الفهرس 
MRI Anatomy of Brain
At the third ventricular levelOnly 14 pages are availabe for public view
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Abstract
MS is a challenging disease in all aspects ranging
from etiology to diagnosis and treatment. It is also a
disease that has greater heterogeneity in terms of clinical
forms, imaging appearance, and treatment response. With
the ever-advancing technology, MR imaging will certainly
further improve our understanding of the MS disease and
continue to play an extremely important role going forward
(Ge, 2006).
Despite technological advances in imaging, multiple
sclerosis (MS) remains a clinical diagnosis that is
supported, but not replaced, by laboratory or imaging
findings. However, imaging is essential in the current
diagnostic criteria of MS, for prediction of the likelihood
of MS for patients with clinically isolated syndromes,
correlation with lesion pathology and assessment of
treatment outcome (Ramli et al., 2010).
Complementary to the clinical evaluation,
conventional magnetic resonance imaging (c MRI) plays a
prominent role for diagnosis and assessment of patients
with multiple sclerosis. It provides reliable detection and
quantitative estimation of focal white matter lesions in
vivo. Modern criteria involve MRI parameters for the diagnosis of MS and for predicting conversion to clinically
definite MS in patients who present with a first clinical
episode suggestive of disease onset. A diagnosis of
multiple sclerosis is based on showing disease
dissemination in space and time and excluding other
neurological disorders that can clinically and radiologically
mimic multiple sclerosis (Andreadou, 2012). cMRI the
most important paraclinical tool in supporting a diagnosis
of MS and establishing a prognosis at the clinical onset of
the disease (Filippi et al., 2011b).
However, neurological impairment of patients with
MS is poorly associated with the lesion load observed on
conventional MRI scans. The discrepancy between clinical
and conventional MRI findings in MS is explained, at least
partially, by the low sensitivity of conventional MRI in the
detection of grey-matter involvement and diffuse damage
in white matter (Andreadou, 2012).
And, for clinicians, it still remains unclear how and
when cMRI should be used, not only at the onset of the
disease, but also during the subsequent disease phases
(Filippi et al., 2011b).
These inherent limitations of cMRI have prompted
the development and application of quantitative MR ‘non -conventional’ techniques (Filippi et al., 2011b). (eg, MR
spectroscopy, DTI, perfusion-weighted imaging) offer
opportunities for improved specificity and sensitivity in
diagnosing and monitoring MS (Lövblad et al., 2010).
These advances are expected to help in
understanding the underlying disease processes and the
accumulation of irreversible disability and therefore are
promising tools in studies of disease evolution and clinical
trials (Andreadou, 2012).
Conventional MRI describes the physical
characteristics of a region of tissue relative to surrounding
regions by measuring alterations in tissue water content and
dynamics by proton excitation. Proton MR spectroscopy
(1H-MRS) is a non invasive method that depicts the
chemical properties of a region of brain tissue by
investigating other proton-containing cellular metabolites.
It provides information on tissue metabolism and function
of a selected brain area volume relative to surrounding
regions. Therefore it could be used to study
biochemical changes occurring in lesions and normal
appearing white matter over the course of MS (Andreadou,
2012). 1H-MRS is a valuable tool that could contribute in
objectively following the evolution of MS, to the understanding of its pathogenesis, evaluating disease
severity, establishing prognosis, and assessing the efficacy
of therapeutic interventions (Sajja et al., 2009).
MRS is emerging as a valuable tool to demonstrate
widespread changes in the brain (Narayana, 2005)., At
long echo times four major resonance peaks are revealed
from choline-containing phospholipids (Cho), creatine and
phospho-creatine (Cr), N-acetyl-aspartate (NAA), and
lactate (Lac) (Andreadou, 2012).
Deficiency of the axonal marker NAA (NAA,
normally present in axons and neurons, reflects
neuronal/axonal integrity and therefore appears to be a
sensitive biomarker of disease progression), found not
only in MRI-defined lesions but also in normal
appearing CNS tissue, even early in MS. The MRS
findings support pathological studies suggesting
widespread tissue destruction extending beyond white
matter plaques. Within this complexity, nerve fiber loss in
NAWM and neuronal loss in NAGM may make a
significant contribution to MS-related physical and
neuropsychological disabilities (Narayana, 2005).
Cho and Lac reflect cell membrane metabolism.
Increases in these metabolites are considered as chemical correlates of acute inflammatory or demyelinating
changes. Indeed, increases in Cho and Lac resonance
intensities have been found in acute MS lesions. In large,
acute demyelinating lesions, decreases of Cr have also
been seen (Andreadou, 2012).
1H-MRS studies with shorter echo times can detect
additional metabolites, such as lipids and myoinositol (mI),
which are also regarded as markers of progressing myelin
damage. Increase of levels of myoinositol, which is mainly
localised in astrocytes, has been shown in early MS and
also in chronic lesions, indicating neuronal injury and
ongoing astrogliosis (Andreadou, 2012).
Amino acids acting as neurotransmitters, such as
glutamate, glutamine, and GABA (γ-aminobutyric acid),
can also be measured. Glutamate levels were found to be
increased in acute lesions. A reduced concentration of
glutamate and glutamine in the cortical GM of patients with
PPMS has been found, which was significantly correlated
with the EDSS score (Andreadou, 2012).
1H-MRS. Metabolic abnormalities, consisting of a
reduction of the concentration of N – acetylasparate (NAA)
of the whole brain and in an increase of myo - inositol (mI)
and creatine (Cr) in NAWM have been shown in CIS patients, suggesting that widespread axonal pathology, glial
injury, and an increase in cell turnover or metabolism are
rather early phenomena in the course of the disease.
Metabolic abnormalities in CIS patients have been found
to be more pronounced in those patients with evolution
to CDMS over a relatively short period of time (Filippi
et al., 2011b).
Nevertheless, a few studies have been conducted to
evaluate the effect of disease - modifying treatments on 1
H- MRS- derived parameters (Filippi et al., 2011b).
Based on the success of measuring NAA, choline,
and myo-inositol with proton MRS, it has become
desirable to add this imaging technique to the clinical
diagnostic battery. However, MRS is highly sensitive to
imaging parameters and pulse sequences, with different
echo times being preferred for the measurement of
different compounds (e.g., a longer echo time will
produce greater sensitivity to NAA but lesser sensitivity to
myo-inositol). Therefore, a set of standardized
guidelines has recently been proposed to increase the
potential for proton MRS to become a standard MS
detection and tracking technique (Fu et al., 2008).However, a number of technical factors that include
poor SNR, long acquisition times, poor spatial resolution,
limited spatial coverage, and complex data processing have
so far limited the use of 1H-MRS in routine clinical
practice. Recent developments of high field MRI scanners
for improved SNR and spectral resolution, introduction of
parallel imaging, fast analysis techniques, and the
availability of free analysis tools should greatly facilitate
a more widespread use of 1H-MRS in the diagnosis and
management of MS. Another aspect of MRS that needs to
be addressed is the standardization of both acquisition and
analysis protocols. A first step towards achieving the
standardization, based on single voxel MRS, has recently
been proposed. While this is an appropriate first step,
standardized protocols that include multivoxel MRS for
increased spatial coverage and exploit the full potential of
MR hardware and software are needed (Sajja et al., 2009).
1H-MRS is relatively time - consuming and
requires experienced personnel, which limits its use in the
context of multicentre studies.,1H- MRS could also be
used as a diagnostic tool, although it has not yet
moved to clinical practice (Andreadou, 2012).Diffusion weighted (DWI) and diffusion tensor
imaging (DTI) provide information about the tissue
fibers by measuring the motion of tissue water
molecules in vivo. The mobility of water molecules is
diminished in highly organized tissue, like white and gray
matter, and consequently, the apparent diffusion
coefficient (ADC) is lower in those tissues than in free
water. Pathological processes that alter tissue organization
can result in abnormal water motion, thus modifying ADC
values. Tissue damage in MS, mainly demyelination and
axonal degeneration, results in abnormal water motion, and
therefore in alteration of the ADC values. Diffusion
abnormalities may precede Gd-enhancement in hyperacute
MS lesions (Andreadou, 2012).
Diffusion-weighted imaging is a new MRI technique
which has been widely applied in MS to improve our
understanding of the disease. In particular, diffusion tensor
imaging (DTI), which best describes the diffusion
properties of a living tissue, has been employed to
investigate the structural damage occurring in the MS
brain. from the DT several indices can be derived, such
as fractional anisotropy (FA), which quantifies the
preferential direction of diffusion within a voxel, and mean
diffusivity (MD), which measures the magnitude of water diffusion without regard to its directionality (Ciccarelli,
2006). And the longitudinal and transverse diffusivities of
the diffusion tensor are considered valuable tools in the
assessment of focal and widespread white matter tissue
damage in patients with MS (Andreadou, 2012).
In the last few years, the growing number of DT
studies investigating diffusion abnormalities in MS have
consistently reported that diffusion changes are present not
only in the demyelinating lesions, but also in the normalappearing tissue. The fact that DTI can detect pathological
changes which are not visible on conventional MRI has
important clinical relevance because of the potential of
pathology in NAWM and NAGM to contribute to
disability in patients with MS (Ciccarelli, 2006).
FA was found to be decreased, whereas MD was
consistently shown to be increased in MS plaques as well
as in normal appearing white matter of MS patients
However, FA values have been found to be increased in
intracortical MS lesions, possibly reflecting intralesional
loss of dendrites and activation of microglia. Transverse
diffusivity, which refers to the diffusion across fibers, is
believed to be a specific marker for axonal loss and
demyelination associated with MS. Relative increase of TD has been shown in MS, correlating with demyelination and
axonal loss. This finding suggests that fragmented or
missing myelin permits greater diffusion of water
molecules across fibers. Moreover, quantitative variables
derived from DTI were found to correlate with clinical
disability (Andreadou, 2012).
DTI is not routinely used for the diagnosis or
differential diagnosis of MS. DTI appears to be sensitive to
disease-related changes occurring in MS brain over time
Therefore, it has the potential to be used as a treatment
outcome measure. However, it has not been employed so
far in treatment trials mainly because of the lack of
standardization of measurements for multi-centre studies.
Its ability to detect changes beyond the lesions and its
sensitivity to structural damage, combined with the
dissemination of high resolution scans and hardware
improvements, are encouraging its growing use at multiple
clinical sites (Ciccarelli, 2006).
Fiber tractography is a diffusion technique based on
the directional movement of water, which allows the
generation of non-invasive three- dimensional images of
white matter fiber tracts. It is a promising method for in
vivo segmentation of the major WM tract fiber bundles in the brain. In MS patients, DT MRI tractography holds
promise in enabling visualization and quantification of the
degree of axonal loss and demyelination in vivo
(Andreadou, 2012). It can distinguish between regions
where fibers are highly aligned in the voxel from those
where fibers are less coherent (Ciccarelli, 2006).
However, the application of DTI tractography in MS
is limited by the presence of both focal and diffuse
alterations of tissue structure, which cause a decrease in
anisotropy and consequently an increase in uncertainty of
the primary eigenvector of the DT (Andreadou, 2012).
The possibility of a non-invasive assessment of
white matter pathways in MS may increase our
understanding of the disease. However, the employment of
tractography in MS is still preliminary, and only a few
studies have so far examined patients with MS using
tractography algorithms (Ciccarelli, 2006).
Cerebral Perfusion MRI is becoming an increasingly
important method for diagnosing and staging brain
diseases. Perfusion MRI techniques can be categorized in
two different groups based on tracer type. First, Dynamic
Susceptibility Contrast (DSC-) MRI is a method based on
the injection of an exogenous tracer, The second technique,arterial spin labeling (ASL), is a completely non-invasive
technique that employs water protons as an endogenous
tracer (Bleeker and Osch, 2010).
Perfusion MRI may provide unique information
about the pathophysiology of the disease and help identify
new targets of treatment. However (Filippi et al., 2010)
Both bolus-tracking and arterial spin labelling need further
development to improve quantification of cerebral blood
flow and volume (Bakshi et al., 2008). The reliability and
reproducibility of absolute measures of brain perfusion
warrant further investigation. In addition, the sensitivity
and clinical relevance of perfusion MRI scans in detecting
longitudinal, MS-related changes also need to be
established before the technique can be used for
monitoring MS evolution and treatment efficacy in
multicenter clinical trials (Filippi et al., 2010).
Chronic cerebrospinal venous insufficiency
(CCSVI) is a vascular condition described in multiple
sclerosis (MS) (Zamboni et al., 2011). CCSVI is a
sonographic construct that is poorly reproducible and
questionable in terms of known pathophysiologic factors
established in MS. (Filippi et al., 2011a). However, one
can in no way state that enough research has been done to conclude that CCSVI is a true pathologic entity occurring
with an increased frequency in MS patients, that this entity
is responsible for the symptoms and disease progression
seen with MS, and that treatment significantly improves
the quality of life in these patients. As a result, additional
research is going to be critically important moving forward
(Sisken et al., 2011).
Although non - conventional MRI techniques
may provide essential and critical information about
patients with CIS, and their application for monitoring
treatment might provide a more accurate assessment of
efficacy on inflammation, axonal protection, and
demyelination / remyelination, their use in clinical practice
is currently not recommended. All these techniques are
yet to be adequately compared to cMRI for sensitivity
and specificity in detecting tissue damage in MS and for
predicting the development of MS and disability (Filippi et
al., 2011b).
The application of non - conventional MRI
techniques in monitoring patients with established MS in
clinical practice is, at the moment, not advisable. All these
techniques still need to be evaluated for sensitivity and specificity in detecting tissue damage in MS and its
changes over time (Filippi et al., 2011b).
Although these techniques have provided important
insight into the pathobiology of MS, their practical value in
the assessment of MS patients in clinical practice has yet
to be realized (Filippi et al., 2011b). The new techniques
and analysis procedures need to be refined and validated
before they can be properly integrated into clinical research
and practice. Until that time cMRI metrics will continue to
play an important role in clinical practice and in clinical
trials. Overuse of MRI in clinical practice, however, should
be avoided. It is important to keep in mind that clinical
judgment remains essential in the management of the
disease and that careful interpretation of the MRI data is
needed to avoid misdiagnosis (Andreadou, 2012).