68Ga-DOTA PET for Diagnosis of Spinal Cerebrospinal Fluid Leaks.

Abstract

Spontaneous intracranial hypotension due to spinal cerebrospinal fluid (CSF) leakage causes substantial disease burden. In many patients, the course is protracted and refractory to conservative treatment, requiring targeted therapy. We propose PET of the CSF space with 68Ga-DOTA as a state-of-the-art approach to radionuclide cisternography (RC) and validate its diagnostic value. Methods: This study is a retrospective analysis of patients with suspected intracranial hypotension due to spinal CSF leaks and who underwent whole-body PET/CT at 1, 3, and 5 h after intrathecal lumbar injection of 68Ga-DOTA. Two independent raters unaware of the clinical data analyzed all scans for direct and indirect RC signs of CSF leakage. Volume-of-interest analysis was performed to assess the biologic half-life of the tracer in the CSF space and the ratio of decay-corrected activity in the CSF space at 5 and 3 h (simplified marker of tracer clearance). Comprehensive stepwise neuroradiologic work-up served as a reference; additional validation was provided by surgical findings and follow-up. Results: Of 40 consecutive patients, 39 patients with a working diagnosis of intracranial hypotension due to a spinal CSF leak (spontaneous, n = 31; postintervention, n = 8) could be analyzed. A spinal CSF leak was verified by the neuroradiologic reference method in 18 of 39 patients. As the only direct and indirect diagnostic signs, extrathecal tracer accumulation at the cervicothoracic junction (67% sensitivity and 90% specificity) and lack of activity over the cerebral convexities (5 h; 94% sensitivity and 67% specificity) revealed a high diagnostic value for spinal CSF leaks. Their combination provided little improvement (71% sensitivity and 95% specificity). Additional quantitative analyses yielded no benefit (94% sensitivity and 53% specificity for biological half-life; 94% sensitivity and 58% specificity for the ratio of total radioactivity within the CSF space at 5 and 3 h). The location of direct signs (extrathecal tracer accumulation) did not correlate with verified sites of spinal CSF leakage. Conclusion: We propose CSF PET with 68Ga-DOTA as a novel, fast, and convenient approach to RC for verification but not localization of spinal CSF leaks with high sensitivity and specificity. CSF PET may fulfill an important gatekeeper function for stratifying patients toward escalation (ruling in) or deescalation (ruling out) of diagnostic and therapeutic measures. Further prospective studies are needed to validate the present results and determine the potential of the methods to reduce the burden to patients.