Diederich 1 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 Diederich 2 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 Diederich 3 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). Diederich 4 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.) Diederich 5 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 Diederich 6 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 Diederich 7 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. Diederich 8 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. . .