Noninvasive thyroid histotripsy treatment: proof of concept study in a porcine model.

INTRODUCTION: This study was performed to determine the feasibility and safety of creating superficial histotripsy treatment in a live porcine thyroid model. METHODS: The porcine thymus comparable in size, shape and location to the human thyroid was used for this study. This model has been used for thyroid surgery studies due to the diminutive size of the porcine thyroid. Four female swine underwent a total of eight histotripsy treatments performed with a prototype therapy system (HistoSonics, Inc., Ann Arbor, MI). Two treatments were performed in each animal: a spherical 1.0 × 1.0 × 1.0 cm and ovoid 1.0 × 1.0 × 2.0 cm treatment zones. MRI immediately post-procedure was evaluated for histotripsy treatment zone size and imaging appearance, followed immediately by sacrifice. Tissue was then reviewed for percent cellular destruction and precision. RESULTS: Treatment zones measured on post treatment MRI were similar to prescribed volumes (spherical = 0.60 (+/- 0.11) cm3, ovoid = 1.23 (+/- 0.40) cm3, p > 0.05 vs. prescribed). MRI demonstrated well demarcated treatment zones and imaging findings consistent with cellular destruction. Histology demonstrated sharp transitions to normal tissue (mean 0.33 (+/- 0.13) cm), and high degrees of cellular destruction (mean 76% (+/- 12.5), range of 50-100%) in the treated tissue. Edema within the overlying muscle was seen in 2/8 treatments. CONCLUSION: Histotripsy is capable of safely creating precise histotripsy treatments within the superficial neck of a porcine thyroid model without evidence of considerable complications.

Percutaneous Microwave Tumor Ablation Is Safe in Patients with Cardiovascular Implantable Electronic Devices: A Single-Institutional Retrospective Review.

The risk of electromagnetic interference between microwave (MW) ablation and cardiac implantable electronic devices (CIEDs), ie, pacemakers and defibrillators, has not been fully evaluated. Fourteen MW ablations (kidney, n = 8; liver, n = 5; lung, n = 1) were performed in 13 patients with CIEDs in normal operating mode. Electrocardiography tracings, cardiovascular complications, tumor size, tumor-to-CIED distance, and tumor-to-device lead distance were recorded. Mean tumor size was 2.9 cm, mean tumor-to-CIED distance was 26.4 cm (range, 9-30 cm), and mean tumor-to-lead distance was 12.1 cm (range, 3.5-20 cm). No device-based cardiovascular complications or class C or higher complications per Society of Interventional Radiology criteria were identified. MW ablation appears to be safe in select patients with CIEDs.

Robotically-Assisted Sonic Therapy for Renal Ablation in a Live Porcine Model: Initial Preclinical Results.

PURPOSE: To demonstrate the feasibility of Robotically Assisted Sonic Therapy (RAST)-a noninvasive and nonthermal focused ultrasound therapy based on histotripsy-for renal ablation in a live porcine model. MATERIALS AND METHODS: RAST ablations (n = 11) were performed in 7 female swine: 3 evaluated at 1 week (acute) and 4 evaluated at 4 weeks (chronic). Treatment groups were acute bilateral (3 swine, 6 ablations with immediate computed tomography [CT] and sacrifice); chronic single kidney (3 swine, 3 ablations; CT at day 0, week 1, and week 4 after treatment, followed by sacrifice); and chronic bilateral (1 swine, 2 ablations). Treatments were performed using a prototype system (VortxRx; HistoSonics, Inc) and targeted a 2.5-cm-diameter sphere in the lower pole of each kidney, intentionally including the central collecting system. RESULTS: Mean treatment time was 26.4 minutes. Ablations had a mean diameter of 2.4 ± 0.3 cm, volume of 8.5 ± 2.4 cm3, and sphericity index of 1.00. Median ablation volume decreased by 96.1% over 4 weeks. Histology demonstrated complete lysis with residual blood products inside the ablation zone. Temporary collecting system obstruction by thrombus was observed in 4/11 kidneys (2 acute and 2 chronic) and resolved by 1 week. There were no urinary leaks, main vessel thromboses, or adjacent organ injuries on imaging or necropsy. CONCLUSIONS: In this normal porcine model, renal RAST demonstrated complete histologic destruction of the target renal tissue while sparing the urothelium.

Ultrasound risk stratification for malignancy using the 2015 American Thyroid Association Management Guidelines for Children with Thyroid Nodules and Differentiated Thyroid Cancer.

BACKGROUND: The 2015 American Thyroid Association (ATA) Management Guidelines for Children with Thyroid Nodules and Differentiated Thyroid Cancer provides selection criteria for nodules prior to ultrasound-guided fine-needle aspiration biopsy. OBJECTIVE: To evaluate the diagnostic performance of pediatric thyroid nodule risk stratification for predicting malignancy when applying the ultrasound (US) criteria recommended. MATERIALS AND METHODS: US characteristics of 39 thyroid nodules in 33 pediatric patients who underwent US fine-needle aspiration biopsy were reviewed by two radiologists. Based on the aggregated US criteria from the ATA Guidelines, each nodule was assigned a level of malignancy risk. Kappa coefficients were estimated to assess intra- and interobserver reliability. Using each patient's largest nodule observation (n = 33), univariable exact logistic regression analyses of US parameters were then conducted to estimate the odds of a malignant pathology diagnosis. A penalized Firth correction was employed in the univariable models analyzing composition, shape and level of suspicion due to quasi-complete data separation. RESULTS: Twenty-seven nodules in 21 patients (median age: 16 years; 17 female) were benign and 12 nodules in 12 patients (median age: 16.5 years; 11 female) were malignant. Intraobserver agreement was substantial to almost perfect for composition, echogenicity, shape and margins. Interobserver agreement was almost perfect for composite level of suspicion. High level of suspicion was assigned to all 12 malignant nodules versus 9/21 (43%) of the benign nodules. Level of suspicion, solid/predominantly solid composition, irregular margins and echogenic foci emerged as significant predictors of malignancy with odds ratios (OR) of 8.5 (95% confidence interval [CI]: 1.7-1,130, P = 0.001), 10.5 (95% CI: 1.1-1,417, P = 0.04), 53.2 (95% CI: 5.1-2,988, P < 0.0001) and 3.5 (95% CI: 1.1-23.2, P = 0.03), respectively. CONCLUSION: The composite, US-based risk stratification criteria from the 2015 ATA Guidelines may provide an appropriate and reproducible method for estimating risk of malignancy for pediatric thyroid nodules.

Histotripsy of Subcutaneous Fat in a Live Porcine Model.

PURPOSE: This study was designed to evaluate the feasibility and safety of histotripsy subcutaneous (SQ) fat treatment in an in-vivo porcine model, and evaluate evolution of the treated volume on MRI and pathology. METHODS/MATERIALS: 10 histotripsy SQ fat treatments were completed in 5 swine, divided into four groups based on pre-determined survival: day 0 (n = 4), day 7 (n = 2), day 28 (n = 2), and day 56 (n = 2). A 4.0 × 4.0x2.0 cm ovoid treatment was created in the fat pad of the posterior thorax. MRI of survived animals were obtained on day 7 (n = 6), day 28 (n = 4), and day 56 (n = 2), and reviewed for size and imaging characteristics. Technical success was defined as the creation of a treatment zone in the targeted SQ fat. Skin firmness and indentation were qualitatively scored. RESULTS: Histotripsy had a 100% (10/10) technical success for creation of SQ fat treatments. Mean treatment time was 35.5 min (range 35-36.5). The volume of treated SQ fat demonstrated 92% volume reduction over the study. Day 0 gross pathology treatment had a mean volume of 12.6 cm3 (± 2.1) (prescribed volume of 16.7 cm3), which decreased to 8.3 cm3 (± 2.8) by day 7 (34% overall decrease), 3.0 cm3 (± 0.5) by day 28 (76% overall decrease), and 1.0 cm3 (± 1.2) by day 56 (92% overall decrease). Mean firmness and indentation scores showed no change from baseline at all time points, with no overlying skin injury. CONCLUSION: Histotripsy safely and effectively treated SQ fat of an in-vivo porcine model, with volume reduction over time.

Transcostal Histotripsy Ablation in an In Vivo Acute Hepatic Porcine Model.

PURPOSE: To determine whether histotripsy can create human-scale transcostal ablations in porcine liver without causing severe thermal wall injuries along the beam path. MATERIALS AND METHODS: Histotripsy was applied to the liver using a preclinical prototype robotic system through a transcostal window in six female swine. A 3.0 cm spherical ablation zone was prescribed. Duration of treatment (75 min) was longer than a prior subcostal treatment study (24 min, 15 s) to minimize beam path heating. Animals then underwent contrast-enhanced MRI, necropsy, and histopathology. Images and tissue were analyzed for ablation zone size, shape, completeness of necrosis, and off-target effects. RESULTS: Ablation zones demonstrated complete necrosis with no viable tissue remaining in 6/6 animals by histopathology. Ablation zone volume was close to prescribed (13.8 ± 1.8 cm3 vs. prescribed 14.1 cm3). Edema was noted in the body wall overlying the ablation on T2 MRI in 5/5 (one animal did not receive MRI), though there was no gross or histologic evidence of injury to the chest wall at necropsy. At gross inspection, lung discoloration in the right lower lobe was present in 5/6 animals (mean size: 1 × 2 × 4 cm) with alveolar hemorrhage, preservation of blood vessels and bronchioles, and minor injuries to pneumocytes noted at histology. CONCLUSION: Transcostal hepatic histotripsy ablation appears feasible, effective, and no severe injuries were identified in an acute porcine model when prolonged cooling time is added to minimize body wall heating.

Microwave Ablation of Adrenal Tumors in Patients With Continuous Intra-Arterial Blood Pressure Monitoring Without Prior Alpha-Adrenergic Blockade: Safety and Efficacy.

PURPOSE: Evaluate the safety and efficacy of adrenal microwave ablation performed with continuous intra-arterial blood pressure monitoring (IABPM) and without alpha-adrenergic blockade (AAB) as pretreatment. MATERIAL AND METHODS: A single-center, retrospective review of all percutaneous adrenal microwave ablation performed between 2011 and 2018. Microwave ablation was completed on 11 patients, with a total of 15 adrenal tumors with a mean size of 3.3 cm (1.4-6.9 cm) treated metastatic RCC, HCC, esophageal carcinoma, adrenal adenoma. Cases were performed without prior AAB, but with continuous IABPM and rapid intervention using short-acting antihypertensive medications. RESULTS: There were no post-procedural episodes of hypertension, no neurological or cardiovascular complications, and no SIR moderate or worse adverse event complications. Mean intraprocedural maximum systolic blood pressure (SBP) was 211 mmHg (range: 132-288), with an average increase in SBP of 100 mmHg (range: 23-180). A hypertensive crisis (SBP ≥ 180 and/or DBP ≥ 120) occurred in 9 of the 15 procedures (60%) with a mean length of 3.0 min (range: 1-12). The technical success rate was 100% (15/15 procedures). The mean follow-up time was 2.4 years (range: 0.9-7.7 years), with primary and secondary efficacy rates of 77% and 87%, respectively, and an overall survival of 82%. CONCLUSION: In this single-center retrospective study, microwave ablation of adrenal tumors without AAB was safe and effective when performed with continuous arterial line monitoring of vital signs and the use of short-acting, rapid-onset antihypertensive medications. LEVEL OF EVIDENCE: Level 4, Case Series.

Histotripsy Ablations in a Porcine Liver Model: Feasibility of Respiratory Motion Compensation by Alteration of the Ablation Zone Prescription Shape.

BACKGROUND: Previous human-scale porcine liver model studies of histotripsy have resulted in ablation zones elongated in the cranial-caudal (CC) dimension due to uninterrupted respiratory motion during the ablation procedure. PURPOSE: The purpose of this study is to compensate for elongation of hepatic histotripsy ablation zones in the cranial-caudal (CC) dimension caused by respiratory motion by prescribing ellipsoid-shaped ablations. METHODS: Six female swine underwent 12 hepatic histotripsy ablations using a prototype clinical histotripsy system under general anesthesia. Each animal received two ablation zones prescribed as either an ellipsoid (2.5 cm (AP) × 2.5 cm (ML) × 1.7 cm (CC), prescribed volume = 5.8 cc) or a sphere (2.5 cm all dimensions, prescribed volume 8.2 cc). Ventilatory tidal volume was held constant at 400 cc for all ablations. Post-procedure MRI was followed by sacrifice and gross and microscopic histology. RESULTS: Ablations on MRI were slightly larger than prescribed in all dimensions. Ellipsoid plan ablations (2.8 × 3.0 × 3.1 cm, volume 13.2 cc, sphericity index 0.987) were closer to prescribed volume than spherical plan ablations (2.9 × 3.1 × 3.7 cm, volume 17.1 cc, sphericity index 0.953). Ellipsoid plan ablations were more spherical than sphere plan ablations, but the difference did not reach statistical significance (p = .0.06). Pathologic analysis confirmed complete necrosis within the center of each ablation zone with no widening of the zone of partial ablation on the superior and inferior as compared to the lateral borders (p = .0.22). CONCLUSION: Altering ablation zone prescription shape when performing hepatic histotripsy ablations can partially mitigate respiratory motion effects to achieve the desired ablation shape and volume.

Robotically Assisted Sonic Therapy (RAST) for Noninvasive Hepatic Ablation in a Porcine Model: Mitigation of Body Wall Damage with a Modified Pulse Sequence.

PURPOSE: Robotically assisted sonic therapy (RAST) is a nonthermal, noninvasive ablation method based on histotripsy. Prior animal studies have demonstrated the ability to create hepatic ablation zones at the focal point of an ultrasound therapy transducer; however, these treatments resulted in thermal damage to the body wall within the path of ultrasound energy delivery. The purpose of this study was to evaluate the efficacy and safety of a pulse sequence intended to mitigate prefocal body wall injury. MATERIALS AND METHODS: Healthy swine (n = 6) underwent hepatic RAST (VortxRx software version 1.0.1.3, HistoSonics, Ann Arbor MI) in the right hepatic lobe. A 3.0 cm spherical ablation zone was prescribed for each. Following treatment, animals underwent MRI which was utilized for ablation zone measurement, evaluation of prefocal injury, and assessment of complications. Each animal was euthanized, underwent necropsy, and the tissue was processed for histopathologic analysis of the ablation zone and any other sites concerning for injury. RESULTS: No prefocal injury was identified by MRI or necropsy in the body wall or tissues overlying the liver. Ablation zones demonstrated uniform cell destruction, were nearly spherical (sphericity index = 0.988), and corresponded closely to the prescribed size (3.0 × 3.1 × 3.4 cm, p = 0.70, 0.36, and 0.01, respectively). Ablation zones were associated with portal vein (n = 3, one occlusive) and hepatic vein thrombosis (n = 4, one occlusive); however, bile ducts remained patent within ablation zones (n = 2). CONCLUSIONS: Hepatic RAST performed with a modified ultrasound pulse sequence in a porcine model can mitigate prefocal body wall injuries while maintaining treatment efficacy. Further study of hepatic RAST appears warranted, particularly in tumor models.