**5. Protocols for capturing thermal images**

making them more tortuous due to formation of bends [18–20]. In fact, it is experimentally

In addition, it has been empirically observed that tumor temperature is higher than the neighboring temperatures with the help of contact temperature measurements. In Ref. [21], Gautherie claimed that this high heat is due to high metabolic activity at tumor location. Hence, this region appears brighter and hotter in thermographic images when compared to surroundings. It is also observed that tumor temperature is warmer compared to the blood vessels feeding the tumor region [21]. Aggressiveness of cancer cells makes the boundary of tumor irregular as they break the boundary formed by basal laminas to invade the neighbor‐ ing tissues [19, 20]. This is not seen in case of benign tumors whose cells behave similar to

The size of tumor indicates the stage of cancer and largely affects the survival rate. A survey conducted by Narod [2] observed drastic decrease in survival rate with increase in tumor size. Early detection of cancer increases the chances of survival. Thermography outperforms other modalities when it comes to early detection. Changes such as vasodilation, neo‐angiogenesis and high tortuosity of blood vessels which are found in initial stages of cancer result in ther‐ mal impressions and hence can be detected in thermography [15–19]. These might not be observed in other modalities which depend upon detecting architectural distortions that appear only when tumor is sufficiently grown. A study by Gautherie and Gros [3] over 58,000 patients for 12 years showed that thermography detected breast cancer five years earlier in

Abnormality in thermogram is not the sole criterion for malignancy. Increase in heat pattern might even be observed due to hormonal response, lactation and presence of benign tumors such as fibrocystic and fibroadenoma. However, these non‐malignant conditions have different projections in the thermographic image when compared to malignant tumors. Unlike in malignant breasts where there is asymmetrical heat map, heat response is mostly symmetrical across the two breasts with high hormonal response. Estrogen released during hormonal activity produces nitric oxide that causes increase in heat and vessel dilation [12]. Similar activity happens in the case of lactating mothers except that a little asymmetry in heat map is seen due to uneven lactation in both breasts. There is an increase in heat signature even in benign cases such as fibro‐ cystic and fibroadenoma [21, 22]. In contrast to malignant tumors, these cells are not aggressive and behave similar to normal cells [19, 23]. Other than these cases, abnormal heat pattern leading to vasodilation and angiogenesis can also occur during inflam‐ mation caused by infection or wound healing [12, 14]. Though these abnormalities are formed, they have distinct features compared to malignancy that can be distinguished. Some recent explorations have shown that thermography can even help in prognosis. Since the increase of temperature in malignant tumors is primarily due to the release of nitric oxide, which is caused due to hormonal activity, the temperature distribution on the breasts also pro‐ vides signals on the hormonal receptor status of malignant tumors. Zore et al. [9] have studied the effect of hormone receptor status of malignant tumors on thermograph through a quanti‐ tative analysis of average or maximum temperatures of the tumor, the mirror tumor site and

evident that this high tortuosity is observed much before angiogenesis [18].

normal cells. This makes the benign tumor boundaries regular.

94 New Perspectives in Breast Imaging

around 400 patients than mammography and ultrasonography.

A standard imaging protocol has to be followed for any modality to make it a repeatable and operator agnostic procedure that can reduce subjectivity and errors in image capture. Likewise, a set of instructions has to be followed in thermography as well [25, 26].

Most importantly, before capturing the images, patient must be cooled for minimum period of 10–15 min in a room maintained at a temperature of 16‐22 °C. This helps in attaining ther‐ mal equilibrium with the surrounding environment [25]. Cooling is mandatory as it helps in removal of extraneous heat caused due to external reasons such as tight clothing, apparel and friction from a hand bag or outside temperature. Cooling also helps in enhancing the temper‐ ature pattern of tumorous regions compared to non‐tumourous regions [27–30]. It is observed that normal tissue reacts quickly to external cooling, whereas malignant reacts slowly, mak‐ ing it appear hotter compared to rest of the breast region. For quick cooling of images, cold challenge can be used where patient hands are immersed in cold water causing the regulation of body temperature with sympathetic stimulus [30].

When it comes to capturing the actual thermal images, imaging protocols can be categorized into discrete and continuous imaging protocols.

*Discrete imaging protocols:* These protocols are interested in specific set of static fixed views. The basic views which are observed in most discrete protocols include frontal view (0°), oblique views (±30°) and lateral views (±90°). Some variations of different protocols in the way of the mentioned views are captured, such as (a) seated position, (b) supine position, (c) standing position and (d) combinations of {a,b,c}. Subset of mentioned views/changing the angle of views/ adding more view angles are also being used in some studies.

A tumor has less effect with cooling compared to normal tissues whose heat signatures decrease drastically [28, 30]. To study the nature of cancer cells further, some protocols include the above combinations of different views after cooling the breasts. Some protocols consider only fully cooled breasts, while some capture the breast image before and after cooling and analyze the thermal patterns of the cooled breast and uncooled breasts [31].

*Continuous imaging protocols:* Continuous imaging protocols capture videos of the breast as they are cooled, instead of static images. These protocols are not as popular as discrete due to the large processing time needed to analyze. However, much larger information can be captured in a video. For example, tumorous regions do not cool as fast as rest of the tissues.

#### **6. Advances in thermal cameras**

Medical thermography is also benefiting from the rapid advancement in the quality of ther‐ mal imaging too. Temperature capture has evolved from a complicated probe‐based method to a camera‐based registration.

Over the years, improvements in silicon technology have made a huge impact on the tech‐ nology used in IR detectors. Many use cases of thermal imaging are evolving in biomedi‐ cal, transport, energy and environmental applications, and they have been the key business driver for this growth, as well. **Figure 1** depicts the history of development of infrared sen‐ sors, which is very well described in Ref. [32]. The real breakthroughs were focal plane arrays and bi‐dimensional arrays improving spatial resolution and thermal sensitivity.

Broadly, infrared cameras can be divided into cooled and uncooled detectors. Cooled ther‐ mal cameras have infrared detectors integrated with cryocoolers and enable measurement of very low temperatures as well as very high resolution and improved sensitivity as thermally‐ induced noise is reduced. However, cooled cameras are expensive and may be needed only for applications that require very high resolution and high sensitivity.

Microbolometer focal plane arrays (FPAs) have tremendously modified the way of image capture by allowing an array of sensors at the focal plane of lens to detect the LWIR wavelengths [32, 33]. This integration has led to the development of uncooled infrared detectors that are typically small, handheld and also restricted the need for expensive cooling techniques. The current uncooled cameras work on the principle of change in resistance or voltage or current due to the emitted infrared radiation. The resolution is direct function of number of pixels in the microbolometer array per unit area. With the advances in silicon technology, these digital infrared uncooled cam‐ eras have massively transformed from a low resolution to high resolution of 640 × 480 pixels to 1024 × 768 pixels or more. The current cameras also have improved the sensors to obtain a thermal sensitivity and accuracy error of at most 20 mK and 1°C respectively. To detect the infrared radia‐ tion, vanadium oxide (VOx) and amorphous silicon are common materials in microbolometer [32].

The lens is costly compared to lens found in normal video‐shoot cameras, since normal glass cannot be used to make the lens due to its property of blocking LWIR radiation and reflecting the LWIR incident on the lens. Hence, Germanium (Ge), Chalcogenide glass, Zinc Selenide (ZnSe) and Zinc Sulfide (ZnS) that are LWIR‐transmissive are used for the lens preparation.

**Figure 1.** Advances in thermal sensor technology (reproduced from Ref. [32]).

These uncooled cameras have also reduced the cost and heavy maintenance that would be needed for the cooled detectors. Some popular camera models used for medical purposes are shown in **Figure 2**. Today, FLIR, Fluke and Meditherm are thermal camera vendors preferred by thermographers for medical thermography as many of these camera models are already FDA‐certified for tele‐thermology.

#### **6.1. Visual interpretation of thermal images**

**6. Advances in thermal cameras**

to a camera‐based registration.

96 New Perspectives in Breast Imaging

Medical thermography is also benefiting from the rapid advancement in the quality of ther‐ mal imaging too. Temperature capture has evolved from a complicated probe‐based method

Over the years, improvements in silicon technology have made a huge impact on the tech‐ nology used in IR detectors. Many use cases of thermal imaging are evolving in biomedi‐ cal, transport, energy and environmental applications, and they have been the key business driver for this growth, as well. **Figure 1** depicts the history of development of infrared sen‐ sors, which is very well described in Ref. [32]. The real breakthroughs were focal plane arrays

Broadly, infrared cameras can be divided into cooled and uncooled detectors. Cooled ther‐ mal cameras have infrared detectors integrated with cryocoolers and enable measurement of very low temperatures as well as very high resolution and improved sensitivity as thermally‐ induced noise is reduced. However, cooled cameras are expensive and may be needed only

Microbolometer focal plane arrays (FPAs) have tremendously modified the way of image capture by allowing an array of sensors at the focal plane of lens to detect the LWIR wavelengths [32, 33]. This integration has led to the development of uncooled infrared detectors that are typically small, handheld and also restricted the need for expensive cooling techniques. The current uncooled cameras work on the principle of change in resistance or voltage or current due to the emitted infrared radiation. The resolution is direct function of number of pixels in the microbolometer array per unit area. With the advances in silicon technology, these digital infrared uncooled cam‐ eras have massively transformed from a low resolution to high resolution of 640 × 480 pixels to 1024 × 768 pixels or more. The current cameras also have improved the sensors to obtain a thermal sensitivity and accuracy error of at most 20 mK and 1°C respectively. To detect the infrared radia‐ tion, vanadium oxide (VOx) and amorphous silicon are common materials in microbolometer [32]. The lens is costly compared to lens found in normal video‐shoot cameras, since normal glass cannot be used to make the lens due to its property of blocking LWIR radiation and reflecting the LWIR incident on the lens. Hence, Germanium (Ge), Chalcogenide glass, Zinc Selenide (ZnSe) and Zinc Sulfide (ZnS) that are LWIR‐transmissive are used for the lens preparation.

and bi‐dimensional arrays improving spatial resolution and thermal sensitivity.

for applications that require very high resolution and high sensitivity.

**Figure 1.** Advances in thermal sensor technology (reproduced from Ref. [32]).

There are different protocols followed by thermographers for analyzing and interpreting thermal images, especially for breast cancer screening. Most of this work in creating the pro‐ tocols have taken place in the 1970s and 1980s, such as the Marseille protocol [13–15], Hobbins protocol [30], Gautherie protocol [21], Hoekstra protocol [34] and, more recently, with newer thermal cameras, the Villa Marie protocol [12]. An attempt to obtain an agreement of different experienced thermographers was also made in 1975 to provide a consistent set of observations to be noted [17].

All of these protocols give different thermographic category ratings of four to five lev‐ els, starting from normal to highly suspicious of malignancy. Multiple criteria are noted, using both vascular and non‐vascular observations. These criteria are generally qualita‐ tive rather than quantitative. The visual interpretation necessitates heuristic rules to com‐ bine these observations to determine a thermographic category. Some protocols assign numbers to each observation and combine them using a mathematical function for catego‐ rization. This also shows the need for experience and proper training for thermographic interpretation.

Regardless of the variations across protocols, these criteria can be broadly classified into vas‐ cular and non‐vascular criteria, with some generality in these criteria, as follows:

**Figure 2.** Two thermal camera models from different vendors (a) FLIR T650SC (b) Meditherm IRIS 2000.

#### **Non-vascular criteria:**


#### **Vascular criteria:**


The general interpretation from these protocols is that with few and mild abnormal find‐ ings, the categorization is toward normal and likely benign. With increased abnormality, the observations tend toward increased suspicion of malignancy. Another important point to note is that benign diseases also exhibit some abnormal thermal vascular/non‐vascular cri‐ teria [30]. The diagnosis for benign conditions is made by follow‐up of thermography over a few months, by which time the abnormal thermal findings change or reduce or disappear.

Due to these multiple diverse metrics used by practitioners and no standardized way of inter‐ pretation across different expert thermographers, the thermological interpretation becomes very subjective and many times results in high false positives. Many efforts are therefore underway to remove subjectivity using computer‐aided diagnostic methods—some of which are described later in this chapter.

### **7. Clinical validations**

Thermography is not a new technique for breast cancer screening. Its presence has been there since 1960 [26]. There have been many longitudinal and clinical trials performed to show its efficacy. In 1982, FDA approved thermography as an adjunct modality for breast cancer screening. **Table 1** lists out the studies that has been done to show the potential of thermog‐ raphy. This technique is undervalued due to the difficulty in interpreting the thermograms with naked eye. The interpretation varies from observer to observer and needs high expertise to correctly validate the diagnosis result, limiting to few thermographers. With advent of technology, in both hardware and software, automated analysis of thermograms is emerging to obtain high sensitivity and specificity.


**Table 1.** List of large‐scale studies.

**Non-vascular criteria:**

98 New Perspectives in Breast Imaging

regions in the same side

**Vascular criteria:**

**1.** Vascular asymmetry

**5.** Number of vessels **6.** Caliber of vessels

**3.** Increased vascular density

are described later in this chapter.

**7. Clinical validations**

**1.** Focal increase in temperature by a fixed interval, e.g., 1, 2, 3°C

**3.** Regional increase in temperature, including specific quadrants

**6.** Abnormal physical observations: bulging/size variation, retraction

**4.** Abnormal directions of clusters of vessels, such as vertical, horizontal

**7.** Abnormal location of vascularity and avascularity

**2.** Global increase in temperature compared to the contralateral breast by, say, 1.5°C

**5.** Abnormal location of focal increase including areolar regions or along edges/bulges

**2.** Vascular anarchy, including tortuous or serpentine or loops or clusters or bifurcations

The general interpretation from these protocols is that with few and mild abnormal find‐ ings, the categorization is toward normal and likely benign. With increased abnormality, the observations tend toward increased suspicion of malignancy. Another important point to note is that benign diseases also exhibit some abnormal thermal vascular/non‐vascular cri‐ teria [30]. The diagnosis for benign conditions is made by follow‐up of thermography over a few months, by which time the abnormal thermal findings change or reduce or disappear. Due to these multiple diverse metrics used by practitioners and no standardized way of inter‐ pretation across different expert thermographers, the thermological interpretation becomes very subjective and many times results in high false positives. Many efforts are therefore underway to remove subjectivity using computer‐aided diagnostic methods—some of which

Thermography is not a new technique for breast cancer screening. Its presence has been there since 1960 [26]. There have been many longitudinal and clinical trials performed to show its efficacy. In 1982, FDA approved thermography as an adjunct modality for breast cancer

**4.** Differences in temperature between contralateral regions or between different quadrants/
