Biomarkers Renal

Biomarker

Acquisition Modality

Acquisition

Target/Rationale

Potential application(s)

References

Level of evidence

Issues

Volumetry

T1 and/or T2 weighted structural images, typically in axial or coronal orientation

The kidney is manually or semi-automatically segmented on each slice, and the total renal volume is calculated by summing the segmented areas and multiplying by the slice thickness. Advanced methods, such as automated segmentation using deep learning or 3D reconstruction techniques, can improve accuracy and efficiency.

Gold standard technique

FDA approved renal imaging biomarker

Kidney length and volume and their change over time is a key measure in patients with ADPKD, but may also be important in CKD progression, primary and secondary hyperfiltration in diabetic nephropathy, renal transplants, renal artery stenosis, vesicoureteral reflux.

[^1-4!]

Moderate

Level 2 (Oxford)

Cortical thickness may be more variable within the kidney, limiting reproducibility.

Blood flow

Phase contrast (PC-MRI)

Exploits the different properties of moving versus static protons in a magnetic field. A moving proton have a ‘phase shift’ proportional to its velocity allowing calculation of flow. 

Blood flow velocity and volume

Increased renal resistance to flow due to downstream microvascular obstruction, large-vessel arterial disease or changes in systemic haemodynamics.

[^5,6!]

Low

In Oxford classification this is does not classify as evidence

Breathing-induced kidney motion can cause phase inconsistencies, requiring respiratory gating or navigator techniques.

Further, PC-MRI sequences often require multiple cardiac phases, which increases the scan duration.

Arterial Spin Labelling (ASL)

2D or 3D pulsed or continuous ASL method

Magnetically labelled water protons in blood that act as a diffusible tracer providing an internal endogenous contrast, following which labelled images are subtracted from control images to generate perfusion maps.

Tissue perfusion

Cortical perfusion, which can be affected by a number of pathophysiological processes in acute and chronic renal disease.

[^7,8!]

High

Level 2 (Oxford)

Variability in arterial blood flow and labeling efficiency can impact renal ASL perfusion quantification, particularly in cases of renal artery stenosis or hemodynamic alterations. Additionally, ASL has lower sensitivity to medullary perfusion due to longer transit times and lower blood flow rates, making differentiation between cortical and medullary perfusion challenging.

Diffusion Weighted Imaging (DWI)

EPI-Sequence

Detects the displacement of water molecules within the architecture of tissues and quantifies this as the Apparent Diffusion Coefficient (ADC)

ADC may be affected by tubular flow and capillary perfusion, so true diffusion (D) can be measured using the Intravoxel Incoherent Motion (IVIM) model, alongside pseudo-diffusion (tubular/vascular flow, D*) and flowing fraction (F)

Assessment of AKI by evaluating edema and ischemia. Track of CKD progression by monitoring renal fibrosis, and provide insights into renal tumor differentiation, as malignant tumors typically show lower ADC values.

In renal transplantation, ADC helps detect graft rejection or ischemic injury, while in hydronephrosis, it can assess kidney damage from obstruction.

Additionally, ADC may aid in the early detection of diabetic nephropathy and quantify renal fibrosis in ADPKD, assisting in therapeutic monitoring.

[^9-12!]

Low

Level 3

Differences in MRI hardware, diffusion-weighting schemes, and post-processing methods can introduce variability and affect reproducibility of ADC measurements.

Diffusion Tensor Imaging (DTI)

EPI-Sequence

Similar to DWI but also assesses directionality of diffusion (Brownian motion), which is quantified as percentage of spatially oriented diffusion signal (fractional anisotropy, FA).

Assessment of the degree of organisation in space of oriented tissues.

Any changes in the microstructure that lead to a change in the preferred direction of water diffusion, for instance tubular dilatation, tubular obstruction, or a loss in the organisation of medullary tubules.

Monitoring kidney transplant function, detect early signs of rejection or ischemia, and evaluate the impact of hydronephrosis on renal tissue. Additionally, DTI may assist in tracking microstructural changes in diabetic nephropathy and provide insights into renal microvascular changes in conditions like hypertension and renal artery stenosis.

[^9-12!]

Low

Level 4/5

The kidney's varying microstructure (cortex, medulla, and interstitial space) can lead to significant heterogeneity in diffusion properties, complicating the interpretation of DTI metrics.

Blood Oxygen Level Dependent (BOLD) MRI

Gradient echo sequence

Paramagnetic properties of deoxygenated haemoglobin act to shorten the transverse relaxation time constant (T₂*).

Changes in renal oxygenation, or changes in the microstructure of the capillary bed.

Tissue hypoxia plays a key role in the development and progression of many kidney diseases.

CKD patients with the lowest cortical oxygenation have the worst renal outcome.

[^13-16!]

Low

Level 3

Other factors such as hydration status, dietary sodium and susceptibility effects T₂*.

Quantitative susceptibility mapping (QSM)

Gradient echo sequence

Multiple phase images at different echo times to reduce background field inhomogeneities, followed by sophisticated post-processing algorithms to generate the susceptibility map.

This technique provides insights into tissue composition, such as iron content or calcifications, and is useful for evaluating renal diseases like fibrosis, ischemia, or iron overload.

QSM may help detect early changes in renal tissue composition associated with fibrosis, providing insights into disease progression.

[^17,18!]

Low

Level 4

Limited experience in human kidney

T₁ mapping

Inversion Recovery (IR) or Look-Locker Sequence

Application of an inversion pulse followed by a series of images at different time intervals after inversion to capture the recovery of longitudinal magnetization.

Provides a quantitative map over the whole kidney for T₁ values. T₁ is a tissue-specific time variable that can distinguish different tissues.

Changes in the molecular environment, e.g. water content, viscosity, temperature, fibrosis.

[^19,20!]

Low

Level 4

Factors like hydration, blood flow, or disease can alter T1 relaxation times, making interpretation challenging in pathologic conditions.

T₂ mapping

Multi-Echo Spin-Echo (SE) Sequence

The signal decay over the different echo times is used to calculate the T2 relaxation time by fitting the data to an exponential decay model.

In the same way as T₁ mapping, provides quantification of T₂ as tissue-specific time parameter.

Assessment of AKI by detecting early tissue changes, monitoring CKD progression through fibrosis and inflammation, and evaluating renal transplant function or rejection. Characterization of renal tumors, detection of microstructural changes in diabetic nephropathy, and assessment of tissue damage from hydronephrosis. Additionally, monitoring of cyst formation in APDKD and detection of iron overload in conditions like hemochromatosis.

[^19,20!]

Low

Level 4

Limited experience in human kidney disease to date.

Changes in the molecular environment but assumed to be more sensitive to the effects of oedema and/or inflammation.

MR Renography

Dynamic contrast enhanced (DCE) MRI

Quantitative analysis of contrast agent (CA) transient in soft tissues.

Allows measurement of perfusion filtration per unit tissue, vascularity and tubular transit times.

Important and well-established tool.

[^21-24!]

Low

Level 4

Uses gadolinium-based contrast agents to change the T₁ relaxation time of water in tissues.

Magnetization Transfer (MT)

A spin-echo or gradient-echo sequence is modified to include MT pulses

These MT pulses selectively saturate the macromolecular pool of protons (e.g., proteins, collagen) without affecting free water protons.

Allows fraction quantification of large macromolecules or immobilized cell membranes in tissue

Assessment of renal fibrosis, monitoring inflammation and characterizing renal tumors. It can also be used to evaluate renal transplant function, detect tissue damage in hydronephrosis, and monitor structural changes in diabetic nephropathy.

[^25-27!]

Low

Level 5

Kidney movement due to respiration can lead to inaccuracies in quantification Low SNR, especially in patients with impaired kidney function.

Limited experience in human kidney

PDFF

Dixon Method

Chemical shift encoding-based water-fat separation techniques

A non-invasive, accurate method for assessing renal fat content.

Diagnosing and monitoring conditions such as fatty kidney disease, obesity, and metabolic syndrome.

[^28-30!]

Low

Level 4

Post-processing software is required to accurately separate fat and water signals and provide a reliable fat fraction map for analysis.