John Y K Lee1, John T Pierce2, Ryan Zeh2, Steve S Cho2, Ryan Salinas2, Shuming Nie3, Sunil Singhal4. 1. Department of Neurosurgery, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA. Electronic address: leejohn@uphs.upenn.edu. 2. Department of Neurosurgery, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA. 3. Department of Biochemistry, Emory University, Atlanta, Georgia, USA. 4. Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Abstract
INTRODUCTION: Approximately 100,000 brain metastases are diagnosed annually in the United States. Our laboratory has pioneered a novel technique, second window indocyanine green (SWIG), which allows for real-time intraoperative visualization of brain metastasis through normal brain parenchyma and intact dura. METHODS: Thirteen patients with intraparenchymal brain metastases were administered indocyanine green (ICG) at 5 mg/kg the day before surgery. A near-infrared (NIR)- capable camera was used intraoperatively to identify the tumor and to inspect surgical margins. Neuropathology was used to assess the accuracy and precision of the fluorescent dye for identifying tumor. RESULTS: ICG was infused at 24.7 ± 3.45 hours before visualization. All 13 metastases fluoresced with an average signal-to-background ratio (SBR) of 6.62. The SBR with the dura intact was 67.2% of the mean SBR once the dura was opened. The NIR signal could be visualized through normal brain parenchyma up to 7 mm. For the 39 total specimens, the mean SBR for tumor specimens (n = 28) was 6.9, whereas the SBR for nontumor specimens (n = 11) was 3.7. The sensitivity, specificity, positive predictive value, and negative predictive value of NIR imaging for tumor was 96.4%, 27.3%, 77.1%, and 75.0%. DISCUSSION: SWIG relies on the passive accumulation of dye in abnormal tumor tissue via the enhanced permeability and retention effect. It provides strong NIR optical contrast, which can be used to localize tumors before dural opening. The use of SWIG for margin assessment remains limited by its lack of specificity (high false-positive rate); however, ongoing improvements in imaging parameters show great potential to reduce false-positive results.
INTRODUCTION: Approximately 100,000 brain metastases are diagnosed annually in the United States. Our laboratory has pioneered a novel technique, second window indocyanine green (SWIG), which allows for real-time intraoperative visualization of brain metastasis through normal brain parenchyma and intact dura. METHODS: Thirteen patients with intraparenchymal brain metastases were administered indocyanine green (ICG) at 5 mg/kg the day before surgery. A near-infrared (NIR)- capable camera was used intraoperatively to identify the tumor and to inspect surgical margins. Neuropathology was used to assess the accuracy and precision of the fluorescent dye for identifying tumor. RESULTS:ICG was infused at 24.7 ± 3.45 hours before visualization. All 13 metastases fluoresced with an average signal-to-background ratio (SBR) of 6.62. The SBR with the dura intact was 67.2% of the mean SBR once the dura was opened. The NIR signal could be visualized through normal brain parenchyma up to 7 mm. For the 39 total specimens, the mean SBR for tumor specimens (n = 28) was 6.9, whereas the SBR for nontumor specimens (n = 11) was 3.7. The sensitivity, specificity, positive predictive value, and negative predictive value of NIR imaging for tumor was 96.4%, 27.3%, 77.1%, and 75.0%. DISCUSSION: SWIG relies on the passive accumulation of dye in abnormal tumor tissue via the enhanced permeability and retention effect. It provides strong NIR optical contrast, which can be used to localize tumors before dural opening. The use of SWIG for margin assessment remains limited by its lack of specificity (high false-positive rate); however, ongoing improvements in imaging parameters show great potential to reduce false-positive results.
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: Clare W Teng; Ahmad Amirshaghaghi; Steve S Cho; Shuting S Cai; Emma De Ravin; Yash Singh; Joann Miller; Saad Sheikh; Edward Delikatny; Zhiliang Cheng; Theresa M Busch; Jay F Dorsey; Sunil Singhal; Andrew Tsourkas; John Y K Lee Journal: J Neurooncol Date: 2020-09-10 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
Authors: John Y K Lee; Steve S Cho; Walter Stummer; Janos L Tanyi; Alexander L Vahrmeijer; Eben Rosenthal; Barbara Smith; Eric Henderson; David W Roberts; Amy Lee; Constantinos G Hadjipanayis; Jeffrey N Bruce; Jason G Newman; Sunil Singhal Journal: J Biomed Opt Date: 2019-12 Impact factor: 3.170
Authors: Thinzar M Lwin; Michael A Turner; Siamak Amirfakhri; Hiroto Nishino; Robert M Hoffman; Michael Bouvet Journal: Cells Date: 2022-01-12 Impact factor: 6.600