Can we make the voxel smaller?

A common question that comes up with new collaborators (or old ones!) is "Can we make the voxel smaller?" or "Can we make the measurement shorter?", or sometimes, for the most ambitious, both.

My usual reply is "Yes, you can. But you should be aware of the consequences".

MRS in general, and edited MRS particularly, works at low levels of signal-to-noise.  MR is an inherently insensitive technique and we are detecting signals from millimolar metabolites within the head using an array of coils outside the head.  

SNR is determined by several factors, most of which are unchangeable: coil size; coil geometry; field strength; etc.  The main variables that are, well, variable are the number of averages (i.e. scan time) and the voxel size.  

SNR is directly proportional to voxel size, so the SNR of a 3x3x3 cm^3 voxel is over three times that of a 2x2x2 cm^3 voxel.  Even reducing voxel size by 10% linearly (which has an almost negligible impact on its apparent size) will reduce SNR by 30%. So my feeling is that you lose SNR far more quickly than you feel like you are gaining resolution.

SNR is also proportional to the square-root of the number of averages. This means that 'buying back' SNR losses from reducing voxel size with increased scan time is very expensive.  To regain that 30% signal, you would have to scan for twice as long... not a good trade.  The flip side of this is that reducing scan time hurts you relatively slowly.  Decreasing the scan time by 20% only impacts SNR by 10%.

The reason that this question often comes up it that people want spatial specificity to be as high as possible, and either want good temporal resolution or rapid scan times.  This is almost universally true, so experiments are already defaulted to the lowest SNR that I feel comfortable with.  For GABA, the 3x3x3 voxel scanned for 10 minutes also coincides with the mean SNR-factor from a literature review of GABA-edited  MRS.

But the quick answer is, "yes, you can reduce voxel size or scan time, but they will impact SNR".  If you want to do both, reducing scan time will hurt you less.