Abstract
Calcification is one of the most significant indicators for early breast cancer detection. In X-ray mammography, the size, number and clustering of calcifications (composed of hydroxyapatite (HA) most frequently) are important features for grading the suspiciousness of the tissue. Despite being the golden standard for calcifications identification, X-ray mammography is still suffering from low accuracy especially for young women with dense breast. Because of speckle noises, ultrasound (US) imaging owns low contrast between breast tissues and micro-calcifications and thus low detectability. Photoacoustic (PA) imaging has overcome the drawback of pure optical imaging by combining rich optical contrast with ultrasonic spatial resolution for deep imaging. PA imaging of angiogenesis is of particular importance for noninvasive breast cancer diagnosis because of the high absorption coefficient of hemoglobin. However, it is not clear if a calcification has good contrast by photoacoustic imaging. In this dissertation, we first explored the feasibility of photoacoustic imaging of calcification imbedded chicken breast phantom by using photoacoustic microscopy with a NIR laser. The measured signal of calcification is comparable to blood in NIR between 670 nm to 850 nm. Based on this encouraging result, we further optimized the wavelength to around 700 nm by achieving maximum PA signal ratio of calcification to blood. At 700 nm, the intralipid or chicken breast phantom study demonstrated that an imaging depth of 3 cm of calcifications could be achieved for medical ultrasound array system. In order to increase the penetration depth additional for full figure patients, the contrast agent of photoacoustic imaging with molecularly targeting to hydroxyapatite was used. We demonstrated that the average SNR of calcification particles in photoacoustic B-mode image could be improved by 7 dB with IR-Dye incubation as excited at 675 nm. That is equivalent to 0.5 cm improvement of penetration depth in human breast in vivo. The human study was conducted to validate the study. Human breast tissue ex vivo experiments with photoacoustic calcification imaging confirmed the visualization of 0.9 mm human breast calcification at the acoustic depth of 2 cm with a 5-MHz probe. This study provides a new window for the tissue calcification imaging not limited in breast calcifications. It may used for vascular calcification, thyroid calcification and many other form of biogenic calcifications with further evaluation from clinical point of view.