Spatial Resolution Fidelity Comparison Between Energy Integrating and Deep Silicon Photon Counting CT: Implications for Pulmonary Imaging.

PURPOSE: We investigated spatial resolution loss away from isocenter for a prototype deep silicon photon-counting detector (PCD) CT scanner and compare with a clinical energy-integrating detector (EID) CT scanner. MATERIALS AND METHODS: We performed three scans on a wire phantom at four positions (isocenter, 6.7, 11.8, and 17.1 cm off isocenter). The acquisition modes were 120 kV EID CT, 120 kV high-definition (HD) EID CT, and 120 kV PCD CT. HD mode used double the projection view angles per rotation as the "regular" EID scan mode. The diameter of the wire was calculated by taking the full width of half max (FWHM) of a profile drawn over the radial and azimuthal directions of the wire. Change in wire diameter appearance was assessed by calculating the ratio of the radial and azimuthal diameter relative to isocenter. t tests were used to make pairwise comparisons of the wire diameter ratio with each acquisition and mean ratios' difference from unity. RESULTS: Deep silicon PCD CT had statistically smaller (P<0.05) changes in diameter ratio for both radial and azimuthal directions compared with both regular and HD EID modes and was not statistically different from unity (P<0.05). Maximum increases in FWMH relative to isocenter were 36%, 12%, and 1% for regular EID, HD EID, and deep silicon PCD, respectively. CONCLUSION: Deep silicon PCD CT exhibits less change in spatial resolution in both the radial and azimuthal directions compared with EID CT.

Targeting Neuroinflammation by Pharmacologic Downregulation of Inflammatory Pathways Is Neuroprotective in Protein Misfolding Disorders.

Neuroinflammation plays a crucial role in the development of neurodegenerative protein misfolding disorders. This category of progressive diseases includes, but is not limited to, Alzheimer's disease, Parkinson's disease, and prion diseases. Shared pathogenesis involves the accumulation of misfolded proteins, chronic neuroinflammation, and synaptic dysfunction, ultimately leading to irreversible neuronal loss, measurable cognitive deficits, and death. Presently, there are few to no effective treatments to halt the advancement of neurodegenerative diseases. We hypothesized that directly targeting neuroinflammation by downregulating the transcription factor, NF-κB, and the inflammasome protein, NLRP3, would be neuroprotective. To achieve this, we used a cocktail of RNA targeting therapeutics (SB_NI_112) shown to be brain-penetrant, nontoxic, and effective inhibitors of both NF-κB and NLRP3. We utilized a mouse-adapted prion strain as a model for neurodegenerative diseases to assess the aggregation of misfolded proteins, glial inflammation, neuronal loss, cognitive deficits, and lifespan. Prion-diseased mice were treated either intraperitoneally or intranasally with SB_NI_112. Behavioral and cognitive deficits were significantly protected by this combination of NF-κB and NLRP3 downregulators. Treatment reduced glial inflammation, protected against neuronal loss, prevented spongiotic change, rescued cognitive deficits, and significantly lengthened the lifespan of prion-diseased mice. We have identified a nontoxic, systemic pharmacologic that downregulates NF-κB and NLRP3, prevents neuronal death, and slows the progression of neurodegenerative diseases. Though mouse models do not always predict human patient success and the study was limited due to sample size and number of dosing methods utilized, these findings serve as a proof of principle for continued translation of the therapeutic SB_NI_112 for prion disease and other neurodegenerative diseases. Based on the success in a murine prion model, we will continue testing SB_NI_112 in a variety of neurodegenerative disease models, including Alzheimer's disease and Parkinson's disease.

Targeted-Neuroinflammation Mitigation Using Inflammasome-Inhibiting Nanoligomers is Therapeutic in an Experimental Autoimmune Encephalomyelitis Mouse Model.

Multiple sclerosis (MS) is a debilitating autoimmune disease that impacts millions of patients worldwide, disproportionately impacting women (4:1), and often presenting at highly productive stages of life. This disease affects the spinal cord and brain and is characterized by severe neuroinflammation, demyelination, and subsequent neuronal damage, resulting in symptoms like loss of mobility. While untargeted and pan-immunosuppressive therapies have proven to be disease-modifying and manage (or prolong the time between) symptoms in many patients, a significant fraction are unable to achieve remission. Recent work has suggested that targeted neuroinflammation mitigation through selective inflammasome inhibition can offer relief to patients while preserving key components of immune function. Here, we show a screening of potential therapeutic targets using inflammasome-inhibiting Nanoligomers (NF-κB1, TNFR1, TNF-α, IL-6) that meet or far-exceed commercially available small-molecule counterparts like ruxolitinib, MCC950, and deucravacitinib. Using the human brain organoid model, top Nanoligomer combinations (NF-κB1 + TNFR1: NI111, and NF-κB1 + NLRP3: NI112) were shown to significantly reduce neuroinflammation without any observable negative impact on organoid function. Further testing of these top Nanoligomer combinations in an aggressive experimental autoimmune encephalomyelitis (EAE) mouse model for MS using intraperitoneal (IP) injections showed that NF-κB1 and NLRP3 targeting Nanoligomer combination NI112 rescues mice without observable loss of mobility or disability, minimal inflammation in brain and spinal cord histology, and minimal to no immune cell infiltration of the spinal cord and no demyelination, similar to or at par with mice that received no EAE injections (negative control). Mice receiving NI111 (NF-κB1 + TNFR1) also showed reduced neuroinflammation compared to saline (sham)-treated EAE mice and at par/similar to other inflammasome-inhibiting small molecule treatments, although it was significantly higher than NI112 leading to subsequent worsening clinical outcomes. Furthermore, treatment with an oral formulation of NI112 at lower doses showed a significant reduction in EAE severity, albeit with higher variance owing to administration and formulation/fill-and-finish variability. Overall, these results point to the potential of further development and testing of these inflammasome-targeting Nanoliogmers as an effective neuroinflammation treatment for multiple neurodegenerative diseases and potentially benefit several patients suffering from such debilitating autoimmune diseases like MS.

Role of Radiology in Assessment of Postoperative Complications of Heart Transplantation.

Heart transplantation is a pivotal treatment of end-stage heart failure, and recent advancements have extended median posttransplant life expectancy. However, despite the progress in surgical techniques and medical treatment, heart transplant patients still face complications such as rejection, infections, and drug toxicity. CT is a reliable tool for detecting most of these complications, whereas MR imaging is particularly adept at identifying pericardial pathologies and signs of rejection. Awareness of these nuances by radiologists, cardiologists, and surgeons is desired to optimize care, reduce morbidities, and enhance survival.

Computed Tomography Angiography for Aortic Diseases.

Aortic pathologies encompass a heterogeneous group of disorders, including acute aortic syndrome, traumatic aortic injury , aneurysm, aortitis, and atherosclerosis. The clinical manifestations of these disorders can be varied and non-specific, ranging from acute presentations in the emergency department to chronic incidental findings in an outpatient setting. Given the non-specific nature of their clinical presentations, the reliance on non-invasive imaging for screening, definitive diagnosis, therapeutic strategy planning, and post-intervention surveillance has become paramount. Commonly used imaging modalities include ultrasound, computed tomography (CT), and MR imaging. Among these modalities, computed tomography angiography (CTA) has emerged as a first-line imaging modality owing to its excellent anatomic detail, widespread availability, established imaging protocols, evidence-proven indications, and rapid acquisition time.

NF-κB/NLRP3 Translational Inhibition by Nanoligomer Therapy Mitigates Ethanol and Advanced Age-Related Neuroinflammation.

Binge alcohol use is increasing among aged adults (>65 years). Alcohol-related toxicity in aged adults is associated with neurodegeneration, yet the molecular underpinnings of age-related sensitivity to alcohol are not well described. Studies utilizing rodent models of neurodegenerative disease reveal heightened activation of Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and Nod like receptor 3 (NLRP3) mediate microglia activation and associated neuronal injury. Our group, and others, have implicated hippocampal-resident microglia as key producers of inflammatory mediators, yet the link between inflammation and neurodegeneration has not been established in models of binge ethanol exposure and advanced age. Here, we report binge ethanol increased the proportion of NLRP3+ microglia in the hippocampus of aged (18-20 months) female C57BL/6N mice compared to young (3-4 months). In primary microglia, ethanol-induced expression of reactivity markers and NLRP3 inflammasome activation were more pronounced in microglia from aged mice compared to young. Making use of an NLRP3-specific inhibitor (OLT1177) and a novel brain-penetrant Nanoligomer that inhibits NF-κB and NLRP3 translation (SB_NI_112), we find ethanol-induced microglial reactivity can be attenuated by OLT1177 and SB_NI_112 in microglia from aged mice. In a model of intermittent binge ethanol exposure, SB_NI_112 prevented ethanol-mediated microglia reactivity, IL-1ß production, and tau hyperphosphorylation in the hippocampus of aged mice. These data suggest early indicators of neurodegeneration occurring with advanced age and binge ethanol exposure are NF-κB- and NLRP3-dependent. Further investigation is warranted to explore the use of targeted immunosuppression via Nanoligomers to attenuate neuroinflammation after alcohol consumption in the aged.

Vessel and Airway Characteristics in One-Year CT-defined Rapid Emphysema Progression: SPIROMICS.

Rationale: Rates of emphysema progression vary in chronic obstructive pulmonary disease (COPD), and the relationship with vascular and airway pathophysiology remain unclear. Objective: We sought to determine if indices of peripheral (segmental and beyond) pulmonary arterial (PA) dilation measured via computed tomography (CT) are associated with a 1-year index of emphysema (EI: %voxels<-950HU) progression. Methods: 599 GOLD 0-3 former and never-smokers were evaluated from the SubPopulations and InterMediate Outcome Measures in COPD Study (SPIROMICS) cohort: rapid-emphysema-progressors (RP, n=188; 1-year ΔEI>1%), non-progressors (NP, n=301; 1-year ΔEI±0.5%) and never-smokers (NS: N=110). Segmental PA cross-sectional areas were standardized to associated airway luminal areas (Segmental : Pulmonary Artery-to-Airway Ratio: PAARseg). Full inspiratory CT scan-derived total (arteries + veins) pulmonary vascular volume (TPVV) was compared to vessel volume with radius smaller than 0.75mm (SVV.75/TPVV). Airway-to-lung ratios (an index of dysanapsis and COPD risk) were compared to TPVV-lung-volume-ratios. Results: Compared with NP, RP exhibited significantly larger PAARseg (0.73±0.29 vs. 0.67±0.23; p=0.001), lower TPVV-to-lung-volume ratio (3.21%±0.42% vs. 3.48%±0.38%; p=5.0 x 10-12), lower airway-to-lung-volume ratio (0.031±0.003 vs. 0.034±0.004; p=6.1 x 10-13) and larger SVV.75/TPVV (37.91%±4.26% vs. 35.53±4.89; p=1.9 x 10-7). In adjusted analyses, a 1-SD increment in PAARseg was associated with a 98.4% higher rate of severe exacerbations (95%CI: 29 to 206%; p = 0.002) and 79.3% higher in odds of being in the rapid emphysema progression group (95%CI: 24% to 157%; p = 0.001). At year-2 followup, the CT-defined RP group demonstrated a significant decline in post-bronchodilator-FEV1% predicted. Conclusion: Rapid one-year progression of emphysema was associated with indices indicative of higher peripheral pulmonary vascular resistance and a possible role played by pulmonary vascular-airway dysanapsis.

Nanoligomers targeting NF-κB and NLRP3 reduce neuroinflammation and improve cognitive function with aging and tauopathy.

Neuroinflammation contributes to impaired cognitive function in brain aging and neurodegenerative disorders like Alzheimer's disease, which is characterized by the aggregation of pathological tau. One major driver of both age- and tau-associated neuroinflammation is the NF-κB and NLRP3 signaling axis. However, current treatments targeting NF-κB or NLRP3 may have adverse/systemic effects, and most have not been clinically translatable. Here, we tested the efficacy of a novel, nucleic acid therapeutic (Nanoligomer) cocktail specifically targeting both NF-κB and NLRP3 in the brain for reducing neuroinflammation and improving cognitive function in old wildtype mice, and in a mouse model of tauopathy. We found that 4 weeks of NF-κB/NLRP3-targeting Nanoligomer treatment strongly reduced neuro-inflammatory cytokine profiles in the brain and improved cognitive-behavioral function in both old and tauopathy mice. These effects of NF-κB/NLRP3-targeting Nanoligomer treatment were associated with reduced glial cell activation in old wildtype mice, less pathology in tauopathy mice, favorable changes in transcriptome signatures of inflammation (reduced) and neuronal health (increased) in both mouse models, and positive systemic effects. Collectively, our results provide a basis for future translational studies targeting NF-κB/NLRP3 in the brain, perhaps using Nanoligomers, to inhibit neuroinflammation and improve cognitive function with aging and neurodegenerative disease.

Utilizing Artificial Intelligence-Based Deformable Registration for Global and Layer-Specific Cardiac MRI Strain Analysis in Healthy Children and Young Adults.

RATIONALE AND OBJECTIVES: The absence of published reference values for multilayer-specific strain measurement using cardiac magnetic resonance (CMR) in young healthy individuals limits its use. This study aimed to establish normal global and layer-specific strain values in healthy children and young adults using a deformable registration algorithm (DRA). MATERIALS AND METHODS: A retrospective study included 131 healthy children and young adults (62 males and 69 females) with a mean age of 16.6 ± 3.9 years. CMR examinations were conducted using 1.5T scanners, and strain analysis was performed using TrufiStrain research prototype software (Siemens Healthineers, Erlangen, Germany). Global and layer-specific strain parameters were extracted from balanced Steady-state free precession cine images. Statistical analyses were conducted to evaluate the impact of demographic variables on strain measurements. RESULTS: The peak global longitudinal strain (LS) was -16.0 ± 3.0%, peak global radial strain (RS) was 29.9 ± 6.3%, and peak global circumferential strain (CS) was -17.0 ± 1.8%. Global LS differed significantly between males and females. Transmural strain analysis showed a consistent pattern of decreasing LS and CS from endocardium to epicardium, while radial strain increased. Basal-to-apical strain distribution exhibited decreasing LS and increasing CS in both global and layer-specific analysis. CONCLUSION: This study uses DRA to provide reference values for global and layer-specific strain in healthy children and young adults. The study highlights the impact of sex and age on LS and body mass index on RS. These insights are vital for future cardiac assessments in children, particularly for early detection of heart diseases.

Optimizing Deep Learning for Cardiac MRI Segmentation: The Impact of Automated Slice Range Classification.

RATIONALE AND OBJECTIVES: Cardiac magnetic resonance imaging is crucial for diagnosing cardiovascular diseases, but lengthy postprocessing and manual segmentation can lead to observer bias. Deep learning (DL) has been proposed for automated cardiac segmentation; however, its effectiveness is limited by the slice range selection from base to apex. MATERIALS AND METHODS: In this study, we integrated an automated slice range classification step to identify basal to apical short-axis slices before DL-based segmentation. We employed publicly available Multi-Disease, Multi-View & Multi-Center Right Ventricular Segmentation in Cardiac MRI data set with short-axis cine data from 160 training, 40 validation, and 160 testing cases. Three classification and seven segmentation DL models were studied. The top-performing segmentation model was assessed with and without the classification model. Model validation to compare automated and manual segmentation was performed using Dice score and Hausdorff distance and clinical indices (correlation score and Bland-Altman plots). RESULTS: The combined classification (CBAM-integrated 2D-CNN) and segmentation model (2D-UNet with dilated convolution block) demonstrated superior performance, achieving Dice scores of 0.952 for left ventricle (LV), 0.933 for right ventricle (RV), and 0.875 for myocardium, compared to the stand-alone segmentation model (0.949 for LV, 0.925 for RV, and 0.867 for myocardium). Combined classification and segmentation model showed high correlation (0.92-0.99) with manual segmentation for biventricular volumes, ejection fraction, and myocardial mass. The mean absolute difference (2.8-8.3 mL) for clinical parameters between automated and manual segmentation was within the interobserver variability range, indicating comparable performance to manual annotation. CONCLUSION: Integrating an initial automated slice range classification step into the segmentation process improves the performance of DL-based cardiac chamber segmentation.

Light-Driven Metabolic Pathways in Non-Photosynthetic Biohybrid Bacteria.

Biomanufacturing via microorganisms relies on carbon substrates for molecular feedstocks and a source of energy to carry out enzymatic reactions. This creates metabolic bottlenecks and lowers the efficiency for substrate conversion. Nanoparticle biohybridization with proteins and whole cell surfaces can bypass the need for redox cofactor regeneration for improved secondary metabolite production in a non-specific manner. Here we propose using nanobiohybrid organisms (Nanorgs), intracellular protein-nanoparticle hybrids formed through the spontaneous coupling of core-shell quantum dots (QDs) with histidine-tagged enzymes in non-photosynthetic bacteria, for light-mediated control of bacterial metabolism. This proved to eliminate metabolic constrictions and replace glucose with light as the source of energy in Escherichia coli, with an increase in growth by 1.7-fold in 75 % reduced nutrient media. Metabolomic tracking through carbon isotope labeling confirmed flux shunting through targeted pathways, with accumulation of metabolites downstream of respective targets. Finally, application of Nanorgs with the Ehrlich pathway improved isobutanol titers/yield by 3.9-fold in 75 % less sugar from E. coli strains with no genetic alterations. These results demonstrate the promise of Nanorgs for metabolic engineering and low-cost biomanufacturing.

"From Vision to Reality: Virtual Reality's Impact on Baffle Planning in Congenital Heart Disease".

This study aims to evaluate the feasibility and utility of virtual reality (VR) for baffle planning in congenital heart disease (CHD), specifically by creating patient-specific 3D heart models and assessing a user-friendly VR interface. Patient-specific 3D heart models were created using high-resolution imaging data and a VR interface was developed for baffle planning. The process of model creation and the VR interface were assessed for their feasibility, usability, and clinical relevance. Collaborative and interactive planning within the VR space were also explored. The study findings demonstrate the feasibility and usefulness of VR in baffle planning for CHD. Patient-specific 3D heart models generated from imaging data provided valuable insights into complex spatial relationships. The developed VR interface allowed clinicians to interact with the models, simulate different baffle configurations, and assess their impact on blood flow. The VR space's collaborative and interactive planning enhanced the baffle planning process. This study highlights the potential of VR as a valuable tool in baffle planning for CHD. The findings demonstrate the feasibility of using patient-specific 3D heart models and a user-friendly VR interface to enhance surgical planning and patient outcomes. Further research and development in this field are warranted to harness the full benefits of VR technology in CHD surgical management.

Utilizing Atmospheric Carbon Dioxide and Sunlight in Graphene Quantum Dot-Based Nano-Biohybrid Organisms for Making Carbon-Negative and Carbon-Neutral Products.

Increasing emissions of greenhouse gases compounded with legacy emissions in the earth's atmosphere poses an existential threat to human survival. One potential solution is creating carbon-negative and carbon-neutral materials, specifically for commodities used heavily throughout the globe, using a low-cost, scalable, and technologically and economically feasible process that can be deployed without the need for extensive infrastructure or skill requirements. Here, we demonstrate that nickel-functionalized graphene quantum dots (GQDs) can effectively couple to nonphotosynthetic bacteria at a cellular, molecular, and optoelectronic level, creating nanobiohybrid organisms (nanorgs) that enable the utilization of sunlight to convert carbon dioxide, air, and water into high-value-added chemicals such as ammonia (NH3), ethylene (C2H4), isopropanol (IPA), 2,3-butanediol (BDO), C11-C15 methyl ketones (MKs), and degradable bioplastics poly hydroxybutyrate (PHB) with high efficiency and selectivity. We demonstrate a high turnover number (TON) of up to 108 (mol of product per mol of cells), ease of application, facile scalability (demonstrated using a 30 L tank in a lab), and sustainable generation of carbon nanomaterials from recovered bacteria for creating nanorgs without the use of any toxic chemicals or materials. These findings can have important implications for the further development of sustainable processes for making carbon-negative materials using nanorgs.

Incidental Coronary Artery Calcium on Chest CT in Persons Without Known Atherosclerotic Cardiovascular Disease.

This cross-sectional study examines the expected prevalence of coronary artery calcium (CAC) on chest computed tomography (CT) in people without clinical atherosclerotic cardiovascular disease (ASCVD) by age, sex, and race and ethnicity.

ComBat Harmonization of Myocardial Radiomic Features Sensitive to Cardiac MRI Acquisition Parameters.

Purpose: To investigate the effect of ComBat harmonization methods on the robustness of cardiac MRI-derived radiomic features to variations in imaging parameters. Materials and Methods: This Health Insurance Portability and Accountability Act-compliant retrospective study used a publicly available data set of 11 healthy controls (mean age, 33 years ± 16 [SD]; six men) and five patients (mean age, 52 years ± 16; four men). A single midventricular short-axis section was acquired with 3-T MRI using cine balanced steady-state free precision, T1-weighted, T2-weighted, T1 mapping, and T2 mapping imaging sequences. Each sequence was acquired using baseline parameters and after variations in flip angle, spatial resolution, section thickness, and parallel imaging. Image registration was performed for all sequences at a per-individual level. Manual myocardial contouring was performed, and 1652 radiomic features per sequence were extracted using baseline and variations in imaging parameters. Radiomic feature stability to change in imaging parameters was assessed using Cohen d sensitivity. The stability of radiomic features was assessed both without and after ComBat harmonization of radiomic features. Three ComBat methods were studied: parametric, nonparametric, and Gaussian mixture model (GMM). Results: For all sequences combined, 51.4% of features were robust to changes in imaging parameters when no ComBat method was applied. ComBat harmonization substantially increased the number of stable features to 95.1% (95% CI: 94.9, 95.3) when parametric ComBat was used and 90.9% (95% CI: 90.6, 91.2) when nonparametric ComBat was used. GMM combat resulted in only 52.6% stable features. Conclusion: ComBat harmonization improved the stability of radiomic features to changes in imaging parameters across all cardiac MRI sequences.Keywords: Cardiac MRI, Radiomics, ComBat, Harmonization Supplemental material is available for this article. © RSNA, 2023.

MR Angiography for Aortic Diseases.

Aortic pathologic conditions represent diverse disorders, including aortic aneurysm, acute aortic syndrome, traumatic aortic injury, and atherosclerosis. Given the nonspecific clinical features, noninvasive imaging is critical in screening, diagnosis, management, and posttherapeutic surveillance. Of the commonly used imaging modalities, including ultrasound, computed tomography, and MR imaging, the final choice often depends on a combination of factors: acuity of clinical presentation, suspected underlying diagnosis, and institutional practice. Further research is needed to identify the potential clinical role and define appropriate use criteria for advanced MR applications such as four-dimenional flow to manage patients with aortic pathologic conditions.

MR Angiography: Contrast-Enhanced Acquisition Techniques.

Contrast-enhanced MR angiography (CE-MRA) is a frequently used MR imaging technique for evaluating cardiovascular structures. In many ways, it is similar to contrast-enhanced computed tomography (CT) angiography, except a gadolinium-based contrast agent (instead of iodinated contrast) is injected. Although the physiological principles of contrast injection overlap, the technical factors behind enhancement and image acquisition are different. CE-MRA provides an excellent alternative to CT for vascular evaluation and follow-up without requiring nephrotoxic contrast and ionizing radiation. This review describes the physical principles, limitations, and technical applications of CE-MRA techniques.