C. What Life Scientists Should Know About Molecular Imaging
2. MR Fundamentals for Life Scientists: Part 1
Chaired by Joseph Ackerman, St. Louis, Missouri, USA and Michal Neeman, Rehovot, Israel
Presentation 1: Introduction to MR Physics
- Understanding of the underlying physics of MRI
- Familiarity with the main components of an MRI scanner
- Introduction to the basics of image acquisition
The MRI technique depends on the phenomenon of Nuclear Magnetic Resonance (NMR) which, as the name suggests, is based on a fundamental magnetic property of certain atomic nuclei and their resonant interaction with externally applied electromagnetic photons. The use of the word “resonant” is critical in this context, and refers to the fact that the energy of the photons must be very exact for the interaction to occur. The specific energy required is governed by the properties of the nuclei in question (usually hydrogen) and the magnetic field in which the sample containing these nuclei are situated (usually several Tesla in magnitude). Thus we may “excite” a sample of, say, water (contains many 1H nuclei) by irradiating the sample with photons with energies in the radio frequency range; the trick is then to observe how the signal we measure decays over time, and also to observe how the sample relaxes back to its unexcited, equilibrium state. These decay and relaxation times are exquisitely dependent on the molecular environment within each tissue type, and hence we can design experiments wherein we use these inherent tissue properties to determine the magnitude of our signal and ultimately to produce images with a wide variety of contrasts (for example, to enhance white matter signal over grey matter, etc.).
Although the NMR phenomena has been known to physicists and chemists since the 1950’s, it was not until the 1970’s that the idea to adapt it to imaging was conceived. The core concept enabling us to spatially-localize the measured signal involves the application of additional magnetic fields whose magnitude varies with position &ndash the so-called “magnetic field gradients” – which add to the existing large static magnetic field, effectively rendering the resonant condition dependent on position in 3D space. This allows us to selectively measure a signal from every position within the sample, a process which requires the repetitive application of gradients of varying strength and direction, typically resulting in image acquisition times of many tens of seconds (although sub-second scans are also possible, albeit with lower image quality).
The inherent dependence of the measured signal on the molecular properties of the constituent tissues in the sample enable us to design experiments, so-called imaging pulse sequences, to acquire images with contrast influenced or weighted by factors such as tissue density, the ability of water molecules to diffuse through tissue, the flow of blood through large vessels or its perfusion through tissue, the blood oxygenation level, the local temperature and/or pH levels, and many more physical mechanisms.
This talk with provide an introduction to the world of MRI, explaining some of the underlying physics of the NMR phenomenon, giving a brief overview of the main components in a modern scanner, and describing the basics of image acquisition.
Presentation 2: Intoduction to MR Hardware
Dominik von Elverfeldt
- The basic principles of MRI RF-coil function the main facts in SNR optimization
- Different application adapted coil designs
- The issues when reducing coil sizes towards animals and microscope
This lectures aim is to give an overview on RF coils in MRI. It will cover the basic physics of LC circuits in strong magnetic fields, the principles of sample excitation and signal reception as well as issues determining and optimizing the achievable SNR. The most common coil geometries including phased arrays with their design trade-offs, advantages and limitations for specialized applications will be introduced. Furthermore the miniaturization of MRI RF-coils from man to mouse and further to MR microscopy will be discussed in terms of design and SNR optimization.
Presentation 3: Contemporary MR: Pushing the Limits
Joel R. Garbow
Biomedical MR Laboratory, Mallinckrodt Institute of Radiology, Washington University in St.Louis, Missouri, USA
- Understand the importance of contrast in MR imaging
- Describe T1, T2, and T2* relaxation phenomena and how they are measured
- Understand relaxation as a source of image contrast
- Understand the role of magnetization exchange in relaxation and as a source of contrast (MT)
- Describe more technically advanced, endogenous-contrast experiments (diffusion, per fusion, flow, BOLD, CEST)
- Describe the role of exogenous contrast agents
- Describe more technically advanced, exogenous-contrast experiments (DCE, DSC, ParaCEST)
The vast majority of clinical magnetic resonance (MR) imaging experiments involve 1H imaging of the water, which is ubiquitous in biological tissue. Water has a wide variety of biophysical magnetic signatures that are characteristic of specific tissues and organs. The exquisite sensitivity of water’s MR properties to its local environment can be used to enhance image contrast and provide detailed structural information. MR image contrast distinguishes organs and soft tissues and helps to identify normal vs. abnormal, healthy vs. damaged, and viable vs. pathologic tissue. The key to tissue MR contrast is effective encoding of the physical properties of tissue into the MR image.
The question of which physical property to encode often reduces to questions of “What are we trying to measure?” and “What MR property generates the best contrast?” Herein, we will discuss different MR contrast mechanisms, including longitudinal relaxation (T1), transverse relaxation (T2 and T2*), diffusion, velocity (perfusion and flow), and blood oxygen level dependence (BOLO) MRI, the mechanism that serves as the underpinning for functional MRI. We will explore the role of exogenous agents in generating contrast and describe their use in dynamic MR experiments that can provide measures of perfusion and vascular permeability.
We begin with a phenomenological discussion of T1 and T2 relaxation and a description of how the corresponding relaxation rate constants, R1 (=1/T1) and R2 (=1/T2), are measured. The manner in which tissue differences in R1 or R2 can provide a source of image contrast will be illustrated. Exchange processes are central to MR and MR relaxation. Contrast arising from magnetization transfer (MT), in which 1H magnetization is exchanged between macromolecules not visible by MR and mobile water molecules, will be discussed. We will then describe the basic role of MR contrast agents. Built around paramagnetic centers, MR contrast agents are fundamentally different than optical tracers or PET probes, in that the agents themselves are never directly observed. Instead, MR contrast agents function by changing the 1H relaxation properties in nearby water molecules. The consequences of such indirect observation of these agents in terms of contrast and quantitative detection and modeling will be explored. Examples of both T1 agents (e.g., Gd-based), which brighten images, and T2/T2* agents (e. g., iron oxides), which darken images, will be provided. The use of contrast agents in a static mode – inject an agent and wait for it to be distributed within the body – provides a powerful and versatile source of contrast. However, these same agents can also be used in a dynamic mode to provide information about vascular structure and function. Two such experiments, dynamic contrast enhanced (DCE) and dynamic susceptibility contrast (DSC) MRI, will be described. Both DCE and DSC experiments begin with injection of a bolus of contrast agent- the DSC experiment focuses on measuring tissue perfusion, while DCE highlights both perfusion and vascular permeability (vessel “leakiness”). The use of iron-oxide contrast agents to label and track cells will also be reviewed.