A review of ¹H nuclear magnetic resonance relaxation in pathology: Are T₁ and T₂ diagnostic?

The longitudinal (T₁) and transverse (T₂) proton (¹H) nuclear magnetic resonance (NMR) relaxation times of pathological human and animal tissues in the frequency range 1–100 MHz are archived, reviewed, and analyzed as a function of tissue of origin, NMR frequency, temperature, species, and in vivo versus in vitro status. T₁ data from specific disease states of the bone, brain, breast, kidney, liver, muscle, pancreas, and spleen can be characterized by simple dispersions of the form T₁=Aν^B in the range 1–100 MHz with A and B empirically determined pathology dependent constants. Pathological tissue T₂ values are essentially independent of NMR frequency. Raw relaxation data, best fit T₁ parameters A and B, and the mean T₂ values, are tabulated along with standard deviations and sample size to establish the normal range of pathological tissue relaxation times applicable to NMR imaging or in vitro NMR examination. Statistical analysis of relaxation data, assumed independent, reveals that most tumor and edematous tissue T₁ values and some breast, liver, and muscle tumor T₂ values are significantly elevated (p≤0.95) relative to normal, but do not differ significantly from other tumors and pathologies. Statistically significant abnormalities in the T₁ values of some brain, breast, and lung tumors, and most pathological tissue T₂ values could not, however, be demonstrated in the presence of large statistical errors. Both T₁ and T₂ in uninvolved tissue from tumor bearing animals or organs do not demonstrate statistically significant differences from normal when considered as a group, suggesting no appreciable systemic effects associated with the presence of tumors compared to the statistical uncertainty. Statistical prediction analysis for both T₁ and T₂ indicates that of all the tissues studied, only liver hepatoma can be reliably distinguished from normal liver based on a single T₁ measurement (p≤0.95) given the scatter in the current published data. Indeed, data scatter, not easily attributable to temperature, species, in vivo versus in vitro status, the inclusion of implanted or chemical induced tumors, or the possible existence of multiple component relaxation, is recognized as the major factor inhibiting the diagnostic utility of quantitative NMR relaxation measurements. Malignancy indexes that combine T₁ and T₂ data as a diagnostic indicator suffer similar problems of uncertainty. The literature review reveals a dearth of information on the temperature and frequency dependence of pathological tissue relaxation and the possible existence of multiple relaxation components. The causes of differences in pathological tissue relaxation times are presently ambiguous, although increases in tissue water content, growth rate, Na⁺ and K⁺ concentrations, and reductions in tissue glycogen and protein content have been correlated with elevated tumor T₁ values.