I. Jakobsen et al., MRI OF HUMAN TUMOR XENOGRAFTS IN-VIVO - PROTON RELAXATION-TIMES AND EXTRACELLULAR TUMOR VOLUME, Magnetic resonance imaging, 13(5), 1995, pp. 693-700
Proton T-1 and T-2 differ substantially between tumors, but the tumor
properties causing heterogeneity in T-1 and T2 have not been fully rec
ognized. The purpose of the study reported here was to investigate whe
ther differences in T-1 and T-2 between tumors are mainly a consequenc
e of differences in the fractional volume of the extracellular compart
ment. The study was performed using a single human tumor xenograft lin
e showing large naturally occurring intratumor heterogeneity in the si
ze of the extracellular compartment. The size of the extracellular com
partment was calculated from the volume and the density of the tumor c
ells. Cell volume was measured by an electronic particle counter. Cell
density was determined by stereological analysis of histological prep
arations. T-1 and T-2 were measured by MRI in vivo both in the absence
and presence of Gd-DTPA. Two spin-echo pulse sequences were used, one
with a repetition time (TR) of 600 ms and echo times (TEs) of 20, 40,
60, and 80 ms and the other with a TR of 2,000 ms and TEs of 20, 40,
60, and 80 ms. Measurements of T-1 and T-2 in the presence of Gd-DTPA
were performed in a state of semi-equilibrium between uptake and clear
ance of Gd-DTPA. MR-images and histological preparations of tumor subr
egions homogeneous in extracellular volume were analysed in pairs. The
extracellular volume differed between tumor subregions from 5 to 70%.
T-1 and T-2 measured in the absence of Gd-DTPA differed between tumor
subregions by a factor of approximately 1.5 and increased with increa
sing extracellular volume. The relative decrease in T-1 caused by Gd-D
TPA, represented by (T-1 (control)- T-1 (Gd-DTPA))/T-1 (control), also
increased with increasing extracellular volume. The relative decrease
in T-2 did not change significantly as the extracellular volume incre
ased. These observations strongly suggest that the size of the extra-c
ellular compartment is a major determinant of proton T(1)s and T(2)s o
f tumors, possibly because the ratios of free to structured and free t
o bound water increase with increasing extracellular tumor volume.