Automatic Parotid Gland Segmentation in MVCT Using Deep Convolutional Neural Networks

Radiation-induced xerostomia, as a major problem in radiation treatment of the head and neck cancer, is mainly due to the overdose irradiation injury to the parotid glands. Helical Tomotherapy-based megavoltage computed tomography (MVCT) imaging during the Tomotherapy treatment can be applied to monitor the successive variations in the parotid glands. While manual segmentation is time consuming, laborious, and subjective, automatic segmentation is quite challenging due to the complicated anatomical environment of head and neck as well as noises in MVCT images. In this article, we propose a localization-refinement scheme to segment the parotid gland in MVCT. After data pre-processing we use mask region convolutional neural network (Mask R-CNN) in the localization stage after data pre-processing, and design a modified U-Net in the following fine segmentation stage. To the best of our knowledge, this study is a pioneering work of deep learning on MVCT segmentation. Comprehensive experiments based on different data distribution of head and neck MVCTs and different segmentation models have demonstrated the superiority of our approach in terms of accuracy, effectiveness, flexibility, and practicability. Our method can be adopted as a powerful tool for radiation-induced injury studies, where accurate organ segmentation is crucial.

Correlations Between Single-Photon Emission Computed Tomography Parameters of Salivary Glands and Dry Eye Tests in Patients With Sjögren's Syndrome

ObjectiveTo evaluate the correlations between Single-Photon Emission Computed Tomography (SPECT) parameters of salivary glands and dry eye parameters in patients with Sjögren's syndrome (SS).MethodsA total of 28 patients with SS participated in this prospective study. Dry eye assessments include tear film break-up time (TBUT), corneal fluorescein staining scoring (CFS), Schirmer's I test (SIT) examination and SPECT of salivary gland. The following quantitative parameters were derived from SPECT imaging for salivary glands: Uptake index (UI), the time needed to achieve the minimum counts after Vit C stimulation (Ts), and excretion fraction (EF). The relation between the aforementioned parameters and TBUT, CFS and SIT were analyzed with SPSS 22.0 software.ResultsAll the 28 eyes of the 28 subjects were examined. The mean SIT was 6.04 ± 4.64 mm/5 min (0–18 mm/5 min); the mean CFS was 3.07 ± 2.65 (0–10) and the mean BUT was 2.11 ± 1.97 s (0–9 s). The mean EF value was 0.52 ± 0.12 (0.26–0.75) in parotid glands and 0.45 ± 0.10 (0.30–0.67) in submandibular glands, respectively. The mean UI value was 9.33 ± 1.68 (6.03–13.20) in parotid glands and 9.92 ± 1.48 (7.08–12.60) in submandibular glands, respectively. The mean Ts (min) was 5.32 ± 3.01 (2.00–12.00) in parotid glands and 11.09 ± 7.40 (2.00- 29.00 min) in submandibular glands, respectively. It was found that EF positively correlates with SIT in patients with SS (r = 0.499 and 0.426 in parotid glands and submandibular glands, with P < 0.05), while no significant correlation was found between the UI, Ts and CFS, TBUT (P > 0.05).ConclusionsThe EF was positively correlated with SIT in patients with SS, it could reflex the dysfunction of salivary glands in SS patients. So, EF may be a valuable parameter for the diagnosis of SS patients with lacrimal gland secretion dysfunction.

Evaluation of plan robustness on the dosimetry of volumetric arc radiotherapy (VMAT) with set-up uncertainty in Nasopharyngeal carcinoma (NPC) radiotherapy

Purpose To evaluate the sensitivity to set up the uncertainty of VMAT plans in Nasopharyngeal carcinoma (NPC) treatment by proposing a plan robustness evaluation method. Methods 10 patients were selected for this study. A 2-arc volumetric-modulated arc therapy (VMAT) plan was generated for each patient using Varian Eclipse (13.6 Version) treatment planning system (TPS). 5 uncertainty plans (U-plans) were recalculated based on the first 5 times set-up errors acquired from cone-beam computer tomography (CBCT). The dose differences of the original plan and perturbed plan corresponded to the plan robustness for the structure. Tumor control probability (TCP) and normal tissues complication probability (NTCP) were calculated for biological evaluation. Results The mean dose differences of D98% and D95% (ΔD98% and ΔD95%) of PTVp were respectively 3.30 Gy and 2.02 Gy. The ΔD98% and ΔD95% of CTVp were 1.12 Gy and 0.58 Gy. The ΔD98% and ΔD95% of CTVn were 1.39 Gy and 1.03 Gy, distinctively lower than those in PTVn (2.8 Gy and 2.0 Gy). The CTV-to-PTV margin increased the robustness of CTVs. The ΔD98% and ΔD95% of GTVp were 0.56 Gy and 0.33 Gy. GTVn exhibited strong robustness with little variation of D98% (0.64 Gy) and D95% (0.39 Gy). No marked mean dose variations of Dmean were seen. The mean reduction of TCP (ΔTCP) in GTVp and CTVp were respectively 0.4% and 0.3%. The mean ΔTCPs of GTVn and CTVn were 0.92% and 1.3% respectively. The CTV exhibited the largest ΔTCP (2.2%). In OARs, the brain stem exhibited weak robustness due to their locations in the vicinity of PTV. Bilateral parotid glands were sensitive to set-up uncertainty with a mean reduction of NTCP (ΔNTCP) of 6.17% (left) and 7.70% (right). The Dmax of optical nerves and lens varied slightly. Conclusion VMAT plans had a strong sensitivity to set-up uncertainty in NPC radiotherapy, with increasing risk of underdose of tumor and overdose of vicinal OARs. We proposed an effective method to evaluate the plan robustness of VMAT plans. Plan robustness and complexity should be taken into account in photon radiotherapy.

Estimating the Entrance Surface Dose in the Eyes, Thyroid, and Parotid Gland Regions in Adult and Pediatric Groups: A Cone-Beam Computed Tomography Technique

Purpose: This study aimed to determine the Entrance Surface Dose (ESD) of sensitive organs in Cone-Beam Computed Tomography (CBCT) imaging of the maxillofacial region in the two age groups of adult and pediatric. Materials and Methods: In this work, the measurements were performed using Thermo Luminescent Dosimeters (TLD-GR200). The imaging was performed using a PROMAX 3D CBCT scanner for 30 adults and 20 pediatric patients. The ESD value for each patient in the region of eyes, thyroid, and parotid glands was measured by 15 TLDs during CBCT of maxillofacial. Results: The highest and lowest mean values of ESDs were related to the parotid and thyroid gland regions in adults, 4.77 ± 0.61 mGy and 0.37 ± 0.16 mGy, respectively. In addition, these values were obtained 2.97 ± 0.36 mGy and 0.35 ± 0.12 mGy in pediatric groups as the highest and lowest values in that order. The results showed that the ESD values of the parotid gland regions in maxilla and mandible examinations had a significant difference (P <0.05). In addition, there was a significant difference between the ESD values of the parotid gland regions among the adults and pediatric groups (P <0.05). Conclusion: According to the results, the ESD values in both age groups were higher in the parotid gland region during maxillofacial CBCT examinations. Therefore, it is recommended to set radiation parameters like mAs as low as possible for reducing the patient dose, especially pediatric patients due to the more sensitive organs.

Transient Activation of Hedgehog Signaling Inhibits Cellular Senescence and Inflammation in Radiated Swine Salivary Glands through Preserving Resident Macrophages

Salivary gland function is commonly and irreversibly damaged by radiation therapy for head and neck cancer. This damage greatly decreases the patient’s quality of life and is difficult to remedy. Previously, we found that the transient activation of Hedgehog signaling alleviated salivary hypofunction after radiation in both mouse and pig models through the inhibition of radiation-induced cellular senescence that is mediated by resident macrophages in mouse submandibular glands. Here we report that in swine parotid glands sharing many features with humans, the Hedgehog receptor PTCH1 is mainly expressed in macrophages, and levels of PTCH1 and multiple macrophage markers are significantly decreased by radiation but recovered by transient Hedgehog activation. These parotid macrophages mainly express the M2 macrophage marker ARG1, while radiation promotes expression of pro-inflammatory cytokine that is reversed by transient Hedgehog activation. Hedgehog activation likely preserves parotid macrophages after radiation through inhibition of P53 signaling and consequent cellular senescence. Consistently, VEGF, an essential anti-senescence cytokine downstream of Hedgehog signaling, is significantly decreased by radiation but recovered by transient Hedgehog activation. These findings indicate that in the clinically-relevant swine model, transient Hedgehog activation restores the function of irradiated salivary glands through the recovery of resident macrophages and the consequent inhibition of cellular senescence and inflammation.

Quality Assurance Assessment of Diffusion-Weighted and T2-Weighted Magnetic Resonance Imaging Registration and Contour Propagation for Head and Neck Cancer Radiotherapy

Background/Purpose: Adequate image registration of anatomic and functional MRI scans is necessary for MR-guided head and neck cancer (HNC) adaptive radiotherapy planning. Despite the quantitative capabilities of diffusion-weighted imaging (DWI) MRI for treatment plan adaptation, geometric distortion remains a considerable limitation. Therefore, we systematically investigated various deformable image registration (DIR) algorithms to co-register DWI and T2-weighted (T2W) images. Materials/Methods: We compared post-acquisition registration algorithms from three software packages (ADMIRE, Velocity, and 3D Slicer) applied to T2W and DWI MRI images in twenty HNC patients. In addition, we investigated implicit rigid registration (no algorithm applied) as a control comparator. Ground truth segmentations of radiotherapy structures (tumor and organs at risk) were generated by a physician expert on both image sequences. Three additional experts provided segmentations for five cases for interobserver variability studies. For each registration approach, structures were propagated from T2W to DWI images. These propagated structures were then compared with ground truth DWI structures using the Dice similarity coefficient (DSC), false-negative DSC, false-positive DSC, surface DSC, 95% Hausdorff distance, and mean surface distance. Results: 19 left submandibular glands, 18 right submandibular glands, 20 left parotid glands, 20 right parotid glands, 20 spinal cords, 9 brainstems, and 12 tumors were delineated. ADMIRE, the atlas-based auto segmentation DIR algorithm, demonstrated improved performance over implicit rigid registrations for most comparison metrics and structures (Bonferroni-corrected p < 0.05), while Velocity and 3D Slicer algorithms did not. Moreover, the ADMIRE methods significantly improved performance in individual and pooled analysis compared to all other methods. Interobserver variability analysis revealed no significant difference between observers (p > 0.05). Conclusions: Certain deformable registration software packages, such as those provided by ADMIRE, may be favorable for registering T2W and DWI images. These results are important to ensure the appropriate selection of registration strategies for MR-guided radiotherapy.

Bilateral Submandibular Gland Aplasia: An Unusual Cause of Sublingual Swelling—The Role of Imaging in Patient Management

There are very limited reports of aplasia of bilateral submandibular glands. We report the case of a 55-year-old male who presented with nontender palpable sublingual masses. On computed tomography and magnetic resonance imaging, bilateral submandibular gland aplasia and compensatory hypertrophy of bilateral parotid and sublingual glands were seen with herniation of hypertrophied sublingual glands through the bilateral mylohyoid muscles presenting as palpable sublingual region masses. Additional finding of bilateral accessory parotid glands was also noted. Prolapsed hypertrophied sublingual glands should be considered in patients presenting with bilateral sublingual masses to avoid unnecessary invasive procedures. We suggest radiological evaluation of such cases prior to any intervention.

Imaging Features and Pathological Analysis of 43 Parotid Basal Cell Adenomas

Purpose. To investigate the correlation between sonographic and computed tomography and pathological features of basal cell adenomas (BCAs) of the parotid gland. Methods. This retrospective study included 41 patients (43 tumors) with BCAs. The tumors were divided into three types based on their location in the parotid gland and their imaging features. The features of the tumors were analyzed. Results. Imaging manifestations and corresponding pathological results of most BCAs of the parotid glands resembled those of benign parotid gland tumors. Malignant transformation occurred in membranous BCAs and in those with extensive cribriform structures. Type-II and type-III tumors accounted for 82.93% of the total proportion. Thirteen tumors showed cystic degeneration with 30.23%, among which type-III tumors could easily develop cystic degeneration. These cystic areas might correspond to cystic degeneration or focal necrosis. Cystic change was not dependent on the tumor size. The pathological features of the tumors were correlated to their imaging manifestations. Conclusion. Most BCAs of the parotid glands have imaging manifestations similar to those of benign parotid gland tumors. BCAs with extensive cribriform structures and of the membranous type can show malignant transformation and should be treated with caution in clinical practice.

Quantitative assessment of dry mouth in scrub typhus using salivary scintigraphy

Scrub typhus is an acute febrile illness caused by the intracellular pathogen Orientia tsutsugamushi. The clinical features include fever, myalgia, lymphadenopathy, and dry mouth. However, no studies have assessed the symptom of dry mouth in patients with scrub typhus. We investigated the pattern of salivary scintigraphy during the acute febrile state and compared it with any changes after treatment. Fourteen patients underwent both pre- and post-treatment salivary scintigraphy. Imaging analysis was conducted using radioactivity in the oral cavity, parotid glands, and submandibular glands. During the acute phase, the radioactivity in the oral cavity markedly decreased, while that in the parotid and submandibular glands was preserved. After treatment, radioactivity in the oral cavity showed a significant increase at 20-min, 40-min, and after wash-out. The ejection fraction (%) of the parotid glands also increased after treatment. In contrast, the radioactivity levels of the parotid and submandibular glands were not statistically different after treatment. Salivary scintigraphy indicated that insufficient saliva excretion from the salivary glands into the oral cavity was one reason for the dry mouth reported by patients with scrub typhus. In the future, salivary scintigraphy imaging could contribute to the evaluation of dry mouth in patients with scrub typhus.

Dosimetric Results for Adjuvant Proton Radiation Therapy of HPV-Associated Oropharynx Cancer

Purpose One significant advantage of proton therapy is its ability to improve normal tissue sparing and toxicity mitigation, which is relevant in the treatment of oropharyngeal squamous cell carcinoma (OPSCC). Here, we report our institutional experience and dosimetric results with adjuvant proton radiation therapy (PRT) versus intensity-modulated radiotherapy (IMRT) for Human Papilloma Virus (HPV)-associated OPSCC. Materials and Methods This was a retrospective, single institutional study of all patients treated with adjuvant PRT for HPV-associated OPSCC from 2015 to 2019. Each patient had a treatment-approved equivalent IMRT plan to serve as a reference. Endpoints included dosimetric outcomes to the organs at risk (OARs), local regional control (LRC), progression-free survival (PFS), and overall survival (OS). Descriptive statistics, a 2-tailed paired t test for dosimetric comparisons, and the Kaplan-Meier method for disease outcomes were used. Results Fifty-three patients were identified. Doses delivered to OARs compared favorably for PRT versus IMRT, particularly for the pharyngeal constrictors, esophagus, larynx, oral cavity, and submandibular and parotid glands. The achieved normal tissue sparing did not negatively impact disease outcomes, with 2-year LRC, PFS, and OS of 97.0%, 90.3%, and 97.5%, respectively. Conclusion Our study suggests that meaningful normal tissue sparing in the postoperative setting is achievable with PRT, without impacting disease outcomes.