Dose-response modeling and treatment plan assessment with a python software toolkit.

This software assistant aims at calculating the dose-response relations of tumors and normal tissues, or clinically assessing already determined values by other researchers. It can also indicate the optimal dose prescription by optimizing the expected treatment outcome. The software is developed solely in python programming language, and it employs PSFL license for its Graphical User Interface (GUI), NUMPY, MATPLOTLIB, and SCIPY libraries. It comprises of two components. The first is the Dose-response relations derivation component, which takes as input the dose volume histograms (DVHs) of patients and their recorded responses regarding a given clinical endpoint to determine the parameters of different tumor control probability (TCP) or normal tissue complication probability (NTCP) models. The second is the Treatment Plan Assessment component, which uses the DVHs of a plan and the dose-response parameters values of the involved tumors and organs at risk (OARs) to calculate their expected responses. Additionally, the overall probabilities of benefit (PB), injury (PI) and complication-free tumor control (P+) are calculated. The software calculates rapidly the corresponding generalized equivalent uniform doses (gEUD) and biologically effective uniform doses (D‾‾) for the Lyman-Kutcher-Burman (LKB), parallel volume (PV) and relative seriality (RS) models respectively, determining the model parameters. In the Dose-Response Relations Derivation component, the software plots the dose-response curves of the irradiated organ with the relevant confidence internals along with the data of the patients with and without toxicity. It also calculates the odds ratio (OR) and the area under the curve (AUC) of different dose metrics or model parameter values against the individual patient outcomes to determine their discrimination capacity. It also performs a goodness-of-fit evaluation of any model parameter set. The user has the option of viewing plots like Scatter, 3D surfaces, and Bootstrap plots. In the Treatment Plan Assessment part, the software calculates the TCP and NTCP values of the involved tumors and OARs, respectively. Furthermore, it plots the dose-response curves of the TCPs, NTCPs, PB, PI, and P+ for a range of prescription doses for different treatment plans. The presented software is ideal for efficiently conducting studies of radiobiological modeling. Furthermore, it is ideal for performing treatment plan assessment, comparison, and optimization studies.

Comparison Between EPI DWI and PROPELLER DWI in Brain MR Imaging.

OBJECTIVE: EPI DWI is a routinely used sequence in brain imaging but it has limitations when it comes to SNR and artifact reduction. PROPELLER DWI has the benefit of improving image quality compared to EPI DWI. The aim of this study is to compare the EPI DWI sequence in brain MR imaging with the PROPELLER DWI sequence. The objective is to identify which sequence is more beneficial in brain imaging by evaluating image quality and the depiction of pathologies. MATERIALS AND METHODS: A total of 101 patients (55 females and 46 males, mean age 56 years) underwent brain MRI examination on a 1.5 T scanner. EPI DWI and PROPELLER DWI sequences were acquired in every exam and were reviewed by 2 radiologists. The images were evaluated by performing a quantitative analysis based on Relative Contrast and a qualitative analysis (overall image quality, conspicuousness of lesions, artifact reduction, etc.). RESULTS: In both the qualitative and quantitative analysis PROPELLER DWI achieved better results than EPI DWI. PROPELLER DWI showed statistical significance in the overall image quality (P < 0.001), the elimination of susceptibility (P < 0.001) and flow pulsation artifacts (P < 0.001), as well as in the contrast between CSF with white (P < 0.001) and grey matter (P < 0.001). Also, PROPELLER DWI presented better delineation of pathologies like ischemic strokes, metastasis, tumors and vasogenic edemas than conventional EPI DWI. CONCLUSION: PROPELLER DWI was the preferred sequence during the image evaluation. Compared to EPI DWI, PROPELLER DWI managed to reduce susceptibility and flow pulsation whilst achieving higher image quality and lesion delineation and earlier depiction of ischemic strokes than the conventional EPI DWI. PROPELLER DWI may be incorporated in brain MR imaging replacing EPI DWI.

NTCP modelling of xerostomia after radiotherapy for oropharyngeal cancer using the PRO-CTCAE and CTCAE scoring systems at different time-points post-RT.

PURPOSE: This study aims at determining the parameter values of three normal tissue complication probability (NTCP) models for the contralateral parotid gland, contralateral submandibular gland (SMG) and contralateral salivary glands regarding the endpoint of xerostomia 6-24 months after radiotherapy for oropharynx cancer. METHODS: The treatment and outcome data of 231 patients with favorable risk, HPV-associated oropharyngeal squamous cell carcinoma are analyzed. 60 Gy intensity modulated radiotherapy was delivered to all the patients. The presence and severity of xerostomia was recorded (pre- and post- radiotherapy) by the PRO-CTCAE and the CTCAE scoring systems. In both scoring systems, patients with a change in symptom severity (from baseline) of ≥ 2 were considered responders. RESULTS: Xerostomia was observed in 61.3 %, 39.2 %, 28.6 % and 27.0 % of the patients based on the PRO-CTCAE scoring system at 6-, 12-, 18- and 24-months post-RT, respectively. The AUCs of the contralateral salivary glands ranged between 0.58-0.64 in the LKB model with the gEUD ranging between 20.3 Gy and 24.7 Gy. CONCLUSIONS: Based on the PRO-CTCAE scores, mean dose < 22 Gy, V50 < 10 % for the contralateral salivary glands and mean dose < 18 Gy, V45 < 10 % for the contralateral parotid were found to significantly reduce by a factor of 2-3 the risk for radiation induced xerostomia that is observed at 6-24 months post-RT, respectively. Also, gEUD < 22 Gy to the contralateral salivary glands and < 18 Gy to the contralateral parotid was found to significantly reduce the risk for radiation induced xerostomia that is observed at 6-24 months post-RT by 2.0-2.3 times.

Value of sildenafil treatment for the prevention of vasospasm­related delayed ischemic neurological deficits and delayed brain infarction following aneurysmal subarachnoid hemorrhage.

Cerebral vasospasm (CV) or delayed cerebral ischemia (DCI) constitutes the main reason for the unfavorable outcomes of patients with aneurysmal subarachnoid hemorrhage (aSAH). The present retrospective cohort study, through an evaluation with computed tomography (CT) perfusion (CTP), aimed to examine the utility of an intravenous or oral administration of sildenafil in preventing DCI that develops due to vasospasm in these patients. A retrospective cohort study was conducted, which included 34 patients in a tertiary care hospital. Of these patients, 18 were males (52.9%), and the median age was 54.4 years. Of these patients, 18 (52.9%) had undergone surgery, and 16 (47.1%) had an endovascular procedure. CTP was performed on the 3rd to the 6th day. The clinical outcome was documented at 30 days using a CT scan and a complete neurological evaluation, including the Glasgow Coma Scale assessment. There was a statistically significant difference in the number of patients who developed an ischemic event at 1 month between those who did not receive sildenafil compared to those who received sildenafil (P<0.05). In addition, the multivariate analysis revealed that cerebral blood flow was an independent factor for detecting an ischemic event in 1 month (P=0.001). On the whole, the findings of the present study indicate that the intravenous or oral administration of sildenafil may be beneficial for the prevention of DCI.

Analysis of ADORA2A rs5760423 and CYP1A2 rs762551 Genetic Variants in Patients with Alzheimer's Disease.

Various studies have been conducted, exploring the genetic susceptibility of Alzheimer's disease (AD). Adenosine receptor subtype A2a (ADORA2A) and cytochrome P450 1A2 (CYP1A2) are implicated in pathways such as oxidative stress and caffeine metabolism, which are associated with AD. The aim of this study was to explore for any potential association between the ADORA2A rs5760423 and the CYP1A2 rs762551 genetic variants and AD. A case-control study was performed with a total of 654 subjects (327 healthy controls and 327 patients with AD). Five genetic models were assumed. We also examined the allele-allele combination of both variants. The value of 0.05 was considered as the statistical significance threshold. A statistically significant association was found between ADORA2A rs5760423 and AD, as the "T" allele was associated with increased AD risk in recessive (OR = 1.51 (1.03-2.21)) and log-additive (OR = 1.30 (1.04-1.62)) genetic modes. In the codominant model, the TT genotype was more prevalent compared to the GG genotype (OR = 1.71 (1.09-2.66)). The statistical significance was maintained after adjustment for sex. No association between CYP1A2 rs762551 or allele-allele combination and AD was detected. We provide preliminary indication for a possible association between the ADORA2A rs5760423 genetic polymorphism and AD.

Uncommon and atypical meningiomas and imaging variants: A report of 7 cases.

Meningiomas constitute the most common extra-axial tumor of the central nervous system and can have a wide-ranging manifestation of imaging. There are several types of unusual depictions depicted with the magnetic resonance imaging (MRI) of meningiomas that have been established thus far. It is thus crucial for the reporting radiologist or neurosurgeon to have an in-depth knowledge of their variable manifestations in order to be able to differentiate these neoplasms from the numerous tumors that can mimic their appearance. Meningioma is frequently challenging to diagnose when imaging variants are present. Nevertheless, a number of unusual histological variants have imaging or clinical features which are related to typical meningiomas and, in numerous cases, these require specific surgical management. The present study describes 7 cases of meningiomas, which were either simple atypical, unusual gigantic extracranial intracranial parasagittal, or not visible meningiomas. These uncommon and atypical imaging variants of meningiomas are described herein in an aim to underline their various potential presentations.

GPU-enabled design of an adaptable pattern recognition system for discriminating squamous intraepithelial lesions of the cervix.

The aim of the present study was to design an adaptable pattern recognition (PR) system to discriminate low- from high-grade squamous intraepithelial lesions (LSIL and HSIL, respectively) of the cervix using microscopy images of hematoxylin and eosin (H&E)-stained biopsy material from two different medical centers. Clinical material comprised H&E-stained biopsies of 66 patients diagnosed with LSIL (34 cases) or HSIL (32 cases). Regions of interest were selected from each patient's digitized microscopy images. Seventy-seven features were generated, regarding the texture, morphology and spatial distribution of nuclei. The probabilistic neural network (PNN) classifier, the exhaustive search feature selection method, the leave-one-out (LOO) and the bootstrap validation methods were used to design the PR system and to assess its precision. Optimal PR system design and evaluation were made feasible by the employment of graphics processing unit (GPU) and Compute Unified Device Architecture (CUDA) technologies. The accuracy of the PR-system was 93% and 88.6% when using the LOO and bootstrap validation methods, respectively. The proposed PR system for discriminating LSIL from HSIL of the cervix was designed to operate in a clinical environment, having the capability of being redesigned when new verified cases are added to its repository and when data from other medical centers are included, following similar biopsy material preparation procedures.

Multifeature Quantification of Nuclear Properties from Images of H&E-Stained Biopsy Material for Investigating Changes in Nuclear Structure with Advancing CIN Grade.

Background: Cervical dysplasia is a precancerous condition, and if left untreated, it may lead to cervical cancer, which is the second most common cancer in women. The purpose of this study was to investigate differences in nuclear properties of the H&E-stained biopsy material between low CIN and high CIN cases and associate those properties with the CIN grade. Methods: The clinical material comprised hematoxylin and eosin- (H&E-) stained biopsy specimens from lesions of 44 patients diagnosed with cervical intraepithelial neoplasia (CIN). Four or five nonoverlapping microscopy images were digitized from each patient's H&E specimens, from regions indicated by the expert physician. Sixty-three textural and morphological nuclear features were generated for each patient's images. The Wilcoxon statistical test and the point biserial correlation were used to estimate each feature's discriminatory power between low CIN and high CIN cases and its correlation with the advancing CIN grade, respectively. Results: Statistical analysis showed 19 features that quantify nuclear shape, size, and texture and sustain statistically significant differences between low CIN and high CIN cases. These findings revealed that nuclei in high CIN cases, as compared to nuclei in low CIN cases, have more irregular shape, are larger in size, are coarser in texture, contain higher edges, have higher local contrast, are more inhomogeneous, and comprise structures of different intensities. Conclusion: A systematic statistical analysis of nucleus features, quantified from the H&E-stained biopsy material, showed that there are significant differences in the shape, size, and texture of nuclei between low CIN and high CIN cases.

Dosimetric and Radiobiological Evaluation of Patient Setup Accuracy in Head-and-neck Radiotherapy Using Daily Computed Tomography-on-rails-based Corrections.

INTRODUCTION: This study evaluates treatment plans aiming at determining the expected impact of daily patient setup corrections on the delivered dose distribution and plan parameters in head-and-neck radiotherapy. MATERIALS AND METHODS: In this study, 10 head-and-neck cancer patients are evaluated. For the evaluation of daily changes of the patient internal anatomy, image-guided radiation therapy based on computed tomography (CT)-on-rails was used. The daily-acquired CT-on-rails images were deformedly registered to the CT scan that was used during treatment planning. Two approaches were used during data analysis ("cascade" and "one-to-all"). The dosimetric and radiobiological differences of the dose distributions with and without patient setup correction were calculated. The evaluation is performed using dose-volume histograms; the biologically effective uniform dose () and the complication-free tumor control probability (P+) were also calculated. The dose-response curves of each target and organ at risk (OAR), as well as the corresponding P+ curves, were calculated. RESULTS: The average difference for the "one-to-all" case is 0.6 ± 1.8 Gy and for the "cascade" case is 0.5 ± 1.8 Gy. The value of P+ was lowest for the cascade case (in 80% of the patients). DISCUSSION: Overall, the lowest PI is observed in the one-to-all cases. Dosimetrically, CT-on-rails data are not worse or better than the planned data. CONCLUSIONS: The differences between the evaluated "one-to-all" and "cascade" dose distributions were small. Although the differences of those doses against the "planned" dose distributions were small for the majority of the patients, they were large for given patients at risk and OAR.

Computer-based automated estimation of breast vascularity and correlation with breast cancer in DCE-MRI images.

Dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) with gadolinium constitutes one of the most promising protocols for boosting up the sensitivity in breast cancer detection. The aim of this study was twofold: first to design an image processing methodology to estimate the vascularity of the breast region in DCE-MRI images and second to investigate whether the differences in the composition/texture and vascularity of normal, benign and malignant breasts may serve as potential indicators regarding the presence of the disease. Clinical material comprised thirty nine cases examined on a 3.0-T MRI system (SIGNA HDx; GE Healthcare). Vessel segmentation was performed using a custom made modification of the Seeded Region Growing algorithm that was designed in order to identify pixels belonging to the breast vascular network. Two families of features were extracted: first, morphological and textural features from segmented images in order to quantify the extent and the properties of the vascular network; second, textural features from the whole breast region in order to investigate whether the nature of the disease causes statistically important changes in the texture of affected breasts. Results have indicated that: (a) the texture of vessels presents statistically significant differences (p<0.001) between normal, benign and malignant cases, (b) the texture of the whole breast region for malignant and non-malignant breasts, produced statistically significant differences (p<0.001), (c) the relative ratios of the texture between the two breasts may be used for the discrimination of non-malignant from malignant patients, and (d) an area under the receiver operating characteristic curve of 0.908 (AUC) was found when features were combined in a logistic regression prediction rule according to ROC analysis.

A method for limiting pitfalls in the production of enhancement kinetic curves in 3T dynamic magnetic resonance mammography.

PURPOSE: The aim of the present study is to investigate means for the reduction or even elimination of enhancement kinetic curve errors due to breast motion in order to avoid pitfalls and to increase the sensitivity and specificity of the method. METHODS: 115 women underwent breast Magnetic Resonance Imaging (MRI). All patients were properly immobilized in a dedicated bilateral phased array coil. A magnetic resonance unit 3-Tesla (Signa, GE Healthcare) was used. The following sequences were applied: (I) axial Τ2-TSE, (II) axial STIR and (III) Vibrant axial T1-weighted fat saturation (six phases). Kinetic curves were derived semi-automatically using the software of the system and manually by positioning the regions of interest (ROI) from stable reference points in all the phases. RESULTS: 376 abnormalities in 115 patients were investigated. In 81 (21.5%) cases, a change of the enhancement kinetic curve type was found when the two different methods were used. In cases of large fatty breasts, a change of the enhancement kinetic curve type in 13 lesions was found. In cases of small and dense breasts, only in 4 lesions the kinetic curve type changed, whereas in cases of small and fatty breasts, the kinetic curve type changed in 64 lesions (50 were observed in left breasts and 14 in right breasts). CONCLUSIONS: The derivation of enhancement kinetic curves should be performed by controlling and verifying that the ROIs lay at the same location of the lesion in all the phases of the dynamic study.

Perfusion sensitive contrast-enhanced magnetic resonance imaging of dysembryoplastic neuroepithelial tumour: a new neuroimaging finding.

Dysembryoplastic neuroepithelial tumours (DNTs) are benign lesions affecting young people and are associated with epilepsy. There have been described more than 300 cases in the literature and the clinical, pathological and radiological findings are well known. Recent advances in neuroimaging allow the acquisition of cerebral microcirculation parameters by perfusion weighted imaging, giving additional diagnostic information improving the diagnostic accuracy. The aim of this study is to show the perfusion sensitive contrast-enhanced magnetic resonance imaging findings of a case of DNT as an additional neuroradiological finding. Further investigation of microcirculation parameters may be helpful to establish the correct diagnosis of such tumours.

Comparison of T1-weighted fast spin-echo and T1-weighted fluid-attenuated inversion recovery images of the lumbar spine at 3.0 Tesla.

BACKGROUND: T1-weighted fluid-attenuated inversion recovery (FLAIR) sequence has been reported to provide improved contrast between lesions and normal anatomical structures compared to T1-weighted fast spin-echo (FSE) imaging at 1.5T regarding imaging of the lumbar spine. PURPOSE: To compare T1-weighted FSE and fast T1-weighted FLAIR imaging in normal anatomic structures and degenerative and metastatic lesions of the lumbar spine at 3.0T. MATERIAL AND METHODS: Thirty-two consecutive patients (19 females, 13 males; mean age 44 years, range 30-67 years) with lesions of the lumbar spine were prospectively evaluated. Sagittal images of the lumbar spine were obtained using T1-weighted FSE and fast T1-weighted FLAIR sequences. Both qualitative and quantitative analyses measuring the signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and relative contrast (ReCon) between degenerative and metastatic lesions and normal anatomic structures were conducted, comparing these sequences. RESULTS: On quantitative evaluation, SNRs of cerebrospinal fluid (CSF), nerve root, and fat around the root of fast T1-weighted FLAIR imaging were significantly lower than those of T1-weighted FSE images (P<0.001). CNRs of normal spinal cord/CSF and disc herniation/ CSF for fast T1-weighted FLAIR images were significantly higher than those for T1-weighted FSE images (P<0.001). ReCon of normal spinal cord/CSF, disc herniation/CSF, and vertebral lesions/CSF for fast T1-weighted FLAIR images were significantly higher than those for T1-weighted FSE images (P<0.001). On qualitative evaluation, it was found that CSF nulling and contrast at the spinal cord (cauda equina)/CSF interface for T1-weighted FLAIR images were significantly superior compared to those for T1-weighted FSE images (P<0.001), and the disc/spinal cord (cauda equina) interface was better for T1-weighted FLAIR images (P<0.05). CONCLUSION: The T1-weighted FLAIR sequence may be considered as the preferred lumbar spine imaging sequence compared to T1-weighted FSE, as it has demonstrated superior CSF nulling, better conspicuousness of normal anatomic structures and degenerative and metastatic lesions, and improved image contrast.