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Magnetic Resonance Imaging Biomarker Calibration Service: NMR Measurement of Isotropic Water Diffusion Coefficient



Stephen E. Russek, Katy Keenan, Karl Stupic, Nikki Rentz, Michael Boss, Kevin J. Coakley, Amanda Koepke, Cassandra Stoffer


This document describes a calibration service to measure the water diffusion coefficient, or diffusivity, in reference materials and tissue mimics using nuclear magnetic resonance (NMR) techniques. This calibration is restricted to materials which exhibit isotropic Gaussian water diffusion. The measurement uses the water proton spin as a tag and standard NMR gradient techniques to measure diffusion of the proton magnetization, which, in low viscosity fluids, is largely determined by the physical diffusion of water molecules. The calibrated materials are meant to be used in phantoms (calibration devices) to verify the accuracy of magnetic resonance imaging (MRI)-based water diffusion measurements. The local diffusion coefficient (often referred to as the apparent diffusion coefficient in complex materials) and other associated parameters, are used as image-based biomarkers to assess the state of tissue cellular density, detect tissue anomalies, characterize tumor type, evaluate treatment efficacy, and assess neural connectivity and neural tissue degeneration. A biomarker, as defined by the U.S. Food and Drug Administration, is "a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or biological responses to a therapeutic intervention." [1] Diffusion coefficients, which describe the rate that water protons move due to random thermal motion, are phenomenological parameters that must be carefully defined and measured to enable rigorous quantification and their use as biomarkers for clinical decision making. Diffusion parameters, in addition to being dependent on local material properties, are dependent on environmental parameters such as temperature, which must be controlled and precisely and accurately measured.
Special Publication (NIST SP) - 250-100
Report Number


Biomarker, MRI, magnetic resonance imaging, water diffusion, NMR, nuclear magnetic resonance, proton magnetization diffusion, MRI phantoms


Russek, S. , Keenan, K. , Stupic, K. , Rentz, N. , Boss, M. , Coakley, K. , Koepke, A. and Stoffer, C. (2023), Magnetic Resonance Imaging Biomarker Calibration Service: NMR Measurement of Isotropic Water Diffusion Coefficient, Special Publication (NIST SP), National Institute of Standards and Technology, Gaithersburg, MD, [online],, (Accessed June 17, 2024)


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Created March 30, 2023