## 2 Thermal Signature of Malignancy
### Breast Cancers  
The important role of infrared thermography in assessing the risk of breast cancer was revealed thanks to the study carried out by [PERSON] et al. [17] in 2000. These authors, using second-generation focal-plane indium-antimonide IR detector systems, demonstrated that women with abnormal IR breast images had an increased risk of about 30% of developing breast cancer. They also showed the prognostic value of IR thermography for breast cancer patients. Indeed, at that time, they found that 65% of the examined subjects with a breast cancer diagnosis had abnormal IR images within the one-year period leading up to their diagnosis, while 88% of the patients who died of breast cancer had abnormal IR images during the same period.  
Invasive ductal carcinoma (IDC), ductal carcinoma in situ (DCIS), and invasive lobular carcinoma (ILC) are the three most common types of breast cancers [18]. Each of them affects specific cells of the mammary tissue. In particular, DCIS affects the cells lining the ducts, whereas when the walls of the ducts are involved, IDC occurs. The ILC affects the lobules, i.e., the milk-producing glands. It is generally recognized that these tumors have an increased metabolic rate and an increased blood supply, which leads to a temperature spike on the breast surface that can be observed using IR thermography. Additionally, as revealed by [PERSON] et al. [19], the high density of blood vessels in breast cancer may play a role in the tumor and surrounding tissue temperatures.  
To detect less pronounced surface temperature variations due to deeper tumors, a cold stimulation is often applied. The underlying principle is that when applying cold stress to a healthy breast, the peripheral blood flow is redirected through deeper veins, leading to a decrease in surface temperature [20]. On the contrary, an abnormal breast does not exhibit this vasoconstriction, as blood vessels produced by cancer are devoid of a muscular layer and cannot restrict in response to a cold stimulus [5]. Consequently, the affected regions appear hyperthermic in an IR image. Moreover, vasodilitation in the same regions was also observed; indeed, it was found that tumors under thermal stress produce a chemical mediator able to dilate subcutaneous vessels [14], thus increasing the surface temperature of the affected region.  
Thermal images of cancerous breasts may reveal highly asymmetric temperature distributions between the left and right breasts (in the assumption that one of them is healthy), localized hot spots, and changes in hypothermia vascular patterns or variation in heat patterns in the areolar and periaveolar regions [14]. In detail, according to the Ville Marie Infrared Grading Scale, a breast thermogram should be considered abnormal when at least one of the following abnormal signs is present [21]: a significant vascular asymmetry, unusual heat patterns, a temperature difference of 1 or 2 \({}^{\circ}\)C between the area of clinical interest and the contralateral site, a 3 \({}^{\circ}\)C temperature difference between the area of clinical interest and the ipsilateral breast, and a global temperature difference of 1.5 \({}^{\circ}\)C between the cancerous and the healthy breast.  
Recently, in an attempt to isolate the blood vessels from breast thermograms to detect deeper, static heat sources (lesions), [PERSON] and [PERSON] [22] recognized the thermal images of the vasoconstriction of the veins due to the application of a cold stimulus. They applied the virtual wave transform technique, which is usually used in the thermal non-destructive testing field. These authors, although working with limited data, reported that the magnitude of vasoconstriction seems to be related to the presence of cancer. Due to the limitation of their data, the authors promoted future studies involving diagnostic and clinical data to validate this new paradigm.