Label‐Free Enhancement of Adrenal Gland Visualization Using Near‐Infrared Autofluorescence for Surgical Guidance

Abstract

Background During adrenalectomy, surgeons have traditionally relied on their subjective visual skills to distinguish adrenal glands (AGs) from retroperitoneal fat and surrounding structures, while ultrasound and exogenous contrast agents have been employed for intraoperative AG visualization, all of which have their limitations. We present a novel label‐free approach that uses near‐infrared autofluorescence (NIRAF) detection, which demonstrates potential for enhanced intraoperative AG visualization and efficient tumor resection during adrenalectomies. Methods Patients undergoing adrenalectomy or nephrectomy were enrolled for this feasibility study. NIRAF emitted beyond 800 nm was detected in vivo from AGs and surrounding tissues during open adrenalectomies or nephrectomies. NIRAF was also measured ex vivo in excised AGs following robotic adrenalectomies. NIRAF images of tissues were captured using near‐infrared (NIR) camera systems, whereas NIRAF intensities were recorded concurrently using fiber‐optic probe‐based NIR devices. Normalized NIRAF intensities (expressed as mean ± standard error) were analyzed and compared. Results Among the 55 enrolled patients, NIRAF intensity was elevated significantly for AGs versus retroperitoneal fat and other structures. NIR images of AGs also revealed a distinct demarcation of NIRAF between adrenal cortex and other periadrenal structures. NIRAF intensity in AGs was decreased markedly in malignant adrenal tumors, while benign adrenal cortical tumors and healthy adrenal cortex exhibited the strongest NIRAF levels. Conclusions Our preliminary findings indicate that NIRAF detection could be a promising label‐free technology to enhance intraoperative AG visualization and holds immense potential for effective tumor demarcation during cortical‐sparing adrenalectomies or adrenal‐conserving surgeries.

A Comparison of Near-Infrared Autofluorescence Findings in Benign Versus Malignant Adrenal Tumors

“…The results of our study strengthen the previously published, yet smaller initial experiences published at three separate academic, high-volume adrenal institutions, including our institution, that benign adrenocortical tumors exhibit significantly more intense AF compared with pheochromocytomas and malignant tumors. [11][12][13] In our initial study, the average AF for all benign adrenocortical tumors was 2.23 (n = 16), for pheochromocytomas was 0.90 (n = 3), and for malignant tumors was 0.90 (n = 5). 11 While the normalized AF values calculated in the current study are slightly higher compared with our initially published experience using the same commercially available NIRAF imaging system, the trend remains the same.…”

“…Thomas et al in their series of 55 patients using another similar commercially available NIRAF imaging system, PDE-Neo II (760-nm camera), found benign adrenocortical tumors to also exhibit more intense AF compared with malignant tumors and pheochromocytomas, with ratios of 1.57 and 1.43 respectively. 12 Rajan et al, in their series of 22 patients also using the PDE-Neo II camera system, found benign adrenocortical tumors to harbor the most intense AF, with them being 1.50 times more intense than "suspicious/ growing" adrenal masses (final pathology not reported to confirm these were in fact malignant tumors) and 1.97 times…”

“…NIRAF technology was initially advocated for parathyroid imaging, with recent studies, including the current one, showing that the adrenal gland exhibits AF in the same spectrum. [11][12][13][14] As with parathyroid tissue, however, the fluorophore responsible for NIRAF in adrenal tissue has not been identified yet, but there may be some commonality between the two, given the increased fluorescence in both of these endocrine organs compared with other tissues studied. 12,15,17 Due to the AF properties of the adrenal, NIRAF imaging holds promise as an additional intraoperative adjunct for gland identification and delineation of the borders to assist with dissection, similar to ICG, but with the added advantages of not requiring injection/re-injection of dye and lack of allergic complications.…”

“…11 However, ultrasound and ICG each have their own inherent limitations. [11][12][13] Recent studies have shown that adrenal tissue, particularly the adrenal cortex, exhibits intense near infrared autofluorescence (NIRAF) properties similar to parathyroid tissue, introducing the prospect of a new adjunct to assist dissection in adrenalectomies. [11][12][13][14][15] The purpose of this study was to determine whether NIRAF could be used to differentiate benign versus malignant adrenal tumors during adrenalectomy.…”

Near‐Infrared Autofluorescence to Improve Visualization During Adrenal Surgery: A New Frontier for Interdisciplinary Collaboration

“…Improved visualization could be particularly helpful for low-volume surgeons, or in patients with excess visceral fat. This paper by Thomas et al [ 4 ], a collaboration between surgeons and engineers, is an elegant pilot study investigating the optical characteristics of normal and pathologic adrenal glands compared with surrounding structures, using commercial and custom-built cameras and handheld probes to assess fluorescence.…”