# Photoacoustic Imaging for Management of Breast Cancer: A Literature Review and Future Perspectives
## 4 Discussion
### Questions Raised by [PERSON]'s Research Group and Answers
They correlated the case of PA 'non-mass' appearance with vascular pattern most pronounced in non-cohesively organized vasculature fields. Non-cohesively organized vasculature fields are scattered or unconnected vasculature fields. For the case of PA 'ring' appearance, they observed the vasculature to be confined to the border. They also provided the physiological explanation for the few cases in which the PA lesion appearance do not fall within the above mentioned three major categories, or they  
Figure 5: Example of MR, PA and their fusion images of two cases. Case 1 (**a–d**): A 40-year-old woman with IBC. Case 2 (**e–h**): A 46-year-old woman with DCIS in upper-outer area in right breast. (**a,e**) Original MR image, lesion is indicated by a red circle; (**b,f**) the enlarged MR images around the lesion after deforming into the shape to PA images; (**c,g**) and (**d,h**) are original PA images, and fusion images of PA (cyan) and MR (red), respectively; these figures are after eliminating the PA signals from subcutaneous blood vessels by a depth of 4 mm. Reproduced from [PERSON] et al. [39], which is licensed under a Creative Commons Attribution 4.0 International License ([[http://creativecommons.org/licenses/by/4.0/](http://creativecommons.org/licenses/by/4.0/)]([http://creativecommons.org/licenses/by/4.0/](http://creativecommons.org/licenses/by/4.0/))). contradict the corresponding MRI findings. As mentioned in the previous paragraph containing the evidence in support of Question 1, [PERSON] et al. [39] attempted to analyze the different varieties of breast cancer by detecting five different PA markers related to lesion vasculature. For the above-mentioned studies, specific PA appearances for a limited number of cases were correlated with the corresponding physiology. However, these studies did not evaluate the diagnostic capabilities of those specific PA appearances/markers. [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. They reported that among PA-US features, the sum of internal features was useful to differentiate between triple-negative breast cancer (TNBC) and HER2 enriched breast cancer subtypes. Internal vessels, the sum of all internal features, the sum of all internal and external features of PA-US images were useful to differentiate between Luminal A (LUMA) and Luminal B (LUMB) molecular subtypes. All internal features, the sum of all internal features, the sum of all internal and external features, and the ratio of internal and external features of PA-US images were useful to differentiate between LUMA and TNBC molecular subtypes. They also found that the same features could be useful to differentiate between LUMA and TNBC from other 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 reported that the means of total external PA-US feature scores, i.e., boundary zone, peripheral zone vessels for luminal (A and B) breast cancers were higher, and total internal PA-US features scores, i.e., internal vessels, internal blush, and internal hemoglobin were lower than that of the triple-negative and HER2-positive breast cancers. _Question 3: Whether it is possible to identify PA image markers for differentiating between contralateral breast and the healthy breast?_  
A small number of clinical studies show that there were significant differences among the PA images of the healthy breast and the contralateral breast. In their in vivo study, [PERSON] et al. [109] observed that the saturated oxygen level of the affected breast masses was lower than the contralateral breasts and healthy breasts. [PERSON] et al. [39] observed that the contralateral breasts are having lower PA signals than that of the affected breast.