Diffusion imaging is an MRI method that produces in vivo magnetic resonance images of biological tissues sensitized with the local characteristics of molecular diffusion, generally water (but other moieties can also be investigated using MR spectroscopic approaches). MRI can be made sensitive to the Brownian motion of molecules. Regular MRI acquisition utilizes the behaviour of protons in water to generate contrast between clinically relevant features of a particular subject. The versatile nature of MRI is due to this capability of producing contrast related to the structure of tissues at microscopic level. In a typical -weighted image, water molecules in a sample are excited with the imposition of a strong magnetic field. This causes many of the protons in water molecules to precess simultaneously, producing signals in MRI. In -weighted images, contrast is produced by measuring the loss of coherence or synchrony between the water protons. When water is in an environment where it can freely tumble, relaxation tends to take longer. In certain clinical situations, this can generate contrast between an area of pathology and the surrounding healthy tissue.
To sensitize MRI images to diffusion, instead of a homogeneous magnetic field, the homogeneity is varied linearly by a pulsed field gradient. Since precession is proportional to the magnet strength, the protons begin to precess at different rates, resulting in dispersion of the phase and signal loss. Another gradient pulse is applied in the same magnitude but with opposite direction to refocus or rephase the spins. The refocusing will not be perfect for protons that have moved during the time interval between the pulses, and the signal measured by the MRI machine is reduced. This “field gradient pulse” method was initially devised for NMR by Stejskal and Tanner who derived the reduction in signal due to the application of the pulse gradient related to the amount of diffusion that is occurring through the following equation:
where is the signal intensity without the diffusion weighting, is the signal with the gradient, is the gyromagnetic ratio, is the strength of the gradient pulse, is the duration of the pulse, is the time between the two pulses, and finally, is the diffusion-coefficient.
In order to localize this signal attenuation to get images of diffusion one has to combine the pulsed magnetic field gradient pulses used for MRI (aimed at localization of the signal, but those gradient pulses are too weak to produce a diffusion related attenuation) with additional “motion-probing” gradient pulses, according the Stejskal and Tanner method. This combination is not trivial, as cross-terms arise between all gradient pulses. The equation set by Stejskal and Tanner then becomes inaccurate and 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 simplication, Le Bihan suggested to gather 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 all the more attenuated that diffusion is fast and the b factor is large. 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.
The first successful clinical application of DWI was in imaging the brain following stroke in adults. Areas which were injured during a stroke showed up "darker" on an ADC map compared to healthy tissue. At about the same time as it became evident to researchers that DWI could be used to assess the severity of injury in adult stroke patients, they also noticed that ADC values varied depending on which way the pulse gradient was applied. This orientation-dependent contrast is generated by diffusion anisotropy, meaning that the diffusion in parts of the brain has directionality. This may be useful for determining structures in the brain which could restrict the flow of water in one direction, such as the myelinated axons of nerve cells (which is affected by multiple sclerosis). However, in imaging the brain following a stroke, it may actually prevent the injury from being seen. To compensate for this, it is necessary to use a mathematical construct, called a tensor, to fully characterize the motion of water in all directions.
Diffusion-weighted images are very useful to diagnose vascular strokes in the brain. It is also used more and more in the staging of non-small-cell lung cancer, where it is a serious candidate to replace positron emission tomography as the 'gold standard' for this type of disease. Diffusion tensor imaging is being developed for studying the diseases of the white matter of the brain as well as for studies of other body tissues (see below).
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