Initial Assessment of Boiling Histotripsy for Mechanical Ablation of Ex Vivo Human Prostate Tissue

Khokhlova, Vera A.; Rosnitskiy, Pavel B.; Tsysar, S. A.; Buravkov, S. V.; Ponomarchuk, Ekaterina M.; Sapozhnikov, Oleg A.; Karzova, Maria M.; Khokhlova, Tatiana D.; Maxwell, Adam D.; Wang, Yak-Nam; Кадрев, А.В.; Chernyaev, A. L.; Chernikov, Valery P.; Okhobotov, Dmitriy A.; Камалов, А А; Schade, George R.

doi:10.1016/j.ultrasmedbio.2022.07.014

Cited by 19 publications

(5 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For instance, a single-cycle histotripsy pulsing regime was used to break down uterine fibroids [ 58 ] and multi-cycle shock-scattering histotripsy effectively broke down cholangiocarcinoma liver tumors [ 59 ]. This work also aligns with other work demonstrating boiling histotripsy’s ability to break down fibrotic prostate tissue [ 60 ]. Additionally, these studies showed that single-cycle intrinsic threshold histotripsy performed better than the 5-cycle shock-scattering regime due to the formation of a denser nucleated bubble cloud.…”

Section: Discussionsupporting

confidence: 90%

Ultrasound-guided noninvasive pancreas ablation using histotripsy: feasibility study in an in vivo porcine model

Gannon,

Imran,

Hendricks-Wenger

et al. 2023

International Journal of Hyperthermia

View full text Add to dashboard Cite

Pancreatic cancer is a malignant disease associated with poor survival and nearly 80% present with unresectable tumors. Treatments such as chemotherapy and radiation therapy have shown overall improved survival benefits, albeit limited. Histotripsy is a noninvasive, non-ionizing, and non-thermal focused ultrasound ablation modality that has shown efficacy in treating hepatic tumors and other malignancies. In this novel study, we investigate histotripsy for noninvasive pancreas ablation in a pig model. In two studies, histotripsy was applied to the healthy pancreas in 11 pigs using a custom 32-element, 500 kHz histotripsy transducer attached to a clinical histotripsy system, with treatments guided by real-time ultrasound imaging. A pilot study was conducted in 3 fasted pigs with histotripsy applied at a pulse repetition frequency (PRF) of 500 Hz. Results showed no pancreas visualization on coaxial ultrasound imaging due to overlying intestinal gas, resulting in off-target injury and no pancreas damage. To minimize gas, a second group of pigs ( n = 8) were fed a custard diet containing simethicone and bisacodyl. Pigs were euthanized immediately ( n = 4) or survived for 1 week ( n = 4) post-treatment. Damage to the pancreas and surrounding tissue was characterized using gross morphology, histological analysis, and CT imaging. Results showed histotripsy bubble clouds were generated inside pancreases that were visually maintained on coaxial ultrasound ( n = 4), with 2 pigs exhibiting off-target damage. For chronic animals, results showed the treatments were well-tolerated with no complication signs or changes in blood markers. This study provides initial evidence suggesting histotripsy’s potential for noninvasive pancreas ablation and warrants further evaluation in more comprehensive studies.

show abstract

Section: Discussionsupporting

confidence: 90%

Ultrasound-guided noninvasive pancreas ablation using histotripsy: feasibility study in an in vivo porcine model

Gannon,

Imran,

Hendricks-Wenger

et al. 2023

International Journal of Hyperthermia

View full text Add to dashboard Cite

show abstract

“…This was validated by the presence of globular collagen that is consistent with ndings from Wang et al 15 , when using higher duty cycle BH pulses. At the lesion borders, there was presence of frayed collagen, similar to BH outcomes of treated ex vivo prostate cancer samples 31 , and we also observed some thermal damage in the form of blanched tissue at the outer rim of the lesion which was reported in other studies using 10ms pulses 15,36 BH parameters. There was also an increased presence of tissue fragments possibly due to the vapor cavity created by the boiling bubble leading to an acoustic fountain effect that causes tissue disruption into several smaller fragments 37 .…”

Section: Discussionsupporting

confidence: 89%

“…Both CH and BH can spare brous tissue 26 , but other studies have demonstrated complete disintegration of brous tissues, such as Peyronie's plaque 27 , ureteroceles 28 , cholangiocarcinoma 29 , uterine broids 30 etc., requiring a higher dose per point. A recent pilot study has also shown the ability of BH to ablate the ex vivo human BPH prostate 31 . The inconsistency between these studies indicates that a gap in knowledge exists in choosing the right treatment parameters to produce safe and effective ablation of these different tissues.…”

Section: Introductionmentioning

confidence: 97%

A Comparative Study of Histotripsy Parameters for the Treatment of Fibrotic ex-vivo Human Benign Prostatic Hyperplasia Tissue

Kumar,

Singh,

Wang

et al. 2024

Preprint

Self Cite

View full text Add to dashboard Cite

Histotripsy is a noninvasive focused ultrasound therapy that mechanically fractionates tissue to create well-defined lesions. In a previous clinical pilot trial to treat benign prostatic hyperplasia (BPH), histotripsy did not result in consistent objective improvements in symptoms, potentially because of the fibrotic and mechanically tough nature of this tissue. In this study, we aimed to identify the dosage required to homogenize BPH tissue by different histotripsy modalities, including boiling histotripsy (BH) and cavitation histotripsy (CH). A method for histotripsy lesion quantification via entropy (HLQE) analysis was developed and utilized to quantify lesion area of the respective treatments. These data were correlated to changes in mechanical stiffness measured by ultrasound shear-wave elastography before and after treatment with each parameter set and dose. Time points corresponding to histologically observed complete lesions were qualitatively evaluated and quantitatively measured. For the BH treatment, complete lesions occurred with >=30s treatment time, with a corresponding maximum reduction in stiffness of -90.9±7.2(s.d.)%. High pulse repetition frequency (PRF) CH achieved a similar reduction to that of BH at 288s (-91.6±6.0(s.d.)%), and low-PRF CH achieved a (-82.1±5.1(s.d.)%) reduction in stiffness at dose >=144s. Receiver operating characteristic curve analysis showed that a >~75% reduction in stiffness positively correlated with complete lesions observed histologically, and can provide an alternative metric to track treatment progression.

show abstract

“…10,11 Recently, small transrectal transducers for histotripsy have also been designed, fabricated, and evaluated, however, they are only for prostate histotripsy. 12,13 The human body fundamentally lacks a good acoustic window, except for superficial organs such as the breast.…”

Section: Introductionmentioning

confidence: 99%

“…This may create problems in clinical practice because these treatments require a wide acoustic window for ultrasound (US) penetration, which rarely exist 10,11 . Recently, small transrectal transducers for histotripsy have also been designed, fabricated, and evaluated, however, they are only for prostate histotripsy 12,13 . The human body fundamentally lacks a good acoustic window, except for superficial organs such as the breast.…”

Section: Introductionmentioning

confidence: 99%

A new sonoablation using acoustic droplet vaporization and focused ultrasound: A feasibility study

Li,

He,

Tang

et al. 2023

Medical Physics

View full text Add to dashboard Cite

BackgroundHistotripsy and boiling histotripsy are two methods of mechanical ablation that use high‐pressure focused ultrasound (FUS).PurposeHere, a new bubble sonoablation technique was investigated using low‐pressure FUS in combination with local injection of perfluoropentane (PFP) in rabbit liver.MethodsFifteen healthy New Zealand white rabbits were treated with FUS alone, FUS + PFP or PFP alone. FUS was performed using a single‐element focused transducer (frequency 596 kHz, 0.27 ms pulses, 0.54% duty cycle, and peak negative pressure 2.0 MPa). Ten minutes before FUS treatment, the PFP droplet was locally injected into the rabbit liver, where the ultrasound was focused. Contrast‐enhanced ultrasound (CEUS) of the liver was performed, and the temperature at the liver surface in the targeted liver region was recorded during treatment. The livers were collected for pathological examination. Statistical significance was set at p < 0.05. Paired t‐tests were used to compare the pre‐ and post‐treatment values. One‐way analysis of variance was performed to compare multiple groups, and the least significant difference method was used for further comparisons between the two groups.ResultsAnalysis of CEUS data showed that the values of area under the curve (AUC) were significantly different in the PFP + FUS group pre‐ (10453.644 ± 1182.93) and post‐treatment (4058.098 ± 2720.41), and the AUC values of PFP + FUS post‐treatment (4058.098 ± 2720.41) were also significantly lower than those of the FUS (9946.694 ± 1071.54) and the PFP (10364.794 ± 2181.53) groups. The peak intensity values also showed the same results, the value of peak intensity of PFP+FUS post‐treatment was 82.958 ± 13.99, whereas there was no difference between FUS (106.61 ± 7.61) and PFP (104.136 ± 10.55). Hematoxylin and eosin (H&E) staining revealed that the pathological damage ratings of the PFP + FUS, PFP, and FUS groups were grade 3, grade 1, and grade 0, respectively. Specifically, the area of liver necrosis in the PFP + FUS group (0.99 ± 0.29 cm2) was 198 times higher than that in the PFP group (0.005 ± 0.008 cm2), whereas no necrosis was observed in the livers treated with FUS alone. Simultaneously, the number of vacuoles in the liver of the PFP + FUS group (35.50 ± 23.31) was approximately five times that of the PFP group (7.00 ± 12.88), whereas no vacuoles were found in the liver treated with FUS alone.ConclusionPFP droplets combined with FUS can destroy liver tissue and cause tissue necrosis in the droplet injection area, without affecting the structure of surrounding tissue.

show abstract

Initial Assessment of Boiling Histotripsy for Mechanical Ablation of Ex Vivo Human Prostate Tissue

Cited by 19 publications

References 39 publications

Ultrasound-guided noninvasive pancreas ablation using histotripsy: feasibility study in an in vivo porcine model

Ultrasound-guided noninvasive pancreas ablation using histotripsy: feasibility study in an in vivo porcine model

A Comparative Study of Histotripsy Parameters for the Treatment of Fibrotic ex-vivo Human Benign Prostatic Hyperplasia Tissue

A new sonoablation using acoustic droplet vaporization and focused ultrasound: A feasibility study

Contact Info

Product

Resources

About