the signal attenuation must be calculated, either analytically or numerically, integrating all gradient pulses present in the MRI sequence and their interactions. The result quickly becomes very complex given the many pulses present in the MRI sequence, and as a simplification, Le Bihan suggested gathering all the gradient terms in a "b factor" (which depends only on the acquisition parameters) so that the signal attenuation simply becomes: Also, the diffusion coefficient, , is replaced by an apparent diffusion coefficient, , to indicate that the diffusion process is not free in tissues, but hindered and modulated by many mechanisms (restriction in closed spaces, tortuosity around obstacles, etc.) and that other sources of IntraVoxel Incoherent Motion (IVIM) such as blood flow in small vessels or cerebrospinal fluid in ventricles also contribute to the signal attenuation. At the end, images are "weighted" by the diffusion process: In those diffusion-weighted images (DWI) the signal is more attenuated the faster the diffusion and the larger the b factor is. However, those diffusion-weighted images are still also sensitive to T1 and T2 relaxivity contrast, which can sometimes be confusing. It is possible to calculate "pure" diffusion maps (or more exactly ADC maps where the ADC is the sole source of contrast) by collecting images with at least 2 different values, and , of the b factor according to: Although this ADC concept has been extremely successful, especially for clinical applications, it has been challenged recently, as new, more comprehensive models of diffusion in biological tissues have been introduced. Those models have been made necessary, as diffusion in tissues is not free. In this condition, the ADC seems to depend on the choice of b values (the ADC seems to decrease when using larger b values), as the plot of ln(S/So) is not linear with the b factor, as expected from the above equations. This deviation from a free diffusion behavior is what makes diffusion MRI so successful, as the ADC is very sensitive to changes in tissue microstructure. On the other hand, modeling diffusion in tissues is becoming very complex. Among most popular models are the biexponential model, which assumes the presence of 2 water pools in slow or intermediate exchange and the cumulant-expansion (also called Kurtosis) model, which does not necessarily require the presence of 2 pools. Diffusion model Given the concentration and flux , Fick's first law gives a relationship between the flux and