The major protons responsible for the MR signal or its modulation: free water, bound water, macromolecules, and fats. Lipid stores are usually in isolated compartments hence the dotted line. Small organic molecules make a very minor contribution to overall signal (except in water suppressed MRS) and are not pictured.
- "Free" water. This is the largest and most important source of the NMR signal in most tissues (except for fat). "Free" water is called such because it is largely unstructured except by transient hydrogen bonding to similar molecules. CSF would be considered nearly exclusively composed of this type of proton. High concentrations of "free" water are also present in cytosol and cellular interstitium. Because these ¹H2O molecules rotate very quickly and over a wide range of frequencies, they are associated with very ineffecient (i.e. long) T1 and T2 values (several seconds at 1.5T).
- Fat. Besides protons in ¹H2O, the only ¹H nuclei making a significant direct contributions to the MR signal occur in tissues containing fats/lipids/trigylcerides such as adipose tissue, skeletal muscle, and bone marrow. The ¹H nuclei responsible for this signal principally are found in the long chain fatty acid components. Because their motion is relatively restricted, these protons demonstrate short T1 values (a few hundred msec) and short T2 values (a few dozen msec). It should be noted that this "fat" pool does not include membrane phospholipids or myelin sphingolipids. These substances have very short T2 values and only an indirect effect on the MR signal. They are considered below under the category of macromolecules.
- Macromolecules. This category includes the diverse and vast array or organic molecules besides water and fat present in biological tissues. Despite the name, macromolecules do not have to be "huge" to fit this classification — any protein or fragment more than several hundred daltons (Da) would qualify. Most ¹H nuclei in macromolecules have highly restricted motions and are subjected to the static and low frequency magnetic fields from neighboring nuclei and paramagnetic ions. As such, the macromolecular pool typically has very short T2 values (ranging from a few hundred μsec to just a couple of msec). The signal from these protons decay much too quickly to be recorded on conventional MR imaging sequences. However, macromolecules do significantly modulate the signal from water protons as described in the prior Q&A.
- "Bound" water. This pool consists of a few layers of ¹H2O molecules closely associated with the surface of macromolecules. Water in this "hydration layer" is moderately structured and restricted in motion through hydrogen bonding with sites on macromolecules. Because of its restricted motion, bound water has relatively short T2 values (on the order of a few to dozens of msec), and likely explains the fact that in tissues T2 is much shorter than T1 compared to simple solutions. "Bound" water may undergo both dipole-dipole cross-relaxation as well as chemical exchange with macromolecular ¹H nuclei. "Bound" water also interfaces with "free" water on its outer surface, so a pathway exists for the transfer of magnetization between the macromolecular and free water pools.
- Small organic molecules. MR signals are emitted from a wide range of amino acids, sugars, organic acids, and the like. These are the primary subject of MR spectroscopy. However, their concentrations are several hundred fold smaller than water protons, so their contributions to the overall MR signal is insignificant. In order to observe and measure them in MRS, the water signal must be suppressed.
Advanced Discussion (show/hide)»
The signals from macromolecular protons are not directly imaged on conventional MRI due to their very short T2 values. These nuclei do produce an MR signal, but it decays too quickly to be recorded under normal circumstances. However, several new ultrashort TE (UTE) sequences are now commercially available with more in development allowing the signals from these nuclei to be detected. This exciting research will be described in several later Q&A's.
Elster AD, Burdette JH. Questions and Answers in MRI, 2nd ed. St. Louis: Mosby, 2001.
How does the presence of macromolecules affect T1 and T2?