Hamid Abdollahi

The impact of image reconstruction settings on 18F-FDG PET radiomic features: multi-scanner phantom and patient studies

AbstractObjectivesThe purpose of this study was to investigate the robustness of different PET/CT image radiomic features over a wide range of different reconstruction settings.MethodsPhantom and patient studies were conducted, including two PET/CT scanners. Different reconstruction algorithms and parameters including number of sub-iterations, number of subsets, full width at half maximum (FWHM) of Gaussian filter, scan time per bed position and matrix size were studied. Lesions were delineated and one hundred radiomic features were extracted. All radiomics features were categorized based on coefficient of variation (COV).ResultsForty seven percent features showed COV ≤ 5% and 10% of which showed COV > 20%. All geometry based, 44% and 41% of intensity based and texture based features were found as robust respectively. In regard to matrix size, 56% and 6% of all features were found non-robust (COV > 20%) and robust (COV ≤ 5%) respectively.ConclusionsVariability and robustness of PET/CT image radiomics in advanced reconstruction settings is feature-dependent, and different settings have different effects on different features. Radiomic features with low COV can be considered as good candidates for reproducible tumour quantification in multi-center studies.Key Points• PET/CT image radiomics is a quantitative approach assessing different aspects of tumour uptake. • Radiomic features robustness is an important issue over different image reconstruction settings. • Variability and robustness of PET/CT image radiomics in advanced reconstruction settings is feature-dependent. • Robust radiomic features can be considered as good candidates for tumour quantification

Reduction–oxidation (redox) system in radiation-induced normal tissue injury: molecular mechanisms and implications in radiation therapeutics

Every year, millions of cancer patients undergo radiation therapy for treating and destroying abnormal cell growths within normal cell environmental conditions. Thus, ionizing radiation can have positive therapeutic effects on cancer cells as well as post-detrimental effects on surrounding normal tissues. Previous studies in the past years have proposed that the reduction and oxidation metabolism in cells changes in response to ionizing radiation and has a key role in radiation toxicity to normal tissue. Free radicals generated from ionizing radiation result in upregulation of cyclooxygenases (COXs), nitric oxide synthase (NOSs), lipoxygenases (LOXs) as well as nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase), and their effected changes in mitochondrial functions are markedly noticeable. Each of these enzymes is diversely expressed in multiple cells, tissues and organs in a specific manner. Overproduction of reactive oxygen radicals (ROS), reactive hydroxyl radical (ROH) and reactive nitrogen radicals (RNS) in multiple cellular environments in the affected nucleus, cell membranes, cytosol and mitochondria, and other organelles, can specifically affect the sensitive and modifying enzymes of the redox system and repair proteins that play a pivotal role in both early and late effects of radiation. In recent years, ionizing radiation has been known to affect the redox functions and metabolism of NADPH oxidases (NOXs) as well as having destabilizing and detrimental effects on directly and indirectly affected cells, tissues and organs. More noteworthy, chronic free radical production may continue for years, increasing the risk of carcinogenesis and other oxidative stress-driven degenerative diseases as well as pathologies, in addition to late effect complications of organ fibrosis. Hence, knowledge about the mechanisms of chronic oxidative damage and injury in affected cells, tissues and organs following exposure to ionizing radiation may help in the development of treatment and management strategies of complications associated with radiotherapy (RT) or radiation accident victims. Thus, this medically relevant phenomenon may lead to the discovery of potential antioxidants and inhibitors with promising results in targeting and modulating the ROS/NO-sensitive enzymes in irradiated tissues and organ injury systems.

Mechanisms of Radiation Bystander and Non-Targeted Effects: Implications to Radiation Carcinogenesis and Radiotherapy

BACKGROUND Knowledge of radiobiology is of paramount importance to be able to grasp and have an in-depth understanding of the consequences of ionizing radiation. One of the most important effects of this physical stressors interaction to targeted and non-targeted cells, tissues and organs is on the late effects on the development of primary and secondary cancers. Thus, an in-depth understanding of the mechanisms of radiation carcinogenesis remains to be elucidated, and some studies have demonstrated or proposed a role of non-targeted effect in excess risk of cancer incidence. The non-targeted effect in radiobiology refers to a dynamic complex response in non-irradiated tissues caused by the release of presumably of clastogenic factors from irradiated cells. Although, most of these responses in non-targeted tissues have marked similarities to irradiated tissues, other studies have shown some differences. Also, the non-targeted effect has shown sex and tissue specificity that are seen in irradiated tissues too. So far, several studies have been conducted to depict mechanisms that may be involved in this phenomenon. Epigenetic dysfunctions, DNA damage and cell death are responsible for initiation of several signaling pathways that finally result in secretion of clastogenic factors. Moreover, studies have shown that damage to both nucleus and mitochondrial DNA, membrane and some organelles is involved. Oxidized DNA associated with other cell death factors stimulates secretion of inflammatory as well as some anti-inflammatory cytokines from irradiated area. Additionally, oxidative stress that results in damage to cellular structures to include cell membranes can affect secretion of exosomes and miRNAs. These bystander effect exogenous mediators migrate to distant tissues and stimulate various signaling pathways which can lead to changes in immune responses, epigenetic modulations and radiation carcinogenesis. CONCLUSION In this review, we focus on descriptive and hierarchical events with emphasis on the molecular and functional interactions of ionizing radiation with cells to the mechanisms involved in cancer induction in non-targeted tissues.

Mechanisms of inflammatory responses to radiation and normal tissues toxicity: clinical implications

Abstract Purpose: Cancer treatment is one of the most challenging diseases in the present era. Among a few modalities for cancer therapy, radiotherapy plays a pivotal role in more than half of all treatments alone or combined with other cancer treatment modalities. Management of normal tissue toxicity induced by radiation is one of the most important limiting factors for an appropriate radiation treatment course. The evaluation of mechanisms of normal tissue toxicity has shown that immune responses especially inflammatory responses play a key role in both early and late side effects of exposure to ionizing radiation (IR). DNA damage and cell death, as well as damage to some organelles such as mitochondria initiate several signaling pathways that result in the response of immune cells. Massive cell damage which is a common phenomenon following exposure to a high dose of IR cause secretion of a lot of inflammatory mediators including cytokines and chemokines. These mediators initiate different changes in normal tissues that may continue for a long time after irradiation. In this study, we reviewed the mechanisms of inflammatory responses to IR that are involved in normal tissue toxicity and considered as the most important limiting factors in radiotherapy. Also, we introduced some agents that have been proposed for management of these responses. Conclusions: The early inflammation during the radiation treatment is often a limiting factor in radiotherapy. In addition to the limiting factors, chronic inflammatory responses may increase the risk of second primary cancers through continuous free radical production, attenuation of tumor suppressor genes, and activation of oncogenes. Moreover, these effects may influence non-irradiated tissues through a mechanism named bystander effect.

Cochlea CT radiomics predicts chemoradiotherapy induced sensorineural hearing loss in head and neck cancer patients: A machine learning and multi-variable modelling study

OBJECTIVES Immediately or after head-and-neck (H&N) cancer chemoradiotherapy (CRT), patients may undergone significant sensorineural hearing loss (SNHL) which could affect their quality of life. Radiomic feature analysis is proposed to predict SNHL induced by CRT. MATERIAL AND METHODS 490 image features of 94 cochlea from 47 patients treated with three dimensional conformal RT (3DCRT) for different H&N cancers were extracted from CT images. Different machine learning (ML) algorithms and also least absolute shrinkage and selection operator (LASSO) penalized logistic regression were implemented on radiomic features for feature selection, classification and prediction. Also, LASSO penalized logistic model was used for outcome modelling. RESULTS The predictive power of ten ML methods was more than 70% (in accuracy, precision and area under the curve of receiver operating characteristic curve (AUC)). According to the LASSO penalized logistic modelling, 10 of the 490 radiomic features selected as the associated features with SNHL status. All of the 10 features were statistically associated with SNHL (all of adjusted P-values < .001). CONCLUSION CT radiomic analysis proposed in this study, could help in the prediction of hearing loss induced by chemoradiation. Our study also, demonstrates that combination of radiomic features with clinical and dosimetric variables can model radiotherapy outcome such as SNHL.

Beneficial effects of cellular autofluorescence following ionization radiation: Hypothetical approaches for radiation protection and enhancing radiotherapy effectiveness

Ionization radiation (IR) is a main part of modern technologies with a double-edge sword manner. Finding the most feasible therapies to reduce adverse effects of IR and also enhancing radiotherapy effectiveness is a debating issue that has been challenged and studied for years. The main aim of the present hypothetical research was to theorize and suggest a new biological radiation protection approach and also increasing radiotherapy outcomes based on cellular autofluorescence following IR. In this hypothesis, we suggested that this cellular autofluorescence can activate some synthetic drugs called photo-activated agents that are injected in human body after radiation exposures scenarios. Photo activated agents can activate biological pathways such as DNA repair and immunostimulation pathways, bystander signals blocking, and so survive cells and tissues. In the other hand, light emitted by cellular response to radiation can be used as like as photodynamic therapy and therefore more cancer cells killing via apoptosis and necrosis. These ideas can be performed in future using more animal and in vivo/in vitro studies and clinical trials. In conclusion, cellular autofluorescence after radiation exposure can be used as a source for activation specific drugs for radiation protection and also radiation therapy effectiveness. These hypothetical therapeutic approaches can be served as personalized therapy based on individual radiosensitivity.

Rectal wall MRI radiomics in prostate cancer patients: prediction of and correlation with early rectal toxicity

Abstract Purpose: To investigate MRI radiomic analysis to assess IMRT associated rectal wall changes and also for predicting radiotherapy induced rectal toxicity. Material and methods: At first, a machine learning radiomic analysis was applied on T2-weighted (T2W) and apparent diffusion coefficient (ADC) rectal wall MR images of prostate cancer patients’ pre- and post-IMRT to predict rectal toxicity. Next, Wilcoxon singed ranked test was performed to find radiomic features with significant changes pre- and post-IMRT. A logistic regression classifier was used to find correlation between features with significant changes and radiation toxicity. Area under the curve (AUC) of receiver operating characteristic (ROC) curve was used in two levels of study for finding performances. Results: AUCmean, 0.68 ± 0.086 and 0.61 ± 0.065 were obtained for pre- and post-IMRT T2 radiomic models, respectively. For ADC radiomic models, AUCmean was 0.58 ± 0.034 for pre-IMRT and was 0.56 ± 0.038 for post-IMRT. Wilcoxon-signed rank test revealed that 9 T2 radiomic features vary significantly post-IMRT. The AUC of logistic-regression was in the range of 0.46–0.58 for single significant features and was 0.81 when all significant features were combined. Conclusions: Pre-IMRT MR image radiomic features could predict rectal toxicity in prostate cancer patients. Radiotherapy associated complications may be assessed by studying the changes in the MR radiomic features.

Radiation dose in cardiac SPECT/CT: An estimation of SSDE and effective dose

AIMS The dose levels for Computed Tomography (CT) localization and attenuation correction of Single Photon Emission Computed Tomography (SPECT) are limited and reported as Volume Computed Tomography Dose Index (CTDIvol) and Dose-Length Product (DLP). This work presents CT dose estimation from Cardiac SPECT/CT based on new American Association of Physicists in Medicine (AAPM) Size Specific Dose Estimation (SSDE) parameter, effective dose, organ doses and also emission dose from nuclear issue. MATERIAL AND METHODS Myocardial perfusion SPECT/CT for 509 patients was included in the study. SSDE, effective dose and organ dose were calculated using AAPM guideline and Impact-Dose software. Data were analyzed using R and SPSS statistical software. Spearman-Pearson correlation test and linear regression models were used for finding correlations and relationships among parameters. RESULTS The mean CTDIvol was 1.34 mGy±0.19 and the mean SSDE was 1.7 mGy±0.16. The mean±SD of effective dose from emission, CT and total dose were 11.5±1.4, 0.49±0.11 and 12.67±1.73 (mSv) respectively. The mean±SD of effective dose from emission, CT and total dose were 11.5±1.4, 0.49±0.11 and 12.67±1.73 (mSv) respectively. The spearman test showed that correlation between body size and organ doses is significant except thyroid and red bone marrow. CTDIvol was strongly dependent on patient size, but SSDE was not. Emission dose was strongly dependent on patient weight, but its dependency was lower to effective diameter. CONCLUSION The dose parameters including CTDIvol, DLP, SSDE, effective dose values reported here are very low and below the reference level. This data suggest that appropriate CT acquisition parameters in SPECT/CT localization and attenuation correction are very beneficial for patients and lowering cancer risks.

Stem Cell Tracing Through MR Molecular Imaging

Stem cell therapy opens a new window in medicine to overcome several diseases that remain incurable. It appears such diseases as cardiovascular disorders, brain injury, multiple sclerosis, urinary system diseases, cartilage lesions and diabetes are curable with stem cell transplantation. However, some questions related to stem cell therapy have remained unanswered. Stem cell imaging allows approval of appropriated strategies such as selection of the type and dose of stem cell, and also mode of cell delivery before being tested in clinical trials. MRI as a non-invasive imaging modality provides proper conditions for this aim. So far, different contrast agents such as superparamagnetic or paramagnetic nanoparticles, ultrasmall superparamagnetic nanoparticles, fluorine, gadolinium and some types of reporter genes have been used for imaging of stem cells. The core subject of these studies is to investigate the survival and differentiation of stem cells, contrast agent’s toxicity and long term following of transplanted cells. The promising results of in vivo and some clinical trial studies may raise hope for clinical stem cells imaging with MRI.

Magnetic resonance image markers to improve patient-specific prediction of IMRT-induced rectal toxicity in prostate cancer patients

Hamid Abdollahi, Seied Rabi Mahdavi, Shayan Mostafaei, Bahram Mofid, Abolfazl Razzaghdoust, Afshin Saadipoor, Mohsen Bakhshandeh, Shahram Teimourian. (2018) Magnetic resonance image markers to improve patient-specific prediction of IMRT-induced rectal toxicity in prostate cancer patients.1 The above article, published online on 4 September 2018 in Wiley Online Library (wileyonlinelibrary.com), has been withdrawn by agreement between the authors, the journal Editor in Chief, and John Wiley and Sons Ltd. The withdrawal has been agreed due to major overlap with a previously published article: Rectal Wall MRI Radiomics in Prostate Cancer Patients: Prediction of and Correlation with Early Rectal Toxicity in International Journal of Radiation Biology 94:9. Published Online 10 September 2018. https://doi.org/10.1080/09553002.2018.1492756 Reference 1. Abdollahi H, Mahdavi SR, Mostafaei S, et al. Magnetic resonance image markers to improve patient-specific prediction of IMRT-induced rectal toxicity in prostate cancer patients. Med Phys. 2018. https://doi.org/10.1002/mp.13166.