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20 March 2013
Methods to Measure Grey and White Matter Lesions Efficiently for Patients with Multiple
Sclerosis
Multiple Sclerosis (MS) is a degenerative disease concerning the central nervous system
(CNS) where grey matter (GM) and white matter (WM) play a significant role in cognitive
impairment and also physical disablement causing physical and mental disablement. Individuals
actively participating in the treatment or measurement of MS need to be required to understand,
read, and interpret the images produced by each measuring technique; additional training is most
likely a possibility for the less popular clinically used techniques or those that are not in standard
use. ‘Standard’ is to be understood as a usual repertoire and regularly performed diagnostic
imaging machine by clinics nationwide/ worldwide. The measuring techniques being used today
are magnetic resonance imaging (MRI) which is a form of radiology that helps see the body
internally via in vivo, double inversion recovery (DIR) MRI, as defined by Madelin, “combines
two inversion pulses in order to simultaneously suppress signals from tissues with different
longitudinal [repeated] relaxation times [being the time and process of which nuclear
magnetization takes to reach equilibrium]” is also a form of MRI. T1-weighted MRIs: spin echo
transverse relaxation rate (R2) is by Farflex’s free medical dictionary, “a magnetic resonance
pulse sequence in which echoes are generated by rephrasing spins in the transverse plane using
radiofrequency pulses or magnetic field gradients”, and gradient echo transverse relaxation rate
(R2*) by definition it is an echo produced as a result of gradient rephrasing and can be acquired
easily because it uses short inter-pulse repetition times (Madelin). T2-weighted MRI is another
basic MRI but the fat in the image shows darker and water shows up lighter, and T*2-weighted
MRI is more susceptible to losses at air or tissue boundaries but the increased contrast for some
types of tissue is effective; the difference between these are subtle but important in the
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interpretation. All are very high field strength (VHF) systems meaning that they can negatively
affect living organisms with the radio frequency energy; this is why there are limits on radio
frequency exposure. With the disease affecting the living the measurements must be in vivo—
within a living organism, the imaging and testing of disease pathways is performed through
optical and X- ray modalities. The Philips Gyroscan, another addition to the classic MRI, it has
real-time scanning that can measure anything from musculoskeletal and body examination to
neuro-studies (Boer 2). Finally the neuropsychological tests that demonstrate cognitive disability
are Selective Reminding Test, Spatial Recall Test, Paced Auditory Serial Addition Test, Symbol
Digit Modalities Test, and Word List Generation (Rossi).
R. Marc Lebel et. al. in “Quantitative High-Field Imaging of Sub-Cortical Gray Matter in
Multiple Sclerosis” describe the findings of MRI measuring techniques as well as using T2weighted images in order to better identify iron in the brain as there is a correlation between iron
in grey matter and the cognitive disability of MS. Similarly Filippi and Rocca’s “The
Neurologist’s Dilemma: MS is a Grey Matter Disease That Standard Clinical and MRI Measures
Cannot Assess Adequately- No” suggest that other techniques such as DIR should be used more
routinely and can identify clinical phonotypes and clinically isolated syndromes better than a
normal MRI (Filippi 557). It would require more training on an ad hoc basis and needs to be
implemented as a standard measuring technique in clinics (Filippi 557). Francesca Rossi, et. al.
in “Relevance of Brain Lesion Location to Cognition in Relapsing Multiple Sclerosis” concur
that several measuring techniques should be obtained in order to better address the amount and
extent of lesion distribution in the brain by using probability maps and creating a “symmetric
study-template” for relapsing-remitting MS patients that will average out all brain images they
measure or study (Rossi et. al.). Jeroen J. G. Geurts et. al. identify that GM atrophy is the key
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source to understanding the clinical effects of MS and its’ patients. The in-vivo measurement of
GM can help develop understanding about early involvement and the progression of the disease
but MRI alone does not do justice when finding lesions. MRI has been used for years to identify
white matter and grey matter lesions; however there are several other options in order to
correctly identify each in the brain along with its effects cognitively. As a result of MS becoming
a greater topic of discussion in the medical field, more of these measuring techniques should
become “standard” (Filippi 558). There are many MRI derived approaches that would work
sufficiently as a tool to study the dispersal and the prospect of appearance of lesions in the brain.
Grey matter is associated with physical and cognitive impairment, which is why it is necessary to
develop the most reliable imaging.
MRI is more frequently used to identify WM and GM lesions than most any other
measuring technique. Lebel et. al. conclude that MRI contributes to the knowledge of MS, but
“[c]urrently no absolute quantitative measure of iron is possible using MRI; however, numerous
methods are highly sensitive to its effects.” Of course the MRI images cannot stand alone in this
case when measuring iron near GM. The source makes a point that with very high field strength
systems, sensitivity to iron in GM regions increase, however the problem with VHF systems is
that it can be limiting because it requires excessive radiofrequency in order to produce the
needed train of spin echoes. Relative to VHF, the spin echo transverse relaxation rate “may
prove sufficiently sensitive and specific to become a reliable measure of brain iron” (Lebel 434).
Similarly the R2* proves to be sensitive enough to identify iron, but R2* is “influenced by
magnetic field gradients surrounding air/tissue boundaries, large draining veins, and tissue
microvasculature,” but there have been efforts to rescale the intensity of the signal (Lebel 434).
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Additional and more accurate measuring techniques need to be ‘standard’. By ‘standard’
Filippi and Rocca mean “measures that are sensitive, easily available, practical and standardized”
(557). The source describes the measures used when monitoring clinical activity and progression
are relapse rate and the Expanded Disability Status Scale (EDSS) which quantifies disability, but
the article states that it does not do any justice when measuring GM (557). They might measure
cognitive impairment as far as fatigue, depression, and memory is concerned but the major
involvement of the GM is not being reflected (557-558). The double inversion recovery
sequences seems to be the authors’ choice that adequately addresses the GM factors playing into
MS patients’ lives, “DIR sequences have shown GM lesions in all the major MS clinical
phenotypes” (557). The observable characteristics, such as the locomotor disabilities, depression
and cognitive impairment often inherited by MS patients can be recognized using longitudinal
studies showing “an increased rate of cortical [cerebral cortex] tissue loss” (557). With more
accurate and efficient techniques we can correctly identify lesions, “in patients with MS an
association has been found between the extent of GM lesions and cognitive impairment as well
as their predictive role for subsequent development of irreversible disability” (557).
There are many MRI derived approaches that would work sufficiently as a tool to study
the dispersal and the prospective appearance of lesions in the brain. Rossi et. al. suggest that the
tools we need to better understand the disease are already in practice:
Since magnetic resonance imaging is the most sensitive tool to investigate in vivo
tissue damage occurring in the MS brains, many recent studies have used
quantitative MRI-based techniques to improve the knowledge of the substrates
underlying cognitive impairment in MS. (n.p.n.)
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The source also suggests that lesion mapping has been successful in the way that it is
being used to study the occurrence of brain lesions using spatial patterns. The study used the
Gyroscan, duel-echo turbo spin-echo sequence, T2-weighted images, and T1-weighted gradient
echo images, along with five neuropsychological tests (Rossi). The study performed by the
source found that indeed patients had higher lesion frequency in the left corpus collosum
according to the T2 tests conducted. The neuropsychological tests showed that there are cognition
deficits in patients with MS who typically failed two or more of the neuropsychological tests.
The comparison between those who are cognitively preserved--living without MS, and those
who are cognitively impaired and living with MS, was blatantly obvious that the brain suffers
greatly with the presence of lesions. This set of techniques measured and efficiently identified
lesions in the brain, but the source does not correctly identify if the use of these accommodations
are standard practice for all clinics and physicians.
Grey matter is associated with physical and cognitive impairment, which is why it is
necessary to develop the most reliable imaging. Geurts et. al. takes a stance as a fan of the
involvement and coming of age additions to the MRI itself, but is not pleased with MRI as a
whole. Grey matter is indistinct to the traditional MRI sequences, but because of this knowledge
it has become an expansive search to develop and apply new methods (1082). These newer
methods, such as the involvement and evolution of in-vivo, have helped show that GM is in
association with neuropsychological disability (1082). In-vivo, studying on living beings,
“reflect[s] combinations of demyelination, neurite transection, and reduced synapse or glial
densities” which has been suggested, has a connection to tissue degeneration in the cerebral
cortex of the brain (1084). The help of in vivo may also answer questions concerning
spatiotemporal development, continual demyelination and neurodegeneration in patients with
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MS (1085). Although this technique seems to be answering questions, it is causing just as many.
In-vivo technique DIR detects up to five times the GM of the T2-weighted sequence, but even
with the noted lesions, there is about 80% unaccounted for (1085). Despite the lack of identified
GM lesions there is an association with physical disability, and this cortical lesion “burden” in
MS patients (1086). The effect of this cortical pathology is clinical disability and cognitive
dysfunction (1086).
Behind all of the fancy verbage and exhaustive definitions, there is a real issue here. The
fact that a person’s life can be so easily altered, to the point where they are unable to walk or
even think properly, is a cause worthy of attention. Addressing the cold heart of the issue—the
necessity of stable and safe use of equipment; doctors, physicians, and scientists that can perform
their tasks properly for the benefit of people with the disease; and appropriate measures that can
capture every lesion in the brain. Because one day, I believe, we’ll find a way to help those with
MS; without them having to inject themselves every day for the rest of their lives, or visiting a
hospital so many miles away every month for a three hour infusion--like my sister. I want her to
grow up and go to college, meet the man that will love her for the rest of her life, and have a
beautiful family together. All of this will happen, but she’ll have to deal with MS along with all
of life’s curveballs. Accuracy, reliability, and standardization will help those with MS get the
treatment they deserve, because life is difficult enough, at times, without having to use a
wheelchair and live solely on the first floor of your two story home with an inadequate bathroom
and sleeping on a couch—like my father’s best friend Bill. Obviously this disease has caught my
attention through first-hand experience. Baylee, my sister, will go through life forever choosing
the location of her home in consideration of the nearest hospital to receive an infusion, and Bill
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will never walk again; there isn’t any amount of data that can tell me that there will never be a
cure or a more strategic way to deal with this disease, we simply need to keep searching for one.
Works Cited
Boer, R. W. de. Philips Healthcare. n.d. 03 2000. Web. 28 03 2013.
Farflex. The Free Dictionary. n.d. n.d. 2013. Web. 27 3 2013.
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Filippi, M, and MA Rocca. "The Neurologist’s Dilemma: MS Is a Grey Matter Disease That
Standard Clinical and MRI Measures Cannot Assess Adequately – No." Multiple
Sclerosis Journal 18.5 (2012): 557-558. Academic Search Premier. Web. 24 Feb.
2013
Francesca Rossi, et al. "Relevance Of Brain Lesion Location To Cognition In Relapsing
Multiple Sclerosis." Plos ONE 7.11 (2012): 1-7. Academic Search Premier. Web.
24 Feb. 2013.
Geurts, Jeroen JG. "The Neurologist’s Dilemma: MS Is a Grey Matter Disease That Standard
Clinical and MRI Measures Cannot Assess Adequately – Yes." Multiple Sclerosis
Journal 18.5 (2012): 559-560. Academic Search Premier. Web. 24 Feb. 2013
Madelin, Inglese, Oesingmann. "Double Inversion Recovery MRI with Fat Suppression at 3T
and 7T." n.d. n.d. 2008. NYU Langone Medical Center. Web. 27 3 2013.
R. Marc Lebel, et al. "Quantitative High-Field Imaging Of Sub-Cortical Gray Matter
Multiple Sclerosis." Multiple Sclerosis Journal 18.4 (2012): 433-441. Academic
Search Premier. Web. 24 Feb. 2013.
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Methods to Measure Grey and White Matter