@article{le_hoang_azarang_lance_natoli_gatrell_blogg_dayton_tillmans_lindholm_et al._2023, title={An open-source framework for synthetic post-dive Doppler ultrasound audio generation}, volume={18}, ISSN={["1932-6203"]}, DOI={10.1371/journal.pone.0284922}, abstractNote={Doppler ultrasound (DU) measurements are used to detect and evaluate venous gas emboli (VGE) formed after decompression. Automated methodologies for assessing VGE presence using signal processing have been developed on varying real-world datasets of limited size and without ground truth values preventing objective evaluation. We develop and report a method to generate synthetic post-dive data using DU signals collected in both precordium and subclavian vein with varying degrees of bubbling matching field-standard grading metrics. This method is adaptable, modifiable, and reproducible, allowing for researchers to tune the produced dataset for their desired purpose. We provide the baseline Doppler recordings and code required to generate synthetic data for researchers to reproduce our work and improve upon it. We also provide a set of pre-made synthetic post-dive DU data spanning six scenarios representing the Spencer and Kisman-Masurel (KM) grading scales as well as precordial and subclavian DU recordings. By providing a method for synthetic post-dive DU data generation, we aim to improve and accelerate the development of signal processing techniques for VGE analysis in Doppler ultrasound.}, number={4}, journal={PLOS ONE}, author={Le, David Q. and Hoang, Andrew H. and Azarang, Arian and Lance, Rachel M. and Natoli, Michael and Gatrell, Alan and Blogg, S. Lesley and Dayton, Paul A. and Tillmans, Frauke and Lindholm, Peter and et al.}, year={2023}, month={Apr} }
 @article{azarang_le_hoang_blogg_dayton_lance_natoli_gatrell_tillmans_moon_et al._2023, title={Deep Learning-Based Venous Gas Emboli Grade Classification in Doppler Ultrasound Audio Recordings}, volume={70}, ISSN={["1558-2531"]}, DOI={10.1109/TBME.2022.3217711}, abstractNote={Objective: Doppler ultrasound (DU) is used to detect venous gas emboli (VGE) post dive as a marker of decompression stress for diving physiology research as well as new decompression procedure validation to minimize decompression sickness risk. In this article, we propose the first deep learning model for VGE grading in DU audio recordings. Methods: A database of real-world data was assembled and labeled for the purpose of developing the algorithm, totaling 274 recordings comprising both subclavian and precordial measurements. Synthetic data was also generated by acquiring baseline DU signals from human volunteers and superimposing laboratory-acquired DU signals of bubbles flowing in a tissue mimicking material. A novel squeeze-and-excitation deep learning model was designed to effectively classify recordings on the 5-class Spencer scoring system used by trained human raters. Results: On the real-data test set, we show that synthetic data pretraining achieves average ordinal accuracy of 84.9% for precordial and 90.4% for subclavian DU which is a 24.6% and 26.2% increase over training with real-data and time-series augmentation only. The weighted kappa coefficients of agreement between the model and human ground truth were 0.74 and 0.69 for precordial and subclavian respectively, indicating substantial agreement similar to human inter-rater agreement for this type of data. Conclusion: The present work demonstrates the first application of deep-learning for DU VGE grading using a combination of synthetic and real-world data. Significance: The proposed method can contribute to accelerating DU analysis for decompression research.}, number={5}, journal={IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING}, author={Azarang, Arian and Le, David Q. and Hoang, Andrew H. and Blogg, S. Lesley and Dayton, Paul A. and Lance, Rachel M. and Natoli, Michael and Gatrell, Alan and Tillmans, Frauke and Moon, Richard E. and et al.}, year={2023}, month={May}, pages={1436–1446} }
 @article{azarang_blogg_currens_lance_moon_lindholm_papadopoulou_2023, title={Development of a graphical user interface for automatic separation of human voice from Doppler ultrasound audio in diving experiments}, volume={18}, ISSN={["1932-6203"]}, DOI={10.1371/journal.pone.0283953}, abstractNote={Doppler ultrasound (DU) is used in decompression research to detect venous gas emboli in the precordium or subclavian vein, as a marker of decompression stress. This is of relevance to scuba divers, compressed air workers and astronauts to prevent decompression sickness (DCS) that can be caused by these bubbles upon or after a sudden reduction in ambient pressure. Doppler ultrasound data is graded by expert raters on the Kisman-Masurel or Spencer scales that are associated to DCS risk. Meta-analyses, as well as efforts to computer-automate DU grading, both necessitate access to large databases of well-curated and graded data. Leveraging previously collected data is especially important due to the difficulty of repeating large-scale extreme military pressure exposures that were conducted in the 70-90s in austere environments. Historically, DU data (Non-speech) were often captured on cassettes in one-channel audio with superimposed human speech describing the experiment (Speech). Digitizing and separating these audio files is currently a lengthy, manual task. In this paper, we develop a graphical user interface (GUI) to perform automatic speech recognition and aid in Non-speech and Speech separation. This constitutes the first study incorporating speech processing technology in the field of diving research. If successful, it has the potential to significantly accelerate the reuse of previously-acquired datasets. The recognition task incorporates the Google speech recognizer to detect the presence of human voice activity together with corresponding timestamps. The detected human speech is then separated from the audio Doppler ultrasound within the developed GUI. Several experiments were conducted on recently digitized audio Doppler recordings to corroborate the effectiveness of the developed GUI in recognition and separations tasks, and these are compared to manual labels for Speech timestamps. The following metrics are used to evaluate performance: the average absolute differences between the reference and detected Speech starting points, as well as the percentage of detected Speech over the total duration of the reference Speech. Results have shown the efficacy of the developed GUI in Speech/Non-speech component separation.}, number={8}, journal={PLOS ONE}, author={Azarang, Arian and Blogg, S. Lesley and Currens, Joshua and Lance, Rachel M. and Moon, Richard E. and Lindholm, Peter and Papadopoulou, Virginie}, year={2023}, month={Aug} }
 @article{durham_upadhyay_navarro-becerra_moon_borden_dayton_papadopoulou_2023, title={Effect of Anesthetic Carrier Gas on In Vivo Circulation Times of Intravenously Administered Phospholipid Oxygen Microbubbles in Rats}, volume={49}, ISSN={["1879-291X"]}, DOI={10.1016/j.ultrasmedbio.2023.04.016}, abstractNote={For the treatment of tumor hypoxia, microbubbles comprising oxygen as a majority component of the gas core with a stabilizing shell may be used to deliver and release oxygen locally at the tumor site through ultrasound destruction. Previous work has revealed differences in circulation half-life in vivo for perfluorocarbon-filled microbubbles, typically used as ultrasound imaging contrast agents, as a function of anesthetic carrier gas. These differences in circulation time in vivo were likely due to gas diffusion as a function of anesthetic carrier gas, among other variables. This work has motivated studies to evaluate the effect of anesthetic carrier gas on oxygen microbubble circulation dynamics.Circulation time for oxygen microbubbles was derived from ultrasound image intensity obtained during longitudinal kidney imaging. Studies were constructed for rats anesthetized on inhaled isoflurane with either pure oxygen or medical air as the anesthetic carrier gas.Results indicated that oxygen microbubbles were highly visible via contrast-specific imaging. Marked signal enhancement and duration differences were observed between animals breathing air and oxygen. Perhaps counterintuitively, oxygen microbubbles disappeared from circulation significantly faster when the animals were breathing pure oxygen compared with medical air. This may be explained by nitrogen counterdiffusion from blood into the bubble, effectively changing the gas composition of the core, as has been observed in perfluorocarbon core microbubbles.Our findings suggest that the apparent longevity and persistence of oxygen microbubbles in circulation may not be reflective of oxygen delivery when the animal is anesthetized breathing air.}, number={8}, journal={ULTRASOUND IN MEDICINE AND BIOLOGY}, author={Durham, Phillip G. and Upadhyay, Awaneesh and Navarro-Becerra, J. Angel and Moon, Richard E. and Borden, Mark A. and Dayton, Paul A. and Papadopoulou, Virginie}, year={2023}, month={Aug}, pages={1861–1866} }
 @article{papadopoulou_sidders_lu_velez_durham_bui_angeles-solano_dayton_rowe_2023, title={Overcoming biological barriers to improve treatment of a Staphylococcus aureus wound infection}, volume={30}, ISSN={["2451-9448"]}, DOI={10.1016/j.chembiol.2023.04.009}, abstractNote={<h2>Summary</h2> Chronic wounds frequently become infected with bacterial biofilms which respond poorly to antibiotic therapy. Aminoglycoside antibiotics are ineffective at treating deep-seated wound infections due to poor drug penetration, poor drug uptake into persister cells, and widespread antibiotic resistance. In this study, we combat the two major barriers to successful aminoglycoside treatment against a biofilm-infected wound: limited antibiotic uptake and limited biofilm penetration. To combat the limited antibiotic uptake, we employ palmitoleic acid, a host-produced monounsaturated fatty acid that perturbs the membrane of gram-positive pathogens and induces gentamicin uptake. This novel drug combination overcomes gentamicin tolerance and resistance in multiple gram-positive wound pathogens. To combat biofilm penetration, we examined the ability of sonobactericide, a non-invasive ultrasound-mediated-drug delivery technology to improve antibiotic efficacy using an <i>in vivo</i> biofilm model. This dual approach dramatically improved antibiotic efficacy against a methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) wound infection in diabetic mice.}, number={5}, journal={CELL CHEMICAL BIOLOGY}, author={Papadopoulou, Virginie and Sidders, Ashelyn E. and Lu, Kuan-Yi and Velez, Amanda Z. and Durham, Phillip G. and Bui, Duyen T. and Angeles-Solano, Michelle and Dayton, Paul A. and Rowe, Sarah E.}, year={2023}, month={May}, pages={513-+} }
 @misc{papadopoulou_stride_borden_eisenbrey_dayton_2023, title={Radiotherapy Sensitization With Ultrasound-Stimulated Intravenously Injected Oxygen Microbubbles Can Have Contrary Effects Depending on the Study Model}, volume={49}, ISSN={["1879-291X"]}, DOI={10.1016/j.ultrasmedbio.2023.06.006}, abstractNote={We are writing to share our collective experience over the last few years working on radiosensitization strategies using intravenously administered, ultrasound-stimulated, oxygen microbubbles. There has been considerable pre-clinical success reported to date, including from our own groups, using oxygen microbubbles as a cancer theranostic agent to improve radiotherapy, sonodynamic therapy and brachytherapy treatments [ 1 Eisenbrey JR Shraim R Liu JB Li J Stanczak M Oeffinger B et al. Sensitization of hypoxic tumors to radiation therapy using ultrasound-sensitive oxygen microbubbles. Int J Radiat Oncol Biol Phys. 2018; 101: 88-96 Abstract Full Text Full Text PDF PubMed Scopus (68) Google Scholar , 2 Fix SM Papadopoulou V Velds H Kasoji SK Rivera JN Borden MA et al. Oxygen microbubbles improve radiotherapy tumor control in a rat fibrosarcoma model—a preliminary study. PLoS One. 2018; 13e0195667 Crossref Scopus (31) Google Scholar , 3 McEwan C Owen J Stride E Fowley C Nesbitt H Cochrane D et al. Oxygen carrying microbubbles for enhanced sonodynamic therapy of hypoxic tumours. J Control Release. 2015; 203: 51-56 Crossref PubMed Scopus (198) Google Scholar , 4 Peng S Song R Lin Q Zhang Y Yang Y Luo M et al. A robust oxygen microbubble radiosensitizer for iodine-125 brachytherapy. Adv Sci (Weinh). 2021; 82002567 Google Scholar ]. However, we have recently come across several unexpected findings that warrant further study and caution as these techniques move toward translation. As we work toward publishing these in the coming months, we believe that their implications are important to communicate quickly and we therefore outline key observations in this letter.}, number={9}, journal={ULTRASOUND IN MEDICINE AND BIOLOGY}, author={Papadopoulou, Virginie and Stride, Eleanor P. and Borden, Mark A. and Eisenbrey, John R. and Dayton, Paul A.}, year={2023}, month={Sep}, pages={2203–2204} }
 @misc{currens_dayton_buzzacott_papadopoulou_2022, title={Hyperbaric exposure in rodents with non- invasive imaging assessment of decompression bubbles: A scoping review protocol}, volume={17}, ISSN={["1932-6203"]}, DOI={10.1371/journal.pone.0274241}, abstractNote={Hyperbaric pressure experiments have provided researchers with valuable insights into the effects of pressure changes, using various species as subjects. Notably, extensive work has been done to observe rodents subjected to hyperbaric pressure, with differing imaging modalities used as an analytical tool. Decompression puts subjects at a greater risk for injury, which often justifies conducting such experiments using animal models. Therefore, it is important to provide a broad view of previously utilized methods for decompression research to describe imaging tools available for researchers to conduct rodent decompression experiments, to prevent duplicate experimentation, and to identify significant gaps in the literature for future researchers. Through a scoping review of published literature, we will provide an overview of decompression bubble information collected from rodent experiments using various non-invasive methods of ultrasound for decompression bubble assessment. This review will adhere to methods outlined by the Joanna Briggs Institute Manual for Evidence Synthesis and be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Reviews (PRISMA-ScR). Literature will be obtained from the PubMed, Embase, and Scopus databases. Extracted sources will first be sorted to a list for inclusion based on title and abstract. Two independent researchers will then conduct full-text screening to further refine included papers to those relevant to the scope. The final review manuscript will cover methods, data, and findings for each included publication relevant to non-invasive in vivo bubble imaging.}, number={9}, journal={PLOS ONE}, author={Currens, Joshua and Dayton, Paul A. and Buzzacott, Peter and Papadopoulou, Virginie}, year={2022}, month={Sep} }