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

Cho, Steve S.; Teng, Clare W; Ravin, Emma De; Singh, Yash; Lee, John Y.K.

doi:10.3340/jkns.2021.0202

Cited by 5 publications

(5 citation statements)

References 34 publications

(42 reference statements)

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“…However, the instrument's sensitivity for ICG is rather low, as reported previously. 40 Despite this, and notwithstanding the fact that the approach to convert the RBG images of PPIX fluorescence to grayscale maximized the TNR, favoring 5-ALA, we obtained similar TNRs for 6QC-ICG and 5-ALA. These results suggest that 6QC-ICG can provide a contrast superior to that of 5-ALA when high-sensitivity platforms optimized for NIR fluorophores are used.…”

Section: Discussionmentioning

confidence: 67%

Molecularly targeted protease-activated probes for visualization of glioblastoma: a comparison with 5-ALA

Konečná,

Výmola,

Ternerová

et al. 2024

Journal of Neurosurgery

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OBJECTIVE The highly infiltrative growth of glioblastoma (GBM) makes distinction between the tumor and normal brain tissue challenging. Therefore, fluorescence-guided surgery is often used to improve visual identification of radiological tumor margins. The aim of this study was to evaluate the ability of recently developed molecularly targeted near-infrared (NIR) protease-activated probes to visualize GBM tissue and to compare the most promising candidate with the gold standard, 5-aminolevulinic acid (5-ALA). METHODS Single-substrate probes 6QC-ICG and 6QC-Cy5 (cysteine cathepsin cleavable), double-substrate probes AG2-FNIR and AG2-Cy5 (cysteine cathepsin and caspase 3 cleavable), and 5-ALA were administered intravenously to mice with orthotopic tumors. Activation of the probes was also evaluated in cell cultures in vitro and in biopsy material from patients with GBM ex vivo. The tumor to normal brain tissue fluorescence ratio (TNR) was quantified in brain sections using preclinical and clinical visualization platforms, and in tissue homogenates and cell suspensions using spectrofluorimetry. Subcellular localization of the fluorophores was visualized by confocal microscopy. RESULTS In vitro, the single-substrate probe 6QC-ICG was cleaved in glioma cells and macrophages, and the resulting fluorophore accumulated intracellularly. In experimental GBMs, both single- and double-substrate probes visualized tumor tissue, while in healthy brain tissue the signal was minimal. TNR was highest for 6QC-ICG and AG2-FNIR, but the signal intensity was higher for 6QC-ICG. Using xenograft and syngeneic mouse models, as well as human GBM biopsy material ex vivo, the authors confirmed the ability of 6QC-ICG to specifically visualize the glioma tissue using preclinical and clinical visualization platforms. Finally, a comparison with 5-ALA in animals coadministered with both compounds revealed a higher TNR for 6QC-ICG in experimental GBMs. CONCLUSIONS The cysteine cathepsin–cleavable probe 6QC-ICG is activated by glioma cells and tumor-associated macrophages, leading to a high contrast between tumor and nontumorous brain tissue that is superior to that of the current standard, 5-ALA. In addition to a well-defined mechanism of action, protease-activated probes that use NIR fluorophores (e.g., indocyanine green) have the advantage of low absorption and scattering of the NIR light and lower tissue autofluorescence. These results suggest that 6QC-ICG has the potential to become the targeted agent in intraoperative detection of GBM tissue using fluorescence imaging.

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Section: Discussionmentioning

confidence: 67%

Molecularly targeted protease-activated probes for visualization of glioblastoma: a comparison with 5-ALA

Konečná,

Výmola,

Ternerová

et al. 2024

Journal of Neurosurgery

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“…Perhaps certain FI systems need to be adapted for specific uses such as angiographic assessment, sentinel node detection, or evaluation of different types of tumoral tissue. However, currently, there is no recommended device specifically tailored for ICG-FI in BC tumors, and a comparative evaluation of the existing FI systems is necessary to determine the optimal imaging approach [ 53 ].…”

Section: Discussionmentioning

confidence: 99%

Fluorescence imaging for real-time detection of breast cancer tumors using IV injection of indocyanine green with non-conventional imaging: a systematic review of preclinical and clinical studies of perioperative imaging technologies

Pop,

Veys,

Bormans

et al. 2024

Breast Cancer Res Treat

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Background This review summarizes the available data on the effectiveness of indocyanine green fluorescence imaging (ICG-FI) for real-time detection of breast cancer (BC) tumors with perioperative imaging technologies. Methods PubMed and Scopus databases were exhaustively searched for publications on the use of the real-time ICG-FI evaluation of BC tumors with non-conventional breast imaging technologies. Results Twenty-three studies were included in this review. ICG-FI has been used for BC tumor identification in 12 orthotopic animal tumor experiences, 4 studies on animal assessment, and for 7 human clinical applications. The BC tumor-to-background ratio (TBR) was 1.1–8.5 in orthotopic tumor models and 1.4–3.9 in animal experiences. The detection of primary human BC tumors varied from 40% to 100%. The mean TBR reported for human BC varied from 2.1 to 3.7. In two studies evaluating BC surgical margins, good sensitivity (93.3% and 100%) and specificity (60% and 96%) have been reported, with a negative predictive value of ICG-FI to predict margin involvement intraoperatively of 100% in one study. Conclusions The use of ICG-FI as a guiding tool for the real-time identification of BC tumors and for the assessment of tumor boundaries is promising. There is great variability between the studies with regard to timing and dose. Further evidence is needed to assess whether ICG-guided BC surgery may be implemented as a standard of care.

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“…ICG is a compound that has traditionally been used for intraoperative video angiography for cerebrovascular surgery and has recently been described for intraoperative visualization of brain tumors [61,62]. ICG relies on the disrupted BBB for accumulation in brain tumors and is administered systemically over 24 h prior to surgery [63]. ICG emits fluorescence in the near-infrared range and is visualized with modified visualization devices.…”

Section: Fluorescence-guided Neurosurgerymentioning

confidence: 99%

“…The landscape of intraoperative imaging is constantly evolving, fueled by converging technological forces that are revolutionizing neurosurgical procedures [18,33,63]. This transformation in neurosurgical imaging is being driven by three key developments: the integration of multiple real-time imaging modalities, the incorporation of augmented reality (AR)/virtual reality (VR), and the incorporation of artificial intelligence (AI) and ML [63,[127][128][129][130]. The integration of multiple modalities in intraoperative imaging is proving instrumental in advancing neurosurgical innovation.…”

Section: Conventional Imaging Techniques For Intraoperative Tumor Res...mentioning

confidence: 99%

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Intraoperative Imaging and Optical Visualization Techniques for Brain Tumor Resection: A Narrative Review

Bin-Alamer,

Abou-Al-Shaar,

Gersey

et al. 2023

Cancers

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Advancements in intraoperative visualization and imaging techniques are increasingly central to the success and safety of brain tumor surgery, leading to transformative improvements in patient outcomes. This comprehensive review intricately describes the evolution of conventional and emerging technologies for intraoperative imaging, encompassing the surgical microscope, exoscope, Raman spectroscopy, confocal microscopy, fluorescence-guided surgery, intraoperative ultrasound, magnetic resonance imaging, and computed tomography. We detail how each of these imaging modalities contributes uniquely to the precision, safety, and efficacy of neurosurgical procedures. Despite their substantial benefits, these technologies share common challenges, including difficulties in image interpretation and steep learning curves. Looking forward, innovations in this field are poised to incorporate artificial intelligence, integrated multimodal imaging approaches, and augmented and virtual reality technologies. This rapidly evolving landscape represents fertile ground for future research and technological development, aiming to further elevate surgical precision, safety, and, most critically, patient outcomes in the management of brain tumors.

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

Cited by 5 publications

References 34 publications

Molecularly targeted protease-activated probes for visualization of glioblastoma: a comparison with 5-ALA

Molecularly targeted protease-activated probes for visualization of glioblastoma: a comparison with 5-ALA

Fluorescence imaging for real-time detection of breast cancer tumors using IV injection of indocyanine green with non-conventional imaging: a systematic review of preclinical and clinical studies of perioperative imaging technologies

Intraoperative Imaging and Optical Visualization Techniques for Brain Tumor Resection: A Narrative Review

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