Citations

Abstract Background Photon counting detector CT (PCD‐CT) has the potential to sort detected x‐ray photons into more than two energy bins to perform multi‐material decomposition using K‐edge materials without additional mathematical constraints/assumptions. The availability of multiple energy thresholds in PCD‐CT opens the possibility for unique clinical applications such as simultaneous multi‐contrast‐agent imaging. Purpose To evaluate the technical performance of a PCD‐CT system with four energy thresholds for conducting multi‐material decomposition of iodine, gadolinium, and water after a comprehensive system calibration procedure. Methods Experiments were performed on a commercial PCD‐CT scanner (NAEOTOM Alpha, Siemens Healthineers) using a research mode with four energy thresholds. Material calibration was performed by scanning contrast materials with known concentration placed in various sizes of cylindrical water‐equivalent phantoms at various tube currents and positions. From these data, per‐voxel contrast models were derived for each material by multiple linear regressions up to second order, where the predictor variables were combinations of tube current, phantom diameter, and distance to isocenter. After calibration, small (20 cm diameter) and large (30 cm × 40 cm) uniform multi‐energy CT phantoms and an anthropomorphic thorax phantom (31 cm × 39 cm), each containing bone, soft tissue, and several quantitative inserts of iodine (0.2–5.0 mg/ml), gadolinium (0.3–5.0 mg/ml), and a mixture of both (5.0 mg/ml each) were scanned using the four‐energy threshold mode at 140 kV with energy thresholds set at 20, 52, 75, and 82 keV. Images for each energy threshold were reconstructed with a filtered back‐projection algorithm and a quantitative kernel (Qr44). Subsequent image‐based material decomposition was performed on individual voxels of the energy threshold images using the models derived from the calibration process to generate water, iodine, and gadolinium basis images. Quantitative material concentrations and image noise magnitudes, and noise power spectra (NPS) were measured. Results Iodine and gadolinium concentrations above 1.25 mg/ml were visible in the material basis images in all phantoms. Averaged quantitative accuracy for iodine and gadolinium in the small, large, and thorax phantoms were 0.39 ± 0.30 mg/ml, 0.96 ± 0.53 mg/ml, and 0.53 ± 0.35 mg/ml, respectively. In the water basis images, accuracy was within 24 HU in all phantoms. Noise magnitudes in iodine and gadolinium basis images were 2.91 and 3.52 times that of the lowest energy threshold image for the small phantom, and were 6.92 and 7.17 times that of the lowest threshold image for the large phantom. Noise texture did not change between the energy threshold and material basis images for either size phantom as measured by the NPS. Conclusions After a comprehensive system calibration, a commercial PCD‐CT with four energy thresholds performed multiple material decomposition of iodine, gadolinium, and water for concentrations above 1.25 mg/ml in human‐sized phantoms. Noise amplification and quantitative accuracy from the decomposition greatly depended on object size.

Abstract Chimeric antigen receptor (CAR) T-cell (CAR-T) treatment for B-cell acute lymphoblastic leukemia (ALL) induces high initial response rates, but most patients relapse. Low disease burden (often defined as <5% blasts in the bone marrow) is associated with better outcomes. CAR HEMATOTOX (HT) is a score using prelymphodepletion hematologic and inflammatory parameters to predict outcomes in lymphoma. Here, we assess its prognostic utility in a large multicenter adult B-cell ALL cohort. Patients who received brexucabtagene autoleucel across 33 centers in North America were included as part of the Real-World Outcomes Collaborative of CAR-T in Adult ALL (ROCCA) consortium. An independent cohort of 61 patients with ALL treated with an investigational CD19 CAR-T therapy at 1 center was also described. Among 199 ROCCA consortium patients, 43 (22%) patients with HTlow scores had lower rates of delayed neutrophil recovery than those with HThigh scores (26% vs 52%, P = .002) and fewer severe infections (2.5% vs 18.8%, P = .011). They also had higher response rates, overall survival (OS), and event-free survival (EFS), as well as lower nonrelapse mortality and cumulative incidence of relapse. The survival differences remained significant after multivariable adjustment for disease burden and other covariates. In the investigational cohort of 61 patients, patients with HTlow scores had improved OS and EFS, as well as higher peak CAR-T expansion. In summary, CAR HT score is a prognostic factor independent of disease burden in adult ALL. HTlow score is associated with superior outcomes after CD19 CAR-Ts and higher CAR-T expansion in a single-center cohort. These trials were registered at www.clinicaltrials.gov as #NCT01044069 and #NCT01860937.

Introduction: Percutaneous nephrolithotomy (PCNL) has been a mainstay treatment for large stone burdens since the 1980s, historically offering improved stone-free rates over retrograde intrarenal surgery (RIRS). Gaining optimal access into the renal collecting system can be challenging, requiring advanced skills or interventional radiology assistance. The learning curve for fluoroscopic and ultrasonography access can be steep, with only a minority of PCNL access performed by urologists in the United States. This study compares robotic-assisted electromagnetic (EM) guidance to traditional fluoroscopy for obtaining percutaneous renal access between cohorts of novice and expert urologists. Methods: Ten novices and five expert urologists used robotic-assisted EM guidance to obtain access in a modified supine position compared with using fluoroscopy in a traditional prone position in human cadavers. Primary success was defined as papillary access. Performance metrics, including number of puncture attempts, time to access, radiation exposure, and participant confidence, were compared between novices and experts. Results: Robotic-assisted EM guidance improved success rates for both novices (100% vs 70%) and experts (93% vs 87%) compared with fluoroscopy. Novices showed greater accuracy using robotic assistance (97% vs 37%). The number of insertion attempts decreased with robotic guidance for both groups (novices: 3.42 ± 0.44 vs 1.47 ± 0.19; experts: 2.13 ± 0.36 vs 1.40 ± 0.24; p < 0.002). EM guidance ( p < 0.05) and experience ( p < 0.05) significantly reduced the time from needle insertion to access (novices: 12.86 ± 2.41 minutes vs 4.49 ± 0.96 minutes; experts: 4.90 ± 1.40 minutes vs 4.09 ± 1.12 minutes). Radiation exposure was notably lower with EM guidance (novices, 1.12 ± 0.17 mGy vs 4.86 ± 0.70 mGy; experts, 0.69 ± 0.12 mGy vs 4.11 ± 1.21 mGy; p < 0.001). Novices felt more confident (5[3–5] vs 2[1–4], p < 0.001) and at ease (5[3–5] vs 2.75[1–3], p < 0.001) with EM guidance. Conclusion: Robotic-assisted EM guidance improves percutaneous access success, reduces attempts and radiation exposure, and enhances novice confidence and accuracy. This technology could enable urologists to more effectively and safely perform PCNL, especially for less experienced practitioners.

Purpose: Surgical video review can be used in urologic training, yet significant barriers to the implementation of video review programs exist, and formal assessment of usage and utility for trainees is limited. Here, we evaluate a novel video review platform to describe patterns of use and determine perceived utility. Materials and Methods: We analyzed learning points entered by trainees during video review of radical prostatectomy cases using our surgical intelligence–enabled Film Room platform between September 2023 and July 2024. Learning point content was categorized according to surgical coaching domains as technical, cognitive, nontechnical, or descriptive. Entries were compared by surgical step and level of training. Anonymous surveys were distributed to trainees to determine perceived utility and reveal patterns of video review. Results: Thirteen trainees entered 480 unique learning points across all radical prostatectomy steps and spanning surgical coaching domains during the study period. Learning points varied by training level, with junior trainees entering points more often than senior trainees for Retzius-space dissection ( N = 73 vs 17, p < 0.01) and seminal vesicle and posterior dissection ( N = 58 vs 27, p < 0.01). Trainees used video review in preparation for both upcoming cases and performance analysis. Ninety-four percent of survey respondents reported they either agreed or strongly agreed that video review helped them develop surgical skills. Conclusions: We found usage across training levels and high perceived utility of our Film Room platform for video review of robotic prostatectomy. Implementation of video review platforms holds promise to augment existing urologic training and should be explored further.

Abstract Smith-Lemli-Opitz syndrome (SLOS) is a rare, autosomal recessive disorder characterized by congenital malformations, intellectual disability, and behavioral abnormalities. SLOS results from mutations in the DHCR7 gene, leading to impaired cholesterol biosynthesis due to dysregulation of 7-dehydrocholesterol reductase. Cholesterol plays crucial roles in neurophysiology, including synaptic formation and neurotransmitter receptor regulation, which likely contribute to neurological manifestations in SLOS patients. While astrocytes are the main cholesterol producing cells in the brain, their specific role in SLOS pathogenesis remains unclear. In this study, we utilized induced pluripotent stem cell (iPSC)-derived astrocytes from a SLOS patient with DHCR7 c.C278T mutation and the isogenic control. We found decreased lipid droplet formation in SLOS iPSC astrocytes compared to controls, accompanied with diminished efflux of cholesterol and apolipoprotein E. Lipidomics revealed reduced cholesterol and cholesterol esters, as well as altered profiles of other lipids in SLOS iPSC astrocytes. While RNA-sequencing identified various genes and pathways affected by the disease status, those related to mitochondria functions were top-ranked. Mitochondrial electron transport chain oxidative phosphorylation gene expression decreased in SLOS iPSC astrocytes, alongside impaired mitochondrial respiration. Furthermore, SLOS iPSC astrocytes less effectively mediated neuroprotection on iPSC neurons than control astrocytes in serum-starvation conditions. SLOS iPSC astrocytes also poorly contributed to synaptic networks when co-cultured with iPSC neurons. Overall, our findings provide mechanistic insights into how DHCR7 disruption impacts astrocyte function, contributing to SLOS neuropathology by dysregulating lipid metabolism, mitochondrial respiration, and impaired neuroprotection.

Background. The spirometric response to standard-of-care (SOC) immunosuppressive therapy for the management of bronchiolitis obliterans syndrome (BOS) has been sparsely reported in the literature. Data from a Medicare-approved Registry were analyzed to characterize the effectiveness/durability of a wide range of SOC interventions to manage the decline of lung function and to validate the study spirometric criteria for initiation of rescue therapy. Methods. Lung transplant recipients with refractory BOS at 21 US collaborating centers were enrolled in the Registry. Data included both nonspirometric (eg, demographic, Immunosuppressive Regimens for management of BOS) and spirometric parameters (ie, forced expiratory volume in 1 s [FEV 1 ] measurements and derived indices). The utility of study FEV 1 criteria for treatment (ie, statistically significant rate of FEV 1 decline >30 mL/mo) was evaluated by comparing the spirometric course between participants who met or did not meet this criterion. Results. Only 21% of participants treated with SOC therapy had >50% decrease (76 ± 25% decrease) in the rate of FEV 1 decline. Although 51% of participants had a partial response (rate of FEV 1 decline decreased on average 71%), 49% of participants had a substantial increase (mean increase 224%). The FEV 1 criterion for treatment was able to identify 19% of participants (48/258) who achieved durable stabilization (ie, nonsignificant rate of FEV 1 <30 mL/mo) with SOC therapy. Conclusions. Patients with BOS have a widely variable response to SOC therapy. Our findings support the use of FEV 1 rate of decline to assess response to SOC therapy and to ensure appropriate assignment of participants with refractory BOS to rescue therapy treatment cohorts.

Abstract Medical imaging is undergoing a transformation driven by the advent of new, highly effective, machine learning techniques paired with increases in computational capabilities (Cheng et al. 2021; Gilson et al. 2023; Almeida et al. 2024; Krishna et al. 2024). These advanced algorithms have the potential to improve disease detection, diagnosis, prognosis, and treatment outcomes. However, the complexity of machine learning models, the large amounts of curated and annotated data required by some methods, and the potential for bias and error make it challenging for individuals to safely and effectively leverage these methods (Lin et al. 2024; Guo et al. 2024; Xu et al. 2024; Linguraru et al. 2024; Wood et al. 2019). To address these challenges, the American Association of Physicists in Medicine (AAPM), American College of Radiology (ACR), Radiological Society of North America (RSNA), and Society for Imaging Informatics in Medicine (SIIM) have worked together to develop a syllabus detailing a recommended set of competencies for medical imaging professionals interacting with these systems. This guide is aimed at four different personas: users of AI systems, purchasers of AI systems, individuals who provide clinical expertise during the development of AI systems (“clinical collaborators”), and developers of AI systems.1 This is a syllabus, not a curriculum, and is intentional in this scope. Recognizing that individuals may benefit from different presentations of the same material, this work enumerates a series of relevant competencies but does not prescribe, nor offer, a method of instruction (Schuur, Rezazade Mehrizi, and Ranschaert 2021; Garin et al. 2023). By addressing the task‐specific demands of each role, this guide will enable medical imaging professionals to utilize machine learning systems more safely and effectively, ultimately improving patient care and outcomes.

Ischemic cardiomyopathy (ICM) is a leading cause of heart failure characterized by extensive remodeling of the cardiac extracellular matrix (ECM). While initially adaptive, ECM deposition following ischemic injury eventually turns maladaptive, promoting adverse cardiac remodeling. The strong link between the extent of fibrosis and adverse clinical outcomes has led to growing interest in ECM-targeted therapies to prevent or reverse maladaptive cardiac remodeling in ICM; yet, the precise composition of the ECM in ICM remains poorly defined. In this study, we employed sequential protein extraction enabled by the photocleavable surfactant Azo to enrich ECM proteins from left ventricular tissues of patients with end-stage ICM and nonfailing donor hearts. High-resolution mass spectrometry–based quantitative proteomics identified and quantified over 6,000 unique protein groups, including 315 ECM proteins. We discovered significant upregulation of key ECM components, particularly glycoproteins, proteoglycans, collagens, and ECM regulators. Notably, LOXL1 , FBLN1 , and VCAN were among the most differentially expressed. Functional enrichment analyses revealed enhanced TGFB signaling, integrin-mediated adhesion, and complement activation in ICM tissues, suggesting a feedback loop driving continued ECM deposition in the end-stage failing heart. Together, our findings provide a comprehensive proteomic landscape of ECM alterations in the end-stage ICM myocardium and identify promising molecular targets for therapeutic intervention.