Introduction:
Prostate cancer (PCa) is the second leading cause of cancer death in American men. Transrectal ultrasound (TRUS) guided prostate biopsy, the standard procedure for diagnosing PCa, involves tissue extractions. The microarchitecture of the biopsied tissue is afterwards visualized by histological or immunohistochemical procedures, and characterized by a Gleason score, a highly prognostic factor describing PCa aggressiveness. TRUS, despite its ability to delineate prostate contour, often struggles with low sensitivity in identifying cancerous tissues. Small yet clinically important tumors are frequently missed. To address these problems, preprocedural magnetic resonance imaging (MRI) has been integrated for targeted biopsies. Unfortunately, the availability of MRI is limited, and the imperfect co-registration between the preprocedural MRI and the real-time TRUS produces 10-20% false negative cases. Moreover, the diagnosis with experienced surgeons can be distinctive due to the small sampling volume. This project aims to develop a real-time, large-volume sensing or imaging technology capable of mapping the distribution of malignancies in the prostate, enabling more accurate biopsy guidance to ensure at least one sample is obtained from the region containing the most aggressive cancer.
Photoacoustic (PA) imaging and sensing combine optical sensitivity to tissue components and ultrasound (US) resolution to discern the microarchitectures formed by individual components. Most previous studies on optical or PA imaging of PCa have attempted transrectal imaging as well as transurethral illumination. However, due to the optical and acoustic attenuation, it is difficult to capture the high frequency signals encoding the microscopic architecture information at 10s of microns, which is the key diagnostic factor in Gleason scoring system. As a trade-off between invasiveness and diagnostic reliability, 1) we developed an interstitial measurement approach, where a needle PA sensing probe with identical dimensions as a biopsy needle is inserted into the prostate for PA measurements; 2) we also developed a PA spectral analysis (PASA) method to quantify the tissue microarchitecture information encoded in the measurements; 3) with a tunable laser, we are able to independently target and quantify the relative content of hemoglobin, lipid , collagen and cell nuclei, and averaged architectural dimensions formed by these tissue components, which are directly correlated with those described in the Gleason scoring system.
All-optical Sensing Probe, Control System :
Fig. 1 Design and Application of the all-optical sensing needle PA probe in human subjects. (a-d) Pictures of the 18G all-optical PA sensing probe. (a) Optical components without the needle sheath. FOD: Fiber optic diffuser. FOH: Fiber optic hydrophone. (b) Side view and (c) Top view of the functional segment of the needle probe in the red-dashed box in (d) with 700nm laser coupled into the needle. (e) The data acquisition system on cart. (f) A urological surgeon operating the needle probe during a biopsy procedure.
Example results:
Fig. 2 (a) Experiment setup simulating a US guided transperineal prostate biopsy. (b) Gross pathology by slicing the prostate into 4-5 mm thick samples. The blue spots are the spatial markers of the PA measurements. The 2D contours of the cancers were delineated. (c-e) are box plots showing the quantified spectral slopes of the three categories of tissues measured at the wavelength of 1220 nm, 1370 nm, and 266 nm, respectively. Median values are marked by red lines. (f-h) Representative histology photographs of the measured human prostate tissue samples, including a benign sample, a nonaggressive cancer tissue with GS=6, and an aggressive cancer tissue with GS=7. 100× objective magnification.
Fig. 3 2D PASA in a transgenic mouse model. (a)–(c) Gross pathology picture with prostate cancer progresses. (d)–(f) PA images of the prostates in (ac). The dotted line depicts the prostate contours delineated according to the photos in (a)–(c). (g)–(i) Pixel-wise PASA slopes overlaid on top of the prostate contours. (j)–(l) Hematoxylin and eosin (H&E) histology examples of the same prostates in (a)–(i). Scale bars in (a)–(i) and (j)–(l) represent 5 mm and 100 µm, respectively.