Student Poster Presentation #15 (Session 2)
Dynamic Quantitative Imaging of Sodium During Onset of a Rat
Migraine Model and Its Propagation at 21.1 T
Nastaren Abad 1,2 , Jens T. Rosenberg 2 , Michael G. Harrington 3 , Samuel C. Grant 1,2
Department of Chemical and Biomedical Engineering, FAMU-FSU College of Engineering, Tallahassee, FL, USA 2 The
National High Magnetic Field Laboratory, Florida State University, Tallahassee, FL, USA 3 Molecular Neurology Program,
Huntington Medical Research Institutes, Pasadena, CA, USA
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Abstract
Purpose
Ionic instability and dysfunctional regulation is implicit in migraineurs. The brain allocates over
50% of its energy reserves on a cellular basis to the regulation of sodium homeostasis; therefore, the alteration
of sodium concentrations and fluxes related to these distributions are critical 1 . Accordingly, it is hypothesized
that migraineurs have a distinct a prevailing mechanism that induces excess sodium to be pumped into the
extracellular space, resulting in neuronal excitability that is sustained with the onset and progression of migraine.
More specifically, the purpose of this study was to evaluate dynamic in vivo ( 23 Na ) fluxes in the brain, using a
migraine analogue in rodent. Ultra-high field of 21.1 T was utilized to allow for higher spatial and temporal
resolution to quantify bulk sodium distributions during and following the onset of central sensitization, to study
a longitudinal time course of >3hrs. This time course allowed for investigation of bulk sodium changes during
the onset and propagation of central sensitization, while rigorously accounting for any cyclical or circadian
variations in biological sodium.
Methods
Animal Model: A total of 12 male Sprague-Dawley rats were used in this study. While in the
MRI scanner and sedated with isoflurane, they were administered in situ with an IP injection of either 10 mg/kg
of NTG (n=6) to induce central sensitization (CS), or saline (n=6) as controls. MRI protocol: Slice selective
sodium images were acquired using a multi-slice FID-based Chemical Shift Imaging (CSI) sequence yielding
an in-plane acquisition resolution of 1.1 x 1.1 mm and through-plane resolution of 3-mm. Using a repetition time
(TR) of 180 ms, and with 6 averages, the complete dataset was acquired in 9 minutes. A total of twenty-seven
repeated scans were acquired starting from pre-injection, followed by 3-h post injection scanning. Data Analysis:
CSI data sets were analyzed using AMIRA (FEI Corp, Hillsboro OR). Images were manually segmented with
ROIs placed in the eyes, olfactory bulb, third ventricle, neocortex, fourth ventricle, cerebellum, brainstem and
cisterna magna along with a muscular region in the rat jaw to serve as an internal control for the 23 Na signal.
Results and Discussion
Increase of 23 Na MRI signal was evident for NTG treated animals in the brainstem,
th
4 ventricle and the cisterna magna almost immediately after injection, gaining significance about 30-45 min
post-injection. The cerebellum and 3 rd ventricle also showed increasing trends of increased 23 Na post -injection,
gaining delayed significance >1.5hrs. These dynamic changes (rapid increases in sodium concentration
compared to the controls) indicate that the mechanism of Central sensitization is dependent on, specific to, and
localized in certain anatomical regions. These time dependent fluctuations could provide prominent insight into
dysregulations of migraine and subsequent therapeutic measures.
Reference
1. Harrington M, Fonteh A, Cowan R, Perrine K, Pogoda J, Biringer R, Huhmer A. Cerebrospinal fluid sodium increases
in migraine. Headache 2006;46(7):1128-35.
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