Characterization of the colorectal cancer by combining high-frequency endoscopic ultrasound and quantitative ultrasound

Abstract

Colorectal cancer (CRC) is the third most common cancer for both men and women in the US, predicted in 2012 to account for 9% of new cases and cancer related deaths. The fact that only 39% of pre-cancerous colorectal tumors are detected at an early stage is the main factor that leads to metastasis and high mortality rate. The invasion depth of early CRC limits to superficial layers of colorectal wall with few vascular and lymphatic vessels. CRC at early stage often has no symptoms, which causes delay of successful treatments. Colonoscopy is clinically performed for screening, during which biopsy may be conducted; however, it is difficult to determine early stage CRC by ordinary endoscopy even with dye due to the insufficient superficial scope of colorectal surface for pre-cancerous diagnosis. Endoscopic ultrasound (EUS) has been widely used to visualize overall depth-view five-layered structural alteration of colorectal tract. With high-frequency transducer (20MHz-30MHz), EUS is capable of delineating the mucosa-submucosa layer of normal human colon with micron-scale resolution anatomical information; however, the current high-frequency EUS is still insufficient to distinguish cancer from polyp and adenoma due to the lack of patho-physiological information. An open high-frequency EUS system, compatible with regular endoscope, which allows acquisition of radio frequency (RF) data for acoustic tissue characterization and combination with other functional imaging modalities (e.g. photoacoustic imaging) may bring values to diagnose colorectal malignancies. The development of a novel high-frequency EUS system which allows quantitative acoustic tissue characterization and easy fusion of multiple functional modalities for complementary structural & patho-physiological information is presented in this chapter. Processed B-mode images or unprocessed raw RF data could be stored, displayed and post-processed in PC. A miniaturized 30.5 MHz single element mechanical side-view EUS transducer was fabricated using PMN-0.28PT single crystal. Phantom test, ex vivo imaging of swine, mouse and rabbit colon specimen, and in vivo imaging of rabbit were conducted to evaluate the performance of the system. New Zealand White male rabbits surgically implanted with VX2 tumor cell were used for characterization of CRC tissue and normal colon tissue. Ex vivo scan was performed to acquire B-mode images and raw RF data. The acoustic spectra analysis was performed. Intercept, slope and midband fit were obtained and compared between the region-of interests (ROIs) representing colorectal tumors and normal colon tissue. The results of ex vivo B-mode image, color-coded image were compared with histology. Testing results showed that the system could detect a minimum signal of 25 μV, allowing a 50 dB dynamic range at 45 dB gain, with a frequency range from 20 MHz to 100 MHz. Finally, phantom imaging, in vivo imaging of normal colon in ICR mouse and New Zealand White rabbit model were conducted to demonstrate the performance of the system. Significant differences were observed between the parameters from cancerous ROIs and normal tissue region. The results showed that the complementary information derived from quantitative high-frequency EUS may create better sensitivity and specificity to colorectal cancer diagnosis