This study aims to investigate the influence of adaptive statistical iterative reconstruction-V (ASIR-V) and deep learning image reconstruction (DLIR) on CT radiomics feature robustness. A standardized phantom was scanned under single-energy CT (SECT) and dual-energy CT (DECT) modes at standard and low (20 and 10 mGy) dose levels. Images of SECT 120 kVp and corresponding DECT 120 kVp-like virtual monochromatic images were generated with filtered back-projection (FBP), ASIR-V at 40% (AV-40) and 100% (AV-100) blending levels, and DLIR algorithm at low (DLIR-L), medium (DLIR-M), and high (DLIR-H) strength levels. Ninety-four features were extracted via Pyradiomics. Reproducibility of features was calculated between standard and low dose levels, between reconstruction algorithms in reference to FBP images, and within scan mode, using intraclass correlation coefficient (ICC) and concordance correlation coefficient (CCC). The average percentage of features with ICC > 0.90 and CCC > 0.90 between the two dose levels was 21.28% and 20.75% in AV-40 images, and 39.90% and 35.11% in AV-100 images, respectively, and increased from 15.43 to 45.22% and from 15.43 to 44.15% with an increasing strength level of DLIR. The average percentage of features with ICC > 0.90 and CCC > 0.90 in reference to FBP images was 26.07% and 25.80% in AV-40 images, and 18.88% and 18.62% in AV-100 images, respectively, and decreased from 27.93 to 17.82% and from 27.66 to 17.29% with an increasing strength level of DLIR. DLIR and ASIR-V algorithms showed low reproducibility in reference to FBP images, while the high-strength DLIR algorithm provides an opportunity for minimizing radiomics variability due to dose reduction.

The anti-tumor function of CD8+ T cells is dependent on their proximity to tumor cells. Current studies have focused on the infiltration level of CD8+ T cells in the tumor microenvironment, while further spatial information, such as spatial localization and inter-cellular communication, have not been defined. In this study, co-detection by indexing (CODEX) was designed to characterize PDAC tissue regions with seven protein markers in order to identify the spatial architecture that regulates CD8+ T cells in human pancreatic ductal adenocarcinoma (PDAC). The cellular neighborhood algorithm was used to identify a total of six conserved and distinct cellular neighborhoods. Among these, one unique spatial architecture of CD8+ T and CD4+ T cell-enriched neighborhoods enriched the majority of CD8+ T cells, but heralded a poor prognosis. The proximity analysis revealed that the CD8+ T cells in this spatial architecture were significantly closer to themselves and the CD4+ T cells than to the tumor cells. Collectively, we identified a unique spatial architecture that restricted the proximity of CD8+ T cells to tumor cells in the tumor microenvironment, indicating a novel immune evasion mechanism of pancreatic ductal adenocarcinoma in a topologically regulated manner and providing new insights into the biology of PDAC.

Deep learning reconstruction (DLR) has exhibited potential in saving scan time. There is limited research on the evaluation of accelerated acquisition with DLR in staging rectal cancers. Our first objective was to explore the best DLR level in saving time through phantom experiments. Resolution and number of excitations (NEX) adjusted for different scan time, image quality of conventionally reconstructed T2W images were measured and compared with images reconstructed with different DLR level. The second objective was to explore the feasibility of accelerated T2W imaging with DLR in image quality and diagnostic performance for rectal cancer patients. 52 patients were prospectively enrolled to undergo accelerated acquisition reconstructed with highly-denoised DLR (DLR_H40sec) and conventional reconstruction (ConR2min). The image quality and diagnostic performance were evaluated by observers with varying experience and compared between protocols using κ statistics and area under the receiver operating characteristic curve (AUC). The phantom experiments demonstrated that DLR_H could achieve superior signal-to-noise ratio (SNR), detail conspicuity, sharpness, and less distortion within the least scan time. The DLR_H40sec images exhibited higher sharpness and SNR than ConR2min. The agreements with pathological TN-stages were improved using DLR_H40sec images compared to ConR2min (T: 0.846vs. 0.771, 0.825vs. 0.700, and 0.697vs. 0.512; N: 0.527vs. 0.521, 0.421vs. 0.348 and 0.517vs. 0.363 for junior, intermediate, and senior observes, respectively). Comparable AUCs to identify T3-4 and N1-2 tumors were achieved using DLR_H40sec and ConR2min images (P > 0.05). Consequently, with 2/3-time reduction, DLR_H40sec images showed improved image quality and comparable TN-staging performance to conventional T2W imaging for rectal cancer patients.

This study is aimed to evaluate effects of deep learning image reconstruction (DLIR) on image quality in single-energy CT (SECT) and dual-energy CT (DECT), in reference to adaptive statistical iterative reconstruction-V (ASIR-V). The Gammex 464 phantom was scanned in SECT and DECT modes at three dose levels (5, 10, and 20 mGy). Raw data were reconstructed using six algorithms: filtered back-projection (FBP), ASIR-V at 40

An increasing body of evidence has suggested that reprogrammed metabolism plays a critical role in the progression of pancreatic ductal adenocarcinoma (PDAC) by affecting the tumor and stromal cellular components in the tumor microenvironment (TME). By analyzing the KRAS pathway and metabolic pathways, we found that calcium and integrin-binding protein 1 (CIB1) corresponded with upregulation of glucose metabolism pathways and was associated with poor prognosis in patients with PDAC from The Cancer Genome Atlas (TCGA). Elevated CIB1 expression combined with upregulated glycolysis, oxidative phosphorylation (Oxphos), hypoxia pathway activation, and cell cycle promoted PDAC tumor growth and increased tumor cellular com-ponents. Furthermore, we confirmed the mRNA overexpression of CIB1 and co-expression of CIB1 and KRAS mutation in cell lines from the Expression Atlas. Subsequently, immunohistochemistry staining from the Human Protein Atlas (HPA) showed that high expression of CIB1 in tumor cells was associated with an increased tumor compartment and reduced stromal cellular abundance. Furthermore, using multiplexed immunohistochemistry (mIHC), we verified that low stromal abundance was correlated with low infiltration of CD8 + PD-1 − T cells which led to suppressed anti-tumor immunity. Overall, our findings identify CIB1 as a metabolic pathway-mediated factor for the restriction of immune cell infiltration in the stromal compartment of PDAC and highlight the potential value of CIB1 as a prognostic biomarker involved in metabolic reprogramming and immune modulation.

Objectives To evaluate robustness of dual-energy CT (DECT) radiomics features of virtual unenhanced (VUE) image and virtual monoenergetic image (VMI) among different imaging platforms. Methods A phantom with sixteen clinical-relevant densities was scanned on ten DECT platforms with comparable scan parameters. Ninety-four radiomic features were extracted via Pyradiomics from VUE images and VMIs at energy level of 70 keV (VMI 70keV ). Test–retest repeatability was assessed by Bland–Altman analysis. Inter-platform reproducibility of VUE images and VMI 70keV was evaluated by coefficient of variation (CV) and quartile coefficient of dispersion (QCD) among platforms, and by intraclass correlation coefficient (ICC) and concordance correlation coefficient (CCC) between platform pairs. The correlation between variability of CT number radiomics reproducibility was estimated. Results 92.02% and 92.87% of features were repeatable between scan–rescans for VUE images and VMI 70keV , respectively. Among platforms, 11.30% and 28.39% features of VUE images, and 15.16% and 28.99% features of VMI 70keV were with CV < 10% and QCD < 10%. The average percentages of radiomics features with ICC > 0.90 and CCC > 0.90 between platform pairs were 10.00% and 9.86% in VUE images and 11.23% and 11.23% in VMI 70keV . The CT number inter-platform reproducibility using CV and QCD showed negative correlations with percentage of the first-order radiomics features with CV < 10% and QCD < 10%, in both VUE images and VMI 70keV ( r 2 0.3870–0.6178, all p < 0.001). Conclusions The majority of DECT radiomics features were non-reproducible. The differences in CT number were considered as an indicator of inter-platform DECT radiomics variation. Critical relevance statement: The majority of radiomics features extracted from the VUE images and the VMI70keV were non-reproducible among platforms, while synchronizing energy levels of VMI to reduce the CT number value variability may be a potential way to mitigate radiomics instability. Graphical Abstract

The crosstalk between tumor cells and macrophages under hypoxic conditions has been acknowledged as a pivotal determinant in the progression of colorectal cancer (CRC). Previous research has underscored the significance of exosomes derived from hypoxic tumor cells in facilitating tumor progression through inducing the polarization of macrophages towards the M2-like phenotype. The precise influence of hypoxic macrophage-derived exosomes (HMDEs) on the progression of CRC has not yet been fully elucidated. The objective of this study was to investigate the role of HMDEs in the progression of CRC. We discovered that there was an elevated release of exosomes derived from macrophages in hypoxic conditions. Additionally, the hypoxia-induced macrophage-derived exosomes played a crucial role in promoting the progression of CRC. We have also demonstrated that HMDEs have the ability to induce cell cycle transition and inhibit cell apoptosis, thereby promoting the growth of CRC cells. Furthermore, the underlying molecular mechanisms of these effects have been identified. The overexpression of Hif-1α results in its direct interaction with distinct regions (-521− -516 bp and -401− -391 bp) of the Hsp90 promoter during hypoxic circumstances. This binding event led to the overexpression of Hsp90 and the subsequent elevation of Hsp90 protein levels within HMDEs. Importantly, the crucial interaction between Hsp90 and Lats1 resulted in the deactivation of Lats1 and the inhibition of Yap phosphorylation. Ultimately, this series of events lead to the deactivation of the Hippo signaling pathway. Our in vivo and in vitro studies presented compelling evidence for the crucial role of hypoxic macrophage-derived exosomal Hsp90 in promoting CRC progression through the inhibition of the Hippo signaling pathway. These findings represented a significant advancement in our comprehension of the complex interplay between macrophages and CRC cells under hypoxic conditions.

To evaluate inter- and intra- scan mode and scanner repeatability and reproducibility of radiomics features within and between single-energy CT (SECT) and dual-energy CT (DECT). A standardized phantom with sixteen rods of clinical-relevant densities was scanned on seven DECT-capable scanners and three SECT-only scanners. The acquisition parameters were selected to present typical abdomen-pelvic examinations with the same voxel size. Images of SECT at 120 kVp and corresponding 120 kVp-like virtual monochromatic images (VMIs) in DECT which were generated according to scanners were analyzed. Regions of interest were drawn with rigid registrations to avoid variations due to segmentation. Radiomics features were extracted via Pyradiomics platform. Test-retest repeatability was evaluated by Bland-Altman analysis for repeated scans. Intra-scanner reproducibility for different scan modes was tested by intraclass correlation coefficient (ICC) and concordance correlation coefficient (CCC). Inter-scanner reproducibility among different scanners for same scan mode was assessed by coefficient of variation (CV) and quartile coefficient of dispersion (QCD). The test-retest analysis presented that 92.91% and 87.02% of the 94 assessed features were repeatable for SECT 120kVp and DECT 120 kVp-like VMIs, respectively. The intra-scanner analysis for SECT 120kVp vs DECT 120 kVp-like VMIs demonstrated that 10.76% and 10.28% of features were with ICC > 0.90 and CCC > 0.90, respectively. The inter-scanner analysis showed that 17.09% and 27.73% of features for SECT 120kVp were with CV < 10% and QCD < 10%, and 15.16% and 32.78% for DECT 120 kVp-like VMIs, respectively. The majority of radiomics features were non-reproducible within and between SECT and DECT. • Although the test-retest analysis showed high repeatability for radiomics features, the overall reproducibility of radiomics features within and between SECT and DECT was low. • Only about one-tenth of radiomics features extracted from SECT images and corresponding DECT images did match each other, even their average photon energy levels were considered alike, indicating that the scan mode potentially altered the radiomics features. • Less than one-fifth of radiomics features were reproducible among multiple SECT and DECT scanners, regardless of their fixed acquisition and reconstruction parameters, suggesting the necessity of scanning protocol adjustment and post-scan harmonization process.

目的 探索基于扩散峰度成像(DKI)扫描参数的推算序列代替常规扩散加权成像(DWI)序列扫描的应用价值.方法 回顾性分析2019年11月至2020年10月瑞金医院确诊的直肠癌患者62例,其手术前2周内均行MR扫描,将DKI图像经后处理推算出b=1000 s/mm2扩散图像,两名医师分别对推算序列与常规DWI序列的b=1000s/mm2的图像进行比较.结果 DKI推算序列的主观图像质量、信噪比(SNR)、对比噪声比(CNR)及信号强度比(SIR)均优于常规DWI序列(P ＜0.050).两者术前T分期的准确率分别为91.94％ (57/62)、74.19％(46/62),差异有统计学意义(P ＜0.050);N分期的准确率分别为70.97％ (44/62)、66.13％ (41/62),差异无统计学意义(P ＞0.050).结论 DKI推算序列具有代替常规DWI序列、减少扫描时间、优化扫描流程及T分期诊断效能的潜在应用价值.

OBJECTIVES:To compare image quality between a deep learning image reconstruction (DLIR) algorithm and conventional iterative reconstruction (IR) algorithms in dual-energy CT (DECT) and to assess the impact of these algorithms on radiomics robustness.METHODS:A phantom with clinical-relevant densities was imaged on seven DECT scanners with the same voxel size using typical abdominal-pelvis examination protocols. On one DECT scanner, raw data were reconstructed using both conventional IR (adaptive statistical iterative reconstruction-V, ASIR-V) and DLIR. Nine sets of corresponding images were generated on other six DECT scanners using scanner-equipped conventional IR. Regions of interest were delineated through rigid registrations. Image quality was compared. Pyradiomics platform was used for radiomics feature extraction. Test-retest repeatability was assessed by Bland-Altman analysis for repeated scans. Inter-reconstruction algorithm reproducibility between conventional IR and DLIR was tested by intraclass correlation coefficient (ICC) and concordance correlation coefficient (CCC). Inter-scanner reproducibility was evaluated by coefficient of variation (CV) and quartile coefficient of dispersion (QCD). Robust features were identified.RESULTS:DLIR significantly improved image quality. Ninety-four radiomics features were extracted and nine features were considered as robust. 93.87% features were repeatable between repeated scans. ASIR-V images showed higher reproducibility to other conventional IR than DLIR (ICC mean, 0.603 vs 0.558, p = 0.001; CCC mean, 0.554 vs 0.510, p = 0.004). 7.45% and 26.83% features were reproducible among scanners evaluated by CV and QCD, respectively.CONCLUSIONS:DLIR improves quality of DECT images but may alter radiomics features compared to conventional IR. Nine robust DECT radiomics features were identified.KEY POINTS:• DLIR improves DECT image quality in terms of signal-to-noise ratio and contrast-to-noise ratio compared with ASIR-V and showed the highest noise reduction rate and lowest peak frequency shift. • Most of radiomics features are repeatable between repeated DECT scans, while inter-reconstruction algorithm reproducibility between conventional IR and DLIR, and inter-scanner reproducibility, are low. • Although DLIR may alter radiomics features compared to IR algorithms, nine radiomics features survived repeatability and reproducibility analysis among DECT scanners and reconstruction algorithms, which allows further validation and clinical-relevant analysis.

ObjectiveThe aim of the study was to evaluate the computed diffusion-weighted images (DWI) in image quality and diagnostic performance of rectal cancer by comparing with the acquired DWI.MethodsA total of 103 consecutive patients with primary rectal cancer were enrolled in this study. All patients underwent two DWI sequences, namely, conventional acquisition with b = 0 and 1,000 s/mm2 (aDWIb1,000) and another with b = 0 and 700 s/mm2 on a 3.0T MR scanner (MAGNETOM Prisma; Siemens Healthcare, Germany). The images (b = 0 and 700 s/mm2) were used to compute the diffusion images with b value of 1,000 s/mm2 (cDWIb1,000). Qualitative and quantitative analysis of both computed and acquired DWI images was performed, namely, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and signal intensity ratio (SIR), and also diagnostic staging performance. Interclass correlation coefficients, weighted κ coefficient, Friedman test, Wilcoxon paired test, and McNemar or Fisher test were used for repeatability and comparison assessment.ResultsCompared with the aDWIb1,000 images, the cDWIb1,000 ones exhibited significant higher scores of subjective image quality (all P <0.050). SNR, SIR, and CNR of the cDWIb1,000 images were superior to those of the aDWIb1,000 ones (P <0.001). The overall diagnostic accuracy of computed images was higher than that of the aDWIb1,000 images in T stage (P <0.001), with markedly better sensitivity and specificity in distinguishing T1–2 tumors from the T3–4 ones (P <0.050).ConclusioncDWIb1,000 images from lower b values might be a useful alternative option and comparable to the acquired DWI, providing better image quality and diagnostic performance in preoperative rectal cancer staging.

BACKGROUND:Chest computed tomography (CT) has been found to have high sensitivity in diagnosing novel coronavirus pneumonia (NCP) at the early stage, giving it an advantage over nucleic acid detection during the current pandemic. In this study, we aimed to develop and validate an integrated deep learning framework on chest CT images for the automatic detection of NCP, focusing particularly on differentiating NCP from influenza pneumonia (IP). METHODS:A total of 148 confirmed NCP patients [80 male; median age, 51.5 years; interquartile range (IQR), 42.5-63.0 years] treated in 4 NCP designated hospitals between January 11, 2020 and February 23, 2020 were retrospectively enrolled as a training cohort, along with 194 confirmed IP patients (112 males; median age, 65.0 years; IQR, 55.0-78.0 years) treated in 5 hospitals from May 2015 to February 2020. An external validation set comprising 57 NCP patients and 50 IP patients from 8 hospitals was also enrolled. Two deep learning schemes (the Trinary scheme and the Plain scheme) were developed and compared using receiver operating characteristic (ROC) curves. RESULTS:Of the NCP lesions, 96.6% were >1 cm and 76.8% were of a density <-500 Hu, indicating them to have less consolidation than IP lesions, which had nodules ranging from 5-10 mm. The Trinary scheme accurately distinguished NCP from IP lesions, with an area under the curve (AUC) of 0.93. For patient-level classification in the external validation set, the Trinary scheme outperformed the Plain scheme (AUC: 0.87 vs. 0.71) and achieved human specialist-level performance. CONCLUSIONS:Our study has potentially provided an accurate tool on chest CT for early diagnosis of NCP with high transferability and showed high efficiency in differentiating between NCP and IP; these findings could help to reduce misdiagnosis and contain the pandemic transmission.