Appunti esame Neuroimaging techniques, prof Vallesi

Which is the MRI sequence?

In the first step, the subject is inside the MRI scanner and so inside a strong magnetic field. We must apply a strong magnetic field in order to increase the net magnetization, i.e., the sum of all the magnetic moments of the spins in a spin system. A nucleus, indeed, to be useful for MRI must have some properties. First of all, it needs to have an odd number of protons to have spins and then have a magnetic moment and an angular momentum. Because of the positive charge of the protons, the spin will generate an electrical current on its surface that will create a magnetic source and a torque. This quantity is the magnetic moment. While the angular momentum refers to the amount of rotation that an object has.

So, coming back to the application of a strong magnetic field, in its absence, the protons are oriented randomly, and this results in a small net magnetization, unuseful for MRI. In the presence of a strong magnetic field, the protons align along its direction. However, this alignment is not static because the nuclei rotate around the direction of the field while spinning. This motion is called precession. The frequency of precession depends on the strength of the magnetic field and on the nature of the nucleus, and it’s called the Larmor frequency.

The second step regards the application of radiofrequency at the same resonant frequency of the nuclei. This excitation pulse causes the nuclei to flip from a low energy state to a high energy state, and moreover, the spin axis will reverse, taking energy from the applied radiation field. When we turn off the transmitter coil, the nucleus will emit this energy. So as the spins return to the low energy state as they relax following the cessation of the excitation pulse, they emit energy, which is the free induction decay that can be measured with the detector coils.

Signal amplitude decays as the net magnetization gradually realigns to the magnetic field, and this is called T1 decay. Moreover, signal amplitude decays also as the spins lose coherence, so some precess at high frequencies and others at low frequencies, and this decreases the net magnetization. This is called T2 decay. Furthermore, any spatial inhomogeneities in the magnetic field will cause different spins to experience different magnetic strengths and so some precess at different frequencies. This effect is additive to the one of the T2 decay, and indeed the combined effect of the spin-spin interactions and magnetic inhomogeneities is called T2* decay, of key importance for fMRI.

Which are the safety issues?

There are different acute risks of MRI. The subjective experience related to sensory effects like nausea, vertigo, metallic states. Physiological effects: red blood cells may alter shape in a magnetic field. Radiofrequency energy can cause tissue heating and burns. Gradient field changes can cause peripheral nerve stimulation and theoretical risk of cardiac stimulation. Claustrophobia. Quenching, rapid decrease in magnetic field strength due to loss of superconductivity.

Which are the scanner components?

• The "M" represents the main static magnetic field, which is generated by a series of electromagnetic coils that carry very large currents around the bore of the scanner.
• The "R" refers to the delivery of energy at the resonance frequency of the targeted atomic nuclei.
• The "I" refers to image formation, which requires alteration of the magnetic field strength over space by turning on and off the magnetic gradient coils.

Also necessary are the shimming coils that ensure the homogeneity of the static magnetic field; specialized computer systems for controlling the scanner; and the experimental task, and physiological monitoring equipment. Nearly all MRI scanners today create their static magnetic fields through electromagnetism. In general, there are two criteria for a suitable magnetic field in MRI. The first is field uniformity (or homogeneity), and the second is field strength.

If the magnetic field is not homogeneous, the signal measured from a given part of the body could change unexpectedly, depending on where it is located in the magnetic field. To generate an extremely large magnetic field, a huge electric current must be injected into the loops of wire. Modern MRI scanners use superconducting electromagnets whose wires are cooled to temperatures near absolute zero.

Although a strong static magnetic field is needed for MRI, the static field itself does not produce any MR signal. The MR signal is actually produced by the clever use of electromagnetic coils that generate and receive electromagnetic fields at the resonant frequencies of the atomic nuclei within the static magnetic field. This process gives the name “resonance” to magnetic resonance imaging. Because most atomic nuclei of interest for MRI studies have resonant frequencies in the radiofrequency portion of the electromagnetic spectrum (at typical field strengths for MRI), these coils are also called radiofrequency coils.

Unlike the static magnetic field, the radiofrequency fields are turned on during small portions of the image acquisition process and remain off the rest of the time. After a human body is placed into a strong magnetic field, an equilibrium state is reached in which the magnetic moments of atomic nuclei (e.g., hydrogen) within the body become aligned with the magnetic field. The radiofrequency coils then send electromagnetic waves that resonate at a particular frequency (determined by the strength of the magnetic field) into the body, perturbing this equilibrium state. This process is known as excitation.

When atomic nuclei are excited, they absorb the energy of the radiofrequency pulse. When the radiofrequency pulse ends, the atomic nuclei return to the equilibrium state and release the energy that was absorbed during excitation. The resulting release of energy can be detected by the radiofrequency coils in a process known as reception. The detected electromagnetic energy defines the raw MR signal. The amount of energy that can be transmitted or received by a radiofrequency coil depends on its distance from the sample being measured. In the case of fMRI, the radiofrequency coils are typically placed immediately around the head.

• Surface coils: A radiofrequency coil that is placed on the surface of the head, very close to the location of interest. Surface coils have excellent sensitivity to the signal from nearby regions but poor sensitivity to signal from distant regions.
• Volume coils: A radiofrequency coil that surrounds the entire sample, with roughly similar sensitivity throughout.
• Phased arrays: A method for arranging multiple surface detector coils to improve spatial coverage while maintaining high sensitivity.

The ultimate goal of MRI is image formation. By placing an object in a strong static magnetic field and exciting its atomic nuclei using radiofrequency pulses, current can be detected in surrounding receiver coils. This current, which is the MR signal, has no spatial information and thus cannot be used to create an image by itself. By introducing magnetic gradients superimposed on the strong static magnetic field, gradient coils provide the final component necessary for imaging. Separate gradient coils are used to modify the strength of the magnetic field so that it increases or decreases along specific directions. Three gradient coils are typically oriented along the cardinal directions relative to the static magnetic field. The direction represented by z is parallel to the main field, while x and y are perpendicular to the main field and to each other.

In an ideal MR scanner, the main magnet would be perfectly homogeneous, and the gradient coils would be perfectly linear. This is hardly the case in reality. So, additional coils, aptly named shimming coils, are used to generate compensatory magnetic fields that correct for the inhomogeneity in the static magnetic field. All MRI scanners are equipped with at least one central computer to coordinate all hardware components (e.g., gradient coils, radiofrequency coils, digitizers), and often multiple computers are used to control separate hardware clusters.

In addition to the hardware requirements, two categories of specialized software are needed for the collection and analysis of MRI images. The first category sends a series of instructions to the scanner hardware so that images can be acquired. These programs, often called pulse sequences, coordinate a series of commands to turn on or off certain hardware at certain times. The second category of software includes reconstruction and analysis packages that create, display, and analyze the images.

How is spatial localization made possible?

Spatial localization and so the image formation is made possible by the application of gradients, i.e., linear change in magnetic field. So the data from the resonance are used to fill up a matrix of voxel (the k space) and through the Fourier transform, there is the formation of an image. The k space is a matrix used to store data acquired from the application of magnetic field gradients.

First, there is the selection of a slice in which spins will be excited at a particular resonant frequency with the application of a z gradient. Within this slice, there is the collection of raw data in the y and x planes with the application of gradients. The y-plane is called phase encoding direction. To obtain this, one has to apply a field gradient in the vertical (or y-plane) direction. The x-plane is called frequency encoding direction. To obtain this, one has to apply a field gradient in the horizontal (or x-plane) direction. The k space stores image information in the frequency domain rather than in the spatial domain.

Frequency refers to how often some pattern occurs in time. The center of k space is where the contrast information is stored. The periphery is where the details of the image are stored. After k space is filled, a 2D inverse Fourier transform is necessary for conversion of the raw data from k space to image space.

How is image segmentation possible?

That is the partitioning of image into the different types of tissues. Because of the different relative T1 and T2 values of the tissues, different tissues have different relaxation times. So WM, GM, and CSF appear differently in the image depending on whether the image is a T1 weighted image or T2 weighted image. To generate images sensitive to T1 contrast, we must collect those images using a pulse sequence with TR and TE short. The tissue that has a shorter T1 value recovers more rapidly and so has a greater signal. This is the case of WM. While, since water has a long T1 value, CSF appears very dark. While, in T2 weighted images, the fluid-filled regions have the maximal signal and so appear very bright, which is important for clinical applications. We must have a very long TR so that the longitudinal recovery is almost complete and T1 contrast is minimal.

How does fMRI create images of neural activity?

The short answer is that fMRI doesn’t create images of neuronal activity but creates images of physiological activity correlated with neural activity, although indirectly. One physiological change long associated with cellular activity is blood flow. Roy and Sherrington inferred the existence of a stimulus-related increase in cerebral blood flow, which has been termed functional hyperemia. They proposed that functional hyperemia served the metabolic needs of brain tissue.

Indeed, the restoration of ionic concentration following neuronal activity needs an energy supply, which consists of oxygen and glucose, important for the synthesis of ATP. These substances are supplied via the vascular system. So, functional hyperemia results in increased oxygen delivery via the vascular system. Oxygen in the blood is bound with the hemoglobin molecules. Oxygenated hemoglobin is diamagnetic and so has little effect on the magnetic field. However, when oxygen is released, the deoxyhemoglobin is paramagnetic and so has an effect on the magnetic field. So changes in the local concentration of deoxyhemoglobin provide a measure of neuronal activity, based on the blood oxygenation level contrast (BOLD).

The BOLD contrast reflects the difference in the T2* weighted images as an inverse function of the amount of deoxyhemoglobin. Indeed, more deoxyhemoglobin is presented, the lower the T2* signal. This happens because paramagnetic substances distort the surrounding magnetic field and nearby protons experience different magnetic field strengths and so will precess at different frequencies. This results in a more rapid decay of the transverse magnetization, so a reduction of the value of the T2*.

Now, what one should expect is that upon neuronal activity, since the oxygen consumption increases in the blood, the deoxyhemoglobin would increase and the MR signal would decrease. But, what is observed is that the MR signal increases. So MR signal increases although deoxyhemoglobin suppresses it. This is due to an indirect role of the oxyhemoglobin. Increased BOLD signal following neuronal activity occurs not because oxyhomoglobin increases MR signal but because it displaces the deoxyhemoglobin which had been suppressing MR signal. So increased neuronal activity increases MR signal.

The one who discovered the potential role of the BOLD contrast in functional imaging was Ogawa in 1990. He hypothesized that manipulating the proportion of blood oxygen would affect the visibility of blood vessels on T2*-weighted images. He tested this hypothesis by scanning anesthetized rodents using high-field (7.0 T and greater) MRI. To manipulate blood oxygenation, they changed the proportion of oxygen that the animals breathed.

When the rodents breathed pure oxygen, gradient-echo images of their brains showed only structural differences between tissues. But when the rodents breathed normal air (21% oxygen), the images took on a very different character. Thin, dark lines became visible throughout the cerebral cortex. The researchers attributed these thin lines to the magnetic susceptibility effects of paramagnetic deoxygenated hemoglobin in blood vessels. Ogawa and colleagues speculated that this BOLD contrast could identify areas of increased brain activity.

How are the neural (electrophysiological) activity and the BOLD signal related?

A coregistration study performed by Logothetis in 2001 between fMRI and electrocortical activity in monkeys aimed to clarify how the neural activity and the BOLD signal are related. He measured the spike density function, that is the neural firing rate, and the local field potential (LFP), that is the sub-threshold synaptic activity taking place between soma and dendrites. BOLD signal emerged to be related with LFP. BOLD may reflect more the neural activity related to the input and local processing in any given area rather than the spiking activity commonly thought of as the output of an area.

PET

PET measures the relationship between metabolic needs (energy consumption) and neuronal activity. PET uses positron-emitting radioactive tracers that are attached to molecules that enter biological pathways. (Positron: antimatter counterpart of electron.) When positrons collide with an electron they are mutually destroyed and emit two gamma rays (detectors can measure them). FDG (fludeoxyglucose): radioactive isotope of fluorine-18 attached to glucose. Injecting a bolus of FDG into an artery, and using imaging to determine where it is taken up by cells. Brain distribution of glucose uptake can be measured.