Introduction

Our conception about RTM-Diagnosis first of all is based on our own investigations, which we have conducted for 6 years in five leading MoscowOncological Centres. For this period we have performed 3500 RTM-examinations, and 540 women of them were cancer patients. Also our views were formed by investigations of М. Gautheria, who is a French scientist in breast thermobiology. He worked in this field during 16 years. His data published in (13) are based on investigation of 85000 patients. In 247 patients he measured temperature invasively with the help of fine-needle thermoelectric probes. These unique experimental data are a base of the modern concepts about temperature distribution in the breast.

Basis of Microwave Radiometry

1. Problems of Breast Cancer Detection at an Earlier Stage

At present earlier detection of breast cancer is one of the most important problem. This decease in several countries is the main course of depth of women. One in every 9 women in the United States will experience breast cancer during her lifetime.

Specialists say that early detection of the breast cancer by the clinical methods is later biologically. Screening once in 12-24 months is not enough to detect fast growing breast cancer. Note that patients with fast growing breast cancer is a quarter of all breast cancer patients. …So it is expedient to use screening in conjunction with other non-invasive investigative methods [1].

The microwave radiometry [2-5] is based on measuring the intensity of natural electromagnetic radiation from a patient’s tissue. This intensity is proportional to temperature of tissue. The change of the temperature (thermal abnormality), that is a basis of the earlier detection of breast cancer, may be caused by higher metabolic activity of tumors.

It should be noted that thermal changes precede to the anatomical changes that can be detected by traditional methods such as ultrasound, mammography and palpation. Thus microwave radiometry is a very promising method for breast cancer detection at an earlier stage.

2. Basic Concept of Microwave Radiometry

Microwave radiometry  measures natural electromagnetic radiation from a patient’s internal tissue at microwave frequencies.

The intensity of the radiation is proportional to the temperature of tissue. So we can say that microwave radiometry allows us to measure internal temperature of tissue and display it on the monitor of the personal computer.

3. Difference between Microwave Radiometry and Infrared Thermography

4. Breast Cancer Detection Methods

The main diagnostic means used for detection of oncological disease may be divided into three groups that are shown in fig.1.

The first group includes physical examination methods. These methods are effective when the tumor is formed, and when it has a well delineated boundary.

Unfortunately in this phase, when tumors can be detected by physical methods (e.g. in average the tumor only of 1-2 cm can be detected by mammography) metastasis may have occurred.

The inevitable radiation load, used for mammography, does not allow one to conduct screening more than once every six months.

In the second group the most reliable method is histology. However it is applied during or after the operation.

Applying cancer markers is developing, however they are designed for diagnosing oncological diseases of only several organs, and they are not always effective.

5. Advantages of Microwave Radiometry

   Non-hazardous

Microwave radiometry is non-hazardous both to the patients and to the personnel taking the thermograms, as during the examination the intensity of natural electromagnetic radiation from the patient’s tissue is measured only.

   Non-invasive

Temperature is measured non-invasively.

   Earlier detection of diseases

It should be noted that thermal changes precede to the anatomical changes that can be detected by traditional methods such as ultrasound, mammography and palpation. Thus microwave radiometry is a very promising method for breast cancer detection at an earlier stage.

   Detection of fast growing tumors 

The specific heat generation in the tumor is proportional to grow rate of the tumor. So fast growing tumors are “hotter” and they are more contrast in thermograms. Thus microwave radiometry is an unique method that allows to detect first of all fast growing tumors. Using microwave radiometry (RTM-Diagnosis) in conjunction with other tradition methods allows to select patients with fast growing tumors [9].

   Ability to detect patient with increased proliferative activity of cells

The important feature of the microwave radiometry is that it can distinguish mastopathy and fibroadenoma with proliferation from mastopathy and fibroadenoma without proliferation. So the method allows to select patients who are at the greatest risk of having breast cancer.

   Ability to monitor treatment

Microwave radiometry is non-hazardous both to the patients and to the personnel taking the thermal measurements, so it can be effectively used for the monitoring of treatment.

6. Historical Reference

The temperature of the human body (oral temperature) was measured for the first time with the help of a mercurial thermometer (which had been just developed) in Germanyin 1851. Since then temperature and its dynamic analysis has become one of the traditional diagnostic methods. Non-invasive measurement of internal organ temperatures began one hundred years later due to the development of night vision equipment during the Second World War.

By this method skin temperature was measured. The skin temperature partially reflects internal organ temperature, due to heat transfer. 20 years later (1972) the fist investigation of measuring internal tissue temperature (tumors of mammary gland) were held. The measurement was based on receiving natural electromagnetic radiation at microwave frequencies. These studies were successful, as tissue is transparent enough for waves of this frequency range.

may be divided into preclinical and clinical phases. The border between these phases is relative as it is determined by diagnostic equipment abilities. Therefore it is natural to apply the tumor growth behavior studied for the clinical phase to the preclinical phase (doubling time is constant for a specific patient). The tumor growth is shown in fig. 2.

When the doubling time is constant the tumor growth is represented by the exponential curve. It should be noted when the tumor mass doubles the tumor diameter increases  times. Also tumors with short doubling time have a high specific heat generation (Watt/cm³). As when the tumor grows rapidly, energy consumption increases and so heat generation rises. This relationship is shown in fig. 3

Therefore most of dangerous tumors (tumors with short DT) can be detected by thermal methods first of all. It means that the thermal methods allow to select patients with rapidly growing tumors. According to current data these patients are a quarter of all breast cancer patients.

8. Heat Transferring in the Bio-object

Heat transfer within breast tissues. The best explanation of heart transfer was made by Gautherie. Therefore I will quote his work [1]. According to M. Gautherie "temperature and blood flow pattern in cancerous mammary tissues", result from two phenomena: heat transfer from the cancer into the surrounding tissues, and vascular reactions.

Fig. 4   Tumor and blood temperature in breast carcinomas. An example of a series of measurements of tumor temperature and venous and arterial blood temperature taken during surgical management (mastectomy) of mammary carcinomas with various local­izations. Measurements were carried out by means of thermometric fine-needle probes, five times for each temperature (the vertical segment indicates standard deviation from the mean value). In all cases investigated, tumor temperature was significantly higher than blood temperature, and venous blood temperature was higher than arterial blood temperature.

Heat transfer occurs by tissue conduction as well as blood convection. However, from the physiologic viewpoint, it seems to be more appropriate to distinguish between the two following processes (Fig. 5): 1) "effective" conduction, including conduction in the physical sense (Fourier's law) and convection by the capillary vessels assumed to be distributed isotropically (see above); 2) convection through the relatively large vessels, the veins essentially, according to Newton's law. It is noteworthy that maximal capacity of heat transfer by convection through large vessels is much higher than by tissue conduction and capillary convection, up to 100 times, approximately. Never­theless, the relative contribution of the various processes depends on the actual vascularization, which is largely different from one breast to the other, partic­ularly under malignant conditions. Furthermore, conduction of_heat is easier along the galactophorous ducts as was demonstrated by intramammaryjnea-surements too. This anisotropy of thermal conductivity may explain the relative hyperthermia of the nipple observed in some carcinomas, depending on tumor localization.

Fig. 5.

9. Temperature Pattern in Human Tissue

In some parts of a human body the temperature is constant due to homeostasis. This temperature is approximately equal to the temperature measured in axial, oral and rectal areas (36.5°С – 37.0°С). The central nervous system, thorax organs, the abdominal area, all have a constant temperature.

When the room temperature is 20-25°C the skin temperature lowers to 32-33°C so there is a temperature gradient between the skin temperature and the internal temperature.

This temperature gradient and its dynamics, depending on room temperature, are shown in fig. 6.

Fig.7 shows results obtained by Gautherie [1] with the help of fine-needles.

We can see that the temperature in cancer is three degree higher than the temperature in the healthy breast. In this example the skin temperature near the tumour is 2 degree higher than the skin temperature in the healthy breast too.

Also, Gautherie published the diagram, when the skin temperature near the tumour is less than it is in the healthy breast (Fig. 8).

10. Cancer tumor temperature.

Gautheria in [13] published his data of the cancer. These data you can see in Fig.9.

On the base of these data we have written a very simple equation of the tumour temperature.

R – tumour radius

D_T – doubling time of the tumour

B - BIOT'S number

Fig. 9. Rheoelectric simulation of heat transfer conditions in cancerous breasts: Experimental chart giving the specific heat production of cancer tissue (q⁰) versus peritumoral hyperthermia (T = temperature difference between the periphery of the tumor and the symmetrical area on the contralateral healthy breast), Biot's number (B), and tumor diameter (D_T). These curves, fitted by hand from the analog model of heat transfer, allow direct evaluation of q⁰ from measurements of geometric parameters on mammography (s, D_T, and D_B), and thermal parameters (T and _e). On account of the ranges of variations of _e and D_B, q⁰ does not depend on tumor depth. The coefficient h may be assumed to be constant and equal to 1 x 10^-3 W/cm²/ ^oC under controlled conditions (room temperature at 21 ± 1°C, no air draughts).

11. Electromagnetic Radiation from Heated Objects

According to the law of physics, any object above zero degrees Celsius emits radiation at all frequencies and, in particular, in the microwave region, that is used in microwave radiometry.

This feature of heated objects is used for measuring averaged internal tissue temperature and detecting thermal abnormalities (higher or lower temperature of internal tissue).

The noise power received by the antenna contacted an evenly heated absorbing object is:

P= kT Df , where

k - Boltzmann’s constant ( 1.38 х 10^-23 Dg/°K)

Df  - System bandwidth,

T – Temperature of the biologic object

Therefore the power noise received by the antenna is proportional to the tissue temperature.

When the object temperature is 309°K, i.e. 36°C the noise power received by the antenna is 3x10^-13 Watt. This value corresponds with the noise generated by the antenna. Special methods are applied for receiving and processing signals.

12. Propagation of Electromagnetic Waves in The Body

Bio-objects usually examined consist of several layers (e.g. skin – fat – muscle). The radiation power passes through all parts of tissue with different losses and different temperatures, so the temperature measured by the antenna is not equal to the physical temperature of the examined organ, but depends on the temperature of other parties of the body and losses in these parts.

The exponential law of distribution describes propagation of plane waves in the body.

;         

where a- attenuation per unit in environment

b- propagation factor of electromagnetic wave;

P₀ – input power

The attenuation per unit in tissue depends on the water content of tissues. The tissues may be divided into two groups. The first group includes low water content tissue, which is represented by fat and bone. The attenuation per unit of the tissue is low. It is 20-30% (0.5-0.7dB/cm).

The attenuation per unit of skin and muscle (high water content tissue) is greater. It is about 50%
(3 dB/cm).

For infrared, bio-tissue is not transparent thus radiation attenuates at a depth of several microns.

13. Brightness Temperature

The power of radiation from all tissues passes through layers with different losses and different temperatures, so the temperature measured at the output of the antenna is not equal to the physical temperature of the investigated organ. This temperature depends on temperature of several layers of the body and losses in these layers.

This measured temperature is called brightness temperature. The brightness temperature is the averaged temperature in volume (cylinder) under the antenna. The diameter of the cylinder is 5 cm; the depth is 3-7 cm, depending of water content.

Fig. 10 shows the area in which RTM measured the temperature.

We can sea that 30% of energy is placed in the volume 16cm³. The size of the area is 3 x 2 x 3 cm, 70% of energy is placed in the volume 120cm³. The size of the area is 3 x 2 x 3cm.

Also, Fig. 10 shows that the measured volume is rather large. That's why breast RTM-examination very often reflects lung inflammation (especially if the breast is small)

14. Device Structure

            In 1997 RES, Ltd. developed the RTM‑01‑RES computer based microwave radiometer. The system is shown in Fig. 11.

RTM‑01‑RES  is safe and simple in operation. It does not require a calibration procedure and is always ready for measurements.

The system consists of the following items:

         Internal Temperature Sensor with the antenna (ITS)

         Skin Temperature Sensor (STS)

         Data Processing Unit (DPU)

The system includes a personal computer and a printer. The device is connected to a PC through a serial port. The results of RTM-diagnosis are shown on the monitor of the computer or printed as a thermogram and temperature field on the projection of the investigated organ.

The advantage of the method is the expert system for breast cancer detection. The expert system analyzes several parameters, including thermal asymmetry, dispersion of the temperature within the breast, etc.

15. Technical Specifications of RTM‑01‑RES

16. Functional Scheme of RTM-01-RES

The device is a modulated null-radiometer with a slipping circuit for compensating reflection between the biological object and the antenna. The used wavelength is 26 cm. The scheme of the device is protected by the patent of the RussiaFederation [7].The functional scheme is illustrated in Fig. 12.

When the temperature is measured, the antenna’s position on the patient’s skin is in accordance with the computer diagram of the examined organ. The antenna receives microwave radiation from the examined organ as noise at microwave frequencies and the signal is amplified in ITS (2).

The signal amplified in ITS is transmitted to the DPU (data processing unit), where it is processed (3).

The voltage from the skin temperature sensor (STS) (4) is transmitted to the DPU too. The skin temperature sensor is non-contact infrared frequencies receiver.

The buttons located on the front cover of the data processing unit switches the modes. The internal and skin temperature values are displayed on the 3-digit temperature indicator as degrees Celsius with an accuracy of 0.1.

The Data processing unit produces a series of digital signals for interfacing with the PC. 

On the front cover there are a temperature indicator, " (INTERNAL TEMPERATURE SENSOR) and "" (SKIN TEMPERATURE SENSOR) button, and " (POWER) power indicator. On the back cover of the DPU there are connectors for connecting with the internal temperature sensor (15-pin and coaxial connector), as well as a PC 9-pin connector, a coaxial connector for the internal and skin temperature sensors (analog signals that are on this connector has positive polarity with scale factor of 0.01 V/degree). Also the power switch and fuses are on the back cover.

17. Visualization of Internal Temperature Fields

In some works discussing microwave radiometry temperature data is displayed as a diagram (Fig. 13), when the names of the measured points, go along the horizontal axis and the internal temperature values are along the vertical axis.

This method allows analysis of temperature differential between corresponding points on the left and right breasts. However it is difficult to analyze the temperature at various locations on one entire breast by this method.

 Therefore the temperature data are also displayed as a temperature field, that is used in infrared thermography (Fig.14).

In the temperature field, cool areas of the breast are displayed by "cold" colours (i.e. blue) and hot ones are reflected by "warm" colours (red and orange).

Internal temperature fields show temperature abnormalities, in particular, corresponding to the location of a cancer.

18. Clinical Trials of RTM‑01

The clinical trials were held under the direction of leader Russian specialists at five Moscow medical centers. As follows:

   Branch #1 of the Mammology Health Center ;

   Municipal Hospital #40;

   The Russian Oncological Institute under the Science Center of
the Russian Academy of Medicine Sciences;

   The Oncology Health Center of the Moscow Committee of Health.

   The Burdenko Major Military Hospital .

The purpose of the clinical trials was to estimate the ability of the RTM‑01-RES system to detect breast cancer and monitor the treatment of benign tumors. At the Oncology Health Center of the Moscow Committee of Health, specialists estimated the ability of the RTM‑01-RES to select high-risk patients. The high-risk patients are patient that should undergo complex diagnostic investigation. The results of RTM‑diagnosis were compared with ultrasound and mammography.

RTM-diagnosis was carried out independently from clinical, x-ray and other examinations. The results of RTM-diagnosis were compared with results reported by histology. They were blind clinical trials (a doctor did not know results reported by other methods).

The results of the clinical trials are displayed in Fig. 15.

The Fig. 15 shows that all data are coordinated. The sensitivity of the method is 85-94%, the specificity is 75-80%, and the accuracy is 77-90%. These results are comparable with results of mammography.

Within the framework of the investigation the results of RTM-diagnosis, mammography and ultrasound were compared with histology results.

In this trial 60 women aged 28 – 76 (an average age is 51) with suspicion of breast cancer were engaged. 31 of these women were diagnosed with breast cancer, 18 women had non-cancer diseases and 11 women were diagnosed with proliferative mastopathy and fibroadenoma. All patients were examined by RTM-Diagnosis. RTM‑results were compared with results of CBE, mammography, and ultrasound results. Efficiency of RTM-Diagnosis was determined based on the comparison of RTM‑results with histology conclusions.

The results of the clinical trials show that sensitivity of RTM-Diagnosis for breast cancer diagnosis is 90.3%, it is higher than sensitivity of other diagnostic methods: sensitivity of ultrasound is 83,3%, for mammography it is 77,4%. These results are represented in Table 2. The results are illustrated in Fig. 16 

The investigation has shown that RTM‑Diagnosis can distinguish mastopathy and fibroadenoma with proliferation from mastopathy and fibroadenoma without proliferation. Therefore it can select patients who risk to have cancer under unfavorable conditions. These patients should have a complex examination in specialised health centers. The results are represented in Table 3.

This table shows that RTM‑Diagnosis distinguishes mastopathy and fibroadenoma with proliferation from mastopathy and fibroadenoma without proliferation well. Thus one of the advantages of RTM‑Diagnosis is to select patients with proliferative fibroadenoma and mastopathy. Other diagnostic techniques cannot do this as they detect anatomical changes in the breast. RTM‑Diagnosis provides a doctor with information on active processes within the breast.

Thus in 82% of all cases RTM‑Diagnosis selected proliferative mastopathy and fibroadenoma as risk group patients correctly. Ultrasound selected 18% and mammography – 36.3%.