Photon-counting detector CT-based virtual monoenergetic reconstructions: repeatability and reproducibility of radiomics features of an organic phantom and human myocardium.

BACKGROUND: Photon-counting detector computed tomography (PCD-CT) may influence imaging characteristics for various clinical conditions due to higher signal and contrast-to-noise ratio in virtual monoenergetic images (VMI). Radiomics analysis relies on quantification of image characteristics. We evaluated the impact of different VMI reconstructions on radiomic features in in vitro and in vivo PCD-CT datasets. METHODS: An organic phantom consisting of twelve samples (four oranges, four onions, and four apples) was scanned five times. Twenty-three patients who had undergone coronary computed tomography angiography on a first generation PCD-CT system with the same image acquisitions were analyzed. VMIs were reconstructed at 6 keV levels (40, 55, 70, 90, 120, and 190 keV). The phantoms and the patients' left ventricular myocardium (LVM) were segmented for all reconstructions. Ninety-three original radiomic features were extracted. Repeatability and reproducibility were evaluated through intraclass correlations coefficient (ICC) and post hoc paired samples ANOVA t test. RESULTS: There was excellent repeatability for radiomic features in phantom scans (all ICC = 1.00). Among all VMIs, 36/93 radiomic features (38.7%) in apples, 28/93 (30.1%) in oranges, and 33/93 (35.5%) in onions were not significantly different. For LVM, the percentage of stable features was high between VMIs ≥ 90 keV (90 versus 120 keV, 77.4%; 90 versus 190 keV, 83.9%; 120 versus 190 keV, 89.3%), while comparison to lower VMI levels led to fewer reproducible features (40 versus 55 keV, 8.6%). CONCLUSIONS: VMI levels influence the stability of radiomic features in an organic phantom and patients' LVM; stability decreases considerably below 90 keV. RELEVANCE STATEMENT: Spectral reconstructions significantly influence radiomic features in vitro and in vivo, necessitating standardization and careful attention to these reconstruction parameters before clinical implementation. KEY POINTS: • Radiomic features have an excellent repeatability within the same PCD-CT acquisition and reconstruction. • Differences in VMI lead to decreased reproducibility for radiomic features. • VMI ≥ 90 keV increased the reproducibility of the radiomic features.

Impact of Cardiac Motion on coronary artery calcium scoring using a virtual non-iodine algorithm on photon-counting detector CT: a dynamic phantom study.

This study assessed the impact of cardiac motion and in-vessel attenuation on coronary artery calcium (CAC) scoring using virtual non-iodine (VNI) against virtual non-contrast (VNC) reconstructions on photon-counting detector CT. Two artificial vessels containing calcifications and different in-vessel attenuations (500, 800HU) were scanned without (static) and with cardiac motion (60, 80, 100 beats per minute [bpm]). Images were post-processed using a VNC and VNI algorithm at 70 keV and quantum iterative reconstruction (QIR) strength 2. Calcium mass, Agatston scores, cardiac motion susceptibility (CMS)-indices were compared to physical mass, static scores as well as between reconstructions, heart rates and in-vessel attenuations. VNI scores decreased with rising heart rate (p < 0.01) and showed less underestimation than VNC scores (p < 0.001). Only VNI scores were similar to the physical mass at static measurements, and to static scores at 60 bpm. Agatston scores using VNI were similar to static scores at 60 and 80 bpm. Standard deviation of CMS-indices was lower for VNI-based than for VNC-based CAC scoring. VNI scores were higher at 500 than 800HU (p < 0.001) and higher than VNC scores (p < 0.001) with VNI scores at 500 HU showing the lowest deviation from the physical reference. VNI-based CAC quantification is influenced by cardiac motion and in-vessel attenuation, but least when measuring Agatston scores, where it outperforms VNC-based CAC scoring.

Radiation Dose Reduction for Coronary Artery Calcium Scoring Using a Virtual Noniodine Algorithm on Photon-Counting Detector Computed-Tomography Phantom Data.

Background: On the basis of the hypothesis that virtual noniodine (VNI)-based coronary artery calcium scoring (CACS) is feasible at reduced radiation doses, this study assesses the impact of radiation dose reduction on the accuracy of this VNI algorithm on a photon-counting detector (PCD)-CT. Methods: In a systematic in vitro setting, a phantom for CACS simulating three chest sizes was scanned on a clinical PCD-CT. The standard radiation dose was chosen at volumetric CT dose indices (CTDIVol) of 1.5, 3.3, 7.0 mGy for small, medium-sized, and large phantoms, and was gradually reduced by adjusting the tube current resulting in 100, 75, 50, and 25%, respectively. VNI images were reconstructed at 55 keV, quantum iterative reconstruction (QIR)1, and at 60 keV/QIR4, and evaluated regarding image quality (image noise (IN), contrast-to-noise ratio (CNR)), and CACS. All VNI results were compared to true noncontrast (TNC)-based CACS at 70 keV and standard radiation dose (reference). Results: INTNC was significantly higher than INVNI, and INVNI at 55 keV/QIR1 higher than at 60 keV/QIR4 (100% dose: 16.7 ± 1.9 vs. 12.8 ± 1.7 vs. 7.7 ± 0.9; p < 0.001 for every radiation dose). CNRTNC was higher than CNRVNI, but it was better to use 60 keV/QIR4 (p < 0.001). CACSVNI showed strong correlation and agreement at every radiation dose (p < 0.001, r > 0.9, intraclass correlation coefficient > 0.9). The coefficients of the variation in root-mean squared error were less than 10% and thus clinically nonrelevant for the CACSVNI of every radiation dose. Conclusion: This phantom study suggests that CACSVNI is feasible on PCD-CT, even at reduced radiation dose while maintaining image quality and CACS accuracy.

Dual-energy CT iodine overlay improves efficiency of oral contrast leak assessment.

BACKGROUND: Evaluation for gastrointestinal leak is a frequent imaging indication, and dual-energy computed tomography (DECT) with oral or rectally administered contrast can be used to improve efficiency and diagnostic confidence. PURPOSE: To assess the value of the DECT iodine overlay (IO) reconstruction as a stand-alone image set compared to routine CT in assessing oral or rectal contrast leak from the gastrointestinal system. MATERIAL AND METHODS: A blinded, retrospective audit study was performed by three readers who each interpreted 50 studies performed for assessment of oral or rectal contrast leak that were acquired using DECT. Each reader independently assessed both the routine CT images and the images of the reconstructed IO for contrast leak in random order with a six-week "wash-out period" between readings. Clinical follow-up provided the reference standard. Readers recorded the presence/absence of a leak, diagnostic confidence, image quality score, and interpretation time for each image set. RESULTS: Pooled data for overall accuracy in identification of a leak increased from 0.81 (95% confidence interval [CI]=0.74-0.87) for routine CT to 0.91 (95% CI=0.85-0.95) with IO, and the area under the curve (AUC) was significantly higher for IO than routine CT (P = 0.015). Readers required significantly less time to interpret IO than routine CT (median improvement of 12.5 s per image using pooled data; P < 0.001) while maintaining diagnostic confidence and perceived image quality. CONCLUSION: Use of DECT IO reconstructions for identification of oral or rectal contrast leak requires less time to interpret than routine CT with improved accuracy and maintained diagnostic confidence and perceived image quality.

Development and validation of a nonenhanced CT based radiomics model to detect brown adipose tissue.

Purpose: It has been reported that brown adipose tissue (BAT) has a protective effect regarding cardiovascular disease. Positron emission tomography-computed tomography (PET-CT) is the reference method for detecting active BAT; however, it is not feasible to screen for BAT due to the required radionuclides and high-cost. The purpose of this study is to develop and validate a nonenhanced CT based radiomics model to detect BAT and to explore the relationship between CT radiomics derived BAT and cardiovascular calcification. Patients and methods: 146 patients undergoing 18F-FDG PET-CT were retrospectively included from two centers for model development (n = 86) and external validation (n = 60). The data for the model development were randomly divided into a training cohort and an internal validation cohort with a 7:3 ratio, while the external validation data were divided 1:1 into a propensity score matching (PSM) cohort and a randomly sex matched cohort. Radiomics features of BAT and non-BAT depots were extracted from regions of interest (ROI) on nonenhanced CT corresponding to PET studies. Inter-class correlation coefficient (ICC) and Pearson's correlation analysis were performed to select radiomics features with high consistency. Next, least absolute shrinkage and selection operator (LASSO) with linear regression model was used to select radiomics features for model construction. Support vector machine (SVM) was used to develop the model and a radiomics score (RS) was calculated for each depot. The diagnostic performance of the radiomics model was evaluated both on a per-depot and per-patient basis by calculating the area under the receiver operating characteristic curve (AUROC). We further divided patients into BAT-RS group and non-BAT-RS group based on radiomics score and compared their cardiovascular calcification by calculating calcium volume and score. Results: A total of 22 radiomics features were selected for model construction. On a per-depot basis, the AUROCs were 0.87 (95% CI: 0.83-0.9), 0.85 (95% CI: 0.79-0.90), 0.72 (95% CI: 0.67-0.77) and 0.74 (95% CI: 0.69-0.79) for detecting BAT in the training, internal validation, external validation 1 and external validation 2 cohorts, respectively. On a per-patient basis, the radiomics model had high AUROCs of 0.91 (95% CI: 0.84-0.98), 0.77 (95% CI: 0.61-0.92) and 0.85 (95% CI: 0.72-0.98) in the training, external validation 1 and external validation 2 cohorts, respectively. When grouping based on the radiomics model, the BAT-RS group had lower odds of coronary artery calcium (CAC) and thoracic aorta calcium (TAC) compared with the non-BAT-RS group (CAC: 2.8% vs. 20.3%, p = 0.001; TAC: 19.4% vs. 39.2%, p = 0.009). The BAT-RS group had less CAC volume (4.1 ± 4.0 mm3 vs. 147.4 ± 274.3 mm3; p = 0.001), CAC score (2.8 ± 3.0 vs. 169.1 ± 311.5; p = 0.001), TAC volume (301.4 ± 450.2 mm3 vs. 635.3 ± 1100.7 mm3; p = 0.007) and TAC score (496.2 ± 132.6 vs. 749.2 ± 1297.3; p = 0.007) than the non-BAT-RS group. Conclusion: We developed and validated a nonenhanced CT based reliable radiomics model for detecting BAT with PET-CT findings as reference standard. Radiomics signatures from nonenhanced CT can reliably detect BAT and have promising potential to be used in routine clinical settings. Importantly, our study showed that patients with BAT had less cardiovascular calcification.

Ultra-high resolution photon-counting coronary CT angiography improves coronary stenosis quantification over a wide range of heart rates - A dynamic phantom study.

PURPOSE: To investigate the effect of using photon-counting detector (PCD)-CT with ultra-high resolution (UHR) on stenosis quantification accuracy and blooming artifacts from low to high heart rates in a dynamic motion phantom. METHOD: Two vessel phantoms (diameter: 4 mm) containing solid calcified lesions (25%, 50% stenoses), filled with different concentrations of iodine, inside an anthropomorphic thorax phantom attached to a coronary motion simulator were used. Scanning was performed on a PCD-CT system using an ECG-gated mode at UHR and standard resolution (SR) (0.2, 0.6 mm slice thickness, respectively). Images were reconstructed at 60, 80 and 100 beats per minute (bpm) (UHR: Bv56 kernel, quantum iterative reconstruction (QIR) level 3; SR: 55 keV, Bv40 kernel, QIR3). Percent diameter stenosis (PDS) and blooming artifacts were measured by two readers. RESULTS: PDS measurements derived from UHR were more accurate than SR for both lesions at every heart rate (p ≤ 0.005 for all, e.g. 50% lesion SR vs. UHR: at 60 bpm 57.1% [55.2-59.2] vs. 50.0% [48.5-51.2], at 100 bpm 61.0% [58.6-64.3] vs. 52.4% [51.3-54.3]). Overall mean difference across heart rates and lesions compared to the nominal stenoses was 9.2% (Limit of Agreement (LoA), 2.4%/16.0%) for SR vs. 2.4% (LoA, -2.8%/7.5%) for UHR. Blooming artifacts decreased with UHR compared to SR for both lesions at every heart rate (p < 0.001 for all, e.g. 50% lesion SR vs. UHR: at 60 bpm 63.8% [60.6-69.5] vs. 52.5% [50.0-57.5], at 100 bpm 70.2% [64.8-78.1] vs. 56.1% [51.2-60.8]). CONCLUSIONS: This motion phantom study demonstrates improved stenosis quantification accuracy and reduced blooming artifacts with UHR-PCD-CT compared to SR, independent of heart rate.

Photon Counting Detector CT-Based Virtual Noniodine Reconstruction Algorithm for In Vitro and In Vivo Coronary Artery Calcium Scoring: Impact of Virtual Monoenergetic and Quantum Iterative Reconstructions.

OBJECTIVES: The aim of this study was to evaluate the impact of virtual monoenergetic imaging (VMI) and quantum iterative reconstruction (QIR) on the accuracy of coronary artery calcium scoring (CACS) using a virtual noniodine (VNI) reconstruction algorithm on a first-generation, clinical, photon counting detector computed tomography system. MATERIALS AND METHODS: Coronary artery calcium scoring was evaluated in an anthropomorphic chest phantom simulating 3 different patient sizes by using 2 extension rings (small: 300 × 200 mm, medium: 350 × 250 mm, large: 400 × 300 mm) and in patients (n = 61; final analyses only in patients with coronary calcifications [n = 34; 65.4 ± 10.0 years; 73.5% male]), who underwent nonenhanced and contrast-enhanced, electrocardiogram-gated, cardiac computed tomography on a photon counting detector system. Phantom and patient data were reconstructed using a VNI reconstruction algorithm at different VMI (55-80 keV) and QIR (strength 1-4) levels (CACS VNI ). True noncontrast (TNC) scans at 70 keV and QIR "off" were used as reference for phantom and patient studies (CACS TNC ). RESULTS: In vitro and in vivo CACS VNI showed strong correlation ( r > 0.9, P < 0.001 for all) and excellent agreement (intraclass correlation coefficient > 0.9 for all) with CACS TNC at all investigated VMI and QIR levels. Phantom and patient CACS VNI significantly increased with decreasing keV levels (in vitro: from 475.2 ± 26.3 at 80 keV up to 652.5 ± 42.2 at 55 keV; in vivo: from 142.5 [7.4/737.7] at 80 keV up to 248.1 [31.2/1144] at 55 keV; P < 0.001 for all), resulting in an overestimation of CACS VNI at 55 keV compared with CACS TNC at 70 keV in some cases (in vitro: 625.8 ± 24.4; in vivo: 225.4 [35.1/959.7]). In vitro CACS increased with rising QIR at low keV. In vivo scores were significantly higher at QIR 1 compared with QIR 4 only at 60 and 80 keV (60 keV: 220.3 [29.6-1060] vs 219.5 [23.7/1048]; 80 keV: 152.0 [12.0/735.6] vs 142.5 [7.4/737.7]; P < 0.001). CACS VNI was closest to CACS TNC at 60 keV, QIR 2 (+0.1%) in the small; 55 keV, QIR 1 (±0%) in the medium; 55 keV, QIR 4 (-0.1%) in the large phantom; and at 60 keV, QIR 1 (-2.3%) in patients. CONCLUSIONS: Virtual monoenergetic imaging reconstructions have a significant impact on CACS VNI . The effects of different QIR levels are less consistent and seem to depend on several individual conditions, which should be further investigated.

Use of dual energy CT to identify gastrointestinal anastomotic leak by assessment of percutaneous drain contents.

Anastomotic leakage is a feared complication of many different types of gastrointestinal surgery. It is important to identify patients with leaks early because sepsis may develop quickly. Suspected leaks are typically confirmed by either fluoroscopy or computed tomography with oral contrast. This article presents a novel method to confirm the presence of a gastrointestinal anastomotic leak when standard imaging and clinical presentation are ambiguous.

Intra-individual comparison of coronary calcium scoring between photon counting detector- and energy integrating detector-CT: Effects on risk reclassification.

Purpose: To compare coronary artery calcium volume and score (CACS) between photon-counting detector (PCD) and conventional energy integrating detector (EID) computed tomography (CT) in a phantom and prospective patient study. Methods: A commercially available CACS phantom was scanned with a standard CACS protocol (120 kVp, slice thickness/increment 3/1.5 mm, and a quantitative Qr36 kernel), with filtered back projection on the EID-CT, and with monoenergetic reconstruction at 70 keV and quantum iterative reconstruction off on the PCD-CT. The same settings were used to prospectively acquire data in patients (n = 23, 65 ± 12.1 years), who underwent PCD- and EID-CT scans with a median of 5.5 (3.0-12.5) days between the two scans in the period from August 2021 to March 2022. CACS was quantified using a commercially available software solution. A regression formula was obtained from the aforementioned comparison and applied to simulate risk reclassification in a pre-existing cohort of 514 patients who underwent a cardiac EID-CT between January and December 2021. Results: Based on the phantom experiment, CACS PCD-CT showed a more accurate measurement of the reference CAC volumes (overestimation of physical volumes: PCD-CT 66.1 ± 1.6% vs. EID-CT: 77.2 ± 0.5%). CACS EID-CT and CACS PCD-CT were strongly correlated, however, the latter measured significantly lower values in the phantom (CACS PCD-CT : 60.5 (30.2-170.3) vs CACS EID-CT 74.7 (34.6-180.8), p = 0.0015, r = 0.99, mean bias -9.7, Limits of Agreement (LoA) -36.6/17.3) and in patients (non-significant) (CACS PCD-CT : 174.3 (11.1-872.7) vs CACS EID-CT 218.2 (18.5-876.4), p = 0.10, r = 0.94, mean bias -41.1, LoA -315.3/232.5). The systematic lower measurements of Agatston score on PCD-CT system led to reclassification of 5.25% of our simulated patient cohort to a lower classification class. Conclusion: CACS PCD-CT is feasible and correlates strongly with CACS EID-CT , however, leads to lower CACS values. PCD-CT may provide results that are more accurate for CACS than EID-CT.

Author Correction: Naturally-occurring cholesterol analogues in lipid nanoparticles induce polymorphic shape and enhance intracellular delivery of mRNA.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Naturally-occurring cholesterol analogues in lipid nanoparticles induce polymorphic shape and enhance intracellular delivery of mRNA.

Endosomal sequestration of lipid-based nanoparticles (LNPs) remains a formidable barrier to delivery. Herein, structure-activity analysis of cholesterol analogues reveals that incorporation of C-24 alkyl phytosterols into LNPs (eLNPs) enhances gene transfection and the length of alkyl tail, flexibility of sterol ring and polarity due to -OH group is required to maintain high transfection. Cryo-TEM displays a polyhedral shape for eLNPs compared to spherical LNPs, while x-ray scattering shows little disparity in internal structure. eLNPs exhibit higher cellular uptake and retention, potentially leading to a steady release from the endosomes over time. 3D single-particle tracking shows enhanced intracellular diffusivity of eLNPs relative to LNPs, suggesting eLNP traffic to productive pathways for escape. Our findings show the importance of cholesterol in subcellular transport of LNPs carrying mRNA and emphasize the need for greater insights into surface composition and structural properties of nanoparticles, and their subcellular interactions which enable designs to improve endosomal escape.