Creating Patient-Specific Computational Head Models for the Study of Tissue-Electric Field Interactions Using Deformable Templates

Abstract INTRODUCTION Tumor Treating Fields (TTFields) are an approved therapy for glioblastoma (GBM). A recent study combining post-hoc analysis of clinical trial data and extensive computational modelling demonstrated that TTFields dose at the tumor has a direct impact on patient survival (Ballo MT, et al. Int J Radiat Oncol Biol Phys, 2019). Hence, there is rationale for developing TTFields treatment planning tools that rely on numerical simulations and patient-specific computational models. To assist in the development of such tools is it important to understand how inaccuracies in the computational models influence the estimation of the TTFields dose delivered to the tumor bed. Here we analyze the effect of local perturbations in patient-specific head models on TTFields dose at the tumor bed. METHODS Finite element models of human heads with tumor were created. To create defects in the models, conductive spheres with varying conductivities and radii were placed into the model’s brains at different distances from the tumor. Virtual transducer arrays were placed on the models, and delivery of TTFields numerically simulated. The error in the electric field induced by the defects as a function of defect conductivity, radius, and distance to tumor was investigated. RESULTS Simulations showed that when a defect of radius R is placed at a distance, d >7R, the error is below 1% regardless of the defect conductivity. Further the defects induced errors in the electric field that were below 1% when σrR/d < 0.16, where σrR/d < 0.16, where σr = (σsphere – σsurrounding)/(σsphere + σsurrounding).σsurroundings is the average conductivity around the sphere and σsphere is the conductivity of the sphere. CONCLUSIONS This study demonstrates the limited impact of local perturbations in the model on the calculated field distribution. These results could be used as guidelines on required model accuracy for TTFields treatment planning.

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P14.69 Evaluation of electric field intensity delivered by Tumor-Treating Fields therapy to PET-defined metabolic volumes in recurrent glioblastomas

Neuro-Oncology ◽

10.1093/neuonc/noz126.304 ◽

2019 ◽

Vol 21 (Supplement_3) ◽

pp. iii83-iii84

Author(s):

S Mittal ◽

F John ◽

A Naveh ◽

Z Bomzon ◽

G R Barger ◽

...

Keyword(s):

Amino Acid ◽

Electric Field ◽

Tumor Volume ◽

Metabolic Tumor Volume ◽

Patient Specific ◽

Factors Affecting ◽

Tumor Mass ◽

Tumor Treating Fields ◽

Treatment Responses

Abstract BACKGROUND Tumor-Treating Fields (TTFields) therapy is a clinical treatment option for patients with newly-diagnosed and recurrent glioblastomas. Electric field intensities (EFIs) delivered to the tumor mass may affect treatment responses. In this study, we used the patients’ neuroimaging data to create realistic head models and evaluate: (i) the magnitude of EFIs delivered to the tumor mass; (ii) factors affecting the EFI values; and (iii) factors affecting treatment responses as assessed by amino acid PET. MATERIAL AND METHODS Fourteen recurrent glioblastomas in 9 patients were evaluated with α-[11C]-methyl-L-tryptophan (AMT)-PET before and up to 3 months after TTFields therapy (mean follow-up: 2.3 months). Individual MRI and CT scans were used to create patient-specific realistic head models and simulate TTFields delivery to the tumors. For each direction of treatment (antero-posterior, left-right), two 9-disk transducer arrays were simulated using disks placed according to the patients’ NovoTAL System™ based treatment plan. To generate TTFields, an alternating voltage difference (200V peak-to-peak, 200 kHz) was imposed on the outer surfaces of the disks. The simulations were performed using the Sim4Life V3.0 (ZMT-Zurich) quasi-electrostatic solver. The field intensities were normalized to simulate 2A peak-to-peak current supplied by the device. 3D EFI maps were created and fused with the pre- and post-TTFields PET images to measure EFIs delivered to the PET-defined metabolic tumor volume. Interval changes of static AMT uptake and kinetic PET variables were also evaluated. RESULTS The mean EFI delivered to the tumors varied between 1.34–2.43 V/cm (mean: 1.86 V/cm). Fronto-parietal tumors received higher mean EFI than temporal lobe tumors (p=0.05). Most tumors showed decreasing (n=9) or stable (n=4) AMT uptake on follow-up PET imaging after TTFields therapy. Higher EFIs delivered to the tumors (r=-0.56, p=0.04) and concomitant bevacizumab treatment (n=7, p=0.01) were associated with a greater PET response. On tracer kinetic analysis, the AMT uptake responses correlated with transport rate changes (p=0.04). CONCLUSION TTFields treatment of recurrent glioblastomas delivers variable EFIs to the metabolic tumor volume. Treatment responses on PET are driven by decreased amino acid transport rates, whose magnitude is associated with higher EFIs delivered to the tumor mass and also with concomitant antiangiogenic treatment in those with combined therapy. (The cost of the PET scans was supported by a grant from NovoCure Ltd., Haifa, Israel)

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Patient-Specific Simulations of Deep Brain Stimulation Electric Field with Aid of In-house Software ELMA

2019 41st Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC) ◽

10.1109/embc.2019.8856307 ◽

2019 ◽

Cited By ~ 2

Author(s):

Johannes D. Johansson ◽

Fabiola Alonso ◽

Karin Wardell

Keyword(s):

Deep Brain Stimulation ◽

Electric Field ◽

Brain Stimulation ◽

Patient Specific ◽

Deep Brain

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P.160 Impact of peritumoral edema during tumor treatment field therapy: a computational modelling study

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/cjn.2021.436 ◽

2021 ◽

Vol 48 (s3) ◽

pp. S65-S66

Author(s):

S Lang ◽

L Gan ◽

C McLennan ◽

O Monchi ◽

J Kelly

Keyword(s):

Electric Field ◽

Field Distribution ◽

Electric Field Distribution ◽

Computational Modelling ◽

Electrical Current ◽

Patient Specific ◽

Peritumoral Edema ◽

Tumor Treatment ◽

Electric Field Magnitude ◽

Field Magnitude

Background: Tumor treatment fields (TTFields) are an approved adjuvant therapy for glioblastoma. The magnitude of applied electrical field is related to the anti-tumoral response. However, peritumoral edema (ptE) may result in shunting of electrical current around the tumor, thereby reducing the intra-tumoral electric field. In this study, we address this issue with computational simulations. Methods: Finite element models were created with varying amounts of ptE surrounding a virtual tumor. The electric field distribution was simulated using the standard TTFields electrode montage. Electric field magnitude was extracted from the tumor and related to edema thickness. Two patient specific models were created to confirm these results. Results: The inclusion of ptE decreased the magnitude of the electric field within the tumor. In the model considering a frontal tumor and an anterior-posterior electrode configuration, ≥ 6 mm of ptE decreased the electric field by 52%. In the patient specific models, ptE decreased the electric field within the tumor by an average of 26%. The effect of ptE on the electric field distribution was spatially heterogenous. Conclusions: Given the importance of electric field magnitude for the anti-tumoral effects of TTFields, the presence of edema should be considered both in future modelling studies and as a predictor of non-response.

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Investigation of the mechanisms of action behind Electromotive Drug Administration (EMDA)

PeerJ ◽

10.7717/peerj.2309 ◽

2016 ◽

Vol 4 ◽

pp. e2309 ◽

Cited By ~ 5

Author(s):

Bor Kos ◽

Juan Luis Vásquez ◽

Damijan Miklavčič ◽

Gregers G.G. Hermann ◽

Julie Gehl

Keyword(s):

Electric Field ◽

Mitomycin C ◽

Electric Fields ◽

Drug Administration ◽

Mechanism Of Action ◽

Bladder Wall ◽

Whole Body ◽

Patient Specific ◽

The Mean ◽

Electromotive Drug Administration

ObjectiveBladder cancer is a cause of considerable morbidity worldwide. Electromotive Drug Administration is a method that combines intravesical chemotherapy with local electric field application. Electroporation has been suggested among other mechanisms as having a possible role in the therapy, so the goal of the present study was to investigate the electric fields present in the bladder wall during the treatment to determine which mechanisms might be involved.Material and MethodsElectromotive Drug Administration involves applying intravesical mitomycin C with direct current of 20 mA delivered through a catheter electrode for 30 min. For numerical electric field computation we built a 3-D nonhomogeneous patient specific model based on CT images and used finite element method simulations to determine the electric fields in the whole body.ResultsResults indicate that highest electric field in the bladder wall was 37.7 V/m. The mean electric field magnitude in the bladder wall was 3.03 V/m. The mean magnitude of the current density in the bladder wall was 0.61 A/m2.ConclusionsThe present study shows that electroporation is not the mechanism of action in EMDA. A more likely explanation of the mechanism of action is iontophoretic forces increasing the mitomycin C concentration in the bladder wall.

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High-Density Transcranial DC Stimulation (HD-tDCS): Targeting Software

Journal of Medical Devices ◽

10.1115/1.3136423 ◽

2009 ◽

Vol 3 (2) ◽

Author(s):

A. Datta ◽

V. Bansal ◽

J. Diaz ◽

J. Patel ◽

L. Oliveira ◽

...

Keyword(s):

Electric Field ◽

Current Density ◽

Performance Enhancement ◽

Invasive Procedure ◽

High Density ◽

Rapid Screening ◽

Patient Specific ◽

Fatty Tissue ◽

Non Invasive ◽

Stimulation Electrode

Transcranial Direct Current Stimulation (tDCS) is a non-invasive procedure where a weak electrical current (260 μA to 2 mA) is applied across the scalp to modulate brain function. tDCS has been applied for therapeutic purposes (e.g., addiction, depression, mood and sleep disorders) as well as cognitive performance enhancement (e.g., memory consolidation, motor learning, language recall). Despite safety and cost advantages, the developments of tDCS therapies have been restricted by spatial targeting concerns using existing two-channel systems. We have developed novel technology for High-Density tDCS (HD-tDCS) that improves spatial focality. To determine optimal stimulation electrode configurations, based on application specific constraints, we developed a HD-tDCS targeting software. High resolution (gyri/sulci precise) MRI derived finite element (FE) human head models are generated by segmenting grey matter, white matter, CSF, skull, muscle, fatty tissue, eyes, blood vessels, scalp, etc. The models comprised >10 million elements with >15 million degrees of freedom. The induced cortical electric field/current density values are calculated; activation of either radially and tangentially oriented neuronal structures are considered. Our HD-tDCS hardware (4×1-C1, 4×4-S1) currently supports the ‘4×1-Ring’ and the ‘4×4-Strip’ electrode configurations. The peak cortical electric field was matched to ‘conventional’ large rectangular-pad tDCS stimulation; however, the spatial focality was significantly enhanced by 4×1 configuration. Using patient specific head models, our software interface allows simple and rapid screening of stimulation electrode configurations. After selecting a target region, clinicians can customize the electrode configuration to balance: 1) cortical surface and brain depth stimulation focality; 2) total applied current/voltage; and 3) electrode/scalp current density. Our HD-tDCS system allows non-invasive, safe, and targeted modulation of selected cortical structures for electrotherapies that are individualized as well as optimized for a range of therapeutic applications.

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