Artificial intelligence-based joint attenuation and scatter correction strategies for multi-tracer total-body PET.

BACKGROUND: Low-dose ungated CT is commonly used for total-body PET attenuation and scatter correction (ASC). However, CT-based ASC (CT-ASC) is limited by radiation dose risks of CT examinations, propagation of CT-based artifacts and potential mismatches between PET and CT. We demonstrate the feasibility of direct ASC for multi-tracer total-body PET in the image domain. METHODS: Clinical uEXPLORER total-body PET/CT datasets of [18F]FDG (N = 52), [18F]FAPI (N = 46) and [68Ga]FAPI (N = 60) were retrospectively enrolled in this study. We developed an improved 3D conditional generative adversarial network (cGAN) to directly estimate attenuation and scatter-corrected PET images from non-attenuation and scatter-corrected (NASC) PET images. The feasibility of the proposed 3D cGAN-based ASC was validated using four training strategies: (1) Paired 3D NASC and CT-ASC PET images from three tracers were pooled into one centralized server (CZ-ASC). (2) Paired 3D NASC and CT-ASC PET images from each tracer were individually used (DL-ASC). (3) Paired NASC and CT-ASC PET images from one tracer ([18F]FDG) were used to train the networks, while the other two tracers were used for testing without fine-tuning (NFT-ASC). (4) The pre-trained networks of (3) were fine-tuned with two other tracers individually (FT-ASC). We trained all networks in fivefold cross-validation. The performance of all ASC methods was evaluated by qualitative and quantitative metrics using CT-ASC as the reference. RESULTS: CZ-ASC, DL-ASC and FT-ASC showed comparable visual quality with CT-ASC for all tracers. CZ-ASC and DL-ASC resulted in a normalized mean absolute error (NMAE) of 8.51 ± 7.32% versus 7.36 ± 6.77% (p < 0.05), outperforming NASC (p < 0.0001) in [18F]FDG dataset. CZ-ASC, FT-ASC and DL-ASC led to NMAE of 6.44 ± 7.02%, 6.55 ± 5.89%, and 7.25 ± 6.33% in [18F]FAPI dataset, and NMAE of 5.53 ± 3.99%, 5.60 ± 4.02%, and 5.68 ± 4.12% in [68Ga]FAPI dataset, respectively. CZ-ASC, FT-ASC and DL-ASC were superior to NASC (p < 0.0001) and NFT-ASC (p < 0.0001) in terms of NMAE results. CONCLUSIONS: CZ-ASC, DL-ASC and FT-ASC demonstrated the feasibility of providing accurate and robust ASC for multi-tracer total-body PET, thereby reducing the radiation hazards to patients from redundant CT examinations. CZ-ASC and FT-ASC could outperform DL-ASC for cross-tracer total-body PET AC.

BAF-Net: bidirectional attention-aware fluid pyramid feature integrated multimodal fusion network for diagnosis and prognosis.

Objective. To go beyond the deficiencies of the three conventional multimodal fusion strategies (i.e. input-, feature- and output-level fusion), we propose a bidirectional attention-aware fluid pyramid feature integrated fusion network (BAF-Net) with cross-modal interactions for multimodal medical image diagnosis and prognosis.Approach. BAF-Net is composed of two identical branches to preserve the unimodal features and one bidirectional attention-aware distillation stream to progressively assimilate cross-modal complements and to learn supplementary features in both bottom-up and top-down processes. Fluid pyramid connections were adopted to integrate the hierarchical features at different levels of the network, and channel-wise attention modules were exploited to mitigate cross-modal cross-level incompatibility. Furthermore, depth-wise separable convolution was introduced to fuse the cross-modal cross-level features to alleviate the increase in parameters to a great extent. The generalization abilities of BAF-Net were evaluated in terms of two clinical tasks: (1) an in-house PET-CT dataset with 174 patients for differentiation between lung cancer and pulmonary tuberculosis. (2) A public multicenter PET-CT head and neck cancer dataset with 800 patients from nine centers for overall survival prediction.Main results. On the LC-PTB dataset, improved performance was found in BAF-Net (AUC = 0.7342) compared with input-level fusion model (AUC = 0.6825;p< 0.05), feature-level fusion model (AUC = 0.6968;p= 0.0547), output-level fusion model (AUC = 0.7011;p< 0.05). On the H&N cancer dataset, BAF-Net (C-index = 0.7241) outperformed the input-, feature-, and output-level fusion model, with 2.95%, 3.77%, and 1.52% increments of C-index (p= 0.3336, 0.0479 and 0.2911, respectively). The ablation experiments demonstrated the effectiveness of all the designed modules regarding all the evaluated metrics in both datasets.Significance. Extensive experiments on two datasets demonstrated better performance and robustness of BAF-Net than three conventional fusion strategies and PET or CT unimodal network in terms of diagnosis and prognosis.

Semi-supervised model based on implicit neural representation and mutual learning (SIMN) for multi-center nasopharyngeal carcinoma segmentation on MRI.

BACKGROUND: The issue of using deep learning to obtain accurate gross tumor volume (GTV) and metastatic lymph nodes (MLN) segmentation for nasopharyngeal carcinoma (NPC) on heterogeneous magnetic resonance imaging (MRI) images with limited labeling remains unsolved. METHOD: We collected 918 patients with MRI images from three hospitals to develop and validate models and proposed a semi-supervised framework for the fine delineation of multi-center NPC boundaries by integrating uncertainty-based implicit neural representations named SIMN. The framework utilizes the deep mutual learning approach with CNN and Transformer, incorporating dynamic thresholds. Additionally, domain adaptive algorithms are employed to enhance the performance. RESULTS: SIMN predictions have a high overlap ratio with the ground truth. Under the 20 % labeled cases, for the internal test cohorts, the average DSC in GTV and MLN are 0.7981 and 0.7804, respectively; for external test cohort Wu Zhou Red Cross Hospital, the average DSC in GTV and MLN are 0.7217 and 0.7581, respectively; for external test cohorts First People Hospital of Foshan, the average DSC in GTV and MLN are 0.7004 and 0.7692, respectively. No significant differences are found in DSC, HD95, ASD, and Recall for patients with different clinical categories. Moreover, SIMN outperformed existing classical semi-supervised methods. CONCLUSIONS: SIMN showed a highly accurate GTV and MLN segmentation for NPC on multi-center MRI images under Semi-Supervised Learning (SSL), which can easily transfer to other centers without fine-tuning. It suggests that it has the potential to act as a generalized delineation solution for heterogeneous MRI images with limited labels in clinical deployment.

Optimal batch determination for improved harmonization and prognostication of multi-center PET/CT radiomics feature in head and neck cancer.

Objective. To determine the optimal approach for identifying and mitigating batch effects in PET/CT radiomics features, and further improve the prognosis of patients with head and neck cancer (HNC), this study investigated the performance of three batch harmonization methods.Approach. Unsupervised harmonization identified the batch labels by K-means clustering. Supervised harmonization regarding the image acquisition factors (center, manufacturer, scanner, filter kernel) as known/given batch labels, and Combat harmonization was then implemented separately and sequentially based on the batch labels, i.e. harmonizing features among batches determined by each factor individually or harmonizing features among batches determined by multiple factors successively. Extensive experiments were conducted to predict overall survival (OS) on public PET/CT datasets that contain 800 patients from 9 centers.Main results. In the external validation cohort, results show that compared to original models without harmonization, Combat harmonization would be beneficial in OS prediction with C-index of 0.687-0.740 versus 0.684-0.767. Supervised harmonization slightly outperformed unsupervised harmonization in all models (C-index: 0.692-0.767 versus 0.684-0.750). Separate harmonization outperformed sequential harmonization in CT_m+clinic and CT_cm+clinic models with C-index of 0.752 and 0.722, respectively, while sequential harmonization involved clinical features in PET_rs+clinic model further improving the performance and achieving the highest C-index of 0.767.Significance. Optimal batch determination especially sequential harmonization for Combat holds the potential to improve the prognostic power of radiomics model in multi-center HNC dataset with PET/CT imaging.

Multimodality radiomics analysis based on [18F]FDG PET/CT imaging and multisequence MRI: application to nasopharyngeal carcinoma prognosis.

OBJECTIVES: To determine whether radiomics models developed from 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) PET/CT combined with multisequence MRI could contribute to predicting the progression-free survival (PFS) of nasopharyngeal carcinoma (NPC) patients. METHODS: One hundred thirty-two NPC patients who underwent both PET/CT and MRI scanning were retrospectively enrolled (88 vs. 44 for training vs. testing). For each modality/sequence (i.e., PET, CT, T1, T1C, and T2), 1906 radiomics features were extracted from the primary tumor volume. Univariate Cox model and correlation analysis were used for feature selection. A multivariate Cox model was used to establish radiomics signature. Prognostic performances of 5 individual modality models and 12 multimodality models (3 integrations × 4 fusion strategies) were assessed by the concordance index (C-index) and log-rank test. A clinical-radiomics nomogram was built to explore the clinical utilities of radiomics signature, which was evaluated by discrimination, calibration curve, and decision curve analysis (DCA). RESULTS: The radiomics signatures of individual modalities showed limited prognostic efficacy with a C-index of 0.539-0.664 in the testing cohort. Different fusion strategies exhibited a slight difference in predictive performance. The PET/CT and MRI integrated model achieved the best performance with a C-index of 0.745 (95% CI, 0.619-0.865) in the testing cohort (log-rank test, p < 0.05). Clinical-radiomics nomogram further improved the prognosis, which also showed satisfactory discrimination, calibration, and net benefit. CONCLUSIONS: Multimodality radiomics analysis by combining PET/CT with multisequence MRI could potentially improve the efficacy of PFS prediction for NPC patients. KEY POINTS: • Individual modality radiomics models showed limited performance in prognosis evaluation for NPC patients. • Combined PET, CT and multisequence MRI radiomics signature could improve the prognostic efficacy. • Multilevel fusion strategies exhibit comparable performance but feature-level fusion deserves more attention.

Impact of Aggregation Methods for Texture Features on Their Robustness Performance: Application to Nasopharyngeal 18F-FDG PET/CT.

PURPOSE: This study aims to investigate the impact of aggregation methods used for the generation of texture features on their robustness of nasopharyngeal carcinoma (NPC) based on 18F-FDG PET/CT images. METHODS: 128 NPC patients were enrolled and 95 texture features were extracted for each patient including six feature families under different aggregation methods. For GLCM and GLRLM features, six aggregation methods were considered. For GLSZM, GLDZM, NGTDM and NGLDM features, three aggregation methods were considered. The robustness of the features affected by aggregation methods was assessed by the pair-wise intra-class correlation coefficient (ICC). Furthermore, the effects of discretization and partial volume correction (PVC) on the percent of ICC categories of all texture features were evaluated by overall ICC instead of the pair-wise ICC. RESULTS: There were 12 features with excellent pair-wise ICCs varying aggregation methods, namely joint average, sum average, autocorrelation, long run emphasis, high grey level run emphasis, short run high grey level emphasis, long run high grey level emphasis, run length variance, SZM high grey level emphasis, DZM high grey level emphasis, high grey level count emphasis and dependence count percentage. For GLCM and GLRLM features, 19/25 and 14/16 features showed excellent pair-wise ICCs varying aggregation methods (averaged and merged) on the same dimensional features (2D, 2.5D or 3D). Different discretization levels and partial volume corrections lead to consistent robustness of textural features affected by aggregation methods. CONCLUSION: Different dimensional features with the same aggregation methods showed worse robustness compared with the same dimensional features with different aggregation methods. Different discretization levels and PVC algorithms had a negligible effect on the percent of ICC categories of all texture features.

Prognostic value of 18F-FDG PET/CT-based radiomics combining dosiomics and dose volume histogram for head and neck cancer.

OBJECTIVES: By comparing the prognostic performance of 18F-FDG PET/CT-based radiomics combining dose features [Includes Dosiomics feature and the dose volume histogram (DVH) features] with that of conventional radiomics in head and neck cancer (HNC), multidimensional prognostic models were constructed to investigate the overall survival (OS) in HNC. MATERIALS AND METHODS: A total of 220 cases from four centres based on the Cancer Imaging Archive public dataset were used in this study, 2260 radiomics features and 1116 dosiomics features and 8 DVH features were extracted for each case, and classified into seven different models of PET, CT, Dose, PET+CT, PET+Dose, CT+Dose and PET+CT+Dose. Features were selected by univariate Cox and Spearman correlation coefficients, and the selected features were brought into the least absolute shrinkage and selection operator (LASSO)-Cox model. A nomogram was constructed to visually analyse the prognostic impact of the incorporated dose features. C-index and Kaplan-Meier curves (log-rank analysis) were used to evaluate and compare these models. RESULTS: The cases from the four centres were divided into three different training and validation sets according to the hospitals. The PET+CT+Dose model had C-indexes of 0.873 (95% CI 0.812-0.934), 0.759 (95% CI 0.663-0.855) and 0.835 (95% CI 0.745-0.925) in the validation set respectively, outperforming the rest models overall. The PET+CT+Dose model did well in classifying patients into high- and low-risk groups under all three different sets of experiments (p < 0.05). CONCLUSION: Multidimensional model of radiomics features combining dosiomics features and DVH features showed high prognostic performance for predicting OS in patients with HNC.

Functional-structural sub-region graph convolutional network (FSGCN): Application to the prognosis of head and neck cancer with PET/CT imaging.

BACKGROUND AND OBJECTIVE: Accurate risk stratification is crucial for enabling personalized treatment for head and neck cancer (HNC). Current PET/CT image-based prognostic methods include radiomics analysis and convolutional neural network (CNN), while extracting radiomics or deep features in grid Euclidean space has inherent limitations for risk stratification. Here, we propose a functional-structural sub-region graph convolutional network (FSGCN) for accurate risk stratification of HNC. METHODS: This study collected 642 patients from 8 different centers in The Cancer Imaging Archive (TCIA), 507 patients from 5 centers were used for training, and 135 patients from 3 centers were used for testing. The tumor was first clustered into multiple sub-regions by using PET and CT voxel information, and radiomics features were extracted from each sub-region to characterize its functional and structural information, a graph was then constructed to format the relationship/difference among different sub-regions in non-Euclidean space for each patient, followed by a residual gated graph convolutional network, the prognostic score was finally generated to predict the progression-free survival (PFS). RESULTS: In the testing cohort, compared with radiomics or FSGCN or clinical model alone, the model PETCTFea_CTROI + Cli that integrates FSGCN prognostic score and clinical parameter achieved the highest C-index and AUC of 0.767 (95% CI: 0.759-0.774) and 0.781 (95% CI: 0.774-0.788), respectively for PFS prediction. Besides, it also showed good prognostic performance on the secondary endpoints OS, RFS, and MFS in the testing cohort, with C-index of 0.786 (95% CI: 0.778-0.795), 0.775 (95% CI: 0.767-0.782) and 0.781 (95% CI: 0.772-0.789), respectively. CONCLUSIONS: The proposed FSGCN can better capture the metabolic or anatomic difference/interaction among sub-regions of the whole tumor imaged with PET/CT. Extensive multi-center experiments demonstrated its capability and generalization of prognosis prediction in HNC over conventional radiomics analysis.

Deep learning-based harmonization of CT reconstruction kernels towards improved clinical task performance.

OBJECTIVES: To develop a deep learning-based harmonization framework, assessing whether it can improve performance of radiomics models given different kernels in different clinical tasks and additionally generalize to mitigate the effects of new/unobserved kernels on radiomics features. METHODS: Patient data with 2 reconstruction kernels and phantom data with 22 reconstruction kernels were included. Eighty-five patients were studied for lymph node metastasis (LNM) prediction, and 164 patients for differential diagnosis between lung cancer (LC) and pulmonary tuberculosis (TB). Two convolutional neural network (CNN) models were developed to convert images (i) from B70f to B30f (CNNa) and (ii) from B30f to B70f (CNNb). Model performance between the two kernels was evaluated using AUC and compared with other well-known harmonization methods. Patient-normalized feature difference (PNFD) was used to identify the incompatible kernels (i.e., kernel with median PNFD > 1) with baseline (B30f/B70f), and measure the ability of the CNN models to convert the non-comparable kernels. RESULTS: For LC versus pulmonary TB diagnosis, AUCs of CNNa vs. others were 0.85 vs. 0.54-0.74 (p = 0.0001-0.0003), and for CNNb vs. others: 0.87 vs. 0.54-0.86 (p = 0.0001-0.55). For LNM prediction, AUCs of CNNa vs. others were 0.68 vs. 0.56-0.61 (p = 0.10-0.39), and for CNNb vs. others: 0.78 vs. 0.70-0.73 (p = 0.07-0.40). After CNN harmonization, 17 of 20 (85%) of investigated unknown kernels produced comparable radiomics feature values relative to baseline (median PNFD from 1.10-2.31 to 0.23-1.13). CONCLUSION: The CNN harmonization effectively improved performance of radiomics models between reconstruction kernels in different clinical tasks, and reduced feature differences between unknown kernels vs. baseline. KEY POINTS: • The soft (B30f) and sharp (B70f) kernels strongly affect radiomics reproducibility and generalizability. • The convolutional neural network (CNN) harmonization methods performed better than location-scale (ComBat and centering-scaling) and matrix factorization harmonization methods (based on singular value decomposition (SVD) and independent component analysis (ICA)) in both clinical tasks. • The CNN harmonization methods improve feature reproducibility not only between specific kernels (B30f and B70f) from the same scanner, but also between unobserved kernels from different scanners of different vendors.

Prognostic generalization of multi-level CT-dose fusion dosiomics from primary tumor and lymph node in nasopharyngeal carcinoma.

PURPOSE: To investigate the prognostic performance of multi-level computed tomography (CT)-dose fusion dosiomics at the image-, matrix-, and feature-levels from the gross tumor volume (GTV) at nasopharynx and the involved lymph node for nasopharyngeal carcinoma (NPC) patients. METHODS: Two hundred and nineteen NPC patients (175 vs. 44 for training vs. internal validation) were used to train prediction model, and 32 NPC patients were used for external validation. We first extracted CT and dose information from intratumoral nasopharynx (GTV_nx) and lymph node (GTV_nd) regions. Then, the corresponding peritumoral regions (RING_3 mm and RING_5 mm) were also considered. Thus, the individual and combination of intratumoral and peritumoral regions were as follows: GTV_nx, GTV_nd, RING_3 mm_nx, RING_3 mm_nd, RING_5 mm_nx, RING_5 mm_nd, GTV_nxnd, RING_3 mm_nxnd, RING_5 mm_nxnd, GTV + RING_3 mm_nxnd, and GTV + RING_5 mm_nxnd. For each region, 11 models were built by combining five clinical parameters and 127 features from: (1) dose images alone; (2-7) fused dose and CT images via wavelet-based fusion using CT weights of 0.2, 0.4, 0.6, and 0.8, gradient transfer fusion, and guided-filtering-based fusion (GFF); (8) fused matrices (sumMat); (9-10) fused features derived via feature averaging (avgFea) and feature concatenation (conFea); and finally, (11) CT images alone. The concordance index (C-index) and Kaplan-Meier curves with log-rank test were used to assess model performance. RESULTS: The fusion models' performance was better than single CT/dose model on both internal and external validation. Models that combined the information from both GTV_nx and GTV_nd regions outperformed the single region model. For internal validation, GTV + RING_3 mm_nxnd GFF model achieved the highest C-index both in recurrence-free survival (RFS) and metastasis-free survival (MFS) predictions (RFS: 0.822; MFS: 0.786). The highest C-index in external validation set was achieved by RING_3 mm_nxnd model (RFS: 0.762; MFS: 0.719). The GTV + RING_3 mm_nxnd GFF model is able to significantly separate patients into high-risk and low-risk groups compared to dose-only or CT-only models. CONCLUSION: Fusion dosiomics model combining the primary tumor, the involved lymph node, and 3 mm peritumoral information outperformed single-modality models for different outcome predictions, which is helpful for clinical decision-making and the development of personalized treatment.

Context-Aware Saliency Guided Radiomics: Application to Prediction of Outcome and HPV-Status from Multi-Center PET/CT Images of Head and Neck Cancer.

PURPOSE: This multi-center study aims to investigate the prognostic value of context-aware saliency-guided radiomics in 18F-FDG PET/CT images of head and neck cancer (HNC). METHODS: 806 HNC patients (training vs. validation vs. external testing: 500 vs. 97 vs. 209) from 9 centers were collected from The Cancer Imaging Archive (TCIA). There were 100/384 and 60/123 oropharyngeal carcinoma (OPC) patients with human papillomavirus (HPV) status in training and testing cohorts, respectively. Six types of images were used for radiomics feature extraction and further model construction, namely (i) the original image (Origin), (ii) a context-aware saliency map (SalMap), (iii, iv) high- or low-saliency regions in the original image (highSal or lowSal), (v) a saliency-weighted image (SalxImg), and finally, (vi) a fused PET-CT image (FusedImg). Four outcomes were evaluated, i.e., recurrence-free survival (RFS), metastasis-free survival (MFS), overall survival (OS), and disease-free survival (DFS), respectively. Multivariate Cox analysis and logistic regression were adopted to construct radiomics scores for the prediction of outcome (Rad_Ocm) and HPV-status (Rad_HPV), respectively. Besides, the prognostic value of their integration (Rad_Ocm_HPV) was also investigated. RESULTS: In the external testing cohort, compared with the Origin model, SalMap and SalxImg achieved the highest C-indices for RFS (0.621 vs. 0.559) and MFS (0.785 vs. 0.739) predictions, respectively, while FusedImg performed the best for both OS (0.685 vs. 0.659) and DFS (0.641 vs. 0.582) predictions. In the OPC HPV testing cohort, FusedImg showed higher AUC for HPV-status prediction compared with the Origin model (0.653 vs. 0.484). In the OPC testing cohort, compared with Rad_Ocm or Rad_HPV alone, Rad_Ocm_HPV performed the best for OS and DFS predictions with C-indices of 0.702 (p = 0.002) and 0.684 (p = 0.006), respectively. CONCLUSION: Saliency-guided radiomics showed enhanced performance for both outcome and HPV-status predictions relative to conventional radiomics. The radiomics-predicted HPV status also showed complementary prognostic value.

Imbalanced Data Correction Based PET/CT Radiomics Model for Predicting Lymph Node Metastasis in Clinical Stage T1 Lung Adenocarcinoma.

OBJECTIVES: To develop and validate the imbalanced data correction based PET/CT radiomics model for predicting lymph node metastasis (LNM) in clinical stage T1 lung adenocarcinoma (LUAD). METHODS: A total of 183 patients (148/35 non-metastasis/LNM) with pathologically confirmed LUAD were retrospectively included. The cohorts were divided into training vs. validation cohort in a ratio of 7:3. A total of 487 radiomics features were extracted from PET and CT components separately for radiomics model construction. Four clinical features and seven PET/CT radiological features were extracted for traditional model construction. To balance the distribution of majority (non-metastasis) class and minority (LNM) class, the imbalance-adjustment strategies using ten data re-sampling methods were adopted. Three multivariate models (denoted as Traditional, Radiomics, and Combined) were constructed using multivariable logistic regression analysis, where the combined model incorporated all of the significant clinical, radiological, and radiomics features. One hundred times repeated Monte Carlo cross-validation was used to assess the application order of feature selection and imbalance-adjustment strategies in the machine learning pipeline. Prediction performance of each model was evaluated using the area under the receiver operating characteristic curve (AUC) and Geometric mean score (G-mean). RESULTS: A total of 2 clinical parameters, 2 radiological features, 3 PET, and 5 CT radiomics features were significantly associated with LNM. The combined model with Edited Nearest Neighbors (ENN) re-sampling methods showed strong prediction performance than traditional model or radiomics model with the AUC of 0.94 (95%CI = 0.86-0.97) vs. 0.89 (95%CI = 0.79-0.93), 0.92 (95%CI = 0.85-0.97), and G-mean of 0.88 vs. 0.82, 0.80 in the training cohort, and the AUC of 0.75 (95%CI = 0.57-0.91) vs. 0.68 (95%CI = 0.36-0.83), 0.71 (95%CI = 0.48-0.83) and G-mean of 0.76 vs. 0.64, 0.51 in the validation cohort. The combination of performing feature selection before data re-sampling obtains a better result than the reverse combination (AUC 0.76 ± 0.06 vs. 0.70 ± 0.07, p<0.001). CONCLUSIONS: The combined model (consisting of age, histological type, C/T ratio, MATV, and radiomics signature) integrated with ENN re-sampling methods had strong lymph node metastasis prediction performance for imbalance cohorts in clinical stage T1 LUAD. Radiomics signatures extracted from PET/CT images could provide complementary prediction information compared with traditional model.

Identification of Stage IIIC/IV EGFR-Mutated Non-Small Cell Lung Cancer Populations Sensitive to Targeted Therapy Based on a PET/CT Radiomics Risk Model.

OBJECTIVES: This project aimed to construct an individualized PET/CT prognostic biomarker to accurately quantify the progression risk of patients with stage IIIC-IV epidermal growth factor receptor (EGFR)-mutated Non-small cell lung cancer (NSCLC) after first-line first and second generation EGFR- tyrosine kinase inhibitor (TKI) drug therapy and identify the first and second generation EGFR-TKI treatment-sensitive population. METHODS: A total of 250 patients with stage IIIC-IV EGFR-mutated NSCLC underwent first-line first and second generation EGFR-TKI drug therapy were included from two institutions (140 patients in training cohort; 60 patients in internal validation cohort, and 50 patients in external validation cohort). 1037 3D radiomics features were extracted to quantify the phenotypic characteristics of the tumor region in PET and CT images, respectively. A four-step feature selection method was performed to enable derivation of stable and effective signature in the training cohort. According to the median value of radiomics signature score (Rad-score), patients were divided into low- and high-risk groups. The progression-free survival (PFS) behaviors of the two subgroups were compared by Kaplan-Meier survival analysis. RESULTS: Our results shown that higher Rad-scores were significantly associated with worse PFS in the training (p < 0.0001), internal validation (p = 0.0153), and external validation (p = 0.0006) cohorts. Rad-score can effectively identify patients with a high risk of rapid progression. The Kaplan-Meier survival curves of the three cohorts present significant differences in PFS between the stratified slow and rapid progression subgroups. CONCLUSION: The PET/CT-derived Rad-score can realize the precise quantitative stratification of progression risk after first-line first and second generation EGFR-TKI drug therapy for NSCLC and identify EGFR-mutated NSCLC populations sensitive to targeted therapy, which might help to provide precise treatment options for NSCLC.

GapFill-Recon Net: A Cascade Network for simultaneously PET Gap Filling and Image Reconstruction.

PET image reconstruction from incomplete data, such as the gap between adjacent detector blocks generally introduces partial projection data loss, is an important and challenging problem in medical imaging. This work proposes an efficient convolutional neural network (CNN) framework, called GapFill-Recon Net, that jointly reconstructs PET images and their associated sinogram data. GapFill-Recon Net including two blocks: the Gap-Filling block first address the sinogram gap and the Image-Recon block maps the filled sinogram onto the final image directly. A total of 43,660 pairs of synthetic 2D PET sinograms with gaps and images generated from the MOBY phantom are utilized for network training, testing and validation. Whole-body mouse Monte Carlo (MC) simulated data are also used for evaluation. The experimental results show that the reconstructed image quality of GapFill-Recon Net outperforms filtered back-projection (FBP) and maximum likelihood expectation maximization (MLEM) in terms of the structural similarity index metric (SSIM), relative root mean squared error (rRMSE), and peak signal-to-noise ratio (PSNR). Moreover, the reconstruction speed is equivalent to that of FBP and was nearly 83 times faster than that of MLEM. In conclusion, compared with the traditional reconstruction algorithm, GapFill-Recon Net achieves relatively optimal performance in image quality and reconstruction speed, which effectively achieves a balance between efficiency and performance.

Evaluation and optimization of radiomics features stability to respiratory motion in 18 F-FDG 3D PET imaging.

PURPOSE: To evaluate the impact of respiratory motion on radiomics features in 18 F-fluoro-2-deoxy-D-glucose three dimensional positron emission tomography (18 F-FDG 3D PET) imaging and optimize feature stability by combining preprocessing configurations and aggregation strategies. METHODS: An in-house developed respiratory motion phantom was imaged in 3D PET scanner under nine respiratory patterns including one reference pattern. In total, 487 radiomics features were extracted for each respiratory pattern. Feature stability to respiratory motion was first evaluated by metrics of coefficient of variation (COV) and relative difference (RD) in a fixed preprocessing configuration. Further, one-way ANOVA and trend analysis were performed to evaluate the impact of preprocessing configuration (voxel size, discretization scheme) and aggregation strategy on feature stability. Finally, an optimization framework was proposed by selected feature-specific configurations with minimum COV value, and the diagnostic performance was validated in stable versus unstable features and fixed versus optimal features by a set of 46 patients with lung disease. RESULTS: PET radiomics features were sensitive to respiratory motion, only 79/487 (16%) features were identified to be very stable in the fixed configuration. Preprocessing configuration and aggregation strategy had an impact on feature stability. For different voxel size, bin number, bin size and aggregation strategy, 188/487 (39%), 70/487 (15%), 148/487 (30%), and 38/95 (29%) features appeared significant changes in feature stability. The optimized configuration had the potential to improve feature stability compared to fixed configuration, with the COV decreased from 22% ±24% to 16% ±20%. Regarding the diagnostic performance, the stable and optimal configuration features outperformed the unstable and fixed configuration features, respectively (AUC 0.88, 0.87 vs. 0.83, 0.85). CONCLUSIONS: Respiratory motion shows considerable impact on feature stability in 3D PET imaging, while optimizing preprocessing configuration may improve feature stability and diagnostic performance.

Integration of PET/CT Radiomics and Semantic Features for Differentiation between Active Pulmonary Tuberculosis and Lung Cancer.

PURPOSE: We aim to accurately differentiate between active pulmonary tuberculosis (TB) and lung cancer (LC) based on radiomics and semantic features as extracted from pre-treatment positron emission tomography/X-ray computed tomography (PET/CT) images. PROCEDURES: A total of 174 patients (77/97 pulmonary TB/LC as confirmed by pathology) were retrospectively selected, with 122 in the training cohort and 52 in the validation cohort. Four hundred eighty-seven radiomics features were initially extracted to quantify phenotypic characteristics of the lesion region in both PET and CT images. Eleven semantic features were additionally defined by two experienced nuclear medicine physicians. Feature selection was performed in 5 steps to enable derivation of robust and effective signatures. Multivariable logistic regression analysis was subsequently used to develop a radiomics nomogram. The calibration, discrimination, and clinical usefulness of the nomogram were evaluated in both the training and independent validation cohorts. RESULTS: The individualized radiomics nomogram, which combined PET/CT radiomics signature with semantic features, demonstrated good calibration and significantly improved the diagnostic performance with respect to the semantic model alone or PET/CT signature alone in training cohort (AUC 0.97 vs. 0.94 or 0.91, p = 0.0392 or 0.0056), whereas did not significantly improve the performance in validation cohort (AUC 0.93 vs. 0.89 or 0.91, p = 0.3098 or 0.3323). CONCLUSION: The radiomics nomogram showed potential for individualized differential diagnosis between solid active pulmonary TB and solid LC, although the improvement of performance was not significant relative to semantic model.

Evaluation of the diagnostic value of joint PET myocardial perfusion and metabolic imaging for vascular stenosis in patients with obstructive coronary artery disease.

BACKGROUND: To investigate the diagnostic value of joint PET myocardial perfusion and metabolic imaging for vascular stenosis in patients with suspected obstructive coronary artery disease (CAD). METHODS: Eighty-eight patients (53 and 35 applied for training and validation, respectively) with suspected obstructive CAD were referred to 13N-NH3 PET/CT myocardial perfusion imaging (MPI) and 18F-FDG PET/CT myocardial metabolic imaging (MMI) with available coronary angiography for analysis. One semi-quantitative indicator summed rest score (SRS) and five quantitative indicators, namely, perfusion defect extent (EXT), total perfusion deficit (TPD), myocardial blood flow (MBF), scar degree (SCR), and metabolism-perfusion mismatch (MIS), were extracted from the PET rest MPI and MMI scans. Different combinations of indicators and seven machine learning methods were used to construct diagnostic models. Diagnostic performance was evaluated using the sum of four metrics (noted as sumScore), namely, area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity. RESULTS: In univariate analysis, MIS outperformed other individual indicators in terms of sumScore (2.816-3.042 vs 2.138-2.908). In multivariate analysis, support vector machine (SVM) consisting of three indicators (MBF, SCR, and MIS) achieved the best performance (AUC 0.856, accuracy 0.810, sensitivity 0.838, specificity 0.757, and sumScore 3.261). This model consistently achieved significantly higher AUC compared with the SRS method for four specific subgroups (0.897, 0.839, 0.875, and 0.949 vs 0.775, 0.606, 0.713, and 0.744; P = 0.041, 0.005, 0.034 0.003, respectively). CONCLUSIONS: The joint evaluation of PET rest MPI and MMI could improve the diagnostic performance for obstructive CAD. The multivariate model (MBF, SCR, and MIS) combined with SVM outperformed other methods.

Multi-Level Multi-Modality Fusion Radiomics: Application to PET and CT Imaging for Prognostication of Head and Neck Cancer.

To characterize intra-tumor heterogeneity comprehensively, we propose a multi-level fusion strategy to combine PET and CT information at the image-, matrix-and feature-levels towards improved prognosis. Specifically, we developed fusion radiomics in the context of 3 prognostic outcomes in a multi-center setting (4 centers) involving 296 head & neck cancer patients. Eight clinical parameters were first utilized to build a (1) clinical model. We also built models by extracting 127 radiomics features from (2) PET images alone; (3-8) PET and CT images fused via wavelet-based fusion (WF) using CT-weights of 0.2, 0.4, 0.6 and 0.8, gradient transfer fusion (GTF), and guided filtering-based fusion (GFF); (9) fused matrices (sumMat); (10-11) fused features constructed via feature averaging (avgFea) and feature concatenation (conFea); and finally, (12) CT images alone; above models were also expanded to include both clinical and radiomics features. Seven variations of training and testing partitions were investigated. Highest performance in 5, 6 and 5 partitions was achieved by image-level fusion strategies for RFS, MFS and OS prediction, respectively. Among all partitions, WF0.6 and WF0.8 showed significantly higher performance than CT model for RFS (C-index: 0.60 ± 0.04 vs. 0.56 ± 0.03, p-value: 0.015) and MFS (C-index: 0.71 ± 0.13 vs. 0.62 ± 0.08, p-value: 0.020) predictions, respectively. In partition CER 23 vs. 14, WF0.6 significantly outperformed Clinical model for RFS prediction (C-index: 0.67 vs. 0.53, p-value: 0.003); both avgFea and WF0.6 showed C-index of 0.64 and significantly higher than that of PET only (C-index: 0.51, p-value: 0.018 and 0.031, respectively) for OS prediction. Fusion radiomics modeling showed varying improvements compared to single modality models for different outcome predictions in different partitions, highlighting the importance of generalizing radiomics models. Image-level fusion holds potential to capture more useful characteristics.

Machine Learning Methods for Optimal Radiomics-Based Differentiation Between Recurrence and Inflammation: Application to Nasopharyngeal Carcinoma Post-therapy PET/CT Images.

PURPOSE: To identify optimal machine learning methods for radiomics-based differentiation of local recurrence versus inflammation from post-treatment nasopharyngeal positron emission tomography/X-ray computed tomography (PET/CT) images. PROCEDURES: Seventy-six nasopharyngeal carcinoma (NPC) patients were enrolled (41/35 local recurrence/inflammation as confirmed by pathology). Four hundred eighty-seven radiomics features were extracted from PET images for each patient. The diagnostic performance was investigated for 42 cross-combinations derived from 6 feature selection methods and 7 classifiers. Of the original cohort, 70 % was applied for feature selection and classifier development, and the remaining 30 % used as an independent validation set. The diagnostic performance was evaluated using area under the ROC curve (AUC), test error, sensitivity, and specificity. Furthermore, the performance of the radiomics signatures against routine features was statistically compared using DeLong's method. RESULTS: The cross-combination fisher score (FSCR) + k-nearest neighborhood (KNN), FSCR + support vector machines with radial basis function kernel (RBF-SVM), FSCR + random forest (RF), and minimum redundancy maximum relevance (MRMR) + RBF-SVM outperformed others in terms of accuracy (AUC 0.883, 0.867, 0.892, 0.883; sensitivity 0.833, 0.864, 0.831, 0.750; specificity 1, 1, 0.873, 1) and reliability (test error 0.091, 0.136, 0.150, 0.136). Compared with conventional metrics, the radiomics signatures showed higher AUC values (0.867-0.892 vs. 0.817), though the differences were not statistically significant (p = 0.462-0.560). CONCLUSION: This study identified the most accurate and reliable machine learning methods, which could enhance the application of radiomics methods in the precision of diagnosis of NPC.