DESCRIPTION (provided by applicant): We have developed a new method of imaging the mechanical properties of tissues based on short duration (<1 ms), localized applications of acoustic radiation force and imaging the tissues' response using ultrasonic methods. Initial results with this technique demonstrate its ability to image mechanical properties of the mucosal and muscular layers of the esophagus, stomach, and rectum ex vivo, as well as providing clinically relevant architectural information in lymph nodes in vivo. We have labeled this method Acoustic Radiation Force Impulse (ARFI) imaging, and have developed a real-time ARFI imaging system utilizing a Beowulf cluster combined with modified commercial ultrasonic scanners and transducers for transcutaneous imaging. We propose both ex vivo and in vivo studies to evaluate the ability of ARFI imaging to determine the degree of bowel wall invasion of colorectal cancers (T-stage) and to evaluate the malignant involvement of the associated local lymph nodes (N-stage) for the purpose of preoperative staging in order to guide treatment decisions. Rectal cancers that have penetrated through the muscularis propria into the peri-rectal tissue (uT3-uT4) and those exhibiting local lymph node involvement (N+) are generally treated with neoadjuvant chemotherapy and radiation in order to reduce tumor size prior to radical resection. Tumors contained within the rectal layers (mucosa, submucosa and muscularis propria, uTO-uT2) without nodal involvement (N-) generally require only local transanal excision, and no neoadjuvant treatment. The latter approach is better tolerated, with fewer complications and appreciably less cost than the former. Current methods for preoperative staging of colorectal cancers report accuracies of only 69-90% for T-staging, and less than 65% for N-staging. Overstaging occurs most often at the critical distinction between uT2 and uT3. ARFI images distinguish tissues based upon their mechanical properties and geometric structure, which is exactly the information required for T-staging. We propose finite element modeling studies and phantom trials to guide signal acquisition and processing methods, to explore the fundamental issues of resolution and contrast, and to optimize the performance of ARFI imaging of layered organs. We propose to evaluate the relationship between colorectal tissues' response to ARFI excitation and their histology, including the assessment of desmoplasia and increased cellularity which are associated with malignancy, and to correlate ARFI displacement images with mechanical indenter tests. We propose to evaluate the ability of ARFI imaging to stage colorectal tumors and nodes in ex vivo tissue samples, comparing it with conventional ultrasound and histology as the gold standard. Finally, we propose a pilot clinical study comparing ARFI and ultrasonic staging of colorectal cancers in vivo. |