Diffuse reflectance spectroscopy for breach detection during pedicle screw placement: a first in vivo investigation in a porcine model.

BACKGROUND: The safe and accurate placement of pedicle screws remains a critical step in open and minimally invasive spine surgery, emphasizing the need for intraoperative guidance techniques. Diffuse reflectance spectroscopy (DRS) is an optical sensing technology that may provide intraoperative guidance in pedicle screw placement. PURPOSE: The study presents the first in vivo minimally invasive procedure using DRS sensing at the tip of a Jamshidi needle with an integrated optical K-wire. We investigate the effect of tissue perfusion and probe-handling conditions on the reliability of fat fraction measurements for breach detection in vivo. METHODS: A Jamshidi needle with an integrated fiber-optic K-wire was gradually inserted into the vertebrae under intraoperative image guidance. The fiber-optic K-wire consisted of two optical fibers with a fiber-to-fiber distance of 1.024 mm. DRS spectra in the wavelength range of 450 to 1600 nm were acquired at several positions along the path inside the vertebrae. Probe-handling conditions were varied by changing the amount of pressure exerted on the probe within the vertebrae. Continuous spectra were recorded as the probe was placed in the center of the vertebral body while the porcine specimen was sacrificed via a lethal injection. RESULTS: A typical insertion of the fiber-optic K-wire showed a drop in fat fraction during an anterior breach as the probe transitioned from cancellous to cortical bone. Fat fraction measurements were found to be similar irrespective of the amount of pressure exerted on the probe (p = 0.65). The 95% confidence interval of fat fraction determination was found in the narrow range of 1.5-3.6% under various probe-handling conditions. The fat fraction measurements remained stable during 70 min of decreased blood flow after the animal was sacrificed. DISCUSSIONS: These findings indicate that changes in tissue perfusion and probe-handling conditions have a relatively low measureable effect on the DRS signal quality and thereby on the determination of fat fraction as a breach detection signal. CONCLUSIONS: Fat fraction quantification for intraoperative pedicle screw breach detection is reliable, irrespective of changes in tissue perfusion and probe-handling conditions.

Review: in vivo optical spectral tissue sensing-how to go from research to routine clinical application?

Innovations in optical spectroscopy have helped the technology reach a point where performance previously seen only in laboratory settings can be translated and tested in real-world applications. In the field of oncology, spectral tissue sensing (STS) by means of optical spectroscopy is considered to have major potential for improving diagnostics and optimizing treatment outcome. The concept has been investigated for more than two decades and yet spectral tissue sensing is not commonly employed in routine medical practice. It is therefore important to understand what is needed to translate technological advances and insights generated through basic scientific research in this field into clinical practice. The aim of the discussion presented here is not to provide a comprehensive review of all work published over the last decades but rather to highlight some of the challenges found in literature and encountered by our group in the quest to translate optical technologies into useful clinical tools. Furthermore, an outlook is proposed on how translational researchers could proceed to eventually have STS incorporated in the process of clinical decision-making.

In vivo tumor identification of colorectal liver metastases with diffuse reflectance and fluorescence spectroscopy.

BACKGROUND AND OBJECTIVE: Over the last decade, an increasing effort has been put towards the implementation of optical guidance techniques to aid surgeons during cancer surgery. Diffuse reflectance spectroscopy (DRS) and fluorescence spectroscopy (FS) are two of these new techniques. The objective of this study is to investigate whether in vivo optical spectroscopy is able to accurately discriminate colorectal liver metastases (CRLM) from normal liver tissue in vivo. MATERIALS AND METHODS: DRS and FS were incorporated at the tip of a needle and were used for in vivo tissue differentiation during resection of CRLM. Measurements were taken in and around the tumor lesions and measurement sites were marked and correlated to histology (i.e., normal liver tissue or tumor tissue). Patients with and without neoadjuvant systemic chemotherapy were included into the study. RESULTS: Four hundred and eighty-four measurements were taken in and near 19 liver lesions prior to resection. Overall sensitivity and specificity for DRS was 95% and 92%, respectively. Bile was the most discriminative parameter. The addition of FS did not improve the overall accuracy. Sensitivity and specificity was not hampered by neo-adjuvant chemotherapy; sensitivity and specificity after neo-adjuvant chemotherapy were 92% and 100%, respectively. CONCLUSION: We have successfully integrated spectroscopy technology into a disposable 15 Gauge optical needle and we have shown that DRS and FS can accurately discriminate CRLM from normal liver tissue in the in vivo setting regardless of whether the patient was pre-treated with systemic therapy. This technique makes in vivo guidance accessible for common surgical practice. Lasers Surg. Med. 48:820-827, 2016. © 2016 Wiley Periodicals, Inc.

Diffuse reflectance spectroscopy: toward real-time quantification of steatosis in liver.

Assessment of fatty liver grafts during orthotopic liver transplantation is a challenge due to the lack of real-time analysis options during surgery. Diffuse reflectance spectroscopy (DRS) could be a new diagnostic tool to quickly assess steatosis. Eight hundred and seventy-eight optical measurements were performed in vivo in 17 patients in liver tissue during surgery and ex vivo on liver resection specimens from 41 patients. Liver steatosis was quantified from the collected optical spectra and compared with the histology analysis from the measurement location by three independent pathologists. Twenty two patients were diagnosed with <5% steatosis, 15 patients had mild steatosis, and four had moderate steatosis. Severe steatosis was not identified. Intraclass correlation between the pathologists analysis was 0.949. A correlation of 0.854 was found between the histology and DRS analyses of liver steatosis ex vivo. For the same liver tissue, a correlation of 0.925 was demonstrated between in vivo and ex vivo DRS analysis for steatosis quantification. DRS can quantify steatosis in liver tissue both in vivo and ex vivo with good agreement compared to histopathology analysis. This analysis can be performed real time and may therefore be useful for fast objective assessment of liver steatosis in liver surgery.

Validation of diffuse reflectance spectroscopy with magnetic resonance imaging for accurate vertebral bone fat fraction quantification.

Safe and accurate placement of pedicle screws remains a critical step in open and minimally invasive spine surgery. The diffuse reflectance spectroscopy (DRS) technique may offer the possibility of intra-operative guidance for pedicle screw placement. Currently, Magnetic Resonance Imaging (MRI) is one of the most accurate techniques used to measure fat concentration in tissues. Therefore, the purpose of this study is to compare the accuracy of fat content measured invasively in vertebrae using DRS and validate it against the Proton density fat fraction (PDFF) derived via MRI. Chemical shift-encoding-based water-fat imaging of the spine was first performed on six cadavers. PDFF images were computed and manually segmented. 23 insertions using a custom-made screw probe with integrated optical fibers were then performed under cone beam computer tomography (CBCT). DR spectra were recorded at several positions along the trajectory as the optical screw probe was inserted turn by turn into the vertebral body. Fat fractions determined via DRS and MRI techniques were compared by spatially correlating the optical screw probe position within the vertebrae on CBCT images with respect to the PDFF images. The fat fraction determined by DRS was found to have a high correlation with those determined by MRI, with a Pearson coefficient of 0.950 (P< 0.001) as compared with PDFF measurements calculated from the MRI technique. Additionally, the two techniques were found to be comparable for fat fraction quantification within vertebral bodies (R2 = 0.905).

Diffuse reflectance spectroscopy accurately identifies the pre-cortical zone to avoid impending pedicle screw breach in spinal fixation surgery.

Pedicle screw placement accuracy during spinal fixation surgery varies greatly and severe misplacement has been reported in 1-6.5% of screws. Diffuse reflectance (DR) spectroscopy has previously been shown to reliably discriminate between tissues in the human body. We postulate that it could be used to discriminate between cancellous and cortical bone. Therefore, the purpose of this study is to validate DR spectroscopy as a warning system to detect impending pedicle screw breach in a cadaveric surgical setting using typical clinical breach scenarios. DR spectroscopy was incorporated at the tip of an integrated pedicle screw and screw driver used for tissue probing during pedicle screw insertions on six cadavers. Measurements were collected in the wavelength range of 400-1600 nm and each insertion was planned to result in a breach. Measurements were labelled as cancellous, cortical or representing a pre-cortical zone (PCZ) in between, based on information from cone beam computed tomographies at corresponding positions. In addition, DR spectroscopy data was recorded after breach. Four typical pedicle breach types were performed, and a total of 45 pedicle breaches were recorded. For each breach direction, the technology was able to detect the transition of the screw tip from the cancellous bone to the PCZ (P < 0.001), to cortical bone (P < 0.001), and to a subsequent breach (P < 0.001). Using support vector machine (SVM) classification, breach could reliably be detected with a sensitivity of 98.3 % [94.3-100 %] and a specificity of 97.7 % [91.0-100 %]. We conclude that DR spectroscopy reliably identifies the area of transition from cancellous to cortical bone in typical breach scenarios and can warn the surgeon of impending pedicle breach, thereby resulting in safer spinal fixation surgeries.

Diffuse reflectance spectroscopy, a potential optical sensing technology for the detection of cortical breaches during spinal screw placement.

Safe and accurate placement of screws remains a critical issue in open and minimally invasive spine surgery. We propose to use diffuse reflectance (DR) spectroscopy as a sensing technology at the tip of a surgical instrument to ensure a safe path of the instrument through the cancellous bone of the vertebrae. This approach could potentially reduce the rate of cortical bone breaches, thereby resulting in fewer neural and vascular injuries during spinal fusion surgery. In our study, DR spectra in the wavelength ranges of 400 to 1600 nm were acquired from cancellous and cortical bone from three human cadavers. First, it was investigated whether these spectra can be used to distinguish between the two bone types based on fat, water, and blood content along with photon scattering. Subsequently, the penetration of the bone by an optical probe was simulated using the Monte-Carlo (MC) method, to study if the changes in fat content along the probe path would still enable distinction between the bone types. Finally, the simulation findings were validated via an experimental insertion of an optical screw probe into the vertebra aided by x-ray image guidance. The DR spectra indicate that the amount of fat, blood, and photon scattering is significantly higher in cancellous bone than in cortical bone (p < 0.01), which allows distinction between the bone types. The MC simulations showed a change in fat content more than 1 mm before the optical probe came in contact with the cortical bone. The experimental insertion of the optical screw probe gave similar results. This study shows that spectral tissue sensing, based on DR spectroscopy at the instrument tip, is a promising technology to identify the transition zone from cancellous to cortical vertebral bone. The technology therefore has the potential to improve the safety and accuracy of spinal screw placement procedures.

Spectral sensing for tissue diagnosis during lung biopsy procedures: The importance of an adequate internal reference and real-time feedback.

OBJECTIVES: Difficulties in obtaining a representative tissue sample are a major obstacle in timely selecting the optimal treatment for patients with lung cancer or other malignancies. Having a modality to provide needle guidance and confirm the biopsy site selection could be of great clinical benefit, especially when small masses are targeted. The objective of this study was to evaluate whether diffuse reflectance spectroscopy (DRS) at the tip of a core biopsy needle can be used for biopsy site confirmation in real time, thereby enabling optimized biopsy acquisition and improving diagnostic capability. MATERIALS AND METHODS: We included a total of 23 patients undergoing a routine computed tomography (CT) guided transthoracic needle biopsy of a lesion suspected for lung cancer or metastatic disease. DRS measurements were acquired during needle insertion and clinically relevant parameters were extracted from the spectral data along the needle paths. Histopathology results were compared with the DRS data at the final measurement position. RESULTS: Analysis of the collective data acquired from all enrolled subjects showed significant differences (p<0.01) for blood content, stO2, water content, and scattering amplitude. The identified spectral contrast matched the final pathology in 20 out of 22 clinical cases that could be used for analysis, which corresponds with an overall diagnostic performance of 91%. Three cases underlined the importance of adequate reference measurements and the need for real time diagnostic feedback. Continuous real time DRS measurements performed during a biopsy procedure in one patient provided clear information with respect to the variation in tissue and allowed identification of the tumour boundary. CONCLUSIONS: The presented technology creates a basis for the design and clinical implementation of integrated fibre-optic tools for a variety of minimal invasive applications.

Real-time In Vivo Tissue Characterization with Diffuse Reflectance Spectroscopy during Transthoracic Lung Biopsy: A Clinical Feasibility Study.

PURPOSE: This study presents the first in vivo real-time tissue characterization during image-guided percutaneous lung biopsies using diffuse reflectance spectroscopy (DRS) sensing at the tip of a biopsy needle with integrated optical fibers. EXPERIMENTAL DESIGN: Tissues from 21 consented patients undergoing lung cancer surgery were measured intraoperatively using the fiber-optic platform capable of assessing various physical tissue properties highly correlated to tissue architecture and composition. In addition, the method was tested for clinical use by performing DRS tissue sensing during 11 routine biopsy procedures in patients with suspected lung cancer. RESULTS: We found that water content and scattering amplitude are the primary discriminators for the transition from healthy lung tissue to tumor tissue and that the reliability of these parameters is not affected by the amount of blood at the needle tip. In the 21 patients measured intraoperatively, the water-to-scattering ratio yielded a 56% to 81% contrast difference between tumor and surrounding tissue. Analysis of the 11 image-guided lung biopsy procedures showed that the tissue diagnosis derived from DRS was diagnostically discriminant in each clinical case. CONCLUSIONS: DRS tissue sensing integrated into a biopsy needle may be a powerful new tool for biopsy guidance that can be readily used in routine diagnostic lung biopsy procedures. This approach may not only help to increase the successful biopsy yield for histopathologic analysis, but may also allow specific sampling of vital tumor tissue for genetic profiling.

In vivo characterization of colorectal metastases in human liver using diffuse reflectance spectroscopy: toward guidance in oncological procedures.

There is a strong need to develop clinical instruments that can perform rapid tissue assessment at the tip of smart clinical instruments for a variety of oncological applications. This study presents the first in vivo real-time tissue characterization during 24 liver biopsy procedures using diffuse reflectance (DR) spectroscopy at the tip of a core biopsy needle with integrated optical fibers. DR measurements were performed along each needle path, followed by biopsy of the target lesion using the same needle. Interventional imaging was coregistered with the DR spectra. Pathology results were compared with the DR spectroscopy data at the final measurement position. Bile was the primary discriminator between normal liver tissue and tumor tissue. Relative differences in bile content matched with the tissue diagnosis based on histopathological analysis in all 24 clinical cases. Continuous DR measurements during needle insertion in three patients showed that the method can also be applied for biopsy guidance or tumor recognition during surgery. This study provides an important validation step for DR spectroscopy-based tissue characterization in the liver. Given the feasibility of the outlined approach, it is also conceivable to make integrated fiber-optic tools for other clinical procedures that rely on accurate instrument positioning.

Monitoring of tumor radio frequency ablation using derivative spectroscopy.

Despite the widespread use of radio frequency (RF) ablation, an effective way to assess thermal tissue damage during and after the procedure is still lacking. We present a method for monitoring RF ablation efficacy based on thermally induced methemoglobin as a marker for full tissue ablation. Diffuse reflectance (DR) spectra were measured from human blood samples during gradual heating of the samples from 37 to 60, 70, and 85°C. Additionally, reflectance spectra were recorded real-time during RF ablation of human liver tissue ex vivo and in vivo. Specific spectral characteristics of methemoglobin were extracted from the spectral slopes using a custom optical ablation ratio. Thermal coagulation of blood caused significant changes in the spectral slopes, which is thought to be caused by the formation of methemoglobin. The time course of these changes was clearly dependent on the heating temperature. RF ablation of liver tissue essentially led to similar spectral alterations. In vivo DR measurements confirmed that the method could be used to assess the degree of thermal damage during RF ablation and long after the tissue cooled.

Monitoring of tumor response to Cisplatin using optical spectroscopy.

INTRODUCTION: Anatomic imaging alone is often inadequate for tuning systemic treatment for individual tumor response. Optically based techniques could potentially contribute to fast and objective response monitoring in personalized cancer therapy. In the present study, we evaluated the feasibility of dual-modality diffuse reflectance spectroscopy-autofluorescence spectroscopy (DRS-AFS) to monitor the effects of systemic treatment in a mouse model for hereditary breast cancer. METHODS: Brca1(-/-); p53(-/-) mammary tumors were grown in 36 mice, half of which were treated with a single dose of cisplatin. Changes in the tumor physiology and morphology were measured for a period of 1 week using dual-modality DRS-AFS. Liver and muscle tissues were also measured to distinguish tumor-specific alterations from systemic changes. Model-based analyses were used to derive different optical parameters like the scattering and absorption coefficients, as well as sources of intrinsic fluorescence. Histopathologic analysis was performed for cross-validation with trends in optically based parameters. RESULTS: Treated tumors showed a significant decrease in Mie-scattering slope and Mie-to-total scattering fraction and an increase in both fat volume fraction and tissue oxygenation after 2 days of follow-up. Additionally, significant tumor-specific changes in the fluorescence spectra were seen. These longitudinal trends were consistent with changes observed in the histopathologic analysis, such as vital tumor content and formation of fibrosis. CONCLUSIONS: This study demonstrates that dual-modality DRS-AFS provides quantitative functional information that corresponds well with the degree of pathologic response. DRS-AFS, in conjunction with other imaging modalities, could be used to optimize systemic cancer treatment on the basis of early individual tumor response.

Improved identification of peripheral lung tumors by using diffuse reflectance and fluorescence spectroscopy.

INTRODUCTION: A significant number of transthoracic diagnostic biopsy procedures for lung lesions show indeterminate results. Such failures are potentially due to inadequate recognition of vital tumor tissue. The objective of this study was to evaluate whether optical spectroscopy at the tip of a biopsy needle device can improve the accuracy of transthoracic lung biopsies. METHODS: Ex vivo optical measurements were performed on lung tissue from 13 patients who underwent either lobectomy or segmental resection for primary non-small cell lung cancer or pulmonary metastases from various origins. From Diffuse Reflectance Spectroscopy (DRS) and Fluorescence Spectroscopy (FS) measurements, different parameters were derived such as tissue composition as well as physiological and metabolic characteristics. Subsequently, a classification and regression trees (CART) algorithm was used to classify the type of tissue based on the derived parameters. Histology analysis was used as gold standard to report sensitivity and specificity of the tissue classification based on the present optical method. RESULTS: Collective analysis of all DRS measurements showed an overall discrimination between lung parenchyma and tumor tissue with a sensitivity and specificity of 98 and 86%, respectively. When the data were analyzed per individual patient, eliminating inter-patient variation, 100% sensitivity and specificity was achieved. Furthermore, based on FS parameters, necrotic and non-necrotic tumor tissue could be distinguished with 91% sensitivity and specificity. CONCLUSION: This study demonstrates that DRS provides accurate diagnosis of malignant lung lesions, whereas FS enables identification of necrotic tissue. When both optical techniques are combined within a biopsy device, the diagnostic performance and the quality of transthoracic biopsies could significantly be enhanced.