Peripheral liver metastases are more frequently missed than central metastases in contrast-enhanced CT: insights from a 25-reader performance study.

PURPOSE: Subtle liver metastases may be missed in contrast enhanced CT imaging. We determined the impact of lesion location and conspicuity on metastasis detection using data from a prior reader study. METHODS: In the prior reader study, 25 radiologists examined 40 CT exams each and circumscribed all suspected hepatic metastases. CT exams were chosen to include a total of 91 visually challenging metastases. The detectability of a metastasis was defined as the fraction of radiologists that circumscribed it. A conspicuity index was calculated for each metastasis by multiplying metastasis diameter with its contrast, defined as the difference between the average of a circular region within the metastasis and the average of the surrounding circular region of liver parenchyma. The effects of distance from liver edge and of conspicuity index on metastasis detectability were measured using multivariable linear regression. RESULTS: The median metastasis was 1.4 cm from the edge (interquartile range [IQR], 0.9-2.1 cm). Its diameter was 1.2 cm (IQR, 0.9-1.8 cm), and its contrast was 38 HU (IQR, 23-68 HU). An increase of one standard deviation in conspicuity index was associated with a 6.9% increase in detectability (p = 0.008), whereas an increase of one standard deviation in distance from the liver edge was associated with a 5.5% increase in detectability (p = 0.03). CONCLUSION: Peripheral liver metastases were missed more frequently than central liver metastases, with this effect depending on metastasis size and contrast.

Improved Pulmonary Artery Evaluation Using High-Pitch Photon-Counting CT Compared to High-Pitch Conventional or Routine-Pitch Conventional Dual-Energy CT.

OBJECTIVE: Pulmonary CT angiography (CTA) to detect pulmonary emboli can be performed using conventional dual-source CT with single-energy acquisition at high-pitch (high-pitch conventional CT), which minimizes motion artifacts, or routine-pitch, dual-energy acquisitions (routine-pitch conventional DECT), which maximize iodine signal. We compared iodine signal, radiation dose, and motion artifacts of pulmonary CTA between these conventional CT modalities and dual-source photon-counting detector CT with high-pitch, multienergy acquisitions (high-pitch photon-counting CT). METHODS: Consecutive clinically indicated pulmonary CTA exams were collected. CT number/noise was measured from the main to right lower lobe segmental pulmonary arteries using 120 kV threshold low, 120 kV, and mixed kV (0.6 linear blend) images. Three radiologists reviewed anonymized, randomized exams, rating them using a 4- or 5-point Likert scale (1 = worst, and 4/5 = best) for contrast enhancement in pulmonary arteries, motion artifacts in aortic root to subsegmental pulmonary arteries, lung image quality; pulmonary blood volume (PBV) map image quality (for multienergy or dual-energy exams), and contribution to reader confidence. RESULTS: One hundred fifty patients underwent high-pitch photon-counting CT (n = 50), high-pitch conventional CT (n = 50), and routine-pitch conventional DECT (n = 50). High-pitch photon-counting CT had lower radiation dose (CTDIvol: 8.1 ± 2.5 vs 9.6 ± 6.8 and 16.2 ± 8.5 mGy, respectively; P < 0.001), and routine-pitch conventional DECT had significantly less contrast (P < 0.009). CT number and CNR measurements were significantly greater at high-pitch photon-counting CT (P < 0.001). Across readers, high-pitch photon-counting CT demonstrated significantly higher subjective contrast enhancement in the pulmonary arteries compared to the other modalities (4.7 ± 0.6 vs 4.4 ± 0.7 vs 4.3 ± 0.7; P = 0.011) and lung image quality (3.4 ± 0.5 vs 3.1 ± 0.5 vs 3.1 ± 0.5; P = 0.013). High-pitch photon-counting CT and high-pitch conventional CT had fewer motion artifacts at all levels compared to DECT (P < 0.001). High-pitch photon-counting CT PBV maps had superior image quality (P < 0.001) and contribution to reader confidence (P < 0.001) compared to routine-pitch conventional DECT. CONCLUSION: High-pitch photon-counting pulmonary CTA demonstrated higher contrast in pulmonary arteries at lower radiation doses with improved lung image quality and fewer motion artifacts compared to high-pitch conventional CT and routine-pitch conventional dual-energy CT.

Comparative sensitivity of early cystic fibrosis lung disease detection tools in school aged children.

BACKGROUND: Effective detection of early lung disease in cystic fibrosis (CF) is critical to understanding early pathogenesis and evaluating early intervention strategies. We aimed to compare ability of several proposed sensitive functional tools to detect early CF lung disease as defined by CT structural disease in school aged children. METHODS: 50 CF subjects (mean±SD 11.2 ± 3.5y, range 5-18y) with early lung disease (FEV1≥70 % predicted: 95.7 ± 11.8 %) performed spirometry, Multiple breath washout (MBW, including trapped gas assessment), oscillometry, cardiopulmonary exercise testing (CPET) and simultaneous spirometer-directed low-dose CT imaging. CT data were analysed using well-evaluated fully quantitative software for bronchiectasis and air trapping (AT). RESULTS: CT bronchiectasis and AT occurred in 24 % and 58 % of patients, respectively. Of the functional tools, MBW detected the highest rates of abnormality: Scond 82 %, MBWTG RV 78 %, LCI 74 %, MBWTG IC 68 % and Sacin 51 %. CPET VO2peak detected slightly higher rates of abnormality (9 %) than spirometry-based FEV1 (2 %). For oscillometry AX (14 %) performed better than Rrs (2 %) whereas Xrs and R5-19 failed to detect any abnormality. LCI and Scond correlated with bronchiectasis (r = 0.55-0.64, p < 0.001) and AT (r = 0.73-0.74, p < 0.001). MBW-assessed trapped gas was detectable in 92 % of subjects and concordant with CT-assessed AT in 74 %. CONCLUSIONS: Significant structural and functional deficits occur in early CF lung disease, as detected by CT and MBW. For MBW, additional utility, beyond that offered by LCI, was suggested for Scond and MBW-assessed gas trapping. Our study reinforces the complementary nature of these tools and the limited utility of conventional oscillometry and CPET in this setting.

Visual and Quantitative Evaluation of Low-Concentration Bismuth in Dual-Contrast Imaging of Iodine and Bismuth Using Clinical Photon-Counting CT.

Simultaneous dual-contrast imaging of iodine and bismuth has shown promise in prior phantom and animal studies utilizing spectral CT. However, it is noted that in previous studies, Pepto-Bismol has frequently been employed as the source of bismuth, exceeding the recommended levels for human subjects. This investigation sought to assess the feasibility of visually differentiating and precisely quantifying low-concentration bismuth using clinical dual-source photon-counting CT (PCCT) in a scenario involving both iodinated and bismuth-based contrast materials. Four bismuth samples (0.6, 1.3, 2.5, and 5.1 mg/mL) were prepared using Pepto-Bismol, alongside three iodine rods (1, 2, and 5 mg/mL), inserted into multi-energy CT phantoms with three different sizes, and scanned on a PCCT system at three tube potentials (120, 140, and Sn140 kV). A generic image-based three-material decomposition method generated iodine and bismuth maps, with mean mass concentrations and noise levels measured. The root-mean-square errors for iodine and bismuth determined the optimal tube potential. The tube potential of 140 kV demonstrated optimal quantification performance when both iodine and bismuth were considered. Distinct differentiation of iodine rods with all three concentrations and bismuth samples with mass concentrations ≥ 1.3 mg/mL was observed across all phantom sizes at the optimal kV setting.

Development and validation of a noise insertion algorithm for photon-counting-detector CT.

BACKGROUND: Inserting noise into existing patient projection data to simulate lower-radiation-dose exams has been frequently used in traditional energy-integrating-detector (EID)-CT to optimize radiation dose in clinical protocols and to generate paired images for training deep-learning-based reconstruction and noise reduction methods. Recent introduction of photon counting detector CT (PCD-CT) also requires such a method to accomplish these tasks. However, clinical PCD-CT scanners often restrict the users access to the raw count data, exporting only the preprocessed, log-normalized sinogram. Therefore, it remains a challenge to employ projection domain noise insertion algorithms on PCD-CT. PURPOSE: To develop and validate a projection domain noise insertion algorithm for PCD-CT that does not require access to the raw count data. MATERIALS AND METHODS: A projection-domain noise model developed originally for EID-CT was adapted for PCD-CT. This model requires, as input, a map of the incident number of photons at each detector pixel when no object is in the beam. To obtain the map of incident number of photons, air scans were acquired on a PCD-CT scanner, then the noise equivalent photon number (NEPN) was calculated from the variance in the log normalized projection data of each scan. Additional air scans were acquired at various mA settings to investigate the impact of pulse pileup on the linearity of NEPN measurement. To validate the noise insertion algorithm, Noise Power Spectra (NPS) were generated from a 30 cm water tank scan and used to compare the noise texture and noise level of measured and simulated half dose and quarter dose images. An anthropomorphic thorax phantom was scanned with automatic exposure control, and noise levels at different slice locations were compared between simulated and measured half dose and quarter dose images. Spectral correlation between energy thresholds T1 and T2, and energy bins, B1 and B2, was compared between simulated and measured data across a wide range of tube current. Additionally, noise insertion was performed on a clinical patient case for qualitative assessment. RESULTS: The NPS generated from simulated low dose water tank images showed similar shape and amplitude to that generated from the measured low dose images, differing by a maximum of 5.0% for half dose (HD) T1 images, 6.3% for HD T2 images, 4.1% for quarter dose (QD) T1 images, and 6.1% for QD T2 images. Noise versus slice measurements of the lung phantom showed comparable results between measured and simulated low dose images, with root mean square percent errors of 5.9%, 5.4%, 5.0%, and 4.6% for QD T1, HD T1, QD T2, and HD T2, respectively. NEPN measurements in air were linear up until 112 mA, after which pulse pileup effects significantly distort the air scan NEPN profile. Spectral correlation between T1 and T2 in simulation agreed well with that in the measured data in typical dose ranges. CONCLUSIONS: A projection-domain noise insertion algorithm was developed and validated for PCD-CT to synthesize low-dose images from existing scans. It can be used for optimizing scanning protocols and generating paired images for training deep-learning-based methods.

Association of serum ferritin and all-cause mortality in AKI patients: a retrospective cohort study.

Background: Serum ferritin (SF) is clinically found to be elevated in many disease conditions, and our research examines serum ferritin in patients with acute kidney injury (AKI) and its implication on the risk of short-term mortality in AKI. Methods: Data were extracted from the Medical Information Mart for Intensive Care IV 2.2 (MIMIC-IV 2.2) database. Adult patients with AKI who had serum ferritin tested on the first day of ICU admission were included. The primary outcome was 28-day mortality. Kaplan-Meier survival curves and Cox proportional hazards models were used to test the relationship between SF and clinical outcomes. Subgroup analyses based on the Cox model were further conducted. Results: Kaplan-Meier survival curves showed that a higher SF value was significantly associated with an enhanced risk of 28-day mortality, 90-day mortality, ICU mortality and hospital mortality (log-rank test: p < 0.001 for all clinical outcomes). In multivariate Cox regression analysis, high level of SF with mortality was significantly positive in all four outcome events (all p < 0.001). This result remains robust after adjusting for all variables. Subgroup analysis of SF with 28-day mortality based on Cox model-4 showed that high level of SF was associated with high risk of 28-day mortality in patients regardless of the presence or absence of sepsis (p for interaction = 0.730). Positive correlations of SF and 28-day mortality were confirmed in all other subgroups (p for interaction>0.05). Conclusion: High level of SF is an independent prognostic predictor of 28-day mortality in patients with AKI.

Multi-institutional Protocol Guidance for Pediatric Photon-counting CT.

Performing CT in children comes with unique challenges such as greater degrees of patient motion, smaller and densely packed anatomy, and potential risks of radiation exposure. The technical advancements of photon-counting detector (PCD) CT enable decreased radiation dose and noise, as well as increased spatial and contrast resolution across all ages, compared with conventional energy-integrating detector CT. It is therefore valuable to review the relevant technical aspects and principles specific to protocol development on the new PCD CT platform to realize the potential benefits for this population. The purpose of this article, based on multi-institutional clinical and research experience from pediatric radiologists and medical physicists, is to provide protocol guidance for use of PCD CT in the imaging of pediatric patients.

Low-contrast detectability of photon-counting-detector CT at different scan modes and image types in comparison with energy-integrating-detector CT.

Purpose: We aim to compare the low-contrast detectability of a clinical whole-body photon-counting-detector (PCD)-CT at different scan modes and image types with an energy-integrating-detector (EID)-CT. Approach: We used a channelized Hotelling observer (CHO) previously optimized for quality control purposes. An American College of Radiology CT accreditation phantom was scanned on both PCD-CT and EID-CT with 10 phantom positionings. For PCD-CT, images were generated using two scan modes, standard resolution (SR) and ultra-high-resolution (UHR); two image types, virtual monochromatic images at 70 keV and low-energy threshold (T3D); both filtered-back-projection (FBP) and iterative reconstruction (IR) reconstruction methods; and three reconstruction kernels. For each positioning, three repeated scans were acquired for each scan mode, image type, and CTDIvol of 6, 12, and 24 mGy. For EID-CT, images acquired from scans (10 positionings × 3 repeats × 3 doses) were reconstructed using the closest counterpart FBP and IR kernels. CHO was applied to calculate the index of detectability (d') on both scanners. Results: With the smooth Br44 kernel, the d' of UHR was mostly comparable with that of the SR mode (difference: -11.4% to 8.3%, p=0.020 to 0.956), and the T3D images had a higher d' (difference: 0.7% to 25.6%) than 70 keV images on PCD-CT. Compared with the EID-CT, UHR-T3D of PCD-CT had non-inferior d' (difference: -2.7% to 12.9%) with IR and non-superior d' (difference: 0.8% to 11.2%) with FBP using the Br44 kernel. PCD-CT produced higher d' than EID-CT by 61.8% to 247.1% with the sharper reconstruction kernels. Conclusions: The comparison between PCD-CT and EID-CT was significantly influenced by the reconstruction method and kernel. With a smooth kernel that is typically used in low-contrast detection tasks, the PCD-CT demonstrated low-contrast detectability that was comparable to EID-CT with IR and showed no superiority when using FBP. With the use of sharper kernels, the PCD-CT significantly outperformed EID-CT in low-contrast detectability.

3D printed phantom with 12 000 submillimeter lesions to improve efficiency in CT detectability assessment.

BACKGROUND: The detectability performance of a CT scanner is difficult to precisely quantify when nonlinearities are present in reconstruction. An efficient detectability assessment method that is sensitive to small effects of dose and scanner settings is desirable. We previously proposed a method using a search challenge instrument: a phantom is embedded with hundreds of lesions at random locations, and a model observer is used to detect lesions. Preliminary tests in simulation and a prototype showed promising results. PURPOSE: In this work, we fabricated a full-size search challenge phantom with design updates, including changes to lesion size, contrast, and number, and studied our implementation by comparing the lesion detectability from a nonprewhitening (NPW) model observer between different reconstructions at different exposure levels, and by estimating the instrument sensitivity to detect changes in dose. METHODS: Designed to fit into QRM anthropomorphic phantoms, our search challenge phantom is a cylindrical insert 10 cm wide and 4 cm thick, embedded with 12 000 lesions (nominal width of 0.6 mm, height of 0.8 mm, and contrast of -350 HU), and was fabricated using PixelPrint, a 3D printing technique. The insert was scanned alone at a high dose to assess printing accuracy. To evaluate lesion detectability, the insert was placed in a QRM thorax phantom and scanned from 50 to 625 mAs with increments of 25 mAs, once per exposure level, and the average of all exposure levels was used as high-dose reference. Scans were reconstructed with three different settings: filtered-backprojection (FBP) with Br40 and Br59, and Sinogram Affirmed Iterative Reconstruction (SAFIRE) with strength level 5 and Br59 kernel. An NPW model observer was used to search for lesions, and detection performance of different settings were compared using area under the exponential transform of free response ROC curve (AUC). Using propagation of uncertainty, the sensitivity to changes in dose was estimated by the percent change in exposure due to one standard deviation of AUC, measured from 5 repeat scans at 100, 200, 300, and 400 mAs. RESULTS: The printed insert lesions had an average position error of 0.20 mm compared to printing reference. As the exposure level increases from 50 mAs to 625 mAs, the lesion detectability AUCs increase from 0.38 to 0.92, 0.42 to 0.98, and 0.41 to 0.97 for FBP Br40, FBP Br59, and SAFIRE Br59, respectively, with a lower rate of increase at higher exposure level. FBP Br59 performed best with AUC 0.01 higher than SAFIRE Br59 on average and 0.07 higher than FBP Br40 (all P < 0.001). The standard deviation of AUC was less than 0.006, and the sensitivity to detect changes in mAs was within 2% for FBP Br59. CONCLUSIONS: Our 3D-printed search challenge phantom with 12 000 submillimeter lesions, together with an NPW model observer, provide an efficient CT detectability assessment method that is sensitive to subtle effects in reconstruction and is sensitive to small changes in dose.

Evaluation of data uncertainty for deep-learning-based CT noise reduction using ensemble patient data and a virtual imaging trial framework.

Deep learning-based image reconstruction and noise reduction (DLIR) methods have been increasingly deployed in clinical CT. Accurate assessment of their data uncertainty properties is essential to understand the stability of DLIR in response to noise. In this work, we aim to evaluate the data uncertainty of a DLIR method using real patient data and a virtual imaging trial framework and compare it with filtered-backprojection (FBP) and iterative reconstruction (IR). The ensemble of noise realizations was generated by using a realistic projection domain noise insertion technique. The impact of varying dose levels and denoising strengths were investigated for a ResNet-based deep convolutional neural network (DCNN) model trained using patient images. On the uncertainty maps, DCNN shows more detailed structures than IR although its bias map has less structural dependency, which implies that DCNN is more sensitive to small changes in the input. Both visual examples and histogram analysis demonstrated that hotspots of uncertainty in DCNN may be associated with a higher chance of distortion from the truth than IR, but it may also correspond to a better detection performance for some of the small structures.

Automated Web-based Software for CT Quality Control Testing of Low-contrast Detectability using Model Observers.

The Channelized Hotelling observer (CHO) is well correlated with human observer performance in many CT detection/classification tasks but has not been widely adopted in routine CT quality control and performance evaluation, mainly because of the lack of an easily available, efficient, and validated software tool. We developed a highly automated solution - CT image quality evaluation and Protocol Optimization (CTPro), a web-based software platform that includes CHO and other traditional image quality assessment tools such as modulation transfer function and noise power spectrum. This tool can allow easy access to the CHO for both the research and clinical community and enable efficient, accurate image quality evaluation without the need of installing additional software. Its application was demonstrated by comparing the low-contrast detectability on a clinical photon-counting-detector (PCD)-CT with a traditional energy-integrating-detector (EID)-CT, which showed UHR-T3D had 6.2% higher d' than EID-CT with IR (p = 0.047) and 4.1% lower d' without IR (p = 0.122).

Task-based automatic keV selection: leveraging routine virtual monoenergetic imaging for dose reduction on clinical photon-counting detector CT.

Objective. Photon-counting detector (PCD) CT enables routine virtual-monoenergetic image (VMI) reconstruction. We evaluated the performance of an automatic VMI energy level (keV) selection tool on a clinical PCD-CT system in comparison to an automatic tube potential (kV) selection tool from an energy-integrating-detector (EID) CT system from the same manufacturer.Approach.Four torso-shaped phantoms (20-50 cm width) containing iodine (2, 5, and 10 mg cc-1) and calcium (100 mg cc-1) were scanned on PCD-CT and EID-CT. Dose optimization techniques, task-based VMI energy level and tube-potential selection on PCD-CT (CARE keV) and task-based tube potential selection on EID-CT (CARE kV), were enabled. CT numbers, image noise, and dose-normalized contrast-to-noise ratio (CNRd) were compared.Main results. PCD-CT produced task-specific VMIs at 70, 65, 60, and 55 keV for non-contrast, bone, soft tissue with contrast, and vascular settings, respectively. A 120 kV tube potential was automatically selected on PCD-CT for all scans. In comparison, EID-CT used x-ray tube potentials from 80 to 150 kV based on imaging task and phantom size. PCD-CT achieved consistent dose reduction at 9%, 21% and 39% for bone, soft tissue with contrast, and vascular tasks relative to the non-contrast task, independent of phantom size. On EID-CT, dose reduction factor for contrast tasks relative to the non-contrast task ranged from a 65% decrease (vascular task, 70 kV, 20 cm phantom) to a 21% increase (soft tissue with contrast task, 150 kV, 50 cm phantom) due to size-specific tube potential adaptation. PCD-CT CNRdwas equivalent to or higher than those of EID-CT for all tasks and phantom sizes, except for the vascular task with 20 cm phantom, where 70 kV EID-CT CNRdoutperformed 55 keV PCD-CT images.Significance. PCD-CT produced more consistent CT numbers compared to EID-CT due to standardized VMI output, which greatly benefits standardization efforts and facilitates radiation dose reduction.

Benefits of Photon-Counting CT Myelography for Localization of Dural Tears in Spontaneous Intracranial Hypotension.

Photon-counting CT is an increasingly used technology with numerous advantages over conventional energy-integrating detector CT. These include superior spatial resolution, high temporal resolution, and inherent spectral imaging capabilities. Recently, photon-counting CT myelography was described as an effective technique for the detection of CSF-venous fistulas, a common cause of spontaneous intracranial hypotension. It is likely that photon-counting CT myelography will also have advantages for the localization of dural tears, a separate type of spontaneous spinal CSF leak that requires different myelographic techniques for accurate localization. To our knowledge, prior studies on photon-counting CT myelography have been limited to techniques for detecting CSF-venous fistulas. In this technical report, we describe our technique and early experience with photon-counting CT myelography for the localization of dural tears.

Photon-counting CT in Thoracic Imaging: Early Clinical Evidence and Incorporation Into Clinical Practice.

Photon-counting CT (PCCT) is an emerging advanced CT technology that differs from conventional CT in its ability to directly convert incident x-ray photon energies into electrical signals. The detector design also permits substantial improvements in spatial resolution and radiation dose efficiency and allows for concurrent high-pitch and high-temporal-resolution multienergy imaging. This review summarizes (a) key differences in PCCT image acquisition and image reconstruction compared with conventional CT; (b) early evidence for the clinical benefit of PCCT for high-spatial-resolution diagnostic tasks in thoracic imaging, such as assessment of airway and parenchymal diseases, as well as benefits of high-pitch and multienergy scanning; (c) anticipated radiation dose reduction, depending on the diagnostic task, and increased utility for routine low-dose thoracic CT imaging; (d) adaptations for thoracic imaging in children; (e) potential for further quantitation of thoracic diseases; and (f) limitations and trade-offs. Moreover, important points for conducting and interpreting clinical studies examining the benefit of PCCT relative to conventional CT and integration of PCCT systems into multivendor, multispecialty radiology practices are discussed.

Image quality evaluation in deep-learning-based CT noise reduction using virtual imaging trial methods: Contrast-dependent spatial resolution.

BACKGROUND: Deep-learning-based image reconstruction and noise reduction methods (DLIR) have been increasingly deployed in clinical CT. Accurate image quality assessment of these methods is challenging as the performance measured using physical phantoms may not represent the true performance of DLIR in patients since DLIR is trained mostly on patient images. PURPOSE: In this work, we aim to develop a patient-data-based virtual imaging trial framework and, as a first application, use it to measure the spatial resolution properties of a DLIR method. METHODS: The patient-data-based virtual imaging trial framework consists of five steps: (1) insertion of lesions into projection domain data using the acquisition geometry of the patient exam to simulate different lesion characteristics; (2) insertion of noise into projection domain data using a realistic photon statistical model of the CT system to simulate different dose levels; (3) creation of DLIR-processed images from projection or image data; (4) creation of ensembles of DLIR-processed patient images from a large number of noise and lesion realizations; and (5) evaluation of image quality using ensemble DLIR images. This framework was applied to measure the spatial resolution of a ResNet based deep convolutional neural network (DCNN) trained on patient images. Lesions in a cylindrical shape and different contrast levels (-500, -100, -50, -20, -10 HU) were inserted to the lower right lobe of the liver in a patient case. Multiple dose levels were simulated (50%, 25%, 12.5%). Each lesion and dose condition had 600 noise realizations. Multiple reconstruction and denoising methods were used on all the noise realizations, including the original filtered-backprojection (FBP), iterative reconstruction (IR), and the DCNN method with three different strength setting (DCNN-weak, DCNN-medium, and DCNN-strong). Mean lesion signal was calculated by performing ensemble averaging of all the noise realizations for each lesion and dose condition and then subtracting the lesion-present images from the lesion absent images. Modulation transfer functions (MTFs) both in-plane and along the z-axis were calculated based on the mean lesion signals. The standard deviations of MTFs at each condition were estimated with bootstrapping: randomly sampling (with replacement) all the DLIR/FBP/IR images from the ensemble data (600 samples) at each condition. The impact of varying lesion contrast, dose levels, and denoising strengths were evaluated. Statistical analysis with paired t-test was used to compare the z-axis and in-plane spatial resolution of five algorithms for five different contrasts and three dose levels. RESULTS: The in-plane and z-axis spatial resolution degradation of DCNN becomes more severe as the contrast or radiation dose decreased, or DCNN denoising strength increased. In comparison with FBP, a 59.5% and 4.1% reduction of in-plane and z-axis MTF (in terms of spatial frequencies at 50% MTF), respectively, was observed at low contrast (-10 HU) for DCNN with the highest denoising strength at 25% routine dose level. When the dose level reduces from 50% to 12.5% of routine dose, the in-plane and z-axis MTFs reduces from 92.1% to 76.3%, and from 98.9% to 95.5%, respectively, at contrast of -100 HU, using FBP as the reference. For most conditions of contrasts and dose levels, significant differences were found among the five algorithms, with the following relationship in both in-plane and cross-plane spatial resolution: FBP > DCNN-Weak > IR > DCNN-Medium > DCNN-Strong. The spatial resolution difference among algorithms decreases at higher contrast or dose levels. CONCLUSIONS: A patient-data-based virtual imaging trial framework was developed and applied to measuring the spatial resolution properties of a DCNN noise reduction method at different contrast and dose levels using real patient data. As with other non-linear image reconstruction and post-processing techniques, the evaluated DCNN method degraded the in-plane and z-axis spatial resolution at lower contrast levels, lower radiation dose, and higher denoising strength.

When will the immune-stimulating antibody conjugates (ISACs) be transferred from bench to bedside?

Immunostimulatory antibody conjugates (ISACs) as a promising new generation of targeted therapeutic antibody-drug conjugates (ADCs), that not only activate innate immunity but also stimulate adaptive immunity, providing a dual therapeutic effect to eliminate tumor cells. However, several ISACs are still in the early stages of clinical development or have already failed. Therefore, it is crucial to design ISACs more effectively to overcome their limitations, including high toxicity, strong immunogenicity, long development time, and poor pharmacokinetics. This review aims to summarize the composition and function of ISACs, incorporating current design considerations and ongoing clinical trials. Additionally, the review delves into the current issues with ISACs and potential solutions, such as adjusting the drug-antibody ratio (DAR) to improve the bioavailability of ISACs. By leveraging the affinity and bioavailability-enhancing properties of bispecific antibodies, the utility between antibodies and immunostimulatory agents can be balanced. Commonly used immunostimulatory agents may induce systemic immune reactions, and BTK (Bruton's tyrosine kinase) inhibitors can regulate immunogenicity. Finally, the concept of grafting ADC's therapeutic principles is simple, but the combination of payload, linker, and targeted functional molecules is not a simple permutation and combination problem. The development of conjugate drugs faces more complex pharmacological and toxicological issues. Standing on the shoulders of ADC, the development and application scenarios of ISAC are endowed with broader space.

Channelized hotelling observer-based low-contrast detectability on the ACR CT accreditation phantom: Part II. Repeatability study.

BACKGROUND: Objective and quantitative evaluation for low-contrast detectability that correlates with human observer performance is lacking for routine CT quality control testing. Channelized Hotelling observer (CHO) is considered a strong candidate to fill the need but has long been deemed impractical to implement due to its requirement of a large number of repeated scans in order to provide accurate and precise estimates of index of detectability (d'). In our previous work, we optimized a CHO model observer on the American College of Radiology (ACR) CT accreditation phantom and achieved accurate measurement of d' with only 1-3 repeat scans. PURPOSE: In this work, we aim to validate the repeatability of the proposed CHO-based low-contrast evaluation on four scanner models using the ACR CT accreditation phantom. METHODS: The repeatability test was performed on four different scanners from two major CT manufacturers: Siemens Force and Alpha; Canon Prism and Prime SP. An ACR CT phantom was scanned 10 times, each time after repositioning of the phantom. For each repositioning, 3 repeated scans were acquired at 24, 12, and 6 mGy on all four scanner models. CHO was applied at the measured dose levels for different low-contrast object sizes (4-6 mm). The CHO was also applied to images created using deep learning-based reconstructions on Canon Prism and to four different scan/reconstruction modes on the Siemens Alpha, a photon-counting-detector (PCD)-CT. The repeatability was evaluated by the probability that a measurement would fall within the ±15% tolerance (P<15% ). RESULTS: With the CHO setting optimized for the ACR phantom and the use of 3 repeated scans and 9 non-overlapping slices per scan, the CHO measurement could provide high repeatability with P<15% of 98.8%-99.9% at 12 mGy with IR reconstruction on all four scanners. On scanner A, P<15% were 91.5%-99.9% at the three dose levels and for all three object sizes while the numbers were 93.6%-99.998% on scanner B. P<15% were 96.5%-97.2% for the two deep learning reconstructions and 97.0%-99.97% for the four scan/reconstruction modes on the PCD-CT. CONCLUSION: The CHO provided highly repeatable measurements with over 95% probability that a CHO measurement would lie within the ±15% tolerance for most of the dose levels and object sizes on the ACR phantom. The repeatability was maintained when the CHO was applied to images created with a commercial deep learning-based reconstruction and various scan/reconstruction modes on a PCD-CT. This study demonstrates that practical implementation of CHO for routine quality control and performance evaluation is feasible.

LL-37 improves sepsis-induced acute lung injury by suppressing pyroptosis in alveolar epithelial cells.

BACKGROUND: LL-37 (also known as murine CRAMP) is a human antimicrobial peptide that plays a crucial role in innate immune defence against sepsis through various mechanisms. However, its involvement in sepsis-induced lung injury remains unclear. OBJECTIVES: This work investigates the impact of LL-37 on pyroptosis generated by LPS in alveolar epithelial cells. The research utilizes both in vivo and in vitro sepsis-associated acute lung injury (ALI) models to understand the underlying molecular pathways. METHODS: In vivo, an acute lung injury model induced by sepsis was established by intratracheal administration of LPS in C57BL/6J mice, which were subsequently treated with low-dose CRAMP (recombinant murine cathelicidin, 2.5 mg.kg-1) and high-dose CRAMP (5.0 mg.kg-1). In vitro, pyroptosis was induced in a human alveolar epithelial cell line (A549) by stimulation with LPS and ATP. Treatment was carried out with recombinant human LL-37, or LL-37 was knocked out in A549 cells using small interfering RNA (siRNA). Subsequently, haematoxylin and eosin staining was performed to observe the histopathological changes in lung tissues in the control group and sepsis-induced lung injury group. TUNEL and PI staining were used to observe DNA fragmentation and pyroptosis in mouse lung tissues and cells in the different groups. An lactate dehydrogenase (LDH) assay was performed to measure the cell death rate. The expression levels of NLRP3, caspase1, caspase 1 p20, GSDMD, NT-GSDMD, and CRAMP were detected in mice and cells using Western blotting, qPCR, and immunohistochemistry. ELISA was used to assess the levels of interleukin (IL)-1ß and IL-18 in mouse serum, bronchoalveolar lavage fluid (BALF) and lung tissue and cell culture supernatants. RESULTS: The expression of NLRP3, caspase1 p20, NT-GSDMD, IL 18 and IL1ß in the lung tissue of mice with septic lung injury was increased, which indicated activation of the canonical pyroptosis pathway and coincided with an increase in CRAMP expression. Treatment with recombinant CRAMP improved pyroptosis in mice with lung injury. In vitro, treatment with LPS and ATP upregulated these classic pyroptosis molecules, LL-37 knockdown exacerbated pyroptosis, and recombinant human LL-37 treatment alleviated pyroptosis in alveolar epithelial cells. CONCLUSION: These findings indicate that LL-37 protects against septic lung injury by modulating the expression of classic pyroptotic pathway components, including NLRP3, caspase1, and GSDMD and downstream inflammatory factors in alveolar epithelial cells.

Multiple Kernel Synthesis of Head CT Using a Task-Based Loss Function.

In CT imaging of the head, multiple image series are routinely reconstructed with different kernels and slice thicknesses. Reviewing the redundant information is an inefficient process for radiologists. We address this issue with a convolutional neural network (CNN)-based technique, synthesiZed Improved Resolution and Concurrent nOise reductioN (ZIRCON), that creates a single, thin, low-noise series that combines the favorable features from smooth and sharp head kernels. ZIRCON uses a CNN model with an autoencoder U-Net architecture that accepts two input channels (smooth- and sharp-kernel CT images) and combines their salient features to produce a single CT image. Image quality requirements are built into a task-based loss function with a smooth and sharp loss terms specific to anatomical regions. The model is trained using supervised learning with paired routine-dose clinical non-contrast head CT images as training targets and simulated low-dose (25%) images as training inputs. One hundred unique de-identified clinical exams were used for training, ten for validation, and ten for testing. Visual comparisons and contrast measurements of ZIRCON revealed that thinner slices and the smooth-kernel loss function improved gray-white matter contrast. Combined with lower noise, this increased visibility of small soft-tissue features that would be otherwise impaired by partial volume averaging or noise. Line profile analysis showed that ZIRCON images largely retained sharpness compared to the sharp-kernel input images. ZIRCON combined desirable image quality properties of both smooth and sharp input kernels into a single, thin, low-noise series suitable for both brain and skull imaging.