WO2009018639A2

WO2009018639A2 - A system for diagnostic investigation of metabolic disorders through thermal signature

Info

Publication number: WO2009018639A2
Application number: PCT/BR2008/000232
Authority: WO
Inventors: Nélson Afonso LUTAIF; José Antonio Rocha GONTIJO; Eduardo Melani Rocha
Original assignee: Universidade Estadual De Campinas - Unicamp
Priority date: 2007-08-06
Filing date: 2008-08-06
Publication date: 2009-02-12
Also published as: BRPI0705855B8; BRPI0705855B1; WO2009018639A3; MX2010002717A; BRPI0705855A2

Abstract

The present invention relates to a high-precision apparatus for registering calorimetric variations resulting from pathologic processes. Such registering is performed based on the increasing temperature rise in areas next to the thermal center located on the central nervous system as a consequence of a passive heating carried out by thermal insulation.

Description

Specification of Patent of Invention for "A SYSTEM FOR DIAGNOSTIC INVESTIGATION OF METABOLIC DISORDERS THROUGH THERMAL SIGNATURE" TECHNICAL FIELD

The system of the present invention involves a new approach to calorimetry recording through dynamic infrared thermography, which has the feature of preventing the heat produced by metabolic activity from being irradiated to the environment, thereby improving its diagnostic range.

Thus, this information recorded by thermography will be directly associated with the basal metabolism and enables anticipating functional disorders in key organs of the metabolism and illnesses related to energy production and conservation. Such method developed herein is non-invasive, easy and safe to carry out.

BACKGROUND OF THE INVENTION

Metabolic disorders such as obesity, diabetes mellitus, metabolic syndrome, hypothyroidism, among others, are becoming increasingly prevalent. Preventive measures, as well as changes in cultural habits, have been suggested in order to reverse this scenario.

Recording the calorimetric activity of the basal metabolism is based upon the ability chemical reactions have to release heat during the transfer of free energy from the reagent to the products, as a part of the glucose degradation process and, as a result, to form ATPs. Besides this heat source, living organisms continuously use chemical energy potentially stored in phosphate bridges contained in ATP molecules. Uses for this energy include: keeping electrochemical gradients through cell membranes, synthesis of macromolecules, and muscle contractions. In this process, whose reactions are exothermal in nature, the internal temperature is kept at stable values. Thus, organic heat radiation is made according to the metabolism and is related with ATP synthesis and hydrolysis. This rate, called the thermal signature, is stable and characteristic of each individual, and is determined by genetic and environmental factors.

Dysfunctions in metabolic activity may be anticipated by knowing the thermal signature, and from that, individualized measures may aid in curbing epidemic public health problems.

There are three different methodologies for monitoring the heat irradiated by metabolic activity: a) direct (DC), b) indirect (IC), and c) thermographic calorimetry. DC is a reliable technique for fully quantifying the thermal energy expended by organic chemical reactions. It requires, however, an environment with a surrounding laminar flow and extended periods of measurement in a state of fasting and physical restriction, as well as accurate thermal sensors, complex calibrations, and an infrastructure that cannot be carried to routine medical areas. In clinical studies, taking into account the extended examination period, hormone release influences with circadian rhythms are observed: ACTH and Cortisol.

IC is a more affordable methodology, with a lower operational cost, easier calibration, and has as its guiding principle the oxygen consumption and CO₂ release through respiration, since 90% of reactions used in the formation of ATPs involve oxygen consumption and CO₂ formation. The same shows some drawbacks: lower accuracy, involving other techniques for validation of experiments (markers labeled with stable isotopes; glucose or water molecule), collection of final metabolites other than CO₂ (nitrogenous waste), and influence of external factors (visual and auditory stimuli).

Finally, the concept of thermography involves measuring the infrared radiation emitted by the body surface. This technique is intended to provide the fastest and most direct measurement. While measured values, when compared with IC technique, exhibit a good correlation, a need still remains for validation with DC technique. As a drawback it presents the insuperable obstacle of recording only the cutaneous or peripheral temperature, the value of which is strongly affected by the vasomotor tonus and, consequently, by the autonomic nervous system. Attempts to detect tumoral anomalies, another form of use for thermography, were still not fully incorporated into routine medical practice. Presently researches are directed to cell culture analysis.

SUMMARY OF THE INVENTION

The present invention provides a high-precision system for recording calorimetric variations resulting from pathological processes, taking into account the increasing temperature rise in the areas next to the thermal center located in the central nervous system, as a consequence of a passive heating carried out by thermal insulation. BRIEF DESCRIPTION OF THE

DRAWINGS

Figure 1 shows comparative thermal curves, pointing out the normal response (Sham) and the curve with renal injury (Nx or nephrectomized). It can be clearly seen a detachment of the curves due to the loss of renal functional capacity and the resulting reduced heat generation.

Figure 2 shows a scheme of the system which involves registering the heat production in individuals subjected to an isothermal environment, obtaining the temperature through infrared thermography, calculating the thermal signature, and analyzing the data.

Figure 3 shows a high-precision and high- definition pyrometer model for registering the temperature in areas of the retina. [Model Pyro Microterm with detection of targets up to 0.01 mm in size and wavelength of 18 angstroms] DETAILED DESCRIPTION OF THE INVENTION

Through experiments carried out, we came to the conclusion that monitoring the internal temperature during the thermal insulation caused by immersion in isothermal water (HA) has proven to be a reliable marker of metabolic activity, both in normal and pathologic states.

Thus, in the HA closed system, temperature increases gradually, according to the generation of heat carried out by the metabolism. This mechanism has proven to be sufficiently sensitive to identify renal injuries just by temperature differences in thermal curves, obtained during the experiment, since kidney is a key organ in thermoregulation, and, hence, participates in thermal signature. This experiment, which gives rise to the system, was conduced in a thermal bath with a digital thermostat and a high-precision digital thermometer coupled to a thermal probe, and confirmed, with important data, hypotheses of thermal signature and homeostasis in the closed system. During 30 minutes of immersion in water near to internal temperature, a temperature rise was evidenced at a rate which is proportional to the basal metabolism rate, according to the first law of thermodynamics :

A U (internal energy) = Heat - Work Since in the experiment the heat released into the system is zero due to the absence of temperature difference and the animal is at rest, the work is also zero. Thus:

Δ U=O, or: (final) Energy - (initial) Energy = 0

Being the potential chemical energy (metabolism) correspondent to the initial energy and the transformation of this energy from chemical into thermal correspondent to the final energy, it follows that:

Basal Metabolism Rate = Thermal Energy Variation, or Mass^A(³A) = dT/dt x mass x heat cap.

Where: dT/dt = instantaneous temperature variation (Celsius) with time (hour). This thermal rate variation, in our experiment, showed a result which was very near to the normal theoretical value. In addition to these data, it was also possible to calculate the basal metabolism rate through the area over the curve. Thus, our invention accurately reflects a thermal variation compatible with the normal basal metabolism rate, and in metabolic disorder conditions, such as predisposition towards diabetes mellitus or dysfunction of organs related to the metabolism (liver or kidney), it will be possible to detect them in advance.

As accuracy is of vital importance in this model, a new system was designed for measuring the internal temperature during immersion and detection of thermal irradiation.

It is a dynamic thermographic monitoring, coupled with a system that enhances its information, combining both the advantages of thermography practicality and DC accuracy.

This innovative concept is based on registering the temperature variation caused by HA, directly from hypothalamic thermoregulatory centers, which are located on the central nervous system. This measurement will be made through ocular fundus or tympanic membrane thermography using a pyrometer (shown in figure 3 in the drawings) in order to detect the variation of thermal radiation resulting from intracerebral circulation, which has the characteristic of being stable and faithful to that observed in thermoregulatory centers. This model overcomes the limitations imposed by conventional thermography: superficiality and influence from the vasomotor tonus. On the whole, clinical tests should have a maximum duration of 15 minutes, checking the temperature at every minute. Patients should be immersed or wearing hot-water vests (Figure 2). The ocular fundus should be observed with an infrared- sensitive, portable thermograph, having a detection of 1 to 2 Angstroms and sensitivity to 0.01/0.001 degree Celsius.

Weight and height data from individuals were input into a spreadsheet, and after serial measurements for 15 minutes were taken, individual's thermal signature calculation was obtained and compared with a standard curve for age, gender, and thermal standards of every pathological situation.

The advantages are related to the absence of secondary effects or the need of collecting biological materials or even a costly infrastructure, since clinical tests are easily realizable and have a high diagnostic range (sensitivity).

Claims

1. A system for diagnostic investigation of metabolic disorders, CHARACTERIZED by comprising registering calorimetric variations resulting both from normal and pathologic processes, wherein such variations comprise an increasing temperature rise in areas near the thermal center, as a consequence of a passive heating carried out by thermal insulation.

2. System, according to claim 1, CHARACTERIZED in that the thermal center is located on the central nervous system.

3. System, according to claim 1, CHARACTERIZED in that the thermal insulation is carried out by immersion in isothermal water.

4. System, according to claim 1,

CHARACTERIZED in that the thermal insulation is carried out through the use of hot- water vests.

5. System, according to claim 1, CHARACTERIZED in that the measurement is carried out through ocular fundus or tympanic membrane thermography.

6. System, according to claim 5, CHARACTERIZED in that the ocular fundus or tympanic membrane thermography is carried out with a pyrometer.

7. System, according to claim 1, CHARACTERIZED in that clinical tests should last a maximum of 15 minutes.

8. System, according to claim 1, CHARACTERIZED in that the temperature check must be performed at every minute.

9. System, according to claim 1, CHARACTERIZED in that the ocular fundus or tympanic membrane should be observed with a infrared-sensitive thermograph.

10. System, according to claim 1, CHARACTERIZED in that it can also be used in animals.