Shallow kinetics induced by a metronome (SKIM): A novel contactless respiratory motion management.

OBJECTIVES: As an alternative to conventional compression amidst the COVID-19 pandemic, we developed a contactless motion management strategy. By increasing the patient's breathing rate to induce shallow breathing with the aid of a metronome, our hypothesis is that the motion magnitude of the target may be minimized without physical contact or compression. METHODS: Fourteen lung stereotactic body radiation therapy (SBRT) patients treated under fast shallow-breathing (FSB) were selected for inclusion in this retrospective study. Our proposed method is called shallow kinetics induced by a metronome (SKIM). We induce FSB by setting the beats-per-minute (BPM) high (typically in the range of 50-60). This corresponded to a patient breathing rate of 25-30 (breathing) cycles per minute. The magnitude of target motion in 3D under SKIM was evaluated using 4DCT datasets. Comparison with free breathing (FB) 4DCT was also made for a subset for which FB data available. RESULTS: The overall effectiveness of SKIM was evaluated with 18 targets (14 patients). Direct comparison with FB was performed with 12 targets (10 patients). The vector norm mean ± SD value of motion magnitude under SKIM for 18 targets was 8.2 ± 4.1 mm. The mean ± SD metronome BPM was 54.9 ± 4.0 in this group. The vector norm means ± SD values of target motion for FB and SKIM in the 12 target sub-group were 14.6 ± 8.5 mm and 9.3 ± 3.7 mm, respectively. The mean ± SD metronome BPM for this sub-group was 56.3 ± 2.5. CONCLUSION: Compared with FB, SKIM can significantly reduce respiratory motion magnitude of thoracic targets. The difference in maximum motion reduction in the overall vector norm, S-I, and A-P directions was significant (p = 0.033, 0.042, 0.011). Our proposed method can be an excellent practical alternative to conventional compression due to its flexibility and ease of implementation.

Molecular Imaging Investigations of Polymer-Coated Cerium Oxide Nanoparticles as a Radioprotective Therapeutic Candidate.

Cerium oxide nanoparticles (CONPs) have a unique surface redox chemistry that appears to selectively protect normal tissues from radiation induced damage. Our prior research exploring the biocompatibility of polymer-coated CONPs found further study of poly-acrylic acid (PAA)-coated CONPs was warranted due to improved systemic biodistribution and rapid renal clearance. This work further explores PAA-CONPs' radioprotective efficacy and mechanism of action related to tumor microenvironment pH. An ex vivo TUNEL assay was used to measure PAA-CONPs' protection of the irradiated mouse colon in comparison to the established radioprotector amifostine. [18F]FDG PET imaging of spontaneous colon tumors was utilized to determine the effects of PAA-CONPs on tumor radiation response. In vivo MRI and an ex vivo clonogenic assay were used to determine pH effects on PAA-CONPs' radioprotection in irradiated tumor-bearing mice. PAA-CONPs showed excellent radioprotective efficacy in the normal colon that was equivalent to uncoated CONPs and amifostine. [18F]FDG PET imaging showed PAA-CONPs do not affect tumor response to radiation. Normalization of tumor pH allowed some radioprotection of tumors by PAA-CONPs, which may explain their lack of tumor radioprotection in the acidic tumor microenvironment. Overall, PAA-CONPs meet the criteria for clinical application as a radioprotective therapeutic agent and are an excellent candidate for further study.

Automated Lung Cancer Segmentation Using a PET and CT Dual-Modality Deep Learning Neural Network.

PURPOSE: To develop an automated lung tumor segmentation method for radiation therapy planning based on deep learning and dual-modality positron emission tomography (PET) and computed tomography (CT) images. METHODS AND MATERIALS: A 3-dimensional (3D) convolutional neural network using inputs from diagnostic PETs and simulation CTs was constructed with 2 parallel convolution paths for independent feature extraction at multiple resolution levels and a single deconvolution path. At each resolution level, the extracted features from the convolution arms were concatenated and fed through the skip connections into the deconvolution path that produced the tumor segmentation. Our network was trained/validated/tested by a 3:1:1 split on 290 pairs of PET and CT images from patients with lung cancer treated at our clinic, with manual physician contours as the ground truth. A stratified training strategy based on the magnitude of the gross tumor volume (GTV) was investigated to improve performance, especially for small tumors. Multiple radiation oncologists assessed the clinical acceptability of the network-produced segmentations. RESULTS: The mean Dice similarity coefficient, Hausdorff distance, and bidirectional local distance comparing manual versus automated contours were 0.79 ± 0.10, 5.8 ± 3.2 mm, and 2.8 ± 1.5 mm for the unstratified 3D dual-modality model. Stratification delivered the best results when the model for the large GTVs (>25 mL) was trained with all-size GTVs and the model for the small GTVs (<25 mL) was trained with small GTVs only. The best combined Dice similarity coefficient, Hausdorff distance, and bidirectional local distance from the 2 stratified models on their corresponding test data sets were 0.83 ± 0.07, 5.9 ± 2.5 mm, and 2.8 ± 1.4 mm, respectively. In the multiobserver review, 91.25% manual versus 88.75% automatic contours were accepted or accepted with modifications. CONCLUSIONS: By using an expansive clinical PET and CT image database and a dual-modality architecture, the proposed 3D network with a novel GTVbased stratification strategy generated clinically useful lung cancer contours that were highly acceptable on physician review.

The long-lasting relationship of distress on radiation oncology-specific clinical outcomes.

PURPOSE: The diagnosis and treatment of cancer can have significant mental health ramifications. The National Comprehensive Cancer Network currently recommends using a distress screening tool to screen patients for distress and facilitate referrals to social service resources. Its association with radiation oncology-specific clinical outcomes has remained relatively unexplored. METHODS AND MATERIALS: With institutional review board approval, National Comprehensive Cancer Network distress scores were collected for patients presenting to our institution for external beam radiation therapy during a 1-year period from 2015 to 2016. The association between distress scores (and associated problem list items and process-related outcomes) and radiation oncology-related outcomes, including inpatient admissions during treatment, missed treatment appointments, duration of time between consultation and treatment, and weight loss during treatment, was considered. RESULTS: A total of 61 patients who received either definitive (49 patients) or palliative (12 patients) treatment at our institution and completed a screening questionnaire were included in this analysis. There was a significant association between an elevated distress score (7+) and having an admission during treatment (36% vs 11%; P = .04). Among the patients treated with definitive intent, missing at least 1 appointment (71% vs 26%; P = .03) and having an admission during treatment (57% vs 10%; P = .009) were significantly associated with our institutional definition of elevated distress. We found no correlation between distress score and weight loss during treatment or a prolonged time between initial consult and treatment start. CONCLUSIONS: High rates of distress are common for patients preparing to receive radiation therapy. These levels may affect treatment compliance and increase rates of hospital admissions. There remains equipoise in the best method to address distress in the oncology patient population. These results may raise awareness of the consequences of distress among radiation oncology patients. Specific interventions to improve distress need further study, but we suggest a more proactive approach by radiation oncologists in addressing distress.

Biodistribution and PET imaging of 89-zirconium labeled cerium oxide nanoparticles synthesized with several surface coatings.

Cerium oxide nanoparticles (CONPs) have unique surface chemistry allowing catalyst-like antioxidant properties, and are being investigated for several disease indications in medicine. Studies have utilized surface modified CONPs toward this application, but have been lacking in comprehensive biodistribution and pharmacokinetic data and a direct comparison to uncoated CONPs. We developed an enhanced single-pot synthesis of several coated CONPs and an efficient intrinsic core labeling of CONPs with the clinical PET isotope, zirconium-89, allowing detailed PET imaging and ex vivo biodistribution. All coated [89Zr]-CONPs showed benefit in terms of biodistribution compared to uncoated [89Zr]-CONPs, while retaining the intrinsic antioxidant properties. Among these, poly(acrylic acid) coated CONPs demonstrated excellent candidacy for clinical implementation due to their enhanced renal clearance and low reticuloendothelial system uptake. This work also demonstrates the value of intrinsic core labeling and PET imaging for evaluation of nanoparticle constructs to better inform future studies towards clinical use.

Intrinsically radiolabeled multifunctional cerium oxide nanoparticles for in vivo studies.

Cerium oxide nanoparticles (CONPs) have demonstrated protection properties against oxidation in various cells and tissues. The mechanism of this, however, is poorly understood. Monitoring the interaction of CONPs with biological compartments 'in situ' is crucial to understand their biochemical and physiological properties in vivo. In this paper, a multifunctional nanoparticle platform was obtained through an intrinsic radiolabeling strategy and extrinsic surface functionalization to combine dual imaging components (Single Photon Emission Computed Tomography/Optical Imaging, SPECT/OI) in one nanoparticle. The cell viability, cell uptake and overall in vivo biodistribution of CONPs were also manipulated through surface functionalization. The intrinsic radiolabeling strategy is demonstrated by incorporating radionuclides (141Ce, 111In or 65Zn) into CONPs and a radiolabeled CONP (rCONP) was coated with biocompatible polymers including Dextran T10 (DT10), poly(acrylic acid) (PAA), or functionalized DT10 (DT10-NH2, DT10-PEG and DT10-sulfobetaine). Fluorescent CONPs were obtained through conjugation of fluorescein isothiocyanate (FITC) with DT10-NH2 rCONP and used for cell imaging. The DT10 and DT10-NH2 rCONP did not show decreased viability up to 120 µg mL-1 whilst the PAA rCONP showed decreased viability beyond 40 µg mL-1. Variations in blood circulation and renal/hepatic clearance of rCONPs were demonstrated and were dependent on surface coating and the hydrodynamic size of nanoparticles. The ex vivo biodistribution results were reflected in SPECT imaging of 141Ce-rCONPs, showing accumulation in the liver and spleen of a living mouse over a one week period. The intrinsic radiolabeling and extrinsic surface modifications together determine the biophysical properties of CONPs and their potential applications for in vivo studies and biomedical imaging.