Πέμπτη 23 Αυγούστου 2012

MRI and neurodegenerative diseases.

Introduction 

The MRI is a Sophisticated diagnostic and noninvasive method to extract valuable quantitative and qualitative characteristics that can provide a comprehensive understanding of the mechanisms of brain function.Neurodegeneration is the generic term for the progressive loss of structure or function of neurons, including death of neurons.Many neurodegenerative diseases including Parkinson's, Alzheimer's and Huntington's disease can occur as a result of neurodegenerative processes.As research progresses, many similarities appear which relate these diseases to one another at a subcellular level. Discovering these similarities offers hope for therapeutic progress that could improve the outcome of many diseases.But for better understanding of these processes, the clinical diagnosis and the development of therapy is necessary to display these degenerative changes.In clinically acceptable time (less than one hour)  is possible to study the situation by applying multiparametric MRI (anatomical imaging, DTI, DWI, PWI, fMRI, p1, p2, p2 *) a diagnostic method that provides information functional, biochemical and structural data for the brain. The ultimate goal of this method is the individualized treatment of each incident and the time of treatment to maximize the desired effect and halt disease progression. These techniques are described below and based on the literature are unique and highly effective diagnostic methods to better manage the disease.
 


Magnetic Resonance Imaging - MRI

Magnetic resonance imaging or MRI is the imaging method with the highest sensitivity and specificity that is available to us today. So named because it uses a strong magnet and a specific radio frequency to excite the protons in the region of interest and then to record the signal in order to create images. The images obtained by various techniques, sequences, each of which has certain technical characteristics in order to provide different information to each other.Still, the possibility of multilevel imaging allows better recognition of both the structure of the brain and the normal anatomy and the extent of pathology and its relationship with functional anatomical structures. With this method, illustrated pathological processes that damage the brain anatomical substrate, regardless of etiology. This test is non-invasive because it is done without the use of ionizing radiation and contrast if used, is slightly toxic compared with iodinated contrast used in other radiological examinations (computed tomography).The MRI based on the principle that the core of the hydrogen atoms, which consists of a proton, behaves as a rotating magnet. Under normal conditions, the hydrogen nuclei are oriented randomly, so a piece of tissue (all soft tissues containing water, which contains hydrogen) has no net magnetic dipole. However, when the cores are placed in a strong magnetic field oriented parallel to the magnetic field lines and perform transient motion around the axis of the magnetic lines in a specific rotational frequency (frequency Larmor). This frequency is specific to each person because each type of atomic nucleus performs transient motion with a certain frequency (eigenfrequency), which is different for each person.This transient movement, under certain conditions, can be described by two constants, the T1 and T2, and provides a means to investigate different types of nuclei contained in the various tissues of a patient. More specifically, during the examination, the coils of the MRI RF transmit radio waves (RF) with a frequency equal to the rotation of the cores (frequency Larmor). The kernels absorb the generated electromagnetic energy, the state changes of rotation. After stimulation with pulses RF rails nuclei transitioning to their original state with an exponentially decreasing transient movement described by the two constants, T1 and T2, emitting a weak RF signal RF frequency Larmor (with minor variations).The weak signal, which receive, is the magnetic resonance signal. This signal deteriorates with time and is called free induction decay signal (FID: Free Induction Decay). Then by applying Fourier transformation to the FID (signal in the time domain) receives the signal in its final form, i.e. in the frequency domain. When performing examinations MT spatial determination of the signals is stepped by superimposing the magnetic fields, which change locally the strength of the main field, resulting in little change in the resonance frequency of hydrogen nuclei. In this way the emission of RF pulses with a specific range of frequencies excited specific areas and can determine the position, based on the differences in the frequency and rate of rotation of protons (Kolb & Whishaw, 2008a).


Classic imaging and assay techniques relaxation time T1, T2 and T2 *.


 In MRI anatomical structures are represented by shades of gray. The range of shades of gray that is used is based on the grades of the measured signal intensity. As mentioned high signal intensities are typically "lighter" shades of gray. Contrary to what happens in other imaging with X-rays, magnetic resonance imaging parameters that determine the signal intensity are numerous.The shades of gray, so the contrast in an image are determined by adjusting operating parameters specific MRI that affect the resolution of the images, what tissues and what phenomena will be illustrated best and if you take pictures or quantitative data.Based on the difference signal is possible to draw conclusions about the state of the tissue and recording of quantitative data (by applying technical segmentation and feature extraction - segmentation, feature extraction) as the total surface of the tissue of interest and why surface white / gray matter for analyzing the evolution of the disease and correlation with qualitative characteristics of the disease and the patient's condition in relation to other biomarkers and neuropsychological account of the patient (Avants B., 2004).Also, previous studies examining the usefulness of mapping T1, T2 and T2 * relaxation in the investigation of the characterization of neurological diseases have demonstrated significant changes in relaxation times T1, T2 and T2 * in specific areas of the brain in autism, schizophrenia, epilepsy, Parkinson's disease, multiple sclerosis, and a number of other disorders. Despite the proven value, the volumetric T1 and T2 mapping is not part of the daily clinical assessment, possibly due to the low resolution associated with the conventional methods mapping (Bartozokis G, 2000).The ability to accurately and detailed mapping of T1 and T2 high resolution (less than 1 mm3 voxels) allows for more thorough investigations of the changes in relaxation times in pathological situations.The current methods available for rapid mapping and high resolution anatomical imaging allows scans to a clinically viable time (30 minutes, 1 hour for the total implementation of techniques of spectroscopic imaging and diffusion) (Della Nave R, 2004).The techniques for measuring the relaxation of the tissue offer the possibility for quantitative assessment of the areas affected, to detect changes that are not apparent with conventional imaging and the effect of medication on the region of interest before and after the administration and the effect in time (Deoni SCL, 2003).

 
Typical form of 3D anatomical imaging T1FSPGR (upper image) to properly implement segmentation techniques (segmentation) for extracting quantitative characteristics (total area of ​​the basal ganglia, along interfacial white - gray matter) and relaxation techniques * p2 (T2 *) for estimating status of the tissue of interest with absolute quantification (bottom images).

 functional Magnetic Resonance Imaging - fMRI
 With functional magnetic resonance imaging (lMT / fMRI) is able to collect information not only on the morphological picture of the brain, but also its function. With the application of new techniques, it is possible to study the dynamics of the brain, time performed some basic functions. So, we can get more functional information about the brain, while doing some specific examinee effort, for example, moves his fingers, he sees images, words or listens memorize. This application opens new perspectives in the study and understanding of higher cognitive processes, with applications in both clinical and research studies.It is already known from other methods (PET, EEG) that activation of an area of ​​the brain accompanied by local changes of perfusion and metabolic reflect cerebral activity resulting in local changes of blood oxygenation feeding the activated region. When an area of ​​the brain increases the metabolism of the nerve cells and is increased and blood flow to the region at 20-40%. In the same area is increased and the consumption of oxygen at 5%, to a lesser extent that the degree of increase in perfusion. The disproportion of local perfusion and increased oxygen consumption, the "overcapacity" is oxygen, increases the tendency of oxygen to the activated region. Thus induced focal increase of oxygenated blood in the form intravascular oxyhemoglobin, which has an increased magnetic susceptibility. By applying appropriate pulse sequences (T2 *), it is possible to display the areas stimulated with increased signal compared with the adjacent cerebral parenchyma not stimulated.During an examination lMT alternate blanking periods with stimulation of the brain by the application of a specific stimulus. The images of the rest are removed from the images of the excitation and thus it is possible to display the domains with high signal. Note that the increase in signal strength with the technique BOLD is very small, of the order of 1-4% in a field of 1.5T. These images are finally called maps activation epiprovalontai the anatomical images of the test and we have to combine anatomical and functional information (Kolb & Whishaw, 2008a).
This mode is called the response to the English acronym BOLD (blood oxygenation level dependent response) and depends largely on the intensity of the magnetic field, because the phenomena of magnetic susceptibility (magnetic susceptibility is the degree of magnetization of a substance when there is the influence of a magnetic field. Namely the quotient of the intensity of magnetization to the magnetic field in which the substance is exposed) increase with the magnetic field. Consequently, the method can be applied to a high magnetic field, 1.5 T or T 3, while research used and strongest fields (7, 9 and 11.4 T).


 

Typical fMRI data . These brain regions are indicated by red and yellow indicate response BOLD.
 Clinically, the method can be used for preoperative mapping of functional centers in the brain in cases of invasive processes authorized and epilepsy surgery. The aim is to highlight some central location in relation to the lesion to determine whether surgical removal is safe. As a guideline, it seems that if the threshold is the surgical removal of at least 2 cm from the working area, the exception is secure and the possibility of residual postoperative function is small. There are also applications in psychiatry and neurology (eg dyslexia, schizophrenia, dementia).The fMRI has been widely used in recent years in healthy volunteers for the study of cognitive processes and their neuroanatomy (Jäncke, 2009).


Diffusion Weighted Imaging - DWI / Apeikonisi Tanysti Diffusion (Diffusion Tensor Imaging - DTIThe applications of molecular diffusion imaging are important development in magnetic resonance imaging as possible imaging and quantitative description of the microstructure and the provision of tissue and neurons to be the best description of the course of disease.The diffusion of water in biological tissues are not random or free but depends on the structure and condition. Detected with the help of the imaging technique of diffusion (diffusion weighted imaging - DWI) is also described, quantified by the coefficient ADC (apparent diffusion coefficient - apparent diffusion coefficient) varies depending on the tissue being analyzed and is the ease with which water travels through and around the cells and thus tissue. Normal tissues in all people those prices are fixed and depend on the area being studied. In patients with Alzheimer's dementia have degenerated tissue destruction of their structure, more free and rapid movement of water and consequently increase above the normal range of prices ADC (Worsley KJ, 1999).The water displays different diffusion rates in the tissue relative to the direction of diffusion. This phenomenon is called anisotropy of diffusion. In order to detect this anisotropy is necessary encoding at least six addresses in the area of ​​diffusion in order to draw conclusions about the relative mobility of water molecules in the environment of the tissue. In conventional imaging molecular diffusion is not applied coding. By means of diffusion tensor imaging (diffusion tensor imaging - DTI) is possible to describe the microstructure of the tissue through the observation of the speed of diffusion of water to the given directions.





Three dimensional reconstruction of data obtained from diffusion tensor imaging of superposition with classic images of the brain to find the location of the imaged neurons. The filamentous structures with orange and yellow tint illustrate the groups of neurons and their architecture in space and the different shades show the density of these neurons and thus maintain or destroy the microstructures of the brain.

With these techniques is represented by the arrangement of neurons in the area due to the detection of address during which the rapid diffusion of water molecules. This technique is based on specific algorithms for finding this address. The reconstruction is based on the processing of those data DTI and to all parts of the image. In this way it is possible to record the connections of the structures of the brain and nervous system. The resulting images are characterized by the observation of color filamentous structures in three-dimensional space which represents the shape and the arrangement of neurons. So it is possible to observe the smooth operation and arrangement of neurons and synapses.


The possibility of multiparametric scanning (by applying at least 15 different types of imaging and quantitative information) in a single sccan in less than one hour non-invasive manner and without any cost to the question is a huge weapon for effective clinical diagnostic practice in battle of neurodegenerative diseases that tend to evolve into an epidemic.

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