Jason Chiang

Deep brain stimulation of the anterior nucleus of the thalamus: Effects of electrical stimulation on pilocarpine-induced seizures and status epilepticus

PURPOSE Electrical stimulation of the anterior nucleus of the thalamus appears to be effective against seizures in animals and humans. As the optimal stimulation settings remain elusive, we studied the effects of different stimulation parameters against pilocarpine induced seizures and status epilepticus (SE). METHODS Adult rats had electrodes implanted bilaterally into the AN. Five days later, different groups of animals were stimulated with 1000 microA, 500 microA, or 200 microA and frequencies of either 20 Hz or 130 Hz. Pilocarpine (350 mg/kg i.p.) was injected 5 min after stimulation onset and seizures were monitored. Sham-treated controls had electrodes implanted but did not receive stimulation until they developed SE. After SE, these animals had the electrodes turned on to assess whether AN stimulation could arrest ongoing ictal activity. RESULTS Compared to sham-treated controls (n=8), stimulation at 500 microA (n=13) significantly increased the latency for seizures and SE by 1.9-2.2-fold. In contrast, stimulation at 1000 microA (n=8) produced a non-significant decrease in the latencies to these events. No major effect was observed with stimulation at 200 microA (n=11). Similar results were obtained for each current intensity, regardless of the stimulation frequency used (20 Hz and 130 Hz). In sham-treated controls that had the electrodes turned on after SE, stimulation was not able to arrest ongoing ictal activity. CONCLUSIONS The anticonvulsant effects of AN stimulation against pilocarpine-induced seizures were mainly determined by the current and not the frequency of stimulation. AN stimulation initiated after SE onset was ineffective.

Computational modelling of microwave tumour ablations

Abstract Microwave tissue heating is being increasingly utilised in several medical applications, including focal tumour ablation, cardiac ablation, haemostasis and resection assistance. Computational modelling of microwave ablations is a precise and repeatable technique that can assist with microwave system design, treatment planning and procedural analysis. Advances in coupling temperature and water content to electrical and thermal properties, along with tissue contraction, have led to increasingly accurate computational models. Developments in experimental validation have led to broader acceptability and applicability of these newer models. This review will discuss the basic theory, current trends and future direction of computational modelling of microwave ablations.

Anticonvulsant serotonergic and deep brain stimulation in anterior thalamus

OBJECTIVE Anterior thalamus (AN) has been shown to mediate seizures in both focal and generalized models. Specific regional increase in AN serotonergic activity was observed following AN-DBS in our pentylenetetrazol (PTZ) rodent model of acute seizures, and this increase may inhibit seizures and contribute to the mechanism of anticonvulsant DBS. METHODS Anesthetized rats with AN-directed dialysis cannula with scalp/depth EEG were infused with PTZ at 5.5mg/(kg min) until an EEG seizure occurred. Eight experimental groups of AN-dialysis infusion were evaluated: controls (dialysate-only), 10 and 100 microM serotonin 5-HT(7) agonist 5-carboxamidotryptamine (5-CT), 1, 10 and 100 microM serotonin antagonist methysergide (METH), AN-DBS, and 100 microM METH+AN-DBS. RESULTS Latency for seizures in control animals was 3,120+/-770 s (S.D.); AN-DBS delayed onset to 5018+/-1100 (p<0.01). AN-directed 5-CT increased latency in dose-dependent fashion: 3890+/-430 and 4247+/-528 (p<0.05). Methysergide had an unexpected protective effect at low-dose (3908+/-550, p<0.05) but not at 100 microM (2687+/-1079). The anticonvulsant action of AN-DBS was blocked by prior dialysis using 100 microM METH. Surface EEG burst count and nonlinear analysis (H-Statistic) noted significant (p<0.05) increased pre-ictal epileptiform bursts in 5-CT, methysergide, but not DBS group compared to control. CONCLUSION Increased serotonergic activity in AN raised PTZ seizure threshold, similar to DBS, but without preventing cortical bursting. 5-Carboxamidotryptamine, a 5-HT(7) agonist, demonstrated dose-dependent seizure inhibition. Methysergide proved to have an inverse, dose-dependent agonist property, antagonizing the action of AN-DBS at the highest dose. Anticonvulsant AN-DBS may in part act to selectively alter serotonin neurotransmission to raise seizure threshold.

A Dual-Slot Microwave Antenna for More Spherical Ablation Zones: Ex Vivo and in Vivo Validation

PURPOSE To compare the performance of a microwave antenna design with two annular slots to that of a monopole antenna design in creating a more spherical ablation zone. MATERIALS AND METHODS Animal care and use committee approval was obtained before in vivo experiments were performed. Microwave ablation zones were created by using dual-slot and monopole control antennas for 2, 5, and 10 minutes at 50 and 100 W in ex vivo bovine livers. Dual-slot and monopole antennas were then used to create ablation zones at 100 W for 5 minutes in in vivo porcine livers, which also underwent intraprocedural imaging. Ablation diameter, length, and aspect ratio (diameter ÷ length) were measured at gross pathologic examination and compared at each combination of power and time by using the paired Student t test. A P value less than .05 was considered to indicate a significant difference. Aspect ratios closer to 1 reflected a more spherical ablation zone. RESULTS The dual-slot antenna created ablation zones with a higher aspect ratio at 50 W for 2 minutes (0.75 vs 0.53, P = .003) and 5 minutes (0.82 vs 0.63, P = .053) than did the monopole antenna in ex vivo liver tissue, although the difference was only significant at 2 minutes. At 100 W, the dual-slot antenna had a significantly higher aspect ratio at 2 minutes (0.52 vs 0.42, P = .002). In vivo studies showed significantly higher aspect ratios at 100 W for 5 minutes (0.63 vs 0.53, respectively, P = .029). Intraprocedural imaging confirmed this characterization, showing higher rates of ablation zone growth and heating primarily at the early stages of the ablation procedure when the dual-slot antenna was used. CONCLUSION The dual-slot microwave antenna created a more spherical ablation zone than did the monopole antenna both in vivo and ex vivo liver tissue. Greater control over power delivery can potentially extend the advantages of the dual-slot antenna design to higher power and longer treatment times.

Microwave ablation in primary and secondary liver tumours: technical and clinical approaches.

Abstract Thermal ablation is increasingly being utilised in the treatment of primary and metastatic liver tumours, both as curative therapy and as a bridge to transplantation. Recent advances in high-powered microwave ablation systems have allowed physicians to realise the theoretical heating advantages of microwave energy compared to other ablation modalities. As a result there is a growing body of literature detailing the effects of microwave energy on tissue heating, as well as its effect on clinical outcomes. This article will discuss the relevant physics, review current clinical outcomes and then describe the current techniques used to optimise patient care when using microwave ablation systems.

Modeling and Validation of Microwave Ablations With Internal Vaporization

Numerical simulation is increasingly being utilized for computer-aided design of treatment devices, analysis of ablation growth, and clinical treatment planning. Simulation models to date have incorporated electromagnetic wave propagation and heat conduction, but not other relevant physics such as water vaporization and mass transfer. Such physical changes are particularly noteworthy during the intense heat generation associated with microwave heating. In this paper, a numerical model was created that integrates microwave heating with water vapor generation and transport by using porous media assumptions in the tissue domain. The heating physics of the water vapor model was validated through temperature measurements taken at locations 5, 10, and 20 mm away from the heating zone of the microwave antenna in homogenized ex vivo bovine liver setup. Cross-sectional area of water vapor transport was validated through intraprocedural computed tomography (CT) during microwave ablations in homogenized ex vivo bovine liver. Iso-density contours from CT images were compared to vapor concentration contours from the numerical model at intermittent time points using the Jaccard index. In general, there was an improving correlation in ablation size dimensions as the ablation procedure proceeded, with a Jaccard index of 0.27, 0.49, 0.61, 0.67, and 0.69 at 1, 2, 3, 4, and 5 min, respectively. This study demonstrates the feasibility and validity of incorporating water vapor concentration into thermal ablation simulations and validating such models experimentally.

Predictors of thrombosis in hepatic vasculature during microwave tumor ablation of an in vivo porcine model.

PURPOSE To evaluate and model the risk of in vivo thrombosis in each hepatic vessel type during hepatic microwave ablation as a function of vessel diameter, velocity, and vessel-antenna spacing. MATERIALS AND METHODS A single microwave ablation antenna was inserted into a single porcine lobe (n = 15 total) adjacent to a hepatic artery, hepatic vein, or portal vein branch. Conventional ultrasound and Doppler ultrasound were used to measure the vessel diameter, blood flow velocity, and vessel-antenna spacing. A microwave ablation zone was created at 100 W for 5 minutes. Thrombus formation was evaluated on ultrasound performed immediately after the procedure. Logistic regression was used to evaluate the predictive value of vessel diameter, blood flow velocity, and vessel-antenna spacing on vascular thrombosis. RESULTS Thrombosis was identified in 53% of portal veins, 13% of hepatic veins, and 0% of hepatic arteries. The average peak blood flow rate of the hepatic artery was significantly greater than the average peak blood flow rate of the hepatic vein and portal vein. Peak blood flow velocity < 12.45 cm/s, vessel diameter < 5.10 mm, and vessel-antenna spacing < 3.75 mm were strong predictors of hepatic vein thrombosis. However, these individual factors were not predictive of the more common portal vein thrombosis. CONCLUSIONS Hepatic arteries do not appear to be at risk for thrombosis during microwave ablation procedures. Portal vein thrombosis was more common than hepatic vein thrombosis during microwave ablation treatments but was not as predictable based on vessel diameter, flow velocity, or vessel-antenna spacing alone.

Flow-dependent vascular heat transfer during microwave thermal ablation

Microwave tumor ablation is an attractive option for thermal ablation because of its inherent benefits over radiofrequency ablation (RFA) in the treatment of solid tumors such as hepatocellular carcinoma (HCC). Microwave energy heats tissue to higher temperatures and at a faster rate than RFA, creating larger, more homogenous ablation zones. In this study, we investigate microwave heating near large vasculature using coupled fluid-flow and thermal analysis. Low-flow conditions are predicted to be more likely to cause cytotoxic heating and, therefore, vessel thrombosis and endothelial damage of downstream tissues. Such conditions may be more prevalent in patient with severe cirrhosis or compromised blood flow. High-flow conditions create the more familiar heat-sink effect that can protect perivascular tissues from the intended thermal damage. These results may help guide placement and use of microwave ablation technologies in future studies.

Hardware Accelerator for Genomic Sequence Alignment

To infer homology and subsequently gene function, the Smith-Waterman algorithm is used to find the optimal local alignment between two sequences. When searching sequence databases that may contain billions of sequences, this algorithm becomes computationally expensive. Consequently, in this paper, we focused on accelerating the Smith-Waterman algorithm by modifying the computationally repeated portion of the algorithm by FPGA hardware custom instructions. These simple modifications accelerated the algorithm runtime by an average of 287% compared to the pure software implementation. Therefore, further design of FPGA accelerated hardware offers a promising direction to seeking runtime improvement of genomic database searching

Microwave ablation energy delivery: influence of power pulsing on ablation results in an ex vivo and in vivo liver model.

PURPOSE The purpose of this study was to compare the impact of continuous and pulsed energy deliveries on microwave ablation growth and shape in unperfused and perfused liver models. METHODS A total of 15 kJ at 2.45 GHz was applied to ex vivo bovine liver using one of five delivery methods (n = 50 total, 10 per group): 25 W continuous for 10 min (25 W average), 50 W continuous for 5 min (50 W average), 100 W continuous for 2.5 min (100 W average), 100 W pulsed for 10 min (25 W average), and 100 W pulsed for 5 min (50 W average). A total of 30 kJ was applied to in vivo porcine livers (n = 35, 7 per group) using delivery methods similar to the ex vivo study, but with twice the total ablation time to offset heat loss to blood perfusion. Temperatures were monitored 5-20 mm from the ablation antenna, with values over 60 °C indicating acute cellular necrosis. Comparisons of ablation size and shape were made between experimental groups based on total energy delivery, average power applied, and peak power using ANOVA with post-hoc pairwise tests. RESULTS No significant differences were noted in ablation sizes or circularities between pulsed and continuous groups in ex vivo tissue. Temperature data demonstrated more rapid heating in pulsed ablations, suggesting that pulsing may overcome blood perfusion and coagulate tissues more rapidly in vivo. Differences in ablation size and shape were noted in vivo despite equivalent energy delivery among all groups. Overall, the largest ablation volume in vivo was produced with 100 W continuous for 5 min (265.7 ± 208.1 cm(3)). At 25 W average, pulsed-power ablation volumes were larger than continuous-power ablations (67.4 ± 34.5 cm(3) versus 23.6 ± 26.5 cm(3), P = 0.43). Similarly, pulsed ablations produced significantly greater length (P ≤ 0.01), with increase in diameter (P = 0.09) and a slight decrease in circularity (P = 0.97). When comparing 50 W average power groups, moderate differences in size were noted (P ≥ 0.06) and pulsed ablations were again slightly more circular. CONCLUSIONS Pulsed energy delivery created larger ablation zones at low average power compared to continuous energy delivery in the presence of blood perfusion. Shorter duty cycles appear to provide greater benefit when pulsing.