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Margaret Folaron, Rendall Strawbridge, Kimberley S. Samkoe, Caroline Filan, David W. Roberts and Scott C. Davis

OBJECTIVE

The use of the optical contrast agent sodium fluorescein (NaFl) to guide resection of gliomas has been under investigation for decades. Although this imaging strategy assumes the agent remains confined to the vasculature except in regions of blood-brain barrier (BBB) disruption, clinical studies have reported significant NaFl signal in normal brain tissue, limiting tumor-to-normal contrast. A possible explanation arises from earlier studies, which reported that NaFl exists in both pure and protein-bound forms in the blood, the former being small enough to cross the BBB. This study aims to elucidate the kinetic binding behavior of NaFl in circulating blood and its effect on NaFl accumulation in brain tissue and tumor contrast. Additionally, the authors examined the blood and tissue kinetics, as well as tumor uptake, of a pegylated form of fluorescein selected as a potential optical analog of gadolinium-based MRI contrast agents.

METHODS

Cohorts of mice were administered one of the following doses/forms of NaFl: 1) high human equivalent dose (HED) of NaFl, 2) low HED of NaFl, or 3) pegylated form of fluorescein. In each cohort, groups of animals were euthanized 15, 30, 60, and 120 minutes after administration for ex vivo analysis of fluorescein fluorescence. Using gel electrophoresis and fluorescence imaging of blood and brain specimens, the authors quantified the temporal kinetics of bound NaFl, unbound NaFl, and pegylated fluorescein in the blood and normal brain tissue. Finally, they compared tumor-to-normal contrast for NaFl and pegylated-fluorescein in U251 glioma xenografts.

RESULTS

Administration of NaFl resulted in the presence of unbound and protein-bound NaFl in the circulation, with unbound NaFl constituting up to 70% of the signal. While protein-bound NaFl was undetectable in brain tissue, unbound NaFl was observed throughout the brain. The observed behavior was time and dose dependent. The pegylated form of fluorescein showed minimal uptake in brain tissue and improved tumor-to-normal contrast by 38%.

CONCLUSIONS

Unbound NaFl in the blood crosses the BBB, limiting the achievable tumor-to-normal contrast and undermining the inherent advantage of tumor imaging in the brain. Dosing and incubation time should be considered carefully for NaFl-based fluorescence-guided surgery (FGS) of glioma. A pegylated form of fluorescein showed more favorable normal tissue kinetics that translated to higher tumor-to-normal contrast. These results warrant further development of pegylated-fluorescein for FGS of glioma.

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John E. Ziewacz, Matthew C. Davis, Darryl Lau, Abdulrahman M. El-Sayed, Scott E. Regenbogen, Stephen E. Sullivan and George A. Mashour

Object

The surgical Apgar score (SAS) reliably predicts postoperative death and complications and has been validated in a large cohort of general and vascular surgery patients. However, there has been limited study of the utility of the score in the neurosurgical population. The authors tested the hypothesis that the SAS would predict postoperative complications and length of stay after neurosurgical procedures.

Methods

A cohort of 918 intracranial and spine surgery patients treated over a 3-year period were retrospectively evaluated. The 10-point SAS was calculated and postoperative 30-day mortality and complications rates, intensive care unit (ICU) stay, and hospital stay were assessed by 2 independent raters. Univariate analysis and multivariate logistic regression were performed.

Results

There were 145 patients (15.8%) with at least 1 complication and 24 patients (2.6%) who died within 30 days of surgery. Surgical Apgar scores were significantly associated with the likelihood of postoperative complications (p < 0.001) and death (p = 0.002); scores varied inversely with postoperative complication and mortality risk in a multivariate analysis. Low SASs also predicted prolonged ICU and hospital stay. Patients with scores of 0–2 stayed a mean of 18.9 days (p < 0.001) and patients with scores of 3–4 stayed an average of 14.3 days (p < 0.001) compared with 4.1 days in patients with scores of 9–10.

Conclusions

The application of the surgical Apgar score to a neurosurgical cohort predicted 30-day postoperative mortality and complication rates as well as extended ICU and hospital stay. This readily calculated score may help neurosurgical teams efficiently direct postoperative care to those at highest risk of death and complications.

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Oral Presentations

2010 AANS Annual Meeting Philadelphia, Pennsylvania May 1–5, 2010