المؤلفون: Hariri, Lida, Hogaboam, Cory, Jenkins, R, Kaminski, Naftali, Kim, Grace, Königshoff, Melanie, Kolb, Martin, Kotton, Darrell, Kropski, Jonathan, Lasky, Joseph, Magin, Chelsea, Maher, Toby, McCormick, Mark, Moore, Bethany, Nickerson-Nutter, Cheryl, Oldham, Justin, Podolanczuk, Anna, Raghu, Ganesh, Rosas, Ivan, Rowe, Steven, Schmidt, William, Schwartz, David, Shore, Jessica, Spino, Cathie, Craig, J, Martinez, Fernando, Montesi, Sydney, Gomez, Christian, Beers, Michael, Brown, Robert, Chattopadhyay, Ishanu, Flaherty, Kevin, Garcia, Christine, Gomperts, Brigitte

المصدر: American Journal of Respiratory and Critical Care Medicine. 209(4)

مصطلحات موضوعية: interstitial lung disease, pulmonary fibrosis, United States, Humans, National Heart, Lung, and Blood Institute (U.S.), Lakes, Idiopathic Pulmonary Fibrosis, Risk Factors, Biomedical Research

الوصف: Despite progress in elucidation of disease mechanisms, identification of risk factors, biomarker discovery, and the approval of two medications to slow lung function decline in idiopathic pulmonary fibrosis and one medication to slow lung function decline in progressive pulmonary fibrosis, pulmonary fibrosis remains a disease with a high morbidity and mortality. In recognition of the need to catalyze ongoing advances and collaboration in the field of pulmonary fibrosis, the NHLBI, the Three Lakes Foundation, and the Pulmonary Fibrosis Foundation hosted the Pulmonary Fibrosis Stakeholder Summit on November 8-9, 2022. This workshop was held virtually and was organized into three topic areas: 1) novel models and research tools to better study pulmonary fibrosis and uncover new therapies, 2) early disease risk factors and methods to improve diagnosis, and 3) innovative approaches toward clinical trial design for pulmonary fibrosis. In this workshop report, we summarize the content of the presentations and discussions, enumerating research opportunities for advancing our understanding of the pathogenesis, treatment, and outcomes of pulmonary fibrosis.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/5092667mTest

المؤلفون: Fendler, Wolfgang P, Eiber, Matthias, Beheshti, Mohsen, Bomanji, Jamshed, Calais, Jeremie, Ceci, Francesco, Cho, Steve Y, Fanti, Stefano, Giesel, Frederik L, Goffin, Karolien, Haberkorn, Uwe, Jacene, Heather, Koo, Phillip J, Kopka, Klaus, Krause, Bernd J, Lindenberg, Liza, Marcus, Charles, Mottaghy, Felix M, Oprea-Lager, Daniela E, Osborne, Joseph R, Piert, Morand, Rowe, Steven P, Schöder, Heiko, Wan, Simon, Wester, Hans-Jürgen, Hope, Thomas A, Herrmann, Ken

المصدر: European journal of nuclear medicine and molecular imaging. 50(5)

مصطلحات موضوعية: Humans, Prostatic Neoplasms, Gallium Radioisotopes, Edetic Acid, Oligopeptides, Male, Positron Emission Tomography Computed Tomography, Guideline, PET, PSMA, Prostate cancer, Restaging, Staging, Biomedical Imaging, Urologic Diseases, Aging, Prostate Cancer, Cancer, Other Physical Sciences, Clinical Sciences, Nuclear Medicine & Medical Imaging

الوصف: Here we aim to provide updated guidance and standards for the indication, acquisition, and interpretation of PSMA PET/CT for prostate cancer imaging. Procedures and characteristics are reported for a variety of available PSMA small radioligands. Different scenarios for the clinical use of PSMA-ligand PET/CT are discussed. This document provides clinicians and technicians with the best available evidence, to support the implementation of PSMA PET/CT imaging in research and routine practice.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/47h17394Test

المؤلفون: Parekh, Vishwa S, Lai, Shuhao, Braverman, Vladimir, Leal, Jeff, Rowe, Steven, Pillai, Jay J, Jacobs, Michael A

مصطلحات موضوعية: Electrical Engineering and Systems Science - Image and Video Processing, Computer Science - Artificial Intelligence, Computer Science - Computer Vision and Pattern Recognition, Computer Science - Machine Learning

الوصف: Federated learning is increasingly being explored in the field of medical imaging to train deep learning models on large scale datasets distributed across different data centers while preserving privacy by avoiding the need to transfer sensitive patient information. In this manuscript, we explore federated learning in a multi-domain, multi-task setting wherein different participating nodes may contain datasets sourced from different domains and are trained to solve different tasks. We evaluated cross-domain federated learning for the tasks of object detection and segmentation across two different experimental settings: multi-modal and multi-organ. The result from our experiments on cross-domain federated learning framework were very encouraging with an overlap similarity of 0.79 for organ localization and 0.65 for lesion segmentation. Our results demonstrate the potential of federated learning in developing multi-domain, multi-task deep learning models without sharing data from different domains.
Comment: Under Review for MIDL 2022

الوصول الحر: http://arxiv.org/abs/2112.10001Test

المؤلفون: Basil, Maria C, Cardenas-Diaz, Fabian L, Kathiriya, Jaymin J, Morley, Michael P, Carl, Justine, Brumwell, Alexis N, Katzen, Jeremy, Slovik, Katherine J, Babu, Apoorva, Zhou, Su, Kremp, Madison M, McCauley, Katherine B, Li, Shanru, Planer, Joseph D, Hussain, Shah S, Liu, Xiaoming, Windmueller, Rebecca, Ying, Yun, Stewart, Kathleen M, Oyster, Michelle, Christie, Jason D, Diamond, Joshua M, Engelhardt, John F, Cantu, Edward, Rowe, Steven M, Kotton, Darrell N, Chapman, Harold A, Morrisey, Edward E

المصدر: Nature. 604(7904)

مصطلحات موضوعية: Lung, Stem Cell Research, Stem Cell Research - Embryonic - Non-Human, Aetiology, 2.1 Biological and endogenous factors, Respiratory, Animals, Bronchioles, Cell Lineage, Ferrets, Humans, Mice, Multipotent Stem Cells, Pulmonary Alveoli, Pulmonary Disease, Chronic Obstructive, General Science & Technology

الوصف: The human lung differs substantially from its mouse counterpart, resulting in a distinct distal airway architecture affected by disease pathology in chronic obstructive pulmonary disease. In humans, the distal branches of the airway interweave with the alveolar gas-exchange niche, forming an anatomical structure known as the respiratory bronchioles. Owing to the lack of a counterpart in mouse, the cellular and molecular mechanisms that govern respiratory bronchioles in the human lung remain uncharacterized. Here we show that human respiratory bronchioles contain a unique secretory cell population that is distinct from cells in larger proximal airways. Organoid modelling reveals that these respiratory airway secretory (RAS) cells act as unidirectional progenitors for alveolar type 2 cells, which are essential for maintaining and regenerating the alveolar niche. RAS cell lineage differentiation into alveolar type 2 cells is regulated by Notch and Wnt signalling. In chronic obstructive pulmonary disease, RAS cells are altered transcriptionally, corresponding to abnormal alveolar type 2 cell states, which are associated with smoking exposure in both humans and ferrets. These data identify a distinct progenitor in a region of the human lung that is not found in mouse that has a critical role in maintaining the gas-exchange compartment and is altered in chronic lung disease.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/3qj302pjTest

المؤلفون: Sharma, Ajay Kumar, Gupta, Kuldeep, Mishra, Akhilesh, Lofland, Gabriela, Marsh, Ian, Kumar, Dhiraj, Ghiaur, Gabriel, Imus, Philip, Rowe, Steven P., Hobbs, Robert F., Gocke, Christian B., Nimmagadda, Sridhar

المساهمون: National Institutes of Health

المصدر: Advanced Science ; volume 11, issue 16 ; ISSN 2198-3844 2198-3844

الوصف: The limited availability of molecularly targeted low‐molecular‐weight imaging agents for monitoring multiple myeloma (MM)‐targeted therapies has been a significant challenge in the field. In response, a first‐in‐class peptide‐based radiotracer, [ 68 Ga]Ga‐AJ206, is developed that can be seamlessly integrated into the standard clinical workflow and is specifically designed to noninvasively quantify CD38 levels and pharmacodynamics by positron emission tomography (PET). A bicyclic peptide, AJ206, is synthesized and exhibits high affinity to CD38 ( K D : 19.1 ± 0.99 × 10 −9 m ) by surface plasmon resonance. Further, [ 68 Ga]Ga‐AJ206‐PET shows high contrast within 60 min and suitable absorbed dose estimates for clinical use. Additionally, [ 68 Ga]Ga‐AJ206 detects CD38 expression in cell line‐derived xenografts, patient‐derived xenografts (PDXs), and disseminated disease models in a manner consistent with flow cytometry and immunohistochemistry findings. Moreover, [ 68 Ga]Ga‐AJ206‐PET successfully quantifies CD38 pharmacodynamics in PDXs, revealing increased CD38 expression in the tumor following all‐trans retinoic acid (ATRA) therapy. In conclusion, [ 68 Ga]Ga‐AJ206 exhibits the salient features required for clinical translation, providing CD38‐specific high‐contrast images in multiple models of MM. [ 68 Ga]Ga‐AJ206‐PET could be useful for quantifying total CD38 levels and pharmacodynamics during therapy to evaluate approved and new therapies in MM and other diseases with CD38 involvement.

الإتاحة: https://doi.org/10.1002/advs.202308617Test

المؤلفون: Bennett, Richard, Li, Eric V., Ho, Austin Y., Aguiar, Jonathan A., Neill, Clayton, Rowe, Steven P., Patel, Hiten D., Savas, Hatice, Ross, Ashley E.

المصدر: The Prostate ; volume 84, issue 8, page 717-722 ; ISSN 0270-4137 1097-0045

الوصف: Introduction The Society of Nuclear Medicine and Molecular Imaging (SNMMI) provides appropriate use criteria (AUC) for prostate‐specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) which include guidance on imaging in newly diagnosed prostate cancer and in patients with biochemically recurrent (BCR) disease. This study aims to examine trends in PSMA implementation and the prevalence and outcomes of scans ordered in scenarios deemed rarely appropriate or not meeting SNMMI AUC. Methods We retrospectively identified patients who were diagnosed with presumptive National Comprehensive Cancer Network unfavorable intermediate, high, or very high risk prostate cancer, patients who underwent staging for BCR, and all patients staged with PSMA between July 2021 and March 2023. Positivity was validated by adherence to a predetermined reference standard. Results The frequency of PSMA use increased in initial staging from 24% to 80% and work‐up of BCR from 91% to 99% over our study period. In addition, 5% (17/340) of PSMA scans ordered for initial staging did not meet AUC and 3% (15/557) of posttreatment scans were deemed rarely appropriate. Initial staging orders not meeting SNMMI AUC resulted in no positivity (0/17), while rarely appropriate posttreatment scans were falsely positive in 75% (3/4) of cases. Urologists (53%, 17/32) comprised the largest ordering specialty in rarely appropriate use. Conclusion The frequency of PSMA use rose across the study period. A significant minority of patients received PSMA PET/CT in rarely appropriate scenarios yielding no positivity in initial staging and significant false positivity post‐therapy. Further education of providers and electronic medical record‐based interventions could help limit the rarely appropriate use of PET imaging.

الإتاحة: https://doi.org/10.1002/pros.24687Test

المؤلفون: Rowe, Steven P., Krueger, Sebastian, Gorin, Michael A., Fishman, Elliot K.

المصدر: BJUI Compass ; ISSN 2688-4526 2688-4526

الإتاحة: https://doi.org/10.1002/bco2.324Test

المؤلفون: Singla, Nirmish, Nirschl, Thomas R., Obradovic, Aleksandar Z., Shenderov, Eugene, Lombardo, Kara, Liu, Xiaopu, Pons, Alice, Zarif, Jelani C., Rowe, Steven P., Trock, Bruce J., Hammers, Hans J., Bivalacqua, Trinity J., Pierorazio, Phillip M., Deutsch, Julie S., Lotan, Tamara L., Taube, Janis M., Ged, Yasser M. A., Gorin, Michael A., Allaf, Mohamad E., Drake, Charles G.

المساهمون: Bristol-Myers Squibb

المصدر: Scientific Reports ; volume 14, issue 1 ; ISSN 2045-2322

مصطلحات موضوعية: Multidisciplinary

الوصف: Novel perioperative strategies are needed to reduce recurrence rates in patients undergoing nephrectomy for high-risk, non-metastatic clear cell renal cell carcinoma (ccRCC). We conducted a prospective, phase I trial of neoadjuvant nivolumab prior to nephrectomy in 15 evaluable patients with non-metastatic ccRCC. We leveraged tissue from that cohort to elucidate the effects of PD-1 inhibition on immune cell populations in ccRCC and correlate the evolving immune milieu with anti-PD-1 response. We found that nivolumab durably induces a pro-inflammatory state within the primary tumor, and baseline immune infiltration within the primary tumor correlates with nivolumab responsiveness. Nivolumab increases CTLA-4 expression in the primary tumor, and subsequent nephrectomy increases circulating concentrations of sPD-L1, sPD-L3 (sB7-H3), and s4-1BB. These findings form the basis to consider neoadjuvant immune checkpoint inhibition (ICI) for high-risk ccRCC while the tumor remains in situ and provide the rationale for perioperative strategies of novel ICI combinations.

الإتاحة: https://doi.org/10.1038/s41598-024-51889-9Test
https://www.nature.com/articles/s41598-024-51889-9.pdfTest
https://www.nature.com/articles/s41598-024-51889-9Test

المؤلفون: Ordonez, Alvaro A, Parker, Matthew FL, Miller, Robert J, Plyku, Donika, Ruiz-Bedoya, Camilo A, Tucker, Elizabeth W, Luu, Justin M, Dikeman, Dustin A, Lesniak, Wojciech G, Holt, Daniel P, Dannals, Robert F, Miller, Lloyd S, Rowe, Steven P, Wilson, David M, Jain, Sanjay K

المصدر: JCI Insight. 7(1)

مصطلحات موضوعية: Clinical Research, Infectious Diseases, Emerging Infectious Diseases, Antimicrobial Resistance, Biomedical Imaging, Bioengineering, Aetiology, 2.2 Factors relating to the physical environment, Infection, 4-Aminobenzoic Acid, Adult, Animals, Carbon Radioisotopes, Contrast Media, Female, Humans, Male, Methicillin-Resistant Staphylococcus aureus, Positron-Emission Tomography, Rabbits, Rats, Staphylococcal Infections, Tissue Distribution, Young Adult, Bacterial infections, Diagnostic imaging, Infectious disease

الوصف: Tools for noninvasive detection of bacterial pathogens are needed but are not currently available for clinical use. We have previously shown that para-aminobenzoic acid (PABA) rapidly accumulates in a wide range of pathogenic bacteria, motivating the development of related PET radiotracers. In this study, 11C-PABA PET imaging was used to accurately detect and monitor infections due to pyogenic bacteria in multiple clinically relevant animal models. 11C-PABA PET imaging selectively detected infections in muscle, intervertebral discs, and methicillin-resistant Staphylococcus aureus-infected orthopedic implants. In what we believe to be first-in-human studies in healthy participants, 11C-PABA was safe, well-tolerated, and had a favorable biodistribution, with low background activity in the lungs, muscles, and brain. 11C-PABA has the potential for clinical translation to detect and localize a broad range of bacteria.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/1qg1f3v1Test

المؤلفون: Chen, Junyu, Li, Ye, Luna, Licia P., Chung, Hyun Woo, Rowe, Steven P., Du, Yong, Solnes, Lilja B., Frey, Eric C.

مصطلحات موضوعية: Computer Science - Computer Vision and Pattern Recognition

الوصف: Quantitative bone single-photon emission computed tomography (QBSPECT) has the potential to provide a better quantitative assessment of bone metastasis than planar bone scintigraphy due to its ability to better quantify activity in overlapping structures. An important element of assessing response of bone metastasis is accurate image segmentation. However, limited by the properties of QBSPECT images, the segmentation of anatomical regions-of-interests (ROIs) still relies heavily on the manual delineation by experts. This work proposes a fast and robust automated segmentation method for partitioning a QBSPECT image into lesion, bone, and background. We present a new unsupervised segmentation loss function and its semi- and supervised variants for training a convolutional neural network (ConvNet). The loss functions were developed based on the objective function of the classical Fuzzy C-means (FCM) algorithm. We conducted a comprehensive study to compare our proposed methods with ConvNets trained using supervised loss functions and conventional clustering methods. The Dice similarity coefficient (DSC) and several other metrics were used as figures of merit as applied to the task of delineating lesion and bone in both simulated and clinical SPECT/CT images. We experimentally demonstrated that the proposed methods yielded good segmentation results on a clinical dataset even though the training was done using realistic simulated images. A ConvNet-based image segmentation method that uses novel loss functions was developed and evaluated. The method can operate in unsupervised, semi-supervised, or fully-supervised modes depending on the availability of annotated training data. The results demonstrated that the proposed method provides fast and robust lesion and bone segmentation for QBSPECT/CT. The method can potentially be applied to other medical image segmentation applications.
Comment: This manuscript has been published by Medical Physics (2021)

الوصول الحر: http://arxiv.org/abs/2104.08623Test