Incorporating parotid gland inhomogeneity into head-and-neck treatment optimization through the use of artificial base plans.

Despite a great improvement in target volume dose conformality made possible in recent years by modulated therapies, xerostomia remains a common and severe side effect for head-and-neck radiotherapy patients. It is known that parotid glands exhibit a spatially varying dose response; however, the relative importance of subregions throughout the entire gland has yet to be incorporated into treatment plan optimization, with the current standard being to minimize the mean dose to whole parotid glands. The relative importance of regions within contralateral parotid glands has been recently quantified, creating an opportunity for the development of a method for including this data in plan optimization. We present a universal and straightforward approach for imposing varying sub-parotid gland dose constraints during inverse treatment planning by using patient-specific artificial base plans to penalize dose deposited in sensitive regions. In this work, the proposed method of optimization is demonstrated to reduce dose to regions of high relative importance throughout contralateral parotids and improve predictions for stimulated saliva output at 1-year post-radiotherapy. This method may also be applied to impose varying dose constraints to other organs-at-risk for which regional importance data exists.

Image denoising and model-independent parameterization for IVIM MRI.

Objective. To improve intravoxel incoherent motion imaging (IVIM) magnetic resonance Imaging quality using a new image denoising technique and model-independent parameterization of the signal versusb-value curve.Approach. IVIM images were acquired for 13 head-and-neck patients prior to radiotherapy. Post-radiotherapy scans were also acquired for five of these patients. Images were denoised prior to parameter fitting using neural blind deconvolution, a method of solving the ill-posed mathematical problem of blind deconvolution using neural networks. The signal decay curve was then quantified in terms of several area under the curve (AUC) parameters. Improvements in image quality were assessed using blind image quality metrics, total variation (TV), and the correlations between parameter changes in parotid glands with radiotherapy dose levels. The validity of blur kernel predictions was assessed by the testing the method's ability to recover artificial 'pseudokernels'. AUC parameters were compared with monoexponential, biexponential, and triexponential model parameters in terms of their correlations with dose, contrast-to-noise (CNR) around parotid glands, and relative importance via principal component analysis.Main results. Image denoising improved blind image quality metrics, smoothed the signal versusb-value curve, and strengthened correlations between IVIM parameters and dose levels. Image TV was reduced and parameter CNRs generally increased following denoising.AUCparameters were more correlated with dose and had higher relative importance than exponential model parameters.Significance. IVIM parameters have high variability in the literature and perfusion-related parameters are difficult to interpret. Describing the signal versusb-value curve with model-independent parameters like theAUCand preprocessing images with denoising techniques could potentially benefit IVIM image parameterization in terms of reproducibility and functional utility.

PSMA PET/CT as a predictive tool for subregional importance estimates in the parotid gland.

Objective. Xerostomia and radiation-induced salivary gland dysfunction remain a common side effect for head-and-neck radiotherapy patients, and attempts have been made to quantify the heterogeneity of the dose response within parotid glands. Prostate Specific Membrane Antigen (PSMA) ligands have demonstrated high uptake in salivary glands, which has been shown to correlate with gland functionality. Here we compare several models of parotid gland subregional relative importance with PSMA positron emission tomography (PET) uptake. We then develop a predictive model for Clarket al's relative importance estimates using PSMA PET and CT radiomic features, and demonstrate a methodology for predicting patient-specific importance deviations from the population.Approach. Intra-parotid gland uptake was compared with four regional importance models using 30 [18F]DCFPyL PSMA PET images. The correlation of uptake and importance was ascertained when numerous non-overlapping subregions were defined, while a paired t-test was used to compare binary region pairs. A radiomics-based predictive model of population importance was developed using a double cross-validation methodology. A model was then devised for supplementing population-level subregional importance estimates for each patient using patient-specific radiomic features.Main Results. Anticorrelative relationships were found to exist between PSMA PET uptake and four independent models of subregional parotid gland importance from the literature. Kernel Ridge Regression with principal component analysis feature selection performed best over test sets (Mean Absolute Error = 0.08), with gray level co-occurrence matrix (GLCM) features being particularly important. Deblurring PSMA PET images with neural blind deconvolution strengthened correlations and improved model performance.Significance. This study suggests that regions of relatively low PSMA PET uptake in parotid glands may exhibit relatively high dose-sensitivity. We've demonstrated the utility of PSMA PET radiomic features for predicting relative importance within subregions of parotid glands. PSMA PET appears to be a promising quantitative imaging modality for analyzing salivary gland functionality.

Neural blind deconvolution for deblurring and supersampling PSMA PET.

Objective. To simultaneously deblur and supersample prostate specific membrane antigen (PSMA) positron emission tomography (PET) images using neural blind deconvolution.Approach. Blind deconvolution is a method of estimating the hypothetical 'deblurred' image along with the blur kernel (related to the point spread function) simultaneously. Traditionalmaximum a posterioriblind deconvolution methods require stringent assumptions and suffer from convergence to a trivial solution. A method of modelling the deblurred image and kernel with independent neural networks, called 'neural blind deconvolution' had demonstrated success for deblurring 2D natural images in 2020. In this work, we adapt neural blind deconvolution to deblur PSMA PET images while simultaneous supersampling to double the original resolution. We compare this methodology with several interpolation methods in terms of resultant blind image quality metrics and test the model's ability to predict accurate kernels by re-running the model after applying artificial 'pseudokernels' to deblurred images. The methodology was tested on a retrospective set of 30 prostate patients as well as phantom images containing spherical lesions of various volumes.Main results. Neural blind deconvolution led to improvements in image quality over other interpolation methods in terms of blind image quality metrics, recovery coefficients, and visual assessment. Predicted kernels were similar between patients, and the model accurately predicted several artificially-applied pseudokernels. Localization of activity in phantom spheres was improved after deblurring, allowing small lesions to be more accurately defined.Significance. The intrinsically low spatial resolution of PSMA PET leads to partial volume effects (PVEs) which negatively impact uptake quantification in small regions. The proposed method can be used to mitigate this issue, and can be straightforwardly adapted for other imaging modalities.

Heterogeneous PSMA ligand uptake inside parotid glands.

The purpose of this investigation is to quantify the spatial heterogeneity of prostate-specific membrane antigen (PSMA) positron emission tomography (PET) uptake within parotid glands. We aim to quantify patterns in well-defined regions to facilitate further investigations. Furthermore, we investigate whether uptake is correlated with computed tomography (CT) texture features. METHODS: Parotid glands from [18F]DCFPyL PSMA PET/CT images of 30 prostate cancer patients were analyzed. Uptake patterns were assessed with various segmentation schemes. Spearman's rank correlation coefficient was calculated between PSMA PET uptake and feature values of a Grey Level Run Length Matrix using a long and short run length emphasis (GLRLML and GLRLMS) in subregions of the parotid gland. RESULTS: PSMA PET uptake was significantly higher (p < 0.001) in lateral/posterior regions of the glands than anterior/medial regions. Maximum uptake was found in the lateral half of parotid glands in 50 out of 60 glands. The difference in SUVmean between parotid halves is greatest when parotids are divided by a plane separating the anterior/medial and posterior/lateral halves symmetrically (out of 120 bisections tested). PSMA PET uptake was significantly correlated with CT GLRLML (p < 0.001), and anti-correlated with CT GLRLMS (p < 0.001). CONCLUSION: Uptake of PSMA PET is heterogeneous within parotid glands, with uptake biased towards lateral/posterior regions. Uptake within parotid glands was strongly correlated with CT texture feature maps.

Development of a CT-Based Auto-Segmentation Model for Prostate-Specific Membrane Antigen (PSMA) Positron Emission Tomography-Delineated Tubarial Glands.

Modern inverse planning radiotherapy techniques allow for organs at risk (OARs) to evade radiation doses that they would have been subjected to with earlier techniques. The extent to which patient outcomes may be improved using these techniques depends on the delineation accuracy of target volumes and OARs on medical images as well as clinical dose constraints applied to regions of interest (ROIs). The recent discovery of bilateral "tubarial" salivary glands, which were found in the nasopharynx using prostate-specific membrane antigen (PSMA) positron emission tomography (PET), raises concerns over how dose to this region might affect patient outcomes. The dose response of the major salivary glands is known to be variable, and it is possible that the dose in tubarial glands constitutes a missing variable in the optimization of head and neck (HN) radiotherapy plans. A necessary first step toward conducting clinical studies that include the tubarial glands in plan optimization is to develop methods for delineating these glands without the use of PSMA PET images, as their acquisition is not considered a part of the standard of care for HN patients. In this study, we develop an open-source program, Organogenesis, for the auto-segmentation of tubarial glands using only computed tomography (CT) images. A predictive model is trained using contours derived from PSMA PET images, allowing for accurate delineation of tubarial glands, which cannot be manually contoured using CT only. Organogenesis provides a predictive model for tubarial glands that can be iteratively improved on with additional data, creating a viable pathway to clinical studies that can assess the importance of incorporating tubarial glands into HN radiotherapy plan optimization.