Usefulness of synthetic MRI for differentiation of IDH-mutant diffuse gliomas and its comparison with the T2-FLAIR mismatch sign.

INTRODUCTION: The T2-FLAIR mismatch sign is a characteristic imaging biomarker for astrocytoma, isocitrate dehydrogenase (IDH)-mutant. However, investigators have provided varying interpretations of the positivity/negativity of this sign given for individual cases the nature of qualitative visual assessment. Moreover, MR sequence parameters also influence the appearance of the T2-FLAIR mismatch sign. To resolve these issues, we used synthetic MR technique to quantitatively evaluate and differentiate astrocytoma from oligodendroglioma. METHODS: This study included 20 patients with newly diagnosed non-enhanced IDH-mutant diffuse glioma who underwent preoperative synthetic MRI using the Quantification of Relaxation Times and Proton Density by Multiecho acquisition of a saturation-recovery using Turbo spin-Echo Readout (QRAPMASTER) sequence at our institution. Two independent reviewers evaluated preoperative conventional MR images to determine the presence or absence of the T2-FLAIR mismatch sign. Synthetic MRI was used to measure T1, T2 and proton density (PD) values in the tumor lesion. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic performance. RESULTS: The pathological diagnoses included astrocytoma, IDH-mutant (n = 12) and oligodendroglioma, IDH-mutant and 1p/19q-codeleted (n = 8). The sensitivity and specificity of T2-FLAIR mismatch sign for astrocytoma were 66.7% and 100% [area under the ROC curve (AUC) = 0.833], respectively. Astrocytoma had significantly higher T1, T2, and PD values than did oligodendroglioma (p < 0.0001, < 0.0001, and 0.0154, respectively). A cutoff lesion T1 value of 1580 ms completely differentiated astrocytoma from oligodendroglioma (AUC = 1.00). CONCLUSION: Quantitative evaluation of non-enhanced IDH-mutant diffuse glioma using synthetic MRI allowed for better differentiation between astrocytoma and oligodendroglioma than did conventional T2-FLAIR mismatch sign. Measurement of T1 and T2 value by synthetic MRI could improve the differentiation of IDH-mutant diffuse gliomas.

Improved dose compensation model owing to short irradiation interruption time for hypoxic tumor using a microdosimetric kinetic model.

Background: The objective was to enhance the biological compensation factor related to irradiation interruption in a short time (short irradiation interruption) in hypoxic tumors using a refined microdosimetric kinetic model (MKM) for photon radiation therapy. Materials and methods: The biological dose differences were calculated for CHO-K1 cells exposed to a photon beam, considering interruptions of (τ) of 0-120 min and pO2 at oxygen levels of 0.075-160 mm Hg. The interrupted dose fraction (IDF) was defined as the percentage ratio of the dose delivered before short irradiation interruption to the total dose, which ranged from 10-90%. The compensated dose was calculated based on an IDF of 10-90% for a dose of 2-8 Gy and oxygen levels of 0.075-160 mm Hg. Results: The Δ with and without short irradiation interruption was more pronounced with a higher dose and increased pO2. It exceeded 3% between IDF of 50% and either 10% or 90% and occurred more than τ = 50 min at 0.075 mm Hg, τ = 20 min at 3 mm Hg, τ = 20 min at 8 mm Hg, τ = 20 min at 15 mm Hg, τ = 20 min at 38 mm Hg, and τ = 20 min at 160 mm Hg. The dose compensation factor was greater at higher IDF rates. Conclusion: The biological dose decreased with longer interruption times and higher oxygen concentrations. The improved model can compensate for the biological doses at various oxygen concentrations. Advances in knowledge: The current study improved the dose compensation method for the decrease in the biological effect owing to short irradiation interruption by considering the oxygen concentration.

Radiomics-based prediction of recurrence for head and neck cancer patients using data imbalanced correction.

OBJECTIVES: To propose a radiomics-based prediction model for head and neck squamous cell carcinoma (HSNCC) recurrence after radiation therapy using a novel data imbalance correction method known as Gaussian noise upsampling (GNUS). MATERIALS AND METHODS: The dataset includes 97 HNSCC patients treated with definitive radiotherapy alone or concurrent chemoradiotherapy at two institutions. We performed radiomics analysis using nine segmentations created on pretreatment positron emission tomography and computed tomography images. Feature selection was performed by the least absolute shrinkage and selection operator analysis via five-fold cross-validation. The proposed GNUS was compared with seven conventional data-imbalance correction methods. Classification models of HNSCC recurrence were constructed on oversampled features using the machine learning algorithms of linear regression. Their predictive performance was evaluated based on accuracy, sensitivity, specificity, and the area under the curve (AUC) of the receiver operating performance characteristic curve via five-fold cross-validation using the same combinations as for feature selection. RESULT: The prediction model without data imbalance correction shows sensitivity, specificity, accuracy, and AUC values of 83 %, 96 %, 92 %, and 0.96, respectively. The conventional model with the best performance is the random over-sampler model, which shows sensitivity, specificity, accuracy, and AUC values of 93 %, 91 %, 92 %, 0.97, respectively, whereas the GNUS model shows values of 93 %, 94 %, 94 %, 0.98, respectively. CONCLUSION: Oversampling methods can reduce sensitivity and specificity bias. The proposed GNUS can improve accuracy as well as reduce sensitivity and specificity bias.

Prediction of prognosis in glioblastoma with radiomics features extracted by synthetic MRI images using cycle-consistent GAN.

To propose a style transfer model for multi-contrast magnetic resonance imaging (MRI) images with a cycle-consistent generative adversarial network (CycleGAN) and evaluate the image quality and prognosis prediction performance for glioblastoma (GBM) patients from the extracted radiomics features. Style transfer models of T1 weighted MRI image (T1w) to T2 weighted MRI image (T2w) and T2w to T1w with CycleGAN were constructed using the BraTS dataset. The style transfer model was validated with the Cancer Genome Atlas Glioblastoma Multiforme (TCGA-GBM) dataset. Moreover, imaging features were extracted from real and synthesized images. These features were transformed to rad-scores by the least absolute shrinkage and selection operator (LASSO)-Cox regression. The prognosis performance was estimated by the Kaplan-Meier method. For the accuracy of the image quality of the real and synthesized MRI images, the MI, RMSE, PSNR, and SSIM were 0.991 ± 2.10 × 10 - 4 , 2.79 ± 0.16, 40.16 ± 0.38, and 0.995 ± 2.11 × 10 - 4 , for T2w, and .992 ± 2.63 × 10 - 4 , 2.49 ± 6.89 × 10 - 2 , 40.51 ± 0.22, and 0.993 ± 3.40 × 10 - 4 for T1w, respectively. The survival time had a significant difference between good and poor prognosis groups for both real and synthesized T2w (p < 0.05). However, the survival time had no significant difference between good and poor prognosis groups for both real and synthesized T1w. On the other hand, there was no significant difference between the real and synthesized T2w in both good and poor prognoses. The results of T1w were similar in the point that there was no significant difference between the real and synthesized T1w. It was found that the synthesized image could be used for prognosis prediction. The proposed prognostic model using CycleGAN could reduce the cost and time of image scanning, leading to a promotion to build the patient's outcome prediction with multi-contrast images.

A nomogram based on pretreatment radiomics and dosiomics features for predicting overall survival associated with esophageal squamous cell cancer.

OBJECTIVES: To propose a nomogram-based survival prediction model for esophageal squamous cell carcinoma (ESCC) treated with definitive chemoradiotherapy using pretreatment computed tomography (CT), positron emission tomography (PET) radiomics and dosiomics features, and common clinical factors. METHODS: Radiomics and dosiomics features were extracted from CT and PET images and dose distribution from 2 institutions. The least absolute shrinkage and selection operator (LASSO) with logistic regression was used to select radiomics and dosiomics features by calculating the radiomics and dosiomics scores (Rad-score and Dos-score), respectively, in the training model. The model was trained in 81 patients and validated in 35 patients at Center 1 using 10-fold cross validation. The model was externally tested in 26 patients at Center 2. The predictive clinical factors, Rad-score, and Dos-score were identified to develop a nomogram model. RESULTS: Using LASSO Cox regression, 13, 11, and 19 CT, PET-based radiomics, and dosiomics features, respectively, were selected. The clinical factors T-stage, N-stage, and clinical stage were selected as significant prognostic factors by univariate Cox regression. In the external validation cohort, the C-index of the combined model of CT-based radiomics, PET-based radiomics, and dosiomics features with clinical factors were 0.74, 0.82, and 0.92, respectively. Significant differences in overall survival (OS) in the combined model of CT-based radiomics, PET-based radiomics, and dosiomics features with clinical factors were observed between the high- and low-risk groups (P = 0.019, 0.038, and 0.014, respectively). CONCLUSION: The dosiomics features have a better predicter for OS than CT- and PET-based radiomics features in ESCC treated with radiotherapy. CLINICAL RELEVANCE STATEMENT: The current study predicted the overall survival for esophageal squamous cell carcinoma patients treated with definitive chemoradiotherapy. The dosiomics features have a better predicter for overall survival than CT- and PET-based radiomics features.

Advantages of Persistent Cohomology in Estimating Animal Location From Grid Cell Population Activity.

Many cognitive functions are represented as cell assemblies. In the case of spatial navigation, the population activity of place cells in the hippocampus and grid cells in the entorhinal cortex represents self-location in the environment. The brain cannot directly observe self-location information in the environment. Instead, it relies on sensory information and memory to estimate self-location. Therefore, estimating low-dimensional dynamics, such as the movement trajectory of an animal exploring its environment, from only the high-dimensional neural activity is important in deciphering the information represented in the brain. Most previous studies have estimated the low-dimensional dynamics (i.e., latent variables) behind neural activity by unsupervised learning with Bayesian population decoding using artificial neural networks or gaussian processes. Recently, persistent cohomology has been used to estimate latent variables from the phase information (i.e., circular coordinates) of manifolds created by neural activity. However, the advantages of persistent cohomology over Bayesian population decoding are not well understood. We compared persistent cohomology and Bayesian population decoding in estimating the animal location from simulated and actual grid cell population activity. We found that persistent cohomology can estimate the animal location with fewer neurons than Bayesian population decoding and robustly estimate the animal location from actual noisy data.

Dosiomics for intensity-modulated radiotherapy in patients with prostate cancer: survival analysis stratified by baseline prostate-specific antigen and Gleason grade group in a 2-institutional retrospective study.

OBJECTIVE: This study evaluated the prognostic impact of the quality of dose distribution using dosiomics in patients with prostate cancer, stratified by pretreatment prostate-specific antigen (PSA) levels and Gleason grade (GG) group. METHODS: A total of 721 patients (Japanese Foundation for Cancer Research [JFCR] cohort: N = 489 and Tokyo Radiation Oncology Clinic [TROC] cohort: N = 232) with localized prostate cancer treated by intensity-modulated radiation therapy were enrolled. Two predictive dosiomic features for biochemical recurrence (BCR) were selected and patients were divided into certain groups stratified by pretreatment PSA levels and GG. Freedom from biochemical failure (FFBF) was estimated using the Kaplan-Meier method based on each dosiomic feature and univariate discrimination was evaluated using the log-rank test. As an exploratory analysis, a dosiomics hazard (DH) score was developed and its prognostic power for BCR was examined. RESULTS: The dosiomic feature extracted from planning target volume (PTV) significantly distinguished the high- and low-risk groups in patients with PSA levels >10 ng/mL (7-year FFBF: 86.7% vs 76.1%, P < .01), GG 4 (92.2% vs 76.9%, P < .01), and GG 5 (83.1% vs 77.8%, P = .04). The DH score showed significant association with BCR (hazard score: 2.04; 95% confidence interval: 1.38-3.01; P < .001). CONCLUSION: The quality of planned dose distribution on PTV may affect the prognosis of patients with poor prognostic factors, such as PSA levels >10 ng/mL and higher GGs. ADVANCES IN KNOWLEDGE: The effects of planned dose distribution on prognosis differ depending on the patient's clinical background.

A simulation study on the radiation-induced immune response of tumors after single fraction high-dose irradiation.

PURPOSE: We investigated radiation-induced antitumor immunity and its suppression by hypoxia-inducible factor (HIF-1α) for radiosurgery (SRS) using an improved cellular automata (CA) model. METHOD: A two-dimensional Cellular Automata (CA) model was employed to simulate the impact of radiation on cancer cell death and subsequent immune responses. Cancer cells died from direct cell death from radiation and indirect cell death due to radiation-induced vascular damage. The model also incorporated radiation-induced immunity and immuno-suppression. It was incorporated into the model assuming that the death of cancer cells generates effector cells, forming complexes with cancer cells, and high radiation doses lead to vascular damage, inducing tumor hypoxia and increasing HIF-1α expression. The model was validated and subjected to sensitivity analysis by evaluating tumor volume changes post-irradiation and exploring the effects and sensitivity of radiation-induced immune responses. RESULTS: The ratios of the tumor volume at 360 days post-irradiation and the SRS day (rTV) decreased with a higher PME, a higher Pcomp, and a lower ThHIF. The rTVs were 4.6 and 2.0 for PME = 0.1 and 0.9, 12.0 and 2.2 for Pcomp = 0.1 and 0.9, and 1.5 and 15.3 for ThHIF = 0.1 and 10.0, respectively. CONCLUSIONS: By modeling the activation and deactivation of the effectors, the improved CA model showed that the radiation-induced immunogenic cell death in the tumor caused a decrease in the post-irradiation volume by a factor of four for the therapeutic doses relative to non-immune reaction cases. Furthermore, the suppressive effects of HIF-1α induced by hypoxia decreased radiation-induced immune effects by more than 50.

Artificial intelligence-based diagnosis of the depth of laryngopharyngeal cancer.

OBJECTIVE: Transoral surgery (TOS) is a widely used treatment for laryngopharyngeal cancer. There are some difficult cases of setting the extent of resection in TOS, particularly in setting the vertical margins. However, positive vertical margins require additional treatment. Further, excessive resection should be avoided as it increases the risk of bleeding as a postoperative complication and may lead to decreased quality of life, such as dysphagia. Considering these issues, determining the extent of resection in TOS is an important consideration. In this study, we investigated the possibility of accurately diagnosing the depth of laryngopharyngeal cancer using radiomics, an image analysis method based on artificial intelligence (AI). METHODS: We included esophagogastroduodenoscopic images of 95 lesions that were pathologically diagnosed as squamous cell carcinoma (SCC) and treated with transoral surgery at our institution between August 2009 and April 2020. Of the 95 lesions, 54 were SCC in situ, and 41 were SCC. Radiomics analysis was performed on 95 upper gastrointestinal endoscopic NBI images of these lesions to evaluate their diagnostic performance for the presence of subepithelial invasion. The lesions in the endoscopic images were manually delineated, and the accuracy, sensitivity, specificity, and area under the curve (AUC) were evaluated from the features obtained using least absolute shrinkage and selection operator analysis. In addition, the results were compared with the depth predictions made by skilled endoscopists. RESULTS: In the Radiomics study, the average cross-validation was 0.833. The mean AUC for cross-validation calculated from the receiver operating characteristic curve was 0.868. These results were equivalent to those of the diagnosis made by a skilled endoscopist. CONCLUSION: The diagnosis of laryngopharyngeal cancer depth using radiomics analysis has potential clinical applications. We plan to use it in actual surgery in the future and prospectively study whether it can be used for diagnosis.

Unbiased evaluation of predicted gamma passing rate by an event-mixing technique.

BACKGROUND: Predicting models of the gamma passing rate (GPR) have been studied to substitute the measurement-based gamma analysis. Since these studies used data from different radiotherapy systems comprising TPS, linear accelerator, and detector array, it has been difficult to compare the performances of the predicting models among institutions with different radiotherapy systems. PURPOSE: We aimed to develop unbiased scoring methods to evaluate the performance of the models predicting the GPR, by introducing both best and worst limits for the performance of the GPR prediction. METHODS: Two hundred head-and-neck VMAT plans were used to develop a framework. The GPRs were measured using the ArcCHECK device. The predicted GPR [p] was generated using a deep learning-based model [pDL ]. The predicting model was evaluated using four metrics: standard deviation (SD) [σ], Pearson's correlation coefficient (CC) [r], mean squared error (MSE) [s], and mean absolute error (MAE) [a]. The best limit [ σ m ${\sigma _m}$ , r m ${r_m}$ , s m ${s_m}$ , and a m ${a_m}$ ] was estimated by measuring the SD of measured GPR [m] by shifting the device along the longitudinal direction to measure different sampling points. Mimicked best and worst p's [pbest and pworst ] were generated from pDL . The worst limit was defined such that m and p have no correlation [CC ∼ 0]. The worst limit [σMix , rMix , sMix , and aMix ] was generated using the event-mixing (EM) technique originally introduced in high-energy physics experiments. The range of σ, r, s, and a was defined to be [ σ m , σ Mix ] $[ {{\sigma _m},{\sigma _{{\mathrm{Mix}}}}} ]$ , [ 0 , r m ] $[ {0,{r_m}} ]$ , [ s m , s Mix ] $[ {{s_m},{s_{{\mathrm{Mix}}}}} ]$ , and [ a m , a Mix ] $[ {{a_m},{a_{{\mathrm{Mix}}}}} ]$ . The achievement score (AS) independently based on σ, r, s, and a were calculated for pDL , pbest and pworst . The probability that p fails the gamma analysis (alert frequency; AF) was estimated as a function of σ d ${\sigma _d}$ values within the [ σ m ${\sigma _m}$ , σMix ] range for the 3%/2 mm data with a 95% criterion. RESULTS: SDs of the best limit were well reproduced by σ m = 0.531 100 - m ${\sigma _m} = \;0.531\sqrt {100 - m} $ . The EM technique successfully generated the ( m , p ) $( {m,p} )$ pairs with no correlation. The AS using four metrics showed good agreement. This agreement indicates successful definitions of both best and worst limits, consistent definitions of the AS, and successful generations of mixed events. The AF for the DL-based model with the 3%/2 mm tolerance was 31.5% and 63.0% with CL's 99% and 99.9%, respectively. CONCLUSION: We developed the AS to evaluate the predicting model of the GPR in an unbiased manner by excluding the effects of the precision of the radiotherapy system and the spreading of the GPR. The best and worst limits of the GPR prediction were successfully generated using the measured precision of the GPR and the EM technique, respectively. The AS and σ p ${\sigma _p}$ are expected to enable objective evaluation of the predicting model and setting exact achievement goal of precision for the predicted GPR.

Radiomics and dosiomics for predicting complete response to definitive chemoradiotherapy patients with oesophageal squamous cell cancer using the hybrid institution model.

OBJECTIVES: To develop a multi-institutional prediction model to estimate the local response to oesophageal squamous cell carcinoma (ESCC) treated with definitive radiotherapy based on radiomics and dosiomics features. METHODS: The local responses were categorised into two groups (incomplete and complete). An external validation model and a hybrid model that the patients from two institutions were mixed randomly were proposed. The ESCC patients at stages I-IV who underwent chemoradiotherapy from 2012 to 2017 and had follow-up duration of more than 5 years were included. The patients who received palliative or pre-operable radiotherapy and had no FDG PET images were excluded. The segmentations included the GTV, CTV, and PTV which are used in treatment planning. In addition, shrinkage, expansion, and shell regions were created. Radiomic and dosiomic features were extracted from CT, FDG PET images, and dose distribution. Machine learning-based prediction models were developed using decision tree, support vector machine, k-nearest neighbour (kNN) algorithm, and neural network (NN) classifiers. RESULTS: A total of 116 and 26 patients enrolled at Centre 1 and Centre 2, respectively. The external validation model exhibited the highest accuracy with 65.4% for CT-based radiomics, 77.9% for PET-based radiomics, and 72.1% for dosiomics based on the NN classifiers. The hybrid model exhibited the highest accuracy of 84.4% for CT-based radiomics based on the kNN classifier, 86.0% for PET-based radiomics, and 79.0% for dosiomics based on the NN classifiers. CONCLUSION: The proposed hybrid model exhibited promising predictive performance for the local response to definitive radiotherapy in ESCC patients. CLINICAL RELEVANCE STATEMENT: The prediction of the complete response for oesophageal cancer patients may contribute to improving overall survival. The hybrid model has the potential to improve prediction performance than the external validation model that was conventionally proposed. KEY POINTS: • Radiomics and dosiomics used to predict response in patients with oesophageal cancer receiving definitive radiotherapy. • Hybrid model with neural network classifier of PET-based radiomics improved prediction accuracy by 8.1%. • The hybrid model has the potential to improve prediction performance.

CT number calibration audit in photon radiation therapy.

BACKGROUND: Inadequate computed tomography (CT) number calibration curves affect dose calculation accuracy. Although CT number calibration curves registered in treatment planning systems (TPSs) should be consistent with human tissues, it is unclear whether adequate CT number calibration is performed because CT number calibration curves have not been assessed for various types of CT number calibration phantoms and TPSs. PURPOSE: The purpose of this study was to investigate CT number calibration curves for mass density (ρ) and relative electron density (ρe ). METHODS: A CT number calibration audit phantom was sent to 24 Japanese photon therapy institutes from the evaluating institute and scanned using their individual clinical CT scan protocols. The CT images of the audit phantom and institute-specific CT number calibration curves were submitted to the evaluating institute for analyzing the calibration curves registered in the TPSs at the participating institutes. The institute-specific CT number calibration curves were created using commercial phantom (Gammex, Gammex Inc., Middleton, WI, USA) or CIRS phantom (Computerized Imaging Reference Systems, Inc., Norfolk, VA, USA)). At the evaluating institute, theoretical CT number calibration curves were created using a stoichiometric CT number calibration method based on the CT image, and the institute-specific CT number calibration curves were compared with the theoretical calibration curve. Differences in ρ and ρe over the multiple points on the curve (Δρm and Δρe,m , respectively) were calculated for each CT number, categorized for each phantom vendor and TPS, and evaluated for three tissue types: lung, soft tissues, and bones. In particular, the CT-ρ calibration curves for Tomotherapy TPSs (ACCURAY, Sunnyvale, CA, USA) were categorized separately from the Gammex CT-ρ calibration curves because the available tissue-equivalent materials (TEMs) were limited by the manufacturer recommendations. In addition, the differences in ρ and ρe for the specific TEMs (ΔρTEM and Δρe,TEM , respectively) were calculated by subtracting the ρ or ρe of the TEMs from the theoretical CT-ρ or CT-ρe calibration curve. RESULTS: The mean ± standard deviation (SD) of Δρm and Δρe,m for the Gammex phantom were -1.1 ± 1.2 g/cm3 and -0.2 ± 1.1, -0.3 ± 0.9 g/cm3 and 0.8 ± 1.3, and -0.9 ± 1.3 g/cm3 and 1.0 ± 1.5 for lung, soft tissues, and bones, respectively. The mean ± SD of Δρm and Δρe,m for the CIRS phantom were 0.3 ± 0.8 g/cm3 and 0.9 ± 0.9, 0.6 ± 0.6 g/cm3 and 1.4 ± 0.8, and 0.2 ± 0.5 g/cm3 and 1.6 ± 0.5 for lung, soft tissues, and bones, respectively. The mean ± SD of Δρm for Tomotherapy TPSs was 2.1 ± 1.4 g/cm3 for soft tissues, which is larger than those for other TPSs. The mean ± SD of Δρe,TEM for the Gammex brain phantom (BRN-SR2) was -1.8 ± 0.4, implying that the tissue equivalency of the BRN-SR2 plug was slightly inferior to that of other plugs. CONCLUSIONS: Latent deviations between human tissues and TEMs were found by comparing the CT number calibration curves of the various institutes.

Biological dosimetric impact of dose-delivery time for hypoxic tumour with modified microdosimetric kinetic model.

Background: An improved microdosimetric kinetic model (MKM) can address radiobiological effects with prolonged delivery times. However, these do not consider the effects of oxygen. The current study aimed to evaluate the biological dosimetric effects associated with the dose delivery time in hypoxic tumours with improved MKM for photon radiation therapy. Materials and methods: Cell survival was measured under anoxic, hypoxic, and oxic conditions using the Monte Carlo code PHITS. The effect of the dose rate of 0.5-24 Gy/min for the biological dose (Dbio) was estimated using the microdosimetric kinetic model. The dose per fraction and pressure of O2 (pO2) in the tumour varied from 2 to 20 Gy and from 0.01 to 5.0% pO2, respectively. Results: The ratio of the Dbio at 1.0-24 Gy/min to that at 0.5 Gy/min (RDR) was higher at higher doses. The maximum RDR was 1.09 at 1.0 Gy/min, 1.12 at 12 Gy/min, and 1.13 at 24 Gy/min. The ratio of the Dbio at 0.01-2.0% of pO2 to that at 5.0% of pO2 (Roxy) was within 0.1 for 2-20 Gy of physical dose. The maximum Roxy was 0.42 at 0.01% pO2, 0.76 at 0.4% pO2, 0.89 at 1% pO2, and 0.96 at 2% pO2. Conclusion: Our proposed model can estimate the cell killing and biological dose under hypoxia in a clinical and realistic patient. A shorter dose-delivery time with a higher oxygen distribution increased the radiobiological effect. It was more effective at higher doses per fraction than at lower doses.

Novel simulation for dosimetry impact of diaphragm respiratory motion in four-dimensional volumetric modulated arc therapy for esophageal cancer.

BACKGROUND AND PURPOSE: The diaphragm respiratory motion (RM) could impact the target dose robustness in the lower esophageal cancer (EC). We aimed to develop a framework evaluating the impact of different RM patterns quantitatively in one patient, by creating virtual four-dimensional computed-tomography (v4DCT) images, which could lead to tailored treatment for the breathing pattern. We validated virtual 4D radiotherapy (v4DRT) along with exploring the acceptability of free-breathing volumetric modulated arc therapy (FB-VMAT). METHODS AND MATERIALS: We assessed 10 patients with superficial EC through their real 4DCT (r4DCT) scans. v4DCT images were derived from the end-inhalation computed tomography (CT) image (reference CT) and the v4DRT dose was accumulated dose over all phases. r4DRT diaphragm shifts were applied with magnitudes derived from r4DCT scans; clinical target volume (CTV) dose of v4DRT was compared with that of r4DRT to validate v4DRT. CTV dosage modifications and planning organ at risk volume (PRV) margins of the spinal cord were examined with the diaphragm movement. The percentage dose differences (ΔDx) were determined between the v4DRT and the dose calculated on the reference CT image. RESULTS: The CTV ΔDx between the r4DRT and v4DRT were within 1% in cases with RM ≦ 15 mm. The average ΔD100% and ΔDmean of the CTV ranging from 5 to 15 mm of diaphragm motion was 0.3% to 1.7% and 0.1% to 0.4%, respectively. All CTV index changes were within 3% and ΔD1cc and ΔD2cc of Cord PRV were within 1%. CONCLUSION: We postulate a novel method for evaluating the CTV robustness, comparable to the conventional r4DCT method under the diaphragm RM ≦ 15 mm permitting an impact of within 3% in FB-VMAT for EC on the CTV dose distribution.

Dose uncertainty due to energy dependence in dual-energy computed tomography.

Purpose: To evaluate the absolute dose uncertainty at 2 different energies and for the large and small bowtie filters in dual-energy computed tomography (DECT). Material and methods: Measurements were performed using DECT at 80 kV and 140 kilovoltage peak (kVp), and single-energy computed tomography (CT) at 120 kV. The absolute dose was calculated from the mass-energy absorption obtained from the half-value layer (HVL) of aluminium. Results: The difference in the water-to-air ratio of the mean mass energy-absorption coefficients at 80 kV and 140 kV was 2.0% for the small bow-tie filter and 3.0% for the large bow-tie filter. At lower tube voltages, the difference in the absorbed dose with the large and small bow-tie filters was larger. Conclusions: The absolute dose uncertainty due to energy dependence was 3.0%, which could be reduced with single-energy beams at 120 kV or by using the average effective energy measurement with dual-energy beams.

Prognostic Value of Radiomics Analysis of Skeletal Muscle After Radical Irradiation of Esophageal Cancer.

BACKGROUND/AIM: Sarcopenia is an independent survival predictor in several tumor types. Computed tomography (CT) is the standard measurement for body composition assessment. Radiomics analysis of CT images allows for the precise evaluation of skeletal muscles. This study aimed to construct a prognostic survival model for patients with esophageal cancer who underwent radical irradiation using skeletal muscle radiomics. PATIENTS AND METHODS: We retrospectively identified patients with esophageal cancer who underwent radical irradiation at our institution between April 2008 and December 2017. Skeletal muscle radiomics were extracted from an axial pretreatment CT at the third lumbar vertebral level. The prediction model was constructed using machine learning coupled with the least absolute shrinkage and selection operator (LASSO). The predictive nomogram model comprised clinical factors with radiomic features. Three prediction models were created: clinical, radiomics, and combined. RESULTS: Ninety-eight patients with 98 esophageal cancers were enrolled in this study. The median observation period was 57.5 months (range=1-98 months). Thirty-five radiomics features were selected by LASSO analysis, and a prediction model was constructed using training and validation data. The average of the accuracy, specificity, sensitivity, and area under the concentration-time curve for predicting survival in esophageal cancer in the combined model were 75%, 92%, and 0.86, respectively. The C-indices of the clinical, radiomics, and combined models were 0.76, 0.80, and 0.88, respectively. CONCLUSION: A prediction model with skeletal muscle radiomics and clinical data might help determine survival outcomes in patients with esophageal cancer treated with radical radiotherapy.

Image masking using convolutional networks improves performance classification of radiation pneumonitis for non-small cell lung cancer.

Radiation pneumonitis (RP) is a serious side effect of radiotherapy in patients with locally advanced non-small-cell lung cancer (NSCLC). Image cropping reduces training noise and may improve classification accuracy. This study proposes a prediction model for RP grade ≥ 2 using a convolutional neural network (CNN) model with image cropping. The 3D computed tomography (CT) images cropped in the whole-body, normal lung (nLung), and nLung regions overlapping the region over 20 Gy (nLung∩20 Gy) used in treatment planning were used as the input data. The output classifies patients as RP grade < 2 or RP grade ≥ 2. The sensitivity, specificity, accuracy, and area under the curve (AUC) were evaluated using the receiver operating characteristic curve (ROC). The accuracy, specificity, sensitivity, and AUC were 53.9%, 80.0%, 25.5%, and 0.58, respectively, for the whole-body method, and 60.0%, 81.7%, 36.4%, and 0.64, respectively, for the nLung method. For the nLung∩20 Gy method, the accuracy, specificity, sensitivity, and AUC improved to 75.7%, 80.0%, 70.9%, and 0.84, respectively. The CNN model, in which the input image is segmented in the normal lung considering the dose distribution, can help predict an RP grade ≥ 2 for NSCLC patients after definitive radiotherapy.

A synthesized gamma distribution-based patient-specific VMAT QA using a generative adversarial network.

BACKGROUND: Artificial intelligence (AI)-based gamma passing rate (GPR) prediction has been proposed as a time-efficient virtual patient-specific QA method for the delivery of volumetric modulation arc therapy (VMAT). However, there is a limitation that the GPR value loses the locational information of dose accuracy. PURPOSE: The objective was to predict the failing points in the gamma distribution and the GPR using a synthesized gamma distribution of VMAT QA with a deep convolutional generative adversarial network (GAN). METHODS: The fluence maps of 270 VMAT beams for prostate cancer were measured using an electronic portal imaging device and analyzed using gamma evaluation with 3%/2-mm, 2%/1-mm, 1%/1-mm, and 1%/0.5-mm tolerances. The 270 gamma distributions were divided into two datasets: 240 training datasets for creating a model and 30 test datasets for evaluation. The image prediction network for the fluence maps calculated by the treatment planning system (TPS) to the gamma distributions was created using a GAN. The sensitivity, specificity, and accuracy of detecting failing points were evaluated using measured and synthesized gamma distributions. In addition, the difference between measured GPR (mGPR) and predicted GPR (pGPR) values calculated from the synthesized gamma distributions was evaluated. RESULTS: The root mean squared errors between mGPR and pGPR were 1.0%, 2.1%, 3.5%, and 3.6% for the 3%/2-mm, 2%/1-mm, 1%/1-mm, and 1%/0.5-mm tolerances, respectively. The accuracies for detecting failing points were 98.9%, 96.9%, 94.7%, and 93.7% for 3%/2-mm, 2%/1-mm, 1%/1-mm, and 1%/0.5-mm tolerances, respectively. The sensitivity and specificity were the highest for 1%/0.5-mm and 3%/2-mm tolerances, which were 82.7% and 99.6%, respectively. CONCLUSIONS: We developed a novel system using a GAN to generate a synthesized gamma distribution-based patient-specific VMAT QA. The system is promising from the point of view of quality assurance in radiotherapy because it shows high performance and can detect failing points.

Physical and biological dosimetric margin according to prescription method for stereotactic body radiation therapy.

This study aimed to expand the biological conversion factor (BCF) model, which converts the physical dosimetric margin (PDM) to the biological dosimetric margin (BDM) for point prescription with 3-dimensional conformal radiation therapy (3DCRT) and the marginal prescription method with volumetric-modulated arc radiotherapy (VMAT). The VMAT of the marginal prescription and the 3DCRT of the point prescription with lung stereotactic body radiation therapy (SBRT) by using RayStation were planned. The biological equivalent dose (BED) for a dose per fraction (DPF) of 3-20 Gy was calculated from these plans. The dose was perturbed with the calculation using a 1-mm step isocenter shift. The dose covering 95% of the target was greater than or equal to 90% of the prescribed physical dose, and the BED were defined as the PDM and BDM, respectively. The BCF was created as a function of the DPF. The PDM and BDM for all DPFs were larger with the point prescription method than with the marginal prescription method. The marginal prescription method with a 60% isodose line had a larger PDM and BDM. The BCF with the point prescription was smaller than that with the marginal prescription in the left-right (LR), anterior-posterior (AP) and cranio-caudal (CC) directions. In the marginal prescription method, the 60% isodose line had a higher BCF. In conclusion, the improved BCF method could be converted to BDM for point prescription with 3DCRT and marginal prescription method with VMAT, which is required for stereotactic radiation therapy in radiobiology-based treatment planning.

MRI image synthesis for fluid-attenuated inversion recovery and diffusion-weighted images with deep learning.

This study aims to synthesize fluid-attenuated inversion recovery (FLAIR) and diffusion-weighted images (DWI) with a deep conditional adversarial network from T1- and T2-weighted magnetic resonance imaging (MRI) images. A total of 1980 images of 102 patients were split into two datasets: 1470 (68 patients) in a training set and 510 (34 patients) in a test set. The prediction framework was based on a convolutional neural network with a generator and discriminator. T1-weighted, T2-weighted, and composite images were used as inputs. The digital imaging and communications in medicine (DICOM) images were converted to 8-bit red-green-blue images. The red and blue channels of the composite images were assigned to 8-bit grayscale pixel values in T1-weighted images, and the green channel was assigned to those in T2-weighted images. The prediction FLAIR and DWI images were of the same objects as the inputs. For the results, the prediction model with composite MRI input images in the DWI image showed the smallest relative mean absolute error (rMAE) and largest mutual information (MI), and that in the FLAIR image showed the largest relative mean-square error (rMSE), relative root-mean-square error (rRMSE), and peak signal-to-noise ratio (PSNR). For the FLAIR image, the prediction model with the T2-weighted MRI input images generated more accurate synthesis results than that with the T1-weighted inputs. The proposed image synthesis framework can improve the versatility and quality of multi-contrast MRI without extra scans. The composite input MRI image contributes to synthesizing the multi-contrast MRI image efficiently.