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Sodium MRI for Acute Stroke Imaging

The cellular sodium-potassium pump, a trans-membrane enzyme which regulates the intracellular sodium concentration, keeps it at approximately 10 mM compared to an extracellular concentration of ~140 mM. In many diseases, these concentrations are known to change and hence measurements of sodium concentration in tissue can provide information on the status of the tissue, potentially aiding in disease diagnosis or therapy monitoring. For example, in cancer, tumours have altered sodium concentrations, while these values are known to change during therapy, and thus could potentially be used to monitor therapy efficacy. A further example is in stroke - here, the bioenergetic failure which occurs within minutes of the ischaemic event disrupts the Na+/K+-ATPase pump function (which, depending on the cell type, is responsible for between one and two thirds of the cell's energy expenditure), having a consequent effect on the intracellular and hence total tissue sodium concentration (TSC).

The aim of our research was to develop a technique for measuring the TSC in the rodent brain in the acute phase of an ischaemic stroke.

The Problem

The signal from 23Nais approx. 105 times less than that for conventionally-detected 1H nuclei

The Solution

To overcome this sensitivity problem, we focussed on developing dual-tuned (1H/23Na) radiofrequency volume resonators for uniform and efficient irradiation of the sample, and sensitive surface detector coils.


Dual-tuned (1H/23Na) birdcage volume resonator, with shield on left


Surface detector coil and associated electronics

Publications

  1. Wetterling F, Gallagher L, Macrae IM, Junge S, Fagan AJ, "A double-tuned 1H/23Na dual resonator system for tissue sodium concentration measurements in the rat brain via Na-MRI", Physics in Medicine and Biology 55, 7681-7695, 2010, PMID 21113090
  2. Wetterling F, M. Hogler, U. Molkenthin, Junge S, Gallagher L, Macrae IM, Fagan AJ, "The design of a double-tuned two-port surface resonator and its application to in vivo Hydrogen- and Sodium-MRI", Journal of Magnetic Resonance, 217, 10-18, 2012, PMID 22391488
  3. Fagan AJ, "Is there a role for Sodium-MRI in the management of acute stroke patients?", Imaging in Medicine, 4 (3), 367-379, 2012

 

Acute Stroke Imaging

The vast majority of cerebral strokes are caused by a blockage in one of the arteries in the brain. The cells within the brain tissue which were being fed by the blocked artery will suffer bioenergetic failure and die within minutes of the blockage. However, tissue in the surrounding areas of the brain may have a residual flow of blood which may allow them to survive for several hours. This tissue area is called the penumbra and it is precisely this tissue that could be saved with a timely therapeutic intervention in the Emergency Department. The more tissue that is saved, the less damage there is to the brain.

However, to date, the difficulty has been in determining whether a patient has any penumbra tissue, or tissue that can still be saved, by the time they present at the Emergency Department and because of possible side effects with current clot busting drugs for stroke, clinicians must be conservative in administering it. In fact current guidelines only allow for this administration within a 4.5 hour time window from stroke onset, which means that only a small percentage of patients can avail of this treatment. Traditional MRI scanning techniques which scan for water molecules in the body do not provide clear enough data on the existence of penumbra tissue

The research from our group may open up the time window, by providing a non-invasive imaging technique that can detect the presence of penumbra tissue. This is based on subtle changes in the concentration of sodium atoms in the cells affected by the reduced blood flow which alters the functioning of the energy-hungry sodium-potassium pump across the cellular membrane in the cells. Using the sodium-MRI technique, we were able to demonstrate that the sodium concentration decreased by approximately 12% in penumbra tissue, thereby providing a novel way of detecting the presence or indeed absence of this tissue.


Tissue sodium concentration as a function of time in several slices through the brain, in the acute phase of a stroke

Publications

  1. Wetterling F, Tabbert M, Junge S, Gallagher L, Macrae IM, Fagan AJ, "Regional and temporal variations in tissue sodium concentration during the acute stroke phase", Magnetic Resonance in Medicine, 67(3), 740-749, 2012, PMID 21678490
  2. Wetterling F, Gallagher L, Mullin J, Holmes WM, McCabe C, Macrae IM, Fagan AJ, "Sodium-23 Magnetic Resonance Imaging has potential for improving penumbra detection but not for estimating stroke onset time", Journal of Cerebral Blood Flow and Metabolism 35, 103-110, 2015, doi: 10.1038/jcbfm.2014.174, PMID: 25335803