Rachel B. Ger

Dynamic contrast-enhanced MRI detects acute radiotherapy-induced alterations in mandibular microvasculature: Prospective assessment of imaging biomarkers of normal tissue injury

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.

A Multi-Institutional Comparison of Dynamic Contrast-Enhanced Magnetic Resonance Imaging Parameter Calculations

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.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.

Effect of tube current on computed tomography radiomic features

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.

Investigation of radiomic signatures for local recurrence using primary tumor texture analysis in oropharyngeal head and neck cancer patients

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.

Accuracy of deformable image registration on magnetic resonance images in digital and physical phantoms

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 with synthetic MR images. These images were generated from interpatient and intrapatient variation models trained on 28 patients. Four synthetic post‐treatment 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 pretreatment 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, and 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.

Guidelines and experience using imaging biomarker explorer (IBEX) for radiomics

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 IBEXs 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.

Comprehensive Investigation on Controlling for CT Imaging Variabilities in Radiomics Studies

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.

Publisher Correction: A Multi-Institutional Comparison of Dynamic Contrast-Enhanced Magnetic Resonance Imaging Parameter Calculations (Scientific Reports (2017) DOI: 10.1038/s41598-017-11554-w)

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Erratum: Dynamic contrast-enhanced magnetic resonance imaging for head and neck cancers

This corrects the article DOI: 10.1038/sdata.2018.8.

Data descriptor: Dynamic contrastenhanced magnetic resonance imaging for head and neck cancers

Dynamic myraidpro 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.