J Korean Neurosurg Soc.  2022 Jul;65(4):572-581. 10.3340/jkns.2021.0202.

Assessment and Comparison of Three Dimensional Exoscopes for Near-Infrared Fluorescence-Guided Surgery Using Second-Window Indocyanine-Green

• Cho SS
• Teng CW
• De Ravin E
• Singh YB
• Lee JY

• KMID: 2531626
• DOI: http://doi.org/10.3340/jkns.2021.0202

Abstract

Objective
: Compared to microscopes, exoscopes have advantages in field-depth, ergonomics, and educational value. Exoscopes are especially well-poised for adaptation into fluorescence-guided surgery (FGS) due to their excitation source, light path, and image processing capabilities. We evaluated the feasibility of near-infrared FGS using a 3-dimensional (3D), 4 K exoscope with nearinfrared fluorescence imaging capability. We then compared it to the most sensitive, commercially-available near-infrared exoscope system (3D and 960 p). In-vitro and intraoperative comparisons were performed.
Methods
: Serial dilutions of indocyanine-green (1–2000 μg/mL) were imaged with the 3D, 4 K Olympus Orbeye (system 1) and the 3D, 960 p VisionSense Iridium (system 2). Near-infrared sensitivity was calculated using signal-to-background ratios (SBRs). In addition, three patients with brain tumors were administered indocyanine-green and imaged with system 1, with two also imaged with system 2 for comparison.
Results
: Systems 1 and 2 detected near-infrared fluorescence from indocyanine green concentrations of >250 μg/L and >31.3 μg/L, respectively. Intraoperatively, system 1 visualized strong near-infrared fluorescence from two, strongly gadoliniumenhancing meningiomas (SBR=2.4, 1.7). The high-resolution, bright images were sufficient for the surgeon to appreciate the underlying anatomy in the near-infrared mode. However, system 1 was not able to visualize fluorescence from a weakly-enhancing intraparenchymal metastasis. In contrast, system 2 successfully visualized both the meningioma and the metastasis but lacked high resolution stereopsis.
Conclusion
: Three-dimensional exoscope systems provide an alternative visualization platform for both standard microsurgery and near-infrared fluorescent guided surgery. However, when tumor fluorescence is weak (i.e., low fluorophore uptake, deep tumors), highly sensitive near-infrared visualization systems may be required.

Keyword

Neuroimaging; 3D exoscope; Fluorescence; Indocyanine-green; Central nervous system neoplasms; Molecular imaging

Figure

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  Fig. 1. Excitation and emission profile for system 1 and system 2. A : System 1 is a high-resolution exoscope offering 3-dimensional (3D), 4 K visualization to those wearing circular polarization glasses. It uses light-emitting diodes (LEDs) for illumination. In its near-infrared (NIR) mode, the IR LED turns on, which emits photons of 730–740 nm to excite NIR fluorophores. All returning photons are then collected and filtered by a long-pass filter that blocks photons below 800 nm. A portion of photons <800 nm are let through in order to increase the overall field brightness and allow surgeons to operate in the NIR mode. These photons are then captured by a digital sensor. B : System 2 does not offer stereopsis in its NIR mode but provides enhanced NIR sensitivity. It uses a laser that is tuned to 805 nm to match the peak excitation wavelength of ICG, as seen above. The resulting fluorescence is then filtered through a band-pass filter that allows only photons 820–860 nm to pass. Then, there is an advanced signal processing algorithm which amplifies weaker NIR signal without significant increases in background noise, which enhances NIR signal to background contrast when fluorescence is relatively weaker. Adopted from Cho et al. [8] with permission from the publisher.

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  Fig. 2. In-vitro analysis of near-infrared (NIR) sensitivity of the two exoscope systems. A : The two exoscope systems were compared directly by imaging serial dilutions of indocyanine green (ICG) from 1.0-2000 μg/L; the results are plotted on a log-scale for the X-axis. System 1 began discriminating the ICG from the control at 250 μg/L, while system 2 was able to detect down to 31.3 μg/L. B : Serial dilution images using system 1. System 1 achieved a signal-to-background ratio (SBR) of 9.7 at the highest concentration of 2000 μg/L. Although image analysis demonstrated the SBR to be 1.9 at 250 μg/L, NIR fluorescence was not visually distinguishable on the screen until the ICG concentration was 500 μg/L. C : Serial dilution images using system 2. System 2 achieved an SBR of 19.2 at the highest concentration of 2000 μg/L. Although image analysis demonstrated the SBR to be 1.5 at 31.3 μg/L, NIR fluorescence was not visually distinguishable on the screen until the ICG concentration was 62.5 μg/L.

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  Fig. 3. Demonstration of near-infrared (NIR) fluorescence visualization of a meningioma using system 1 (see Supplementary Video 1). A : Preoperative axial T1 magnetic resonance imaging (MRI) with gadolinium showed a left parietal parasagittal meningioma measuring 17×16×15 mm. The tumor (arrow) enhanced strongly and homogenously with gadolinium. Over the intact dura, white-light imaging (B) did not visualize this superficial tumor (arrow). However, under NIR fluorescence visualization (C), the tumor (arrow) outline was clearly delineated. The tumor demonstrated signal to background ratio of 2.1. With the dura open and the tumor in direct line of sight, the white-light imaging (D) successfully visualized the highly vascular tumor (arrow). Under NIR fluorescence (E), the tumor (arrow) fluoresced even more brightly, with a signal-to-background ratio of 2.4. F : Postoperative axial T1 MRI with gadolinium showed gross total resection of the parietal meningioma without residual neoplasm.

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  Fig. 4. Demonstration of near-infrared (NIR) fluorescence visualization of a meningioma using system 1 and system 2. A : Preoperative axial T1 magnetic resonance imaging (MRI) with gadolinium showed a right parietal convexity meningioma measuring 46×30×22 mm. The tumor (arrow) enhanced strongly and homogenously with gadolinium. B-E : Over the intact dura, white-light imaging (B) did not visualize this superficial tumor. NIR imaging with system 1 (C) delineated the tumor (arrow) boundaries, with a signal-to-background ratio (SBR) of 1.6. NIR imaging with system 2 in black and white (D) and pseudocolor overlay (E) delineated the tumor more clearly with an SBR of 8.0. F-I : With the dura open and the tumor in direct line of sight, the white-light imaging (F) successfully visualized the tumor (arrow). NIR imaging with system 1 (G) demonstrated high indocyanine green (ICG) accumulation in the tumor, with an NIR SBR of 1.7. System 2 imaging (H and I) demonstrated higher contrast, with an SBR of 10.1. J-M : After devascularization and resection under white-light visualization (J), the tumor specimen was examined under both exoscopes. System 1 (K) again confirmed high ICG accumulation in the tumor, with an SBR of 1.9. System 2 (L and M) also demonstrated very high contrast between the tumor tissue and normal brain, with an SBR of 12.8. N : Postoperative axial T1 MRI with gadolinium showed gross total resection of the convexity meningioma without residual neoplasm.

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  Fig. 5. Demonstration of near-infrared (NIR) fluorescence visualization in a weakly-enhancing metastasis using system 1 and system 2. A : Preoperative axial T1 magnetic resonance imaging (MRI) with gadolinium showed a cystic, right parietal metastasis. The cystic portion did not enhance with gadolinium and the enhancing portion of the tumor (arrow) did not enhance as intensely as the previous meningiomas. B-E : Over the intact dura, neither white-light imaging (B), system 1 NIR imaging (C), nor system 2 NIR imaging (D and E) could reliably delineate the tumor borders. F-I : With the dura open and over the intact cortex, white-light imaging (F) could not visualize the tumor (arrow). NIR imaging with system 1 (G) also did not detect any NIR fluorescence above that of the surrounding parenchyma (signal-to-background ratio [SBR], 1.15). With system 2 (H and I), NIR fluorescence with an SBR of 2.5 was detected through the cortex in an area consistent with the tumor location. J-M : After exposing the tumor under white-light visualization (J), system 1 NIR visualization showed faint NIR fluorescence in the tumor (K); however, there was not enough signal to distinguish the tumor from the surrounding parenchyma (SBR, 1). With system 2 (L and M), more NIR signal was detected from the tumor, resulting in an SBR of 2.9. N : Postoperative axial T1 MRI with gadolinium showed gross total resection of the parietal metastasis without residual neoplasm.

Reference

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