Molecular Imaging and Biology

, Volume 20, Issue 2, pp 213–220 | Cite as

Comparison of Near-Infrared Imaging Camera Systems for Intracranial Tumor Detection

  • Steve S. Cho
  • Ryan Zeh
  • John T. Pierce
  • Ryan Salinas
  • Sunil Singhal
  • John Y. K. Lee
Research Article



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).


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.


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.


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.

Key words

Brain tumor Comparison Fluorescence Imaging Near-infrared 



Thank you to Jun Jeon, a medical student at the Perelman School of Medicine, for helping with the Figures.

Compliance with Ethical Standards


This work was partially supported by the National Institutes of Health R01 CA193556 (SS) and the Institute for Translational Medicine and Therapeutics of the Perelman School of Medicine at the University of Pennsylvania (JYKL). In addition, research reported in this publication was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health under Award Number UL1TR000003 (JKYL). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Conflict of Interest

JYKL owns stock options in VisionSense™. SS holds patent rights over technologies presented in this manuscript.


  1. 1.
    Stummer W, Pichlmeier U, Meinel T et al (2006) Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial. Lancet Oncol 7:392–401CrossRefPubMedGoogle Scholar
  2. 2.
    Koizumi N, Harada Y, Minamikawa T et al (2016) Recent advances in photodynamic diagnosis of gastric cancer using 5-aminolevulinic acid. World J Gastroenterol 22:1289–1296CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Frangioni JV (2003) In vivo near-infrared fluorescence imaging. Curr Opin Chem Biol 7:626–634CrossRefPubMedGoogle Scholar
  4. 4.
    Lavazza M, Liu X, Wu C et al (2016) Indocyanine green-enhanced fluorescence for assessing parathyroid perfusion during thyroidectomy. Gland Surg 5:512–521CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Yeoh MS, Kim DD, Ghali GE (2013) Fluorescence angiography in the assessment of flap perfusion and vitality. Oral Maxillofacial Surg Clinics North Am 25:61–66CrossRefGoogle Scholar
  6. 6.
    Lee JYK, Pierce J, Thawani JP et al (2017) Near-infrared fluorescent image-guided surgery for intracranial meningioma. J Neurosurg 7:1–11Google Scholar
  7. 7.
    Lee JYK, Cho SS, Zeh R et al (2017) Folate receptor overexpression can be visualized in real time during pituitary adenoma endoscopic transsphenoidal surgery with near-infrared imaging. J Neurosurg. doi: 10.3171/2017.2.JNS163191
  8. 8.
    Lee JYK, Thawani JP, Pierce J et al (2016) Intraoperative near-infrared optical imaging can localize gadolinium-enhancing gliomas during surgery. Neurosurgery 79:856–871CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    DSouza AV, Lin H, Henderson ER et al (2016) Review of fluorescence guided surgery systems: identification of key performance capabilities beyond indocyanine green imaging. J Biomed Opt 21(8):80901CrossRefPubMedGoogle Scholar
  10. 10.
    Sturgis M. (2006) Section 5. 510(k) summary for Leica FL800, submitted to the Food and Drug Administration, Division of General, Restorative and Neurological DevicesGoogle Scholar
  11. 11.
    Madajewski B, Judy BF, Mouchli A et al (2012) Intraoperative near-infrared imaging of surgical wounds after tumor resections can detect residual disease. Clin Cancer Res 18:5741–5751CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Jiang JX, Keating JJ, Jesus EM et al (2015) Optimization of the enhanced permeability and retention effect for near-infrared imaging of solid tumors with indocyanine green. Am J Nucl Med Mol Imaging 5:390–400PubMedPubMedCentralGoogle Scholar
  13. 13.
    Colditz MJ, van Leyen K, Jeffree RL (2012) Aminolevulinic acid (ALA)–protoporphyrin IX fluorescence guided tumour resection. Part 2: theoretical, biochemical and practical aspects. J Clin Neurosci 19:1611–1616CrossRefPubMedGoogle Scholar
  14. 14.
    Colditz MJ, Jeffree RL (2012) Aminolevulinic acid (ALA)–protoporphyrin IX fluorescence guided tumour resection. Part 1: clinical, radiological and pathological studies. J Clin Neurosci 19:1471–1474CrossRefPubMedGoogle Scholar
  15. 15.
    Gossedge G, Vallance A, Jayne D (2015) Diverse applications for near infra-red intraoperative imaging. Color Dis 17:7–11CrossRefGoogle Scholar
  16. 16.
    Ewelt C, Nemes A, Senner V et al (2015) Fluorescence in neurosurgery: its diagnostic and therapeutic use. Rev Lit J Photochem Photobiol B: Biol 148:302–309CrossRefGoogle Scholar
  17. 17.
    Iyer AK, Khaled G, Fang J, Maeda H (2006) Exploiting the enhanced permeability and retention effect for tumor targeting. Drug Discov Today 11:812–818CrossRefPubMedGoogle Scholar
  18. 18.
    Sato T, Suzuki K, Sakuma J et al (2015) Development of a new high-resolution intraoperative imaging system (dual-image videoangiography, DIVA) to simultaneously visualize light and near-infrared fluorescence images of indocyanine green angiography. Acta Neurochir 157:1295–1301CrossRefPubMedGoogle Scholar

Copyright information

© World Molecular Imaging Society 2017

Authors and Affiliations

  • Steve S. Cho
    • 1
    • 2
  • Ryan Zeh
    • 1
  • John T. Pierce
    • 1
  • Ryan Salinas
    • 1
  • Sunil Singhal
    • 3
  • John Y. K. Lee
    • 1
  1. 1.Department of NeurosurgeryHospital of the University of PennsylvaniaPhiladelphiaUSA
  2. 2.Perelman School of Medicine at the University of PennsylvaniaPhiladelphiaUSA
  3. 3.Department of SurgeryHospital of the University of PennsylvaniaPhiladelphiaUSA

Personalised recommendations