Prostate cancer (PCa) is the most common non-cutaneous cancer in men in the United States, with over 185,000 cases newly diagnosed, and over 28,000 deaths annually [1, 2]. Screening methods are now widely used in the United States and Europe to detect PCa, which include digital rectal examination (DRE), and prostate-specific antigen (PSA) analysis. When suspicion is raised through these screening mechanisms, prostate biopsies are performed to diagnose PCa, which depends upon the presence of adenocarcinoma in biopsy cores, with clinical significance being determined by the presence of 50% or more PCa tumor tissue in 3 or more biopsy cores, a Gleason sum (GS, histologic analysis) greater than 6, and a PSA density (PSA divided by ultrasound derived volume of prostate) more than 0.15[3]. The clinical standard for performing prostate biopsy is ultrasound-guided, transrectal, laterally directed 18G needle cores, with the number of cores ranging from 6-12, systematically sampling different regions of the prostate[4]. This standard does not involve targeting needles to suspicious regions since PCa does not have unique B-mode ultrasound image characteristics that can delineate diseased from normal structures and benign pathologies of the prostate (e.g., benign prostatic hyperplasia (BPH) and inflammation). The current standard of care has a dismal sensitivity (only 53% using octant systematic biopsy in a cohort of radical prostatectomy specimens with previously diagnosed, clinically significant disease, [5]), mainly because the sampling grid only randomly intersects the pathologic tissues. Over 1,000,000 prostate biopsies are performed annually in the United States[6], with PCa detection rates being low (25-36%)[6]. PCa detection rates on repeat biopsies (cases with negative first biopsies) are again 10-35% [7, 8]. The fact that these rates are identical suggests that as many cancers are detected as are missed during a single systematic biopsy session. In addition, many of the cancers that are detected with this approach are clinically insignificant[3]. Elastography imaging methods have shown promise for PCa visualization and prostate biopsy guidance based upon stiffness differences between normal and pathologic tissues[9]. However, elastography methods can be limited by an inability to apply uniform compression (stress) to the prostate using a hand-held transrectal ultrasonic transducer. Acoustic Radiation Force Impulse (ARFI) imaging is an elastography imaging method that we have developed at Duke University that overcomes these challenges through the use of focused acoustic beams for the application of stress. We have obtained promising initial ex vivo and in vivo results, in which normal prostatic structures and focal PCa lesions are clearly visualized in ARFI images that are not visualized in matched B-mode images. The in vivo data demonstrate a clear advantage of ARFI imaging over conventional elastography for PCa visualization, in that the acoustic energy is coupled directly into the prostate. We propose to develop and optimize dedicated 2D and 3D transrectal in vivo ARFI imaging methods for the purpose of visualizing PCa and differentiating PCa from benign processes in the prostate;to evaluate the correlation between suspicious regions in ARFI images and tissue histology, to investigate the correlation between local PCa Gleason pattern (measure of histologic aggressiveness) and PCa visibility in ARFI images, and to evaluate the potential increase in biopsy detection rate of clinically significant PCa under ARFI image guidance. If successful, this research has the potential to greatly improve cancer detection rates for clinically significant grade PCa (i.e. GS 7 or more) during first time biopsies, to reduce the number of biopsy cores taken during biopsy, to facilitate longitudinal monitoring of PCa growth or recurrence after in situ therapies, and to provide image guidance for focal PCa therapies.

Public Health Relevance

Prostate cancer (PCa) is the most common non-cutaneous cancer in men in the United States, with over 185,000 cases newly diagnosed, and over 28,000 deaths annually [1];PCa is currently diagnosed by ultrasonic guided biopsy in which systematic sampling of the prostate is performed because PCa is not generally visualized in ultrasonic images, thus, PCa biopsy is reported to have poor sensitivity (53%)[5]. We propose to develop ultrasonic radiation force based stiffness imaging methods capable of visualizing focal cancers in the prostate, thus providing targeting for biopsy procedures. If successful, this research has the potential to greatly improve the cancer detection yield for clinically significant grade cancers on first time biopsies, to reduce the number of biopsy cores taken during biopsy, to facilitate longitudinal monitoring of PCa growth or recurrence after in situ therapies, and to provide image guidance for focal PCa therapies.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA142824-04
Application #
8403817
Study Section
Biomedical Imaging Technology Study Section (BMIT)
Program Officer
Tandon, Pushpa
Project Start
2010-01-18
Project End
2014-12-31
Budget Start
2013-01-01
Budget End
2013-12-31
Support Year
4
Fiscal Year
2013
Total Cost
$346,205
Indirect Cost
$121,793
Name
Duke University
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705
Doherty, Joshua R; Trahey, Gregg E; Nightingale, Kathryn R et al. (2013) Acoustic radiation force elasticity imaging in diagnostic ultrasound. IEEE Trans Ultrason Ferroelectr Freq Control 60:685-701
Rouze, Ned C; Wang, Michael H; Palmeri, Mark L et al. (2013) Finite element modeling of impulsive excitation and shear wave propagation in an incompressible, transversely isotropic medium. J Biomech 46:2761-8
Wang, Michael; Byram, Brett; Palmeri, Mark et al. (2013) On the precision of time-of-flight shear wave speed estimation in homogeneous soft solids: initial results using a matrix array transducer. IEEE Trans Ultrason Ferroelectr Freq Control 60:758-70
Rotemberg, Veronica; Byram, Brett; Palmeri, Mark et al. (2013) Ultrasonic characterization of the nonlinear properties of canine livers by measuring shear wave speed and axial strain with increasing portal venous pressure. J Biomech 46:1875-81
Zhai, Liang; Polascik, Thomas J; Foo, Wen-Chi et al. (2012) Acoustic radiation force impulse imaging of human prostates: initial in vivo demonstration. Ultrasound Med Biol 38:50-61
Rotemberg, V; Palmeri, M; Nightingale, R et al. (2012) The impact of hepatic pressurization on liver shear wave speed estimates in constrained versus unconstrained conditions. Phys Med Biol 57:329-41
Palmeri, Mark L; Nightingale, Kathryn R (2011) What challenges must be overcome before ultrasound elasticity imaging is ready for the clinic? Imaging Med 3:433-444
Anderson, Pamela G; Rouze, Ned C; Palmeri, Mark L (2011) Effect of graphite concentration on shear-wave speed in gelatin-based tissue-mimicking phantoms. Ultrason Imaging 33:134-42
Rosenzweig, Stephen; Palmeri, Mark; Nightingale, Kathryn (2011) GPU-based real-time small displacement estimation with ultrasound. IEEE Trans Ultrason Ferroelectr Freq Control 58:399-405
Rotemberg, Veronica; Palmeri, Mark; Rosenzweig, Stephen et al. (2011) Acoustic Radiation Force Impulse (ARFI) imaging-based needle visualization. Ultrason Imaging 33:1-16

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