Intraoperative confocal laser endomicroscopy: prospective in vivo feasibility study of a clinical-grade system for brain tumors.

OBJECTIVE: The authors evaluated the feasibility of using the first clinical-grade confocal laser endomicroscopy (CLE) system using fluorescein sodium for intraoperative in vivo imaging of brain tumors. METHODS: A CLE system cleared by the FDA was used in 30 prospectively enrolled patients with 31 brain tumors (13 gliomas, 5 meningiomas, 6 other primary tumors, 3 metastases, and 4 reactive brain tissue). A neuropathologist classified CLE images as interpretable or noninterpretable. Images were compared with corresponding frozen and permanent histology sections, with image correlation to biopsy location using neuronavigation. The specificities and sensitivities of CLE images and frozen sections were calculated using permanent histological sections as the standard for comparison. A recently developed surgical telepathology software platform was used in 11 cases to provide real-time intraoperative consultation with a neuropathologist. RESULTS: Overall, 10,713 CLE images from 335 regions of interest were acquired. The mean duration of the use of the CLE system was 7 minutes (range 3-18 minutes). Interpretable CLE images were obtained in all cases. The first interpretable image was acquired within a mean of 6 (SD 10) images and within the first 5 (SD 13) seconds of imaging; 4896 images (46%) were interpretable. Interpretable image acquisition was positively correlated with study progression, number of cases per surgeon, cumulative length of CLE time, and CLE time per case (p ≤ 0.01). The diagnostic accuracy, sensitivity, and specificity of CLE compared with frozen sections were 94%, 94%, and 100%, respectively, and the diagnostic accuracy, sensitivity, and specificity of CLE compared with permanent histological sections were 92%, 90%, and 94%, respectively. No difference was observed between lesion types for the time to first interpretable image (p = 0.35). Deeply located lesions were associated with a higher percentage of interpretable images than superficial lesions (p = 0.02). The study met the primary end points, confirming the safety and feasibility and acquisition of noninvasive digital biopsies in all cases. The study met the secondary end points for the duration of CLE use necessary to obtain interpretable images. A neuropathologist could interpret the CLE images in 29 (97%) of 30 cases. CONCLUSIONS: The clinical-grade CLE system allows in vivo, intraoperative, high-resolution cellular visualization of tissue microstructure and identification of lesional tissue patterns in real time, without the need for tissue preparation.

Redosing of Fluorescein Sodium Improves Image Interpretation During Intraoperative Ex Vivo Confocal Laser Endomicroscopy of Brain Tumors.

BACKGROUND: Fluorescein sodium (FNa) is a fluorescence agent used with a wide-field operating microscope for intraoperative guidance and with confocal laser endomicroscopy (CLE) to evaluate brain tissue. Susceptibility of FNa to degradation over time may affect CLE image quality during prolonged surgeries. This study describes improved characteristics of CLE images after intraoperative redosing with FNa. METHODS: A retrospective analysis was performed using CLE images obtained ex vivo from samples obtained during tumor resections with FNa-based fluorescence guidance with a wide-field operating microscope. The comparison groups included CLE images acquired after FNa redosing (redose imaging group), images from the same patients acquired after the initial FNa dose (initial-dose imaging group), and images from patients in whom redosing was not used (single-dose imaging group). A detailed assessment of image quality and interpretation regarding different FNa dosage and timing of imaging after FNa administration was conducted for all comparison groups. RESULTS: The brightest and most contrasting images were observed in the redose group compared to the initial-dose and single-dose groups (P<0.001). The decay of FNa signal negatively correlated with brightness (rho = -0.52, P<0.001) and contrast (rho = -0.57, P<0.001). Different doses of FNa did not significantly affect the brightness (P=0.15) or contrast (P=0.09) in CLE images. As the mean timing of imaging increased, the percentage of accurately diagnosed images decreased (P=0.03). CONCLUSIONS: The decay of the FNa signal is directly associated with image brightness and contrast. The qualitative interpretation scores of images were highest for the FNa redose imaging group. Redosing with FNa to improve the utility of CLE imaging should be considered a safe and beneficial strategy during prolonged surgeries.

Race and socioeconomic disparity in treatment and outcome of traumatic cervical spinal cord injury with fracture: Nationwide Inpatient Sample database, 1998-2009.

STUDY DESIGN: A retrospective national administrative database study. OBJECTIVE: Advances in treatment of traumatic cervical spinal cord injury with fracture (TCSCIF) have led to significant improvements in clinical outcomes; however, progress in healthcare is seldom ubiquitous across demographic groups. Therefore, we explored if disparities in treatment and outcome after TCSCIF exist across race and socioeconomic status. SETTING: USA. METHODS: We queried the Nationwide Inpatient Sample database from 1998 to 2009 for TCSCIF hospitalizations. Multivariate analysis was used to identify the correlation between socioeconomic status and race to injury, treatment type, and outcome. RESULTS: There were 21,985 admissions for TCSCIF, 66.9% of whom had a favorable discharge disposition. In-hospital mortality rate was 12.5%. A total of 43.7% underwent surgery. Overall, surgery was associated with lower in-hospital mortality (OR 0.30, 95% CI 0.27-0.34, p < 0.01) and better discharge disposition (OR 0.68, 95% CI 0.62-0.74, p < 0.01) versus nonsurgical or no intervention. African-American (AA) race and low socioeconomic status (LSES) were significant predictors of lower odds to undergo surgery and unfavorable discharge disposition, respectively; potentially explained by a higher odds of increased New Injury Severity Score classification at presentation. Surgical and favorable discharge rates for LSES and non-Caucasian races, however, have been steadily improving over the study period. CONCLUSIONS: Despite trending improved outcomes after TCSCIF, LSES, or AA race were more likely to have worse outcomes compared to their counterparts. In addition, LSES, AA, and Hispanic groups were less likely to undergo surgical treatment, suggesting disparities in management and outcome effect.

Impact of Timing of Intervention Among 397 Consecutively Treated Brainstem Cavernous Malformations.

BACKGROUND: Surgical resection of brainstem cavernous malformations (BSCMs) is challenging, and patient selection and timing of intervention remain controversial. OBJECTIVE: To evaluate the impact of surgical timing and predictors of neurological outcome after surgical resection of BSCMs. METHODS: Consecutive adult patients (≥18 years) with BSCMs undergoing surgical resection between 1985 and 2014 by the senior author (RFS) were retrospectively reviewed. Patient demographics, lesion characteristics, imaging results, surgical approach, and perioperative and long-term neurological morbidity were analyzed. RESULTS: Data were analyzed for a total of 397 adult patients (160, 40% male). On univariate analysis, a greater proportion of patients treated within 6 weeks of hemorrhage had an improved Glasgow Outcome Scale score (P = .06). On logistic regression analysis, patients treated within 6 weeks of hemorrhage experienced improved clinical outcomes (odds ratio = 1.73; 95% confidence interval = 1.06-2.83; P = .03). CONCLUSIONS: Although BSCM surgery is associated with significant perioperative morbidity and mortality, favorable long-term hemorrhage rates and symptom resolution can be achieved in a carefully selected group of patients. Overall, patients treated acutely, within 6 weeks, benefited the most from surgical intervention.