Intrathecal 99m Tc-DTPA imaging of molecular passage from lumbar cerebrospinal fluid to brain and periphery in humans

Alzheimers Dement (Amst). 2020 Apr 29;12(1):e12030. doi: 10.1002/dad2.12030. eCollection 2020.

Abstract

Introduction: Cerebrospinal fluid (CSF) molecular exchange with brain interstitial fluid (ISF) and periphery is implicated in neurological disorders but needs better quantitative clinical assessment approaches.

Methods: Following intrathecal (ITH) dosing via lumbar puncture, Technetium-99 m (99mTc-) diethylenetriaminepentaacetic acid (DTPA) imaging was used to quantify neuraxial spread, CSF-brain molecular exchange, and CSF-peripheral clearance in 15 normal human volunteers. The effect of experimental convection manipulation on these processes was also assessed.

Results: Rostral cranial 99mTc-DTPA exposures were influenced by the volume of artificial CSF in the formulation. Signal translocation to the cranial cisterns and the brain parenchyma was observable by 3 hours. 99mTc-DTPA penetrated cortical ISF but showed lower signal in deeper structures. Urinary 99mTc-DTPA signal elimination was accelerated by higher formulation volumes and mechanical convection.

Discussion: Widely used for detecting CSF leaks, ITH 99mTc-DTPA imaging can also become a useful clinical biomarker for measuring molecular exchange physiology between the CSF, brain, and periphery.

Keywords: biomarker; brain clearance; cerebrospinal fluid; imaging; intrathecal.