Multiple-Quantum Coherence Techniques

Healthy cells maintain a sodium concentration gradient across cell membrane of ~150 mM extracellular to ~10-15 mM intracellular. If the cell is damaged, this gradient is lost; this is also true for certain types of cancer cells. Thus, tracking changes in these concentrations can significantly contribute to the diagnosis of existing or emerging pathology. In the case of damaged or cancerous cells, it is the observation of the concentration of intracellular sodium that is of interest as; extracellular sodium concentration does not notably change. However, the separation of extra- and intracellular signal is difficult.

The quadrupolar moment of the sodium nucleus couples to the electric field gradients of the local biological micro-environment. If the correlation time with complex proteins and molecules is sufficiently long, alterations in the NMR signal can be observed. The multiexponential relaxation behaviour is one of these. Additionally, multiple-quantum coherences may evolve. These coherences are functions of the quadrupole moment, the order of the environment and the correlation time of restricted sodium nuclei. This is the case for intracellular sodium. In order to separate between intra- and extracellular signal, novel sequences must be developed, in order to enable evolution and detection of multiple quantum coherences. 

Studies have shown that the most promising approach for observing multiple-quantum coherences in vivo is observing the triple-quantum coherence, since it has a higher sensitivity and longer relaxation times than the double-quantum coherence.

However, triple-quantum filtering (TQF) techniques pose a series of technical and experimental challenges. Hard RF pulses demand powerful hardware and cause high SAR values. The TQF NMR signal is lower than the conventional single-quantum signal, leading to coarse resolution for acceptable SNR. Also, measurement time is long since averaging has to be applied. In order to address this, our group (Dr. D. Fiege) has developed the SISTINA sequence, which allows simultaneous measurement of single- and triple-quantum coherences and enables timesaving acquisition of multiple contrasts. 

Triple-Quantum filtered images of a healthy volunteer

Both rows show several slices of a healthy human brain. The anatomical proton images (black and white) are overlaid by sodium concentration images (orange, top row). The row below shows identical proton images, overlaid by triple-quantum filtered sodium images. Notably, the eyes do not contribute to the TQF image, despite their high sodium.