Quantitative Assessment of Renal Perfusion and Oxygenation by Invasive Probes: Basic Concepts

Renal tissue hypoperfusion and hypoxia are early key elements in the pathophysiology of acute kidney injury of various origins, and may also promote progression from acute injury to chronic kidney disease. Here we describe basic principles of methodology to quantify renal hemodynamics and tissue oxygenation by means of invasive probes in experimental animals. Advantages and disadvantages of the various methods are discussed in the context of the heterogeneity of renal tissue perfusion and oxygenation.This chapter is based upon work from the COST Action PARENCHIMA, a community-driven network funded by the European Cooperation in Science and Technology (COST) program of the European Union, which aims to improve the reproducibility and standardization of renal MRI biomarkers. This introduction chapter is complemented by a separate chapter describing the experimental procedure and data analysis.

Recommendations for Preclinical Renal MRI: A Comprehensive Open-Access Protocol Collection to Improve Training, Reproducibility, and Comparability of Studies

Renal MRI holds incredible promise for making a quantum leap in improving diagnosis and care of patients with a multitude of diseases, by moving beyond the limitations and restrictions of current routine clinical practice. Clinical and preclinical renal MRI is advancing with ever increasing rapidity, and yet, aside from a few examples of renal MRI in routine use, it is still not good enough. Several roadblocks are still delaying the pace of progress, particularly inefficient education of renal MR researchers, and lack of harmonization of approaches that limits the sharing of results among multiple research groups.Here we aim to address these limitations for preclinical renal MRI (predominantly in small animals), by providing a comprehensive collection of more than 40 publications that will serve as a foundational resource for preclinical renal MRI studies. This includes chapters describing the fundamental principles underlying a variety of renal MRI methods, step-by-step protocols for executing renal MRI studies, and detailed guides for data analysis. This collection will serve as a crucial part of a roadmap toward conducting renal MRI studies in a robust and reproducible way, that will promote the standardization and sharing of data.This chapter is based upon work from the COST Action PARENCHIMA, a community-driven network funded by the European Cooperation in Science and Technology (COST) program of the European Union, which aims to improve the reproducibility and standardization of renal MRI biomarkers.

Renal Diffusion-Weighted Imaging (DWI) for Apparent Diffusion Coefficient (ADC), Intravoxel Incoherent Motion (IVIM), and Diffusion Tensor Imaging (DTI): Basic Concepts

The specialized function of the kidney is reflected in its unique structure, characterized by juxtaposition of disorganized and ordered elements, including renal glomerula, capillaries, and tubules. The key role of the kidney in blood filtration, and changes in filtration rate and blood flow associated with pathological conditions, make it possible to investigate kidney function using the motion of water molecules in renal tissue. Diffusion-weighted imaging (DWI) is a versatile modality that sensitizes observable signal to water motion, and can inform on the complexity of the tissue microstructure. Several DWI acquisition strategies are available, as are different analysis strategies, and models that attempt to capture not only simple diffusion effects, but also perfusion, compartmentalization, and anisotropy. This chapter introduces the basic concepts of DWI alongside common acquisition schemes and models, and gives an overview of specific DWI applications for animal models of renal disease.This chapter is based upon work from the COST Action PARENCHIMA, a community-driven network funded by the European Cooperation in Science and Technology (COST) program of the European Union, which aims to improve the reproducibility and standardization of renal MRI biomarkers. This introduction chapter is complemented by two separate chapters describing the experimental procedure and data analysis.

Experimental Protocols for MRI Mapping of Renal T1

The water proton longitudinal relaxation time, T1, is a common and useful MR parameter in nephrology research. Here we provide three step-by-step T1-mapping protocols suitable for different types of nephrology research. Firstly, we provide a single-slice 2D saturation recovery protocol suitable for studies of global pathology, where whole-kidney coverage is unnecessary. Secondly, we provide an inversion recovery type imaging protocol that may be optimized for specific kidney disease applications. Finally, we also provide imaging protocol for small animal kidney imaging in a clinical scanner.This chapter is based upon work from the COST Action PARENCHIMA, a community-driven network funded by the European Cooperation in Science and Technology (COST) program of the European Union, which aims to improve the reproducibility and standardization of renal MRI biomarkers. This analysis protocol chapter is complemented by two separate chapters describing the basic concept and experimental procedure.

Ultrasound and Photoacoustic Imaging of the Kidney: Basic Concepts and Protocols

Noninvasive, robust, and reproducible methods to image kidneys are provided by different imaging modalities. A combination of modalities (multimodality) can give better insight into structure and function and to understand the physiology of the kidney. Magnetic resonance imaging can be complemented by a multimodal imaging approach to obtain additional information or include interventional procedures. In the clinic, renal ultrasound has been essential for the diagnosis and management of kidney disease and for the guidance of invasive procedures for a long time. Adapting ultrasound to preclinical requirements and for translational research, the combination with photoacoustic imaging expands the capabilities to obtain anatomical, functional, and molecular information from animal models. This chapter describes the basic concepts of how to image kidneys using different and most appropriate modalities.This chapter is based upon work from the COST Action PARENCHIMA, a community-driven network funded by the European Cooperation in Science and Technology (COST) program of the European Union, which aims to improve the reproducibility and standardization of renal MRI biomarkers. This introduction chapter is complemented by two separate chapters describing the experimental procedure and data analysis.

Sodium (23Na) MRI of the Kidney: Basic Concept

The handling of sodium by the renal system is a key indicator of renal function. Alterations in the corticomedullary distribution of sodium are considered important indicators of pathology in renal diseases. The derangement of sodium handling can be noninvasively imaged using sodium magnetic resonance imaging (23Na MRI), with data analysis allowing for the assessment of the corticomedullary sodium gradient. Here we introduce sodium imaging, describe the existing methods, and give an overview of preclinical sodium imaging applications to illustrate the utility and applicability of this technique for measuring renal sodium handling.This chapter is based upon work from the COST Action PARENCHIMA, a community-driven network funded by the European Cooperation in Science and Technology (COST) program of the European Union, which aims to improve the reproducibility and standardization of renal MRI biomarkers. This introduction chapter is complemented by two separate chapters describing the experimental procedure and data analysis.

Renal pH Imaging Using Chemical Exchange Saturation Transfer (CEST) MRI: Basic Concept

Magnetic Resonance Imaging (MRI) has been actively explored in the last several decades for assessing renal function by providing several physiological information, including glomerular filtration rate, renal plasma flow, tissue oxygenation and water diffusion. Within MRI, the developing field of chemical exchange saturation transfer (CEST) has potential to provide further functional information for diagnosing kidney diseases. Both endogenous produced molecules as well as exogenously administered CEST agents have been exploited for providing functional information related to kidney diseases in preclinical studies. In particular, CEST MRI has been exploited for assessing the acid-base homeostasis in the kidney and for monitoring pH changes in several disease models. This review summarizes several CEST MRI procedures for assessing kidney functionality and pH, for monitoring renal pH changes in different kidney injury models and for evaluating renal allograft rejection.This chapter is based upon work from the COST Action PARENCHIMA, a community-driven network funded by the European Cooperation in Science and Technology (COST) program of the European Union, which aims to improve the reproducibility and standardization of renal MRI biomarkers. This introduction chapter is complemented by two separate chapters describing the experimental procedure and data analysis.

Reversible (Patho)Physiologically Relevant Test Interventions: Rationale and Examples

Renal tissue hypoperfusion and hypoxia are early key elements in the pathophysiology of acute kidney injury of various origins, and may also promote progression from acute injury to chronic kidney disease. Here we describe test interventions that are used to study the control of renal hemodynamics and oxygenation in experimental animals in the context of kidney-specific control of hemodynamics and oxygenation. The rationale behind the use of the individual tests, the physiological responses of renal hemodynamics and oxygenation, the use in preclinical studies, and the possible application in humans are discussed.This chapter is based upon work from the COST Action PARENCHIMA, a community-driven network funded by the European Cooperation in Science and Technology (COST) program of the European Union, which aims to improve the reproducibility and standardization of renal MRI biomarkers.

Dynamic Contrast Enhancement (DCE) MRI–Derived Renal Perfusion and Filtration: Basic Concepts

Dynamic contrast-enhanced (DCE) MRI monitors the transit of contrast agents, typically gadolinium chelates, through the intrarenal regions, the renal cortex, the medulla, and the collecting system. In this way, DCE-MRI reveals the renal uptake and excretion of the contrast agent. An optimal DCE-MRI acquisition protocol involves finding a good compromise between whole-kidney coverage (i.e., 3D imaging), spatial and temporal resolution, and contrast resolution. By analyzing the enhancement of the renal tissues as a function of time, one can determine indirect measures of clinically important single-kidney parameters as the renal blood flow, glomerular filtration rate, and intrarenal blood volumes. Gadolinium-containing contrast agents may be nephrotoxic in patients suffering from severe renal dysfunction, but otherwise DCE-MRI is clearly useful for diagnosis of renal functions and for assessing treatment response and posttransplant rejection.Here we introduce the concept of renal DCE-MRI, describe the existing methods, and provide an overview of preclinical DCE-MRI applications to illustrate the utility of this technique to measure renal perfusion and glomerular filtration rate in animal models.This publication is based upon work from the COST Action PARENCHIMA, a community-driven network funded by the European Cooperation in Science and Technology (COST) program of the European Union, which aims to improve the reproducibility and standardization of renal MRI biomarkers. This introduction is complemented by two separate publications describing the experimental procedure and data analysis.

Denoising for Improved Parametric MRI of the Kidney: Protocol for Nonlocal Means Filtering

In order to tackle the challenges caused by the variability in estimated MRI parameters (e.g., T2* and T2) due to low SNR a number of strategies can be followed. One approach is postprocessing of the acquired data with a filter. The basic idea is that MR images possess a local spatial structure that is characterized by equal, or at least similar, noise-free signal values in vicinities of a location. Then, local averaging of the signal reduces the noise component of the signal. In contrast, nonlocal means filtering defines the weights for averaging not only within the local vicinity, bur it compares the image intensities between all voxels to define “nonlocal” weights. Furthermore, it generally compares not only single-voxel intensities but small spatial patches of the data to better account for extended similar patterns. Here we describe how to use an open source NLM filter tool to denoise 2D MR image series of the kidney used for parametric mapping of the relaxation times T2* and T2.This chapter is based upon work from the COST Action PARENCHIMA, a community-driven network funded by the European Cooperation in Science and Technology (COST) program of the European Union, which aims to improve the reproducibility and standardization of renal MRI biomarkers.