Publications by authors named "Punit Prakash"

58 Publications

Hyperthermia and Tumor Immunity.

Cancers (Basel) 2021 May 21;13(11). Epub 2021 May 21.

Department of Interventional Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

Thermal ablation is a cornerstone in the management of cancer patients. Typically, ablation procedures are performed for patients with a solitary or oligometastatic disease with the intention of eradicating all sites of the disease. Ablation has traditionally played a less prominent role for patients with a widely metastatic disease. For such patients, attempting to treat numerous sites of disease compounds potential risks without a clear clinical benefit and, as such, a compelling justification for performing an intervention that is unlikely to alter a patient's clinical trajectory is uncommon. However, the discovery of immune checkpoints and the development of immune checkpoint inhibitors have brought a new perspective to the relevance of local cancer therapies such as ablation for patients with a metastatic disease. It is becoming increasingly apparent that local cancer therapies can have systemic immune effects. Thus, in the new perspective of cancer care centered upon immunologic principles, there is a strong interest in exploring the utility of ablation for patients with a metastatic disease for its immunologic implications. In this review, we summarize the unmet clinical need for adjuvant interventions such as ablation to broaden the impact of systemic immunotherapies. We additionally highlight the extant preclinical and clinical data for the immunogenicity of common thermal ablation modalities.
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http://dx.doi.org/10.3390/cancers13112507DOI Listing
May 2021

Transcervical microwave ablation in type 2 uterine fibroids via a hysteroscopic approach: analysis of ablation profiles.

Biomed Phys Eng Express 2021 Jun 1;7(4). Epub 2021 Jun 1.

Department of Electrical and Computer Engineering, Kansas State University, Manhattan, Kansas, United States of America.

Type 2 uterine fibroids are challenging to resect surgically as ≥ 50% volume of myoma lies within the myometrium. A hysteroscopic approach for ablating fibroids is minimally-invasive, but places a considerable burden on the operator to accurately place the ablation applicator within the target. We investigated the sensitivity of transcervical microwave ablation outcome with respect to position of the ablation applicator within 1 - 3 cm type 2 fibroids.A finite element computer model was developed to simulate 5.8 GHz microwave ablation of fibroids and validated with experiments intissue. The ablation outcome was evaluated with respect to applicator insertion angles (30°, 45°, 60°) , depth and offset from the fibroid center (±2 mm for 3 cm fibroid and ±1 mm for 1 cm fibroid) with 35 W and 15 W applied power for 3 cm and 1 cm fibroids, respectively. Power deposition was stopped when thermal dose of 40 cumulative equivalent minutes at 43 °C (CEM43) was accrued in adjacent myometrium.Within the range of all evaluated insertion angles, depths and offsets, the ablation coverage was less sensitive to variation in angle as compared to depth and offset, and ranged from 34.9 - 83.6% for 3 cm fibroid in 140 - 400 s and 34.1 - 67.9% for 1 cm fibroid in 30 - 50 s of heating duration. Maximum achievable ablation coverage in both fibroid cases reach ∼ 90% if thermal dose is allowed to exceed 40 CEM43 in myometrium.The study demonstrates the technical feasibility of transcervical microwave ablation for fibroid treatment and the relationship between applicator position within the fibroid and fraction of fibroid that can be ablated while limiting thermal dose in adjacent myometrium.
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http://dx.doi.org/10.1088/2057-1976/abffe4DOI Listing
June 2021

Microwave ablation of lung tumors: A probabilistic approach for simulation-based treatment planning.

Med Phys 2021 May 8. Epub 2021 May 8.

Department of Electrical and Computer Engineering, Kansas State University Manhattan, KS, 66506, USA.

Purpose: Microwave ablation (MWA) is a clinically established modality for treatment of lung tumors. A challenge with existing application of MWA, however, is local tumor progression, potentially due to failure to establish an adequate treatment margin. This study presents a robust simulation-based treatment planning methodology to assist operators in comparatively assessing thermal profiles and likelihood of achieving a specified minimum margin as a function of candidate applied energy parameters.

Methods: We employed a biophysical simulation-based probabilistic treatment planning methodology to evaluate the likelihood of achieving a specified minimum margin for candidate treatment parameters (i.e., applied power and ablation duration for a given applicator position within a tumor). A set of simulations with varying tissue properties was evaluated for each considered combination of power and ablation duration, and for four different scenarios of contrast in tissue biophysical properties between tumor and normal lung. A treatment planning graph was then assembled, where distributions of achieved minimum ablation zone margins and collateral damage volumes can be assessed for candidate applied power and treatment duration combinations. For each chosen power and time combination, the operator can also visualize the histogram of ablation zone boundaries overlaid on the tumor and target volumes. We assembled treatment planning graphs for generic 1, 2, and 2.5 cm diameter spherically shaped tumors and also illustrated the impact of tissue heterogeneity on delivered treatment plans and resulting ablation histograms. Finally, we illustrated the treatment planning methodology on two example patient-specific cases of tumors with irregular shapes.

Results: The assembled treatment planning graphs indicate that 30 W, 6 min ablations achieve a 5-mm minimum margin across all simulated cases for 1-cm diameter spherical tumors, and 70 W, 10 min ablations achieve a 3-mm minimum margin across 90% of simulations for a 2.5-cm diameter spherical tumor. Different scenarios of tissue heterogeneity between tumor and lung tissue revealed 2 min overall difference in ablation duration, in order to reliably achieve a 4-mm minimum margin or larger each time for 2-cm diameter spherical tumor.

Conclusions: An approach for simulation-based treatment planning for microwave ablation of lung tumors is illustrated to account for the impact of specific geometry of the treatment site, tissue property uncertainty, and heterogeneity between the tumor and normal lung.
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http://dx.doi.org/10.1002/mp.14923DOI Listing
May 2021

Short pulsed microwave ablation: computer modeling and experiments.

Int J Hyperthermia 2021 ;38(1):409-420

BioMIT, Department of Applied Mathematics, Universitat Politècnica de València, Valencia, Spain.

Purpose: To study the differences between continuous and short-pulse mode microwave ablation (MWA).

Methods: We built a computational model for MWA including a 200 mm long and 14 G antenna from Amica-Gen and solved an electromagnetic-thermal coupled problem using COMSOL Multiphysics. We compared the coagulation zone (CZ) sizes created with pulsed and continuous modes under and conditions. The model was used to compare long vs. short pulses, and 1000 W high-powered short pulses. experiments were conducted to validate the model.

Results: The computational models predicted the axial diameter of the CZ with an error of 2-3% and overestimated the transverse diameter by 9-11%. For short pulses, the computer modeling results showed a trend toward larger CZ when duty cycles decreases. In general, short pulsed mode yielded higher CZ diameters and volumes than continuous mode, but the differences were not significant (<5%), as in terms of CZ sphericity. The same trends were observed in the simulations mimicking conditions. Both CZ diameter and sphericity were similar with short and long pulses. Short 1000 W pulses produced smaller sphericity and similar CZ sizes under and conditions.

Conclusions: The characteristics of the CZ created by continuous and pulsed MWA show no significant differences from experiments and computer simulations. The proposed idea of enlarging coagulation zones and improving their sphericity in pulsed mode was not evident in this study.
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http://dx.doi.org/10.1080/02656736.2021.1894358DOI Listing
January 2021

Influence of injection technique, drug formulation and tumor microenvironment on intratumoral immunotherapy delivery and efficacy.

J Immunother Cancer 2021 Feb;9(2)

Interventional Radiology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA

Background: Intratumoral delivery of immunotherapeutics represents a compelling solution to directly address local barriers to tumor immunity. However, we have previously shown that off-target delivery is a substantial problem during intratumoral injections; this can lead to diminished drug efficacy and systemic toxicities. We have identified three variables that influence intratumoral drug delivery: injection technique, drug formulation and tumor microenvironment. The purpose of this study was to characterize the impact of modifications in each variable on intratumoral drug delivery and immunotherapy efficacy.

Methods: Intratumoral injections were performed in a hybrid image-guided intervention suite with ultrasound, fluoroscopy and CT scanning capabilities in both rat and mouse syngeneic tumor models. Intratumoral drug distribution was quantified by CT volumetric imaging. The influence of varying needle design and hydrogel-based drug delivery on the immune response to a stimulator of interferon genes (STING) agonist was evaluated using flow cytometry and single cell RNA sequencing. We also evaluated the influence of tumor stiffness on drug injection distribution.

Results: Variations in needle design, specifically with the use of a multiside hole needle, led to approximately threefold improvements in intratumoral drug deposition relative to conventional end-hole needles. Likewise, delivery of a STING agonist through a multiside hole needle led to significantly increased expression of type I interferon-associated genes and 'inflammatory' dendritic cell gene signatures relative to end-hole STING agonist delivery. A multidomain peptide-based hydrogel embedded with a STING agonist led to substantial improvements in intratumoral deposition; however, the hydrogel was noted to generate a strong immune response against itself within the target tumor. Evaluation of tumor stroma on intratumoral drug delivery revealed that there was a greater than twofold improvement in intratumoral distribution in soft tumors (B16 melanoma) compared with firm tumors (MC38 colorectal).

Conclusions: Injection technique, drug formulation and tumor stiffness play key roles in the accurate delivery of intratumoral immunotherapeutics.
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http://dx.doi.org/10.1136/jitc-2020-001800DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7887346PMC
February 2021

Bronchoscopically delivered microwave ablation in an porcine lung model.

ERJ Open Res 2020 Oct 13;6(4). Epub 2020 Oct 13.

Dept of Electrical and Computer Engineering, Kansas State University Manhattan, Manhattan, KS, USA.

Background: Percutaneous microwave ablation is clinically used for inoperable lung tumour treatment. Delivery of microwave ablation applicators to tumour sites within lung parenchyma under virtual bronchoscopy guidance may enable ablation with reduced risk of pneumothorax, providing a minimally invasive treatment of early-stage tumours, which are increasingly detected with computed tomography (CT) screening. The objective of this study was to integrate a custom microwave ablation platform, incorporating a flexible applicator, with a clinically established virtual bronchoscopy guidance system, and to assess technical feasibility for safely creating localised thermal ablations in porcine lungs .

Methods: Pre-ablation CTs of normal pigs were acquired to create a virtual model of the lungs, including airways and significant blood vessels. Virtual bronchoscopy-guided microwave ablation procedures were performed with 24-32 W power (at the applicator distal tip) delivered for 5-10 mins. A total of eight ablations were performed in three pigs. Post-treatment CT images were acquired to assess the extent of damage and ablation zones were further evaluated with viability stains and histopathologic analysis.

Results: The flexible microwave applicators were delivered to ablation sites within lung parenchyma 5-24 mm from the airway wall a tunnel created under virtual bronchoscopy guidance. No pneumothorax or significant airway bleeding was observed. The ablation short axis observed on gross pathology ranged 16.5-23.5 mm and 14-26 mm on CT imaging.

Conclusion: We have demonstrated the technical feasibility for safely delivering microwave ablation in the lung parenchyma under virtual bronchoscopic guidance in an porcine lung model.
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http://dx.doi.org/10.1183/23120541.00146-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7553114PMC
October 2020

Assessment of thermal damage to myometrium during microwave ablation of uterine fibroids.

Annu Int Conf IEEE Eng Med Biol Soc 2020 07;2020:5263-5266

Thermal ablation techniques are increasingly used for the treatment of symptomatic uterine fibroids. Thermal protection of myometrial tissue adjacent to the fibroid from ablation is critical to maximally preserve the uterus. This study presents a bench top experimental setup, using ex vivo bovine muscle as a surrogate tissue, for evaluating collateral thermal damage in tissues during fibroid ablation. The study reports on the effect of applicator insertion angles (67.5° and 90°) into a mock fibroid on the efficacy of treatment. 6 experiments were performed (3 for each insertion angle) with 30 W applied power at 2.45 GHz. The heating duration was restricted to the time at which a thermal dose of 10 cumulative equivalent minutes at 43 °C (10 CEM 43) was accrued at the boundary of the mock fibroid. Results showed that the volume of ablation inside the mock fibroid dropped considerably from 66% to 17% when the applicator insertion angle was changed from 90º to 67.5º, suggesting that insertion angle plays an important role during microwave ablation of fibroid. The proposed setup provides a method for validating computational models for accurate and safe delivery of ablation to target tissues in fibroid treatment.
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http://dx.doi.org/10.1109/EMBC44109.2020.9176092DOI Listing
July 2020

Temperature estimation for MR-guided microwave hyperthermia using block-based compressed sensing

Annu Int Conf IEEE Eng Med Biol Soc 2020 07;2020:5057-5060

Mild hyperthermia has been clinically employed as an adjuvant for radiation/chemotherapy and is under investigation for precise thermally-mediated delivery of cancer therapeutic agents. Magnetic Resonance Imaging (MRI) facilitates non-invasive, real-time spatial thermometry for monitoring and guiding hyperthermia procedures. Long image acquisition time during MR-guided hyperthermia may fail to capture rapid changes in temperature. This may lead to unwanted heating of healthy tissue and/or temperature rise above hyperthermic range. We have developed a block-based compressed sensing approach to reconstruct volumetric MR-derived microwave hyperthermia temperature profiles using a subset of measured data. This algorithm exploits the sparsity of MR images due to the presence of inter- and intra-slice correlation of hyperthermic MR-derived temperature profiles. We have evaluated the performance of our developed algorithm on a phantom and in vivo in mice using previously implemented microwave applicators. This algorithm reconstructs 3D temperature profiles with PSNR of 33 dB - 49 dB in comparison to the original profiles. In summary, this study suggests that microwave hyperthermia induced temperature profiles can be reconstructed using subsamples to reduce MR image acquisition time.
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http://dx.doi.org/10.1109/EMBC44109.2020.9176206DOI Listing
July 2020

Simulation-based design and characterization of a microwave applicator for MR-guided hyperthermia experimental studies in small animals.

Biomed Phys Eng Express 2020 01 27;6(1). Epub 2019 Nov 27.

Department of Electrical and Computer Engineering, Kansas State University, Manhattan, KS 66506, USA.

Purpose: The objective of this study was to design and characterize a 2.45 GHz microwave hyperthermia applicator for delivering hyperthermia in experimental small animals to 2 - 4 mm diameter targets located 1 - 3 mm from the skin surface, with minimal heating of the surrounding tissue, under 14.1 T MRI real-time monitoring and feedback control.

Materials And Methods: An experimentally validated 3D computational model was employed to design and characterize a non-invasive directional water-cooled microwave hyperthermia applicator. We assessed the effects of: reflector geometry, monopole shape, cooling water temperature, and flow rate on spatial-temperature profiles. The system was integrated with real-time MR thermometry and feedback control to monitor and maintain temperature elevations in the range of 4 - 5 °C at 1 - 3 mm from the applicator surface. The quality of heating was quantified by determining the fraction of the target volume heated to the desired temperature, and the extent of heating in non-targeted regions.

Results: Model-predicted hyperthermic profiles were in good agreement with experimental measurements (Dice Similarity Coefficient of 0.95 - 0.99). Among the four considered criteria, a reflector aperture angle of 120 °, S-shaped monopole antenna with 0.6 mm displacement, and coolant flow rate of 150 ml/min were selected as the end result of the applicator design. The temperature of circulating water and input power were identified as free variables, allowing considerable flexibility in heating target sizes within varying distances from the applicator surface. 2 - 4 mm diameter targets positioned 1 - 3 mm from the applicator surface were heated to hyperthermic temperatures, with target coverage ratio ranging between 76 - 93 % and 11 - 26 % of non-targeted tissue heated.

Conclusion: We have designed an experimental platform for MR-guided hyperthermia, incorporating a microwave applicator integrated with temperature-based feedback control to heat deep-seated targets for experimental studies in small animals.
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http://dx.doi.org/10.1088/2057-1976/ab36ddDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7521833PMC
January 2020

How large is the periablational zone after radiofrequency and microwave ablation? Computer-based comparative study of two currently used clinical devices.

Int J Hyperthermia 2020 ;37(1):1131-1138

BioMIT, Department of Electronic Engineering, Universitat Politècnica de València, Valencia, Spain.

Purpose: To compare the size of the coagulation (CZ) and periablational (PZ) zones created with two commercially available devices in clinical use for radiofrequency (RFA) and microwave ablation (MWA), respectively.

Methods: Computer models were used to simulate RFA with a 3-cm Cool-tip applicator and MWA with an Amica-Gen applicator. The Arrhenius model was used to compute the damage index (). CZ was considered when  > 4.6 (>99% of damaged cells). Regions with 0.6< < 2.1 were considered as the PZ (tissue that has undergone moderate sub-ablative hyperthermia). The ratio of PZ volume to CZ volume (PZ/CZ) was regarded as a measure of performance, since a low value implies achieving a large CZ while keeping the PZ small.

Results: Ten-min RFA (51 W) created smaller periablational zones than 10-min MWA (11.3 cm vs. 17.2-22.9 cm, for 60-100 W MWA, respectively). Prolonging duration from 5 to 10 min increased the PZ in MWA more than in RFA (2.7 cm for RFA vs. 8.3-11.9 cm for 60-100 W MWA, respectively). PZ/CZ for RFA were relatively high (65-69%), regardless of ablation time, while those for MWA were highly dependent on the duration (increase of up to 25% between 5 and 10 min) and on the applied power (smaller values as power was raised, 102% for 60 W vs. 81% for 100 W, both for 10 min). The lowest PZ/CZ across all settings was 56%, obtained with 100 W-5 min MWA.

Conclusions: Although RFA creates smaller periablational zones than MWA, 100 W-5 min MWA provides the lowest PZ/CZ.
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http://dx.doi.org/10.1080/02656736.2020.1823022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7714001PMC
January 2020

Smart bed based daytime behavior prediction in Children with autism spectrum disorder - A Pilot Study.

Med Eng Phys 2020 09 15;83:15-25. Epub 2020 Jul 15.

Department of Electrical and Computer Engineering, Kansas State University, Manhattan, KS 66506, United States. Electronic address:

Monitoring the sleep patterns of children with autism spectrum disorders (ASD) and understanding how sleep quality influences their daytime behavior is an important issue that has received very limited attention. Polysomnography (PSG) is commonly used as a gold standard for evaluating sleep quality in children and adults. However, the intrusive nature of sensors used as part of PSG can themselves affect sleep and is, therefore, not suitable for children with ASD. In this study, we evaluate an unobtrusive and inexpensive bed system for in-home, long-term sleep quality monitoring using ballistocardiogram (BCG) signals. Using the BCG signals from this smart bed system, we define "restlessness" as a surrogate sleep quality estimator. Using this sleep feature, we build predictive models for daytime behavior based on 1-8 previous nights of sleep. Specifically, we use two supervised machine learning algorithms namely support vector machine (SVM) and artificial neural network (ANN). For all daytime behaviors, we achieve more than 78% and 79% accuracy of correctly predicting behavioral issues with both SVM and ANN classifiers, respectively. Our findings indicate the usefulness of our designed bed system and how the restlessness feature can improve the prediction performance.
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http://dx.doi.org/10.1016/j.medengphy.2020.07.004DOI Listing
September 2020

Effect of position on transdiaphragmatic pressure and hemodynamic variables in anesthetized horses.

Can J Vet Res 2020 Jul;84(3):205-211

Department of Clinical Sciences, Kansas State University Veterinary Health Center, Manhattan, Kansas 66506, USA (Youngblood, Hodgson, Beard, Heflin); Department of Electrical and Computer Engineering, Kansas State University, Manhattan, Kansas 66506, USA (Song, Prakash).

Recumbency affects respiratory mechanics and oxygenation in anesthetized horses. Changes in pleural and abdominal pressures that can impair ventilation have not been described in all recumbencies. The objective of this study was to determine the effects of patient positioning on transdiaphragmatic pressure and selected hemodynamic variables. Horses were maintained under total intravenous general anesthesia with nasal oxygen supplementation. Transnasal balloon catheters in the stomach and thoracic esophagus were used to measure intrathoracic and gastric pressures in standing horses and in anesthetized horses positioned in right and left lateral recumbency, dorsal recumbency, reverse Trendelenburg position, and Trendelenburg position. Transdiaphragmatic pressure was calculated as the difference between gastric and intrathoracic pressures. Measurements of oxygen saturation (SpO), heart rate, systolic, diastolic and mean arterial pressures, and respiratory rate were obtained every 5 minutes. When compared to dorsal recumbency, gastric expiratory pressure is decreased in the standing position. Thoracic expiratory pressure is decreased in standing and reverse Trendelenburg. Transdiaphragmatic expiratory pressure and SpO are decreased in Trendelenburg. Heart rate is increased in reverse Trendelenburg. Systolic, diastolic, and mean arterial pressures are decreased in reverse Trendelenburg and increased in left lateral and right lateral recumbency. We found that there is wide variation in respiratory pressures between horses and positions and they are not predictive of associated changes in hemodynamic variables.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7301668PMC
July 2020

Broadband Dielectric Properties of Ex Vivo Bovine Liver Tissue Characterized at Ablative Temperatures.

IEEE Trans Biomed Eng 2021 01 21;68(1):90-98. Epub 2020 Dec 21.

Objective: To investigate the thermal and frequency dependence of dielectric properties of ex vivo liver tissue - relative permittivity and effective conductivity - over the frequency range 500 MHz to 6 GHz and temperatures ranging from 20 to 130 °C.

Methods: We measured the dielectric properties of fresh ex vivo bovine liver tissue using the open-ended coaxial probe method (n = 15 samples). Numerical optimization techniques were utilized to obtain parametric models for characterizing changes in broadband dielectric properties as a function of temperature and thermal isoeffective dose. The effect of heating tissue at rates over the range 6.4-16.9 °C/min was studied. The measured dielectric properties were used in simulations of microwave ablation to assess changes in simulated antenna return loss compared to experimental measurements.

Results: Across all frequencies, both relative permittivity and effective conductivity dropped sharply over the temperature range 89 - 107 °C. Below 91 °C, the slope of the effective conductivity changes from positive values at lower frequencies (0.5-1.64 GHz) to negative values at higher frequencies (1.64-6 GHz). The maximum achieved correlation values between transient reflection coefficients from measurements and simulations ranged between 0.83 - 0.89 and 0.68 - 0.91, respectively, when using temperature-dependent and thermal-dose dependent dielectric property parameterizations.

Conclusion: We have presented experimental measurements and parametric models for characterizing changes in dielectric properties of bovine liver tissue at ablative temperatures.

Significance: The presented dielectric property models will contribute to the development of ablation systems operating at frequencies other than 2.45 GHz, as well as broadband techniques for monitoring growth of microwave ablation zones.
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http://dx.doi.org/10.1109/TBME.2020.2996825DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7680390PMC
January 2021

Experimental assessment of microwave ablation computational modeling with MR thermometry.

Med Phys 2020 Sep 16;47(9):3777-3788. Epub 2020 Jul 16.

Mike Wiegers Department of Electrical and Computer Engineering, Kansas State University, Manhattan, KS, 66506, USA.

Purpose: Computational models are widely used during the design and characterization of microwave ablation (MWA) devices, and have been proposed for pretreatment planning. Our objective was to assess three-dimensional (3D) transient temperature and ablation profiles predicted by MWA computational models with temperature profiles measured experimentally using magnetic resonance (MR) thermometry in ex vivo bovine liver.

Materials And Methods: We performed MWA in ex vivo tissue under MR guidance using a custom, 2.45 GHz water-cooled applicator. MR thermometry data were acquired for 2 min prior to heating, during 5-10 min microwave exposures, and for 3 min following heating. Fiber-optic temperature sensors were used to validate the accuracy of MR temperature measurements. A total of 13 ablation experiments were conducted using 30-50 W applied power at the applicator input. MWA computational models were implemented using the finite element method, and incorporated temperature-dependent changes in tissue physical properties. Model-predicted ablation zone extents were compared against MRI-derived Arrhenius thermal damage maps using the Dice similarity coefficient (DSC).

Results: Prior to heating, the observed standard deviation of MR temperature data was in the range of 0.3-0.7°C. Mean absolute error between MR temperature measurements and fiber-optic temperature probes during heating was in the range of 0.5-2.8°C. The mean DSC between model-predicted ablation zones and MRI-derived Arrhenius thermal damage maps for 13 experimental set-ups was 0.95. When comparing simulated and experimentally (i.e. using MRI) measured temperatures, the mean absolute error (MAE %) relative to maximum temperature change was in the range 5%-8.5%.

Conclusion: We developed a system for characterizing 3D transient temperature and ablation profiles with MR thermometry during MWA in ex vivo liver tissue, and applied the system for experimental validation of MWA computational models.
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http://dx.doi.org/10.1002/mp.14318DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7719571PMC
September 2020

Directional Microwave Ablation: Experimental Evaluation of a 2.45-GHz Applicator in Ex Vivo and In Vivo Liver.

J Vasc Interv Radiol 2020 07 11;31(7):1170-1177.e2. Epub 2020 Mar 11.

Department of Electrical and Computer Engineering, Kansas State University, Manhattan, Kansas. Electronic address:

Purpose: To experimentally characterize a microwave (MW) ablation applicator designed to produce directional ablation zones.

Materials And Methods: Using a 14-gauge, 2.45-GHz side-firing MW ablation applicator, 36 ex vivo bovine liver ablations were performed. Ablations were performed at 60 W, 80 W, and 100 W for 3, 5, and 10 minutes (n = 4 per combination). Ablation zone forward and backward depth and width were measured and directivity was calculated as the ratio of forward to backward depth. Thirteen in vivo ablations were performed in 2 domestic swine with the applicator either inserted into the liver (80 W, 5 min, n = 3; 100 W, 5 min, n = 3; 100 W, 10 min, n = 2) or placed on the surface of the liver with a nontarget tissue placed on the back side of the applicator (80 W, 5 min, n = 5). The animals were immediately euthanized after the procedure; the livers were harvested and sectioned perpendicular to the axis of the applicator. In vivo ablation zones were measured following viability staining and assessed on histopathology.

Results: Mean ex vivo ablation forward depth was 8.3-15.5 mm. No backward heating was observed at 60 W, 3-5 minutes; directivity was 4.7-11.0 for the other power and time combinations. In vivo ablation forward depth was 10.3-11.5 mm, and directivity was 11.5-16.1. No visible or microscopic thermal damage to nontarget tissues in direct contact with the back side of the applicator was observed.

Conclusions: The side-firing MW ablation applicator can create directional ablation zones in ex vivo and in vivo tissues.
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http://dx.doi.org/10.1016/j.jvir.2020.01.016DOI Listing
July 2020

Differences in Transient Thermal Response of Commercial Esophageal Temperature Probes: Insights From an Experimental Study.

JACC Clin Electrophysiol 2019 11 2;5(11):1280-1288. Epub 2019 Oct 2.

Kansas City Heart Rhythm Institute and Research Foundation, Overland Park, Kansas. Electronic address:

Objectives: The purpose of this study was to evaluate the differences in transient thermal response (TTR) among various types of commercial esophageal temperature probes (ETPs) in the United States in an experimental model.

Background: There is little information regarding the variation in TTR among various commercial ETPs that are approved for atrial fibrillation ablation.

Methods: We compared various thermodynamic characteristics including, mean thermal time constant (τ), time to rise 1°C (T), time to peak temperature (T), and decay time among 22 different ETPs. Each probe was submerged in a constant-temperature water bath maintained at 37 ± 0.5°C and then quickly (<0.5 s) submerged into another water bath at 45 ± 0.5°C. The experiments were repeated 3 times with each probe. TTR properties were compared on the basis of probe size, design, and number of sensors.

Results: The τ was significantly higher with the larger 24- and 18-F ETPs compared with the smaller 9-F ETPs. Compared with the 18-F probe, T (11.9 s vs. 5 s), T (40.3 s vs. 14.4 s), and T (92.4 s vs. 32.4 s) was shorter with the 9-F ETPs. Solid-shaft ETPs had shorter τ (8.6 s vs. 20.5 s), T (4.4 s vs. 10.1 s) and T (13.5 s vs. 32.5 s) compared with acoustascopes. Multisensor ETPs had shorter τs (3.9 s vs. 9.1 s), T (2.3 s vs. 5 s), and T (6.2 s vs. 14.4 s) compared with single-sensor ETPs.

Conclusions: There is a significant variation in TTR among the various commercially available ETPs. The use of certain ETPs might result in underestimation of luminal esophageal temperature, which can potentially lead to adverse events.
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http://dx.doi.org/10.1016/j.jacep.2019.07.013DOI Listing
November 2019

Using microwave thermal ablation to develop a subtotal, cortical-sparing approach to the management of primary aldosteronism.

Int J Hyperthermia 2019 ;36(1):905-914

Discipline of Pharmacology and Therapeutics, School of Medicine, National University of Ireland , Galway , Ireland.

To investigate the feasibility and efficacy of localized, subtotal, cortical-sparing microwave thermal ablation (MTA) as a potential curative management for primary aldosteronism. The study investigated with equal importance the selected ablation of small volumes of adrenal cortex while sparing adjacent cortex. An study was carried out in swine ( = 8) where MTA was applied under direct visualization, to the adrenal glands at 45 W or 70 W for 60 s, using a lateral, side-firing probe and a non-penetrative approach. Animals were survived for 48 h post-procedurally. Animals were investigated for markers of histological, immunohistochemical and biochemical evidence of adrenal function and adrenal damage by assessing samples drawn intra-operatively and at the time of euthanasia. Selected MTA (70 W for 60 s) successfully ablated small adrenocortical volumes (∼0.8 cm) characterized by coagulative necrosis and abnormal expression of functional markers (CYP11B1 and CYP17). Non-ablated, adjacent cortex was not affected and preserved normal expression of functional markers, without increased expression of markers of heat damage (HSP-70 and HMGB-1). Limited adrenal medullary damage was demonstrated histologically, clinically and biochemically. MTA offers potential as an efficient methodology for delivering targeted subtotal cortical-sparing adrenal ablation. Image-guided targeted MTA may also represent a safe future modality for curative management of PA, in the setting of both unilateral and bilateral disease.
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http://dx.doi.org/10.1080/02656736.2019.1650205DOI Listing
January 2020

Broadband lung dielectric properties over the ablative temperature range: Experimental measurements and parametric models.

Med Phys 2019 Oct 10;46(10):4291-4303. Epub 2019 Aug 10.

Department of Electrical and Computer Engineering, Kansas State University, 1701D Platt st., Manhattan, KS, 66506, USA.

Purpose: Computational models of microwave tissue ablation are widely used to guide the development of ablation devices, and are increasingly being used for the development of treatment planning and monitoring platforms. Knowledge of temperature-dependent dielectric properties of lung tissue is essential for accurate modeling of microwave ablation (MWA) of the lung.

Methods: We employed the open-ended coaxial probe method, coupled with a custom tissue heating apparatus, to measure dielectric properties of ex vivo porcine and bovine lung tissue at temperatures ranging between 31 and 150  C, over the frequency range 500 MHz to 6 GHz. Furthermore, we employed numerical optimization techniques to provide parametric models for characterizing the broadband temperature-dependent dielectric properties of tissue, and their variability across tissue samples, suitable for use in computational models of microwave tissue ablation.

Results: Rapid decreases in both relative permittivity and effective conductivity were observed in the temperature range from 94 to 108  C. Over the measured frequency range, both relative permittivity and effective conductivity were suitably modeled by piecewise linear functions [root mean square error (RMSE) = 1.0952 for permittivity and 0.0650 S/m for conductivity]. Detailed characterization of the variability in lung tissue properties was provided to enable uncertainty quantification of models of MWA.

Conclusions: The reported dielectric properties of lung tissue, and parametric models which also capture their distribution, will aid the development of computational models of microwave lung ablation.
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http://dx.doi.org/10.1002/mp.13704DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6893909PMC
October 2019

Therapeutic Systems and Technologies: State-of-the-Art Applications, Opportunities, and Challenges.

IEEE Rev Biomed Eng 2020 2;13:325-339. Epub 2019 Apr 2.

In this review, we present current state-of-the-art developments and challenges in the areas of thermal therapy, ultrasound tomography, image-guided therapies, ocular drug delivery, and robotic devices in neurorehabilitation. Additionally, intellectual property and regulatory aspects pertaining to therapeutic systems and technologies are addressed.
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http://dx.doi.org/10.1109/RBME.2019.2908940DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7341980PMC
November 2020

Antenna Designs for Microwave Tissue Ablation.

Crit Rev Biomed Eng 2018 ;46(6):495-521

Department of Electrical and Computer Engineering, Kansas State University, Manhattan, Kansas.

Microwave (MW) ablation has emerged as a minimally invasive therapeutic modality and is in clinical use for treatment of unresectable tumors and cardiac arrhythmias, neuromodulation, endometrial ablation, and other applications. Components of image-guided MW ablation systems include high-power MW sources, ablation applicators that deliver power from the generator to the target tissue, cooling systems, energy-delivery control algorithms, and imaging guidance systems tailored to specific clinical indications. The applicator incorporates a MW antenna that radiates MW power into the surrounding tissue. A variety of antenna designs have been developed for MW ablation with the objective of efficiently transferring MW power to tissue, with a radiation pattern well matched to the size and shape of the targeted tissue. Here, we survey advances in percutaneous, endocavitary, and endoscopic antenna designs as an integral element of MW ablation applicators for a diverse set of clinical applications.
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http://dx.doi.org/10.1615/CritRevBiomedEng.2018028554DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6391890PMC
October 2019

A Pilot Study of an Unobtrusive Bed-Based Sleep Quality Monitor for Severely Disabled Autistic Children.

Annu Int Conf IEEE Eng Med Biol Soc 2018 Jul;2018:4343-4346

The link between daytime performance and sleep quality for severely disabled autistic children is not entirely understood. This paper presents nighttime data collected from a child with severe disabilities during a three-night pilot study conducted at Heartspring, Wichita, KS, using a bed-based system capable of unobtrusively tracking parameters for sleep quality assessment. The 'average sample correlation coefficient signal-to-noise ratio' is compared for ballistocardiograms acquired using four electromechanical film sensors versus four load cell sensors. The "best" signal or sensing modality depends on the subject's sleeping position. These results affirm the importance of a bed system that is robust in its ability to track sleep quality accurately regardless of sleeping position.
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http://dx.doi.org/10.1109/EMBC.2018.8513256DOI Listing
July 2018

Evaluation of the Effect of Uterine Fibroids on Microwave Endometrial Ablation Profiles.

Annu Int Conf IEEE Eng Med Biol Soc 2018 Jul;2018:3236-3239

Thermal ablation of the endometrial lining of the uterus is a minimally-invasive technique for treatment of menorrhagia. We have previously presented a 915 MHz microwave triangular loop antenna for endometrial ablation. Uterine fibroids are benign pelvic tumors, of considerably different water content compared to normal uterus, and may change the shape of the uterus. Collectively, these changes introduced by fibroids may alter the pattern of microwave endometrial ablation. In this study, we have investigated the effect of 1 - 3 cm diameter uterine fibroids in different locations around the uterine cavity on ablation profiles following 60 W, 150 s microwave exposure with a loop antenna. Our computational model predicts ablation zone extents within 1 ± 0.8 of ablation zones observed in experiments in ex vivo tissue. The maximum change in simulated ablation depths due to the presence of fibroids was 1.1 mm. In summary, this simulation study suggests that 1 - 3 cm diameter uterine fibroids can be expected to have minimal impact on the extent of microwave endometrial ablation patterns.
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http://dx.doi.org/10.1109/EMBC.2018.8513051DOI Listing
July 2018

An integrated platform for small-animal hyperthermia investigations under ultra-high-field MRI guidance.

Int J Hyperthermia 2018 06 21;34(4):341-351. Epub 2017 Jul 21.

a Department of Electrical and Computer Engineering , Kansas State University , Manhattan , KS , USA.

Purpose: Integrating small-animal experimental hyperthermia instrumentation with magnetic resonance imaging (MRI) affords real-time monitoring of spatial temperature profiles. This study reports on the development and preliminary in vivo characterisation of a 2.45 GHz microwave hyperthermia system for pre-clinical small animal investigations, integrated within a 14 T ultra-high-field MRI scanner.

Materials And Methods: The presented system incorporates a 3.5 mm (OD) directional microwave hyperthermia antenna, positioned adjacent to the small-animal target, radiating microwave energy for localised heating of subcutaneous tumours. The applicator is integrated within the 30 mm bore of the MRI system. 3D electromagnetic and biothermal simulations were implemented to characterise hyperthermia profiles from the directional microwave antenna. Experiments in tissue mimicking phantoms were performed to assess hyperthermia profiles and validate MR thermometry against fibre-optic temperature measurements. The feasibility of delivering in vivo hyperthermia exposures to subcutaneous 4T1 tumours in experimental mice under simultaneous MR thermometry guidance was assessed.

Results: Simulations and experiments in tissue mimicking phantoms demonstrated the feasibility of heating 21-982 mm targets with 8-12 W input power. Minimal susceptibility and electrical artefacts introduced by the hyperthermia applicator were observed on MR imaging. MR thermometry was in excellent agreement with fibre-optic temperatures measurements (max. discrepancy ≤0.6 °C). Heating experiments with the reported system demonstrated the feasibility of heating subcutaneous tumours in vivo with simultaneous MR thermometry.

Conclusions: A platform for small-animal hyperthermia investigations under ultra-high-field MR thermometry was developed and applied to heating subcutaneous tumours in vivo.
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http://dx.doi.org/10.1080/02656736.2017.1339126DOI Listing
June 2018

Experimental Investigation of Magnetic Nanoparticle-Enhanced Microwave Hyperthermia.

J Funct Biomater 2017 Jun 22;8(3). Epub 2017 Jun 22.

Department of Electrical and Computer Engineering, Kansas State University, 3078 Engineering Hall, Manhattan, KS 66506, USA.

The objective of this study was to evaluate microwave heating enhancements offered by iron/iron oxide nanoparticles dispersed within tissue-mimicking media for improving efficacy of microwave thermal therapy. The following dopamine-coated magnetic nanoparticles (MNPs) were considered: 10 and 20 nm diameter spherical core/shell Fe/Fe₃O₄, 20 nm edge-length cubic Fe₃O₄, and 45 nm edge-length/10 nm height hexagonal Fe₃O₄. Microwave heating enhancements were experimentally measured with MNPs dissolved in an agar phantom, placed within a rectangular waveguide. Effects of MNP concentration (2.5-20 mg/mL) and microwave frequency (2.0, 2.45 and 2.6 GHz) were evaluated. Further tests with 10 and 20 nm diameter spherical MNPs dispersed within a two-compartment tissue-mimicking phantom were performed with an interstitial dipole antenna radiating 15 W power at 2.45 GHz. Microwave heating of 5 mg/mL MNP-agar phantom mixtures with 10 and 20 nm spherical, and hexagonal MNPs in a waveguide yielded heating rates of 0.78 ± 0.02 °C/s, 0.72 ± 0.01 °C/s and 0.51 ± 0.03 °C/s, respectively, compared to 0.5 ± 0.1 °C/s for control. Greater heating enhancements were observed at 2.0 GHz compared to 2.45 and 2.6 GHz. Heating experiments in two-compartment phantoms with an interstitial dipole antenna demonstrated potential for extending the radial extent of therapeutic heating with 10 and 20 nm diameter spherical MNPs, compared to homogeneous phantoms (i.e., without MNPs). Of the MNPs considered in this study, spherical Fe/Fe₃O₄ nanoparticles offer the greatest heating enhancement when exposed to microwave radiation. These nanoparticles show strong potential for enhancing the rate of heating and radial extent of heating during microwave hyperthermia and ablation procedures.
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http://dx.doi.org/10.3390/jfb8030021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5618272PMC
June 2017

Design and characterisation of a phased antenna array for intact breast hyperthermia.

Int J Hyperthermia 2018 05 28;34(3):250-260. Epub 2017 Jun 28.

a Department of Electrical and Computer Engineering , Kansas State University , Manhattan , KS , USA.

Purpose: Currently available hyperthermia technology is not well suited to treating cancer malignancies in the intact breast. This study investigates a microwave applicator incorporating multiple patch antennas, with the goal of facilitating controllable power deposition profiles for treating lesions at diverse locations within the intact breast.

Materials And Methods: A 3D-computational model was implemented to assess power deposition profiles with 915 MHz applicators incorporating a hemispheric groundplane and configurations of 2, 4, 8, 12, 16 and 20 antennas. Hemispheric breast models of 90 mm and 150 mm diameter were considered, where cuboid target volumes of 10 mm edge length (1 cm) and 30 mm edge length (27 cm) were positioned at the centre of the breast, and also located 15 mm from the chest wall. The average power absorption (αPA) ratio expressed as the ratio of the PA in the target volume and in the full breast was evaluated. A 4-antenna proof-of-concept array was fabricated and experimentally evaluated.

Results: Computational models identified an optimal inter-antenna spacing of 22.5° along the applicator circumference. Applicators with 8 and 12 antennas excited with constant phase presented the highest αPA at centrally located and deep-seated targets, respectively. Experimental measurements with a 4-antenna proof-of-concept array illustrated the potential for electrically steering power deposition profiles by adjusting the relative phase of the signal at antenna inputs.

Conclusions: Computational models and experimental results suggest that the proposed applicator may have potential for delivering conformal thermal therapy in the intact breast.
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http://dx.doi.org/10.1080/02656736.2017.1337935DOI Listing
May 2018

Computational modeling of 915 MHz microwave ablation: Comparative assessment of temperature-dependent tissue dielectric models.

Med Phys 2017 Sep 7;44(9):4859-4868. Epub 2017 Aug 7.

Department of Electrical and Computer Engineering, Kansas State University, Manhattan, KS, 66506, USA.

Purpose: The objective of this study is to develop a computational model for simulating 915 MHz microwave ablation (MWA), and verify the simulation predictions of transient temperature profiles against experimental measurements. Due to the limited experimental data characterizing temperature-dependent changes of tissue dielectric properties at 915 MHz, we comparatively assess two temperature-dependent approaches of modeling of dielectric properties: model A- piecewise linear temperature dependencies based on existing, but limited, experimental data, and model B- similar to model A, but augmented with linear decrease in electrical conductivity above 95 °C, as guided by our experimental measurements.

Methods: The finite element method was used to simulate MWA procedures in liver with a clinical 915 MHz ablation applicator. A coupled electromagnetic-thermal solver incorporating temperature-dependent tissue biophysical properties of liver was implemented. Predictions of the transient temperature profiles and ablation zone dimensions for both model A and model B were compared against experimental measurements in ex vivo bovine liver tissue. Broadband dielectric properties of tissue within different regions of the ablation zone were measured and reported at 915 MHz and 2.45 GHz.

Results: Model B yielded peak tissue temperatures in closer agreement with experimental measurements, attributed to the inclusion of decrease in electrical conductivity at elevated temperature. The simulated transverse diameters of the ablation zone predicted by both models were greater than experimental measurements, which may be in part due to the lack of a tissue shrinkage model. At both considered power levels, predictions of transverse ablation zone diameters were in closer agreement with measurements for model B (max. discrepancy of 5 mm at 60 W, and 3 mm at 30 W), compared to model A (max. discrepancy of 9 mm at 60 W, and 6 mm at 30 W). Ablation zone lengths with both models were within 2 mm at 30 W, but overestimated by up to 10 mm at 60 W.

Conclusions: The inclusion of decreased electrical conductivity above 95 °C, implemented with model B as guided by our experimental measurements, may be a good approach for approximating the dynamic changes that occur during MWA at 915 MHz. Although a step toward more effectively modeling MWA at 915 MHz, further investigation of the transition in dielectric properties with temperature and tissue shrinkage, especially at high temperatures is needed for more accurate simulations.
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http://dx.doi.org/10.1002/mp.12359DOI Listing
September 2017

Bed-based instrumentation for unobtrusive sleep quality assessment in severely disabled autistic children.

Annu Int Conf IEEE Eng Med Biol Soc 2016 Aug;2016:4909-4912

The relationship between sleep quality and daytime wellness and performance in severely disabled, autistic children is not well understood. While polysomnography and, more recently, actigraphy serve as means to obtain sleep assessment data from neurotypical children and adults, these techniques are not well-suited to severely autistic children. This paper presents recent progress on a bed sensor suite that can unobtrusively track physiological and behavioral parameters used to assess sleep quality. Electromechanical films and load cells provide data that yield heart rate, respiration rate, center of position, in-and-out-of-bed activity, and general movement, while thermocouples are used to detect bed-wetting events.
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http://dx.doi.org/10.1109/EMBC.2016.7591828DOI Listing
August 2016

Design projects motivated and informed by the needs of severely disabled autistic children.

Annu Int Conf IEEE Eng Med Biol Soc 2016 Aug;2016:3015-3018

Technology can positively impact the lives of severely disabled autistic children if used to (a) gather situational awareness data regarding their health, development, and behavior and (b) assist them with learning and day-to-day activities. This paper summarizes student design projects in the Kansas State University (KSU) College of Engineering that are motivated and informed by the needs of severely disabled children at Heartspring, Wichita, KS. These efforts are supported through the National Science Foundation's General and Age-Related Disabilities Engineering (GARDE) program. Projects relate thematically to (1) facets of a bed sensor system that unobtrusively tracks nighttime health parameters and child activity and (2) miscellaneous resources geared toward paraeducator ("para") and child well-being and development.
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http://dx.doi.org/10.1109/EMBC.2016.7591364DOI Listing
August 2016

Introduction to microwave tumour ablation special issue.

Int J Hyperthermia 2017 02;33(1):1-2

b Department of Pediatrics , Medical University of South Carolina , Charleston , SC , USA.

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http://dx.doi.org/10.1080/02656736.2016.1221147DOI Listing
February 2017