Quantitative Biomarkers in Renal MRI: Adding Physiologic Information to the Morphologic Assessment Diffusion Weighted Imaging

Anatomic abnormality such as change in renal size or atrophy is a late marker of irreversible renal dysfunction. Therefore, it is imperative to utilize other measures of renal function to evaluate patients with known or suspected renal disease. Currently blood test based measure of serum creatinine is used to compute glomerular filtration rate (GFR). This is considered the standard of care in the evaluation of kidney function but suffers from number of major limitations such as inability to provide function of each kidney separately, has lower sensitivity for early renal damage, cannot discriminate between reversible and irreversible renal damage, and is inaccurate in elderly, thin and obese subjects.

Over the last 2 decades, magnetic resonance imaging (MRI), conventionally used for tissue anatomic imaging, is also being explored for assessing microstructure and function of various organs including kidneys. MRI techniques, such as, diffusion-weighted MRI, dynamic contrast enhanced (DCE) MRI, and blood oxygenation level dependent (BOLD) MRI, enables evaluation of various aspects of renal structure and function. Diffusion Weighted Imaging (DWI) has shown considerable promise and various flavors of DWI being investigated to study renal structure and function will be discussed (1, 2).

Diffusion Weighted Imaging (DWI)

DWI is a technique that quantifies the motion of water molecules in tissues. It derives image contrast based on differences in the mobility of protons, which are primarily associated with water. DWI is most simply performed with 2 b values, such as 0 or 50 sec/mm2 and 500 to 1000 sec/mm2; with two b values, the exponential decay of signals is approximated using a monoexponential fit to arrive at a decay constant, referred to as the apparent diffusion coefficient (ADC) (3-5). Tissues that are highly cellular or highly complex tend to restrict the motion of water and have lower ADC compared to the tissues that are less complex or less cellular.

Intra-Voxel Incoherent Motion (IVIM)

ADC provides in vivo quantification of the combined effects of capillary perfusion and true diffusion. Le Bihan et al., in pioneering work on intravoxel incoherent motion (IVIM) modeling of diffusion-weighted imaging, suggested that movement of blood in microvasculature could be modeled as a pseudo-diffusion process which is measurable at low b values (< 200 sec/mm2) (6-7). IVIM or perfusion effects can be resolved from true tissue diffusion by using sufficient b-value sampling and a biexponential curve fit analysis.

This model assumes two compartments: (1) a vascular compartment, occupying a perfusion fraction fp of the tissue volume in each voxel and showing a pseudodiffusion coefficient Dp, and (2) a tissue compartment, occupying the remaining volume fraction (1-fp) and showing a tissue diffusivity Dt. Both compartments are assumed to demonstrate exponential signal decay with diffusion weighting factor b (8-10).

Diffusion Tensor Imaging (DTI)

ADC is a scalar property, i.e. it has magnitude but no directionality. However, diffusion of water molecule in a kidney, especially in the renal medulla, is a three dimensional process with both magnitude and direction. This directionality of diffusion also known as anisotropy can be measured by applying diffusion gradients in multiple (at least 6) directions. Anisotropy can provide information about the microstructure and this degree of anisotropy can be expressed by the term fractional anisotropy (FA). FA values range from 0 to 1, with 0 being isotropic diffusion without directionality and 1 being completely anisotropic diffusion in only one direction (1, 9, 11-13). Combined DTI and IVIM analysis although challenging is possible to assess directionality in the slow and fast component of the diffusion signal (14). These techniques are being utilized to study various renal diseases such as kidney tumor, renal artery stenosis, diabetic nephropathy, chronic renal failure, and renal transplant dysfunction. Application of these techniques will be briefly discussed.