Detection of Melanoma Metastases in Resected Human Lymph Nodes by Noninvasive Multispectral Photoacoustic Imaging

Objective. Sentinel node biopsy in patients with cutaneous melanoma improves staging, provides prognostic information, and leads to an increased survival in node-positive patients. However, frozen section analysis of the sentinel node is not reliable and definitive histopathology evaluation requires days, preventing intraoperative decision-making and immediate therapy. Photoacoustic imaging can evaluate intact lymph nodes, but specificity can be hampered by other absorbers such as hemoglobin. Near infrared multispectral photoacoustic imaging is a new approach that has the potential to selectively detect melanin. The purpose of the present study is to examine the potential of multispectral photoacoustic imaging to identify melanoma metastasis in human lymph nodes. Methods. Three metastatic and nine benign lymph nodes from eight melanoma patients were scanned ex vivo using a Vevo LAZR multispectral photoacoustic imager and were spectrally analyzed per pixel. The results were compared to histopathology as gold standard. Results. The nodal volume could be scanned within 20 minutes. An unmixing procedure was proposed to identify melanoma metastases with multispectral photoacoustic imaging. Ultrasound overlay enabled anatomical correlation. The penetration depth of the photoacoustic signal was up to 2 cm. Conclusion. Multispectral three-dimensional photoacoustic imaging allowed for selective identification of melanoma metastases in human lymph nodes

Optical tissue identification:weefseldifferentiatie met behulp van licht

This thesis describes the evaluation of optical tissue identification for surgical applications. Three promising techniques are examined. After exploration of near infra-red fluorescence imaging and photoacoustic imaging, the thesis will focus on diffuse reflectance spectroscopy (DRS) for surgical tissue identification. Chapter two describes the use of an intraoperative fluorescence camera in breast cancer phantoms. The technique provides the surgeon with an image overlay of the fluorescent contrast agent in phantoms mimicking absorption and scattering properties of human breast tissue. Important benefits and drawbacks are described. Chapter three covers the application of photoacoustic imaging in surgery. The research is focused on lymph nodes in melanoma patients. Melanin, a strong optical absorber is imaged photoacoustically. The spectral identification of both tumor and blood vessels is demonstrated in phantoms and human lymph nodes ex vivo. The photoacoustic imager used is a reflective type, with the light source incorporated in the ultrasound detector. Diffuse reflection spectroscopy is presented as an optical technique able to identify both tumor and vital surrounding structures like blood vessels and nerves. Colorectal tumors are frequently in close relation with vital structures. In oncologic rectum surgery, bladder- and sexual dysfunctions are both feared and high in incidence. Chapter four describes the identification of colorectal tumor using DRS. Chapter five and six describe the identification of peripheral nerves in human during surgery. Peripheral nerves are often part of the vital structures surrounding a tumor. Ideally, image guided surgery depicts both tumor and vital surrounding tissue. Chapter five describes the identification of larger nerves as proof of principle. Chapter six is committed to the detection of smaller peripheral nerves. Optimization and validation is not necessarily executed in humans in vivo. Logistically, and patient friendly, more suited for extensive measurements are a post mortem- or animal studies. However, DRS is subject to the morphological composition and biochemical make-up of the tissue, and both will change post mortem and may differ between human and animal. Chapter seven describes the optical similarities and differences between in vivo versus post mortem and human versus swine, focused on nerve identification. In chapter eight we explore to possibilities to incorporate the DRS technique into a clinical device. We choose a bronchoscopic tool to fully utilize the small size and flexibility of the DRS optical fibers. This thesis concludes with a general discussion and outlook on a use of optical tissue identification

Nerve detection during surgery: optical spectroscopy for peripheral nerve localization

Precise nerve localization is of major importance in both surgery and regional anesthesia. Optically based techniques can identify tissue through differences in optical properties, like absorption and scattering. The aim of this study was to evaluate the potential of optical spectroscopy (diffuse reflectance spectroscopy) for clinical nerve identification in vivo. Eighteen patients (8 male, 10 female, age 53 ± 13 years) undergoing inguinal lymph node resection or resection or a soft tissue tumor in the groin were included to measure the femoral or sciatic nerve and the surrounding tissues. In vivo optical measurements were performed using Diffuse Reflectance Spectroscopy (400–1600 nm) on nerve, near nerve adipose tissue, muscle, and subcutaneous fat using a needle-shaped probe. Model-based analyses were used to derive verified quantitative parameters as concentrations of optical absorbers and several parameters describing scattering. A total of 628 optical spectra were recorded. Measured spectra reveal noticeable tissue specific characteristics. Optical absorption of water, fat, and oxy- and deoxyhemoglobin was manifested in the measured spectra. The parameters water and fat content showed significant differences (P < 0.005) between nerve and all surrounding tissues. Classification using k-Nearest Neighbor based on the derived parameters revealed a sensitivity of 85% and a specificity of 79%, for identifying nerve from surrounding tissues. Diffuse Reflectance Spectroscopy identifies peripheral nerve bundles. The differences found between tissue groups are assignable to the tissue composition and structure