Setting Standards for Reporting and Quantification in Fluorescence-Guided Surgery

Molecular Imaging and Biology, May 2018

Purpose Intraoperative fluorescence imaging (FI) is a promising technique that could potentially guide oncologic surgeons toward more radical resections and thus improve clinical outcome. Despite the increase in the number of clinical trials, fluorescent agents and imaging systems for intraoperative FI, a standardized approach for imaging system performance assessment and post-acquisition image analysis is currently unavailable. Procedures We conducted a systematic, controlled comparison between two commercially available imaging systems using a novel calibration device for FI systems and various fluorescent agents. In addition, we analyzed fluorescence images from previous studies to evaluate signal-to-background ratio (SBR) and determinants of SBR. Results Using the calibration device, imaging system performance could be quantified and compared, exposing relevant differences in sensitivity. Image analysis demonstrated a profound influence of background noise and the selection of the background on SBR. Conclusions In this article, we suggest clear approaches for the quantification of imaging system performance assessment and post-acquisition image analysis, attempting to set new standards in the field of FI.

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Setting Standards for Reporting and Quantification in Fluorescence-Guided Surgery

Setting Standards for Reporting and Quantif ication in Fluorescence-Guided Surgery Charlotte Hoogstins 1 2 Jan Jaap Burggraaf 2 Marjory Koller 0 Henricus Handgraaf 2 Leonora Boogerd 2 Gooitzen van Dam 0 Alexander Vahrmeijer 2 Jacobus Burggraaf 0 Department of Surgery , Nuclear Medicine and Molecular Imaging, and Intensive Care , University Medical Center, University of Groningen , Hanzeplein 1, 9713, GZGroningen , the Netherlands 1 Centre for Human Drug Research and Leiden Center for Academic Drug Research , Zernikedreef 8, 2333, CLLeiden , the Netherlands 2 Department of Surgery, Leiden University Medical Center , Albinusdreef 2, 2333, ZALeiden , the Netherlands 3 Leiden Academic Center for Drug Research , Rapenburg 70, 2311 EZ, Leiden , the Netherlands Purpose: Intraoperative fluorescence imaging (FI) is a promising technique that could potentially guide oncologic surgeons toward more radical resections and thus improve clinical outcome. Despite the increase in the number of clinical trials, fluorescent agents and imaging systems for intraoperative FI, a standardized approach for imaging system performance assessment and post-acquisition image analysis is currently unavailable. Procedures: We conducted a systematic, controlled comparison between two commercially available imaging systems using a novel calibration device for FI systems and various fluorescent agents. In addition, we analyzed fluorescence images from previous studies to evaluate signal-to-background ratio (SBR) and determinants of SBR. Results: Using the calibration device, imaging system performance could be quantified and compared, exposing relevant differences in sensitivity. Image analysis demonstrated a profound influence of background noise and the selection of the background on SBR. Conclusions: In this article, we suggest clear approaches for the quantification of imaging system performance assessment and post-acquisition image analysis, attempting to set new standards in the field of FI. Fluorescence; Optical imaging; Quantification; Image analysis; Signal-to-noise ratio; Phantom - 2,4 Introduction Image-guided surgery (IGS) is a relatively new and emerging platform, in which imaging techniques are applied intraoperatively. The goal of IGS is to provide the surgeon with realtime information on tissue in the surgical field, aiding in Charlotte Hoogstins and Jan Jaap Burggraaf contributed equally to this work. surgical decision-making [1]. Fluorescence imaging (FI) is ideal for intraoperative applications due to fast acquisition times (milliseconds), flexibility in application, and portability [2]. Various tumor-targeted near-infrared (NIR) fluorescence agents have been successfully studied in clinical trials [3–6]. Moreover, there is great potential for a broad range of clinical applications besides oncology, such as infectious and inflammatory diseases [7]. Consequently, new study groups, industry as well as hospitals are increasingly interested to explore and implement this technology in clinical care. As NIR light (wavelength 600–900 nm) is invisible to the human eye, dedicated imaging systems are needed to detect the fluorescence signal and to form a twodimensional (2D) image demarking its tissue distribution. The intraoperative detection of an imaging agent depends on various biological and optical factors (Table 1). The considerable increase in the number of clinical trials in the FI field has led to the development of a variety of FI systems [8]. However, as the imaging system represents the last link in the chain, sensitivity (i.e., detection limit) of the imaging system is crucial [9]. It is therefore important to ascertain if an imaging system is sensitive enough for the application of interest. Phantoms that mimic relevant concentrations of a fluorescent agent in scattering and absorption media can aid in the quantification of the imaging system performance. However, guidance or standard documents describing sensitivity assessment for imaging systems, whether or not including phantoms, is currently lacking [10, 11]. The interplay between biological and optical factors ultimately results in a fluorescence image, in which the fluorescence signal in both the target and background can be semi-quantified. Using ImageJ (National Institute of Health, Bethesda, USA, a public domain image processing and analysis program) or proprietary software provided with the imaging system software, area and pixel value statistics in user-defined selections, known as a region of interest (ROI), can be analyzed. Standardized methods for selection of ROIs are not available, making this procedure prone to selection bias. Using the measured fluorescence signal in the ROIs of target and background, the signal-to-background ratio (SBR, also reported as target or tumor-to-background ratio [TBR]) is calculated as: mean signal tumor SBR ¼ mean signal background The SBR is the key determinant of sensitivity and detectability in FI and is freq (...truncated)


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Charlotte Hoogstins, Jan Jaap Burggraaf, Marjory Koller, Henricus Handgraaf, Leonora Boogerd, Gooitzen van Dam, Alexander Vahrmeijer, Jacobus Burggraaf. Setting Standards for Reporting and Quantification in Fluorescence-Guided Surgery, Molecular Imaging and Biology, 2018, pp. 1-8, DOI: 10.1007/s11307-018-1220-0