An intersectoral problem: Non-invasive, inexpensive and accurate assessment of adipose tissue (brown adipose tissue) activity is crucial in the fight against metabolic pandemics such as obesity and in various industries (e.g., foods, pharmaceuticals). However, to this day, the only technique available to measure the activity of this tissue is positron emission tomography / computed tomography imaging of the glucosetracer 18 F-fluorodeoxyglucose, a highly invasive technique that is harmful for human health, expensive and requires extensive equipment and facilities. The development and validation of non-invasive and practical techniques to accurately estimate human brown adipose tissue activity requires the creation of new technology and the advancement of the current state of the art in human brown adipose tissue biology, thermoregulation, image analysis, and hardware/software design. Companies particularly Small - Medium Enterprisies do not have the technical capabilities or the facilities to conduct Research and Development activities at the level of excellence required for such development. Academic institutions have the capacity to conduct the Research & Development necessary to develop the concept into a market product. However, they lack a viable supply chain and the expertise to develop the prototype post project and to exploit the product in the market.
Overall objective: To solve the above intersectoral problem, the ICI-THROUGH project will create a sustainable innovation platform of intersectoral collaboration between two academic, University of Thessaly
and University of Porto and two industrial, Imedica SA and Center of Technology Research and Innovation Ltd., European participants to exchange knowledge on the development of non-invasive techniques to estimate human brown adipose tissue.
Innovation Outcomes: Obesity and its related disorders are a major global health concern. The relatively recent discovery of brown adipose tissue in adult humans has provoked a plethora of theories and experiments on the metabolic capabilities of brown adipose tissue and its potential for the prevention and/or treatment of obesity and obesity-associated diseases, including type 2 diabetes, cardiovascular disease and several cancers. Brown adipose tissue is located in the thorax and its main function is non-shivering thermogenesis, that is, generate heat to maintain body temperature during exposure to cold. This process utilizes high amounts of energy. Thus, measurement of an individual's brown adipose tissue activity has enormous value for weight management and predisposition to cardio-metabolic disease. It is also critical for treating patients suffering from thyroid, metabolic and thermoregulatory abnormalities. Thus the innovative aspects of the ICI-THROUGH, in terms of new products, processes and engineering applications are significant. For instance, developing and commercialising non-invasive devices to accurately estimate brown adipose tissue activity will revolutionise the global anti-obesity products market that is currently estimated at 50 billion euros. Moreover, food or pharmaceutical companies will be able to use these non-invasive devices to test the effects of different products on thermogenesis, metabolic rate, energy balance and/or weight loss.
Existing Solutions: The positron emission tomography / computed tomography imaging of the glucosetracer 18 F-fluorodeoxyglucose scan is a laboratory technique that can accurately assess brow adipose tissue activity but it involves very expensive, time consuming and tedious procedures, requiring very sophisticated equipment, highly trained staff and extensive facilities. More importantly, this method is extremely invasive and harmful for the users’ health due to high radiation exposure (equivalent to ~110 typical X-ray scans). As such, it is performed almost exclusively for cancerous tumour detection.
Because of the aforementioned, high radiation exposure associated with the positron emission tomography of 18 F-fluorodeoxyglucose technique, it is necessary to develop non-invasive, simple, practical and accurate techniques to assess brown adipose tissue activity in healthy individuals. Given that brown adipose tissue is a heat-generating tissue, the ICI-THROUGH project will use two heat-based approaches to develop non-invasive techniques to estimate human brown adipose tissue activity:
Heat flux transducers represent a low cost, simple and valid method of quantifying heat flux from the human skin. A heat flux transducer is analogous to a thermopile, consisting of multiple thermocouples connected in series, placed across a matrix of known thermal resistance. The voltage generated by the heat flux transducers (usually in the magnitude of millivolts) represents the local heat flux and is proportional to the quotient of the temperature gradient and the thermal resistance across the heat flux transducer matrix. Although heat flux transducers represent a simple method of quantifying heat flux from human skin, studies have reported as much as 20% error between manufacturer-supplied calibration constants and those derived experimentally. This error has been attributed to the added thermal resistance caused by the addition of the waterproofing membrane applied post manufacturer calibration. Also, placement of a heat flux transducer on the surface of the skin may compromise the validity of heat measurements due to the additional layer of thermal resistance associated with the sensor itself. Thus, applying heat flux transducers on supraclavicular skin to assess brown adipose tissue activity remains a complex task that requires further research to become commercially exploitable. This is because a large number of equations and approximationsare required and the approach must bevalidated in both laboratory and field settings.
Infrared thermography has extensive applications in several engineering and science fields. It provides a very practical and cost/time effective technique to monitor surface temperatures without the need of precise positioning of sensors attached to the surfaces under scrutiny. Furthermore, it allows the acquisition of temperature maps in a straight forward way, which enables analyses in which the temperature distribution along the surfaces is also of interest (e.g. identification of heat leaks, spotting of non-homogeneous insulation, identification non-even materials properties, identification of inflammation processes in living tissues,etc.). Yet, for improved accuracy, it is crucial to have accurate information about the optical properties of the surfaces to monitor (e.g. emissivity) and to reduce, as much as possible, the sources of interferences during measurements (e.g. other sources of radiant heat, surfaces reflecting radiant heat from distant locations, oscillation of the surface optical properties over time (e.g. in living tissues due to sweating,etc.). Given the advantages of infrared thermography, it has high potential as a non-invasive, simple, practical and accurate technique to assess brown adipose tissue activity in healthy individuals. However, a significant amount of research is still required for the development of appropriate techniques to systematically process the thermal images to allow correlation with brown adipose tissue activity. We recently conducted a pilot study which demonstrated the potential for in frared thermography as a non-invasive, simple, practical and accurate technique to assess brown adipose tissue activity in healthy individuals. In this study, a young male adult 36 years old was exposed to moderate cold for 30 minutes. Immediately following the exposure, we use dinfrared thermography to measure the subject’s upper body skin temperature. The results demonstrated increased heat production in areas known to contain brown adipose tissue that is activated during cold exposure.
In conclusion, while the above logic regarding heat flux transducers as well as the pilot data from infrared thermography demonstrate the potential of these techniques in detecting brown adipose tissue non-invasively, there are significant technical challenges and risks which currently prevent their exploitation. The project’s research and training activities will address the following scientific and technology challenges :
1.The optimum cold exposure protocol to be used as a brown adipose tissue activation stimulus remains to be determined. This protocol will also act to eliminate the effects of previous exposure to hot or cold environments.
2. It is necessary to develop techniques for minimization of interferences during measurements either for heat flux transducers or infrared thermography.
3. Regarding thermography, the procedures for acquisition of thermograms in a systematic and (radiant-wise) reproducible way must be determined, together with algorithms for post-processing of the resulting thermograms.
4. Regarding heat flux transducers, it is necessary to quantify the error between manufacturer-supplied calibration constants and those derived experimentally as well as the error due to the placement of the heat flux transducer on the surface of the skin.
“This project has received funding from the European Union’s Horizon 2020 research and innovation
programme under grant agreement No 645710”