A new technique for measuring tissue cellular volume fraction, based o
n an improved modeling of the dynamic distribution of Gd-DTPA and the
effect of proton exchange, is described, This technique uses peak T-1
enhancement and blood Gd-DTPA concentration to compute tissue cellular
volume fraction, The feasibility of this technique is demonstrated wi
th computer simulations that explore the limits of the simplifying ass
umptions (small vascular space, slow vascular-extravascular proton exc
hange), and by direct comparison of MR and radionuclide cell fraction
measurements made in muscle, liver, and tumor tissue in a rat model, T
he computer simulations demonstrate that with slow to intermediate vas
cular proton exchange and vascular fractions less than 10% the error i
n our cell fraction measurements typically remains less than 10%, Cons
istent with this prediction, a direct comparison between MR and radion
uclide measurements of cell fraction demonstrates mean percent differe
nces of less than 10%: 1.9% in muscle (n = 4); 9% in liver (n = 1) and
9.5% in tumor (n = 4), Similarly, for all rats studied, the MR-measur
ed cell fractions (muscle (0.92 +/- 0.04, n = 20); liver (0.76 +/- 0.1
1, n = 9); whole tumor (0.69 +/- 0.15, n = 22)) agree with the cell fr
action values reported in the literature, In general, the authors' res
ults demonstrate the feasibility of a simple method for measuring tiss
ue cell fraction that is robust across a broad range of vascular volum
e, flow, and exchange conditions, Consequently, this method may prove
to be an important means for evaluating the response of tumors to ther
apy, Key words: Cell fraction; Gd-DTPA; proton exchange.