Red blood cells (RBCs) undergo an autonomous/spontaneous shape change when depleted of glucose or are poisoned with various reagents, including 20 mM NaF. They change from their normal biconcave disc shape (discocyte [1]), to a spiky spherical form (echinocyte), and then on to a sphere (spherocyte), over periods of 10’s of minutes. This shape evolution is called the DEST morphological transformation. Because discocytes align with their flat(ish) faces parallel to B0 in an NMR magnet [2], the average anisotropy of the electric field gradients (EFGs) associated with the cell membrane leads to an enhanced double-quantum filtered (DQF) 23Na+ NMR signal from the ions, especially outside the cell. When the cell shape changes the EFGs becomes progressively spherically averaged, so the DQF declines. A time course of the DQF spectral intensity correlates with an increase in echinocyte and spherocyte numbers in images recorded with differential interference contrast (DIC) light microscopy. Various experimental developments led to control of the rate of the DEST. These will be explained, along with the theoretical basis of the observations that rely on quantum mechanical theory of irreducible spherical tensors [3,4]. Cross-correlation between quadrupolar- and paramagnetic-relaxation mechanisms/pathways means that conversion of haemoglobin to the highly paramagnetic FeIII -containing form (methaemoglobin) leads to emergence of a DQF-signal from 23Na+ even in isotropic haemolysates (RBCs disrupted by freezing and thawing). In other words, a DQF 23Na+ NMR signal from RBCs that have been biochemically manipulated allows the population size of such altered cells to be determined from mixtures with normal RBCs. The rationale for wanting to do this in studies of mechanosensation in RBCs will be explained.