We have investigated the potential of diffusion MRI to provide quantitative estimates of tissue stiffness and compared results with those obtained by standard MR elastography (MRE). We revealed that water diffusion, calculated from 2 key b values, can be directly and quantitatively converted into shear stiffness without using mechanical vibrations. Propagating shear waves can also be simulated leading to a new elasticity-driven IVIM attenuation contrast. Such virtual elastograms give a variety of contrasts by simulating various ranges of vibration frequencies and amplitudes or MRI gradient strengths not limited by MRE hardware capacities.
26 liver patients (23 fibrosis, 3 tumors) were examined using a 3T MRI scanner (Discovery 750; GE Medical Systems) with a 32-channel phased-array coil. 8 patients were excluded because of severe motion artifacts or poor signal-to-noise ratio. Vibration (60Hz) to the liver was induced from a cylindrical driver linked to a vibrator and attached to the right chest wall8. Patients were asked to hold their breath after expiration. MRE acquisition parameters were: TR/TE=50ms/20ms, 23° flip angle, 1 Nex, 256x80 matrix, 5mm thickness, 40x40cm² FOV, motion-sensitizing gradient along Z axis. Stiffness maps were calculated using an inversion algorithm implemented on the scanner2 and liver elasticity, μ was estimated from regions-of-interest (ROIs) on the stiffness maps. For dMRI the acquisition parameters were: SE-EPI, TR/TE=~4000ms/56.6ms, respiratory gating, 2 Nex, 4mm thickness, 100x100 matrix, 40x40cm² FOV, diffusion encoding along [X,Y,Z] using 2 ”key b values” (200, 1500s/mm²) optimized for non-Gaussian diffusion9. ROIs were placed in the liver by an independent reader, blind to the MRE results, and a “shifted ADC” (sADC) was calculated from the signals, S200 and S1500 acquired at b=200 and 15009:
sADC=ln(S200/S1500)/1300 [1]
In a first calibration step an empirical relationship between sADC and mMRE was searched from a statistical correlation analysis using a subpopulation of 5 fibrosis patients. Then, the dMRI derived shear stiffness was estimated, in a reverse way, for all patients as:
μdiff=f-1[ln(S200/S1500)] [2]
In a second step 3D virtual shear stiffness maps mdiff(x,y,z) were calculated using Eq.[2] on a voxel-by-voxel basis (in-house Matlab software). Those maps were used to emulate contrast which would result from propagating shear waves through the tissue, based on an IVIM effect10 in the presence of motion-encoding gradients (Fig.1): Tissues with low stiffness/short wavelengths have strong intravoxel phase dispersion, i.e. a large IVIM signal attenuation, and vice-versa. Such vibration induced IVIM effects can be seen with standard MRE11, but were here emulated from μdiff to produce virtual elastograms with different contrasts. IVIM signal attenuation, SI(b)/SIo at location r which would be obtained from any combination of vibration frequency/amplitude, f/ε, and b value was calculated as:
$$SI(b)/SIo=\int_{r}^{r+p}dr exp[i(ε/π)(48bNf)^{1/2} sin(2πr/λ+θ)] [3]$$
where θ is the phase offset of the virtual shear wave with the oscillating gradients train (period N), λv its spatial wavelength and p the voxel size. The spatial wavelength is linked to the virtual shear modulus as λv=1/f (μdiff/ρ)1/2 with ρ~1g/cm3.
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