The two-compartment IVIM diffusion model proposed by Le Bihan (1) is commonly used for DWI studies in the body. In this model, compartments are taken to represent pseudo-diffusion and true diffusion, which may in turn represent vascular and tissue fractions. Standard diffusion-weighted imaging (DWI) protocols are acquired at a single (usually minimum) TE and incorrectly assume a single (apparent) T₂, thus causing the observed pseudo-diffusion fraction f to be dependent on the TE chosen (2). Distinct transverse relaxation constants for these components (T_2p and T_2t for pseudo- and true diffusion compartments, respectively) modify the standard IVIM model (Eq. 1) for echo time (TE) dependency (Eq. 2), where f is pseudo-diffusion fraction, D and D* are true and pseudodiffusion coefficients, T_2p and T_2t are the transverse relaxations constants for pseudo- and true diffusion compartments, and $$${S_{eff}} ={S_0}.\exp\left(\frac{-TE}{T_{2apparent}}\right)$$$:

$${S_{b}} ={S_{eff}}.\left[ f.\exp\left(-b.D^*\right) + \left(1-f\right).\exp\left(-b.D\right)\right]$$ Eq 1 (standard IVIM model)

$${S_{b,TE}} ={S_0}.\left[ f.\exp\left(\frac{-TE}{T_2p}\right).\exp\left(-b.D^*\right) + \left(1-f\right).\exp\left(\frac{-TE}{T_2t}\right).\exp\left(-b.D\right)\right]$$ Eq 2 (extended T2-IVIM model)

We present additional measurements at low b-values with increased TE as a method of deriving an estimate of f that is independent of TE, a parameter not commonly fixed in clinical MR studies. A b-value of 50mm^-2s is sufficient to remove the pseudo-diffusion component in the liver (3), with the assumption that associated signal decay due to true diffusion is small (<5% for D of 1x10^-3mm²s^-1 in the liver). Full sampling of the b-value/TE space is challenging (4), however a clinical timeframe acquisition is able to give a TE-independent estimation of f that may be more accurate, and thus clinically useful and sensitive to modulation of pseudo-diffusion fraction, as well as providing native estimations of T₂.

Volunteers (n=6) underwent coronal free-breathing DWI of the abdomen using a MAGNETOM Avanto 1.5T scanner (Siemens Healthcare, Erlangen, Germany), acquired twice (24hr separation) using a prototype sequence with the following parameters: diffusion delays δ 16.0ms and Δ 20.2ms, 3-scan trace monopolar diffusion scheme, TR 4000ms, FOV 380x380mm², 16x5mm slices, matrix 128x128 (interpolated to 256x256), bandwidth 1628 Hz/pixel, SPAIR fat suppression, 7/8 partial Fourier, iPAT factor 2, and 12 averages. Seven b-values (0,10,50,100,200,400,800 mm^-2s) were acquired at (minimum) TE 62ms (total 15 minutes), with three additional b-values (0,10,50 mm^-2s) acquired at TE 80 and 100ms (additional 10 minutes). A region of interest (ROI) was drawn for a single slice over the liver for each volunteer (Figure 1a); fitting of the standard IVIM and extended T2-IVIM model was performed for mean ROI signal in each unregistered image (b-value and signal average), and voxel-wise in one volunteer, using custom MATLAB routines. The repeat measures coefficient of variation was calculated for each parameter across the cohort using log-transformed values.Representative ROI and voxel-wise f values for the two models are shown in Figure 1; parameters derived from the IVIM and T2-IVIM models are given in Table 1; the TE-independent f is substantially smaller (mean 35±15% decrease, p=0.002, paired t-test; Figure 2), while both D and D* from the T2-IVIM model are comparable to conventional IVIM values. The T_2t value returned for the liver tissue compartment is consistent with literature (5), although the T_2p returned (77.6±30.2ms) was substantially lower than literature (5) (290ms). In this study, the CoV for D and D* was small in both models (see Table 2), which for D is consistent with previous work but lower for D* than previously observed in tumours (6). In the T2-IVIM model, the CoVs for f and T_2p were large (>20%), which indicates the inherent difficulty in separating these two parameters.DWI studies commonly use a minimum TE dictated by gradient hardware and diffusion scheme. The dependence of the IVIM pseudo-diffusion parameter f on TE may limit its clinical utility; when using the standard IVIM model, failure to account for distinct T₂ values for the two volume fractions may bias estimates of f and lead to misinterpretations of observed changes. An extended T2-IVIM model that includes T₂ for each component can be used to derive TE-independent (TE = 0ms) estimations of IVIM parameters (4). Full sampling of TE/b space is limited by minimum TEs and SNRat larger TE/b combinations, but T2-IVIM parameters derived from the addition of a small number of TE/b combinations (minimum 2 b-values at 1 extra TE, additional ~20% scan time) to a standard IVIM protocol may provide useful estimates for TE-independent f, D, D*, and complementary information from T_2p, and T_2t (7), within clinical DWI examination times.