Edward A. Jasion

Systematic diagnosis of prostate cancer using an optical biopsy needle adjunct with fluorescence spectroscopy

Transrectal ultrasound guided prostate biopsies often fail to diagnose prostate cancer with 90% of cores reported as benign. Thus, it is desirable to target prostate cancer lesions while reducing the sampling of benign tissue. The concentrations of natural fluorophores in prostate tissue fluctuate with disease states. Hence, fluorescence spectroscopy could be used to quantify these fluctuations to identify prostate cancer. An optical biopsy needle with a light sensitive optical probe at the tip of the inner needle was developed to take prostate biopsies after measuring tissue fluorescence with a laboratory fluorometer. The optical probe consists of eight 100 μm fibers for tissue excitation and a single 200 μm fiber to capture fluorescence spectra. Random biopsy cores were taken from 20 surgically excised prostates after measuring fluorescence spectra of tissue between 295-550nm for several excitations between 280-350nm. Each biopsy core was histopathologically classified and correlated with corresponding spectra. Prostate biopsies were grouped into benign or malignant based on the histological findings. Out of 187 biopsy cores, 109 were benign and 78 were malignant. Partial least square analysis of tissue spectra was performed to identify diagnostically significant principal components as potential classifiers. A linear support vector machine and leave-one-out cross validation method was employed for tissue classification. Study results show 86% sensitivity, 87% specificity, 90% negative predictive value, and 83% positive predictive value for benign versus malignant prostate tissue classification. This study demonstrates potential clinical applications of fluorescence spectroscopy guided optical biopsy needle for prostate cancer diagnosis with the consequent improvement of patient care.

Diffuse reflectance spectroscopy can differentiate high grade and low grade prostatic carcinoma

Prostate tumors are graded by the revised Gleason Score (GS) which is the sum of the two predominant Gleason grades present ranging from 6-10. GS 6 cancer exclusively with Gleason grade 3 is designated as low grade (LG) and correlates with better clinical prognosis for patients. GS >7 cancer with at least one of the Gleason grades 4 and 5 is designated as HG indicate worse prognosis for patients. Current transrectal ultrasound guided prostate biopsies often fail to correctly diagnose HG prostate cancer due to sampling errors. Diffuse reflectance spectra (DRS) of biological tissue depend on tissue morphology and architecture. Thus, DRS could potentially differentiate between HG and LG prostatic carcinoma. A 15-gauge optical biopsy needle was prototyped to take prostate biopsies after measuring DRS with a laboratory fluorometer. This needle has an optical sensor that utilizes 8×100 μm optical fibers for tissue excitation and a single 200 μm central optical fiber to measure DRS. Tissue biopsy cores were obtained from 20 surgically excised prostates using this needle after measuring DRS at 5 nm intervals between 500-700 nm wavelengths. Tissue within a measurement window was histopathologically classified as either benign, LG, or HG and correlated with DRS. Partial least square analysis of DRS identified principal components (PC) as potential classifiers. Statistically significant PCs (p<;0.05) were tested for their ability to classify biopsy tissue using support vector machine and leave-one-out cross validation method. There were 29 HG and 49 LG cancers among 187 biopsy cores included in the study. Study results show 76% sensitivity, 80% specificity, 93% negative predictive value, and 50% positive predictive value for HG versus benign, and 76%, 73%, 84%, and 63%, for HG versus LG prostate tissue classification. DRS failed to diagnose 7/29 (24%) HG cancers. This study demonstrated that an optical biopsy needle guided by DRS has sufficient accuracy to differentiate HG from LG carcinoma and benign tissue. It may allow precise targeting of HG prostate cancer providing more accurate assessment of the disease and improvement in patient care.Prostate tumors are graded by the revised Gleason Score (GS) which is the sum of the two predominant Gleason grades present ranging from 6-10. GS 6 cancer exclusively with Gleason grade 3 is designated as low grade (LG) and correlates with better clinical prognosis for patients. GS >7 cancer with at least one of the Gleason grades 4 and 5 is designated as HG indicate worse prognosis for patients. Current transrectal ultrasound guided prostate biopsies often fail to correctly diagnose HG prostate cancer due to sampling errors. Diffuse reflectance spectra (DRS) of biological tissue depend on tissue morphology and architecture. Thus, DRS could potentially differentiate between HG and LG prostatic carcinoma. A 15-gauge optical biopsy needle was prototyped to take prostate biopsies after measuring DRS with a laboratory fluorometer. This needle has an optical sensor that utilizes 8×100 μm optical fibers for tissue excitation and a single 200 μm central optical fiber to measure DRS. Tissue biopsy cores were obtained from 20 surgically excised prostates using this needle after measuring DRS at 5 nm intervals between 500-700 nm wavelengths. Tissue within a measurement window was histopathologically classified as either benign, LG, or HG and correlated with DRS. Partial least square analysis of DRS identified principal components (PC) as potential classifiers. Statistically significant PCs (p<;0.05) were tested for their ability to classify biopsy tissue using support vector machine and leave-one-out cross validation method. There were 29 HG and 49 LG cancers among 187 biopsy cores included in the study. Study results show 76% sensitivity, 80% specificity, 93% negative predictive value, and 50% positive predictive value for HG versus benign, and 76%, 73%, 84%, and 63%, for HG versus LG prostate tissue classification. DRS failed to diagnose 7/29 (24%) HG cancers. This study demonstrated that an optical biopsy needle guided by DRS has sufficient accuracy to differentiate HG from LG carcinoma and benign tissue. It may allow precise targeting of HG prostate cancer providing more accurate assessment of the disease and improvement in patient care.

Human feasibility study of fluorescence spectroscopy guided optical biopsy needle for prostate cancer diagnosis

Current prostate biopsy cores have a very low diagnostic yield. These biopsies often fail to diagnose prostate cancer since 90% of cores are histopathologically classified as benign. The concentrations of endogenous fluorophores in prostate tissue vary with disease states. Thus, fluorescence spectroscopy could be utilized to quantify these variations for identification of malignant lesions. We investigated clinical feasibility of a 14 gauge (1.98 mm) optical biopsy needle guided by fluorescence spectroscopy for real-time in vivo prostate cancer diagnosis. Built-in optical sensor has 8×100μm fibers for tissue excitation and a single 200μm fiber to collect spectral data. Custom-made fluorometer has 2 light-emitting diodes at 290 and 340 nm and a spectrometer. User interface for fluorometer operation and data collection was developed using LabView software. Each spectral data acquisition required ~2 seconds. The in vivo biopsies were performed during radical retropubic prostatectomy surgery on the exposed prostate with blood flow to the gland intact. A tissue biopsy core was obtained from each biopsy site after acquisition of spectral data. Above procedure was repeated ex vivo after surgical excision of the prostate. Biopsy cores were histopathologically classified as either benign or malignant and correlated with corresponding spectral data. Partial Least Square analysis was performed to determine diagnostically significant principal components as potential classifiers. A linear support vector machine and leave-one-out cross validation method was employed for tissue classification. Thirteen patients were consented to the study. Histopathological analysis found cancer in 29/208 in vivo and 51/224 ex vivo viable biopsy cores. Study results show 72% sensitivity, 66% specificity, and 93% negative predictive value for in vivo and 75%, 80%, and 93%, respectively, for ex vivo malignant versus benign prostatic tissue classification. Optical biopsy needle has a very high negative predictive value to indicate benign tissue while sufficient sensitivity for targeting areas suspicious for cancer within the prostate gland. Hence, the optical biopsy needle can increase the diagnostic yield of prostate biopsies with consequent improvement in patient care.