3-D photoacoustic and pulse echo imaging of prostate tumor progression in the mouse window chamber

Abstract

Abstract. Understanding the tumor microenvironment is critical to characterizing how cancers operate and predicting their response to treatment. We describe a novel, high-resolution coregistered photoacoustic (PA) and pulse echo (PE) ultrasound system used to image the tumor microenvironment. Compared to traditional optical systems, the platform provides complementary contrast and important depth information. Three mice are implanted with a dorsal skin flap window chamber and injected with PC-3 prostate tumor cells transfected with green fluorescent protein. The ensuing tumor invasion is mapped during three weeks or more using simultaneous PA and PE imaging at 25 MHz, combined with optical and fluorescent techniques. Pulse echo imaging provides details of tumor structure and the surrounding environment with 100-μm 3 resolution. Tumor size increases dramatically with an average volumetric growth rate of 5.35 mm 3 /day, correlating well with 2-D fluorescent imaging (R = 0.97, p < 0.01). Photoacoustic imaging is able to track the underlying vascular network and identify hemorrhaging, while PA spectroscopy helps classify blood vessels according to their optical absorption spectrum, suggesting variation in blood oxygen saturation. Photoacoustic and PE imaging are safe, translational modalities that provide enhanced depth resolution and complementary contrast to track the tumor microenvironment, evaluate new cancer therapies, and develop molecular contrast agents in vivo. C 2011 Society of Photo-Optical Instrumentation Engineers (SPIE).

Photoacoustic Imaging in Oncology: Translational Preclinical and Early Clinical Experience

“…Several research groups have conducted photoacoustic imaging of prostate cancer in vivo using animal models (76)(77)(78)(79)(80) ) was performed in 0.2-mm increments on three metastatic and nine benign lymph nodes excised from eight melanoma patients undergoing lymphadenectomy by using a 21-MHz linear US array (Vevo LAZR, Fujifilm VisualSonics) at 20-minute scans for each node (98). Results indicate that metastasized melanin was differentially detected from blood in resected human lymph nodes.…”

Photoacoustic imaging of prostate cancer

“…81 Owing to the excellent optical absorption of red blood cells, PAI successfully illustrated angiogenesis and hemorrhage in the implanted tumors that were invisible under pure US imaging (Fig. 4).…”

“…81 Additionally, because US imaging provides good depth information and structural identi¯cation of the prostate, the coregistration of PA and US images can provide complementary information of tumor progression in a 2D and 3D manner. 57,64,81 Oxyhemoglobin (HbO 2 Þ and deoxygenated hemoglobin (dHb) have di®erent optical absorption properties at wavelengths within the range of PAI light sources. 82 Capitalizing on this di®erence in absorption spectra, spectroscopic PAI enables the characterization of red blood cells and is capable of di®erentiating malignant, benign, and normal prostatic tissue.…”

“…81 Compared with°uorescent imaging and US imaging, the distinctive feature of PAI is its ability to image the vascular network at a satisfactory resolution without utilizing contrast agents. 81 Additionally, because US imaging provides good depth information and structural identi¯cation of the prostate, the coregistration of PA and US images can provide complementary information of tumor progression in a 2D and 3D manner. 57,64,81 Oxyhemoglobin (HbO 2 Þ and deoxygenated hemoglobin (dHb) have di®erent optical absorption properties at wavelengths within the range of PAI light sources.…”

In vivo demonstration of reflection artifact reduction in photoacoustic imaging using synthetic aperture photoacoustic-guided focused ultrasound (PAFUSion)

“…PA imaging holds promise in functional imaging of the vasculature [3], in particular for differentiating oxygen levels based on the different optical absorption characteristics of oxy and deoxy-hemoglobin [4][5][6][7]. This technique has potential to diagnose vascular diseases, inflammations and cancer at an early stage [8][9][10][11][12], and for monitoring the disease response to specific medications/treatments [13]. In addition to the tissue chromophores, external contrast agents functionalized for specific biochemical targets hold potential in early detection of diseases [14].…”