Govindarajan Srimathveeravalli

Percutaneous Ablation of Peribiliary Tumors with Irreversible Electroporation

PURPOSE To assess biliary complications after irreversible electroporation (IRE) ablation of hepatic tumors located < 1 cm from major bile ducts. MATERIALS AND METHODS A retrospective review was conducted of all percutaneous IRE ablations of hepatic tumors within 1 cm of the common, left, or right hepatic ducts at a single institution from January 2011 to September 2012. Computed tomography imaging performed before and after treatment was examined for evidence of bile duct dilatation, stricture, or leakage. Serum bilirubin and alkaline phosphatase levels were analyzed for evidence of biliary injury. RESULTS There were 22 hepatic metastases in 11 patients with at least one tumor within 1 cm of the common, left, or right hepatic duct that were treated with IRE ablations in 15 sessions. Median tumor size treated was 3.0 cm (mean, 2.8 cm ± 1.2, range, 1.0-4.7 cm). Laboratory values obtained after IRE were considered abnormal after four treatment sessions in three patients (bilirubin, 2.6-17.6 mg/dL; alkaline phosphatase, 130-1,035 U/L); these abnormal values were transient in two sessions. Two patients had prolonged elevation of values, and one required stent placement; both of these conditions appeared to be secondary to tumor progression rather than bile duct injury. CONCLUSIONS This clinical experience suggests that IRE may be a treatment option for centrally located liver tumors with margins adjacent to major bile ducts where thermal ablation techniques are contraindicated. Further studies with extended follow-up periods are necessary to establish the safety profile of IRE in this setting.

MRI-Safe Robot for Endorectal Prostate Biopsy

This paper reports the development of an MRI-Safe robot for direct (interventional) MRI-guided endorectal prostate biopsy. The robot is constructed of nonmagnetic and electrically nonconductive materials, and is electricity free, using pneumatic actuation and optical sensors. Targeting biopsy lesions of MRI abnormality presents substantial clinical potential for the management of prostate cancer. This paper describes MRI-Safe requirements and presents the kinematic architecture, design, and construction of the robot, and a comprehensive set of preclinical tests for MRI compatibility and needle targeting accuracy. The robot has a compact and simple three degree-of-freedom (DoF) structure, two for orienting a needle-guide and one to preset the depth of needle insertion. The actual insertion is performed manually through the guide and up to the preset depth. To reduce the complexity and size of the robot next to the patient, the depth setting DoF is remote. Experimental results show that the robot is safe to use in any MRI environment (MRI-Safe). Comprehensive MRI tests show that the presence and motion of the robot in the MRI scanner cause virtually no image deterioration or signal-to-noise ratio change. Robots accuracy in bench test, CT-guided in-vitro, MRI-guided in-vitro , and animal tests are 0.37, 1.10, 2.09, and 2.58 mm, respectively. These values are acceptable for clinical use.

The state of irreversible electroporation in interventional oncology.

A new ablation modality, irreversible electroporation (IRE), has been of increasing interest in interventional radiology. Its nonthermal mechanism of action of killing tumor cells allows physicians the ability to ablate tumors in areas previously contraindicated for thermal ablation. This article reviews the current published clinical outcomes, imaging follow-up, and the current knowledge gaps in the procedure for patients treated with IRE.

Pilot Study to Assess Safety and Clinical Outcomes of Irreversible Electroporation for Partial Gland Ablation in Men with Prostate Cancer

PURPOSE Partial prostate gland ablation is a strategy to manage localized prostate cancer. Irreversible electroporation can ablate localized soft tissues. We describe 30 and 90-day complications and intermediate term functional outcomes in men undergoing prostate gland ablation using irreversible electroporation. MATERIALS AND METHODS We reviewed the charts of 25 patients with prostate cancer who underwent prostate gland ablation using irreversible electroporation as a primary procedure and who were followed for at least 6 months. RESULTS Median followup was 10.9 months. Grade 3 complications occurred in 2 patients including epididymitis (1) and urinary tract infection (1). Fourteen patients experienced grade 2 or lower complications, mainly transient urinary symptoms, hematuria and urinary tract infections. Of 25 patients 4 (16%) had cancer in the zone of ablation on routine followup biopsy at 6 months. Of those with normal urinary function at baseline 88% and 94% reported normal urinary function at 6 and 12 months after prostate gland ablation, respectively. By 12 months only 1 patient with normal erectile function at baseline reported new difficulty with potency and only 2 patients (8%) required a pad for urinary incontinence. CONCLUSIONS Prostate gland ablation with irreversible electroporation is feasible and safe in selected men with localized prostate cancer. Intermediate term urinary and erectile function outcomes appear reasonable. Irreversible electroporation is effective in the ablation of tumor bearing prostate tissue as a majority of men had no evidence of residual cancer on biopsy 6 months after prostate gland ablation.

Irreversible Electroporation of the Lumbar Vertebrae in a Porcine Model: Is There Clinical-Pathologic Evidence of Neural Toxicity?

PURPOSE To evaluate the effects of irreversible electroporation (IRE) in the porcine spine. MATERIALS AND METHODS This study was approved by the institutional animal care and use committee. Twenty computed tomographically guided IRE ablations in either a transpedicular location or directly over the posterior cortex were performed in the lumbar vertebrae of 10 pigs by a single operator. T1- and T2-weighted magnetic resonance (MR) imaging was performed with and without contrast material 2 or 7 days after ablation. Mathematical modeling was performed to estimate the extent of ablation. Clinical, radiologic, pathologic, and simulation findings were analyzed. The Miller low-bias back transformation was used to construct 95% confidence intervals for the mean absolute percentage difference between the maximum length and width of the ablation zone on MR images and pathologic measurements by using square-root-transformed data. RESULTS Bipolar IRE electrode placement and ablation were successful in all cases. The mean distances from the IRE electrode to the posterior wall of the vertebral body or the exiting nerve root were 2.93 mm ± 0.77 (standard deviation) and 7.87 mm ± 1.99, respectively. None of the animals had neurologic deficits. Well-delineated areas of necrosis of bone, bone marrow, and skeletal muscle adjacent to the vertebral body were present. Histopathologic changes showed outcomes that matched with simulation-estimated ablation zones. The percentage absolute differences in the ablation measurements between MR imaging and histopathologic examination showed the following average errors: 24.2% for length and 28.8% for width measurements on T2-weighted images, and 26.1% for length and 33.3% for width measurements on T1-weighted contrast material-enhanced images. CONCLUSION IRE ablation in the porcine spine is feasible and safe and produces localized necrosis with minimal neural toxicity. Signal intensity changes on images acquired with standard MR imaging sequences demonstrate the ablation zone to be larger than that at histopathologic examination.

Comparison of simulation-based treatment planning with imaging and pathology outcomes for percutaneous CT-guided irreversible electroporation of the porcine pancreas: a pilot study.

PURPOSE To investigate the reliability of simulations for planning pancreatic irreversible electroporation (IRE) ablations compared with computed tomography (CT) and pathology outcomes in an animal model. MATERIALS AND METHODS Simulations were performed varying treatment parameters, including field strength (1.5-2.5 kV/cm), pulse number (70-90 pulses), and pulse length (70-100 µs). Pancreatic IRE was performed in six pigs under CT guidance. Two animals each were sacrificed for histology after 1 day, 14 days, and 28 days. Follow-up CT scans were performed on day 0, day 1, day 14, and day 28. Biochemical markers were collected before the procedure, 1 day after the procedure, and 14 days after the procedure. RESULTS All ablation zones could be visualized on CT scan immediately after the procedure and on day 1 follow-up CT scan, and all animals survived until the designated endpoints. Histopathology revealed necrosis and edema on day 1 and fibrosis and glandular atrophy after 28 days. Blood vessels close to the ablation zone appeared normal. Laboratory analysis indicated mild to moderate amylasemia and lipasemia with normalization after 14 days. The ablation size on CT scan measured a mean (± SD) 146% ± 18 (day 0, P < .126) and 168% ± 18 (day 1, P < .026) of the simulation and on pathology measured 119% ± 10 (day 1, not significant) of the simulation. CONCLUSIONS Results from simulations for planning IRE ablations, CT, and pathology may differ from each other. Ablation zones on CT and pathology appear larger than simulated, suggesting that clinically used treatment planning may underestimate the ablation size in the pancreas.

MRI-safe robot for targeted transrectal prostate biopsy: Animal experiments

To study the feasibility and safety of using a magnetic resonance imaging (MRI)‐safe robot for assisting MRI‐guided transrectal needle placement and biopsy in the prostate, using a canine model. To determine the accuracy and precision afforded by the use of the robot while targeting a desired location in the organ.

Feasibility of Catheter-Directed Intraluminal Irreversible Electroporation of Porcine Ureter and Acute Outcomes in Response to Increasing Energy Delivery

PURPOSE To evaluate the feasibility of focal intraluminal irreversible electroporation (IRE) in the ureter with a novel electrode catheter and to study the treatment effects in response to increasing pulse strength. MATERIALS AND METHODS Five IRE treatment settings were each evaluated twice for the ablation of normal ureter in 5 Yorkshire pigs (n = 1-4 ablations per animal; total of 10 ablations) with the use of a prototype device under ultrasound and fluoroscopic guidance. Animals received unilateral or bilateral treatment, limited to a maximum of 2 ablations in any 1 ureter. Treatment was delivered with increasing pulse strength (from 1,000 V to 3,000 V in increments of 500 V) while keeping the pulse duration (100 μs) and number of pulses (n = 90) constant. Ureter patency was assessed with antegrade ureteropyelography immediately following treatment. Animals were euthanized within 4 hours after treatment, and treated urinary tract was harvested for histopathologic analysis with hematoxylin and eosin and Masson trichrome stains. RESULTS IRE was successfully performed in all animals, without evidence of ureteral perforation. Hematoxylin and eosin analysis of IRE treatments demonstrated full-thickness ablation at higher field strengths (mucosa to the adventitia). Masson trichrome stains showed preservation of connective tissue at all field strengths. CONCLUSIONS Intraluminal catheter-directed IRE ablation is feasible and produces full-thickness ablation of normal ureters. There was no evidence of lumen perforation even at the maximum voltages evaluated.

Evaluation of an Endorectal Electrode for Performing Focused Irreversible Electroporation Ablations in the Swine Rectum

PURPOSE To study the feasibility of a novel endorectal electrode for the creation of focal ablations of the rectal wall with the use of irreversible electroporation (IRE). MATERIALS AND METHODS A monopolar electrode with a grounding pad (10 ablations in five pigs) and a bipolar electrode (two ablations in one pig) were evaluated in healthy swine rectum. A two-dimensional model of the electrode in the rectum was created and used to solve the Laplace equation to determine field strength. Simulation was used to identify treatment settings for superficial ablation (mucosal layers) or transmural ablation of rectal wall. Animals were euthanized within 4 hours after treatment. RESULTS Treatment was successfully completed without treatment-related complications. Eleven of 12 lesions were successfully located and extracted for pathologic analysis. All lesions were characterized by necrotic cell death with mild inflammation and hyperemia, with a sharp demarcation between ablated and adjacent normal tissue. Depth of lesions corresponded with numeric simulation. Histologic analysis and measurements indicated that lesion creation with the superficial treatment setting resulted in ablation of mucosal and submucosal layers with superficial or no injury to the muscularis propria (9.97 mm ± 0.31 length, 3.3 mm ± 2.92 depth), and that lesion creation with the transmural treatment setting resulted in full-thickness ablation (12.43 mm ± 3.85 length, 4.97 mm ± 2.89 depth) of the rectal wall. CONCLUSIONS An endorectal electrode can be used to deliver IRE and create limited focal ablations in the rectal wall. Treatment parameters can be determined through numeric modeling to control the depth of penetration of ablation.

Peripheral Blood Regulatory T-Cell and Type 1 Helper T-Cell Population Decrease after Hepatic Artery Embolization.

PURPOSE To evaluate changes in T-cell populations in peripheral blood after bland hepatic artery embolization (HAE). MATERIALS AND METHODS Bland HAE was performed in 12 patients to treat primary (n = 5) or metastatic (n = 7) liver tumors, using microspheres and polyvinyl alcohol (n = 8) or microspheres alone (n = 4). Patient peripheral blood samples were collected within 1 month before HAE, within 1 week after HAE (early period after HAE), and 2-8 weeks after HAE (follow-up period). Peripheral blood populations of cytotoxic T lymphocytes, CD4(+) T cells, type 1 helper T cells (Th1) and type 2 helper T cells (Th2), and regulatory T cells (Treg) were evaluated using flow cytometry. Changes in T-cell populations before and after bland HAE were compared using paired t tests. RESULTS Peripheral blood CD4(+) T-cell populations decreased significantly in the early period after HAE (44.0% ± 2.2 to 34.4% ± 3.6, P < .01) and in the follow-up period (44.0% ± 2.2 to 36.3% ± 3.0, P < .01). Among the individual CD4(+) T-cell subtypes, Treg (2.5% ± 0.3 to 1.7% ± 0.2, P < .02) and Th1 (8.1% ± 1.8 to 5.6% ± 1.6, P < .02) decreased significantly in the early period after HAE only. The presence of extrahepatic disease was associated with decreasing Treg (P < .04). CONCLUSIONS After HAE, the peripheral blood T-cell environment is changed with decreases in Treg and Th1.