Teresa Gerhalter1, Rosemary Peralta1, Mickael Tordjman1, Julia Zabludovsky1, Seena Dehkharghani1, Alejandro Zarate2, Soo-Min Shin3, Ilya Aylyarov3, Tamara Bushnick2, Jonathan M. Silver4, Stephen P. Wall3, Brian S. Im2, Ryan Brown1, Guillaume Madelin1, and Ivan I. Kirov1
1Center for Biomedical Imaging, Department of Radiology, New York University School of Medicine, New York, NY, United States, 2Department of Rehabilitation Medicine, New York University School of Medicine, New York, NY, United States, 3Ronald O. Perelman Department of Emergency Medicine, New York University School of Medicine, New York, NY, United States, 4Department of Psychiatry, New York University School of Medicine, New York, NY, United States
Synopsis
In this
quantitative sodium MRI study, 24 mild traumatic brain injury (mTBI) and 9
controls were scanned at 3 T. Total sodium content (TSC) was calculated in five
different subcortical regions, as well as in global grey and white matter.
TSC in mTBI
did not differ statistically from controls for the examined regions. Patients
with findings on conventional 1H imaging (e.g. lesions,
microhemorrhages) did not differ from patients without such findings in their
TSC. More patients and controls are being recruited to strengthen the
statistical power of these comparisons.
Introduction
Traumatic
brain injuries (TBI) secondary to head trauma are one of the main causes of
neurological disabilities worldwide, particularly in young adults1. Despite its low severity,
mild TBI often presents physical, psychiatric, emotional and cognitive
disorders2, however the biological
correlates of these manifestations are not detected on CT and MRI3.
Cerebral 23Na
MRI allows a quantitative assessment of new biochemical information in brain,
such as ion homeostasis, which is vital for cell viability. This advanced
technique has been used in recent years mainly in multiple sclerosis4 and migraine5. In TBI, white matter is
susceptible to injury caused by acceleration, deceleration and rotational
forces. The Na+/K+ exchange pump can be affected by energy deficits due to
mitochondrial dysfunction, as well as by diffuse axonal injury, the
histopathological signature of TBI6,7.
The purpose
of this study was to investigate the total sodium content (TSC) in different
brain regions of patients with mTBI within one month of injury. TSC measures were
correlated to standard imaging and clinical evaluation.Materials & Methods
Twenty-four
patients (18-60 years, 16 females) with confirmed mTBI, and nine age-matched healthy
volunteers (23-54 years, 6 females) were recruited as controls for this
study. Images were acquired 23±9.5 days after the injury on a 3T scanner
(Magnetom Prisma, Siemens Healthineers).
A
20-channel quadrature head coil (Siemens Healthineers) was used for 1H
imaging. The qualitative screening included 3D MPRAGE (TR/TE/TI =
2400/2.24/1060 ms; flip angle = 8°; in plane FOV = 256x256 mm2;
208 slices, slab thickness = 0.8 mm; voxel size = 0.8×0.8x0.8 mm³; TA = 6:38
min), FLAIR (TR/TE/TI = 9000/81/2500 ms; 30 slices, in-plane FOV = 220x220 mm2;
voxel size = 0.7×0.7×5.0 mm³; TA = 2:44 min) and
SWI (TR/TE = 28/20 ms; flip angle = 15°; in-plane FOV = 220x220 mm2;
voxel size = 0.7×0.7×3.0 mm³; TA = 3:46 min). A
radiologist evaluated these images for possible lesions and microhemorrhages.
Sodium
imaging was performed using a 1H/23Na double-tuned head
coil (in-house built). All 23Na images were acquired using a 3D ultrashort
TE non-Cartesian FLORET sequence9. The spin-density weighted
image was acquired with the following parameters: TE = 0.2 ms, TR = 100 ms, 3
hubs at 45°, number of interleaves/hub = 26, resolution = 6 mm isotropic, 46 averages,
TA 5:59 min. 23Na signals were calibrated using the eyes. Brain
segmentation was performed using SPM12 (UCL, UK) from MPRAGE data.
In addition
to global grey matter (GM) and white matter (WM), we estimated the TSC in
different regions on the brain: thalamus (TH), putamen (PU), pallidum (PA), and
the splenium (SP) and genu (GE) of the corpus callosum (see Figure 1).
All TBI
patients also underwent clinical and neurocognitive testing. The clinical
examination included the Rivermead post-concussion symptoms questionnaire (RPQ)10, the ICHD-3 Headache screening11, and the Glasgow Outcome Scale – Extended (GOSE)12. For the neurocognitive assessment, we used the Brief
Test of Adult Cognition by Telephone (BTACT) that addresses episodic memory and
executive functioning13.
The two-sided
Wilcoxon rank sum test was applied to the median of the TSC over the five
different regions and the global GM and WM in all subjects to assess the
significance of their difference between control and TBI. Statistical
difference was defined as p<0.05.Results
The
demographics and cognitive measures are presented in Table 1. The individual tests and the composite z-scores of the
BTACT did not differ between controls and mTBI. One patient had microbleeds,
five patients had FLAIR signal abnormalities and one patient had an axonal
shear injury with corresponding microhemorrhages.
The
presence of these findings did not correlate with the clinical and
neurocognitive testing. There were no differences in TSC between mTBI and
controls for the global GM and global WM nor for any of the subcortical regions
(Figure 2). Five patients had TSC
changes higher than two SD of the mean in at least one of the following
regions: genu, splenium and pallidum.
Figure 3 presents one example of TSC map with the
corresponding FLAIR and SWI images. Patients with findings on conventional 1H
imaging (e.g. lesions, microhemorrhages) did not differ from patients without
such findings in their TSC (Figure 4).
Both patient groups displayed a variety of outcome in the clinical and
neurocognitive tests.Discussion & Conclusion
We
evaluated 23Na MRI for providing quantitative indices related to
pathological changes after mild TBI.
There were
no statistically significant findings for global measurement of TSC in the
examined regions of the brain. However, the median TSC values in mTBI were consistently
lower compared to those in matched controls.
The sample size
of this patient cohort is being increased and is now being investigated with 1H
and 23Na MRI three months and one year after the first exam to
determine the relationship between head trauma indices and the clinical outcome
of mTBI. As importantly, more controls are being added to increase the
statistical power of the above comparisons.Acknowledgements
This
project was supported by grant R01NS097494 from the National Institute of
Health (NIH).References
1. Dang,
B., Chen, W., He, W. & Chen, G. Rehabilitation Treatment and Progress of
Traumatic Brain Injury Dysfunction. Neural Plast. 2017, 1–6
(2017).
2. Maas,
A. I. R. et al. Traumatic brain injury: integrated approaches to improve
prevention, clinical care, and research. Lancet Neurol. 16,
987–1048 (2017).
3. Blennow, K. et
al. Traumatic brain injuries. Nat. Rev. Dis. Prim. 2, 16084
(2016).
4. Petracca, M. et
al. Brain intra- and extracellular sodium concentration in
multiple sclerosis: a 7 T MRI study. Brain 139, 795–806 (2016).
5. Meyer,
M. M. et al. Cerebral sodium (23Na) magnetic resonance imaging in
patients with migraine — a case-control study. Eur. Radiol. (2019).
doi:10.1007/s00330-019-06299-1
6. Saraiva, A. L.
L. et al. Creatine reduces oxidative stress
markers but does not protect against seizure susceptibility after severe
traumatic brain injury. Brain Res. Bull. 87, 180–186 (2012).
7. Lima,
F. D. et al. Na+,K+-ATPase activity impairment after experimental
traumatic brain injury: Relationship to spatial learning deficits and oxidative
stress. Behav. Brain Res. 193, 306–310 (2008).
8. Grover,
H. et al. MRI Evidence of Altered Callosal Sodium in Mild Traumatic
Brain Injury. Am. J. Neuroradiol. 39, 2200–2204 (2018).
9. Pipe,
J. G. et al. A new design and rationale for 3D orthogonally oversampled
k-space trajectories. Magn. Reson. Med. 66, 1303–1311 (2011).
10. King,
N. S., Crawford, S., Wenden, F. J., Moss, N. E. G. & Wade, D. T. The
Rivermead Post Concussion Symptoms Questionnaire: a measure of symptoms commonly
experienced after head injury and its reliability. J. Neurol. 242,
587–592 (1995).
11. Vincent,
M. & Wang, S. Headache Classification Committee of the International
Headache Society (IHS) The International Classification of Headache Disorders,
3rd edition. Cephalalgia 38, 1–211 (2018).
12. Wilson,
J. T., Pettigrew, L. E. & Teasdale, G. M. Structured interviews for the
Glasgow Outcome Scale and the extended Glasgow Outcome Scale: guidelines for
their use. J. Neurotrauma 15, 573–85 (1998).
13. Tun,
P. A. & Lachman, M. E. Telephone assessment of cognitive function in
adulthood: the Brief Test of Adult Cognition by Telephone. Age Ageing 35,
629–632 (2006).