "dusty" fragments produced larger prefocal cavitation clouds. Future work will focus on correlation of such cavitation metrics with stone fragmentation.

Update on clinical trials of kidney stone repositioning and preclinical results of stone breaking with one system.

Our goal is an office-based, handheld ultrasound system to target, detach, break, and/or expel stones and stone fragments from the urinary collecting system to facilitate natural clearance. Repositioning of stones in humans (maximum 2.5 MPa, and 3-second bursts) and breaking of stones in a porcine model (maximum 50 cycles, 20 Hz repetition, 30 minutes, and 7 MPa peak negative pressure) have been demonstrated using the same 350-kHz probe. Repositioning in humans was conducted during surgery with a ureteroscope in the kidney to film stone movement. Independent video review confirmed stone movements (≥ 3 mm) in 15 of 16 kidneys (94%). No serious or unanticipated adverse events were reported. Experiments of burst wave lithotripsy (BWL) effectiveness on breaking human stones implanted in the porcine bladder and kidney demonstrated fragmentation of 8 of 8 stones on post mortem dissection. A 1-week survival study with the BWL exposures and 10 specific-pathogen-free pigs, showed all findings were within normal limits on clinical pathology, hematology, and urinalysis. These results demonstrate that repositioning of stones with ultrasonic propulsion and breaking of stones with BWL are safe and effective.

An in vivo demonstration of efficacy and acute safety of burst wave lithotripsy using a porcine model.

Burst wave lithotripsy (BWL) is a new non-invasive method for stone comminution using bursts of sub-megahertz ultrasound. A porcine model of urolithiasis and techniques to implement BWL treatment has been developed to evaluate its effectiveness and acute safety. Six human calcium oxalate monohydrate stones (6-7 mm) were hydrated, weighed, and surgically implanted into the kidneys of three pigs. Transcutaneous stone treatments were performed with a BWL transducer coupled to the skin via an external water bath. Stone targeting and treatment monitoring were performed with a co-aligned ultrasound imaging probe. Treatment exposures were applied in three 10-minute intervals for each stone. If sustained cavitation in the parenchyma was observed by ultrasound imaging feedback, treatment was paused and the pressure amplitude was decreased for the remaining time. Peak negative focal pressures between 6.5 and 7 MPa were applied for all treatments. After treatment, stone fragments were removed from the kidneys. At least 50% of each stone was reduced to <2 mm fragments. 100% of four stones were reduced to <4 mm fragments. Magnetic resonance imaging showed minimal injury to the functional renal volume. This study demonstrated that BWL could be used to effectively fragment kidney stones with minimal injury.