title: Intraoperative Spectroscopy with Ultrahigh Sensitivity for Image-Guided Surgery of Malignant Brain Tumors.
abstract: Intraoperative cancer imaging and fluorescence-guided surgery have attracted considerable interest because fluorescence signals can provide real-time guidance to assist a surgeon in differentiating cancerous and normal tissues. Recent advances have led to the clinical use of a natural fluorophore called protoporphyrin IX (PpIX) for image-guided surgical resection of high-grade brain tumors (glioblastomas). However, traditional fluorescence imaging methods have only limited detection sensitivity and identification accuracy and are unable to detect low-grade or diffuse infiltrating gliomas (DIGs). Here we report a low-cost hand-held spectroscopic device that is capable of ultrasensitive detection of protoporphyrin IX fluorescence in vivo, together with intraoperative spectroscopic data obtained from both animal xenografts and human brain tumor specimens. The results indicate that intraoperative spectroscopy is at least 3 orders of magnitude more sensitive than the current surgical microscopes, allowing ultrasensitive detection of as few as 1000 tumor cells. For detection specificity, intraoperative spectroscopy allows the differentiation of brain tumor cells from normal brain cells with a contrast signal ratio over 100. In vivo animal studies reveal that protoporphyrin IX fluorescence is strongly correlated with both MRI and histological staining, confirming that the fluorescence signals are highly specific to tumor cells. Furthermore, ex vivo spectroscopic studies of excised brain tissues demonstrate that the hand-held spectroscopic device is capable of detecting diffuse tumor margins with low fluorescence contrast that are not detectable with current systems in the operating room. These results open new opportunities for intraoperative detection and fluorescence-guided resection of microscopic and low-grade glioma brain tumors with invasive or diffusive margins.
authors.affiliation: Department of Biomedical Engineering, Emory University and Georgia Institute of Technology , 1760 Haygood Drive, Suite E116, Atlanta, Georgia 30322, United States.
authors.forename: Brad A
authors.initials: BA
authors.lastname: Kairdolf
authors.affiliation: Department of Neurosurgery, Emory University School of Medicine, Winship Cancer Institute of Emory University , Atlanta, Georgia 30322, United States.|Department of Neurosurgery, Icahn School of Medicine, Tisch Cancer Institute at Mount Sinai , New York, New York 10029, United States.
authors.forename: Alexandros
authors.initials: A
authors.lastname: Bouras
authors.affiliation: Department of Neurosurgery, Emory University School of Medicine, Winship Cancer Institute of Emory University , Atlanta, Georgia 30322, United States.
authors.forename: Milota
authors.initials: M
authors.lastname: Kaluzova
authors.affiliation: Department of Biomedical Engineering, Emory University and Georgia Institute of Technology , 1760 Haygood Drive, Suite E116, Atlanta, Georgia 30322, United States.
authors.forename: Abhinav K
authors.initials: AK
authors.lastname: Sharma
authors.affiliation: Department of Biomedical Engineering, Georgia Institute of Technology , 313 Ferst Drive, UA Whitaker Building 4106, Atlanta, Georgia 30332, United States.
authors.forename: May Dongmei
authors.initials: MD
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Emory University School of Medicine, Winship Cancer Institute of Emory University , Atlanta, Georgia 30322, United States.|Department of Neurosurgery, Icahn School of Medicine, Tisch Cancer Institute at Mount Sinai , New York, New York 10029, United States.
authors.forename: Constantinos G
authors.initials: CG
authors.lastname: Hadjipanayis
authors.affiliation: Department of Biomedical Engineering, Emory University and Georgia Institute of Technology , 1760 Haygood Drive, Suite E116, Atlanta, Georgia 30322, United States.
authors.forename: Shuming
authors.initials: S
authors.lastname: Nie
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000473:pathology* / Q000601:surgery*; D045744:Cell Line, Tumor; D005453:Fluorescence; D005909:Glioblastoma / Q000473:pathology / Q000601:surgery; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D016343:Monitoring, Intraoperative; D013053:Spectrophotometry; D025321:Surgery, Computer-Assisted