Imaging Primary Brain Activity Using Quantitative Maps of Tissue Stiffness

Please join us for a seminar given by Sam Patz, Professor of Radiology at Harvard Medical School and Director of Low Field and Pulmonary MRI Laboratories at Brigham & Women's Hospital.


Magnetic Resonance Elastography (MRE) is a method that utilizes an external vibration device to produce small amplitude (~10 microns) amplitude mechanical waves in tissue. By oscillating the magnetic field gradients at the same frequency as the mechanical waves, one can detect the time-dependent displacement amplitude of the induced shear waves [1]. The displacement amplitudes are then used to solve the Navier equation for the spatially dependent shear modulus. We induced vibrations at 1kHz in mouse brains and measured the shear modulus in 3D during administration of a noxious stimulation, which in this case was electrical stimulation of the hind limb. Localized changes in tissue elasticity of >10% were observed in brain regions associated with such a stimulus. The observed mechanical response persists over two decades of stimulus switching frequencies from 0.1-10 Hz. This demonstrates that the mechanism behind the observed stiffness changes is not of vascular origin, which has a much slower response than 10Hz, but rather is either directly related to, or tightly coupled to primary neuronal activity. While the existence of a neuro-mechanical coupling is not new and dates back to 1950 with measurements of the volume of a cuttlefish fiber with stimulation [2], the observations presented here are the first to show regional changes in the brain’s functional activity by the measurement of a macroscopic regional elasticity via MRE. Accordingly, functional MR elastography (fMRE), which has a spatial resolution typical of MRI and with a temporal resolution approaching that of EEG, may open a new window to explore the spatiotemporal processing of signals in the brain.

  1. Muthupillai R, et al. (1995) Magnetic resonance elastography by direct visualization of propagating acoustic strain waves. Science 269(5232):1854-1857.
  2. Hill DK (1950) The volume change resulting from stimulation of a giant nerve fibre. The Journal of physiology 111(3-4):304-327.


Daniel Fovargue, Katharina Schregel, Navid Nazari, Miklos Palotai, Paul E. Barbone, Ben Fabry, Alexander Hammers, Sverre Holm, Sebastian Kozerke, David A. Nordsletten, and Ralph Sinkus


Samuel Patz received his PhD in Physics from Brandeis University in 1979, where he used NMR as a tool to measure the critical behavior of an antiferromagnet. He spent two years as a postdoc at Brandeis and then worked at Xerox in Rochester, New York as an applied research scientist. 

He decided to return to academia in 1983 when the field of MRI was just getting started. He joined W.S. Moore at Harvard Medical School and the Brigham and Women’s Hospital (BWH) as a postdoc. Moore had just been hired from Nottingham to lead an MRI group. Moore, Patz, and another physicist, R.C. Hawkes, made up the initial MRI group at BWH. By 1986, Patz and Hawkes developed a novel method to measure slow fluid flow using a technique known as Steady State Free Precession (SSFP). This methodology, which did not require a contrast agent, was applied to measure CSF flow as well as capillary blood flow and resulted in Patz receiving his first NIH R01 grant in 1987. 

In the early 1990s, Patz and colleagues M. Hrovat and Y.M. Pulyer developed a novel nonlinear spatial encoding methodology for MRI based on a periodic and linear field: Axsin(ky). The method encodes two dimensions of space and uses a Bessel function reconstruction. It is one of the first examples of nonlinear spatial encoding in MRI. 

In the mid-1990s, Patz became interested in a new technology known as hyperpolarized noble gas MRI. This technology uses a laser to magnetize either 3He or 129Xe gas to polarization levels that are ~105 times larger than the typical Boltzmann polarization achieved by a high field MRI scanner. Together with colleagues from the Harvard Smithsonian Center for Astrophysics, he used this technique to study gas diffusion in porous media. This naturally led to applying this technology to the lung, and this is an area where Patz then devoted a substantial portion of his effort for the next twenty years. 

His pulmonary MRI group obtained the world’s first human images of gas exchange using 129Xe MRI. They also developed an analytical model that is currently used to model the septal uptake of xenon after inhalation. Interest in the lung also led to development of a portable, low field, permanent magnet MRI device, called the Lung Density Monitor (LDM). The LDM, which is still an active project, is designed to be used in the medical ICU to assist pulmonologists in setting safe mechanical ventilation pressures in order to avoid ventilator-induced lung injury. 

Four years ago, Patz became interested in Magnetic Resonance Elastography (MRE). Through a strong collaboration and assistance from R. Sinkus of King’s College London, who is one of the pioneers of MRE, a program in mouse brain MRE was begun. What we discovered, and which is the subject of this talk, is a completely new type of MRI contrast, i.e. a change in the shear modulus that depends on external functional stimulus. In analogy to fMRI, we call this functional MRE or fMRE.

A link to Patz’s publication list can be found at: https://orcid.org/0000-0002-4500-1918.

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