Integration of a Raman spectroscopy system to a robotic-assisted surgical system for real-time tissue characterization during radical prostatectomy procedures.

Surgical excision of the whole prostate through a radical prostatectomy procedure is part of the standard of care for prostate cancer. Positive surgical margins (cancer cells having spread into surrounding nonresected tissue) occur in as many as 1 in 5 cases and strongly correlate with disease recurrence and the requirement of adjuvant treatment. Margin assessment is currently only performed by pathologists hours to days following surgery and the integration of a real-time surgical readout would benefit current prostatectomy procedures. Raman spectroscopy is a promising technology to assess surgical margins: its in vivo use during radical prostatectomy could help insure the extent of resected prostate and cancerous tissue is maximized. We thus present the design and development of a dual excitation Raman spectroscopy system (680- and 785-nm excitations) integrated to the robotic da Vinci surgical platform for in vivo use. Following validation in phantoms, spectroscopic data from 20 whole human prostates immediately following radical prostatectomy are obtained using the system. With this dataset, we are able to distinguish prostate from extra prostatic tissue with an accuracy, sensitivity, and specificity of 91%, 90.5%, and 96%, respectively. Finally, the integrated Raman spectroscopy system is used to collect preliminary spectroscopic data at the surgical margin in vivo in four patients.

Development and first in-human use of a Raman spectroscopy guidance system integrated with a brain biopsy needle.

Navigation-guided brain biopsies are the standard of care for diagnosis of several brain pathologies. However, imprecise targeting and tissue heterogeneity often hinder obtaining high-quality tissue samples, resulting in poor diagnostic yield. We report the development and first clinical testing of a navigation-guided fiberoptic Raman probe that allows surgeons to interrogate brain tissue in situ at the tip of the biopsy needle prior to tissue removal. The 900 µm diameter probe can detect high spectral quality Raman signals in both the fingerprint and high wavenumber spectral regions with minimal disruption to the neurosurgical workflow. The probe was tested in three brain tumor patients, and the acquired spectra in both normal brain and tumor tissue demonstrated the expected spectral features, indicating the quality of the data. As a proof-of-concept, we also demonstrate the consistency of the acquired Raman signal with different systems and experimental settings. Additional clinical development is planned to further evaluate the performance of the system and develop a statistical model for real-time tissue classification during the biopsy procedure.

A new method using Raman spectroscopy for in vivo targeted brain cancer tissue biopsy.

Modern cancer diagnosis requires histological, molecular, and genomic tumor analyses. Tumor sampling is often achieved using a targeted needle biopsy approach. Targeting errors and cancer heterogeneity causing inaccurate sampling are important limitations of this blind technique leading to non-diagnostic or poor quality samples, and the need for repeated biopsies pose elevated patient risk. An optical technology that can analyze the molecular nature of the tissue prior to harvesting could improve cancer targeting and mitigate patient risk. Here we report on the design, development, and validation of an in situ intraoperative, label-free, cancer detection system based on high wavenumber Raman spectroscopy. This optical detection device was engineered into a commercially available biopsy system allowing tumor analysis prior to tissue harvesting without disrupting workflow. Using a dual validation approach we show that high wavenumber Raman spectroscopy can detect human dense cancer with >60% cancer cells in situ during surgery with a sensitivity and specificity of 80% and 90%, respectively. We also demonstrate for the first time the use of this system in a swine brain biopsy model. These studies set the stage for the clinical translation of this optical molecular imaging method for high yield and safe targeted biopsy.

Raman spectroscopy in microsurgery: impact of operating microscope illumination sources on data quality and tissue classification.

Ambient light artifacts can confound Raman spectroscopy measurements performed in a clinical setting such as during open surgery. However, requiring light sources to be turned off during intraoperative spectral acquisition can be impractical because it can slow down the procedure by requiring surgeons to acquire data under light conditions different from the routine clinical practice. Here a filter system is introduced allowing in vivo Raman spectroscopy measurements to be performed with the light source of a neurosurgical microscope turned on, without interfering with the standard procedure. Ex vivo and in vivo results on calf and human brain, respectively, show that when the new filter system is used there is no significant difference between Raman spectra acquired under pitch dark conditions or with the microscope light source turned on. This is important for the clinical translation of Raman spectroscopy because of the resulting decrease in total imaging time for each measurement and because the surgeon can now acquire spectroscopic data with no disruption of the surgical workflow.