Steve S Cho1,2, Ryan Zeh1, John T Pierce1, Ryan Salinas1, Sunil Singhal3, John Y K Lee4. 1. Department of Neurosurgery, Hospital of the University of Pennsylvania, 235 South Eighth Street, Philadelphia, PA, 19106, USA. 2. Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. 3. Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA, USA. 4. Department of Neurosurgery, Hospital of the University of Pennsylvania, 235 South Eighth Street, Philadelphia, PA, 19106, USA. leejohn@uphs.upenn.edu.
Abstract
PURPOSE: Distinguishing neoplasm from normal brain parenchyma intraoperatively is critical for the neurosurgeon. 5-Aminolevulinic acid (5-ALA) has been shown to improve gross total resection and progression-free survival but has limited availability in the USA. Near-infrared (NIR) fluorescence has advantages over visible light fluorescence with greater tissue penetration and reduced background fluorescence. In order to prepare for the increasing number of NIR fluorophores that may be used in molecular imaging trials, we chose to compare a state-of-the-art, neurosurgical microscope (System 1) to one of the commercially available NIR visualization platforms (System 2). PROCEDURES: Serial dilutions of indocyanine green (ICG) were imaged with both systems in the same environment. Each system's sensitivity and dynamic range for NIR fluorescence were documented and analyzed. In addition, brain tumors from six patients were imaged with both systems and analyzed. RESULTS: In vitro, System 2 demonstrated greater ICG sensitivity and detection range (System 1 1.5-251 μg/l versus System 2 0.99-503 μg/l). Similarly, in vivo, System 2 demonstrated signal-to-background ratio (SBR) of 2.6 ± 0.63 before dura opening, 5.0 ± 1.7 after dura opening, and 6.1 ± 1.9 after tumor exposure. In contrast, System 1 could not easily detect ICG fluorescence prior to dura opening with SBR of 1.2 ± 0.15. After the dura was reflected, SBR increased to 1.4 ± 0.19 and upon exposure of the tumor SBR increased to 1.8 ± 0.26. CONCLUSION: Dedicated NIR imaging platforms can outperform conventional microscopes in intraoperative NIR detection. Future microscopes with improved NIR detection capabilities could enhance the use of NIR fluorescence to detect neoplasm and improve patient outcome.
PURPOSE: Distinguishing neoplasm from normal brain parenchyma intraoperatively is critical for the neurosurgeon. 5-Aminolevulinic acid (5-ALA) has been shown to improve gross total resection and progression-free survival but has limited availability in the USA. Near-infrared (NIR) fluorescence has advantages over visible light fluorescence with greater tissue penetration and reduced background fluorescence. In order to prepare for the increasing number of NIR fluorophores that may be used in molecular imaging trials, we chose to compare a state-of-the-art, neurosurgical microscope (System 1) to one of the commercially available NIR visualization platforms (System 2). PROCEDURES: Serial dilutions of indocyanine green (ICG) were imaged with both systems in the same environment. Each system's sensitivity and dynamic range for NIR fluorescence were documented and analyzed. In addition, brain tumors from six patients were imaged with both systems and analyzed. RESULTS: In vitro, System 2 demonstrated greater ICG sensitivity and detection range (System 1 1.5-251 μg/l versus System 2 0.99-503 μg/l). Similarly, in vivo, System 2 demonstrated signal-to-background ratio (SBR) of 2.6 ± 0.63 before dura opening, 5.0 ± 1.7 after dura opening, and 6.1 ± 1.9 after tumor exposure. In contrast, System 1 could not easily detect ICG fluorescence prior to dura opening with SBR of 1.2 ± 0.15. After the dura was reflected, SBR increased to 1.4 ± 0.19 and upon exposure of the tumor SBR increased to 1.8 ± 0.26. CONCLUSION: Dedicated NIR imaging platforms can outperform conventional microscopes in intraoperative NIR detection. Future microscopes with improved NIR detection capabilities could enhance the use of NIR fluorescence to detect neoplasm and improve patient outcome.
Authors: Christian Ewelt; Andrei Nemes; Volker Senner; Johannes Wölfer; Benjamin Brokinkel; Walter Stummer; Markus Holling Journal: J Photochem Photobiol B Date: 2015-05-14 Impact factor: 6.252
Authors: John Y K Lee; John T Pierce; Jayesh P Thawani; Ryan Zeh; Shuming Nie; Maria Martinez-Lage; Sunil Singhal Journal: J Neurosurg Date: 2017-04-07 Impact factor: 5.115
Authors: Jack X Jiang; Jane J Keating; Elizabeth M De Jesus; Ryan P Judy; Brian Madajewski; Ollin Venegas; Olugbenga T Okusanya; Sunil Singhal Journal: Am J Nucl Med Mol Imaging Date: 2015-06-15
Authors: Jun W Jeon; Steve S Cho; Shayoni Nag; Love Buch; John Pierce; YouRong S Su; Nithin D Adappa; James N Palmer; Jason G Newman; Sunil Singhal; John Y K Lee Journal: Oper Neurosurg (Hagerstown) Date: 2019-07-01 Impact factor: 2.703
Authors: Nikita Lakomkin; Jamie J Van Gompel; Kalmon D Post; Steve S Cho; John Y K Lee; Constantinos G Hadjipanayis Journal: J Neurooncol Date: 2021-02-21 Impact factor: 4.130
Authors: Steve S Cho; Saad Sheikh; Clare W Teng; Joseph Georges; Andrew I Yang; Emma De Ravin; Love Buch; Carrie Li; Yash Singh; Denah Appelt; Edward J Delikatny; E James Petersson; Andrew Tsourkas; Jay Dorsey; Sunil Singhal; John Y K Lee Journal: Mol Imaging Biol Date: 2020-10 Impact factor: 3.488
Authors: Steve S Cho; Ryan Zeh; John T Pierce; Jun Jeon; MacLean Nasrallah; Nithin D Adappa; James N Palmer; Jason G Newman; Caitlin White; Julia Kharlip; Peter Snyder; Philip Low; Sunil Singhal; M Sean Grady; John Y K Lee Journal: Oper Neurosurg (Hagerstown) Date: 2019-01-01 Impact factor: 2.703
Authors: Steve S Cho; Clare W Teng; Ashwin Ramayya; Love Buch; Jasmin Hussain; Jessica Harsch; Steven Brem; John Y K Lee Journal: Mol Imaging Biol Date: 2020-12 Impact factor: 3.488
Authors: Yash B Singh; Steve S Cho; Rachel Blue; Clare W Teng; Emma De Ravin; Love Buch; John Y K Lee Journal: Oper Neurosurg (Hagerstown) Date: 2021-02-16 Impact factor: 2.703