BERKELEY, CA (UroToday.com) - For the year 2013, the American Cancer Society estimates that about 238 590 new cases of prostate cancer will be diagnosed and about 29 720 deaths will result from prostate cancer in the United States. From 2006 - 2010, the annual incidence of prostate cancer was 152 per 100 000. Prostate cancer is usually suspected based on an elevated prostate specific antigen (PSA) test or abnormal digital rectal exam, prompting transrectal ultrasound (TRUS) guided biopsy of the prostate for definitive diagnosis. The sensitivity and specificity of TRUS in detecting prostate cancers is reported to be 41% and 81% respectively while the positive predictive value (PPV) and the negative predictive value (NPV) are found to be 52.7% and 72% respectively, with an accuracy of 67%. Thus, TRUS is not reliable for the detection and localization of prostate cancer, but it is currently the only choice to perform biopsies. The prostate biopsies under TRUS guidance are now largely systematic with many popular schemes in use. Typically 5 to 12 core samples are taken from various regions of the gland. Due to sampling errors, there is a more than 30% chance of a misleading diagnosis.
This diagnostic uncertainty has much wider implications for prostate disease management in general. For example, patients who have persistent or rising PSA after several biopsy sessions remain a diagnostic dilemma. There are no definitive guidelines for when to stop performing biopsies. Then there are those who are found to have low Gleason score on their first biopsy. These patients are put on an active surveillance program where they have to have periodic biopsies because ultrasound has no prognostic value. These repeated biopsies cause tremendous anxiety to patients and increase the incidence of possible complications, not to mention added cost burden to the medical system. Upon review of clinical literature, American Urology Association guidelines, updated in 2007, conclude that there is insufficient clinical data to provide definitive guidelines for prostate disease management. Worse yet, there is no adequate imaging modality that could be used to generate such data on which one could build treatment planning guidelines.
To increase the sensitivity of TRUS, ultrasound-based techniques that can be easily integrated to produce co-registered images have been investigated. Notable examples are contrast-enhanced ultrasound (CEUS) and real-time elastography (RTE). The sensitivity of CEUS in detecting prostate cancer is 65-68% while the sensitivity of RTE is only 60.8%. Moreover, the ability of RTE to detect cancer lesions that are less than 10 mm in size is reported to be only 16%; thus it too has limited value in prostate cancer diagnosis. Other imaging modalities including magnetic resonance imaging, computed tomography, positron emission tomography, and radionuclide scintigraphy (Prostascint) have demonstrated limited use in the detection of prostate cancer and are primarily reserved for the evaluation and staging of advanced cancer. Furthermore they are expensive and cannot be easily integrated with TRUS to produce co-registered images to be used during biopsies.
Clearly there is a need for a new imaging technique that accurately detects prostate cancer with high sensitivity. Because of cost efficiency and real time imaging capability, TRUS will remain preferred modality for prostate biopsy. Thus it is highly desirable that any new modality be integrated with US to provide near real time guidance during biopsy. This is an important niche area in prostate cancer diagnosis and disease management. Our approach is to engineer a device that will integrate an emerging functional imaging modality, namely photoacoustic imaging with ultrasound using acoustic lens-based focusing technology.
Photoacoustic imaging promises to become a valuable tool in many clinical areas where there are unmet needs, as evidenced by several review articles written in the past decade. We have been working with photoacoustic imaging technology and investigating its potential for medical diagnostics for the past several years. photoacoustic imaging is based on photoacoustic effect, where a short time duration ultrasound wave, also referred to as photoacoustic signal, is generated due to thermal expansion of light absorbers when it is exposed to a high intensity nanosecond pulses of near-infra-red (NIR) laser light. The tissue and its major constituents (water, oxy and de-oxy hemoglobin in blood, lipid, fat, melanin, collagen, etc.) have widely varying absorption spectra in the NIR region that not only provide abundant contrast features, but also open the door for photoacoustic imaging-based spectroscopy, non-invasive tissue characterization, and functional imaging. With this technology, one can depict optical absorption property of the tissue constituents up to a few centimeters deep with sub-millimeter resolution. Using our prototype photoacoustic imaging probe with lens based focusing for ex-vivo studies, we concluded that cancer regions were found to be more hypoxic than benign regions in prostate tissue. Differentiation of cancerous from benign prostate tissue with high specificity (96.2%) and good sensitivity (81.3%) with a PPV of 92.9% and NPV of 89.3% was demonstrated. Our own ex-vivo data provides us the motivation to explore this technology further for in-vivo use. Our photoacoustic imaging probe will provide the functional information that will address most of the diagnostic and prognostic challenges that exist today and have been outlined earlier.
The ultimate goal is to develop an imaging modality prototype device that can clearly differentiate cancerous from benign prostate tissue in patients with positive PSA results. This will also help identify patients who need no further treatment, as well as aid in reducing false negative results due to poor cancer targeting of TRUS biopsy needles. Due to the functional nature of photoacoustic imaging, it is possible that the photoacoustic combined with ultrasound dual modality imaging probe may be a useful tool to evaluate prostate tumor prognosis, response to drugs, and detection of tumor recurrence.
Written by:
Bhargava Chinni as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.
Research Associate, Department of Imaging Sciences, University of Rochester, Rochester, NY USA
Multispectral photoacoustic imaging of prostate cancer: Preliminary ex-vivo results - Abstract
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