Magnetic resonance imaging and spectroscopy
The introduction of imaging techniques based upon the physics of (nuclear) magnetic resonance (MR) has contributed enormously to the detection, understanding and recognition of abnormalities the brain (central nervous system, CNS).
MR techniques are based upon the physical properties of atomic nuclei. The principal elements of atomic nuclei are protons and neutrons. When these components add up to an odd number, we have a combination of an electric charge and a spinning motion, inducing a (micro)magnetic field. One of the atoms satisfying this condition is the hydrogen atom, the nucleus consisting of one proton and no neutrons. These hydrogen atoms are present in the body in very high concentrations: in water (65-80% of the human body consists of water), in fat and in lower concentrations in other substances. MR imaging using protons is therefore a logical choice.
In a magnetic field of sufficient strength, the microscopic magnets (protons) orient themselves, according to the laws of quantum mechanics, in one of two possible positions: either parallel to the main magnetic field (spin up position, low energetic level) or anti-parallel to the main magnetic field (spin-down position, high energetic level). The energetic gap between these two energy levels (w, resonance frequency) is according to the Larmor equation the product of the gyromagnetic ratio (g, a constant different for each nucleus) and the strength of the main magnetic field in Teslas (unit of strength of the magnetic field): w = g. H0. There are only few more protons in the spin-up than in the spin-down position, sufficient, however, to add up to a magnetic vector aligning with the main magnetic field.
The resulting vector is usually depicted in a frame with three axis, z (along the main magnetic field) and x and y (perpendicular to this field:
The population of protons in a magnetic field can absorb energy with the Larmor frequency. This energy is supplied by electromagnetic pulses of the correct frequency. Under the circumstances used in diagnostic MR instruments, these frequencies are in the range of radio-frequencies (RF). The pulses used are usually referred to as RF pulses. When the RF pulse stops, the protons start to return to their original or equilibrium state, a process called relaxation. This relaxation process is characterized by two independent constants, the T1-relaxation time, characterizing the return of the original magnetization along the main magnetic field, and the T2-relaxation time, characterizing the exponential decay of magnetization in a plane perpendicular to this field.
The total number of protons in a tissue unit and the relaxation time constants T1 and T2 are tissue characteristics and are different for different tissues and fluids. MR sequences can be made proton density-, T1- and T2-dependent. MRI displays consequently differences in proton density, T1- and T2- relaxation times and combinations thereof. As a rule of thumb, T1-weighted images give the best anatomical results, whereas T2-weighted images are most sensitive to abnormalities of the tissue. Present day MR techniques allow combinations of T1- and T2-weighted images with increased sensitivity for abnormalities, while other techniques can improve the image quality by suppressing fat, or suppressing irrelevant background information.
In addition to the structural information available by MRI, it is now also possible to obtain information at the molecular level, for example by measuring the diffusion coefficient of water molecules. The different degrees of freedom of diffusion of water molecules within different tissues under normal and abnormal circumstances can indirectly be made visible. This diffusion-weighted technique can add considerably to the MR diagnosis at the tissue level.
In the Center for Childhood White Matter Disorders an array of the available techniques is used to extract the maximum of information from the examined tissue.
The basis of MR spectroscopy is a phenomenon called chemical shift. The atomic nucleus is surrounded by a cloud of electrons and other atomic nuclei. These induce changes in the local magnetic field and therefore in the resonance frequency. The precise shift is characteristic for a particular atomic nucleus in a particular compound. Because the concentration of water in the human brain is very high, compounds with a concentration in the milimolar range can only be seen when the signal of water protons is suppressed. There are several techniques to achieve this. Once the water is suppressed a number of metabolite peaks can be made visible in the spectrum and can be used as markers for biochemical events in the brain.
N-acetylaspartate is a compound considered to be solely present in neurons and axons and its concentration can be used as a marker of neuronal and axonal integrity. Choline resonance can indicate intensity of membrane turnover, creatine as measure of energy rich phosphates. The presence of lactate means usually obstruction of aerobic glycolysis and a shift towards anaerobic glycolysis. In some of the inborn errors of metabolism abnormal peaks are present sometimes suggestive of a specific diagnosis.
T1-weighted images give excellent anatomic detail.
The great advantage of MRI is that many different techniques can be used, each adding to the information about the morphology, biochemistry, physiological properties and function of the examined tissue.
We have systematically analyzed the MR patterns of many white matter disorders and developed a computer program to assist in pattern recognition
In white matter disorders in infants and children some patterns are diagnostic. Other ones may suggest a diagnosis that still needs further confirmation by other tests. In about 50% of cases MR can not provide a diagnosis and when also laboratory tests fail to find a cause the disorder remains unclassified. One of the goals of the center is to unravel the pathological background of these unclassified disorders.