Evaluating the Gray Level Co-Occurrence Matrix-Based Texture Features of Magnetic Resonance Images for Glioblastoma Multiform Patients' Treatment Response Assessment.

Background: Medical images of cancer patients are usually evaluated qualitatively by clinical specialists which makes the accuracy of the diagnosis subjective and related to the skills of clinicians. Quantitative methods based on the textural feature analysis may be useful to facilitate such evaluations. This study aimed to analyze the gray level co-occurrence matrix (GLCM)-based texture features extracted from T1-axial magnetic resonance (MR) images of glioblastoma multiform (GBM) patients to determine the distinctive features specific to treatment response or disease progression. Methods: 20 GLCM-based texture features, in addition to mean, standard deviation, entropy, RMS, kurtosis, and skewness were extracted from step I MR images (obtained 72 h after surgery) and step II MR images (obtained three months later). Responded and not responded patients to treatment were classified manually based on the radiological evaluation of step II images. Extracted texture features from Step I and Step II images were analyzed to determine the distinctive features for each group of responsive or progressive diseases. MATLAB 2020 was applied to feature extraction. SPSS version 26 was used for the statistical analysis. P value < 0.05 was considered statistically significant. Results: Despite no statistically significant differences between Step I texture features for two considered groups, almost all step II extracted GLCM-based texture features in addition to entropy M and skewness were significantly different between responsive and progressive disease groups. Conclusions: GLCM-based texture features extracted from MR images of GBM patients can be used with automatic algorithms for the expeditious prediction or interpretation of response to the treatment quantitatively besides qualitative evaluations.

Evaluating the effects of variation in CT scanning parameters on the image quality and Hounsfield units for optimization of dose in radiotherapy treatment planning: A semi-anthropomorphic thorax phantom study.

Aim: The diagnosis accuracy of computed tomography (CT) systems and the reliability of calculated Hounsfield Units (HUs) are critical in tumor detection and cancer patients' treatment planning. This study evaluated the effects of scan parameters (Kilovoltage peak or kVp, milli-Ampere-second or mAS reconstruction kernels and algorithms, reconstruction field of view, and slice thickness) on image quality, HUs, and the calculated dose in the treatment planning system (TPS). Materials and Methods: A quality dose verification phantom was scanned several times by a 16-slice Siemens CT scanner. The DOSIsoft ISO gray TPS was applied for dose calculations. The SPSS.24 software was used to analyze the results and the P-value <0.05 was considered significant. Results: Reconstruction kernels and algorithms significantly affected noise, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR). The noise increased and CNR decreased by raising the sharpness of reconstruction kernels. SNR and CNR had considerable increments at iterative reconstruction compared with the filtered back-projection algorithm. The noise decreased by raising mAS in soft tissues. Also, KVp had a significant effect on HUs. TPS--calculated dose variations were less than 2% for mediastinum and backbone and less than 8% for rib. Conclusions: Although HU variation depends on image acquisition parameters across a clinically feasible range, its dosimetric impact on the calculated dose in TPS can be neglected. Hence, it can be concluded that the optimized values of scan parameters can be applied to obtain the maximum diagnostic accuracy and calculate HUs more precisely without affecting the calculated dose in the treatment planning of cancer patients.

Segmentation of the prostate, its zones, anterior fibromuscular stroma, and urethra on the MRIs and multimodality image fusion using U-Net model.

Background: Due to the large variability in the prostate gland of different patient groups, manual segmentation is time-consuming and subject to inter-and intra-reader variations. Hence, we propose a U-Net model to automatically segment the prostate and its zones, including the peripheral zone (PZ), transitional zone (TZ), anterior fibromuscular stroma (AFMS), and urethra on the MRI [T2-weighted (T2W), diffusion-weighted imaging (DWI), and apparent diffusion coefficient (ADC)], and multimodality image fusion. Methods: A total of 91 eligible patients were retrospectively identified; 50 patients were considered for training process in a 10-fold cross-validation fashion and 41 ones for external test. Firstly, images were registered, and cropping was performed through a bounding box. In addition to T2W, DWI, and ADC separately, fused images were used. We considered three combinations, including T2W + DWI, T2W + ADC, and DWI + ADC, using wavelet transform. U-Net was applied to segment the prostate and its zones, AFMS, and urethra in a 10-fold cross-validation fashion. Eventually, dice score (DSC), intersection over union (IoU), precision, recall, and Hausdorff distance (HD) were used to evaluate the proposed model. Results: Using T2W images alone on the external test images, higher DSC, IoU, precision, and recall was achieved than the individual DWI and ADC images. DSC of 95%, 94%,98%, 94%, and 88%, IoU of 88%, 88.5%, 96%, 90%, and 79%, precision of 95.9%, 93.9%, 97.6%, 93.83%, and 87.82%, and recall of 94.2%, 94.2%, 98.3%, 94%, 87.93% was achieved for the whole prostate, PZ, TZ, urethra, and AFMS, respectively. The results clearly show that the best segmentation was obtained when the model is trained using T2W + DWI images. DSC of 99.06%, 99,05%, 99.04%, 99.09%, and 98.08%, IoU of 97.09%, 97.02%, 98.12%, 98.13%, and 96%, precision of 99.24%, 98.22%, 98.91%, 99.23%, and 98.9%, and recall of 98.3%, 99.8%, 99.02%, 98.93%, and 97.51% was achieved for the whole prostate, PZ, TZ, urethra, and AFMS, respectively. The min of the HD in the testing set for three combinations was 0.29 for the T2W + ADC procedure in the whole prostate class. Conclusions: Better performance was achieved using T2W + DWI images than T2W, DWI, and ADC separately or T2W + ADC and DWI + ADC in combination.

Fractionated radiation promotes proliferation and radioresistance in bystander A549 cells but not in bystander HT29 cells.

AIMS: Recent studies suggest that direct exposure of cells to fractionated radiotherapy might induce radioresistance. However, the effects of fractionated radiotherapy on the non-irradiated bystander cells remain unclear. We hypothesized that fractionated radiotherapy could enhance radioresistance and proliferation of bystander cells. MAIN METHODS: Human tumor cell lines, including A549 and HT29 were irradiated (2 Gy per day). The irradiated cells (either A549 or HT29) were co-cultured with non-irradiated cells of the same line using transwell co-culture system. Tumor cell proliferation, radioresistance and apoptosis were measured using MTT assay, clonogenic survival assay and Annexin-V in bystander cells, respectively. In addition, activation of Chk1 (Ser 317), Chk2 (Thr 68) and Akt (Ser473) were measured via western blot. KEY FINDINGS: Irradiated HT29 cells induced conventional bystander effects detected as modulation of clonogenic survival parameters (decreased area under curve, D10 and ED50 and increased α) and proliferation in recipient neighbors. While, irradiated A549 cells significantly enhanced the radioresistance and proliferation of bystander cells. These changes were accompanied with enhanced activation of Chk1, Chk2 and Akt in non-irradiated bystander A549 cells. Moreover, both bystander effects (damaging and protective) were mediated through secreted factors. SIGNIFICANCE: These findings suggest that fractionated radiotherapy could promote proliferation and radioresistance of bystander cells probably through survival and proliferation pathways.

Fractionated radiotherapy might induce epithelial-mesenchymal transition and radioresistance in a cellular context manner.

Despite the fact that radiotherapy is a main therapeutic modality in cancer treatment, recent evidence suggests that fractionated radiotherapy (FR) might confer radioresistance through epithelial-mesenchymal transition (EMT). Nevertheless, the effects of FR on EMT phenotype and the potential link between EMT induction and radioresistance development yet to be clarified. The aim of this study was to assess whether FR could promote EMT, and to elucidate if induction of EMT contributes to the acquisition of radioresistance. To this end, two human cancer cell lines (A549 and HT-29) were irradiated (2 Gy/day) and analyzed using wound healing, transwell migration and invasion assays, real-time polymerase chain reaction (for E-cadherin, N-cadherin, Vimentin, CD44, CD133, Snail, and Twist), clonogenic assay, Annexin V/PI, and 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay. Irradiation of A549 (for 5 or 10 consecutive days) resulted in morphological changes including elongation of cytoplasm and nuclei and pleomorphic nuclei. Also, irradiation-enhanced migratory and invasive potential of A549. These phenotypic changes were in agreement with decreased expression of the epithelial marker (E-cadherin), enhanced expression of mesenchymal markers (N-cadherin, Vimentin, Snail, and Twist) and increased stemness factors (CD44 and CD133). Moreover, induction of EMT phenotype was accompanied with enhanced radioresistance and proliferation of irradiated A549. However, FR (for 5 consecutive days) did not increase HT-29 motility. Furthermore, molecular alterations did not resemble EMT phenotype (downregulation of E-cadherin, Vimentin, ALDH, CD44, CD133, and Snail). Eventually, FR led to enhanced radiosensitivity and decreased proliferation of HT-29. Altogether, our findings suggest that FR might induce EMT and confer radioresistance in a cell context-dependent manner.

Calculation of Equivalent Square Fields in Radiation Therapy by an Improved Vadash Correction Factor for Collimator Exchange Effects

Background and objectives: To determine the head scatter factor, a formalism presented by Vadash and Bjärngard has been employed to assess collimator exchange effects. The aim of this study was to determine the best Vadash correction factor (A) by introducing a new method based on the output factor measured in air for different square and rectangular fields. Materials and Methods: A new simple mathematical method based on selection of the best dosimetric data was proposed to obtain the A value for Vadash to predict the equivalent square field size. Measurements were performed with a Farmer chamber 0.6 cc in SSD 100 cm and build up cap of Plexiglas, 1.5 and 3.5 cm equal to water, for 6 and 18 MV, respectively, with a Perimus Plus linear accelerator. The output factor in air (OFair) was measured for square and rectangular fields. MATLAB software (version R2014a) was employed for calculations and curve fitting. Results: A power model with a constant value was applied to the output factor in air as a function of square field size. The output factor in air ranged from 0.983 to 1.038 at 6MV and from 0.731 to 1.05 at 18 MV with the Y collimator having a greater effect. Obtained values for A were 1.42 and 1.55 with respect to σmin=0.98 and 2.3 for 6 and 18 MV energies, respectively. Conclusion: The proposed A values minimize the collimator exchange effect in calculating equivalent squares, which plays an important role in patient dose calculation and treatment planning.

Radiotherapy Enhancement with Electroporation in Human Intestinal Colon Cancer HT-29 Cells

Background: The efficiency of radiotherapy for tumors can be enhanced with different radiosensitizers. Previous studies have shown that electroporation (EP) can sensitize some cancer cell lines to ionizing radiation (IR). HT-29 is a radiation resistant colorectal cancer cell line, representative of a cancer type which is the second cause of cancer mortalities in developed countries. The present study aimed to evaluate radiosensitizing effects of EP on HT-29 cells in vitro exposed to 6 MV X-ray photon beams. Methods: HT-29 cells were exposed to a 6 MV X-ray photon beam as the control or to a combination of electroporation and irradiation. The response of cells was evaluated by colony formation assay and survival curves. Results: The survival fraction of the HT-29 cells was significantly decreased by electroporation prior to radiotherapy. A single electric pulse increased colorectal HT-29 cancer cell sensitivity to megavoltage radiation by a factor of 1.36. Conclusion: Our findings showed that EP before radiotherapy can significantly enhance tumor cell sensitivity. This combined treatment modality should be assessed for its applicability in clinic settings for employment against radioresistant cancers. However, to facilitate achieving this goal, many different tumors with a broad range of radiosensitivities should be evaluated.

Analytical Consideration of Surface Dose and Kerma for Megavoltage Photon Beams in Clinical Radiation Therapy.

BACKGROUND: In radiation therapy, estimation of surface doses is clinically important. This study aimed to obtain an analytical relationship to determine the skin surface dose, kerma and the depth of maximum dose, with energies of 6 and 18 megavoltage (MV). MATERIALS AND METHODS: To obtain the dose on the surface of skin, using the relationship between dose and kerma and solving differential equations governing the two quantities, a general relationship of dose changes relative to the depth was obtained. By dosimetry all the standard square fields of 5x5cm to 40x40cm, an equation similar to response to differential equations of the dose and kerma were fitted on the measurements for any field size and energy. Applying two conditions: a) equality of the area under dose distribution and kerma changes in versus depth in 6 and 18 MV, b) equality of the kerma and dose at x=dmax and using these results, coefficients of the obtained analytical relationship were determined. By putting the depth of zero in the relation, amount of PDD and kerma on the surface of the skin, could be obtained. RESULTS: Using the MATLAB software, an exponential binomial function with R-Square >0.9953 was determined for any field size and depth in two energy modes 6 and 18MV, the surface PDD and kerma was obtained and both of them increase due to the increase of the field, but they reduce due to increased energy and from the obtained relation, depth of maximum dose can be determined. CONCLUSIONS: Using this analytical formula, one can find the skin surface dose, kerma and thickness of the buildup region.

Determination of an Effective Wedge Angle by Combination of Two Arbitrary Universal Wedge Fields in Radiation Therapy of Cancer Patients with Megavoltage Photon Beams.

BACKGROUND: Wedge filters are commonly used in radiation oncology for eliminating hot spots and creating a uniform dose distribution in optimizing isodose curves in the target volume for clinical aspects. These are some limited standard physical wedges (15°, 30°, 45°, 60°),or creating an arbitrary wedge angle, like motorized wedge or dynamic wedge,... The new formulation is presented by the combination of wedge fields for determining an arbitrary effective wedge angles. The isodose curves also are derived for these wedges. MATERIALS AND METHODS: we performed the dosimetry of Varian Clinac 2100C/D with Scanditronix Wellhofer water blue phantom, CU500E, OmniPro - Accept software and 0.13cc ionization chamber for 6Mv photon beam in depth of 10cm (reference depth) for universal physical wedges (15°, 30°, 45°, and 60°) and reference field 10x10cm2. By combining the isodose curve standard wedge fields with compatible weighting dose for each field, the effective isodose curve is calculated for any wedge angle. RESULTS: The relation between a given effective wedge angle and the weighting of each combining wedge fields was derived. A good agreement was found between the measured and calculated wedge angles and the maximum deviation did not exceed 3°. The difference between the measured and calculated data decreased when the combined wedge angles were closer. The results are in agreement with the motorized single wedge appliance in the literature. CONCLUSIONS: This technique showed that the effective wedge angle that is obtained from this method is adequate for clinical applications and the motorized wedge formalism is a special case of this consideration.

Dose-Response Curves of the FDXR and RAD51 Genes with 6 and 18 MV Beam Energies in Human Peripheral Blood Lymphocytes.

BACKGROUND: Rapid dose assessment using biological dosimetry methods is essential to increase the chance of survival of exposed individuals in radiation accidents. OBJECTIVES: We compared the expression levels of the FDXR and RAD51 genes at 6 and 18 MV beam energies in human peripheral blood lymphocytes. The results of our study can be used to analyze radiation energy in biological dosimetry. METHODS: For this in vitro experimental study, from 36 students in the medical physics and virology departments, seven voluntary, healthy, non-smoking male blood donors of Khuzestan ethnicity with no history of exposure to ionization radiation were selected using simple randomized sampling. Sixty-three peripheral blood samples were collected from the seven healthy donors. Human peripheral blood was then exposed to doses of 0, 0.2, 0.5, 2, and 4 Gy with 6 and 18 MV beam energies in a Linac Varian 2100C/D (Varian, USA) at Golestan hospital in Ahvaz, Iran. After RNA extraction and cDNA synthesis, the expression levels of FDXR and RAD51 were determined 24 hours post-irradiation using the gel-purified reverse transcription polymerase chain reaction (RT-PCR) technique and TaqMan strategy (by real-time PCR). RESULTS: The expression level of FDXR gene was significantly increased at doses of 2 Gy and 4 Gy in the 6 - 18 MV energy range (P < 0.001 and P < 0.008, respectively). The medians with interquartile ranges (IQRs) of the copy numbers of the FDXR gene at 2 Gy and 4 Gy doses under 6 and 18 MV beam energies were 2393.59 (1798.21, 2575.37) and 2983.00 (2199.48, 3643.82) and 3779.12 (3051.40, 5120.74) and 5051.26 (4704.83, 5859.17), respectively. However, RAD51 gene expression levels only showed a significant difference between samples at a dose of 2 Gy with 6 and 18 MV beam energies, respectively (P < 0.040). The medians with IQRs of the copy numbers of the RAD51 gene were 2092.77 (1535.78, 2705.61) and 3412.57 (2979.72, 4530.61) at beam energies of 6 and 18 MV, respectively. CONCLUSIONS: The data suggest that the expression analysis of the FDXR gene, contrary to that of the RAD51 gene, may be suitable for assessment of high-energy X-ray. In addition, RAD51 is not a suitable gene for dose assessment in biological dosimetry.

Gene Expression Biodosimetry: Quantitative Assessment of Radiation Dose with Total Body Exposure of Rats.

BACKGROUND: Accurate dose assessment and correct identification of irradiated from non-irradiated people are goals of biological dosimetry in radiation accidents. OBJECTIVES: Changes in the FDXR and the RAD51 gene expression (GE) levels were here analyzed in response to total body exposure (TBE) to a 6 MV x-ray beam in rats. We determined the accuracy for absolute quantification of GE to predict the dose at 24 hours. MATERIALS AND METHODS: For this in vivo experimental study, using simple randomized sampling, peripheral blood samples were collected from a total of 20 Wistar rats at 24 hours following exposure of total body to 6 MV X-ray beam energy with doses (0.2, 0.5, 2 and 4 Gy) for TBE in Linac Varian 2100C/D (Varian, USA) in Golestan Hospital, in Ahvaz, Iran. Also, 9 rats was irradiated with a 6MV X-ray beam at doses of 1, 2, 3 Gy in 6MV energy as a validation group. A sham group was also included. After RNA extraction and DNA synthesis, GE changes were measured by the QRT-PCR technique and an absolute quantification strategy by taqman methodology in peripheral blood from rats. ROC analysis was used to distinguish irradiated from non-irradiated samples (qualitative dose assessment) at a dose of 2 Gy. RESULTS: The best fits for mean of responses were polynomial equations with a R2 of 0.98 and 0.90 (for FDXR and RAD51 dose response curves, respectively). Dose response of the FDXR gene produced a better mean dose estimation of irradiated "validation" samples compared to the RAD51 gene at doses of 1, 2 and 3 Gy. FDXR gene expression separated the irradiated rats from controls with a sensitivity, specificity and accuracy of 87.5%, 83.5% and 81.3%, respectively, 24 hours after dose of 2 Gy. These values were significantly (p<0.05) higher than the 75%, 75% and 75%, respectively, obtained using gene expression of RAD51 analysis at a dose of 2 Gy. CONCLUSIONS: Collectively, these data suggest that absolute quantification by gel purified quantitative RT-PCR can be used to measure the mRNA copies for GE biodosimetry studies at comparable accuracy to similar methods. In the case of TBE with 6MV energy, FDXR gene expression analysis is more precise than that with RAD51 for quantitative and qualitative dose assessment.