A method for determining one or several signature indices of an observed tissue, representative sensitively of a type of tissue or representative sensitively of a microstructure or biological state of a type of tissue, the signature indices being determined from motion-probing pulses gradient Magnetic Resonance Images of the observed tissue, and the method comprising the steps of: a) providing a generic attenuation model of a diffusion MRI attenuated signal S(b), representative of the type of the tissue to be observed, suited to Intra Voxel Incoherent Motion (IVIM) and/or non-Gaussian signal patterns, and expressed by a model function f(b), depending on a gradient attenuation factor b and on a first set of model parameters p(i) characterizing when valued the type of tissue and the microstructure state, said model parameters p(i) defining a model parameter vector space and NP being the number of model parameters of the first set; b) providing a reference model parameter vector (p R (i)) corresponding to a reference state of the tissue, defining through the generic attenuation model a generic reference diffusion MRI attenuated signal S R (b); then c) for each model parameter p(i), determining a key b value that maximizes a partial differential sensitivity dS i (b) of the generic model diffusion MRI attenuated signal S(b) to the said model parameter p(i) at the reference model parameter vector (p R (i)) over a predetermined interval of b values ranging from zero to a predetermined maximum value b max; then d) determining from the NP key b values determined in the step a key b value subset by removing the key b values that are associated to model parameters with a low sensitivity for tissue type and/or the microstructure or biological state to characterize when the said model parameters are known to be of low interest for the tissue type and/or the microstructure or biological state to characterize; then e) acquiring a set of MRI images of a Field Of View of the observed tissue by means of a motion-probing pulsed Gradient MRI sequence programmed with gradient configured to obtain the determined key b value subset; then f) on a one-per-one voxel basis or on a predetermined Region Of Interest including a set of voxels, determining (22; 56) a signature index (sADC, Sdist, SCdist, Snl, SI) of the voxel V or the ROI as a real number directly sensitive to the microstructure state and the type of the tissue present in the ROI or the voxel V, the signature index being a scalar function depending merely on the voxel signals acquired at the key b values of the key b value subset and that is calculated without using the generic attenuation model and without estimating any parameter of said generic attenuation model. a) providing a generic attenuation model of a diffusion MRI attenuated signal S(b), representative of the type of the tissue to be observed, suited to Intra Voxel Incoherent Motion (IVIM) and/or non-Gaussian signal patterns, and expressed by a model function f(b), depending on a gradient attenuation factor b and on a first set of model parameters p(i) characterizing when valued the type of tissue and the microstructure state, said model parameters p(i) defining a model parameter vector space and NP being the number of model parameters of the first set; b) providing a reference model parameter vector (p R (i)) corresponding to a reference state of the tissue, defining through the generic attenuation model a generic reference diffusion MRI attenuated signal S R (b); then c) for each model parameter p(i), determining a key b value that maximizes a partial differential sensitivity dS i (b) of the generic model diffusion MRI attenuated signal S(b) to the said model parameter p(i) at the reference model parameter vector (p R (i)) over a predetermined interval of b values ranging from zero to a predetermined maximum value b max; then d) determining from the NP key b values determined in the step a key b value subset by removing the key b values that are associated to model parameters with a low sensitivity for tissue type and/or the microstructure or biological state to characterize when the said model parameters are known to be of low interest for the tissue type and/or the microstructure or biological state to characterize; then e) acquiring a set of MRI images of a Field Of View of the observed tissue by means of a motion-probing pulsed Gradient MRI sequence programmed with gradient configured to obtain the determined key b value subset; then f) on a one-per-one voxel basis or on a predetermined Region Of Interest including a set of voxels, determining (22; 56) a signature index (sADC, Sdist, SCdist, Snl, SI) of the voxel V or the ROI as a real number directly sensitive to the microstructure state and the type of the tissue present in the ROI or the voxel V, the signature index being a scalar function depending merely on the voxel signals acquired at the key b values of the key b value subset and that is calculated without using the generic attenuation model and without estimating any parameter of said generic attenuation model.