Background: Despite extensive efforts to obtain accurate segmentation of magnetic resonance imaging (MRI) scans of a head, it remains challenging primarily due to variations in intensity distribution, which depend on the equipment and parameters used. Purpose: The goal of this study is to evaluate the effectiveness of an automatic segmentation method for head MRI scans using a multistep Dense U-Net (MDU-Net) architecture. 

This study was designed to investigate the correlation between the impulse by dielectrophoretic force applied inside a dividing cell during alternating electric fields therapy and the inhibition of cell proliferation. Distributions of the electric field and dielectrophoretic force inside a dividing cell were calculated using the finite element method of COMSOL Multiphysics. Based on the results, the average magnitude of the impulse by the dielectrophoretic force applied to the cleavage furrow inside a dividing cell placed in various directions was calculated as a function of electric field intensity at an extracellular reference point. The simulation results showed that the average magnitude of the impulse to the cleavage furrow inside a dividing cell ranged from 1.51 × 10−9 to 1.49 × 10−7 N s when tumor treating fields with an intensity ranging from 0.1 to 1 V/cm is applied at an extracellular reference point for 6 h. To verify the relationships between the impulse by the dielectrophoretic force and the inhibition of cell proliferation, the survival fractions of the four cancer cell lines were determined as a function of intensity and time duration of the electric field. The correlation between the magnitude and application time of the electric field and the survival fractions of the four cell lines showed similar trends in vitro. These results suggest that both the dielectrophoretic force and the time required for the force to act are proportionally related to the inhibitory effect on dividing cells, enabling this impulse to be used as a reference to quantify the inhibition of cell proliferation.

Purpose: This study evaluated the properties of a scintillation sheet-based dosimetry system for beam monitoring with high spatial resolution, including the effects of this system on the treatment beam. The dosimetric characteristics and feasibility of this system for clinical use were also evaluated. 

Introduction: The purpose of this study was to evaluate a plastic scintillating plate‑based beam monitoring system to perform quality assurance (QA) measurements in pencil beam scanning proton beam. 

This study aimed to quantitatively analyze the effciency of the fast non-local means (FNLM) filter in increasing the nodule detection sensitivity in pediatric chest computed tomography (CT) using 3D-printed lung nodules. For that purpose, we compared filtered back projection (FBP) with FNLM filter with iterative reconstruction (IR) method. The performance of the proposed FNLM filter was compared through various quantitative evaluations by modeling the previously used noise reduction methods. When the FNLM filter was applied to the acquired FBP reconstruction method-based CT image, the coeffcient of variation and contrast-to-noise ratio values in the lung nodule region showed similar values to those of the IR method. In addition, it was demonstrated that the point spread function value that can evaluate sharpness can be improved by using the FNLM filter. In conclusion, the results of this study are expected to maximize the image quality and reduce the dose by fusing the CT image reconstructed by the FBP method and the FNLM filter with excellent characteristics.

The present study investigated the therapeutic potential of combining tumor-treating fields (TTF), a novel cancer treatment modality that employs low-intensity, alternating electric fields, with 5-fluorouracil (5-FU), a standard chemotherapy drug used for treating pancreatic cancer. The HPAF-II and Mia-Paca II pancreatic cancer cell lines were treated with TTF, 5-FU, or their combination. Combination treatment produced a significantly greater inhibitory effect on cancer cell proliferation than each single modality. Furthermore, combination therapy induced a substantially higher rate of pancreatic cancer cell apoptosis and exhibited a synergistic effect in clonogenic assays. Additionally, combination treatment showed a greater inhibition of cancer cell migration and invasion than either TTF or 5-FU alone. In conclusion, these findings suggest that the synergistic properties of TTF and 5-FU result in greater therapeutic efficacy against pancreatic cancer cells than either modality alone and may improve survival rates in patients with pancreatic cancer.

The present study aimed to determine a method for estimating a potential prognostic factor in alternating electric fields for the treatment of solid tumors based on cell survival curves that evaluate cell proliferation capability. In AGS, B16F10, U373, and HPAF-II cancer cell lines, the proportional relationships of the electric field magnitude and the duration of application with the proliferation of cancer cell lines was identified by in vitro alternating current electric field experiments performed under various conditions. A prognostic factor applicable to alternating electric field therapy was developed by identifying proportional relationships of the electric field magnitude and the duration of application with the proliferation of the four cancer cell lines. Through the experimental results, the absorbed energy in tissue has been suggested as a potential prognostic factor in alternating electric field therapy. The absorbed energy in tissue can be used as a reference to quantify the inhibition of cell proliferation related to control, enabling systematic assessment of alternating electric field therapy which, to date, has not been possible.

The present study investigated electrode array structures that maximize the therapeutic electric field intensity to tumors with different shapes and locations, while minimizing electric field intensity to the surrounding organs at risk (OARs). A human body phantom model was created from magnetic resonance images of a patient and divided into regions including a tumor and OARs. The shapes and sizes of the electrode arrays were altered for tumors differing in shape and location, and these electrode array structures were tested in the phantom. Use of a conformal electrode array based on the shape of the tumor maintained therapeutic electric field intensity to the tumor while reducing electric field intensity to the surrounding OARs by approximately 18%. Although the electric field intensity delivered to the tumor was proportional to the size of the electrode array, it was saturated at a critical area. Simulation results showed that optimal sizes of electrode arrays for specific tumors located at depths of 2 cm, 4 cm and 6 cm were 91, 273 and 830 cm2, respectively, indicating that the optimal size of the electrode array is proportional to the depth of tumor in the phantom. These results suggest that a tumor location-dependent optimal ratio between the size of the electrode array and the size of the individual electrodes could be calculated. In summary, this study indicated that customizing the electrode array structure to individual tumors can markedly increase the electric field intensity delivered to the tumor while minimizing the intensity delivered to OARs.

This study was designed to evaluate the effectiveness of a newly developed quality assurance system for electromagnetic field therapy called tumor treating fields therapy, which uses an alternating electric field to treat cancer based on an intermediate frequency of 100–300 kHz. The quality assurance system for electromagnetic field therapy consisted of a water phantom, a probe, and a digital data acquisition (DAQ) board. Low intensity alternating electric fields (200 kHz, 0–.1 V/cm) were created within the water phantom using a function generator and a high voltage amplifier. The electric potential formed inside the water phantom was measured using the probe and DAQ board. The electric field intensity was derived by measuring the electric potential at the 190 points (19 × 10 cm2) of the midplane. Accuracy was evaluated by gamma index analysis, which compared the measured electric field and the simulation result. The mean difference between the simulation result and the measured electric potentials within the water phantom was 0.31 V. The gamma passing rate for the tolerance levels of 0.5 V/5 mm was 95.5% for electric potential comparison showing good agreement between simulation and experimental results. The mean difference between the electric field distribution within the water phantom and the simulated values was 0.09 V/cm and the gamma passing rate for the tolerance levels of (0.2 V/cm)/5 mm was ~ 97.3%. These results confirmed the feasibility of the quality assurance system for electromagnetic field therapy.

Background: Tumor-treating fields (TTFields) therapy is increasingly utilized clinically because of its demonstrated efficacy in cancer treatment. However, the risk of skin burns must still be reduced to improve patient safety and posttreatment quality of life.

Purpose: The purpose of this study was to evaluate the methods of constructing electrode arrays that reduce current density exceeding threshold values, which can cause skin burns during TTFields therapy.

Methods: Electrode and body models were generated using COMSOL software. The body model had the dielectric properties of the scalp. The average current density beneath the central region of the electrode was maintained at ∼31 mA/cm2 RMS. The deviations in current density at the edges of the electrode were reduced by three methods:adjustment of the ceramic thickness ratio of the center to the edge from 1/5 to 4/5, adjustment of the radius of the metal plate from 5.0 to 8.0 mm, and insertion of an insulator of width 0.5 to 2 mm at the edge.

Results: While using a single circular electrode, adjustment of the ceramic thickness ratio, adjustment of the metal plate radius, and insertion of an insulator near the edge reduced the deviations of current density by 14.6%, 67.7%, and 75.3%, respectively. Similarly, while using circular electrode arrays, inserting an insulator at the edge of each electrode reduced the deviations of current density significantly, from 8.62 to 2.40 mA/cm2.

Conclusions: Insertion of an insulator at the edge of each electrode was found to be the most effective method of attaining uniform current density distribution beneath the electrode, thereby lowering the risk of adverse effects of TTFields therapy.

Heehun Sung Geon Oh, Yongha Gi, Jaehyeon Seo

Department of Bioengineering, Korea University, Seoul,Republic of Korea

Yunhui Jo 

Institute of Global Health Technology (IGHT), Korea University, Seoul,Republic of Korea

Hyunwoo Kim, Sangmin Park, Myonggeun Yoon

Department of Bioengineering, Korea University, Seoul,Republic of Korea

FieldCure Ltd, Seoul,Republic of Korea

Med Phys. 2022;49:4837–4844.

Purpose: To evaluate the dosimetric characteristics and applications of a dosimetry system composed of a flexible amorphous silicon thin-film solar cell and scintillator screen (STFSC-SS) for therapeutic X-rays. 

Glioblastoma multiforme (GBM), the most common type of brain tumor, is a very aggressive and treatment-refractory cancer, with a 5-year survival rate of approximately 5%. Hyperthermia (HT) and tumor treating fields (TTF) therapy have been used to treat cancer, either alone or in combination with other treatment methods. Both treatments have been reported to increase the efficacy of other treatment techniques and to improve patient prognosis. The present study evaluated the therapeutic effects of combining HT and TTF on GBM cell lines. Cells were subjected to HT, TTF, HT+TTF, or neither treatment, followed by comparisons of cell proliferation, apoptosis, migration and invasiveness. Clonogenic assays showed that the two treatments had a synergistic effect. The levels of cleaved PARP and cleaved caspase-3 were higher and apoptosis was increased in cells treated with HT+TTF than in cells treated with HT or TTF alone. In addition, HT+TTF showed greater inhibition of GBM cell migration and invasiveness and greater downregulation of STAT3 than either HT or TTF alone. The stronger anticancer effect of HT+TTF suggested that this combination treatment can increase the survival rate of patients with difficult-to-treat cancers such as GBM.

Yunhui Jo, Young In Han

Institute of Global Health Technology (IGHT), Korea University, Seoul, Republic of Korea

Eunjun Lee, Geon Oh, Heehun Sung, Yongha Gi, Hyunwoo Kim, Sangmin Park

Department of Biomedical Engineering, Korea University, Seoul, Republic of Korea

Jaehyeon Seo

Department of Bioconvergence Engineering, Korea University, Seoul, Republic of Korea 

Myonggeun Yoon

Department of Biomedical Engineering, Korea University, Seoul, Republic of Korea

Department of Bioconvergence Engineering, Korea University, Seoul, Republic of Korea

Am J Cancer Res. 2022; 12(3): 1423–1432.

Introduction: This study describes a simple method of inter‑fractional photon beam monitoring to measure the entrance dose of radiation treatment using Gafchromic EBT3 film. 

Background

Tumor-treating fields (TTFields) is an emerging non-invasive cancer-treatment modality using alternating electric fields with low intensities and an intermediate range of frequency. TTFields affects an extensive range of charged and polarizable cellular factors known to be involved in cell division. However, it causes side-effects, such as DNA damage and apoptosis, in healthy cells.

Objective

To investigate whether thymidine can have an effect on the DNA damage and apoptosis, we arrested the cell cycle of human glioblastoma cells (U373) at G1/S phase by using thymidine and then exposed these cells to TTFields.

Methods

Cancer cell lines and normal cell (HaCaT) were arrested by thymidine double block method. Cells were seeded into the gap of between the insulated wires. The exposed in alternative electric fields at 120 kHz, 1.2 V/cm. They were counted the cell numbers and analyzed for cancer malignant such as colony formation, Annexin V/PI staining, γH2AX and RT-PCR.

Results

The colony-forming ability and DNA damage of the control cells without thymidine treatment were significantly decreased, and the expression levels of BRCA1, PCNA, CDC25C, and MAD2 were distinctly increased. Interestingly, however, cells treated with thymidine did not change the colony formation, apoptosis, DNA damage, or gene expression pattern.

Conclusions

These results demonstrated that thymidine can inhibit the TTFields-caused DNA damage and apoptosis, suggesting that combining TTFields and conventional treatments, such as chemotherapy, may enhance prognosis and decrease side effects compared with those of TTFields or conventional treatments alone.

Hyesun Jeong, Sunghoi Hong

School of Biosystems and Biomedical Sciences, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul, 02841, Republic of Korea

Hyesun Jeong, Sunghoi Hong

Department of Public Health Science, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul, 02841, Republic of Korea

Yunhui Jo, Myonggeun Yoon

Department of Bio- Convergence Engineering, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul, 02841, Republic of Korea

Genes Genom 43, 995–1001 (2021)