Jonathan R Birchall1, Ines Horvat-Menih1, Joshua D Kaggie1, Frank Riemer2, Arnold J V Benjamin1, Martin J Graves1, Ian Wilkinson3, Ferdia A Gallagher1, and Mary A McLean1
1Department of Radiology, University of Cambridge, Cambridge, United Kingdom, 2Department of Radiology, Haukeland University Hospital Helse Bergen, Bergen, Norway, 3Cambridge Cardiovascular, University of Cambridge, Cambridge, United Kingdom
Synopsis
Keywords: Quantitative Imaging, Non-Proton, Data Analysis
Motivation: Sodium homeostasis is altered in abdominal pathologies such as cancer and cardiovascular disease, but established quantification techniques require an invasive biopsy.
Goal(s): Quantification of abdominal sodium content and T2* relaxation in abdominal organs and fluid-filled structures using 23Na-MRI.
Approach: Proton and sodium imaging of the abdomen was performed in 18 healthy volunteers using a 3D cones sequence and a sodium-tuned body coil on a clinical 3 T system.
Results: Mean total sodium concentration and long T2* relaxation times were measured in 8 organs and fluid-filled structures; results agreed with previously published work in human and animal models.
Impact: Quantitative 23Na-MRI measurements in healthy volunteers will serve as a baseline to evaluate pathological changes in hypertension and kidney tumour characterisation. This may assist in the assessment of treatment efficacy, thereby reducing the need for invasive biopsy techniques.
INTRODUCTION
Cellular metabolism can be probed
by imaging MR-active X-nuclei such as sodium-23. Sodium exchange between cells
and extra-cellular fluid plays an essential role in regulating blood volume,
pressure and pH, as well as neuronal activation and maintaining cellular
resting potential1.
Existing sodium quantification techniques in routine clinical use are nonspecific
(e.g. urinary osmolarity2)
or require invasive tissue procurement.
Recent human sodium imaging
studies have included tumour characterisation in the ovaries3 and prostate4.
Quantitative proton relaxation time mapping has been demonstrated in tumour
hypoxia imaging5 and rectal cancer prognosis6.
However, measurements of normal sodium concentration across tissues measured
via 23Na-MRI in the literature vary. Establishing 23Na-MRI
as a quantitative imaging biomarker for cellular integrity and metabolism in cancer
staging is therefore important.METHODS
We quantified total 23Na
concentration and T2* relaxation in eight abdominal organs and fluid-filled
structures of healthy volunteers (N=18, 11M/7F) using a clinical 3 T system (MR750,
GE Healthcare, Waukesha MI). Sodium images were acquired using a 48 cm field-of-view,
4-rung birdcage transmit/receive body coil (RAPID Biomedical GmbH, Rimpar,
Germany), providing uniform excitation over a large proportion of the abdomen
in subjects with a range of body habitus7.
Corresponding fat/water proton images were acquired using a breath-hold 3D T1W sequence
with the MR system body T/R coil (TEs=1.1/2.2 ms, TR=3.7 ms, flip=15°, matrix=256x192,
phase FOV=0.7, FOV=40 cm). Two agarose NaCl phantoms (50 ml, 80 mM) provided signal
calibration.
High-resolution total sodium
concentration (TSC) maps were acquired over a 48 cm FOV using a 3D cones
trajectory8 (TE=705 μs,
TR=100 ms, flip=70°, averages=5, voxel size=4x4x8 mm, 1402 transients, bandwidth=167
kHz, duration=11:41 mins)–Figure 2d-f. B1 non-uniformity
correction was performed using the double-angle method9,10 (TE=705 μs,
TR=150 ms, flips=40/80°, averages=3, voxel size=9x9x9 mm)–Figure 2b. Maps
of 23Na long T2* component were generated by linear fitting
of log-transformed signal intensities from variable echo-time data (TEs=2/4/8/16
ms,
TR=150 ms, flip=70°, averages=4, voxel size=9x9x9 mm)–Figure 3b. Low-resolution
images spatially matched the high-resolution counterpart. Regions of interest were
drawn and analysed using MATLAB (MathWorks, Natick MA) for phantoms, kidneys,
CSF, liver, gall bladder, spleen, aorta and inferior vena cava–Figure 1.RESULTS
Mean
TSC (example B1-uncorrected map pictured in Figure 2c) was
highest in the gall bladder (124±44
mM) and CSF (93±19
mM). Values
of 77±14
mM and 72±10
mM were determined in the left and right kidneys, respectively. Blood TSC
values of 78±17
and 83±22 mM were observed in the aorta and inferior
vena cava. The liver and spleen demonstrated the lowest sodium concentrations: 41±10 mM and 40±9
mM, respectively.
23Na long T2*
component values (example map pictured in Figure 3c) for all regions generally fell within the range of previously-reported values1,11:
21.8±2.1
ms and 21.2±2.2
ms (kidneys), 21.7±3.6 ms (CSF), 10.2±2.2 ms (liver) and 10.9±3.5
ms (spleen). A complete summary of results is displayed in Figure 4.DISCUSSION
23Na TSC measurements
in gall bladder and CSF were lower than previous reports of ~150 mM sodium
concentration in bile12 and CSF13.
Mean TSC values in blood corresponded to normal blood TSC ranges for healthy adults of
135-145 mM14,15. Liver TSC values agreed with
previously-reported studies in healthy rat hepatocyte16,17,
but exceeded those seen previously in human studies18.
Kidney TSC values were comparable with previous human 23Na-MRI quantification
estimates in vivo19,20.
23Na long T2*
measurements in the kidneys agreed with previous reports in humans at 3 T20 and 7 T21,22, but values in CSF were substantially lower23.
Shorter liver and spleen 23Na T2* values correlate with
previous proton studies linking short T2* tissue components to high
paramagnetic iron content24-27.
High
variability for both parameters in small regions with high fluid content
was expected due to fluid motion and partial volume effects resulting from
limited spatial resolution achievable in a practicable imaging duration. Comparisons
with findings elsewhere in the literature are presented in Table 1.
Reliability
of 23Na TSC quantification could be improved using a linear fit
through multiple phantoms with different concentrations, as demonstrated in
studies of the leg28 and intervertebral disk29. Analysis of anatomical TSC variation and
correlations with other MR-based metrics could be facilitated by
registration of anatomical 1H and B1-corrected TSC maps.CONCLUSIONS
Reliable
quantification of TSC and 23Na long component T2* was
achieved in the kidneys, liver and spleen across a healthy volunteer group. Greater
variability observed in the gall bladder, blood vessels and CSF could be
improved via higher resolution with longer scan times or ECG-triggered acquisition, but the priority here was for clinical
tolerability. In the future, these techniques will be applied to characterise
patients with kidney cancer, hypertension and other pathologies. Acknowledgements
This
research was supported by the NIHR Cambridge Biomedical Research Centre
(BRC-1215-20014). The views expressed are those of the authors and not
necessarily those of the NIHR or the Department of Health and Social Care. JB
acknowledges support from the National Cancer Imaging Translational Accelerator
(NCITA). MM acknowledges support from the Cambridge Experimental Cancer
Medicine Centre and the Cancer Research UK Cambridge Centre. FG acknowledges
support from Cancer Research UK and The Mark Foundation Institute for
Integrated Cancer Medicine (MFICM).References
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