An accurate algorithm to match imperfectly matched images for lung tumor detection without markers.

In order to locate lung tumors on kV projection images without internal markers, digitally reconstructed radiographs (DRRs) are created and compared with projection images. However, lung tumors always move due to respiration and their locations change on projection images while they are static on DRRs. In addition, global image intensity discrepancies exist between DRRs and projections due to their different image orientations, scattering, and noises. This adversely affects comparison accuracy. A simple but efficient comparison algorithm is reported to match imperfectly matched projection images and DRRs. The kV projection images were matched with different DRRs in two steps. Preprocessing was performed in advance to generate two sets of DRRs. The tumors were removed from the planning 3D CT for a single phase of planning 4D CT images using planning contours of tumors. DRRs of background and DRRs of tumors were generated separately for every projection angle. The first step was to match projection images with DRRs of background signals. This method divided global images into a matrix of small tiles and similarities were evaluated by calculating normalized cross-correlation (NCC) between corresponding tiles on projections and DRRs. The tile configuration (tile locations) was automatically optimized to keep the tumor within a single projection tile that had a bad matching with the corresponding DRR tile. A pixel-based linear transformation was determined by linear interpolations of tile transformation results obtained during tile matching. The background DRRs were transformed to the projection image level and subtracted from it. The resulting subtracted image now contained only the tumor. The second step was to register DRRs of tumors to the subtracted image to locate the tumor. This method was successfully applied to kV fluoro images (about 1000 images) acquired on a Vero (BrainLAB) for dynamic tumor tracking on phantom studies. Radiation opaque markers were implanted and used as ground truth for tumor positions. Although other organs and bony structures introduced strong signals superimposed on tumors at some angles, this method accurately located tumors on every projection over 12 gantry angles. The maximum error was less than 2.2 mm, while the total average error was less than 0.9mm. This algorithm was capable of detecting tumors without markers, despite strong background signals.

Improved accuracy of relative electron density and proton stopping power ratio through CycleGAN machine learning.

Objective. Kilovoltage computed tomography (kVCT) is the cornerstone of radiotherapy treatment planning for delineating tissues and towards dose calculation. For the former, kVCT provides excellent contrast and signal-to-noise ratio. For the latter, kVCT may have greater uncertainty in determining relative electron density (ρe) and proton stopping power ratio (SPR). Conversely, megavoltage CT (MVCT) may result in superior dose calculation accuracy. The purpose of this work was to convert kVCT HU to MVCT HU using deep learning to obtain higher accuracyρeand SPR.Approach. Tissue-mimicking phantoms were created to compare kVCT- and MVCT-determinedρeand SPR to physical measurements. Using 100 head-and-neck datasets, an unpaired deep learning model was trained to learn the relationship between kVCTs and MVCTs, creating synthetic MVCTs (sMVCTs). Similarity metrics were calculated between kVCTs, sMVCTs, and MVCTs in 20 test datasets. An anthropomorphic head phantom containing bone-mimicking material with known composition was scanned to provide an independent determination ofρeand SPR accuracy by sMVCT.Main results. In tissue-mimicking bone,ρeerrors were 2.20% versus 0.19% and SPR errors were 4.38% versus 0.22%, for kVCT versus MVCT, respectively. Compared to MVCT,in vivomean difference (MD) values were 11 and 327 HU for kVCT and 2 and 3 HU for sMVCT in soft tissue and bone, respectively.ρeMD decreased from 1.3% to 0.35% in soft tissue and 2.9% to 0.13% in bone, for kVCT and sMVCT, respectively. SPR MD decreased from 1.8% to 0.24% in soft tissue and 6.8% to 0.16% in bone, for kVCT and sMVCT, respectively. Relative to physical measurements,ρeand SPR error in anthropomorphic bone decreased from 7.50% and 7.48% for kVCT to <1% for both MVCT and sMVCT.Significance. Deep learning can be used to map kVCT to sMVCT, suggesting higher accuracyρeand SPR is achievable with sMVCT versus kVCT.

A generative adversarial inpainting network to enhance prediction of periodontal clinical attachment level.

OBJECTIVES: Bone level as measured by clinical attachment levels (CAL) are critical findings that determine the diagnosis of periodontal disease. Deep learning algorithms are being used to determine CAL which aid in the diagnosis of periodontal disease. However, the limited field-of-view of bitewing x-rays poses a challenge for convolutional neural networks (CNN) because out-of-view anatomy cannot be directly considered. This study presents an inpainting algorithm using generative adversarial networks (GANs) coupled with partial convolutions to predict out-of-view anatomy to enhance CAL prediction accuracy. METHODS: Retrospective purposive sampling of cases with healthy periodontium and diseased periodontium with bitewing and periapical radiographs and clinician recorded CAL were utilized. Data utilized was from July 1, 2016 through January 30, 2020. 80,326 images were used for training, 12,901 images were used for validation and 10,687 images were used to compare non-inpainted methods to inpainted methods for CAL predictions. Statistical analyses were mean bias error (MBE), mean absolute error (MAE) and Dunn's pairwise test comparing CAL at p=0.05. RESULTS: Comparator p-values demonstrated statistically significant improvement in CAL prediction accuracy between corresponding inpainted and non-inpainted methods with MAE of 1.04mm and 1.50mm respectively. The Dunn's pairwise test indicated statistically significant improvement in CAL prediction accuracy between inpainted methods compared to their non-inpainted counterparts, with the best performing methods achieving a Dunn's pairwise value of -63.89. CONCLUSIONS: This study demonstrates the superiority of using a generative adversarial inpainting network with partial convolutions to predict CAL from bitewing and periapical images. CLINICAL SIGNIFICANCE: Artificial intelligence was developed and utilized to predict clinical attachment level compared to clinical measurements. A generative adversarial inpainting network with partial convolutions was developed, tested and validated to predict clinical attachment level. The inpainting approach was found to be superior to non-inpainted methods and within the 1mm clinician-determined measurement standard.

Improved contrast and noise of megavoltage computed tomography (MVCT) through cycle-consistent generative machine learning.

PURPOSE: Megavoltage computed tomography (MVCT) has been implemented on many radiation therapy treatment machines as a tomographic imaging modality that allows for three-dimensional visualization and localization of patient anatomy. Yet MVCT images exhibit lower contrast and greater noise than its kilovoltage CT (kVCT) counterpart. In this work, we sought to improve these disadvantages of MVCT images through an image-to-image-based machine learning transformation of MVCT and kVCT images. We demonstrated that by learning the style of kVCT images, MVCT images can be converted into high-quality synthetic kVCT (skVCT) images with higher contrast and lower noise, when compared to the original MVCT. METHODS: Kilovoltage CT and MVCT images of 120 head and neck (H&N) cancer patients treated on an Accuray TomoHD system were retrospectively analyzed in this study. A cycle-consistent generative adversarial network (CycleGAN) machine learning, a variant of the generative adversarial network (GAN), was used to learn Hounsfield Unit (HU) transformations from MVCT to kVCT images, creating skVCT images. A formal mathematical proof is given describing the interplay between function sensitivity and input noise and how it applies to the error variance of a high-capacity function trained with noisy input data. Finally, we show how skVCT shares distributional similarity to kVCT for various macro-structures found in the body. RESULTS: Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were improved in skVCT images relative to the original MVCT images and were consistent with kVCT images. Specifically, skVCT CNR for muscle-fat, bone-fat, and bone-muscle improved to 14.8 ± 0.4, 122.7 ± 22.6, and 107.9 ± 22.4 compared with 1.6 ± 0.3, 7.6 ± 1.9, and 6.0 ± 1.7, respectively, in the original MVCT images and was more consistent with kVCT CNR values of 15.2 ± 0.8, 124.9 ± 27.0, and 109.7 ± 26.5, respectively. Noise was significantly reduced in skVCT images with SNR values improving by roughly an order of magnitude and consistent with kVCT SNR values. Axial slice mean (S-ME) and mean absolute error (S-MAE) agreement between kVCT and MVCT/skVCT improved, on average, from -16.0 and 109.1 HU to 8.4 and 76.9 HU, respectively. CONCLUSIONS: A kVCT-like qualitative aid was generated from input MVCT data through a CycleGAN instance. This qualitative aid, skVCT, was robust toward embedded metallic material, dramatically improves HU alignment from MVCT, and appears perceptually similar to kVCT with SNR and CNR values equivalent to that of kVCT images.

DoseGAN: a generative adversarial network for synthetic dose prediction using attention-gated discrimination and generation.

Deep learning algorithms have recently been developed that utilize patient anatomy and raw imaging information to predict radiation dose, as a means to increase treatment planning efficiency and improve radiotherapy plan quality. Current state-of-the-art techniques rely on convolutional neural networks (CNNs) that use pixel-to-pixel loss to update network parameters. However, stereotactic body radiotherapy (SBRT) dose is often heterogeneous, making it difficult to model using pixel-level loss. Generative adversarial networks (GANs) utilize adversarial learning that incorporates image-level loss and is better suited to learn from heterogeneous labels. However, GANs are difficult to train and rely on compromised architectures to facilitate convergence. This study suggests an attention-gated generative adversarial network (DoseGAN) to improve learning, increase model complexity, and reduce network redundancy by focusing on relevant anatomy. DoseGAN was compared to alternative state-of-the-art dose prediction algorithms using heterogeneity index, conformity index, and various dosimetric parameters. All algorithms were trained, validated, and tested using 141 prostate SBRT patients. DoseGAN was able to predict more realistic volumetric dosimetry compared to all other algorithms and achieved statistically significant improvement compared to all alternative algorithms for the V100 and V120 of the PTV, V60 of the rectum, and heterogeneity index.

Attention-Aware Discrimination for MR-to-CT Image Translation Using Cycle-Consistent Generative Adversarial Networks.

PURPOSE: To suggest an attention-aware, cycle-consistent generative adversarial network (A-CycleGAN) enhanced with variational autoencoding (VAE) as a superior alternative to current state-of-the-art MR-to-CT image translation methods. MATERIALS AND METHODS: An attention-gating mechanism is incorporated into a discriminator network to encourage a more parsimonious use of network parameters, whereas VAE enhancement enables deeper discrimination architectures without inhibiting model convergence. Findings from 60 patients with head, neck, and brain cancer were used to train and validate A-CycleGAN, and findings from 30 patients were used for the holdout test set and were used to report final evaluation metric results using mean absolute error (MAE) and peak signal-to-noise ratio (PSNR). RESULTS: A-CycleGAN achieved superior results compared with U-Net, a generative adversarial network (GAN), and a cycle-consistent GAN. The A-CycleGAN averages, 95% confidence intervals (CIs), and Wilcoxon signed-rank two-sided test statistics are shown for MAE (19.61 [95% CI: 18.83, 20.39], P = .0104), structure similarity index metric (0.778 [95% CI: 0.758, 0.798], P = .0495), and PSNR (62.35 [95% CI: 61.80, 62.90], P = .0571). CONCLUSION: A-CycleGANs were a superior alternative to state-of-the-art MR-to-CT image translation methods.© RSNA, 2020.

Attention-enabled 3D boosted convolutional neural networks for semantic CT segmentation using deep supervision.

A deeply supervised attention-enabled boosted convolutional neural network (DAB-CNN) is presented as a superior alternative to current state-of-the-art convolutional neural networks (CNNs) for semantic CT segmentation. Spatial attention gates (AGs) were incorporated into a novel 3D cascaded CNN framework to prioritize relevant anatomy and suppress redundancies within the network. Due to the complexity and size of the network, incremental channel boosting was used to decrease memory usage and facilitate model convergence. Deep supervision was used to encourage semantically meaningful deep features and mitigate local minima traps during training. The accuracy of DAB-CNN is compared to seven architectures: a variation of U-Net (UNet), attention-enabled U-Net (A-UNet), boosted U-Net (B-UNet), deeply-supervised U-Net (D-UNet), U-Net with ResNeXt blocks (ResNeXt), life-long learning segmentation CNN (LL-CNN), and deeply supervised attention-enabled U-Net (DA-UNet). The accuracy of each method was assessed based on Dice score compared to manually delineated contours as the gold standard. One hundred and twenty patients who had definitive prostate radiotherapy were used in this study. Training, validation, and testing followed Kaggle competition rules, with 80 patients used for training, 20 patients used for internal validation, and 20 test patients used to report final accuracies. Comparator p -values indicate that DAB-CNN achieved significantly superior Dice scores than all alternative algorithms for the prostate, rectum, and penile bulb. This study demonstrated that attention-enabled boosted convolutional neural networks (CNNs) using deep supervision are capable of achieving superior prediction accuracy compared to current state-of-the-art automatic segmentation methods.

A convolutional neural network algorithm for automatic segmentation of head and neck organs at risk using deep lifelong learning.

PURPOSE: This study suggests a lifelong learning-based convolutional neural network (LL-CNN) algorithm as a superior alternative to single-task learning approaches for automatic segmentation of head and neck (OARs) organs at risk. METHODS AND MATERIALS: Lifelong learning-based convolutional neural network was trained on twelve head and neck OARs simultaneously using a multitask learning framework. Once the weights of the shared network were established, the final multitask convolutional layer was replaced by a single-task convolutional layer. The single-task transfer learning network was trained on each OAR separately with early stoppage. The accuracy of LL-CNN was assessed based on Dice score and root-mean-square error (RMSE) compared to manually delineated contours set as the gold standard. LL-CNN was compared with 2D-UNet, 3D-UNet, a single-task CNN (ST-CNN), and a pure multitask CNN (MT-CNN). Training, validation, and testing followed Kaggle competition rules, where 160 patients were used for training, 20 were used for internal validation, and 20 in a separate test set were used to report final prediction accuracies. RESULTS: On average contours generated with LL-CNN had higher Dice coefficients and lower RMSE than 2D-UNet, 3D-Unet, ST- CNN, and MT-CNN. LL-CNN required ~72 hrs to train using a distributed learning framework on 2 Nvidia 1080Ti graphics processing units. LL-CNN required 20 s to predict all 12 OARs, which was approximately as fast as the fastest alternative methods with the exception of MT-CNN. CONCLUSIONS: This study demonstrated that for head and neck organs at risk, LL-CNN achieves a prediction accuracy superior to all alternative algorithms.

Optimizing beam models for dosimetric accuracy over a wide range of treatments.

This work presents a systematic approach for testing a dose calculation algorithm over a variety of conditions designed to span the possible range of clinical treatment plans. Using this method, a TrueBeam STx machine with high definition multi-leaf collimators (MLCs) was commissioned in the RayStation treatment planning system (TPS). The initial model parameters values were determined by comparing TPS calculations with standard measured depth dose and profile curves. The MLC leaf offset calibration was determined by comparing measured and calculated field edges utilizing a wide range of MLC retracted and over-travel positions. The radial fluence was adjusted using profiles through both the center and corners of the largest field size, and through measurements of small fields that were located at highly off-axis positions. The flattening filter source was adjusted to improve the TPS agreement for the output of MLC-defined fields with much larger jaw openings. The MLC leaf transmission and leaf end parameters were adjusted to optimize the TPS agreement for highly modulated intensity-modulated radiotherapy (IMRT) plans. The final model was validated for simple open fields, multiple field configurations, the TG 119 C-shape target test, and a battery of clinical IMRT and volumetric-modulated arc therapy (VMAT) plans. The commissioning process detected potential dosimetric errors of over 10% and resulted in a final model that provided in general 3% dosimetric accuracy. This study demonstrates the importance of using a variety of conditions to adjust a beam model and provides an effective framework for achieving high dosimetric accuracy.

The application of artificial intelligence in the IMRT planning process for head and neck cancer.

Artificial intelligence (AI) is beginning to transform IMRT treatment planning for head and neck patients. However, the complexity and novelty of AI algorithms make them susceptible to misuse by researchers and clinicians. Understanding nuances of new technologies could serve to mitigate potential clinical implementation pitfalls. This article is intended to facilitate integration of AI into the radiotherapy clinic by providing an overview of AI algorithms, including support vector machines (SVMs), random forests (RF), gradient boosting (GB), and several variations of deep learning. This document describes current AI algorithms that have been applied to head and neck IMRT planning and identifies rapidly growing branches of AI in industry that have potential applications to head and neck cancer patients receiving IMRT. AI algorithms have great clinical potential if used correctly but can also cause harm if misused, so it is important to raise the level of AI competence within radiation oncology so that the benefits can be realized in a controlled and safe manner.

DoseNet: a volumetric dose prediction algorithm using 3D fully-convolutional neural networks.

The goal of this study is to demonstrate the feasibility of a novel fully-convolutional volumetric dose prediction neural network (DoseNet) and test its performance on a cohort of prostate stereotactic body radiotherapy (SBRT) patients. DoseNet is suggested as a superior alternative to U-Net and fully connected distance map-based neural networks for non-coplanar SBRT prostate dose prediction. DoseNet utilizes 3D convolutional downsampling with corresponding 3D deconvolutional upsampling to preserve memory while simultaneously increasing the receptive field of the network. DoseNet was implemented on 2 Nvidia 1080 Ti graphics processing units and utilizes a 3 phase learning protocol to help achieve convergence and improve generalization. DoseNet was trained, validated, and tested with 151 patients following Kaggle completion rules. The dosimetric quality of DoseNet was evaluated by comparing the predicted dose distribution with the clinically approved delivered dose distribution in terms of conformity index, heterogeneity index, and various clinically relevant dosimetric parameters. The results indicate that the DoseNet algorithm is a superior alternative to U-Net and fully connected methods for prostate SBRT patients. DoseNet required ~50.1 h to train, and ~0.83 s to make a prediction on a 128 × 128 × 64 voxel image. In conclusion, DoseNet is capable of making accurate volumetric dose predictions for non-coplanar SBRT prostate patients, while simultaneously preserving computational efficiency.

Correcting TG 119 confidence limits.

PURPOSE: Task Group 119 (TG-119) has been adopted for evaluating the adequacy of intensity-modulated radiation therapy (IMRT) commissioning and for establishing patient-specific IMRT quality assurance (QA) passing criteria in clinical practice. TG-119 establishes 95% confidence limits (CLs), which help clinics identify systematic IMRT QA errors and identify outliers. In TG-119, the 95% CLs are established by fitting the Gamma Γ analysis passing rate results to an assumed distribution, then calculating the limit in which 95% of the data fall. CLs for a given dataset will depend greatly on the type of distribution used, and those determined by following the TG-119 guidelines are only valid if the underlying data follows a Gaussian distribution. Gaussian distributions assume symmetry about the mean, which would imply the possibility of negative Γ analysis failing rates. This study demonstrates that the gamma distribution is a more reasonable assumption for establishing CLs than the Gaussian distribution used in TG-119. Thus, the gamma distribution is suggested as a replacement to the conventional Gaussian statistical model used in TG-119. MATERIALS AND METHODS: The moments estimator (ME) for the gamma family is used to obtain the CLs of the failing rates for all Γ analysis criteria. To demonstrate the congruence of the gamma distribution, the root mean squared error and the CL values for the MEs of the gamma and the Gaussian families were compared. RESULTS: In this study, the empirical 95% CLs generated using 302 plans represent the ground truth, which resulted in a 91.83% passing rate using 3%/3 mm error local criteria. The gamma distribution underestimates the 95% CL by 0.09%, while the Gaussian distribution overestimates the 95% CL by 4.12%. CONCLUSIONS: Although IMRT QA equipment may vary between clinics, the mathematical formalism presented in this study applies to any combination of planning and delivery systems. This study has demonstrated that a gamma distribution should be favored over a Gaussian distribution when establishing CLs for IMRT QA.

An unsupervised convolutional neural network-based algorithm for deformable image registration.

The purpose of the work is to develop a deep unsupervised learning strategy for cone-beam CT (CBCT) to CT deformable image registration (DIR). This technique uses a deep convolutional inverse graphics network (DCIGN) based DIR algorithm implemented on 2 Nvidia 1080 Ti graphics processing units. The model is comprised of an encoding and decoding stage. The fully-convolutional encoding stage learns hierarchical features and simultaneously forms an information bottleneck, while the decoding stage restores the original dimensionality of the input image. Activations from the encoding stage are used as the input channels to a sparse DIR algorithm. DCIGN was trained using a distributive learning-based convolutional neural network architecture and used 285 head and neck patients to train, validate, and test the algorithm. The accuracy of the DCIGN algorithm was evaluated on 100 synthetic cases and 12 hold out test patient cases. The results indicate that DCIGN performed better than rigid registration, intensity corrected Demons, and landmark-guided deformable image registration for all evaluation metrics. DCIGN required ~14 h to train, and ~3.5 s to make a prediction on a 512 × 512 × 120 voxel image. In conclusion, DCIGN is able to maintain high accuracy in the presence of CBCT noise contamination, while simultaneously preserving high computational efficiency.

A continuous arc delivery optimization algorithm for CyberKnife m6.

PURPOSE: This study aims to reduce the delivery time of CyberKnife m6 treatments by allowing for noncoplanar continuous arc delivery. To achieve this, a novel noncoplanar continuous arc delivery optimization algorithm was developed for the CyberKnife m6 treatment system (CyberArc-m6). METHODS AND MATERIALS: CyberArc-m6 uses a five-step overarching strategy, in which an initial set of beam geometries is determined, the robotic delivery path is calculated, direct aperture optimization is conducted, intermediate MLC configurations are extracted, and the final beam weights are computed for the continuous arc radiation source model. This algorithm was implemented on five prostate and three brain patients, previously planned using a conventional step-and-shoot CyberKnife m6 delivery technique. The dosimetric quality of the CyberArc-m6 plans was assessed using locally confined mutual information (LCMI), conformity index (CI), heterogeneity index (HI), and a variety of common clinical dosimetric objectives. RESULTS: Using conservative optimization tuning parameters, CyberArc-m6 plans were able to achieve an average CI difference of 0.036 ± 0.025, an average HI difference of 0.046 ± 0.038, and an average LCMI of 0.920 ± 0.030 compared with the original CyberKnife m6 plans. Including a 5 s per minute image alignment time and a 5-min setup time, conservative CyberArc-m6 plans achieved an average treatment delivery speed up of 1.545x ± 0.305x compared with step-and-shoot plans. CONCLUSIONS: The CyberArc-m6 algorithm was able to achieve dosimetrically similar plans compared to their step-and-shoot CyberKnife m6 counterparts, while simultaneously reducing treatment delivery times.

Deep nets vs expert designed features in medical physics: An IMRT QA case study.

PURPOSE: The purpose of this study was to compare the performance of Deep Neural Networks against a technique designed by domain experts in the prediction of gamma passing rates for Intensity Modulated Radiation Therapy Quality Assurance (IMRT QA). METHOD: A total of 498 IMRT plans across all treatment sites were planned in Eclipse version 11 and delivered using a dynamic sliding window technique on Clinac iX or TrueBeam Linacs. Measurements were performed using a commercial 2D diode array, and passing rates for 3%/3 mm local dose/distance-to-agreement (DTA) were recorded. Separately, fluence maps calculated for each plan were used as inputs to a convolution neural network (CNN). The CNNs were trained to predict IMRT QA gamma passing rates using TensorFlow and Keras. A set of model architectures, inspired by the convolutional blocks of the VGG-16 ImageNet model, were constructed and implemented. Synthetic data, created by rotating and translating the fluence maps during training, was created to boost the performance of the CNNs. Dropout, batch normalization, and data augmentation were utilized to help train the model. The performance of the CNNs was compared to a generalized Poisson regression model, previously developed for this application, which used 78 expert designed features. RESULTS: Deep Neural Networks without domain knowledge achieved comparable performance to a baseline system designed by domain experts in the prediction of 3%/3 mm Local gamma passing rates. An ensemble of neural nets resulted in a mean absolute error (MAE) of 0.70 ± 0.05 and the domain expert model resulted in a 0.74 ± 0.06. CONCLUSIONS: Convolutional neural networks (CNNs) with transfer learning can predict IMRT QA passing rates by automatically designing features from the fluence maps without human expert supervision. Predictions from CNNs are comparable to a system carefully designed by physicist experts.

A Deep Look Into the Future of Quantitative Imaging in Oncology: A Statement of Working Principles and Proposal for Change.

The adoption of enterprise digital imaging, along with the development of quantitative imaging methods and the re-emergence of statistical learning, has opened the opportunity for more personalized cancer treatments through transformative data science research. In the last 5 years, accumulating evidence has indicated that noninvasive advanced imaging analytics (i.e., radiomics) can reveal key components of tumor phenotype for multiple lesions at multiple time points over the course of treatment. Many groups using homegrown software have extracted engineered and deep quantitative features on 3-dimensional medical images for better spatial and longitudinal understanding of tumor biology and for the prediction of diverse outcomes. These developments could augment patient stratification and prognostication, buttressing emerging targeted therapeutic approaches. Unfortunately, the rapid growth in popularity of this immature scientific discipline has resulted in many early publications that miss key information or use underpowered patient data sets, without production of generalizable results. Quantitative imaging research is complex, and key principles should be followed to realize its full potential. The fields of quantitative imaging and radiomics in particular require a renewed focus on optimal study design and reporting practices, standardization, interpretability, data sharing, and clinical trials. Standardization of image acquisition, feature calculation, and statistical analysis (i.e., machine learning) are required for the field to move forward. A new data-sharing paradigm enacted among open and diverse participants (medical institutions, vendors and associations) should be embraced for faster development and comprehensive clinical validation of imaging biomarkers. In this review and critique of the field, we propose working principles and fundamental changes to the current scientific approach, with the goal of high-impact research and development of actionable prediction models that will yield more meaningful applications of precision cancer medicine.

Canny edge-based deformable image registration.

This work focuses on developing a 2D Canny edge-based deformable image registration (Canny DIR) algorithm to register in vivo white light images taken at various time points. This method uses a sparse interpolation deformation algorithm to sparsely register regions of the image with strong edge information. A stability criterion is enforced which removes regions of edges that do not deform in a smooth uniform manner. Using a synthetic mouse surface ground truth model, the accuracy of the Canny DIR algorithm was evaluated under axial rotation in the presence of deformation. The accuracy was also tested using fluorescent dye injections, which were then used for gamma analysis to establish a second ground truth. The results indicate that the Canny DIR algorithm performs better than rigid registration, intensity corrected Demons, and distinctive features for all evaluation matrices and ground truth scenarios. In conclusion Canny DIR performs well in the presence of the unique lighting and shading variations associated with white-light-based image registration.

CyberArc: a non-coplanar-arc optimization algorithm for CyberKnife.

The goal of this study is to demonstrate the feasibility of a novel non-coplanar-arc optimization algorithm (CyberArc). This method aims to reduce the delivery time of conventional CyberKnife treatments by allowing for continuous beam delivery. CyberArc uses a 4 step optimization strategy, in which nodes, beams, and collimator sizes are determined, source trajectories are calculated, intermediate radiation models are generated, and final monitor units are calculated, for the continuous radiation source model. The dosimetric results as well as the time reduction factors for CyberArc are presented for 7 prostate and 2 brain cases. The dosimetric quality of the CyberArc plans are evaluated using conformity index, heterogeneity index, local confined normalized-mutual-information, and various clinically relevant dosimetric parameters. The results indicate that the CyberArc algorithm dramatically reduces the treatment time of CyberKnife plans while simultaneously preserving the dosimetric quality of the original plans.

Design of a portable imager for near-infrared visualization of cutaneous wounds.

A portable imager developed for real-time imaging of cutaneous wounds in research settings is described. The imager consists of a high-resolution near-infrared CCD camera capable of detecting both bioluminescence and fluorescence illuminated by an LED ring with a rotatable filter wheel. All external components are integrated into a compact camera attachment. The device is demonstrated to have competitive performance with a commercial animal imaging enclosure box setup in beam uniformity and sensitivity. Specifically, the device was used to visualize the bioluminescence associated with increased reactive oxygen species activity during the wound healing process in a cutaneous wound inflammation model. In addition, this device was employed to observe the fluorescence associated with the activity of matrix metalloproteinases in a mouse lipopolysaccharide-induced infection model. Our results support the use of the portable imager design as a noninvasive and real-time imaging tool to assess the extent of wound inflammation and infection.

Automated landmark-guided deformable image registration.

The purpose of this work is to develop an automated landmark-guided deformable image registration (LDIR) algorithm between the planning CT and daily cone-beam CT (CBCT) with low image quality. This method uses an automated landmark generation algorithm in conjunction with a local small volume gradient matching search engine to map corresponding landmarks between the CBCT and the planning CT. The landmarks act as stabilizing control points in the following Demons deformable image registration. LDIR is implemented on graphics processing units (GPUs) for parallel computation to achieve ultra fast calculation. The accuracy of the LDIR algorithm has been evaluated on a synthetic case in the presence of different noise levels and data of six head and neck cancer patients. The results indicate that LDIR performed better than rigid registration, Demons, and intensity corrected Demons for all similarity metrics used. In conclusion, LDIR achieves high accuracy in the presence of multimodality intensity mismatch and CBCT noise contamination, while simultaneously preserving high computational efficiency.