Yao Ding

Magnetic Resonance Imaging of Glucose Uptake and Metabolism in Patients with Head and Neck Cancer

Imaging metabolic dysfunction, a hallmark of solid tumors, usually requires radioactive tracers. Chemical exchange saturation transfer (CEST) imaging can potentially detect and visualize glucose uptake and metabolism, without the need for radioisotopes. Here, we tested the feasibility of using glucose CEST (glucoCEST) to image unlabeled glucose uptake in head and neck cancer by using a clinical 3T magnetic resonance imaging (MRI) scanner. The average CEST contrast between tumors and normal tissue in 17 patients was 7.58% (P = 0.006) in the 3–4 ppm offset frequency range and 5.06% (P = 0.02) in 1–5 ppm range. In a subgroup of eight patients, glucoCEST signal enhancement was higher in tumors than in normal muscle (4.98% vs. 1.28%, P < 0.021). We conclude that glucoCEST images of head and neck cancer can be obtained with a clinical 3T MRI scanner.

Prospective observer and software-based assessment of magnetic resonance imaging quality in head and neck cancer: Should standard positioning and immobilization be required for radiation therapy applications?

PURPOSE The purpose of this study was to investigate the potential of a head and neck magnetic resonance simulation and immobilization protocol on reducing motion-induced artifacts and improving positional variance for radiation therapy applications. METHODS AND MATERIALS Two groups (group 1, 17 patients; group 2, 14 patients) of patients with head and neck cancer were included under a prospective, institutional review board-approved protocol and signed informed consent. A 3.0-T magnetic resonance imaging (MRI) scanner was used for anatomic and dynamic contrast-enhanced acquisitions with standard diagnostic MRI setup for group 1 and radiation therapy immobilization devices for group 2 patients. The impact of magnetic resonance simulation/immobilization was evaluated qualitatively by 2 observers in terms of motion artifacts and positional reproducibility and quantitatively using 3-dimensional deformable registration to track intrascan maximum motion displacement of voxels inside 7 manually segmented regions of interest. RESULTS The image quality of group 2 (29 examinations) was significantly better than that of group 1 (50 examinations) as rated by both observers in terms of motion minimization and imaging reproducibility (P < .0001). The greatest average maximum displacement was at the region of the larynx in the posterior direction for patients in group 1 (17 mm; standard deviation, 8.6 mm), whereas the smallest average maximum displacement was at the region of the posterior fossa in the superior direction for patients in group 2 (0.4 mm; standard deviation, 0.18 mm). Compared with group 1, maximum regional motion was reduced in group 2 patients in the oral cavity, floor of mouth, oropharynx, and larynx regions; however, the motion reduction reached statistical significance only in the regions of the oral cavity and floor of mouth (P < .0001). CONCLUSIONS The image quality of head and neck MRI in terms of motion-related artifacts and positional reproducibility was greatly improved by use of radiation therapy immobilization devices. Consequently, immobilization with external and intraoral fixation in MRI examinations is required for radiation therapy application.

Intravoxel incoherent motion imaging kinetics during chemoradiotherapy for human papillomavirus-associated squamous cell carcinoma of the oropharynx: Preliminary results from a prospective pilot study

This study aims to identify the temporal kinetics of intravoxel incoherent motion (IVIM) MRI in patients with human papillomavirus‐associated (HPV+) oropharyngeal squamous cell carcinoma. Patients were enrolled under an Institutional Review Board (IRB)‐approved protocol as part of an ongoing prospective clinical trial. All patients underwent two MRI studies: a baseline scan before chemoradiotherapy and a mid‐treatment scan 3–4 weeks after treatment initiation. Parametric maps representing pure diffusion coefficient (D), pseudo‐diffusion coefficient (D*), perfusion fraction (f) and apparent diffusion coefficient (ADC) were generated. The Mann–Whitney U‐test was used to assess the temporal variation of IVIM metrics. Bayesian quadratic discriminant analysis (QDA) was used to evaluate the extent to which mid‐treatment changes in IVIM metrics could be combined to predict sites that would achieve complete response (CR) in multivariate analysis. Thirty‐one patients were included in the final analysis with 59 lesions. Pretreatment ADC and D values of the CR lesions (n = 19) were significantly lower than those of non‐CR lesions (n = 33). Mid‐treatment ADC, D and f values were significantly higher (p < 0.0001) than pretreatment values for all lesions. Each increase in normalized ΔADC of size 0.1 yielded a 1.45‐fold increase in the odds of CR (p < 0.0003), each increase in normalized ΔD of size 0.1 yielded a 1.53‐fold increase in the odds of CR (p < 0.0002), and each unit increase in Δf yielded a 2.29‐fold increase in the odds of CR (p < 0.02). Combined ΔD and ΔADC were integrated into a multivariate prediction model and attained an AUC of 0.87 (95% confidence interval: 0.79, 0.96), as well as a sensitivity of 0.63, specificity of 0.85 and accuracy of 0.78, under leave‐one‐out cross‐validation. In conclusion, IVIM is feasible and potentially useful in the prediction and assessment of the early response of HPV+ oropharyngeal squamous cell carcinoma to chemoradiotherapy. Copyright

Magnetic resonance imaging of swallowing-related structures in nasopharyngeal carcinoma patients receiving IMRT: Longitudinal dose-response characterization of quantitative signal kinetics

BACKGROUND We aim to characterize serial (i.e., acute and late) MRI signal intensity (SI) changes in dysphagia-associated structures as a function of radiotherapy (RT) in nasopharyngeal cancer (NPC) patients. MATERIALS AND METHODS We retrospectively extracted data on 72 patients with stage III-IV NPC treated with intensity-modulated RT (IMRT). The mean T1- and T2-weighted MRI SIs were recorded for the superior pharyngeal constrictor (SPC) and soft palate (SP) at baseline, early-after IMRT, and last follow up, with normalization to structures receiving <5 Gy. RESULTS All structures had a significant increase in T2 SIs early after treatment, irrespective of the mean dose given. At last follow-up, the increase in T2 SI subsided completely for SPC and partially for SP. The T1 SI did not change significantly in early follow-up images of both structures; on late follow-up, patients with mean doses >62.25 Gy had a significant decrease in the corresponding T1 SI for SPC (1.6 ± 0.4 vs. 1.3 ± 0.4, P=0.007) but decreased non-significantly for SP. CONCLUSIONS Serial MRI acquisitions enable the identification of both early and late radiation-induced changes in swallowing structures after definitive IMRT for NPC. Dose dependent decrease in late T1 SI is associated with higher RT doses to the superior pharyngeal constrictor muscle; while dose independent increase in SI for both structures in early post-RT T2 images is observed and subsides after therapy. Further efforts will seek to elucidate the relationship between dose-dependent muscle SI changes and functional alteration of swallowing muscles.

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.

Matched computed tomography segmentation and demographic data for oropharyngeal cancer radiomics challenges

Cancers arising from the oropharynx have become increasingly more studied in the past few years, as they are now epidemic domestically. These tumors are treated with definitive (chemo)radiotherapy, and have local recurrence as a primary mode of clinical failure. Recent data suggest that ‘radiomics’, or extraction of image texture analysis to generate mineable quantitative data from medical images, can reflect phenotypes for various cancers. Several groups have shown that developed radiomic signatures, in head and neck cancers, can be correlated with survival outcomes. This data descriptor defines a repository for head and neck radiomic challenges, executed via a Kaggle in Class platform, in partnership with the MICCAI society 2016 annual meeting.These public challenges were designed to leverage radiomics and/or machine learning workflows to discriminate HPV phenotype in one challenge (HPV status challenge) and to identify patients who will develop a local recurrence in the primary tumor volume in the second one (Local recurrence prediction challenge) in a segmented, clinically curated anonymized oropharyngeal cancer (OPC) data set.

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.

TU‐F‐CAMPUS‐I‐01: Head and Neck Squamous Cell Carcinoma: Short‐Term Repeatability of Apparent Diffusion Coefficient and Intravoxel Incoherent Motion Parameters at 3.0T

Purpose: Many published studies have recently demonstrated the potential value of intravoxel incoherent motion (IVIM) analysis for disease evaluation. However, few have questioned its measurement repeatability/reproducibility when applied. The purpose of this study was to determine the short-term measurement repeatability of apparent diffusion coefficient ADC, true diffusion coefficient D, pseudodiffusion coefficient D* and perfusion fraction f, in head and neck squamous cell carcinoma (HNSCC) primary tumors and metastatic nodes. Methods: Ten patients with known HNSCC were examined twice using echo-planar DW-MRI with 12 b values (0 to 800 s/mm2) 1hour to 24 hours apart before radiation treatment. All patients were scanned with the customized radiation treatment immobilization devices to reduce motion artifacts and to improve image registration in repeat scans. Regions of interests were drawn in primary tumor and metastases node in each patient (Fig. 1). ADC and IVIM parameters D, D* and f were calculated by least squares data fitting. Short-term test–retest repeatability of ADC and IVIM parameters were assessed by measuring Bland–Altman limits of agreements (BA-LA). Results: Sixteen HNSCC lesions were assessed in 10 patients. Repeatability of perfusion-sensitive parameters, D* and f, in HNSCC lesions was poor (BA-LA: -144% to 88% and −57% to 96% for D* and f, respectively); a lesser extent was observed for the diffusion-sensitive parameters of ADC and D (BA-LA: −34% to 39% and −37% to 40%, for ADC and D, respectively) (Fig. 2). Conclusion: Poor repeatability of D*/f and good repeatability for ADC/D were observed in HNSCC primary tumors and metastatic nodes. Efforts should be made to improve the measurement repeatability of perfusion-sensitive IVIM parameters.

Prospective in silico study of the feasibility and dosimetric advantages of MRI-guided dose adaptation for human papillomavirus positive oropharyngeal cancer patients compared with standard IMRT

Highlights • The average dose to 95% of initial PTV volume was 70.7 Gy for standard plans vs. 58.5 Gy for adaptive plans.• MRI-guided adaptive approach resulted in decrease dose to normal tissue compared with standard plans.• NTCP of post-treatment dysphagia, feeding tube, and hypothyroidism were reduced using the adaptive approach.