Michael Hutchinson, M.D.

At last, a gene therapy for Parkinson's disease?
Hutchinson, Michael
2011 Apr;10(4):290-291, Lancet neurology
— id: 129322, year: 2011, vol: 10, page: 290, stat: Journal Article,

Neuroimaging of movement disorders
Hutchinson, Michael
2009 ;14(4):164-174, Continuum : lifelong learning in neurology
This chapter is a review of neuroimaging techniques for detecting and analyzing movement disorders. It is not intended to be an exhaustive review. The intent is rather to emphasize not merely how imaging plays a role in diagnosis, but how it has changed the way we look at movement disorders, with emphasis on its ability to illuminate the causes, from networks to genetics. Recent developments in PET, MRI, and ultrasound are described as they are applied to Parkinson disease, progressive supranuclear palsy, Huntington disease, essential blepharospasm, and torsion dystonia. This chapter will show how imaging has confirmed an old conjecture as to the etiology of dystonia. Finally, this chapter will discuss how MRI can replace brain biopsy and spinal fluid assays as a way of diagnosing Creutzfeldt-Jakob disease.
— id: 100976, year: 2009, vol: 14, page: 164, stat: Journal Article,

Self-referral of imaging does not imply overutilization
Hutchinson, Michael; Chawluk, John B; Gomez, Camilo; Greenberg, Jack; Hussey, Francis D; Preston, William G; Zimmerman, Earl
2009 Jan;19(1):80-83, Journal of neuroimaging
For several years, some sectors of the specialty of Radiology have complained about the practice of self-referral, where a nonradiologist physician provides and interprets an imaging procedure. It is argued that such practice leads to increased costs since a physician will overutilize technology because of financial incentives. Here we review the literature. The most extensive analysis to date is at odds with the conclusions drawn in the older literature in that it provides little, if any, evidence for overutilization. We performed our own investigation using a poll study and found no suggestion of overutilization in 33 self-referring neurologists when compared with 900 neurologists who referred imaging to radiologists. The main period of growth in demand for imaging was between 1999 and 2002. Since 2002 there has been a steep decline in the rate of growth, so that it is possible to predict roughly zero growth in MRI utilization by 2009 without any intervention. It is shown why the rise in demand for imaging studies cannot be explained by self-referral, and it is argued that the sudden expansion of demand 8 years ago was caused by simultaneous technological improvements in the 3 major imaging modalities. Finally, it is shown how self-referral may actually reduce costs by facilitating the transfer of care from the hospital and ER to the office
— id: 111664, year: 2009, vol: 19, page: 80, stat: Journal Article,

Natalizumab reduces multiple sclerosis severity: Analysis of patients from the AFFIRM and SENTINEL studies using the multiple sclerosis severity scale
Herbert, J; Kappos, L; Calabresi, P; Confavreux, C; Galetta, S; Giovannoni, G; Havrdova, E; Hutchinson, M; Lublin, F; Miller, D; O'Connor, PW; Phillips, J; Polman, C; Radue, EW; Rudick, R; Stuart, W; Wajgt, A; Weinstock-Guttman, B; Wynn, D; Bacon, J; Kister, I; Pace, A; Panzara, M
2008 ;70(11):A212-A212, Neurology
— id: 111998, year: 2008, vol: 70, page: A212, stat: Journal Article,

On radiology referral versus specialist referral
Hutchinson, M; Greenberg, JO
2008 MAY ;247(2):593-593, Radiology
— id: 78718, year: 2008, vol: 247, page: 593, stat: Journal Article,

Detection of Parkinson's disease by MRI: Spin-lattice distribution imaging
Hutchinson, Michael; Raff, Ulrich
2008 Oct 30;23(14):1991-1997, Movement disorders
We have developed an advanced MRI technique for detecting Parkinson's Disease (PD) which depends on an image constructed as a ratio of images from two inversion recovery sequences (one generating a white matter suppressed image, the other a gray matter suppressed image). This technique was designed to be exceptionally sensitive to the spin-lattice relaxation time T(1). It was refined with the introduction of segmentation analysis and given the acronym SIRRIM (Segmented Inversion Recovery Ratio Imaging). Our objectives are, first, to reinvestigate the sensitivity of MRI with new subjects and second, to investigate whether a new form of analysis, using the gray level distribution of signal in the image, may prove more sensitive than SIRRIM. For each subject, a ratio image was constructed (WMS/GMS) and the substantia nigra segmented out to be displayed as an isolated structure. From the segmented image a measure of disease severity, the Radiological Index (RI), was calculated for each subject. Since the pixel value in the ratio image is a strong function of the local T(1) relaxation time, the distribution of pixel values gives the distribution of spin-lattice relaxation times. A refinement in the analysis is introduced, the Spin-Lattice Distribution Index (SI), which is an automated measure of MRI signal in the Substantia Nigra pars compacta (SN(C)). Both RI and SI were calculated for each of 24 subjects, 12 patients and 12 controls. The SI may further improve the separation of patient and control groups, and may therefore be more sensitive than the RI. Unlike the RI it is completely automatic and circumvents two of the limitations of the RI. The work is consistent with the proposition that MRI, when properly configured, is a highly sensitive marker for PD
— id: 97779, year: 2008, vol: 23, page: 1991, stat: Journal Article,

Impact of natalizumab on multiple sclerosis severity: analysis of patients and subgroups from the AFFIRM study using the Multiple Sclerosis Severity Scale
Herbert, J; Kappos, L; Giovannoni, G; Havrdova, E; Hutchinson, M; Lublin, F; Miller, D; O'Connor, P; Phillips, JT; Polman, CH; Wajgt, A; Bacon, J; Kister, I; Pace, A; Panzara, M
2007 OCT ;13(2):S169-S170, Multiple sclerosis
— id: 75898, year: 2007, vol: 13, page: S169, stat: Journal Article,

On false negatives in MRI studies of Parkinson disease
Hutchinson, M; Raff, U
2007 JUL 30 ;22(10):1521-1522, Movement disorders
— id: 73976, year: 2007, vol: 22, page: 1521, stat: Journal Article,

GDNF in Parkinson disease: An object lesson in the tyranny of type II
Hutchinson, Michael; Gurney, Susan; Newson, Roger
2007 Jul 30;163(2):190-192, Journal of neuroscience methods
Type II errors may be having a significant impact on drug discovery. This is of particular importance in the clinical neurosciences, where endpoints are often subjective scores of disability rather than unequivocal events such as survival. Here we examine a recently published study [Lang AE, Gill S, Patel NK, et al. Randomized controlled study of intraputamenal glial cell-derived neurotrophic factor infusion in Parkinson disease. Ann Neurol 2006;59:459-66] in an area of immense importance to neuroscience. This small study found no detectable clinical benefit from infused intraputamenal GDNF as a treatment for Parkinson disease. However the standard deviation of the accrued data turned out to be considerably higher than had been anticipated in the power analysis performed prior to the study. In order to determine what impact, if any, this had on the conclusions that could be drawn, the actual data were analyzed by means of both the t-test and the rank-based Somers'D. The study was found to be underpowered and thus incapable of ruling out a large effect of GDNF on Parkinson disease. It therefore does not contradict the large effects seen in previous open-label studies
— id: 71872, year: 2007, vol: 163, page: 190, stat: Journal Article,

Chaos theory and the treatment of refractory status epilepticus: Who benefits from prolonged anesthesia, and is there a better way?
Hutchinson, Michael; Swanson, Phillip D
2007 ;68(2):439-441, Medical hypotheses
Refractory status epilepticus (SE) is a condition of continuous seizure activity in which there is a regular, rapid, succession of spike discharges in the brain. It is incompatible with normal consciousness and is associated with an extremely high morbidity and mortality. Prior to 1990, prevailing opinion held that a brief period of anesthesia (up to two weeks) was to be recommended, but that if SE persisted this was a sign of irreversible brain damage. Therefore support of the patient in SE was not recommended beyond two weeks. On the basis of the theoretical constructs of chaos theory we hypothesized that, for selected cases, anesthesia should be continued indefinitely until the SE resolved. This became the standard of care at the University of Washington and at other institutions. After several years, the accumulating evidence lends support for this hypothesis and we are now able to propose which patients will benefit from such therapy. It is hypothesized that only those patients for whom there is no underlying brain disease, beyond epilepsy, are likely to benefit. Secondly, chaos theory suggests that a strong perturbation will cause a rapid transition from the stable attractor of SE to the stable attractor representing normal consciousness. In certain ways, SE is analogous to ventricular tachycardia, where the cardiac muscle has an abnormally fast rhythm incompatible with proper cardiac function. Therefore the second hypothesis is that a brain perturbation, analogous to defibrillation, may be even more useful than anesthesia in refractory SE
— id: 71333, year: 2007, vol: 68, page: 439, stat: Journal Article,

On the use of clusters to determine environmental influence on disease
Hutchinson, M; Lebedev, S
2005 FEB ;62(2):331-331, Archives of neurology
— id: 48695, year: 2005, vol: 62, page: 331, stat: Journal Article,

Genetic basis of common diseases: The general theory of Mendelian recessive genetics
Hutchinson, Michael; Spanaki, Cleanthe; Lebedev, Sergey; Plaitakis, Andreas
2005 ;65(2):282-286, Medical hypotheses
Common diseases tend to appear sporadically, i.e., they appear in an individual who has no first or second degree relatives with the disease. Yet diseases are often associated with a slight but definite increase in risk to the children of an affected individual. This weak pattern of inheritability cannot be explained by conventional interpretations of Mendelian genetics, and it is therefore commonly held that there is 'incomplete penetrance' of a gene, or that there are polygenic, or multifactorial modes of inheritance. However, such arguments are heuristic and lack predictive power. Here, we explore the possibility that 'incomplete penetrance' means the existence of a second, disease-related, gene. By examining in detail a specific common condition, Parkinson's disease (PD), we show that the sporadic form of the disease can be fully explained by a compact fully penetrant genotype involving an interaction between two, and only two, genes. In this model, therefore PD is fundamentally genetic. Our digenic model is complementary to Mendelian recessive genetics, but taken together with the latter forms a complete description for recessive genetics on one chromosome. It explains the slight increase in risk to the children if one parent has sporadic PD, and makes strict predictions where both parents coincidentally have sporadic PD. These predictions were verified in two large and carefully selected kindred, where the data also argue against other genetic models, including oligogenic and polygenic schemes. Since the inheritance patterns of sporadic PD are reminiscent of what is seen in many common diseases, it is plausible that similar genetic forms could apply to other diseases. Seen in this light, diseases wash in and out of every family, so that in a sense, over time every human family is equally at risk for most diseases
— id: 56053, year: 2005, vol: 65, page: 282, stat: Journal Article,

Cognitive, psychiatric and motor response to galantamine in Parkinson's disease with dementia
Aarsland, D; Hutchinson, M; Larsen, JP
2003 OCT ;18(10):937-941, International journal of geriatric psychiatry
Background Cholinesterase inhibitors with additional nicotinic activity, such as galantamine, may be useful in PD patients with dementia (PDD) since stimulation of nicotinic receptors may prevent the down-regualation that is likely to accompany cholinesterase inhibition and facilitate dopamine release in the striatum. Methods Sixteen PDD patients (six female) with onset of cognitive impairment after at least one year with parkinsonism participated in this open-label trial of galantamine. Cognitive, psychiatric, and motor symptoms were assessed before and after 8 weeks of treatment with galantamine using unstructured clinical assessment as well as rating scales including the Mini-Mental State Examination (MMSE), clock drawing test, verbal fluency and selected items from the Neuropsychiatric Inventory (NPI). Results Age (mean, SD) was 75.6 (5.2) years, duration of PD 13.4 (5.9), duration of dementia 2.1 (1.7) years, Hoehn and Yahr score was 3.8 (0.8) and baseline MMSE score was 17.7 (63). Side-effects caused discontinuation in three patients, but were rare and mild in the remaining 13. Improvement of global mental symptoms was noted in eight patients, whereas worsening was reported in four. Hallucinations improved in seven of the nine patients with hallucinations before treatment. Parkinsonism improved in six patients, but a mild worsening of tremor was noted in three. Clock-drawing improved (p = 0.016), and trends towards improvement on MMSE (p = 0.09) and verbal fluency (p = 0.16) were found. Conclusions Although controlled trials are needed, the findings suggest that galantamine is useful in patients with PDD.
— id: 55504, year: 2003, vol: 18, page: 937, stat: Journal Article,

MRI correlates of pathology in parkinsonism: segmented inversion recovery ratio imaging (SIRRIM)
Hutchinson, Michael; Raff, Ulrich; Lebedev, Sergey
2003 Dec;20(3):1899-1902, Neuroimage
The two commonest, clinically well-defined, forms of parkinsonism are idiopathic Parkinson's disease (PD) and progressive supranuclear palsy (PSP). Both involve, inter alia, pathological changes in the substantia nigra pars compacta (SN(C)). In PD there is neuronal loss with associated Lewy body pathology and microglial activation. Three morphological features have been identified [Brain 114 (1991), 2283; Greenfield's Neuropathology 2 (1997), 289]. First, there is a gradient of pathological change such that the lateral segments are more affected than the medial. Second, there is thinning of the pigmented tissue, and third, there is a broadening of the overall structure in a dorsal-ventral direction, possibly caused by the migration of melanin-laden macrophages [Greenfield's Neuropathology 2 (1997), 289]. In contrast, PSP is characterized pathologically by intraneuronal neurofibrillary tangles. There are two morphological features in the SN(C) [Brain 114 (1991), 2283]. First, the gradient of pathological change is in the opposite direction to that of PD (i.e., the medial segments are more affected than the lateral). Second, there is atrophy. Any technique sensitive to neuropathology should be capable of detecting these features. We have previously reported on a new approach to detecting signal change in the substantia nigra in PD. This makes use of a ratio of images acquired by two distinct inversion recovery sequences [J. Neurol, Neurosurg. Psychiatry 67 (1999), 815; Am. J. Neuroradiol. 21 (2000) 697]. The prior work suggests that the technique is sensitive to, but not necessarily specific for, PD. We present here a preliminary report on an extension of the work. This is a semiautomated segmentation analysis that enables the substantia nigra to be displayed as an isolated structure. The technique is now given the acronym SIRRIM (segmented inversion recovery ratio imaging). In contrast to our earlier work, it allows for a more accurate assessment of the gross abnormalities. We report typical SIRRIM images of the SN(C). Images are shown for three subjects: a normal control, a patient with PD, and a 'disease control' (a patient with PSP). In these examples all three morphological features of PD, as well as both morphological features of PSP, have radiological correlates. These preliminary findings suggest that SIRRIM may be specific for both diseases
— id: 46068, year: 2003, vol: 20, page: 1899, stat: Journal Article,

The metabolic topography of essential blepharospasm: A focal dystonia with general implications [In Process Citation]
Hutchinson M; Nakamura T; Moeller JR; Antonini A; Belakhlef A; Dhawan V; Eidelberg D
2000 Sep 12;55(5):673-677, Neurology
OBJECTIVE: To determine the metabolic topography of essential blepharospasm (EB). BACKGROUND: EB is a cranial dystonia of unknown etiology and anatomic localization. The authors have used 18F-fluorodeoxyglucose (FDG) and PET with network analysis to identify distinctive patterns of regional metabolic abnormality associated with idiopathic torsion dystonia (ITD), as well as sleep induction during PET imaging to suppress involuntary movements, thereby reducing this potential confound in the analysis. METHODS: Six patients with EB and six normal volunteers were scanned with FDG-PET. Scans were performed twice: once in wakefulness and once following sleep induction. The authors used statistical parametric mapping to compare glucose metabolism between patients with EB and control subjects in each condition. They also quantified the expression of the previously identified ITD-related metabolic networks in each subject in both conditions. RESULTS: With active involuntary movements during wakefulness, the EB group exhibited hypermetabolism of the cerebellum and pons. With movement suppression during sleep, the EB group exhibited superior-medial frontal hypometabolism in a region associated with cortical control of eyelid movement. Network analysis demonstrated a specific metabolic covariance pattern associated with ITD was also expressed in the patients with EB in both the sleep and wake conditions. CONCLUSION: These findings suggest that the clinical manifestations of EB are associated with abnormal metabolic activity in the pons and cerebellum, whereas the functional substrate of the disorder may be associated with abnormalities in cortical eyelid control regions. Furthermore, ITD-related networks are expressed in patients with EB, suggesting a functional commonality between both forms of primary dystonia
— id: 11505, year: 2000, vol: 55, page: 673, stat: Journal Article,

Structural changes of the substantia nigra in Parkinson's disease as revealed by MR imaging
Hutchinson M; Raff U
2000 Apr;21(4):697-701, AJNR. American journal of neuroradiology
BACKGROUND AND PURPOSE: The possibility of using MR imaging as a sensitive marker of the structural changes in Parkinson's disease has been a long-sought goal. We describe a new method for imaging and quantifying the morphologic changes of the substantia nigra in Parkinson's disease and compare radiologic findings with clinical evaluation. METHODS: Using a combination of two MR imaging inversion-recovery pulse sequences, the substantia nigra was imaged in six patients with Parkinson's disease and six age-related control participants. A radiologic index was defined and used to quantify the signal changes that were observed in the patients. The radiologic index was compared with clinical scores obtained from the Unified Parkinson's Disease Rating Scale. RESULTS: The images showed loss of signal in a lateral-to-medial gradient in cases of Parkinson's disease, corresponding to the known neuropathologic pattern of degeneration. The radiologic index was highly correlated with the Unified Parkinson's Disease Rating Scale score, and there was no overlap in radiologic indices between the patient and the control groups (P < .00005). CONCLUSION: This study suggests that MR imaging is sensitive to structural changes in even the earliest cases of Parkinson's disease, thereby indicating the potential for detecting presymptomatic disease. Furthermore, a radiologic measure has been defined that correlates with the conventional clinical measure of disease severity. Therefore, MR imaging could prove to be a sensitive biological marker for objective staging of the disease
— id: 11734, year: 2000, vol: 21, page: 697, stat: Journal Article,

Quantitation of T2 lesion load in patients with multiple sclerosis: a novel semiautomated segmentation technique
Raff U; Rojas GM; Hutchinson M; Simon JH
2000 Apr;7(4):237-247, Academic radiology
RATIONALE AND OBJECTIVES: The authors designed a segmentation technique that requires only minimal operator input at the initial and final supervision stages of segmentation and has computer-driven segmentation as the primary determinant of lesion boundaries. The technique was applied to compute total T2-hyperintense lesion volumes in patients with multiple sclerosis (MS). A semi-automated segmentation technique is presented and shown to have a test-retest reliability of <5%. MATERIALS AND METHODS: The method used a single segmented section with MS lesions. A probabilistic neural net performed segmentation into four tissue classes after supervised training. This reference section was deconstructed into the entire set of possible 4 x 4-pixel subregions, which was used to segment all-brain sections in steps of 4 x 4-pixel, adjacent image blocks. Intra- and interimage variabilities were tested by using 3-mm-thick, T2-weighted, dual-echo, spin-echo MR images from five patients, each of whom was imaged twice on the same day. Five different reference sections and three temporally separated. training sessions involving the same reference section were used to test the segmentation technique. RESULTS: The coefficient of variation ranged from 0.013 to 0.068 (mean +/- standard deviation, 0.037 +/- 0.039) for results from five different reference sections for each brain and from 0.007 to 0.037 (mean, 0.027 +/- 0.021) for brains segmented with the same reference section on three temporally separated occasions. Test-retest (intra-imaging) reliability did not exceed 5% (except for a small lesion load of 1 cm3 in one patient). Interimaging differences were approximately 10%. CONCLUSION: The segmentation technique yielded intra-imaging variabilities (2%-3%, except for very small MS lesion loads) that compare favorably with previously published results. New repositioning techniques that minimize imaging-repeat imaging variability could make this approach attractive for resolving MS lesion detection problems
— id: 11753, year: 2000, vol: 7, page: 237, stat: Journal Article,

Parkinson's disease: a novel MRI method for determining structural changes in the substantia nigra
Hutchinson M; Raff U
1999 Dec;67(6):815-818, Journal of neurology neurosurgery & psychiatry
OBJECTIVES: To use MRI in a novel way to image and quantify the changes occurring in the substantia nigra in Parkinson's disease. METHODS: Six patients with idiopathic Parkinson's disease were compared with six age matched control subjects. The subjects were imaged using a combination of pulse sequences hypothesised to be sensitive to cell loss. RESULTS: The images showed patterns of change in patients with Parkinson's disease. Highly significant differences between the patients and control population were found (p<0.001). CONCLUSIONS: This methodology suggests the possibility of detecting presymptomatic disease in those judged to be at risk, and also in confirming the diagnosis in patients with early disease. Furthermore, the technique seems to hold promise as a means for staging the disease, and possibly differentiating other forms of parkinsonism
— id: 11930, year: 1999, vol: 67, page: 815, stat: Journal Article,

Task-specific deactivation patterns in functional magnetic resonance imaging
Hutchinson M; Schiffer W; Joseffer S; Liu A; Schlosser R; Dikshit S; Goldberg E; Brodie JD
1999 Dec;17(10):1427-1436, Magnetic resonance imaging
In general, image analysis of cognitive experiments using functional magnetic resonance imaging techniques has emphasized those regions of the brain where increases in signal intensity, with regard to the reference state, are associated with activation. Nevertheless, a number of recent papers have shown that there are areas of deactivation as well. In this study, we have used a univariate analysis and echo-planar functional magnetic resonance imaging to address the relationship of the reference state to the deactivations. We employed two dichotomous covert tasks, orthographic lexical retrieval and pure visual retrieval, to contrast with the reference state (baseline) of silent counting. Our analysis yielded extensive, task-specific landscapes of regional incremental and decremental responses. We have specifically demonstrated that the decremental responses are not due to activation in the reference state. We have also demonstrated that they are not an artifact of a specific part of the image analysis, and propose that they represent a physiological, task specific signal that should be considered an integral component of neural networks representing brain function
— id: 11891, year: 1999, vol: 17, page: 1427, stat: Journal Article,

Functional magnetic resonance imaging of human brain activity in a verbal fluency task
Schlosser R; Hutchinson M; Joseffer S; Rusinek H; Saarimaki A; Stevenson J; Dewey SL; Brodie JD
1998 Apr;64(4):492-498, Journal of neurology neurosurgery & psychiatry
OBJECTIVES: Functional MRI (fMRI) holds the promise of non-invasive mapping of human brain function in both health and disease. Yet its sensitivity and reliability for mapping higher cognitive function are still being determined. Using verbal fluency as a task, the objective was to ascertain the consistency of fMRI on a conventional scanner for determining the anatomic substrate of language between subjects and between sexes. Comparison was made with previous PET studies. METHODS: Using a 1.5 Tesla magnet and an echoplanar pulse sequence, whole brain fMRI was obtained from 12 normal right handed subjects (6 males and 6 females) as they performed a verbal fluency task. RESULTS: A broadly consistent pattern of response was seen across subjects. Areas showing activation changes included the left prefrontal cortex and right cerebellum, in agreement with previous PET 15O-H2O studies. In addition, significantly decreased responses were seen in the posterior cingulate and over an extensive area of mesial and dorsolateral parietal and superior temporal cortices. The male cohort showed a slight asymmetry of parietal deactivation, with more involvement on the right, whereas the female cohort showed a small region of activation in the right orbitofrontal cortex. There were individual task related regional changes in all 12 subjects with the area showing the most significant change being the left prefrontal cortex in all cases. CONCLUSIONS: Magnetic resonance scanners of conventional field strength can provide functional brain mapping data with a sensitivity at least that of PET. Activation was seen in left prefrontal and right cerebellar regions, as with PET. However, decremental responses were seen over a much larger area of the posterior cortex than had been anticipated by prior studies. The ability to see a response in each subject individually suggests that fMRI may be useful in the preinterventional mapping of pathological states, and offers a non-invasive alternative to the Wada test for assessment of hemispheric dominance. There were no gross differences in the pattern of activation between male and female subjects
— id: 57250, year: 1998, vol: 64, page: 492, stat: Journal Article,

Segmentation analysis in functional MRI: activation sensitivity and gray-matter specificity of RARE and FLASH
Hutchinson M; Rusinek H; Nenov VI; Feinberg DA; Johnson G
1997 Mar-Apr;7(2):361-364, Journal of magnetic resonance imaging
Brain activation is accompanied by local decreases in vascular deoxyhemoglobin. Theoretically, gradient-echo and spin-echo sequences show similar sensitivity to capillary deoxyhemoglobin, but spin-echo sequences should be less sensitive to venous deoxyhemoglobin. This is an important distinction in the context of cortical localization. We report herein a direct experimental comparison of a gradient-echo sequence (fast low-angle shot [FLASH]) with a spin-echo sequence (rapid acquisition with relaxation enhancement [RARE]) for functional MRI (fMRI) in seven subjects undergoing visual stimulation. A Student t test analysis was used to locate areas of significant activation, and then computerized image segmentation was performed to determine the type of activated tissue. Contrary to previous reports, both sequences proved equally sensitive to overall activation. RARE activation, however, was more specific for gray matter, as suggested by prior theoretical models
— id: 7167, year: 1997, vol: 7, page: 361, stat: Journal Article,

Cholinesterase inhibition in Parkinson's disease
Hutchinson M; Fazzini E
1996 Sep;61(3):324-325, Journal of neurology neurosurgery & psychiatry
— id: 18382, year: 1996, vol: 61, page: 324, stat: Journal Article,