The currently available gold standard tests to determine kidney glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) are invasive, costly and time-consuming (6 hours). Recently, it was suggested that blood fraction, urine fraction and tissue fraction can also be characterized by the tri-exponential intravoxel incoherent motion (IVIM) model for diffusion weighted MR-images (DWI).¹ Potentially, this model can provide a cheaper, faster and non-invasive method to assess similar information as the standard kidney function tests.

In this study, we hypothesize that renal function can be reliably assessed by perfusion fractions derived from a tri-exponential IVIM model. Our aim was to evaluate the sensitivity of these parameters to changes in kidney function and to test the repeatability of the method.

Our DW-scan consisted of twenty 2D coronal slices acquired with an EPI read-out during free breathing. Further sequence parameters were: TE=45ms, TR=1344ms, field of view=336x204mm², voxel size 3.5x3.5mm², slice thickness=3.5mm, BW=35Hz/voxel, b-values=0,2,4,8,12,18,24,32,40,50,75,110,200,300,450 and 600s/mm² with 9 gradient directions.

To compensate for in-plane respiratory motion, we used a 2D rigid registration algorithm (elastix²) to register each slice to the mean b=0 s/mm² image. For each voxel, we fitted a tri-exponential model which returned the diffusion coefficient (D), pseudo-diffusion coefficients (D*¹, D*²) and signal fractions with D*¹, D*² and D (f₁, f₂, f₃). D*¹ and D*² were fixed to values obtained from a fit to data from all subjects at baseline. To assess kidney function, we took the mean parameter values from the voxel-wise fits to data from the kidney medulla and cortex.

To investigate how the model parameters change as a function of kidney function, we acquired DW images in 8 healthy volunteers (aged 18-24 years) on a 3T (Philips, Ingenia) scanner. The volunteers all were subjected to a continuous angiotensin-II infusion (0, 0.3, 0.9 and 3.0 ng/kg/min) during acquisition. During a second visit, the effect of the angiotensin-II on the kidney function, namely GFR and ERPF, were assessed using the gold standard ¹²⁵I-thalamate and ¹³¹I-hippuran clearing tests, during a similar infusion protocol. We applied linear regression fits between the fit parameters and angiotensin-II dose to test if there was any response. In addition, we used a Pearson correlation test to test for correlations between the perfusion fractions, f₁ and f₂, and the GFR and ERPF.

To study potential challenge unrelated trends and in order to test intra-session repeatability, we obtained time-controlled data by repeating the protocol on 6 healthy volunteers (aged 23-28), without injecting angiotensin-II. To study the inter-session repeatability, we also acquired DW images in 6 healthy volunteers (aged 19–22 years) in two separate sessions. We calculated the inter-session and intra-session within-subject coefficients of variation (CVs).

We fixed D*¹ and D*² to 9.7x10^-3mm²/s and 551x10^-3mm²/s, respectively.

The mean parameter values at baseline were 1.93±0.08×10^-3mm²/s, 11.3±2.4%, 7.8±1.9% and 80.8±2.2% for D, f₁, f₂ and f₃, respectively. The perfusion fractions in the kidneys changed as a function of angiotensin-II dose throughout the kidney (Fig 1). There was a significant response in f₁, f₂ and D, which changed by -4.7 (p=0.021), 6.4 (p<0.001) and -1.2 (p<0.001) % per ng/kg/min of angiotensin-II (Fig 2). The correlation coefficient, r, between changes in f₁ and ERPF was 0.42 (p=0.01), and f₂ and GFR was -0.62 (p<0.001, Fig 3). These correlations were higher than those previously reported between BOLD measurements and estimated GFR, for which |r|<0.24.³

The IVIM parameters from the time-controlled data had no significant changes between the first (time-controlled to baseline) and last (time-controlled to max dose) acquisition (Fig 4). For D, f₁, f₂, f₃ the intra-session CVs were 3.5%, 14.4%, 6.5% and 1.9%, and the inter-session CVs were 1.7%, 10.4%, 13.8% and 2.2%, respectively (Fig 5).

We showed that pseudo diffusion signal fraction parameters f₁ and f₂ derived from a tri-exponential model for DWI-data presented has potential as a surrogate marker for kidney function as: (1) they change with angiotensin-II dose, (2) they showed a stronger correlation with the golden standard kidney function tests than other MR-methods and (3) they are highly repeatable.