Infrared Thermography-based Biophotonics: Integrated Diagnostic Technique for Systemic Reaction Monitoring

Infrared Thermography-based Biophotonics: Integrated Diagnostic Technique for Systemic Reaction Monitoring

Available online at www.sciencedirect.com ScienceDirect Physics Procedia 86 (2017) 81 – 85 International Conference on Photonics of Nano- and Bio-St...

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Available online at www.sciencedirect.com

ScienceDirect Physics Procedia 86 (2017) 81 – 85

International Conference on Photonics of Nano- and Bio-Structures, PNBS-2015, 19-20 June 2015, Vladivostok, Russia and the International Conference on Photonics of Nano- and MicroStructures, PNMS-2015, 7-11 September 2015, Tomsk, Russia

Infrared thermography-based biophotonics: Integrated diagnostic technique for systemic reaction monitoring Boris G. Vainer a,b,*, Vitaly V. Morozov c a

Rzhanov Institute of Semiconductor Physics SB RAS, 13 Lavrentyev av., Novosibirsk, 630090, Russia b Novosibirsk State University, 2 Pirogova str., Novosibirsk, 630090, Russia c Institute of Chemical Biology and Fundamental Medicine SB RAS, 8 Lavrentyev av., Novosibirsk, 630090, Russia

Abstract A peculiar branch of biophotonics is a measurement, visualisation and quantitative analysis of infrared (IR) radiation emitted from living object surfaces. Focal plane array (FPA)-based IR cameras make it possible to realize in medicine the so called interventional infrared thermal diagnostics. An integrated technique aimed at the advancement of this new approach in biomedical science and practice is described in the paper. The assembled system includes a high-performance short-wave (2.453.05 Pm) or long-wave (8-14 Pm) IR camera, two laser Doppler flowmeters (LDF) and additional equipment and complementary facilities implementing the monitoring of human cardiovascular status. All these means operate synchronously. It is first ascertained the relationship between infrared thermography (IRT) and LDF data in humans in regard to their systemic cardiovascular reactivity. Blood supply real-time dynamics in a narcotized patient is first visualized and quantitatively represented during surgery in order to observe how the general hyperoxia influences thermoregulatory mechanisms; an abrupt increase in temperature of the upper limb is observed using IRT. It is outlined that the IRT-based integrated technique may act as a take-off runway leading to elaboration of informative new methods directly applicable to medicine and biomedical sciences. © 2017 2016The B.G.Vainer, V.V.Morozov. Published by is Elsevier Authors. Published by Elsevier B.V. This an openB.V. access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Peer-review under responsibility of the organizing committee of PNBS-2015 and PNMS-2015. Peer-review under responsibility of the organizing committee of PNBS-2015 and PNMS-2015. Keywords: infrared thermography; laser Doppler flowmetry; sistemic cardiovascular reaction; integrated approach

* Corresponding author. Tel.: +7-913-910-3246 E-mail address: [email protected]

1875-3892 © 2017 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Peer-review under responsibility of the organizing committee of PNBS-2015 and PNMS-2015. doi:10.1016/j.phpro.2017.01.025

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1. Introduction A heat production taking place in human organs and tissues and resulting in a local temperature increase is the fundamental co-product of all life-sustaining processes. To maintain a stable temperature of the organism, the excessive thermal energy should be released into the ambient. Normally, it proceeds, to a large degree, by means of infrared (IR) radiation. Since heat production is a physiologically conditioned phenomenon, the diagnostics of thermoregulatory and heat exchange status of the organism is highly informative and important for medicine and human physiology (Jones (1998), Vainer (2005)). Infrared thermography (IRT)-based biophotonics is aimed at the measurement, visualisation and quantitative analysis of thermal radiation emitted from living object surfaces. Many pathological processes change normal temperature distribution on a body surface and, in some cases, such changes pass ahead of other clinical manifestations. It is impossible today to visualize and provide an objective quantitative monitoring/analysis of rapid temperature changes over the entire surface of the body by any means other than thermal imaging or IRT. This method has become of greater interest in the past years in different research areas including medicine (Vainer (2008), Fernandes et al. (2014), Lee et al. (2015)). The development of new physically-based methods and techniques aimed at pre-clinical diagnostics is of the highest social significance. One of the recent promising trends here is the approach called interventional infrared thermal diagnostics (Vainer (2012a)). Its realization involves both the purposeful provocative load applied to an organism and subsequent real-time registration of the organism response. The interventional-based approach considers the human body as a kind of "black box", the properties of which can be examined by means of sending disturbances into it from without. It is expected that the recorded responses produced by a healthy body and a body with pathologies will be different, as the external excitation of the organism, initially, has a target diagnostic orientation. The possibility to fulfil such an approach has appeared just recently, with the advent of modern focal plane array (FPA)-based IR cameras whose frame rate (hundreds fps) and temperature sensitivity (hundredths of a degree) many times exceeds similar parameters of the previous, older generation, thermographs. The diversity of systemic vascular reactions observed in different individuals, who were subjected to only IRT examination (Vainer and Markel (2010, 2015), Vainer (2010)), generated a need for integration IRT with different diagnostic techniques in order to advance the degree of diagnostic accuracy. A prototype of such a combined IRTbased diagnostic complex and the results of a pilot study obtained with its use are described in this paper. 2. Methods IR camera TKVr-IFP/SVIT with a built-in InAs-based FPA detector was used as a basic measuring thermal imaging system. It had the following specifications: temperature sensitivity – 0.03 qC; frame rate – up to 100 fps; spectral range – 2.45-3.05 Pm; detector temperature – 78 K. Temperature values indicated on the thermograms acquired by the IR camera depend almost not at all on the distance between the camera and the measured object (a part of body, etc.). A slight deviation of the radiant flux resulted from atmospheric adsorption does not show itself at low distances typical of a laboratory room. An IR camera was set at a distance of 3–4 metres from the subject. As this took place, all four limbs of the subject were falling within the camera view. Besides the short-wave IR camera mentioned above, an alternative one was tested. It contained an uncooled 8-14 Pm 320u240 FPA detector composed of VOX-based microbolometers (Dem'yanenko et al. (2010)). Avoiding the use of liquid cooling agents or micro-refrigerators reduces the weight, size and cost of thermal imaging system. It significantly increases the usability and applicability of this kind of medical instruments as there is no need to have liquid nitrogen at hand. Temperature sensitivity of the uncooled IR camera was about two times worse than that of cooled InAs-based one. This fact, as well as different working spectral ranges of the above-mentioned two types of camera, required at least qualitative comparison of their performances, as regards application to medical problems. Because of our prime interest was connected with the search for a correlation between IRT data and data obtained using independent diagnostic methods, we additionally involved: 1) laser Doppler flowmetry (LDF) as a direct method of microcirculatory perfusion measurement; 2) several means to monitor the key cardiovascular activity indices – pulse oximetry, sphygmography, heart rate monitoring. Sensors (red and IR channels) of two LDF devices (LAKK-01 and LAKK-02) were fastened to the fingers of both hands and to a toe. Pulse-oximetric measurements were performed using a patient monitor sensor, fastened to

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the nail bone of the individual’s finger. Sphygmogram, heart rate and the dynamics of the oxygen content in the blood were displayed on the screen and continuously recorded on digital media in the video mode for further analysis. A typical examination procedure was as follows. Prior to interventional exposure, the examinee with bared hands and feet, resting on the thermally low-conductivity support, took a comfortable sitting position. A circular cuff of a standard tonometer, destined to produce the interventional effect, was put on his right shoulder. During this period, an individual underwent the stage of adaptation to the ambient conditions. This stage, from the very beginning, was accompanied by IRT, LDF and other measurement data records. All the recorded results served as initial data for subsequent digital processing and analysis. They were also synchronously and continuously displayed on monitors. In particular, it allowed judging if the examinee's state was already steady or not as yet. Then, the right-hand cuff was inflated to a pressure of 200 ± 20 mmHg for the purpose of crossclamping (forced compressive occlusion) of shoulder great vessels. In three minutes, the cuff was quickly deflated following which all the involved devices continued recording for a further 10-20 minutes or more. Brief one-sided arm cuff compression was chosen as a basic interventional impact upon the body on the grounds that a similar approach was successfully used before for the same purposes and helped to objectively and reliably demonstrate, via IRT, how the human systemic vascular reactivities were really distinct from each other (Vainer and Markel (2010, 2015), Vainer (2010)). It should be noted that he warmer the skin was, the better the physiological processes were manifested in response to an interventional action on the organism. The initial skin temperature excess of about 4 qC over ambient temperature is usually sufficient to observe most of critical alterations. To get a greater insight into the systemic cardiovascular reactions of the organism, preliminary soft heating of cold limbs can be recommended. Sixteen people were examined with the integrated technique described above. The studies were carried out in accordance with the World Medical Association (WMA) Declaration of Helsinki – Ethical Principles for Medical Research Involving Human Subjects – and were approved by the Institute of Chemical Biology and Fundamental Medicine SB RAS Ethics Committee. An informed consent concerning the participation in relevant tests was obtained from each participant prior to his involvement in the study. 3. Results and discussion 3.1. Blood vessels short-term compressive occlusion as a discriminating test Similar to that shown in (Vainer (2012b)), radically different systemic cardiovascular reactions to short-term crossclamping of the upper limb main vessels were recorded in different individuals: from full synchronism to complete indifference. The supporting examples are demonstrated in Fig. 1. Like the IR data, LDF-signal waveforms also demonstrated the systemic response to interventional load (Fig. 2, left panel), although it was less clearly expressed as compared to that obtained with IRT. In the contralateral limb of the labile patient, the decay of a

Fig. 1. Temperature variation in fingers and toes before, during and after a short (3 min) compressive occlusion of the right hand’s great vessels. Left panel – labile individual, who is sensitive to the above-mentioned interventional exposure, right panel – indifferent individual. RH – right hand, RL – right leg, LH – left hand, LL – left leg.

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Fig. 2. Left panel – comparison of the left (contralateral)-hand fingers LDF responses before, during and after a short (3 min) crossclamping of the right-hand great vessels. Labile and indifferent individuals are the same as those mentioned in Fig. 1. Right panel – temperature change of the examinee’s right hand fingers measured during premedication and initial narcosis. Checkpoints A–D are shown in the inserted thermogram.

high-frequency mode in the perfusion characteristic was observed since the beginning of crossclamping, and the increase of signal alteration was also registered in the lower limb. The behaviour of the indifferent individual's LDF characteristic differed from that of the labile one, and the above-mentioned effects almost did not appear in their extremities. The pulse oximetry results obtained from the labile individual simultaneously with thermal imaging and LDF demonstrated the systemic reaction to external interventional load rather weakly. In the contralateral hand, the blood oxygen content increased by about one percent and the average heart rate also slightly rose. The difference observed in labile and indifferent examinees shown in Fig. 1 and Fig 2, left panel, discloses that IRT-LDF data relationship in fact exists. This anticipates an attacking the important scientific problem on the interrelation between macro-effects in blood supply, which are manifested by surface temperature change, and microcirculation reflected by LDF in the same part of body. We made a rough quantitative comparison of the biomedical results obtained using IR cameras of different spectral ranges, namely, 2.45-3.05 Pm and 8-14 Pm. Thermograms were recorded synchronously with almost the same view angles from the same point. A comparative analysis of the obtained thermal images showed that, despite different spectral characteristics, thermal representations of human skin differed from each other rather poorly. 3.2. Thermal response of the organism to high-oxygen inhaled air IRT method was also tested with reference to its suitability to serve as a tool aimed at monitoring the systemic cardiovascular reactions arisen in response to general hypoxia or hyperoxia applied to the organism. These two conditions appear, particularly, in the course of routine surgical procedures under general anaesthesia with the implementation of artificial pulmonary ventilation (APV) at the stage of initial narcosis. Subsequent to the introduction of short muscle relaxants, respiratory muscles relax, spontaneous respiration stops and trachea intubation is performed with the following implementation of APV using oxygen-air mixture with a different percentage of oxygen. A detailed analysis of the changes observed in a skin thermal pattern may allow revealing the fundamental biophysical mechanisms of the central regulation in humans. A temperature change in the right-hand fingers in the course of a surgical operation, when standard initial narcosis and trachea intubation are applied, is shown in Fig. 2 (right panel). It is clearly seen that the increased oxygen content in the gas mixture causes, on the expiry of about 1 min, a sharp temperature rise in fingers. This phenomenon may take place either due to the intensification of metabolism in the peripheral tissues or due to vasodilation of the vessels that provide such tissue trophism. The expected temperature drop at the stage of hypoxia was not observed in this case, as the fingers initial temperature was comparable to the ambient temperature, and heat exchange mechanisms that could cause further skin cooling were missing.

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4. Conclusion High informativity, absolute harmlessness, ease-of-operation, portability, applicability to all groups of humans prove significant prospects for application of IRT-based technologies to biomedical sphere. It concerns here, in particular, the use of both mid-IR (2.45-3.05 Pm) cameras with an InAs-based cooled FPA-detector and IR cameras equipped with a VOX microbolometric long-wave (8y14 Pm) uncooled detector. The integrated approach to the studies of systemic cardiovascular reactivity in humans is first realized by multimodal measurements with synchronous use of IRT, LDF and pulse oximetry diagnostic facilities. With this approach, the inequality in systemic vascular reactivity is evidenced in human individuals who may be classified as labile and indifferent to transient external load. The obtained results give food to physiologists and functionalists for thought towards the central circulation and microcirculation interplay in the human body. An abrupt increase of skin temperature in distal parts of the upper limb during standard surgical operation is first revealed on the stage of premedication and initial narcosis, once the oxygen content in the ventilation gas mixture is increased. The addition of remote thermal control to anaesthetic monitoring expands awareness of an anaesthesiologist and a surgeon about the state of a patient's organism during surgery. The hardware model of the combined diagnostic system tested in this work is easily reproducible in the form of a ready-made equipment in clinical/rehabilitation practice and human screenings. These systems may be exploited as a part of the patients standard clinical examination protocol. Synchronous use of FPA-based IR cameras and additional independent techniques for body state monitoring as an integrated survey of healthy individuals and patients demonstrate the potential of such an approach for increasing the diagnostic objectivity and reliability. Acknowledgements This work was supported by the Russian Foundation for Basic Research (Grant No. 15-02-07680) and partly by the Siberian Branch of the Russian Academy of Sciences (integration project No. 40B). The authors are grateful to E.V.Kovaleva, Yu.G.Kuleshova, A.I.Molokoedov, Ya.V.Novikova, A.Yu.Patrushev for their assistance in the patients examination; to M.A.Dem'yanenko and I.V.Marchishin for the provision of the uncooled IR camera and for the participation in relevant measurements. References Dem'yanenko M.A., Fomin B.I., Vasil'ieva L.L., Volkov S.A., Marchishin I.V., Esaev D.G., Ovsyuk V.N., Dshhunyan V.L., Volodin E.B., Ermolov A.V., Usov P.P., Chesnokov V.P., Chetverov Yu.S., Kudryavtsev P.N., Zdobnikov A.E., Ignatov A.A., 2010. Uncooled microbolometric 320×240 photo-detector based on sol-gel VOX. Applied Physics 4, 124–130. Fernandes A.A., Amorim P.R.S., Brito C.J., Moura A.G., Moreira D.G., Costa C.M.A., Sillero-Quintana M., Marins J.C.B., 2014. Measuring skin temperature before, during and after exercise: a comparison of thermocouples and infrared thermography. Physiological Measurement 35, 189–203. Jones B.F., 1998. A reappraisal of the use of infrared thermal image analysis in medicine. IEEE Transactions on Medical Imaging 17, 1019– 1027. Lee Y.S., Paeng S.H., Farhadi H.F., Lee W.H., Kim S.T., Lee K.S., 2015. The effectiveness of infrared thermography in patients with whiplash injury. Journal of Korean Neurosurgical Society 57, 283–288. Vainer B.G., 2005. FPA-based infrared thermography as applied to the study of cutaneous perspiration and stimulated vascular response in humans. Physics in Medicine and Biology 50, R63–R94. Vainer B.G., 2008. Focal plane array based infrared thermography in fine physical experiment. Journal of Physics D: Applied Physics 41, 065102. Vainer B.G., 2010. Systemic response of the organism to local break of the blood flow: finding and quantitative characterization using infrared thermography, International Scientific-Practical Conference "High Tech, Basic and Applied Studies in Physiology and Medicine", vol. 2. St.Petersburg, Russia, pp. 165–167. Vainer B.G., 2012a. Interventional infrared thermal diagnostics in medicine and physiology, 11-th International Conference on Quantitative InfraRed Thermography, QIRT 2012. Naples, Italy, paper ID-340. Vainer B.G., 2012b. Investigation of circulation in humans with the use of infrared thermography, in "Circulatory System and Arterial Hypertension: Experimental Investigation, Mathematical and Computer Simulation" . In: Ivanova, L.N., Markel, A.L., Blokhin, A.M., Mishchenko, E.V. (Eds.). Nova Science Publishers, Inc., New York, pp. 207–234. Vainer B.G., Markel, A.L., 2010. Imaging and quantitative characterization of bilateral vasomotor reactions in humans using high-performance thermography, 10-th International Conference on Quantitative Infrared Thermography, QIRT10. Quebec City, Canada, pp. 91–94. Vainer B.G., Markel, A.L., 2015. Systemic vascular response to brachial arteries crossclamping may prognosticate the outcome of remote ischemic preconditioning. Medical Hypotheses 84, 298–300.

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