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Objective: Magnetic resonance imaging (MRI) is essential for multiple sclerosis diagnostics but is conventionally not specific to demyelination. Myelin imaging is often hampered by long scanning times, complex postprocessing, or lack of clinical approval. This study aimed to assess the specificity, robustness, and clinical value of Rapid Estimation of Myelin for Diagnostic Imaging, a new myelin imaging technique based on time-efficient simultaneous T 1 /T 2 relaxometry and proton density mapping in multiple sclerosis., Methods: Rapid myelin imaging was applied using 3T MRI ex vivo in 3 multiple sclerosis brain samples and in vivo in a prospective cohort of 71 multiple sclerosis patients and 21 age/sex-matched healthy controls, with scan-rescan repeatability in a subcohort. Disability in patients was assessed by the Expanded Disability Status Scale and the Symbol Digit Modalities Test at baseline and 2-year follow-up., Results: Rapid myelin imaging correlated with myelin-related stains (proteolipid protein immunostaining and Luxol fast blue) and demonstrated good precision. Multiple sclerosis patients had, relative to controls, lower normalized whole-brain and normal-appearing white matter myelin fractions, which correlated with baseline cognitive and physical disability. Longitudinally, these myelin fractions correlated with follow-up physical disability, even with correction for baseline disability., Interpretation: Rapid Estimation of Myelin for Diagnostic Imaging provides robust myelin quantification that detects diffuse demyelination in normal-appearing tissue in multiple sclerosis, which is associated with both cognitive and clinical disability. Because the technique is fast, with automatic postprocessing and US Food and Drug Administration/CE clinical approval, it can be a clinically feasible biomarker that may be suitable to monitor myelin dynamics and evaluate treatments aiming at remyelination. ANN NEUROL 2020;87:710-724., (© 2020 The Authors. Annals of Neurology published by Wiley Periodicals, Inc. on behalf of American Neurological Association.)

Objective: To compare corpus callosum area (CCA) and corpus callosum index (CCI) in terms of feasibility and their performance as biomarkers for cognitive and physical disability in multiple sclerosis (MS). A secondary aim was to compare these two methods with volumetric measurements., Methods: This study was based on a cohort of 37 MS patients and a group of age- and gender-matched healthy controls. Physical disability was assessed with the expanded disability status scale (EDSS) and cognitive disability with the symbol digit modalities test (SDMT). CCA and CCI were assessed on midsagittal brain MRI by 3 raters with varying radiological experience. Volumes of the brain, gray and white matter, corpus callosum, and MS lesions were acquired with Freesurfer and Lesion Segmentation Toolbox for Statistical Parametric Mapping., Results: CCA and CCI were obtained within seconds with excellent intra- and inter-rater agreement, and outperformed volumetric measurements. CCA had the strongest correlations with both SDMT (r = .82, P < .001) and EDSS (r = -.56, P < .001), and the highest accuracy in differentiating patients from controls (95%) and relapse-remitting MS from progressive forms of MS (77%). CCI performed less well (r = .73, P < .001; r = -.45, P < .001; 94%; 71%). CCA also outperformed the volumetric measurements in these regards., Conclusions: CCA is a time-effective and robust biomarker that has stronger correlations with both EDSS and information processing speed than CCI and volumetric measurements that are commonly used as outcome measures in MS research and clinical trials., (Copyright © 2015 by the American Society of Neuroimaging.)

With increasing availability of magnetic resonance imaging (MRI), there is also an increase in incidental abnormal findings. MRI findings suggestive of multiple sclerosis in persons without typical multiple sclerosis symptoms and with normal neurological findings are defined as radiologically isolated syndrome (RIS). Half of the persons with RIS have their initial MRI because of headache, and some have a subclinical cognitive impairment similar to that seen in multiple sclerosis. Radiological measurements also show a similarity between RIS and multiple sclerosis. Approximately two-thirds of persons with RIS show radiological progression and one-third develop neurological symptoms during mean follow-up times of up to five years. Cervical cord lesions are important predictors of clinical conversion. Management has to be individualised, but initiation of disease modifying therapy is controversial and not recommended outside of clinical trials since its effects have not been studied in RIS. Future studies should try to establish the prevalence and long-term prognosis of RIS, its impact on quality of life, and define the role of disease modifying therapy in RIS.

Introduction: Multiple sclerosis (MS) has a variable progression with an early onset of atrophy. Individual longitudinal radiological evaluations (over decades) are difficult to perform due to the limited availability of magnetic resonance imaging (MRI) in the past, patients lost in follow-up, and the continuous updating of scanners. We studied a cohort with widespread disease duration at baseline. The observed individual atrophy rates over time of 10 years represented four decades of disease span., Methods: Thirty-seven MS patients (age range 24-65 years with disease duration 1-33 years) were consecutively selected and evaluated with MRI at baseline 1995 and in 1996. They were followed up for a decade (mean of 9.25 years, range 7.3-10 years) up to 2003-2005. Brain parenchymal volume and volumes of the supratentorial ventricles were analyzed with semi-automated volumetric measurements at three time points (1995, 1996, and 2003-2005)., Results: Volumetric differences were found over shorter periods of time (1-7 months); however, differences vanished by the end of follow-up. A uniform longitudinal decrease in brain volume and increase in ventricle volumes were found. Frontal horn width (1D) correlated strongest to 3D measures. No statistical differences of atrophy rates between MS courses were found. Supratentorial ventricular volumes were associated with disability and this association persisted during follow-up., Conclusion: Despite variable clinical courses, the degenerative effects of MS progression expressed in brain atrophy seem to uniformly progress over longer periods of time. These volumetric changes can be detected using 1D and 2D measurements performed on a routine PACS workstation.

Objectives: Analysis of and understanding the utilization patterns of diagnostic imaging technologies is important for planning health systems especially in middle- and low-income countries. Almost all published studies have been focused on utilization trends or utilization rates of magnetic resonance imaging (MRI) over time and little has been published about utilization patterns of MRI. This study aims to identify and describe the utilization pattern of MRI in Iran., Methods: Data was collected from referrals and MRI reports of the population covered by one of the largest insurance organizations (Social Security Organization [SSO]) with more than 27 million beneficiaries in the Country. We focused on patients who had undergone an MRI examination during 1 month (October 13 to November 12), 2005. The data collected consisted of 1,656 referrals for MR imaging and 1,547 MRI reports., Results: No clear association was found between the number of referrals per 100,000 population and the number of MRI machines per 100,000 population (r = 0.30; p = .13). Neurosurgeons, orthopedists, and neurologists contributed to more than 88 percent of MRI utilization. The Spinal column (55 percent), brain (25.5 percent), and knee (11.0 percent) were the most common parts of the body scanned by MRI., Conclusions: Having identified some of the most frequent users of MRI technology, any plan for modifying or improving MRI use should focus mainly on these specialties. International evidence on using the technology for examining brain and spine indicate that MRI is mainly used in diagnosing the central nervous system (CNS) diseases.

Objectives: The aim of this article is to describe the diffusion of magnetic resonance imaging (MRI) in Iran, including regional variations during the period of 1990 to 2005 and international comparisons., Methods: Data on the diffusion of MRI were obtained from the Medical Equipment Office of the Ministry of Health (MOH) and, using self-administered questionnaires, from forty-one universities specializing in medical sciences. Data were gathered from the year of first purchase up to mid-2005. Information for international comparisons was obtained from the Organization for Economic Cooperation and Development health data of 2006., Results: Iran purchased its first MRI unit in 1990. Since then, the number of MRI units has increased remarkably. The diffusion curve of MRI in Iran follows an S-shaped curve with a very slow speed in the period of 1991-95. Accelerated adoption occurred later coinciding with a significant influence from the private sector, especially from 1999. Iran had ninety-three MRI units in 2005, and the number of MRI units per million in the population was 1.36., Conclusions: The number of MRI units in provinces is not in direct proportion to the number of their inhabitants. Rational adoption and equitable diffusion of MRI may require the MOH and regulatory bodies to improve their ability in health technology assessment and integrate it into the policy making regarding adoption, diffusion, and utilization of health technologies.

Background and Purpose: Evidence of brain gadolinium retention has affected gadolinium‐based contrast agent usage. It is, however, unclear to what extent macrocyclic agents are retained and whether their in vivo detection may necessitate nonconventional MRI. Magnetization transfer (MT) could prove suitable to detect gadolinium‐related signal changes since dechelated gadolinium ions bind to macromolecules. Therefore, this study aimed to investigate associations of prior gadolinium administrations with MT and T1 signal abnormalities. Methods: A cohort of 23 persons with multiple sclerosis (MS) (18 females, 5 males, 57 ± 8.0 years) with multiple past gadolinium administrations (median 6, range 3‐12) and 23 age‐ and sex‐matched healthy controls underwent 1.5 Tesla MRI with MT, T1‐weighted 2‐dimensional spin echo, and T1‐weighted 3‐dimensional gradient echo. The signal intensity index was assessed by MRI in gadolinium retention predilection sites. Results: There were dose‐dependent associations of the globus pallidus signal on gradient echo (r =.55, p <.001) and spin echo (r =.38, p =.013) T1‐weighted imaging, but not on MT. Relative to controls, MS patients had higher signal intensity index in the dentate nucleus on T1‐weighted gradient echo (1.037 ± 0.040 vs. 1.016 ± 0.023, p =.04) with a similar trend in the globus pallidus on T1‐weighted spin echo (1.091 ± 0.034 vs. 1.076 ± 0.014, p =.06). MT detected no group differences. Conclusions: Conventional T1‐weighted imaging provided dose‐dependent associations with gadolinium administrations in MS, while these could not be detected with 2‐dimensional MT. Future studies could explore newer MT techniques like 3D and inhomogenous MT. Notably, these associations were identified with conventional MRI even though most patients had not received gadolinium administrations in the preceding 9 years, suggestive of long‐term retention. [ABSTRACT FROM AUTHOR]

With increasing availability of magnetic resonance imaging (MRI), there is also an increase in incidental abnormal findings. MRI findings suggestive of multiple sclerosis in persons without typical multiple sclerosis symptoms and with normal neurological findings are defined as radiologically isolated syndrome (RIS). Half of the persons with RIS have their initial MRI because of headache, and some have a subclinical cognitive impairment similar to that seen in multiple sclerosis. Radiological measurements also show a similarity between RIS and multiple sclerosis. Approximately two-thirds of persons with RIS show radiological progression and one-third develop neurological symptoms during mean follow-up times of up to five years. Cervical cord lesions are important predictors of clinical conversion. Management has to be individualised, but initiation of disease modifying therapy is controversial and not recommended outside of clinical trials since its effects have not been studied in RIS. Future studies should try to establish the prevalence and long-term prognosis of RIS, its impact on quality of life, and define the role of disease modifying therapy in RIS. [ABSTRACT FROM AUTHOR]

Objective: Uncontrolled proliferation of health technologies (HT) is one contributor to the increasing pressure on health systems to adopt new technologies. With limited resources, policy-makers encounter difficulties in fulfilling their responsibility to meet the healthcare needs of the population. The aim of this study is to explore how policy-makers' reason about the diffusion and utilization of health technologies in Iran using magnetic resonance imaging (MRI) and interferon beta as tracers.Method: This qualitative exploration complements quantitative data generated in a research project investigating the diffusion and utilization of MRI and interferon beta in Iran. Qualitative semi-structured interviews were conducted with 13 informants in different positions and levels of authority in the Ministry of Health (MOH), University of Medical Sciences, Health Insurance Organizations, and Parliament. The data was analysed using the framework approach.Findings: Although policy-makers appeared to be positive to health technology assessment (HTA), the processes of policy-making described by the interviewees did not seem to be based on a full understanding of this (discipline). Several obstacles to applying knowledge about HT and HTA were described. The current official plan for MRI adoption and diffusion in the country was said not to be followed, and no such plan was described for interferon beta. Instead, market forces such as advertising, and physician and consumer demand, appear to have strong influence on HT diffusion and use. Dual practice may have increased the induced demand and also reduced the supervision of the private sector by the MOH.Conclusion: Management instability and lack of coordination in the MOH were found to be important obstacles to accumulation of knowledge and experience which, in turn, could have led to suboptimal managerial and policy-making processes. Furthermore marketing should be controlled in order to avoid creating unnecessary patient demands and negative influences on physicians' behavior. [ABSTRACT FROM AUTHOR]

Abstract: For over a decade, four immunomodulatory therapies have been available for the treatment of relapsing remitting multiple sclerosis. However, few direct comparative data were available to facilitate the choice of treatment. This choice has been influenced by the perception that interferon-β preparations have greater efficacy than glatiramer acetate, due to apparently more rapid and robust reduction of gadolinium-enhancing lesions seen on magnetic resonance imaging in the pivotal trials of these agents. This situation has changed in the last year, with the outcomes of three randomised clinical trials comparing the efficacy and safety of glatiramer acetate with that of a high-dose interferon-β in relapsing remitting multiple sclerosis. These are the REGARD, BEYOND and BECOME trials. In the REGARD trial, 764 patients were randomised to treatment with either interferon-β 1a sc 44 μg or glatiramer acetate for 96 weeks; no significant difference in the time to first relapse was observed. The largest of the three comparative studies, the BEYOND trial, compared treatment with interferon-β 1b sc 500 μg, interferon-β 1b sc 250 μg or glatiramer acetate for two years in 2,244 patients. The hazard ratio for multiple relapses was close to unity for comparisons between all groups, indicating equivalent efficacy in all three treatment arms. Relapse rates (around 0.3 relapses/year) in all these studies were much lower than anticipated and lower than those reported a decade previously in the pivotal trials of βb-interferons and glatiramer acetate. No unexpected safety issues were identified in any of these studies. The completion of these direct comparative studies has considerably enriched the clinical evidence database by contributing large numbers of patients. This provides an invaluable contribution for helping the physician make an informed choice about treatment. The results of the direct comparative studies provide evidence that glatiramer acetate and high-dose interferon-β preparations have comparable clinical efficacy. [Copyright &y& Elsevier]