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Radiomics involves high-throughput extraction of large numbers of quantitative features from medical images and analysis of these features to predict patients’ outcome and support clinical decision-making. However, radiomics features are sensitive to several factors, including scanning protocols. The purpose of this study was to investigate the robustness of magnetic resonance imaging (MRI) radiomics features with various MRI scanning protocol parameters and scanners using an MRI radiomics phantom. The variability of the radiomics features with different scanning parameters and repeatability measured using a test–retest scheme were evaluated using the coefficient of variation and intraclass correlation coefficient (ICC) for both T1- and T2-weighted images. For variability measures, the features were categorized into three groups: large, intermediate, and small variation. For repeatability measures, the average T1- and T2-weighted image ICCs for the phantom (0.963 and 0.959, respectively) were higher than those for a healthy volunteer (0.856 and 0.849, respectively). Our results demonstrated that various radiomics features are dependent on different scanning parameters and scanners. The radiomics features with a low coefficient of variation and high ICC for both the phantom and volunteer can be considered good candidates for MRI radiomics studies. The results of this study will assist current and future MRI radiomics studies.

Purpose To investigate the impact of computed tomography (CT) image acquisition and reconstruction parameters, including slice thickness, pixel size, and dose, on automatic contouring algorithms. Methods Eleven scans from patients with head‐and‐neck cancer were reconstructed with varying slice thicknesses and pixel sizes. CT dose was varied by adding noise using low‐dose simulation software. The impact of these imaging parameters on two in‐house auto‐contouring algorithms, one convolutional neural network (CNN)‐based and one multiatlas‐based system (MACS) was investigated for 183 reconstructed scans. For each algorithm, auto‐contours for organs‐at‐risk were compared with auto‐contours from scans with 3 mm slice thickness, 0.977 mm pixel size, and 100% CT dose using Dice similarity coefficient (DSC), Hausdorff distance (HD), and mean surface distance (MSD). Results Increasing the slice thickness from baseline value of 3 mm gave a progressive reduction in DSC and an increase in HD and MSD on average for all structures. Reducing the CT dose only had a relatively minimal effect on DSC and HD. The rate of change with respect to dose for both auto‐contouring methods is approximately 0. Changes in pixel size had a small effect on DSC and HD for CNN‐based auto‐contouring with differences in DSC being within 0.07. Small structures had larger deviations from the baseline values than large structures for DSC. The relative differences in HD and MSD between the large and small structures were small. Conclusions Auto‐contours can deviate substantially with changes in CT acquisition and reconstruction parameters, especially slice thickness and pixel size. The CNN was less sensitive to changes in pixel size, and dose levels than the MACS. The results contraindicated more restrictive values for the parameters should be used than a typical imaging protocol for head‐and‐neck.

In many applications based on kinetic evaluation analysis and model fitting, quantitative mapping retrieved on data series from modalites such as MRI is completed on a voxel-by-voxel basis, where motion and low signal to noise ratio (SNR) would considerably degenerate the reliability of estimations. The coherence of image series in space and time can be used as prior knowledge to mitigate this occurrence. In this study, spatial and temporal higher-order total variations (HOTVs) are applied on a data series of MRI signal (e.g. dynamic contrast-enhanced (DCE) MRI and intravoxel incoherent motion (IVIM) MRI) to exploit the coherence of signal in space and time to minimize the variabilities caused by motion as well as improving quality of images with low SNR while retaining the physical details of original data properly. Simultaneously applying spatial and temporal HOTVs on images is non-trivial in implementation since it is a non-smooth optimization problem with multiple regularizers. Therefore, we use the proximal gradient method as well as a primal-dual split proximal mechanism to address the problem properly. In addition to increase the reliability of quantitative parametric map estimations, this preprocessing procedure can be included into many existing map estimation algorithms and pipelines effortlessly. We demonstrate our method on the parametric maps estimation for DCE MRI and IVIM MRI.

Radiomics studies have demonstrated the potential use of quantitative image features to improve prognostic stratification of patients with head and neck cancer. Imaging protocol parameters that can affect radiomics feature values have been investigated, but the effects of artifacts caused by intrinsic patient factors have not. Two such artifacts that are common in patients with head and neck cancer are streak artifacts caused by dental fillings and beam-hardening artifacts caused by bone. The purpose of this study was to test the impact of these artifacts and if needed, methods for compensating for these artifacts in head and neck radiomics studies. The robustness of feature values was tested by removing slices of the gross tumor volume (GTV) on computed tomography images from 30 patients with head and neck cancer; these images did not have streak artifacts or had artifacts far from the GTV. The range of each feature value over a percentage of the GTV was compared to the inter-patient variability at full volume. To determine the effects of beam-hardening artifacts, we scanned a phantom with 5 cartridges of different materials encased in polystyrene buildup. A cylindrical hole through the cartridges contained either a rod of polylactic acid to simulate water or a rod of polyvinyl chloride to simulate bone. A region of interest was drawn in each cartridge flush with the rod. Most features were robust with up to 50% of the original GTV removed. Most feature values did not significantly differ when measured with the polylactic acid rod or the polyvinyl chloride rod. Of those that did, the size of the difference did not exceed the inter-patient standard deviation in most cases. We conclude that simply removing slices affected by streak artifacts can enable these scans to be included in radiomics studies and that contours of structures can abut bone without being affected by beam hardening if needed.

Background and purpose: Postmastectomy radiotherapy (PMRT) is complex to plan and deliver, but could be improved with 3D-printed, patient-specific electron tissue compensators. The purposes of this study were to develop an algorithm to design patient-specific compensators that achieve clinical goals, to 3D-print the planned compensators, and validate calculated dose distributions with film and thermoluminescent dosimeter (TLD) measurements in 3D-printed phantoms of PMRT patients. Materials and methods: An iterative algorithm was developed to design compensators corresponding to single-field, single-energy electron plans for PMRT patients. The 3D-printable compensators were designed to fit into the electron aperture, with cerrobend poured around it. For a sample of eight patients, calculated dose distributions for compensator plans were compared with patients’ (multi-field, multi-energy) clinical treatment plans. For all patients, dosimetric parameters were compared including clinical target volume (CTV), lung, and heart metrics. For validation, compensators were fabricated and irradiated for a set of six 3D-printed patient-specific phantoms. Dose distributions in the phantoms were measured with TLD and film. These measurements were compared with the treatment planning system calculated dose distributions. Results: The compensator treatment plans achieved superior CTV coverage (97% vs 89% of the CTV receiving the prescription dose, p 0.35) to the conventional treatment plans. Average differences between calculated and measured TLD values were 2%, and average film profile differences were

A large number of surveys have been sent to the medical physics community addressing many clinical topics for which the medical physicist is, or may be, responsible. Each survey provides an insight into clinical practice relevant to the medical physics community. The goal of this study was to create a summary of these surveys giving a snapshot of clinical practice patterns. Surveys used in this study were created using SurveyMonkey and distributed between February 6, 2013 and January 2, 2018 via the MEDPHYS and MEDDOS listserv groups. The format of the surveys included questions that were multiple choice and free response. Surveys were included in this analysis if they met the following criteria: more than 20 responses, relevant to radiation therapy physics practice, not single‐vendor specific, and formatted as multiple‐choice questions (i.e., not exclusively free‐text responses). Although the results of free response questions were not explicitly reported, they were carefully reviewed, and the responses were considered in the discussion of each topic. Two‐hundred and fifty‐two surveys were available, of which 139 passed the inclusion criteria. The mean number of questions per survey was 4. The mean number of respondents per survey was 63. Summaries were made for the following topics: simulation, treatment planning, electron treatments, linac commissioning and quality assurance, setup and treatment verification, IMRT and VMAT treatments, SRS/SBRT, breast treatments, prostate treatments, brachytherapy, TBI, facial lesion treatments, clinical workflow, and after‐hours/emergent treatments. We have provided a coherent overview of medical physics practice according to surveys conducted over the last 5 yr, which will be instructive for medical physicists.

Variability in the x-ray tube current used in computed tomography may affect quantitative features extracted from the images. To investigate these effects, we scanned the Credence Cartridge Radiomics phantom 12 times, varying the tube current from 25 to 300 mA∙s while keeping the other acquisition parameters constant. For each of the scans, we extracted 48 radiomic features from the categories of intensity histogram (n = 10), gray-level run length matrix (n = 11), gray-level co-occurrence matrix (n = 22), and neighborhood gray tone difference matrix (n = 5). To gauge the size of the tube current effects, we scaled the features by the coefficient of variation of the corresponding features extracted from images of non-small cell lung cancer tumors. Variations in the tube current had more effect on features extracted from homogeneous materials (acrylic, sycamore wood) than from materials with more tissue-like textures (cork, rubber particles). Thirty-eight of the 48 features extracted from acrylic were affected by current reductions compared with only 2 of the 48 features extracted from rubber particles. These results indicate that variable x-ray tube current is unlikely to have a large effect on radiomic features extracted from computed tomography images of textured objects such as tumors.

Radiomics is one such “big data” approach that applies advanced image refining/data characterization algorithms to generate imaging features that can quantitatively classify tumor phenotypes in a non-invasive manner. We hypothesize that certain textural features of oropharyngeal cancer (OPC) primary tumors will have statistically significant correlations to patient outcomes such as local control. Patients from an IRB-approved database dispositioned to (chemo)radiotherapy for locally advanced OPC were included in this retrospective series. Pretreatment contrast CT scans were extracted and radiomics-based analysis of gross tumor volume of the primary disease (GTVp) were performed using imaging biomarker explorer (IBEX) software that runs in Matlab platform. Data set was randomly divided into a training dataset and test and tuning holdback dataset. Machine learning methods were applied to yield a radiomic signature consisting of features with minimal overlap and maximum prognostic significance. The radiomic signature was adapted to discriminate patients, in concordance with other key clinical prognosticators. 465 patients were available for analysis. A signature composed of 2 radiomic features from pre-therapy imaging was derived, based on the Intensity Direct and Neighbor Intensity Difference methods. Analysis of resultant groupings showed robust discrimination of recurrence probability and Kaplan-Meier-estimated local control rate (LCR) differences between “favorable” and “unfavorable” clusters were noted.

Purpose Accurate deformable image registration is necessary for longitudinal studies. The error associated with commercial systems has been evaluated using computed tomography (CT). Several in-house algorithms have been evaluated for use with magnetic resonance imaging (MRI), but there is still relatively little information about MRI deformable image registration. This work presents an evaluation of two deformable image registration systems, one commercial (Velocity) and one in-house (demons-based algorithm), with MRI using two different metrics to quantify the registration error. Methods The registration error was analyzed first with synthetic MR images. These images were generated from inter-patient and intra-patient variation models trained on 28 patients. Four synthetic posttreatment images were generated for each of four synthetic pretreatment images, resulting in 16 image registrations for both the T1- and T2-weighted images. The synthetic post-treatment images were registered to their corresponding synthetic pre-treatment image. The registration error was calculated between the known deformation vector field and the generated deformation vector field from the image registration system. The registration error was also analyzed using a porcine phantom with ten implanted 0.35-mm diameter gold markers. The markers were visible on CT but not MRI. CT, T1-weighted MR, and T2-weighted MR images were taken in four different positions. The markers were contoured on the CT images and rigidly registered to their corresponding MR images. The MR images were deformably registered and the distance between the projected marker location and true marker location was measured as the registration error. Results The synthetic images were evaluated only on Velocity. Root mean square errors (RMSEs) of 0.76 mm in the left-right (LR) direction, 0.76 mm in the anteroposterior (AP) direction, and 0.69 mm in the superior-inferior (SI) direction were observed for the T1-weighted MR images. RMSEs of 1.1 mm in the LR direction, 0.75 mm in the AP direction, and 0.81 mm in the SI direction were observed for the T2-weighted MR images. The porcine phantom MR images, when evaluated with Velocity, had RMSEs of 1.8, 1.5, and 2.7 mm in the LR, AP, and SI directions for the T1-weighted images and 1.3, 1.2, and 1.6 mm in the LR, AP, and SI directions for the T2-weighted images. When the porcine phantom images were evaluated with the in-house demons-based algorithm, RMSEs were 1.2, 1.5, 2.1 mm in the LR, AP, and SI directions for the T1-weighted images and 0.81, 1.1, and 1.1 mm in the LR, AP, and SI directions for the T2-weighted images. Conclusions The MRI registration error was low for both Velocity and the in-house demons-based algorithm according to both image evaluation methods, with all RMSEs below 3 mm. This implies that both image registration systems can be used for longitudinal studies using MRI. This article is protected by copyright. All rights reserved.

To investigate the inter‐ and intra‐fraction motion associated with the use of a low‐cost tape immobilization technique as an alternative to thermoplastic immobilization masks for whole‐brain treatments. The results of this study may be of interest to clinical staff with severely limited resources (e.g., in low‐income countries) and also when treating patients who cannot tolerate standard immobilization masks. Setup reproducibility of eight healthy volunteers was assessed for two different immobilization techniques. (a) One strip of tape was placed across the volunteer's forehead and attached to the sides of the treatment table. (b) A second strip was added to the first, under the chin, and secured to the table above the volunteer's head. After initial positioning, anterior and lateral photographs were acquired. Volunteers were positioned five times with each technique to allow calculation of inter‐fraction reproducibility measurements. To estimate intra‐fraction reproducibility, 5‐minute anterior and lateral videos were taken for each technique per volunteer. An in‐house software was used to analyze the photos and videos to assess setup reproducibility. The maximum intra‐fraction displacement for all volunteers was 2.8 mm. Intra‐fraction motion increased with time on table. The maximum inter‐fraction range of positions for all volunteers was 5.4 mm. The magnitude of inter‐fraction and intra‐fraction motion found using the “1‐strip” and “2‐strip” tape immobilization techniques was comparable to motion restrictions provided by a thermoplastic mask for whole‐brain radiotherapy. The results suggest that tape‐based immobilization techniques represent an economical and useful alternative to the thermoplastic mask.

Computed tomography (CT) technology has rapidly evolved since its introduction in the 1970s. It is a highly important diagnostic tool for clinicians as demonstrated by the significant increase in utilization over several decades. However, much of the effort to develop and advance CT applications has been focused on improving visual sensitivity and reducing radiation dose. In comparison to these areas, improvements in quantitative CT have lagged behind. While this could be a consequence of the technological limitations of conventional CT, advanced dual-energy CT (DECT) and photon-counting detector CT (PCD-CT) offer new opportunities for quantitation. Routine use of DECT is becoming more widely available and PCD-CT is rapidly developing. This review covers efforts to address an unmet need for improved quantitative imaging to better characterize disease, identify biomarkers, and evaluate therapeutic response, with an emphasis on multi-energy CT applications. The review will primarily discuss applications that have utilized quantitative metrics using both conventional and DECT, such as bone mineral density measurement, evaluation of renal lesions, and diagnosis of fatty liver disease. Other topics that will be discussed include efforts to improve quantitative CT volumetry and radiomics. Finally, we will address the use of quantitative CT to enhance image-guided techniques for surgery, radiotherapy and interventions and provide unique opportunities for development of new contrast agents.

Purpose Routine quality assurance (QA) testing to identify malfunctions in medical imaging devices is a standard practice and plays an important role in meeting quality standards. However, current daily computed tomography (CT) QA techniques have proven to be inadequate for the detection of subtle artifacts on scans. Therefore, we investigated the ability of a radiomics phantom to detect subtle artifacts not detected in conventional daily QA. Methods An updated credence cartridge radiomics phantom was used in this study, with a focus on two of the cartridges (rubber and cork) in the phantom. The phantom was scanned using a Siemens Definition Flash CT scanner, which was reported to produce a subtle line pattern artifact. Images were then imported into the IBEX software program, and 49 features were extracted from the two cartridges using four different preprocessing techniques. Each feature was then compared with features for the same scanner several months previously and with features from controlled CT scans obtained using 100 scanners. Results Of 196 total features for the test scanner, 79 (40%) from the rubber cartridge and 70 (36%) from the cork cartridge were three or more standard deviations away from the mean of the controlled scan population data. Feature values for the artifact‐producing scanner were closer to the population mean when features were preprocessed with Butterworth smoothing. The feature most sensitive to the artifact was co‐occurrence matrix maximum probability. The deviation from the mean for this feature was more than seven times greater when the scanner was malfunctioning (7.56 versus 1.01). Conclusions Radiomics features extracted from a texture phantom were able to identify an artifact‐producing scanner as an outlier among 100 CT scanners. This preliminary analysis demonstrated the potential of radiomics in CT QA to identify subtle artifacts not detected using the currently employed daily QA techniques.

The purpose of this study is to investigate the dosimetric impact of multi‐leaf collimator (MLC) positioning errors on a Varian Halcyon for both random and systematic errors, and to evaluate the effectiveness of portal dosimetry quality assurance in catching clinically significant changes caused by these errors. Both random and systematic errors were purposely added to 11 physician‐approved head and neck volumetric modulated arc therapy (VMAT) treatment plans, yielding a total of 99 unique plans. Plans were then delivered on a preclinical Varian Halcyon linear accelerator and the fluence was captured by an opposed portal dosimeter. When comparing dose–volume histogram (DVH) values of plans with introduced MLC errors to known good plans, clinically significant changes to target structures quickly emerged for plans with systematic errors, while random errors caused less change. For both error types, the magnitude of clinically significant changes increased as error size increased. Portal dosimetry was able to detect all systematic errors, while random errors of ±5 mm or less were unlikely to be detected. Best detection of clinically significant errors, while minimizing false positives, was achieved by following the recommendations of AAPM TG‐218. Furthermore, high‐ to moderate correlation was found between dose DVH metrics for normal tissues surrounding the target and portal dosimetry pass rates. Therefore, it may be concluded that portal dosimetry on the Halcyon is robust enough to detect errors in MLC positioning before they introduce clinically significant changes to VMAT treatment plans.

Radiomics has shown promise in improving models for predicting patient outcomes. However, to maximize the information gain of the radiomics features, especially in larger patient cohorts, the variability in radiomics features owing to differences between scanners and scanning protocols must be accounted for. To this aim, the imaging variability of radiomics feature values was evaluated on 100 computed tomography scanners at 35 clinics by imaging a radiomics phantom using a controlled protocol and the commonly used chest and head protocols of the local clinic. We used a linear mixed-effects model to determine the degree to which the manufacturer and individual scanners contribute to the overall variability. Using a controlled protocol reduced the overall variability by 57% and 52% compared to the local chest and head protocols respectively. The controlled protocol also reduced the relative contribution of the manufacturer to the total variability. For almost all variabilities (manufacturer, scanner, and residual with different preprocesssing), the controlled protocol scans had a significantly smaller variability than the local protocol scans did. For most radiomics features, the imaging variability was small relative to the inter-patient feature variability in non–small cell lung cancer and head and neck squamous cell carcinoma patient cohorts. From this study, we conclude that using controlled scans can reduce the variability in radiomics features, and our results demonstrate the importance of using controlled protocols in prospective radiomics studies.

PURPOSE: Magnetic resonance imaging (MRI) provides non-invasive evaluation of patient’s anatomy without using ionizing radiation. Due to this and the high soft-tissue contrast, MRI use has increased and has potential for use in longitudinal studies where changes in patients’ anatomy or tumors at different time points are compared. Deformable image registration can be useful for these studies. Here we describe two data sets that can be used to evaluate the registration accuracy of systems for MR images, as it cannot be assumed to be the same as that measured on CT images. ACQUISITION AND VALIDATION METHODS: Two sets of images were created to test registration accuracy. (1) A porcine phantom was created by placing ten 0.35 mm gold markers into porcine meat. The porcine phantom was immobilized in a plastic container with movable dividers. T1-weighted, T2-weighted, and CT images were acquired with the porcine phantom compressed in 4 different ways. The markers were not visible on the MR images, due to the selected voxel size, so they did not interfere with the measured registration accuracy, while the markers were visible on the CT images and were used to identify the known deformation between positions. (2) Synthetic images were created using 28 head and neck squamous cell carcinoma patients who had MR scans pre-, mid-, and post-radiotherapy treatment. An inter- and intra-patient variation model was created using these patient scans. Four synthetic pre-treatment images were created using the inter-patient model, and four synthetic post-treatment images were created for each of the pre-treatment images using the intra-patient model. DATA FORMAT AND USAGE NOTES: The T1-weighted, T2-weighted, and CT scans of the porcine phantom in the four positions are provided. Four T1-weighted synthetic pre-treatment images each with four synthetic post-treatment images, and four T2-weighted synthetic pre-treatment images each with four synthetic post-treatment images are provided. Additionally, the applied deformation vector fields to generate the synthetic post-treatment images are provided. The data is available on TCIA under the collection MRI-DIR. POTENTIAL APPLICATIONS: The proposed database provides two sets of images (one acquired and one computer generated) for use in evaluating deformable image registration accuracy. T1- and T2-weighted images are available for each technique as the different image contrast in the two types of images may impact the registration accuracy.

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Radiomics studies often analyze patient computed tomography (CT) images acquired from different CT scanners. This may result in differences in imaging parameters, e.g. different manufacturers, different acquisition protocols, etc. However, quantifiable differences in radiomics features can occur based on acquisition parameters. A controlled protocol may allow for minimization of these effects, thus allowing for larger patient cohorts from many different CT scanners. In order to test radiomics feature variability across different CT scanners a radiomics phantom was developed with six different cartridges encased in high density polystyrene. A harmonized protocol was developed to control for tube voltage, tube current, scan type, pitch, CTDIvol, convolution kernel, display field of view, and slice thickness across different manufacturers. The radiomics phantom was imaged on 18 scanners using the control protocol. A linear mixed effects model was created to assess the impact of inter-scanner variability with decomposition of feature variation between scanners and cartridge materials. The inter-scanner variability was compared to the residual variability (the unexplained variability) and to the inter-patient variability using two different patient cohorts. The patient cohorts consisted of 20 non-small cell lung cancer (NSCLC) and 30 head and neck squamous cell carcinoma (HNSCC) patients. The inter-scanner standard deviation was at least half of the residual standard deviation for 36 of 49 quantitative image features. The ratio of inter-scanner to patient coefficient of variation was above 0.2 for 22 and 28 of the 49 features for NSCLC and HNSCC patients, respectively. Inter-scanner variability was a significant factor compared to patient variation in this small study for many of the features. Further analysis with a larger cohort will allow more thorough analysis with additional variables in the model to truly isolate the interscanner difference.

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has been correlated with prognosis in head and neck squamous cell carcinoma as well as with changes in normal tissues. These studies implement different software, either commercial or in-house, and different scan protocols. Thus, the generalizability of the results is not confirmed. To assist in the standardization of quantitative metrics to confirm the generalizability of these previous studies, this data descriptor delineates in detail the DCE-MRI digital imaging and communications in medicine (DICOM) files with DICOM radiation therapy (RT) structure sets and digital reference objects (DROs), as well as, relevant clinical data that encompass a data set that can be used by all software for comparing quantitative metrics. Variable flip angle (VFA) with six flip angles and DCE-MRI scans with a temporal resolution of 5.5 s were acquired in the axial direction on a 3T MR scanner with a field of view of 25.6 cm, slice thickness of 4 mm, and 256×256 matrix size.

Imaging Biomarker Explorer (IBEX) is an open-source tool for medical imaging radiomics work. The purpose of this paper is to describe how to use IBEX's graphical user interface (GUI) and to demonstrate how IBEX calculated features have been used in clinical studies. IBEX allows for the import of DICOM images with DICOM radiation therapy structure files or Pinnacle files. Once the images are imported, IBEX has tools within the Data Selection GUI to manipulate the viewing of the images, measure voxel values and distances, and create and edit contours. IBEX comes with 27 preprocessing and 132 feature choices to design feature sets. Each preprocessing and feature category has parameters that can be altered. The output from IBEX is a spreadsheet that contains: 1) each feature from the feature set calculated for each contour in a data set, 2) image information about each contour in a data set, and 3) a summary of the preprocessing and features used with their selected parameters. Features calculated from IBEX have been used in studies to test the variability of features under different imaging conditions and in survival models to improve current clinical models.

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) provides quantitative metrics (e.g. Ktrans, ve) via pharmacokinetic models. We tested inter-algorithm variability in these quantitative metrics with 11 published DCE-MRI algorithms, all implementing Tofts-Kermode or extended Tofts pharmacokinetic models. Digital reference objects (DROs) with known Ktrans and ve values were used to assess performance at varying noise levels. Additionally, DCE-MRI data from 15 head and neck squamous cell carcinoma patients over 3 time-points during chemoradiotherapy were used to ascertain Ktrans and ve kinetic trends across algorithms. Algorithms performed well (less than 3% average error) when no noise was present in the DRO. With noise, 87% of Ktrans and 84% of ve algorithm-DRO combinations were generally in the correct order. Low Krippendorff’s alpha values showed that algorithms could not consistently classify patients as above or below the median for a given algorithm at each time point or for differences in values between time points. A majority of the algorithms produced a significant Spearman correlation in ve of the primary gross tumor volume with time. Algorithmic differences in Ktrans and ve values over time indicate limitations in combining/comparing data from distinct DCE-MRI model implementations. Careful cross-algorithm quality-assurance must be utilized as DCE-MRI results may not be interpretable using differing software.

Radiomics studies require many patients in order to power them, thus patients are often combined from different institutions and using different imaging protocols. Various studies have shown that imaging protocols affect radiomics feature values. We examined whether using data from cohorts with controlled imaging protocols improved patient outcome models. We retrospectively reviewed 726 CT and 686 PET images from head and neck cancer patients, who were divided into training or independent testing cohorts. For each patient, radiomics features with different preprocessing were calculated and two clinical variables—HPV status and tumor volume—were also included. A Cox proportional hazards model was built on the training data by using bootstrapped Lasso regression to predict overall survival. The effect of controlled imaging protocols on model performance was evaluated by subsetting the original training and independent testing cohorts to include only patients whose images were obtained using the same imaging protocol and vendor. Tumor volume, HPV status, and two radiomics covariates were selected for the CT model, resulting in an AUC of 0.72. However, volume alone produced a higher AUC, whereas adding radiomics features reduced the AUC. HPV status and one radiomics feature were selected as covariates for the PET model, resulting in an AUC of 0.59, but neither covariate was significantly associated with survival. Limiting the training and independent testing to patients with the same imaging protocol reduced the AUC for CT patients to 0.55, and no covariates were selected for PET patients. Radiomics features were not consistently associated with survival in CT or PET images of head and neck patients, even within patients with the same imaging protocol.

Radiomics studies require large patient cohorts, which often include patients imaged using different imaging protocols. We aimed to determine the impact of variability in imaging protocol parameters and interscanner variability using a phantom that produced feature values similar to those of patients. Positron emission tomography (PET) scans of a Hoffman brain phantom were acquired on GE Discovery 710, Siemens mCT, and Philips Vereos scanners. A standard-protocol scan was acquired on each machine, and then each parameter that could be changed was altered individually. The phantom was contoured with 10 regions of interest (ROIs). Values for 45 features with 2 different preprocessing techniques were extracted for each image. To determine the impact of each parameter on the reliability of each radiomics feature, the intraclass correlation coefficient (ICC) was calculated with the ROIs as the subjects and the parameter values as the raters. For interscanner comparisons, we compared the standard deviation of each radiomics feature value from the standard-protocol images to the standard deviation of the same radiomics feature from PET scans of 224 patients with non-small cell lung cancer. When the pixel size was resampled prior to feature extraction, all features had good reliability (ICC > 0.75) for the field of view and matrix size. The time per bed position had excellent reliability (ICC > 0.9) on all features. When the filter cutoff was restricted to values below 6 mm, all features had good reliability. Similarly, when subsets and iterations were restricted to reasonable values used in clinics, almost all features had good reliability. The average ratio of the standard deviation of features on the phantom scans to that of the NSCLC patient scans was 0.73 using fixed-bin-width preprocessing and 0.92 using 64-level preprocessing. Most radiomics feature values had at least good reliability when imaging protocol parameters were within clinically used ranges. However, interscanner variability was about equal to interpatient variability; therefore, caution must be used when combining patients scanned on equipment from different vendors in radiomics data sets.

Normal tissue toxicity is an important consideration in the continued development of more effective external beam radiotherapy (EBRT) regimens for head and neck tumors. The ability to detect EBRT-induced changes in mandibular bone vascularity represents a crucial step in decreasing potential toxicity. To date, no imaging modality has been shown to detect changes in bone vascularity in real time during treatment. Based on our institutional experience with multi-parametric MRI, we hypothesized that DCE-MRI can provide in-treatment information regarding EBRT-induced changes in mandibular vascularity. Thirty-two patients undergoing EBRT treatment for head and neck cancer were prospectively imaged prior to, mid-course and following treatment. DCE-MRI scans were co-registered to dosimetric maps to correlate EBRT dose and change in mandibular bone vascularity as measured by Ktrans and Ve. DCE-MRI was able to detect dose-dependent changes in both Ktrans and Ve in a subset of patients. One patient who developed ORN during the study period demonstrated decreases in Ktrans and Ve following treatment completion. We demonstrate, in a prospective imaging trial, that DCE-MRI can detect dose-dependent alterations in mandibular bone vascularity during chemoradiotherapy, providing biomarkers that are physiological correlates of acute of acute mandibular vascular injury and recovery temporal kinetics.

Microbeam radiation therapy (MRT) uses an array of high-dose, narrow (~100 μm) beams separated by a fraction of a millimeter to treat various radio-resistant, deep-seated tumors. MRT has been shown to spare normal tissue up to 1000 Gy of entrance dose while still being highly tumoricidal. Current methods of tumor localization for our MRT treatments require MRI and X-ray imaging with subject motion and image registration that contribute to the measurement error. The purpose of this study is to develop a novel form of imaging to quickly and accurately assist in high resolution target positioning for MRT treatments using X-ray fluorescence (XRF). The key to this method is using the microbeam to both treat and image. High Z contrast media is injected into the phantom or blood pool of the subject prior to imaging. Using a collimated spectrum analyzer, the region of interest is scanned through the MRT beam and the fluorescence signal is recorded for each slice. The signal can be processed to show vascular differences in the tissue and isolate tumor regions. Using the radiation therapy source as the imaging source, repositioning and registration errors are eliminated. A phantom study showed that a spatial resolution of a fraction of microbeam width can be achieved by precision translation of the mouse stage. Preliminary results from an animal study showed accurate iodine profusion, confirmed by CT. The proposed image guidance method, using XRF to locate and ablate tumors, can be used as a fast and accurate MRT treatment planning system.

Purpose: To test the feasibility of using 3D-printed patient-specific phantoms for intensity-modulated radiation therapy (IMRT) quality assurance (QA). Methods: We created a patient-specific whole-head phantom using a 3D printer. The printer data file was created from high-resolution DICOM computed tomography (CT) images of 3-year old child treated at our institution for medulloblastoma. A custom-modified extruder system was used to create tissue-equivalent materials. For the printing process, the Hounsfield Units from the CT images were converted to proportional volumetric densities. A 5-field IMRT plan was created from the patient CT and delivered to the 3D- phantom. Dose was measured by an ion chamber placed through the eye. The ion chamber was placed at the posterior edge of the planning target volume in a high dose gradient region. CT scans of the patient and 3D-phantom were fused by using commercial treatment planning software (TPS). The patient’s plan was calculated on the phantom CT images. The ion chamber’s active volume was delineated in the TPS; dose per field and total dose were obtained. Measured and calculated doses were compared. Results: The 3D-phantom dimensions and tissue densities were in good agreement with the patient. However, because of a printing error, there was a large discrepancy in the density in the frontal cortex. The calculated and measured treatment plan doses were 1.74 Gy and 1.72 Gy, respectively. For individual fields, the absolute dose difference between measured and calculated values was on average 3.50%. Conclusion: This study demonstrated the feasibility of using 3D-printed patient-specific phantoms for IMRT QA. Such phantoms would be particularly advantageous for complex IMRT treatment plans featuring high dose gradients and/or for anatomical sites with high variation in tissue densities. Our preliminary findings are promising. We anticipate that, once the printing process is further refined, the agreement between measured and calculated doses will improve.

Micro-beam radiation therapy (MRT) uses parallel planes of high dose narrow (10–100 um in width) radiation beams separated by a fraction of a millimeter to treat cancerous tumors. This experimental therapy method based on synchrotron radiation has been shown to spare normal tissue at up to 1000Gy of entrance dose while still being effective in tumor eradication and extending the lifetime of tumor-bearing small animal models. Motion during the treatment can result in significant movement of micro beam positions resulting in broader beam width and lower peak to valley dose ratio (PVDR), and thus can reduce the effectiveness of the MRT. Recently we have developed the first bench-top image guided MRT system for small animal treatment using a high powered carbon nanotube (CNT) x-ray source array. The CNT field emission x-ray source can be electronically synchronized to an external triggering signal to enable physiologically gated firing of x-ray radiation to minimize motion blurring. Here we report the results of phantom study of respiratory gated MRT. A simulation of mouse breathing was performed using a servo motor. Preliminary results show that without gating the micro beam full width at tenth maximum (FWTM) can increase by 70% and PVDR can decrease up to 50%. But with proper gating, both the beam width and PVDR changes can be negligible. Future experiments will involve irradiation of mouse models and comparing histology stains between the controls and the gated irradiation.

Purpose: To determine the correlation between dose and changes through treatment in dynamic contrast enhanced (DCE) MRI voxel parameters (Ktrans, kep, Ve, and Vp) within salivary glands of head and neck oropharyngeal squamous cell carcinoma (HNSCC) patients. Methods: 17 HNSCC patients treated with definitive radiation therapy completed DCE-MRI scans on a 3T scanner at pre-treatment, mid-treatment, and post-treatment time points. Mid-treatment and post-treatment DCE images were deformably registered to pre-treatment DCE images (Velocity software package). Pharmacokinetic analysis of the DCE images used a modified Tofts model to produce parameter maps with an arterial input function selected from each patient's perivertebral space on the image (NordicICE software package). In-house software was developed for voxel-by-voxel longitudinal analysis of the salivary glands within the registered images. The planning CT was rigidly registered to the pre-treatment DCE image to obtain dose values in each voxel. Voxels within the lower and upper dose quartiles for each gland were averaged for each patient, then an average of the patients’ means for the two quartiles were compared. Dose-relationships were also assessed by Spearman correlations between dose and voxel parameter changes for each patient's gland. Results: Changes in parameters’ means between time points were observed, but inter-patient variability was high. Ve of the parotid was the only parameter that had a consistently significant longitudinal difference between dose quartiles. The highest Spearman correlation was Vp of the sublingual gland for the change in the pre-treatment to mid-treatment values with only a ρ=0.29. Conclusion: In this preliminary study, there was large inter-patient variability in the changes of DCE voxel parameters with no clear relationship with dose. Additional patients may reduce the uncertainties and allow for the determination of the existence of parameter and dose relationships.

Purpose: Microbeam radiation therapy (MRT) uses narrow planes of high dose radiation beams to treat cancerous tumors. This experimental therapy method based on synchrotron radiation has been shown to spare normal tissue at up to 1000 Gy of peak entrance dose while still being effective in tumor eradication and extending the lifetime of tumor-bearing small animal models. Motion during treatment can lead to significant movement of microbeam positions resulting in broader beam width and lower peak to valley dose ratio (PVDR), which reduces the effectiveness of MRT. Recently, the authors have demonstrated the feasibility of generating microbeam radiation for small animal treatment using a carbon nanotube (CNT) x-ray source array. The purpose of this study is to incorporate physiological gating to the CNT microbeam irradiator to minimize motion-induced microbeam blurring. Methods: The CNT field emission x-ray source array with a narrow line focal track was operated at 160 kVp. The x-ray radiation was collimated to a single 280 μm wide microbeam at entrance. The microbeam beam pattern was recorded using EBT2 Gafchromic© films. For the feasibility study, a strip of EBT2 film was attached to an oscillating mechanical phantom mimicking mouse chest respiratory motion. The servo arm was put against a pressure sensor to monitor the motion. The film was irradiated with three microbeams under gated and nongated conditions and the full width at half maximums and PVDRs were compared. An in vivo study was also performed with adult male athymic mice. The liver was chosen as the target organ for proof of concept due to its large motion during respiration compared to other organs. The mouse was immobilized in a specialized mouse bed and anesthetized using isoflurane. A pressure sensor was attached to a mouse's chest to monitor its respiration. The output signal triggered the electron extraction voltage of the field emission source such that x-ray was generated only during a portion of the mouse respiratory cycle when there was minimum motion. Parallel planes of microbeams with 12.4 Gy/plane dose and 900 μm pitch were delivered. The microbeam profiles with and without gating were analyzed using γ-H2Ax immunofluorescence staining. Results: The phantom study showed that the respiratory motion caused a 50% drop in PVDR from 11.5 when there is no motion to 5.4, whereas there was only a 5.5% decrease in PVDR for gated irradiation compared to the no motion case. In thein vivo study, the histology result showed gating increased PVDR by a factor of 2.4 compared to the nongated case, similar to the result from the phantom study. The full width at tenth maximum of the microbeam decreased by 40% in gating in vivo and close to 38% with phantom studies. Conclusions: The CNT field emission x-ray source array can be synchronized to physiological signals for gated delivery of x-ray radiation to minimize motion-induced beam blurring. Gated MRT reduces valley dose between lines during long-time radiation of a moving object. The technique allows for more precise MRT treatments and makes the CNT MRT device practical for extended treatment.

Purpose: Microbeam radiation therapy is a promising experimental radiotherapy method for cancer treatment. Synchrotron studies have shown that MRT can preferentially ablate tumors while mostly preserving the surrounding normal tissues. Our purpose is to develop a compact microbeam irradiator that can be accessible for laboratory research on MRT's therapeutic mechanism, with the ultimate goal of translating this technique for clinical applications. Utilizing a carbon nanotube field emission X-ray source array, our lab has developed a first of its kind table-top microbeam irradiator. The purpose of this study is to investigate the possibility of increasing the total dose to the tumor region using spatial and temporal fractionation. Methods: MRI and CT scans were acquired and registered to locate both the target region and the landmark in the treatment coordinate space. A crossbeam treatment configuration was planned to achieve the desired dosage and tumor coverage. One array of 300 μm-thick microbeams was delivered to the target on the first day. Another array, perpendicular to the first one, was delivered the next day targeting the same region. The feasibility of this image-guided MRT procedure was evaluated using a phantom. Gafchromic EBT2 film was employed to characterize the targeting accuracy and the delivered tumormore » dose. Results: The preliminary phantom study showed that a cross-pattern of microbeam arrays was successfully delivered with sub-millimeter targeting accuracy. The delivered dose in the target region was doubled. The fraction of tumor volume that received the peak dose was increased. Conclusion: Temporal fractionation of crosspatterned microbeams can be delivered to the same target region. The feasibility of this procedure was investigated with a phantom study. Once implemented, this procedure has the potential of increasing the tumor control effect of MRT and of achieving better normal tissue recovery.« less

Purpose: Compact microbeam radiation therapy (MRT) recently became feasible through the development of carbon‐nanotube based distributed x‐ray array technology. This work investigates the feasibility of novel highresolution 3D dosimetry techniques (50μm isotropic) for the challenging task of characterizing microbeam irradiations of nominal width 300–400μm. Methods: A cylindrical PRESAGE 3D dosimeter (20mm diameter, 22mm long) was irradiated with three parallel microbeams generated by a prototype compact MRT system for small animal research developed at UNC. The carbon nanotube field emission x‐ray source array is designed to produce x‐rays up to 160 kV which are collimated to microbeam radiation through an external collimator. The entrance dose used in this study was estimated from EBT2 film to be 32 Gy. A 50μm isotropic 3D dose distribution was obtained by imaging the dosimeter in the Duke Micro Optical‐CT Scanner (DMicrOS), an in‐house, bi‐telecentric optical CT system optimized for high‐resolution optical tomography. Preliminary analysis of microbeam characteristics was performed on a ROI averaged across the central 10mm of the dosimeter. Beam width (FWHM), percent depth dose (PDD), and peak‐to‐valley dose ratio (PVDR) were measured as a function of depth along the irradiated beam paths. Results: Beam width measurements indicated that the average FWHM across all three beams remained constant (405.3μm, σ =13.2μm) between depths of 3.00–14.00mm. PDD measurements were normalized to values at 3.00mm depth (to avoid bias due to possible optical artifact at the dosimeter surface) and showed a falloff to 82.9–90.5% at 14.00mm depth. PVDR increased with depth from 6.3 at 3.00mm depth to 8.6 at 14.00mm depth. Conclusion: These preliminary results from the DMicrOS/PRESAGE 3D dosimetry system show strong potential for uniquely comprehensive verification of microbeam irradiations. Future work is required to investigate the potential of stray‐light artifacts in this extreme geometry. NIH R01CA100835

Purpose: Microbeam radiation therapy (MRT) is an experimental pre‐clinical technique using arrays of microscopically‐thin, low‐energy X‐ray radiation to treat radio‐resistant, deep‐seated tumors. All previous MRT experiments were performed using synchrotron radiation. We have developed a compact MRT small animal system using carbon nanotube (CNT) field emission x‐ray technology. Our purpose is to incorporate respiratory gating to the MRT system, minimizing motion blurring and increasing the peak‐to‐valley‐dose ratio (PVDR), which is important for normal tissue sparing. Methods: A prototype CNT MRT system was employed. The intrinsically divergent radiation is collimated into ∼300um microbeams using an external collimator. Parallel microbeam planes were delivered by translating the object perpendicular to the microbeam plane in a step‐and‐shoot fashion. The device generated an average entrance dose rate of 1Gy/minute. For respiratory‐gated irradiation, electron field emission from CNT cathodes was synchronized with the respiratory cycle of the mouse so x‐ray radiation is only extracted during the motionless phase of respiration.A phantom simulating mouse respiration used a servo motor pushing on a pressure sensor in a typical breathing pattern. A control program used the signal to trigger x‐ray irradiation during the motionless phase. Two experiments were run: a single line irradiation at 160 kVp delivering 0.9 Gy/min for 5 minutes, and three such lines of irradiation separated by 900um. Dose profiles were measured with EBT2 Gafchromic dosimetry films. Results: A single beam showed a FWTM increase from 638 to 1088um with un‐gated motion. With gating, the FWTM was 669um, similar to the motionless case.PVDR quantifies MRT effectiveness in the case of multiple lines. Motion reduces PVDR 50 percent; with gating PVDR is almost entirely recovered, 5.5 percent higher than without motion. Conclusion: Gated MRT largely eliminates microbeam broadening from physiological motion, maintaining high PVDR. The technique increases precision and will be tested during MRT treatments.

Purpose: Currently there is lack of dosimetry technology for the compact microbeam radiation therapy device we recently developed using field emission based carbon nanotube cathode technology. This is due to the fact that our beam width can be as small as 250μm, restricting the use of normal characterization methods. We demonstrate that with proper calibration and analysis that Gafchromic EBT2 film can be used to characterize our microbeam irradiator for radiobiological mechanistic studies in mice. Methods: Our compact microbeam radiation therapy device employs a 160mm × 160um focal line and collimator to deliver an orthovoltage microplanar beam. Specialized phantoms were created to properly measure typical dosimetric quantities including PDD and TMR in addition to other quantities specific to microbeam dose distributions and our source. Gafchromic EBT2 film, cross calibrated earlier to a conventional ion chamber in the uncollimated beam, was used for all measurements. Results: While TMR and PDD results for this study were fairly typical, measurements more specific to our source and beam geometry showed unique results. The beam width as a function of distance from the source displayed a steeper increase than would be expected from strictly geometric considerations, probably due to collimator scatter. In addition, the decline in dose with distance from the source was much less severe than expected, as displayed by a linear fit in the tested domain. Conclusion: Gafchromic EBT2 film was an excellent choice for the initial characterization of our experimental microbeam device, as shown by the expected forms of the PDD and TMR curves. In addition, the slower drop in dose with distance from the source is consistent with the fact that our device uses a focal line and not a point. Finally, data gathered here will provide a good starting point for a customized treatment planning system specific to our irradiator.

Purpose: Most commercial dosimeters are not suitable for microbeam radiation therapy (MRT) due to the extremely small (

Purpose: We demonstrate the feasibility of x‐ray fluorescence for quick and accurate image guidance for targeted irradiation of small animal tumor models in Microbeam Radiation Therapy (MRT). Methods: A reduced‐dose treatment beam excites x‐ray fluorescence from contrast agents preferentially‐accumulating at tumor sites. Intensity profiles of the fluorescence signal are mapped as the mouse injected with the contrast agent is moved through the field of view. The tumor location is identified as the regions with high fluorescence intensities. For this feasibility study, our compact small‐animal MRT system and a mouse head phantom were used. The MRT device uses a carbon nanotube (CNT) field emission x‐ray source array operating at 160kVp and adjustable‐width external collimator to generate microbeam radiation at a microbeam dose rate of ∼1Gy/min. A phantom consisting of an acrylic rod inserted into a mouse skull accurately represents the attenuation of the head. The rod contains ∼1.5mm diameter holes separated by 4mm, filled with 12mg/mL iodine solution, similar to the reported tumor concentration from IC injection. The phantom was translated through the treatment beam in 600um steps, 20 seconds per step. The fluorescence signal was recorded using a slit‐collimated spectrum analyzer. Results: Processed spectra displayed fluorescent intensity peaks corresponding with locations of iodine solution in the phantom. The FWHMs of these peaks are 1.78mm and 1.72mm. The actual diameters of corresponding regions are 1.56mm and 1.47mm, indicating ∼250um uncertainty. Conclusion: Preliminary results demonstrated feasibility of x‐ray fluorescence for guidance in MRT. The acquisition time for a 15mm head phantom is ∼8 minutes, within the reported retention time of the contrast agent. ∼250um uncertainty is comparable to results from our in vivo brain tumor‐bearing mouse experiment using MRI and x‐ray image guidance. The x‐ray fluorescent method is substantially faster. The process will be further optimized and validated with in‐vivo studies.