Scientific foundations of O'Dive PRO and publications produced by Azoth Systems
as well as – in the second part – our own scientific and technical publications.
Use of circulating bubbles for the prevention of decompression sickness accidents
Scientific foundations of O'Dive PRO
By its nature, the Industry searches to attain the two main goals: the performance and the safety. Working targets and operational constraints define the level of performance under safety conditions. In commercial diving, underwater construction and tunnelling, the security constraints are particularly important because these activities are associated with numerous risks, a part of which comes from the hyperbaric exposure of workers.
Indeed, the hyperbaric exposure during a dive or the work in a compressed air environment leads to the production of microbubbles in worker’s body during the decompression. Under the effect of pressure, body tissues (muscles, fat etc.) are progressively charged with inert gas, generally azote from air or nitrox, which is liberated during the decompression and generates microbubbles. The bubbles grow, penetrate the blood circulation and, in some cases, they can become pathogenic and lead to a decompression sickness accident (DCS).
The bubbles are not synonymous of an accident because the human body possesses the numerous mechanisms for eliminating them: they are filtered out by the lungs and eliminated with the respiration. Nevertheless, a great quantity of bubbles significantly increases the risk of an accident because the bubbles can overpass the lung filter and penetrate the arterial circulation or block the blood vessels, while the bubbles in tissues can grow enough to damage the tissues and/or trigger an inflammatory response.
For more than 30 years, Defence Research and Development Canada (DRDC, previously DCIEM), Institute of Environmental Medicine of the University of Pennsylvania (IFEM) and British Health and Safety Executive (HSE) have evaluated the level of decompression stress of diving procedures and tables by measuring the circulating bubbles detectable in blood vessels after exposure [1-7].
Those venous bubbles (VGE) are detected with the Doppler ultrasound (audio detection) or with the echography (imaging) and their number is evaluated on a non-linear scale quantified by grades ranging from 0 (absence of bubbles) to 4 (very numerous bubbles) according to the standard grading systems (Kisman-Masurel  or Spencer  for audio signals, Eftedal-Brubakk  for imaging).
The bubbles grades give an indication of decompression stress because they reflect, at least partially, the quantity of bubbles produced by the organism and their elimination. The numerous studies have shown a strong association between the quantity of bubbles and the risk of DCS [9,11-21]. Even if high bubble grades are a poor predictor of the occurrence of an accident , the absence of VGE is a good safety indicator. For example, within 3234 air, nitrox and heliox dives with 73 DCS analyzed in , 66 cases of DCS were associated with grades 3 or 4 (7.2% DCS rate), while only one DCS case was registered for bubble grade 0 (0.07% DCS rate).
British HSE organized two scientific meetings with working groups on security of industrial diving  and compressed air works . These two conferences confirmed the interest of the VGE measurements with Doppler ultrasound in the evaluation of the quality of procedures in laboratory and field conditions. They have concluded that the evaluation must be founded upon the statistics of bubbles production, especially in the beginning of each project and in case of modification of working conditions .
Based upon a historical data of bubble measurements and DCS cases for different exposures by combining them with the mathematical modelling tools (bubble growth model  and Flook model [24,25]), the following acceptance criteria for procedures in terms of VGE were proposed:
- For under-saturation diving: DRDC fixed experimentally the threshold of 50% of grades 2 or higher to distinguish the acceptable procedures from risky ones .  estimated that the threshold of at least 50% of grades 3 or 4 on a given exposure would insure the level of risk below 5%.
- For compressed air works: a criterion of 20% of grade 3 or 4 observed in the whole of workers was proposed as an indicator of procedure necessitating a detailed analysis or an eventual revision . Nevertheless, the authors pointed out that some procedures with good historical statistics of DCS (with few or no accidents reported) could eventually generate up to 60% of grades 1 or 2 and sometimes up to 10 % of grades 3.
The above criteria were used, for example, in  for showing that a surface decompression procedure (SurDO2) for a dive to 39.4m for 30 min with moderate work load produced high bubble levels: from Doppler measurements on a sample of divers, the authors have estimated that with 95% probability more than 50% of divers would produce a grade 3 or higher on this exposure. It was suggested to use a longer decompression to insure the sufficient elimination of muscular bubbles for this exposure.
In tunnelling, the air was replaced with the oxygen for decompression (sequence of 20 min oxygen/5 minutes air) with Blackpool table after the series of VGE measurements made by HSE showing a high level of risk associated to the air decompression (median grade 3) and its significant reduction with oxygen (median grade 0) . The Doppler ultra-sound was also used in field conditions to insure the safety after operational modification imposed by the TBM reparation needs during the Western Scheldt Tunnelling Project in Netherlands (sub-saturation exposures were replaced by longer saturation exposures, with the use of Trimix in both situations) .
In  the authors proposed a Bayesian approach to prediction of DCS risk using the bubbles measurements, having the advantage to combine the previous knowledge of bubbles production and the relationship between VGE and DCS with the results of new bubbles measurements:
« we present a method for estimating DCS risk of a decompression procedure based on observation of intravascular gas bubbles in test subjects and the correspondence between gas bubbles and DCS risk that has been established previously. The method makes use of Bayesian statistics to combine test observations with previous knowledge and assumptions. »
The data of 1726 experimental dives with air and nitrox  was used to estimate the DCS risk for each bubble grade. The authors applied the Bayesian computation to estimate the probability of DCS on a given exposure from the bubble measurements in a group of divers on this exposure and the prior for bubbles production extracted from 274 dives from . The advantage of this method is that with a small number of trials (7-15) without DCS one can compare two procedures and get the first estimation of DCS risk. For example, with this method the authors estimated the DCS risk to be 4.6% (95%CI: 1.5%-7.9%) on a procedure after just 7 exposures without DCS, but with 4 dives within 7 accompanied with a grade 3 or 4. The questionable hypothesis of this method is the conditional independence of DCS risk of exposure given the bubble grades. In other words, one supposed two exposures with the identical VGE statistics have exactly the same DCS risk.
 have analysed the data of air and nitrox dives from DRDC database from a different point of view: the authors showed that the prediction of risk of DCS necessitates to take into account both the bubble grades and severity of exposure , measured in terms of depth and duration of dive. Moreover, the authors compared the measurements from subclavian area with precordial ones not only from the point of view of agreement of two measures, but also as the indicators of DCS risk, and concluded that subclavian VGE are as good as precordial as DCS risk indicators. This result is in accordance with the observations of , even if the subclavian measurements are generally considered as complementary and used to improve the sensitivity of the precordial measures .
There is growing evidence of long-term effects of subclinical VGE (“silent bubbles”). Several small studies are pointing on endothelial and neuropsychological damages produced by the circulating bubbles.
Several animal and human studies have shown reduced endothelial function after exposure to vascular bubbles [34,35,36], suggesting that this effect may be a central mechanism in the development of serious decompression injury, and possibly also in long-term injury .  reported endothelial dysfunction and increased generation of reactive oxygen species (ROS) after successive trimix dives.
In a small number of recreational divers  showed an association between the subclinical circulating bubbles with an acute increase of platelets and leukocytes, indicating an activation of reactive system. An acute increase in plasma activity of ACE was also observed in subjects with circulating bubbles , that could be a marker of endothelial cell stress and damage.  showed an increased arterial pulmonary pressure in divers with post-dive circulating bubbles, the authors hypotized a mechanism of an increase vascular resistances caused by microembolisation.
Cerebral lesions were observed in experienced military divers  and white-matter lesions in experienced recreational divers were associated with neuropsychological damages (decrease in short-term memory and higher cognitive function) in [42,43] indicating that repeated hyperbaric exposure increases the risk of white-matter damage.
The literature reviewed here shown the interest of Doppler-detected VGE for the evaluation and the improvement of security in commercial diving and compressed air works. This is the only objective quantifiable measure of decompression stress, which serves to indicate stressful procedures well before the first occurrence of DCS. For more than 30 years the official regulatory and military institutions (HSE, IFEM, DRDC, French Navy) worked on guidelines to the use of bubble measurements for procedures evaluation, with several criteria proposed to insure the safety. Those criteria are still empirical, with the main weak point is that they are based upon VGE statistics, while ignoring the inherent risk associated to the exposure expressed by the exposure parameters.
Azoth Systems integrated this knowledge together with the analysis of data of thousands of exposures to develop a combined approach taking into the account both the intrinsic risk associated with the procedure and the statistics of Doppler-detected venous bubbles.
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 Lauckner GR, Nishi RY, Eatock BC. Evaluation of the DCIEM 1983 decompression model for compressaed air diving (series G-K). DCIEM Report n 84-R-73. Downsview, Ontario, Canada: Defence and Civil Institute of Environmental Medicine; 1984. – FULL TEXT
 Lauckner GR, Nishi RY, Eatock BC. Evaluation of the DCIEM 1983 decompression model for compressed air diving (series L-Q). DCIEM Report n° 85-R-18. Downsview, Ontario, Canada: Defence and Civil Institute of Environmental Medicine; 1985. – FULL TEXT
 Nishi R.Y., Eatock B.C., The role of ultrasonic bubble detection in table validation. In: Schreiner H.R., Hamilton R.W., editors. Validation of decompression tables. Proceedings of the 37th Undersea and Hyperbaric Medical Society Workshop, UHMS Publication 74(VAL)1-1-88. Bethesda, MA: Undersea and Hyperbaric Medical Society; 1989. p. 133–7. – ABSTRACT
 Lambertsen C. J., Nishi R. Y., Hopkin E. J., Relationships of Doppler venous gas embolism to decompression sickness. Environmental Biomedical Research Data Center, Institute for Environmental Medicine, University of Pennsylvania Medical Center ; 1997, Report No 7-10-1997. – FULL TEXT
 Simpson ME. , HSE Workshop on decompression safety. November 1998 London: Health and Safety Executive ; 1999, HSE Research Report OTO 1999 007. – FULL TEXT
 Jones A.D., Miller B.G., Colvin A.P. , Evaluation of Doppler monitoring for the control of hyperbaric exposure in tunnelling ; 2007, HSE Research Report OTO 2007 0598. – FULL TEXT
 Kisman K. E., Masurel G., Guillerm R., Bubble evaluation code for Doppler ultrasonic decompression data, Undersea Biomedediacl Research, 1978, vol. 5(1),pp. 28 .
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 Eftedal O., Brubakk A. O., Agreement between trained and untrained observers in grading intravascular bubble signals in ultrasonic images, Undersea and Hyperbaric Medicine, 1997, vol. 24(4), pp. 293-299. FULL TEXT
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 Gardette B. Correlation between decompression sickness and circulating bubbles in 232 divers. Undersea Biomedical Research. 1979; 6:99–107. – ABSTRACT
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 Eatock BC. Correspondence between intravascular bubbles and symptoms of decompression sickness. Undersea Biomedical Research. 1984; 11:326-9.
 Masurel G. Contribution à l’étude du rôle physiopathologique des bulles générées chez l’animal et chez l’homme par un séjour en atmosphère hyperbare. PhD Thesis, Lyon, Claude Bernard-Lyon I University; 1987. (in french) .
 Sawatzky KD. The relationship between intravascular Doppler-detected gas bubbles and decompression sickness after bounce diving in humans. M.Sc. Thesis, York University, Toronto; 1991.
 Sawatzky KD. Nishi RD. Intravascular Doppler-detected bubbles and decompression sickness. Undersea and Hyperbaric Medical Society, Inc. Joint Annual Scientific Meeting with the International Congress for Hyperbaric Medicine and the European Undersea Biomedical Society held 11-18 August 1990. Okura Hotel, Amsterdam, The Netherlands. – ABSTRACT
 Conkin J, Powell MR, Foster PP, Waligora JM. Information about venous gas emboli improves prediction of hypobaric decompression sickness. Aviation, Space and Environmental Medicine. 1998; 69:8–16. – ABSTRACT
 Pilmanis AA, Kannan N, Krause KM, Webb JT. Relating venous gas emboli (VGE) scores to altitude decompression sickness (DCS) symptoms. [Abstract]. Aviation, Space and Environmental Medicine. 1999; pp. 70-364.
 Doolette D.J. Venous gas emboli detected by two-dimensional echocardiography are an imperfect surrogate endpoint for decompression sickness. Diving and Hyperbaric Medicine. 2016; 46(1): pp. 4–10. – FULL TEXT
 Gernhardt M.L, Development and Evaluation of a Decompression Stress Index Based on Tissue Bubble Dynamics. Ph.D Thesis, University of Pennsylvania ; 1991, UMI #9211935. – FULL TEXT
 Flook V., Brubakk A.O. Validation of a mathematical model of decompression gas phase. SINTEF Unimed UK. STF78 F96104 1996.
 Flook V. Application of an advanced physiological model of decompression in the evaluation of decompression stress. Health and Safety Executive ; 1998, Report OTO 98 090 1998. – FULL TEXT
 Eftedal OS, Lydersen S, Brubakk AO. The relationship between venous gas bubbles and adverse effects of decompression after air dives. Undersea and Hyperbaric Medicine. 2007; 34:99–105. – FULL TEXT
 Flook V., Decompression Trials in National Hyperbaric Center ; 1999, London : Offshore Technology Report -OTO 1999 053. – FULL TEXT
 Flook V., Trials of a Blackpool table decompression with oxygen as the breathing gas. Prepared by UNIMED Scientific Limited for the Health and Safety Executive ; 2001, Contract Research Report 369/2001. – FULL TEXT
 Vellinga, T. P., Sterk, W., de Boer, A. G., van der Beek, A. J., Verhoeven, A. C., van Dijk, F. J., Doppler ultrasound surveillance in deep tunneling compressed-air work with Trimix breathing: bounce dive technique compared to saturation-excursion technique. Undersea and Hyperbaric Medicine ; 2008, vol. 35(6), pp. 407-416.- FULL TEXT
 Eftedal, O. S., Tjelmeland, H., & Brubakk, A. O., Validation of decompression procedures based on detection of venous gas bubbles: a Bayesian approach. Aviation, Space, and Environmental Medicine; 2007, vol. 78(2), pp. 94-99.
 Hugon J., Metelkina A., Barbaud A., Nishi R., Bouak F., Blatteau J. E., Gempp, E., Reliability of venous gas embolism detection in the subclavian area for decompression stress assessment following scuba diving. Diving and Hyperbaric Medicine; 2018, vol. 48(3), pp 132-140. – FULL TEXT
 Shannon, J. S. The relationship of inert gas and venous gas emboli to decompression sickness. M.Sc. Thesis, Duke University; 2003. – FULL TEXT
 Møllerløkken, A., Blogg, S. L., Doolette, D. J., Nishi, R. Y., & Pollock, N. W., Consensus guidelines for the use of ultrasound for diving research. Diving and hyperbaric medicine ; 2016, vol. 46(1), pp.26-32. – FULL TEXT
 Nossum, V., Koteng , S., Brubakk, A.O. Endothelial damage by bubbles in the pulmonary artery of the pig; Undersea and Hyperbaric Medicine; 1999, vol. 26(1): pp. 1-8. – ABSTRACT
 Nossum, V., Hjelde, A., Brubakk, A.O. Small amounts of venous gas embolism cause delayed impairment of endothelial function and increase polymorphonuclear neutrophil infiltration. European Journal of Applied Physiology; 2002, vol. 86(3): pp 209-214. – FULL TEXT
 Brubakk, A.O., Duplancic ,D., Valic ,Z., Palada, I., Obad, A., Bakovic, D., Wisloff, U., Dujic, Z. A single air dive reduces arterial endothelial function in man. The Journal of Physiology; 2005, vol. 566: pp. 901–906. – FULL TEXT
 Brubakk AO, Eftedal OS, Wisløff U (2007) Endothelium and diving.In: Aird W (ed) Handbook of the endothelium. Cambridge University Press, Cambridge – ABSTRACT
 Obad, A., Marinovic, J., Ljubkovic, M. Breskovic, T., Modun, D., Boban, M.,Dujic, Z. Successive deep dives impair endothelial functionand enhance oxidative stress in man. Clinical Physiology and Functional Imaging; 2010, vol. 30: pp. 432–438 – FULL TEXT
 Marabotti, C., Chiesa, F., Scalzini, A., Antonelli, F., Lari, R., Franchini, C., Data, P.G. Cardiac and humoral changes induced by recreational scuba diving. Undersea and Hyperbaric Medicine; 1999 vol. 26(3): pp 151-8. – ABSTRACT
 Marabotti, C., Scalzini, A., Chiesa, F. Increase of pulmonary arterial pressure in subjects with venous gas emboli after uncomplicated recreational SCUBA diving. Respiratory Medicine; 2013 vol. 107(4): pp. 596-600.-FULL TEXT
 Erdem, I., Yildiz, Ş., Uzun, G., Sonmez, G., Senol, M.G., Mutluoğlu, M., Mutlu, H., & Oner, B. Cerebral white-matter lesions in asymptomatic military divers. Aviation, Space, and Environmental Medicine ;2009, vol. 80(1), pp. 2-4 . – FULL TEXT
 Balestra, C, Germonpré P. Correlation between Patent Foramen Ovale, Cerebral “Lesions” and Neuropsychometric Testing in Experienced Sports Divers: Does Diving Damage the Brain? Front Psychol. 2016 May 11;7:696. –FULL TEXT
 Seyithanoğlu, M.H., Abdallah, A., Dündar, T.T., Kitiş, S., Aralaşmak, A., Gündağ Papaker, M., Sasani, H.. Investigation of Brain Impairment Using Diffusion-Weighted and Diffusion Tensor Magnetic Resonance Imaging in Experienced Healthy Divers; Medical Science Monitor; 2018, vol. 24: pp. 8279-8289. – FULL TEXT
4 research theses
10 years of R&D
A dedicated technology
Knowledge developed by Azoth Systems
The O’Dive PRO innovation is the result of knowledge developed during 10 years of research and development by Azoth Systems in collaboration with research laboratories, diving doctors, physiologists and scuba diving safety professionals.
In total, some thirty experts from various backgrounds have contributed to this knowledge. It is based on the analysis of hundreds of thousands of dives and the development of a technology shaped by years of testing in contact with users. This dynamic has notably resulted in 4 research theses, numerous scientific articles and several patents.
Hugon, J. (2010). Vers une modélisation biophysique de la décompression. Thèse de doctorat, Université de la Méditerranée, UMR – Physiologie et Physiopathologie en Conditions d’Oxygénation Extrêmes, Institut de Neuroscience Jean Roche, Faculté de Médecine Nord, Marseille. – ABSTRACT, FULL TEXT (in French)
Fouan, D. (2013). Détection et caractérisation d’embolies gazeuses ; application à la prévention des accidents de décompression. Thèse de doctorat, Université Aix-Marseille, Aix-Marseille. – ABSTRACT
Bennani, Y. (2015). Caractérisation de la diversité d’une population à partir de mesures quantifiées d’un modèle non-linéaire. Application à la plongée hyperbare. Thèse de doctorat, Université de Nice – Sophia Antipolis – École Doctorale Sciences et Technologies de l’Information et de la Communication – Laboratoire I3S, Nice. – ABSTRACT, FULL TEXT (in French)
Desailly, Y. (2016). Détection et localisation de microbulles par méthodes ultrasonores. Thèse de doctorat, Université Paris-Diderot – Institut Langevin, Paris VII. – ABASTRACT
Hugon, J., Blatteau, J.-E., Gempp, E., & Castagna, O. (2012). Oxygen breathing or recompression during decompression from nitrox dives with a rebreather: Effects on intravascular bubble burden and ramifications for decompression profiles. European Journal of Applied Physiology, 112, 2257-65. doi:10.1007/s00421-011-2195-6 – ABSTRACT
Barbaud, A., Fiévet, P., Mac Leod, S., & Masseron, R. (2012). Manned underwater operations and decompression sickness outlooks. Total Technoscoop, 60, 72-79.
Hugon, J., Blatteau, J.-E., Castagna, O., & al. (2013). Submarine Rescue Decompression Procedure from Hyperbaric Exposures up to 6 Bar of Absolute Pressure in Man: Effects on Bubble Formation and Pulmonary Function. PLoS ONE, 8(7). doi:10.1371/journal.pone.0067681 – FULL ARTICLE
Hugon, J. (2014). Decompression models: review, relevance and validation capabilities. Undersea and Hyperbaric Medicine, 41(6), 531-556. – ABSTRACT
Hugon, J., Metelkina, A., Barbaud, A., Nishi, R., Bouak, F., Gempp, E., & Blatteau, J.-E. (2018). Reliability of venous gas embolism detection in the subclavian area for decompression stress assessment following scuba diving. Diving and Hyperbaric Medicine Journal, 48(3), 132-140. – FULL ARTICLE, POSTER
Fouan, D., Goursolle, T., Lasaygues, P., & Mensah, S. (2012, April). Pulsed bi-frequency method for characterization of microbubbles in the context of decompression sickness. Acoustics 2012. – FULL ARTICLE
Fouan, D., Achaoui, Y., & Mensah, S. (2014). Improvement of micro-bubble sizing using multi-harmonic excitations under the transducer bandwidth constraint. Applied Physics Letters, 104(11). doi:10.1063/1.4868654 – ABSTRACT
Fouan, D. (2015). Microbubble dynamics monitoring using a dual modulation method. The Journal of the Acoustical Society of America, 137(2). doi:10.1121/1.4905883 – FULL ARTICLE
Bennani, Y., Pronzato, L., & Rendas, M. J. (2015). Most Likely Maximum Entropy for Population Analysis with Region-Censored Data. Entropy, 17(6), 3963-3988. doi:10.3390/e17063963 – FULL ARTICLE
Barbaud, A., Hugon, J., & Quinsac, C. (2013). Towards a customized management of decompression. Underwater Intervention. New Orleans.
Hugon, J., & Blatteau, J.-E. (2011). Biophysical models of decompression: review and perspectives. European Undersea Baromedical Society – 37th Annual Scientific Meeting. Gdansk.
Hugon, J., Bennani, Y., Pronzato, L., & Rendas, J. (2012). Calibration of a new biophysical model dedicated to the prevention of decompression sickness. Undersea and Hyperbaric Medical Society – 45th Annual Scientific Meeting. Phoenix. – ABSTRACT
Hugon, J., Nishi, R., Bouak, F., Blatteau, J.-E., & Gempp, E. (2015). A stress index to enhance DCS risk assessment for both air and mixed gas exposures. Undersea and Hyperbaric Medical Society – 48th Annual Scientific Meeting. Montréal. – POSTER
Fouan, D., & Mensah, S. (2013). Multi frequency excitation for a wide range of bubble detection. International Congress on Ultrasonics. Singapour. – ABSTRACT
Fouan, D., Goursolle, T., Potier, B., & Lasaygues, P. (2011). Release and characterization of a single bubble. Leeds Microbubbles Consortium. Leeds. – ABSTRACT
Fouan, D., Goursolle, T., Pottier, B., & Mensah, S. (2011). Free Single Bubble Ultrasonic Detection : Chirp Frequency Excitations Applied to Nonlinear Mixing Method. Undersea and Hyperbaric Medical Society – 44th Annual Scientific Meeting. Fort Worth. – ABSTRACT
Bennani, Y., Pronzato, L., & Rendas, J. (2014). Nonparametric density estimation with region-censored data. EUSIPCO. Lisbonne. – ABSTRACT
Bennani, Y., Pronzato, L., & Rendas, M. J. (2014). Maximum de vraisemblance non-paramétrique avec régions de censure. Application à un modèle biophysique de décompression. 46èmes Journées de Statistiques. Rennes. – ABSTRACT
Quinsac, C., Sadaghianloo, N., Declemy, S., Metelkina, A., & Barbaud, A. (2019). Etude préliminaire de la concordance de grades de bulles enregistrés grâce à un appareil Doppler connecté O’Dive vs. un Doppler vasculaire de référence. MedSubHyp – Journée Scientifique. Genève. – POSTER