Department of Radiology

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https://hdl.handle.net/1813/116690

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Random Forest-Based Detection of Metastases in Clinically Scanned Lymph Nodes Using Quantitative Ultrasound Imaging
Ghahramani, E.; Hoerig, C.; Wallace, K.; Wu, M.; Mamou, J. (Elsevier, 2025-06-19)
OBJECTIVE: Quantitative ultrasound (QUS) imaging has been used to characterize the microstructural properties of tissue using information contained in the backscattered radiofrequency (RF) echo signals. QUS methods were previously applied to detect metastases in excised human lymph nodes (LNs) that were raster scanned using a 30 MHz single-element transducer ex vivo. In the current study, a QUS-based method to detect in vivo LN metastases using a clinical scanner was developed. METHODS: Parallel RF frames were captured from 46 cervical and axillary LNs in 45 patients and two backscatter coefficient-based and two envelope statistics-based QUS parameters were computed and averaged for each frame. Different combinations of these four QUS parameters, along with the LN's short-axis and short-to-long axis ratio, were used to train random forest models to classify metastatic LNs. RESULTS: The average QUS parameters and radiomics features were significantly different between metastatic and benign LNs (p‚â§10^-4), except for effective scatterer diameter (p = 0.70). The best-performing random forest model, trained using a combination of QUS and radiomics features, identified metastatic LNs with an area under the receiver-operating characteristic curve of 0.91 and 67% specificity at 100% sensitivity. CONCLUSION: These results demonstrate the potential of QUS imaging using a clinical scanner for identifying metastatic LNs in vivo to help clinicians perform a more selective LN biopsy or excision.
Cancer Prognostic Awareness: Relations to Patient and Caregiver Quality of Life and Care Preferences
Krueger, E.; Mosher, C.E.; Lewson, A.; Hickman, S.E.; Wu, W.; Prigerson, H.G. (Elsevier, 2025-06-10)
CONTEXT: Patients who are prognostically aware are more likely to receive end-of-life care consistent with their values. However, prognostic awareness has shown mixed associations with patients' quality-of-life (QoL) outcomes. Theory suggests that acceptance of cancer may moderate relationships between prognostic awareness and outcomes of QoL and end-of-life treatment preferences. Patients' degree of prognostic awareness and illness acceptance may also impact their family caregivers' QoL and end-of-life treatment preferences for the patient. OBJECTIVES: To examine the potential moderating role of patient acceptance of cancer in the relationships between patient prognostic awareness and both patient and caregiver QoL and end-of-life treatment preferences. METHODS: A cross-sectional, secondary analysis was conducted using data from patients with advanced cancer (n=243) and their caregivers (n=87) in the multi-institutional Coping with Cancer-II cohort study. Patient physical, psychological, and existential QoL were examined in a moderation path analysis. Caregiver physical and psychological QoL were examined in separate linear regression analyses. Patient and caregiver end-of-life treatment preferences were examined in multiple logistic regression moderation models. RESULTS: No significant moderations were found. Greater patient illness acceptance was associated with better patient QoL outcomes and caregiver psychological QoL but was unrelated to end-of-life treatment preferences. Greater patient prognostic awareness was associated with worse patient physical QoL and both patients' and caregivers' preference for comfort care. CONCLUSION: Increasing patients' prognostic awareness and cancer acceptance may improve values-consistent end-of-life care and patient and caregiver QoL outcomes. Findings support timely conversations to promote prognostic awareness and further testing of acceptance-based interventions in advanced cancer.
Computational Design of a Bicyclic Peptide Inhibitor Targeting the ICOS/ICOS-L Protein-Protein Interaction.
Calvo-Barreiro, L.; Secor, M.; Damjanovic, J.; Abdel-Rahman, S.A.; Lin, Y.-S.; Gabr, M. (Wiley, 2025-05-01)
The interaction between the inducible T-cell costimulatory molecule (ICOS) and its ligand (ICOS-L) is a critical pathway in T-cell activation and immune regulation. We computationally designed a bicyclic peptide (CP5) that inhibits the ICOS/ICOS-L protein-protein interaction (PPI). Using the structural insights derived from the ICOS/ICOS-L co-crystal structure (PDB: 6X4G) and bias-exchange metadynamics simulations (BE-META), we first designed monocyclic peptide candidates containing the Œ≤-strand (residues 51-55 ⁵¹YVYWQ⁵⁵) of ICOS-L that interact with ICOS. Using Rosetta's flex ddG calculations and further disulfide-bond restraint, we arrived at CP5 (cyclo-RVY[CQPGWC]WVLpG) as a potential ICOS/ICOS-L inhibitor. Using dynamic light scattering (DLS), we examined the interaction between CP5 and ICOS. Importantly, we validated the ICOS/ICOS-L inhibitory activity of CP5 using both TR-FRET assay and ELISA. Notably, CP5 demonstrated satisfactory in vitro pharmacokinetic properties, such as metabolic stability and lipophilicity, positioning it as a promising candidate for further drug development. Our findings provide a foundation for future drug discovery efforts aiming to develop cyclic peptides that specifically target the ICOS/ICOS-L interaction.
Racial health disparities in severe maternal morbidity before and after implementation of an enhanced recovery after cesarean delivery protocol: a retrospective observational study at two New York City hospitals (2016-2020).
Gilman, A.T.; Kim, J.; Jiang, S.Y.; Abramovitz, S.E.; White, R.S. (Elsevier, 2025-03-27)
BACKGROUND: Enhanced recovery after cesarean delivery (ERAC) is an evidence-based pathway that aims to improve the quality of care for all patients. Standardization of care has been seen as a tool to promote equality and equity. Our goal was to evaluate racial differences in severe maternal morbidity (SMM) among patients before and after implementation of an ERAC program. METHODS: A retrospective study was performed among cesarean delivery patients pre- and post-ERAC implementation at two large academic hospitals in New York City from October 2016 to September 2020. Logistic regression models were created to compare peripartum SMM complications pre-ERAC, post-ERAC, and overall, by race. RESULTS: The sample consisted of 7,812 cesarean delivery patients, of which 4,640 were pre-ERAC (59.4%) and 3172 were post-ERAC (40.6%). Within the overall population, Black (aOR 1.57, 95% CI 1.07 to 2.28; P=0.018) and Asian (aOR 1.61, 95% CI 1.20 to 2.14; P=0.001) patients had higher odds of SMM compared to white patients. Pre-ERAC, Black (aOR 1.92, 95% CI 1.16 to 3.14; P=0.010) and Asian patients (aOR 1.86, 95% CI 1.26 to 2.74; P=0.002) had higher odds of SMM relative to white patients. Post-ERAC, this relationship was no longer statistically significant [Black (aOR 1.13, 95% CI 0.61 to 2.01; P=0.69) and Asian (aOR 1.39, 95% CI 0.88 to 2.17; P=0.15)]. CONCLUSION: Implementation of the ERAC protocol improved SMM outcomes by race. Standardization of practices in ERAC protocols can help address disparities by reducing variations in obstetrical care.
SSTR2 expression in neoplastic and normal anterior pituitary is impacted by age, sex, and hormonal status.
Liechty, B.; Kim, S.; Dobri, G.; Schwartz, T.H.; Ivanidze, J.; Pisapia, D. (Oxford University Press, 7/1/25)
Pituitary neuroendocrine tumors (PitNETs) are among the most common tumors encountered in neurooncology. While the majority of PitNETs demonstrate indolent behavior, a subset of tumors demonstrates aggressive behavior, including invasion into surrounding structures. As traditional imaging has limited capacity to distinguish tumor from post-operative changes, better methods of tumor delineation are needed to guide management. Somatotroph adenomas are known to express high levels of SSTR2, and SSTR2-targeting PET imaging has shown clinical utility in the management of neuroendocrine tumors and meningiomas. In this retrospective study of archival PitNETs (n = 271) and autopsy controls (AC) (n = 20), we show that although significant differences in SSTR2 immunostaining are appreciable between adenoma subtypes and ACs, high-staining cases are encountered in all subtypes. In ACs, females demonstrated significantly stronger SSTR2 staining than males. Weak age-related trends towards increasing labelling in females and decreasing labelling in males were noted but these did not reach statistical significance. Decreasing age-related trends were seen in gonadotrophs in both sexes; this was statistically significant in females. Our findings suggest that SSTR2-targeting imaging modalities may assist clinical management of a subset of PitNETs and that these results may need to be interpreted with consideration of patient age and sex.
Brazilian Validation of the Prolonged Grief Disorder Scale - Revised (PG-13-R)
Esperandio, M.R.G.; Rosas, L.S.; Viacava, J.; Prigerson, H.G. (SAGE Publications, 5/31/25)
Studies indicate that Prolonged Grief Disorder (PGD) affects approximately 10% of bereaved individuals. Although this represents a minority, accurate identification through reliable instruments enables effective interventions. This study evaluated the psychometric properties of the PGD Scale Revised (PG-13-R), a 13-item self-administered measure, in the Brazilian context with 516 participants. The validation process included Exploratory Factor Analysis (EFA; n = 251) and Confirmatory Factor Analysis (CFA; n> = 265). The EFA confirmed the unidimensional structure, retaining all 10 symptom items (KMO = 0.916, Bartlett's test 2 = 1264.196, p < .001, df = 45; 56.36% variance explained; Cronbach's alpha = 0.917). The CFA supported the model with adequate fit indices. Predictive validity was also demonstrated, with higher PG-13-R scores significantly associated with lower WHO-5 scores. These findings suggest the Brazilian version of the PG-13-R is a reliable and valid tool for assessing PGD symptoms in both clinical and research contexts.
Homodyned K-Distribution Temporal-Based Characterization of Rat Placenta Microstructure Using the Reduced Uterine Perfusion Pressure Model of Preeclampsia
Gleed, A.D.; Markel, A.C.; Shi, L.; Alencar, A.K.N.; Swan, K.F.; Hoerig, C.; Pridjian, G.C.; Bayer, C.L.; Mamou, J. (Elsevier, 4/15/25)
OBJECTIVE: We characterize rat placenta microstructure in the context of the reduced uterine perfusion pressure (RUPP) model of preeclampsia using the homodyned K-distribution to parameterize envelope-detected signals of ultrasound radiofrequency echo frames obtained in vivo. Preeclampsia is a life-threatening pregnancy syndrome related to abnormal placental tissue microstructure which motivated the quantitative ultrasound-based tissue characterization approach used in this study. METHODS: Ultrasound radiofrequency echo frames against time (or videos) were obtained on 30 and 38 in vivo placentae at gestation day (GD) 14 and 18 respectively, using 9 Sprague-Dawley rats. Preeclampsia-like effects were induced by surgical modification (post GD 14) following the RUPP model, giving a total of 20 RUPP and 18 control placentae at GD 18. The homodyned K-distribution was fit to value distributions of envelope-detected signals of ultrasound radiofrequency echo frames against time, yielding temporal $\alpha$ (scatterer number per resolution cell) and $\kappa$ (ratio of coherent to diffuse signal power) parameters used to characterize the placental tissue microstructure. RESULTS: Visualization of GD 18 $\alpha$ values as a color overlay on B-mode ultrasound video suggested higher values of control compared with RUPP. The mean kurtosis for RUPP was 4.07 ± 0.71 in comparison to 5.08 ± 1.28 for the control using placenta-level kurtosis values (p = 0.0044). There were no significant differences observed in GD 14 placentae, consistent with expectations. Further, we visualized and quantified temporal changes in GD 18 $\alpha$ values with frame-level statistics that support earlier findings. CONCLUSIONS: This study quantitatively characterizes rat placenta microstructure using the homodyned K-distribution and temporal $\alpha$ and $\kappa$ parameters.
Virtual screening: hope, hype, and the fine line in between.
Nada, H.; Meanwell, N.A.; Gabr, M.T. (Taylor and Francis, 1/27/25)
INTRODUCTION: Technological advancements in virtual screening (VS) have rapidly accelerated its application in drug discovery, as reflected by the exponential growth in VS-related publications. However, a significant gap remains between the volume of computational predictions and their experimental validation. This discrepancy has led to a rise in the number of unverified 'claimed' hits which impedes the drug discovery efforts. AREAS COVERED: This perspective examines the current VS landscape, highlighting essential practices and identifying critical challenges, limitations, and common pitfalls. Using case studies and practices, this perspective aims to highlight strategies that can effectively mitigate or overcome these challenges. Furthermore, the perspective explores common approaches for addressing pharmacodynamic and pharmacokinetic issues in optimizing VS hits. EXPERT OPINION: VS has become a tried-and-true technique of drug discovery due to the rapid advances in computational methods and machine learning (ML) over the past two decades. Although each VS workflow varies depending on the chosen approach and methodology, integrated strategies that combine biological and in silico data have consistently yielded higher success rates. Moreover, the widespread adoption of ML has enhanced the integration of VS into the drug discovery pipeline. However, the absence of standardized evaluation criteria hinders the objective assessment of VS studies' success and the identification of optimal adoption methods.
Nontechnical Factors and Postprocedural Considerations for Image-guided Breast Biopsy.
Dodelzon, K.; Bhole, S.; Coffey, K.; Dashevsky, B.Z.; Mullen, L.; Parikh, J.; Reig, B.; Grimm, L. (Oxford University Press, 1/25/25)
Beyond the technical aspects, success and long-term patient outcomes of image-guided breast biopsies depend on the overall patient experience. Patient experience in turn is influenced by intangible factors, such as environmental features during the procedure; patient-centered communication prior to, during, and subsequent to the procedure; and management of expectations and biopsy complications. Here, we review evidence-based literature and results of a national Society of Breast Imaging survey on approaches to both mitigate and manage common image-guided core biopsy complications as well as nontechnical strategies to improve the patient biopsy experience.
Psychometric Properties of the Critical Appraisal Tool for Anatomical Meta-Analysis.
D'Antoni, A. V.; Kamel, N.; Tubbs, R. S.; McCartan, M. G.; Strobel, L. W.; Bubb, K. C. (1/22/25)
The hallmark of evidence-based anatomy (EBA) is the anatomical meta-analysis (AMA). The Critical Appraisal Tool for Anatomical Meta-Analysis (CATAM) was recently published to enable users to appraise AMAs quickly and effectively. The tool is valuable for students and clinicians who need to judge the quality of AMAs, which informs clinical decision making and results in better patient care. Subjective measures of the tool's face and content validity have been established, but establishing its reliability provides a more objective measure of the instrument's dependability. This study investigated the interrater reliability (IRR) of the CATAM between novice and expert raters. Three graduate students and three professors (two anatomists and one pharmacist) read the original CATAM paper, and then had a post hoc meeting to discuss scoring with the tool. Three recent AMAs (published between 2017 and 2022) were randomly chosen from PubMed, and all six raters scored the papers blindly. The intraclass correlation coefficient (ICC) statistic was used to calculate the interrater reliability (IRR) between all scores, and then the ICCs between novice and expert scores were compared. Cronbach's alpha (internal consistency) of the CATAM was also calculated (SPSS 25, Armonk, NY). ICC for AMA-1 was 0.999 (95% CI, 0.997-0.999), p = 0.000, and alpha was 0.999. ICC for AMA-2 was 0.994 (95% CI, 0.988-0.998), p = 0.000, and alpha was 0.994. ICC for AMA-3 was 0.998 (95% CI, 0.995-0.999), p = 0.000, and alpha was 0.998. ANOVA showed no significant differences (p > 0.05) in mean ICCs between raters. The CATAM is a robust tool with excellent IRR (ICC > 0.990) and internal consistency (alpha > 0.990). No significant difference in ICC scores between novices and experts suggests the tool does not require prior expert knowledge to be effective. Now that the reliability of the CATAM is established, it can be more widely adopted by students and physicians worldwide to evaluate the quality of AMAs. The CATAM offers widespread applicability, and can be adopted in medical education, journal clubs, and clinical seminars to critically evaluate AMAs.

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