# Photoacoustic Imaging for Management of Breast Cancer: A Literature Review and Future Perspectives
## 3 Results
### Endogenous Contrast Agents
#### 3.1.4 In Vivo Studies
They reported that 60 benign masses were correctly downgraded to a lower BI-RADS category using their dual mode PA-US imaging system. [PERSON] et al. [113] performed a dual-mode PA-US imaging in addition to internal gray-scale US imaging on 67 malignant breast masses. They used PA-US features to differentiate between breast cancer molecular subtypes. [PERSON] et al. [114] performed a detailed analysis on dual-mode PA US images of 532 IBC lesions of 519 patients from the PIONEER study. They correlated PA-US features with breast molecular subtypes. In a small preclinical study, [PERSON] et al. [103] evaluated the performance of their Twente PAM on six patients at 1064 nm. Out of the results presented in their report, one result indicated malignancy in the breast, which was not indicated by X-ray mammography and US imaging. Using the same system, [PERSON] et al. [67] successfully located the tumors in the in vivo PA images of two patients. [PERSON] et al. [115] performed in vivo study on three patients, two of them suffered from IDC, and one had a benign cyst. Their results showed that they successfully detected malignancies in the two cases with IDC, while the PA images of the patient with cyst did not produce any significantly strong PA signals corresponding to the benign pathology. In vivo PA imaging was conducted by [PERSON] et al. [116] with Twente PAM for a patient with IDC where the malignant lesion was successfully located and visualized. In another in vivo study, performed by the same group [117] on ten patients with breast malignancy and two patients with a cyst, the results showed that the PA contrast generated by malignant pathology exceeded the corresponding X-ray contrast, whereas the two cases of cysts did not produce any significantly strong PA signals corresponding to benign pathology. In another study [36] on four patients with cysts, the results showed that appearances of cysts in the PA images acquired at a single wavelength were similar to that of malignancies. [PERSON] et al. [25] used Twente PAM for the first time to relate tumor vascularization with the PA appearances of malignancies. From the study on a small patient population, they found that there were three specific types of PA lesion appearances--'mass', 'non-mass', and 'ring'. According to the researchers in these studies [25; 118],'mass' is a 3D lesion within the breast. It appears as a narrow region with high intensity. This region can be spatially homogenous or heterogeneous as well as of regular (round, oval, or lobulated) or irregular shape with vascularity spread over the entire lesion. 'Non-mass' appearance consists of a scattered region with multiple moderate to high-intensity foci, completely different in appearance from that of the surrounding healthy tissue. Vascularity was scattered over the entire lesion. 'Ring' appearance points to a high intensity region surrounding either partially or completely a region of low intensity. Vascularity was observed throughout the lesion while it was more pronounced at the border. Further, they [25] found that there was an excellent correspondence in lesion location identified by both PA and MRI and a reasonably good correlation in lesion shape and appearance. They also found that the lesion shape and appearance in PA images were in good correlation with standard histopathology. In their recent in vivo study on 33 breast malignancies with Twente PAM, [PERSON] et al. [35] found that 32 malignancies appeared with high imaging contrast and was independent of radiographic breast density. Among these lesions, four representative cases of which two patients with IDC, one patient with mucinous carcinoma (MC), and 1 patient with ILC whose X-ray mammograms, PA images overlaid on X-ray mammograms and the PA volumes in the region of lesion interest are shown in the Figure 2. The lesions in PA volumes were perfectly localized with X-ray mammograms. These lesions appeared with high contrast in PA images and the lesions located at depths more than 20 mm were visualized on PA images with high contrast.