The Image Biomarker Standardization Initiative: Standardized Convolutional Filters for Reproducible Radiomics and Enhanced Clinical Insights.

Filters are commonly used to enhance specific structures and patterns in images, such as vessels or peritumoral regions, to enable clinical insights beyond the visible image using radiomics. However, their lack of standardization restricts reproducibility and clinical translation of radiomics decision support tools. In this special report, teams of researchers who developed radiomics software participated in a three-phase study (September 2020 to December 2022) to establish a standardized set of filters. The first two phases focused on finding reference filtered images and reference feature values for commonly used convolutional filters: mean, Laplacian of Gaussian, Laws and Gabor kernels, separable and nonseparable wavelets (including decomposed forms), and Riesz transformations. In the first phase, 15 teams used digital phantoms to establish 33 reference filtered images of 36 filter configurations. In phase 2, 11 teams used a chest CT image to derive reference values for 323 of 396 features computed from filtered images using 22 filter and image processing configurations. Reference filtered images and feature values for Riesz transformations were not established. Reproducibility of standardized convolutional filters was validated on a public data set of multimodal imaging (CT, fluorodeoxyglucose PET, and T1-weighted MRI) in 51 patients with soft-tissue sarcoma. At validation, reproducibility of 486 features computed from filtered images using nine configurations × three imaging modalities was assessed using the lower bounds of 95% CIs of intraclass correlation coefficients. Out of 486 features, 458 were found to be reproducible across nine teams with lower bounds of 95% CIs of intraclass correlation coefficients greater than 0.75. In conclusion, eight filter types were standardized with reference filtered images and reference feature values for verifying and calibrating radiomics software packages. A web-based tool is available for compliance checking.

Deep transformer-based personalized dosimetry from SPECT/CT images: a hybrid approach for [177Lu]Lu-DOTATATE radiopharmaceutical therapy.

PURPOSE: Accurate dosimetry is critical for ensuring the safety and efficacy of radiopharmaceutical therapies. In current clinical dosimetry practice, MIRD formalisms are widely employed. However, with the rapid advancement of deep learning (DL) algorithms, there has been an increasing interest in leveraging the calculation speed and automation capabilities for different tasks. We aimed to develop a hybrid transformer-based deep learning (DL) model that incorporates a multiple voxel S-value (MSV) approach for voxel-level dosimetry in [177Lu]Lu-DOTATATE therapy. The goal was to enhance the performance of the model to achieve accuracy levels closely aligned with Monte Carlo (MC) simulations, considered as the standard of reference. We extended our analysis to include MIRD formalisms (SSV and MSV), thereby conducting a comprehensive dosimetry study. METHODS: We used a dataset consisting of 22 patients undergoing up to 4 cycles of [177Lu]Lu-DOTATATE therapy. MC simulations were used to generate reference absorbed dose maps. In addition, MIRD formalism approaches, namely, single S-value (SSV) and MSV techniques, were performed. A UNEt TRansformer (UNETR) DL architecture was trained using five-fold cross-validation to generate MC-based dose maps. Co-registered CT images were fed into the network as input, whereas the difference between MC and MSV (MC-MSV) was set as output. DL results are then integrated to MSV to revive the MC dose maps. Finally, the dose maps generated by MSV, SSV, and DL were quantitatively compared to the MC reference at both voxel level and organ level (organs at risk and lesions). RESULTS: The DL approach showed slightly better performance (voxel relative absolute error (RAE) = 5.28 ± 1.32) compared to MSV (voxel RAE = 5.54 ± 1.4) and outperformed SSV (voxel RAE = 7.8 ± 3.02). Gamma analysis pass rates were 99.0 ± 1.2%, 98.8 ± 1.3%, and 98.7 ± 1.52% for DL, MSV, and SSV approaches, respectively. The computational time for MC was the highest (~2 days for a single-bed SPECT study) compared to MSV, SSV, and DL, whereas the DL-based approach outperformed the other approaches in terms of time efficiency (3 s for a single-bed SPECT). Organ-wise analysis showed absolute percent errors of 1.44 ± 3.05%, 1.18 ± 2.65%, and 1.15 ± 2.5% for SSV, MSV, and DL approaches, respectively, in lesion-absorbed doses. CONCLUSION: A hybrid transformer-based deep learning model was developed for fast and accurate dose map generation, outperforming the MIRD approaches, specifically in heterogenous regions. The model achieved accuracy close to MC gold standard and has potential for clinical implementation for use on large-scale datasets.

TMTV-Net: fully automated total metabolic tumor volume segmentation in lymphoma PET/CT images - a multi-center generalizability analysis.

PURPOSE: Total metabolic tumor volume (TMTV) segmentation has significant value enabling quantitative imaging biomarkers for lymphoma management. In this work, we tackle the challenging task of automated tumor delineation in lymphoma from PET/CT scans using a cascaded approach. METHODS: Our study included 1418 2-[18F]FDG PET/CT scans from four different centers. The dataset was divided into 900 scans for development/validation/testing phases and 518 for multi-center external testing. The former consisted of 450 lymphoma, lung cancer, and melanoma scans, along with 450 negative scans, while the latter consisted of lymphoma patients from different centers with diffuse large B cell, primary mediastinal large B cell, and classic Hodgkin lymphoma cases. Our approach involves resampling PET/CT images into different voxel sizes in the first step, followed by training multi-resolution 3D U-Nets on each resampled dataset using a fivefold cross-validation scheme. The models trained on different data splits were ensemble. After applying soft voting to the predicted masks, in the second step, we input the probability-averaged predictions, along with the input imaging data, into another 3D U-Net. Models were trained with semi-supervised loss. We additionally considered the effectiveness of using test time augmentation (TTA) to improve the segmentation performance after training. In addition to quantitative analysis including Dice score (DSC) and TMTV comparisons, the qualitative evaluation was also conducted by nuclear medicine physicians. RESULTS: Our cascaded soft-voting guided approach resulted in performance with an average DSC of 0.68 ± 0.12 for the internal test data from developmental dataset, and an average DSC of 0.66 ± 0.18 on the multi-site external data (n = 518), significantly outperforming (p < 0.001) state-of-the-art (SOTA) approaches including nnU-Net and SWIN UNETR. While TTA yielded enhanced performance gains for some of the comparator methods, its impact on our cascaded approach was found to be negligible (DSC: 0.66 ± 0.16). Our approach reliably quantified TMTV, with a correlation of 0.89 with the ground truth (p < 0.001). Furthermore, in terms of visual assessment, concordance between quantitative evaluations and clinician feedback was observed in the majority of cases. The average relative error (ARE) and the absolute error (AE) in TMTV prediction on external multi-centric dataset were ARE = 0.43 ± 0.54 and AE = 157.32 ± 378.12 (mL) for all the external test data (n = 518), and ARE = 0.30 ± 0.22 and AE = 82.05 ± 99.78 (mL) when the 10% outliers (n = 53) were excluded. CONCLUSION: TMTV-Net demonstrates strong performance and generalizability in TMTV segmentation across multi-site external datasets, encompassing various lymphoma subtypes. A negligible reduction of 2% in overall performance during testing on external data highlights robust model generalizability across different centers and cancer types, likely attributable to its training with resampled inputs. Our model is publicly available, allowing easy multi-site evaluation and generalizability analysis on datasets from different institutions.

Multi-modality artificial intelligence-based transthyretin amyloid cardiomyopathy detection in patients with severe aortic stenosis.

PURPOSE: Transthyretin amyloid cardiomyopathy (ATTR-CM) is a frequent concomitant condition in patients with severe aortic stenosis (AS), yet it often remains undetected. This study aims to comprehensively evaluate artificial intelligence-based models developed based on preprocedural and routinely collected data to detect ATTR-CM in patients with severe AS planned for transcatheter aortic valve implantation (TAVI). METHODS: In this prospective, single-center study, consecutive patients with AS were screened with [99mTc]-3,3-diphosphono-1,2-propanodicarboxylic acid ([99mTc]-DPD) for the presence of ATTR-CM. Clinical, laboratory, electrocardiogram, echocardiography, invasive measurements, 4-dimensional cardiac CT (4D-CCT) strain data, and CT-radiomic features were used for machine learning modeling of ATTR-CM detection and for outcome prediction. Feature selection and classifier algorithms were applied in single- and multi-modality classification scenarios. We split the dataset into training (70%) and testing (30%) samples. Performance was assessed using various metrics across 100 random seeds. RESULTS: Out of 263 patients with severe AS (57% males, age 83 ± 4.6years) enrolled, ATTR-CM was confirmed in 27 (10.3%). The lowest performances for detection of concomitant ATTR-CM were observed in invasive measurements and ECG data with area under the curve (AUC) < 0.68. Individual clinical, laboratory, interventional imaging, and CT-radiomics-based features showed moderate performances (AUC 0.70-0.76, sensitivity 0.79-0.82, specificity 0.63-0.72), echocardiography demonstrated good performance (AUC 0.79, sensitivity 0.80, specificity 0.78), and 4D-CT-strain showed the highest performance (AUC 0.85, sensitivity 0.90, specificity 0.74). The multi-modality model (AUC 0.84, sensitivity 0.87, specificity 0.76) did not outperform the model performance based on 4D-CT-strain only data (p-value > 0.05). The multi-modality model adequately discriminated low and high-risk individuals for all-cause mortality at a mean follow-up of 13 months. CONCLUSION: Artificial intelligence-based models using collected pre-TAVI evaluation data can effectively detect ATTR-CM in patients with severe AS, offering an alternative diagnostic strategy to scintigraphy and myocardial biopsy.

PRIMIS: Privacy-preserving medical image sharing via deep sparsifying transform learning with obfuscation.

OBJECTIVE: The primary objective of our study is to address the challenge of confidentially sharing medical images across different centers. This is often a critical necessity in both clinical and research environments, yet restrictions typically exist due to privacy concerns. Our aim is to design a privacy-preserving data-sharing mechanism that allows medical images to be stored as encoded and obfuscated representations in the public domain without revealing any useful or recoverable content from the images. In tandem, we aim to provide authorized users with compact private keys that could be used to reconstruct the corresponding images. METHOD: Our approach involves utilizing a neural auto-encoder. The convolutional filter outputs are passed through sparsifying transformations to produce multiple compact codes. Each code is responsible for reconstructing different attributes of the image. The key privacy-preserving element in this process is obfuscation through the use of specific pseudo-random noise. When applied to the codes, it becomes computationally infeasible for an attacker to guess the correct representation for all the codes, thereby preserving the privacy of the images. RESULTS: The proposed framework was implemented and evaluated using chest X-ray images for different medical image analysis tasks, including classification, segmentation, and texture analysis. Additionally, we thoroughly assessed the robustness of our method against various attacks using both supervised and unsupervised algorithms. CONCLUSION: This study provides a novel, optimized, and privacy-assured data-sharing mechanism for medical images, enabling multi-party sharing in a secure manner. While we have demonstrated its effectiveness with chest X-ray images, the mechanism can be utilized in other medical images modalities as well.

Risk Stratification in Nonischemic Dilated Cardiomyopathy Using CMR Imaging: A Systematic Review and Meta-Analysis.

Importance: Accurate risk stratification of nonischemic dilated cardiomyopathy (NIDCM) remains challenging. Objective: To evaluate the association of cardiac magnetic resonance (CMR) imaging-derived measurements with clinical outcomes in NIDCM. Data Sources: MEDLINE, Embase, Cochrane Library, and Web of Science Core Collection databases were systematically searched for articles from January 2005 to April 2023. Study Selection: Prospective and retrospective nonrandomized diagnostic studies reporting on the association between CMR imaging-derived measurements and adverse clinical outcomes in NIDCM were deemed eligible. Data Extraction and Synthesis: Prespecified items related to patient population, CMR imaging measurements, and clinical outcomes were extracted at the study level by 2 independent reviewers. Random-effects models were fitted using restricted maximum likelihood estimation and the method of Hartung, Knapp, Sidik, and Jonkman. Main Outcomes and Measures: All-cause mortality, cardiovascular mortality, arrhythmic events, heart failure events, and major adverse cardiac events (MACE). Results: A total of 103 studies including 29 687 patients with NIDCM were analyzed. Late gadolinium enhancement (LGE) presence and extent (per 1%) were associated with higher all-cause mortality (hazard ratio [HR], 1.81 [95% CI, 1.60-2.04]; P < .001 and HR, 1.07 [95% CI, 1.02-1.12]; P = .02, respectively), cardiovascular mortality (HR, 2.43 [95% CI, 2.13-2.78]; P < .001 and HR, 1.15 [95% CI, 1.07-1.24]; P = .01), arrhythmic events (HR, 2.69 [95% CI, 2.20-3.30]; P < .001 and HR, 1.07 [95% CI, 1.03-1.12]; P = .004) and heart failure events (HR, 1.98 [95% CI, 1.73-2.27]; P < .001 and HR, 1.06 [95% CI, 1.01-1.10]; P = .02). Left ventricular ejection fraction (LVEF) (per 1%) was not associated with all-cause mortality (HR, 0.99 [95% CI, 0.97-1.02]; P = .47), cardiovascular mortality (HR, 0.97 [95% CI, 0.94-1.00]; P = .05), or arrhythmic outcomes (HR, 0.99 [95% CI, 0.97-1.01]; P = .34). Lower risks for heart failure events (HR, 0.97 [95% CI, 0.95-0.98]; P = .002) and MACE (HR, 0.98 [95% CI, 0.96-0.99]; P < .001) were observed with higher LVEF. Higher native T1 relaxation times (per 10 ms) were associated with arrhythmic events (HR, 1.07 [95% CI, 1.01-1.14]; P = .04) and MACE (HR, 1.06 [95% CI, 1.01-1.11]; P = .03). Global longitudinal strain (GLS) (per 1%) was not associated with heart failure events (HR, 1.06 [95% CI, 0.95-1.18]; P = .15) or MACE (HR, 1.03 [95% CI, 0.94-1.14]; P = .43). Limited data precluded definitive analysis for native T1 relaxation times, GLS, and extracellular volume fraction (ECV) with respect to mortality outcomes. Conclusion: The presence and extent of LGE were associated with various adverse clinical outcomes, whereas LVEF was not significantly associated with mortality and arrhythmic end points in NIDCM. Risk stratification using native T1 relaxation times, extracellular volume fraction, and global longitudinal strain requires further evaluation.

A cycle-consistent adversarial network for brain PET partial volume correction without prior anatomical information.

PURPOSE: Partial volume effect (PVE) is a consequence of the limited spatial resolution of PET scanners. PVE can cause the intensity values of a particular voxel to be underestimated or overestimated due to the effect of surrounding tracer uptake. We propose a novel partial volume correction (PVC) technique to overcome the adverse effects of PVE on PET images. METHODS: Two hundred and twelve clinical brain PET scans, including 50 18F-Fluorodeoxyglucose (18F-FDG), 50 18F-Flortaucipir, 36 18F-Flutemetamol, and 76 18F-FluoroDOPA, and their corresponding T1-weighted MR images were enrolled in this study. The Iterative Yang technique was used for PVC as a reference or surrogate of the ground truth for evaluation. A cycle-consistent adversarial network (CycleGAN) was trained to directly map non-PVC PET images to PVC PET images. Quantitative analysis using various metrics, including structural similarity index (SSIM), root mean squared error (RMSE), and peak signal-to-noise ratio (PSNR), was performed. Furthermore, voxel-wise and region-wise-based correlations of activity concentration between the predicted and reference images were evaluated through joint histogram and Bland and Altman analysis. In addition, radiomic analysis was performed by calculating 20 radiomic features within 83 brain regions. Finally, a voxel-wise two-sample t-test was used to compare the predicted PVC PET images with reference PVC images for each radiotracer. RESULTS: The Bland and Altman analysis showed the largest and smallest variance for 18F-FDG (95% CI: - 0.29, + 0.33 SUV, mean = 0.02 SUV) and 18F-Flutemetamol (95% CI: - 0.26, + 0.24 SUV, mean = - 0.01 SUV), respectively. The PSNR was lowest (29.64 ± 1.13 dB) for 18F-FDG and highest (36.01 ± 3.26 dB) for 18F-Flutemetamol. The smallest and largest SSIM were achieved for 18F-FDG (0.93 ± 0.01) and 18F-Flutemetamol (0.97 ± 0.01), respectively. The average relative error for the kurtosis radiomic feature was 3.32%, 9.39%, 4.17%, and 4.55%, while it was 4.74%, 8.80%, 7.27%, and 6.81% for NGLDM_contrast feature for 18F-Flutemetamol, 18F-FluoroDOPA, 18F-FDG, and 18F-Flortaucipir, respectively. CONCLUSION: An end-to-end CycleGAN PVC method was developed and evaluated. Our model generates PVC images from the original non-PVC PET images without requiring additional anatomical information, such as MRI or CT. Our model eliminates the need for accurate registration or segmentation or PET scanner system response characterization. In addition, no assumptions regarding anatomical structure size, homogeneity, boundary, or background level are required.

Decentralized collaborative multi-institutional PET attenuation and scatter correction using federated deep learning.

PURPOSE: Attenuation correction and scatter compensation (AC/SC) are two main steps toward quantitative PET imaging, which remain challenging in PET-only and PET/MRI systems. These can be effectively tackled via deep learning (DL) methods. However, trustworthy, and generalizable DL models commonly require well-curated, heterogeneous, and large datasets from multiple clinical centers. At the same time, owing to legal/ethical issues and privacy concerns, forming a large collective, centralized dataset poses significant challenges. In this work, we aimed to develop a DL-based model in a multicenter setting without direct sharing of data using federated learning (FL) for AC/SC of PET images. METHODS: Non-attenuation/scatter corrected and CT-based attenuation/scatter corrected (CT-ASC) 18F-FDG PET images of 300 patients were enrolled in this study. The dataset consisted of 6 different centers, each with 50 patients, with scanner, image acquisition, and reconstruction protocols varying across the centers. CT-based ASC PET images served as the standard reference. All images were reviewed to include high-quality and artifact-free PET images. Both corrected and uncorrected PET images were converted to standardized uptake values (SUVs). We used a modified nested U-Net utilizing residual U-block in a U-shape architecture. We evaluated two FL models, namely sequential (FL-SQ) and parallel (FL-PL) and compared their performance with the baseline centralized (CZ) learning model wherein the data were pooled to one server, as well as center-based (CB) models where for each center the model was built and evaluated separately. Data from each center were divided to contribute to training (30 patients), validation (10 patients), and test sets (10 patients). Final evaluations and reports were performed on 60 patients (10 patients from each center). RESULTS: In terms of percent SUV absolute relative error (ARE%), both FL-SQ (CI:12.21-14.81%) and FL-PL (CI:11.82-13.84%) models demonstrated excellent agreement with the centralized framework (CI:10.32-12.00%), while FL-based algorithms improved model performance by over 11% compared to CB training strategy (CI: 22.34-26.10%). Furthermore, the Mann-Whitney test between different strategies revealed no significant differences between CZ and FL-based algorithms (p-value > 0.05) in center-categorized mode. At the same time, a significant difference was observed between the different training approaches on the overall dataset (p-value < 0.05). In addition, voxel-wise comparison, with respect to reference CT-ASC, exhibited similar performance for images predicted by CZ (R2 = 0.94), FL-SQ (R2 = 0.93), and FL-PL (R2 = 0.92), while CB model achieved a far lower coefficient of determination (R2 = 0.74). Despite the strong correlations between CZ and FL-based methods compared to reference CT-ASC, a slight underestimation of predicted voxel values was observed. CONCLUSION: Deep learning-based models provide promising results toward quantitative PET image reconstruction. Specifically, we developed two FL models and compared their performance with center-based and centralized models. The proposed FL-based models achieved higher performance compared to center-based models, comparable with centralized models. Our work provided strong empirical evidence that the FL framework can fully benefit from the generalizability and robustness of DL models used for AC/SC in PET, while obviating the need for the direct sharing of datasets between clinical imaging centers.

Differential privacy preserved federated transfer learning for multi-institutional 68Ga-PET image artefact detection and disentanglement.

PURPOSE: Image artefacts continue to pose challenges in clinical molecular imaging, resulting in misdiagnoses, additional radiation doses to patients and financial costs. Mismatch and halo artefacts occur frequently in gallium-68 (68Ga)-labelled compounds whole-body PET/CT imaging. Correcting for these artefacts is not straightforward and requires algorithmic developments, given that conventional techniques have failed to address them adequately. In the current study, we employed differential privacy-preserving federated transfer learning (FTL) to manage clinical data sharing and tackle privacy issues for building centre-specific models that detect and correct artefacts present in PET images. METHODS: Altogether, 1413 patients with 68Ga prostate-specific membrane antigen (PSMA)/DOTA-TATE (TOC) PET/CT scans from 3 countries, including 8 different centres, were enrolled in this study. CT-based attenuation and scatter correction (CT-ASC) was used in all centres for quantitative PET reconstruction. Prior to model training, an experienced nuclear medicine physician reviewed all images to ensure the use of high-quality, artefact-free PET images (421 patients' images). A deep neural network (modified U2Net) was trained on 80% of the artefact-free PET images to utilize centre-based (CeBa), centralized (CeZe) and the proposed differential privacy FTL frameworks. Quantitative analysis was performed in 20% of the clean data (with no artefacts) in each centre. A panel of two nuclear medicine physicians conducted qualitative assessment of image quality, diagnostic confidence and image artefacts in 128 patients with artefacts (256 images for CT-ASC and FTL-ASC). RESULTS: The three approaches investigated in this study for 68Ga-PET imaging (CeBa, CeZe and FTL) resulted in a mean absolute error (MAE) of 0.42 ± 0.21 (CI 95%: 0.38 to 0.47), 0.32 ± 0.23 (CI 95%: 0.27 to 0.37) and 0.28 ± 0.15 (CI 95%: 0.25 to 0.31), respectively. Statistical analysis using the Wilcoxon test revealed significant differences between the three approaches, with FTL outperforming CeBa and CeZe (p-value < 0.05) in the clean test set. The qualitative assessment demonstrated that FTL-ASC significantly improved image quality and diagnostic confidence and decreased image artefacts, compared to CT-ASC in 68Ga-PET imaging. In addition, mismatch and halo artefacts were successfully detected and disentangled in the chest, abdomen and pelvic regions in 68Ga-PET imaging. CONCLUSION: The proposed approach benefits from using large datasets from multiple centres while preserving patient privacy. Qualitative assessment by nuclear medicine physicians showed that the proposed model correctly addressed two main challenging artefacts in 68Ga-PET imaging. This technique could be integrated in the clinic for 68Ga-PET imaging artefact detection and disentanglement using multicentric heterogeneous datasets.

Fully automated accurate patient positioning in computed tomography using anterior-posterior localizer images and a deep neural network: a dual-center study.

OBJECTIVES: This study aimed to improve patient positioning accuracy by relying on a CT localizer and a deep neural network to optimize image quality and radiation dose. METHODS: We included 5754 chest CT axial and anterior-posterior (AP) images from two different centers, C1 and C2. After pre-processing, images were split into training (80%) and test (20%) datasets. A deep neural network was trained to generate 3D axial images from the AP localizer. The geometric centerlines of patient bodies were indicated by creating a bounding box on the predicted images. The distance between the body centerline, estimated by the deep learning model and ground truth (BCAP), was compared with patient mis-centering during manual positioning (BCMP). We evaluated the performance of our model in terms of distance between the lung centerline estimated by the deep learning model and the ground truth (LCAP). RESULTS: The error in terms of BCAP was - 0.75 ± 7.73 mm and 2.06 ± 10.61 mm for C1 and C2, respectively. This error was significantly lower than BCMP, which achieved an error of 9.35 ± 14.94 and 13.98 ± 14.5 mm for C1 and C2, respectively. The absolute BCAP was 5.7 ± 5.26 and 8.26 ± 6.96 mm for C1 and C2, respectively. The LCAP metric was 1.56 ± 10.8 and -0.27 ± 16.29 mm for C1 and C2, respectively. The error in terms of BCAP and LCAP was higher for larger patients (p value < 0.01). CONCLUSION: The accuracy of the proposed method was comparable to available alternative methods, carrying the advantage of being free from errors related to objects blocking the camera visibility. KEY POINTS: • Patient mis-centering in the anterior-posterior direction (AP) is a common problem in clinical practice which can degrade image quality and increase patient radiation dose. • We proposed a deep neural network for automatic patient positioning using only the CT image localizer, achieving a performance comparable to alternative techniques, such as the external 3D visual camera. • The advantage of the proposed method is that it is free from errors related to objects blocking the camera visibility and that it could be implemented on imaging consoles as a patient positioning support tool.

Real-time, acquisition parameter-free voxel-wise patient-specific Monte Carlo dose reconstruction in whole-body CT scanning using deep neural networks.

OBJECTIVE: We propose a deep learning-guided approach to generate voxel-based absorbed dose maps from whole-body CT acquisitions. METHODS: The voxel-wise dose maps corresponding to each source position/angle were calculated using Monte Carlo (MC) simulations considering patient- and scanner-specific characteristics (SP_MC). The dose distribution in a uniform cylinder was computed through MC calculations (SP_uniform). The density map and SP_uniform dose maps were fed into a residual deep neural network (DNN) to predict SP_MC through an image regression task. The whole-body dose maps reconstructed by the DNN and MC were compared in the 11 test cases scanned with two tube voltages through transfer learning with/without tube current modulation (TCM). The voxel-wise and organ-wise dose evaluations, such as mean error (ME, mGy), mean absolute error (MAE, mGy), relative error (RE, %), and relative absolute error (RAE, %), were performed. RESULTS: The model performance for the 120 kVp and TCM test set in terms of ME, MAE, RE, and RAE voxel-wise parameters was - 0.0302 ± 0.0244 mGy, 0.0854 ± 0.0279 mGy, - 1.13 ± 1.41%, and 7.17 ± 0.44%, respectively. The organ-wise errors for 120 kVp and TCM scenario averaged over all segmented organs in terms of ME, MAE, RE, and RAE were - 0.144 ± 0.342 mGy, and 0.23 ± 0.28 mGy, - 1.11 ± 2.90%, 2.34 ± 2.03%, respectively. CONCLUSION: Our proposed deep learning model is able to generate voxel-level dose maps from a whole-body CT scan with reasonable accuracy suitable for organ-level absorbed dose estimation. CLINICAL RELEVANCE STATEMENT: We proposed a novel method for voxel dose map calculation using deep neural networks. This work is clinically relevant since accurate dose calculation for patients can be carried out within acceptable computational time compared to lengthy Monte Carlo calculations. KEY POINTS: • We proposed a deep neural network approach as an alternative to Monte Carlo dose calculation. • Our proposed deep learning model is able to generate voxel-level dose maps from a whole-body CT scan with reasonable accuracy, suitable for organ-level dose estimation. • By generating a dose distribution from a single source position, our model can generate accurate and personalized dose maps for a wide range of acquisition parameters.

Time-to-event overall survival prediction in glioblastoma multiforme patients using magnetic resonance imaging radiomics.

PURPOSE: Glioblastoma Multiforme (GBM) represents the predominant aggressive primary tumor of the brain with short overall survival (OS) time. We aim to assess the potential of radiomic features in predicting the time-to-event OS of patients with GBM using machine learning (ML) algorithms. MATERIALS AND METHODS: One hundred nineteen patients with GBM, who had T1-weighted contrast-enhanced and T2-FLAIR MRI sequences, along with clinical data and survival time, were enrolled. Image preprocessing methods included 64 bin discretization, Laplacian of Gaussian (LOG) filters with three Sigma values and eight variations of Wavelet Transform. Images were then segmented, followed by the extraction of 1212 radiomic features. Seven feature selection (FS) methods and six time-to-event ML algorithms were utilized. The combination of preprocessing, FS, and ML algorithms (12 × 7 × 6 = 504 models) was evaluated by multivariate analysis. RESULTS: Our multivariate analysis showed that the best prognostic FS/ML combinations are the Mutual Information (MI)/Cox Boost, MI/Generalized Linear Model Boosting (GLMB) and MI/Generalized Linear Model Network (GLMN), all of which were done via the LOG (Sigma = 1 mm) preprocessing method (C-index = 0.77). The LOG filter with Sigma = 1 mm preprocessing method, MI, GLMB and GLMN achieved significantly higher C-indices than other preprocessing, FS, and ML methods (all p values < 0.05, mean C-indices of 0.65, 0.70, and 0.64, respectively). CONCLUSION: ML algorithms are capable of predicting the time-to-event OS of patients using MRI-based radiomic and clinical features. MRI-based radiomics analysis in combination with clinical variables might appear promising in assisting clinicians in the survival prediction of patients with GBM. Further research is needed to establish the applicability of radiomics in the management of GBM in the clinic.

Left Ventricular Myocardial Dysfunction Evaluation in Thalassemia Patients Using Echocardiographic Radiomic Features and Machine Learning Algorithms.

Heart failure caused by iron deposits in the myocardium is the primary cause of mortality in beta-thalassemia major patients. Cardiac magnetic resonance imaging (CMRI) T2* is the primary screening technique used to detect myocardial iron overload, but inherently bears some limitations. In this study, we aimed to differentiate beta-thalassemia major patients with myocardial iron overload from those without myocardial iron overload (detected by T2*CMRI) based on radiomic features extracted from echocardiography images and machine learning (ML) in patients with normal left ventricular ejection fraction (LVEF > 55%) in echocardiography. Out of 91 cases, 44 patients with thalassemia major with normal LVEF (> 55%) and T2* ≤ 20 ms and 47 people with LVEF > 55% and T2* > 20 ms as the control group were included in the study. Radiomic features were extracted for each end-systolic (ES) and end-diastolic (ED) image. Then, three feature selection (FS) methods and six different classifiers were used. The models were evaluated using various metrics, including the area under the ROC curve (AUC), accuracy (ACC), sensitivity (SEN), and specificity (SPE). Maximum relevance-minimum redundancy-eXtreme gradient boosting (MRMR-XGB) (AUC = 0.73, ACC = 0.73, SPE = 0.73, SEN = 0.73), ANOVA-MLP (AUC = 0.69, ACC = 0.69, SPE = 0.56, SEN = 0.83), and recursive feature elimination-K-nearest neighbors (RFE-KNN) (AUC = 0.65, ACC = 0.65, SPE = 0.64, SEN = 0.65) were the best models in ED, ES, and ED&ES datasets. Using radiomic features extracted from echocardiographic images and ML, it is feasible to predict cardiac problems caused by iron overload.

Deep Learning-based Non-rigid Image Registration for High-dose Rate Brachytherapy in Inter-fraction Cervical Cancer.

In this study, an inter-fraction organ deformation simulation framework for the locally advanced cervical cancer (LACC), which considers the anatomical flexibility, rigidity, and motion within an image deformation, was proposed. Data included 57 CT scans (7202 2D slices) of patients with LACC randomly divided into the train (n = 42) and test (n = 15) datasets. In addition to CT images and the corresponding RT structure (bladder, cervix, and rectum), the bone was segmented, and the coaches were eliminated. The correlated stochastic field was simulated using the same size as the target image (used for deformation) to produce the general random deformation. The deformation field was optimized to have a maximum amplitude in the rectum region, a moderate amplitude in the bladder region, and an amplitude as minimum as possible within bony structures. The DIRNet is a convolutional neural network that consists of convolutional regressors, spatial transformation, as well as resampling blocks. It was implemented by different parameters. Mean Dice indices of 0.89 ± 0.02, 0.96 ± 0.01, and 0.93 ± 0.02 were obtained for the cervix, bladder, and rectum (defined as at-risk organs), respectively. Furthermore, a mean average symmetric surface distance of 1.61 ± 0.46 mm for the cervix, 1.17 ± 0.15 mm for the bladder, and 1.06 ± 0.42 mm for the rectum were achieved. In addition, a mean Jaccard of 0.86 ± 0.04 for the cervix, 0.93 ± 0.01 for the bladder, and 0.88 ± 0.04 for the rectum were observed on the test dataset (15 subjects). Deep learning-based non-rigid image registration is, therefore, proposed for the high-dose-rate brachytherapy in inter-fraction cervical cancer since it outperformed conventional algorithms.

Post-revascularization Ejection Fraction Prediction for Patients Undergoing Percutaneous Coronary Intervention Based on Myocardial Perfusion SPECT Imaging Radiomics: a Preliminary Machine Learning Study.

In this study, the ability of radiomics features extracted from myocardial perfusion imaging with SPECT (MPI-SPECT) was investigated for the prediction of ejection fraction (EF) post-percutaneous coronary intervention (PCI) treatment. A total of 52 patients who had undergone pre-PCI MPI-SPECT were enrolled in this study. After normalization of the images, features were extracted from the left ventricle, initially automatically segmented by k-means and active contour methods, and finally edited and approved by an expert radiologist. More than 1700 2D and 3D radiomics features were extracted from each patient's scan. A cross-combination of three feature selections and seven classifier methods was implemented. Three classes of no or dis-improvement (class 1), improved EF from 0 to 5% (class 2), and improved EF over 5% (class 3) were predicted by using tenfold cross-validation. Lastly, the models were evaluated based on accuracy, AUC, sensitivity, specificity, precision, and F-score. Neighborhood component analysis (NCA) selected the most predictive feature signatures, including Gabor, first-order, and NGTDM features. Among the classifiers, the best performance was achieved by the fine KNN classifier, which yielded mean accuracy, AUC, sensitivity, specificity, precision, and F-score of 0.84, 0.83, 0.75, 0.87, 0.78, and 0.76, respectively, in 100 iterations of classification, within the 52 patients with 10-fold cross-validation. The MPI-SPECT-based radiomic features are well suited for predicting post-revascularization EF and therefore provide a helpful approach for deciding on the most appropriate treatment.

Myocardial Perfusion SPECT Imaging Radiomic Features and Machine Learning Algorithms for Cardiac Contractile Pattern Recognition.

A U-shaped contraction pattern was shown to be associated with a better Cardiac resynchronization therapy (CRT) response. The main goal of this study is to automatically recognize left ventricular contractile patterns using machine learning algorithms trained on conventional quantitative features (ConQuaFea) and radiomic features extracted from Gated single-photon emission computed tomography myocardial perfusion imaging (GSPECT MPI). Among 98 patients with standard resting GSPECT MPI included in this study, 29 received CRT therapy and 69 did not (also had CRT inclusion criteria but did not receive treatment yet at the time of data collection, or refused treatment). A total of 69 non-CRT patients were employed for training, and the 29 were employed for testing. The models were built utilizing features from three distinct feature sets (ConQuaFea, radiomics, and ConQuaFea + radiomics (combined)), which were chosen using Recursive feature elimination (RFE) feature selection (FS), and then trained using seven different machine learning (ML) classifiers. In addition, CRT outcome prediction was assessed by different treatment inclusion criteria as the study's final phase. The MLP classifier had the highest performance among ConQuaFea models (AUC, SEN, SPE = 0.80, 0.85, 0.76). RF achieved the best performance in terms of AUC, SEN, and SPE with values of 0.65, 0.62, and 0.68, respectively, among radiomic models. GB and RF approaches achieved the best AUC, SEN, and SPE values of 0.78, 0.92, and 0.63 and 0.74, 0.93, and 0.56, respectively, among the combined models. A promising outcome was obtained when using radiomic and ConQuaFea from GSPECT MPI to detect left ventricular contractile patterns by machine learning.

Deep-TOF-PET: Deep learning-guided generation of time-of-flight from non-TOF brain PET images in the image and projection domains.

We aim to synthesize brain time-of-flight (TOF) PET images/sinograms from their corresponding non-TOF information in the image space (IS) and sinogram space (SS) to increase the signal-to-noise ratio (SNR) and contrast of abnormalities, and decrease the bias in tracer uptake quantification. One hundred forty clinical brain 18 F-FDG PET/CT scans were collected to generate TOF and non-TOF sinograms. The TOF sinograms were split into seven time bins (0, ±1, ±2, ±3). The predicted TOF sinogram was reconstructed and the performance of both models (IS and SS) compared with reference TOF and non-TOF. Wide-ranging quantitative and statistical analysis metrics, including structural similarity index metric (SSIM), root mean square error (RMSE), as well as 28 radiomic features for 83 brain regions were extracted to evaluate the performance of the CycleGAN model. SSIM and RMSE of 0.99 ± 0.03, 0.98 ± 0.02 and 0.12 ± 0.09, 0.16 ± 0.04 were achieved for the generated TOF-PET images in IS and SS, respectively. They were 0.97 ± 0.03 and 0.22 ± 0.12, respectively, for non-TOF-PET images. The Bland & Altman analysis revealed that the lowest tracer uptake value bias (-0.02%) and minimum variance (95% CI: -0.17%, +0.21%) were achieved for TOF-PET images generated in IS. For malignant lesions, the contrast in the test dataset was enhanced from 3.22 ± 2.51 for non-TOF to 3.34 ± 0.41 and 3.65 ± 3.10 for TOF PET in SS and IS, respectively. The implemented CycleGAN is capable of generating TOF from non-TOF PET images to achieve better image quality.

Fast and Accurate U-Net Model for Fetal Ultrasound Image Segmentation.

U-Net based algorithms, due to their complex computations, include limitations when they are used in clinical devices. In this paper, we addressed this problem through a novel U-Net based architecture that called fast and accurate U-Net for medical image segmentation task. The proposed fast and accurate U-Net model contains four tuned 2D-convolutional, 2D-transposed convolutional, and batch normalization layers as its main layers. There are four blocks in the encoder-decoder path. The results of our proposed architecture were evaluated using a prepared dataset for head circumference and abdominal circumference segmentation tasks, and a public dataset (HC18-Grand challenge dataset) for fetal head circumference measurement. The proposed fast network significantly improved the processing time in comparison with U-Net, dilated U-Net, R2U-Net, attention U-Net, and MFP U-Net. It took 0.47 seconds for segmenting a fetal abdominal image. In addition, over the prepared dataset using the proposed accurate model, Dice and Jaccard coefficients were 97.62% and 95.43% for fetal head segmentation, 95.07%, and 91.99% for fetal abdominal segmentation. Moreover, we have obtained the Dice and Jaccard coefficients of 97.45% and 95.00% using the public HC18-Grand challenge dataset. Based on the obtained results, we have concluded that a fine-tuned and a simple well-structured model used in clinical devices can outperform complex models.

Robust-Deep: A Method for Increasing Brain Imaging Datasets to Improve Deep Learning Models' Performance and Robustness.

A small dataset commonly affects generalization, robustness, and overall performance of deep neural networks (DNNs) in medical imaging research. Since gathering large clinical databases is always difficult, we proposed an analytical method for producing a large realistic/diverse dataset. Clinical brain PET/CT/MR images including full-dose (FD), low-dose (LD) corresponding to only 5 % of events acquired in the FD scan, non-attenuated correction (NAC) and CT-based measured attenuation correction (MAC) PET images, CT images and T1 and T2 MR sequences of 35 patients were included. All images were registered to the Montreal Neurological Institute (MNI) template. Laplacian blending was used to make a natural presentation using information in the frequency domain of images from two separate patients, as well as the blending mask. This classical technique from the computer vision and image processing communities is still widely used and unlike modern DNNs, does not require the availability of training data. A modified ResNet DNN was implemented to evaluate four image-to-image translation tasks, including LD to FD, LD+MR to FD, NAC to MAC, and MRI to CT, with and without using the synthesized images. Quantitative analysis using established metrics, including the peak signal-to-noise ratio (PSNR), structural similarity index metric (SSIM), and joint histogram analysis was performed for quantitative evaluation. The quantitative comparison between the registered small dataset containing 35 patients and the large dataset containing 350 synthesized plus 35 real dataset demonstrated improvement of the RMSE and SSIM by 29% and 8% for LD to FD, 40% and 7% for LD+MRI to FD, 16% and 8% for NAC to MAC, and 24% and 11% for MRI to CT mapping task, respectively. The qualitative/quantitative analysis demonstrated that the proposed model improved the performance of all four DNN models through producing images of higher quality and lower quantitative bias and variance compared to reference images.

Myocardial Function Prediction After Coronary Artery Bypass Grafting Using MRI Radiomic Features and Machine Learning Algorithms.

The main aim of the present study was to predict myocardial function improvement in cardiac MR (LGE-CMR) images in patients after coronary artery bypass grafting (CABG) using radiomics and machine learning algorithms. Altogether, 43 patients who had visible scars on short-axis LGE-CMR images and were candidates for CABG surgery were selected and enrolled in this study. MR imaging was performed preoperatively using a 1.5-T MRI scanner. All images were segmented by two expert radiologists (in consensus). Prior to extraction of radiomics features, all MR images were resampled to an isotropic voxel size of 1.8 × 1.8 × 1.8 mm3. Subsequently, intensities were quantized to 64 discretized gray levels and a total of 93 features were extracted. The applied algorithms included a smoothly clipped absolute deviation (SCAD)-penalized support vector machine (SVM) and the recursive partitioning (RP) algorithm as a robust classifier for binary classification in this high-dimensional and non-sparse data. All models were validated with repeated fivefold cross-validation and 10,000 bootstrapping resamples. Ten and seven features were selected with SCAD-penalized SVM and RP algorithm, respectively, for CABG responder/non-responder classification. Considering univariate analysis, the GLSZM gray-level non-uniformity-normalized feature achieved the best performance (AUC: 0.62, 95% CI: 0.53-0.76) with SCAD-penalized SVM. Regarding multivariable modeling, SCAD-penalized SVM obtained an AUC of 0.784 (95% CI: 0.64-0.92), whereas the RP algorithm achieved an AUC of 0.654 (95% CI: 0.50-0.82). In conclusion, different radiomics texture features alone or combined in multivariate analysis using machine learning algorithms provide prognostic information regarding myocardial function in patients after CABG.