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Myelin development in visual scene-network tracts beyond late childhood: A multimethod neuroimaging study [article]

Tobias W. Meissner, Erhan Genç, Burkhard Mädler, Sarah Weigelt
2019 bioRxiv   pre-print
., 2018; Meissner, Genç, Mädler, & Weigelt, 2019) . However, scene-network specific data has not been analyzed until now.  ... 
doi:10.1101/662809 fatcat:6e2p357cbrasbi7pkczyfefpsi

Myelination of major white matter tracts continues beyond childhood — combining tractography and myelin water imaging [article]

Tobias W Meissner, Erhan Genç, Burkhard Mädler, Sarah Weigelt
2019 bioRxiv   pre-print
Axonal myelination is a key white matter maturation process as it increases conduction velocity, synchrony, and reliability. While diffusion tensor imaging (DTI) is sensitive to myelination, it is also sensitive to unrelated microstructural properties, thus hindering straightforward interpretations. Myelin water imaging (MWI) provides a more reliable and direct in vivo measure of myelination. Although early histological studies show protracted myelination from childhood to adulthood, reliable
more » ... act-specific in vivo evidence from MWI is still lacking. Here, we combine MWI and DTI tractography to investigate myelination in middle childhood, late childhood, and adulthood in 18 major white matter tracts. In the vast majority of major white matter tracts, myelin water fraction continued to increase beyond late childhood. Our study provides first in vivo evidence for protracted myelination beyond late childhood.
doi:10.1101/622233 fatcat:qaqzv7cy5vaabe6c4lhwf7wfbu

Extracting skeletal muscle fiber fields from noisy diffusion tensor data

David I.W. Levin, Benjamin Gilles, Burkhard Mädler, Dinesh K. Pai
2011 Medical Image Analysis  
Diffusion Tensor Imaging (DTI) allows the non-invasive study of muscle fiber architecture but musculoskeletal DTI suffers from low signal-to-noise ratio. Noise in the computed tensor fields can lead to poorly reconstructed muscle fiber fields. This paper describes an algorithm for producing denoised muscle fiber fields from noisy diffusion tensor data as well as its preliminary validation. The algorithm computes a denoised vector field by finding the components of its Helmholtz-Hodge
more » ... on that optimally match the diffusion tensor field. A key feature of the algorithm is that it performs denoising of the vector field simultaneously with its extraction from the noisy tensor field. This allows the vector field reconstruction to be constrained by the architectural properties of skeletal muscles. When compared to primary eigenvector fields extracted from noisy synthetic data, the denoised vector fields show greater similarity to the ground truth for signal-to-noise ratios ranging from 20 to 5. Similarity greater than 0.9 (in terms of fiber direction) is observed for all signal-to-noise ratios, for smoothing parameter values greater than or equal to 10 (larger values yield more smoothing). Fiber architectures were computed from human forearm diffusion tensor data using extracted primary eigenvectors and the denoised data. Qualitative comparison of the fiber fields showed that the denoised fields were anatomically more plausible than the noisy fields. From the results of experiments using both synthetic and real MR datasets we conclude that the denoising algorithm produces anatomically plausible fiber architectures from diffusion tensor images with a wide range of signal-to-noise ratios.
doi:10.1016/j.media.2011.01.005 pmid:21345716 fatcat:cel7np7nizazddjioshdwgse5a

Rapid Effects of Deep Brain Stimulation for Treatment-Resistant Major Depression

Thomas E. Schlaepfer, Bettina H. Bewernick, Sarah Kayser, Burkhard Mädler, Volker A. Coenen
2013 Biological Psychiatry  
Treatment-resistant major depressive disorder is a prevalent and debilitating condition. Deep brain stimulation to different targets has been proposed as a putative treatment. Methods: In this pilot study, we assessed safety and efficacy of deep brain stimulation to the supero-lateral branch of the medial forebrain bundle in seven patients with highly refractory depression. Primary outcome criterion was severity of treatment-resistant major depressive disorder as assessed with the
more » ... erg Depression Rating Scale. General psychopathologic parameters, social functioning, and tolerance were assessed with standardized scales, the Global Assessment of Functioning scale, quality of life (Short-Form Health Survey Questionnaire), and neuropsychological tests. Results: All patients showed strikingly similar intraoperative effects of increased appetitive motivation. Six patients attained the response criterion; response was rapid-mean Montgomery-Åsberg Depression Rating Scale of the whole sample was reduced by Ͼ50% at day 7 after onset of stimulation. At last observation (12-33 weeks), six patients were responders; among them, four were classified as remitters. Social functioning (Global Assessment of Functioning) improved in the sample as a whole from serious to mild impairment. Mean stimulation current was 2.86 mA; all side effects (strabismus at higher stimulation current, one small intracranial bleeding during surgery, infection at the implanted pulse generator site) could be resolved at short term. Conclusions: These preliminary findings suggest that bilateral stimulation of the supero-lateral branch of the medial forebrain bundle may significantly reduce symptoms in treatment-resistant major depressive disorder. Onset of antidepressant efficacy was rapid (days), and a higher proportion of the population responded at lower stimulation intensities than observed in previous studies.
doi:10.1016/j.biopsych.2013.01.034 pmid:23562618 fatcat:aj3pp3orpzgtjminwiqobvo4xy

Determination of Orientational Order Parameters from 2H NMR Spectra of Magnetically Partially Oriented Lipid Bilayers

Hartmut Schäfer, Burkhard Mädler, Edward Sternin
1998 Biophysical Journal  
The partial orientation of multilamellar vesicles (MLVs) in high magnetic fields is known to affect the shape of 2 H NMR spectra. There are numerical methods for extracting either the orientational order parameters of lipid molecules for a random distribution of domain orientations in the sample, or the distribution of orientations for a known set of spectral anisotropies. A first attempt at determining the orientational order parameters in the presence of an unknown nonrandom distribution of
more » ... ientations is presented. The numerical method is based on the Tikhonov regularization algorithm. It is tested using simulated partially oriented spectra. An experimental spectrum of a phospholipid-ether mixture in water is analyzed as an example. The experimental spectrum is consistent with an ellipsoidal shape of MLVs with a ratio of semiaxes of ϳ3.4.
doi:10.1016/s0006-3495(98)74025-1 pmid:9533713 pmcid:PMC1302581 fatcat:33uwhwnm7jdc5kafqwsf3o43mi

Stem Cell Transplantation for Adult-Onset Krabbe Disease: Report of a Case [chapter]

Madeleine E. Sharp, Cornelia Laule, Stephen Nantel, Burkhard Mädler, Ritu B. Aul, Samuel Yip, Sandra Sirrs
2012 JIMD Reports  
Krabbe disease is an autosomal recessive demyelinating lysosomal storage disorder caused by a deficiency of galactocerebrosidase. The adult-onset variant is very rare. Hematopoietic stem cell transplantation (HSCT) is reported to be successful in treating infants with Krabbe disease prior to the onset of symptoms, but there are no reported cases of its use for adult-onset disease. We report the first follow-up data for a patient with adult-onset Krabbe disease who underwent HSCT at age 41, 16
more » ... ars after the onset of symptoms. HSCT resulted in a sustained normalization of peripheral GALC enzyme activity, halted the progression of symptoms at 24 months post-allograft, and led to improvements in gait and balance. Serial imaging also confirmed that no significant progression of demyelination has occurred. Although long-term follow-up is needed to confirm the effects of HSCT, our 24-month results suggest that HSCT is a viable therapeutic option for symptomatic patients with adult-onset Krabbe disease.
doi:10.1007/8904_2012_203 pmid:23430802 pmcid:PMC3755578 fatcat:6yh7mxiqfrf2ja6ft5kxc42sdq

Myelin water imaging from multi-echo T2 MR relaxometry data using a joint sparsity constraint

Martijn Nagtegaal, Peter Koken, Thomas Amthor, Jeroen de Bresser, Burkhard Mädler, Frans Vos, Mariya Doneva
2020 NeuroImage  
Burkhard M€ adler: Methodology, Validation, Investigation, Writing -review & editing. Frans Vos: Conceptualization, Writing -review & editing, Supervision, Funding acquisition.  ... 
doi:10.1016/j.neuroimage.2020.117014 pmid:32534123 fatcat:6ewiwriaw5eo3mzl4viepe53be

Value of quantitative magnetic resonance imaging T1-relaxometry in predicting contrast-enhancement in glioblastoma patients

Elke Hattingen, Andreas Müller, Alina Jurcoane, Burkhard Mädler, Philip Ditter, Hans Schild, Ulrich Herrlinger, Martin Glas, Sied Kebir
2017 OncoTarget  
The repetitive usage of gadolinium-based contrast agents (GBCA) is critical for magnetic resonance imaging (MRI) evaluation of tumor burden in glioblastoma patients. It is also a crucial tool for determination of radiographical response to treatment. GBCA injection, however, comes with a 2.4% rate of adverse events including life-threatening conditions such as nephrogenic systemic fibrosis (NSF). Moreover, GBCA have been shown to be deposited in brain tissue of patients even with an intact
more » ... -brain barrier (BBB). The present study explores quantitative T1 relaxometry as an alternative non-invasive imaging technique detection of tumor burden and determination of radiographical response. This technique exploits specific properties of brain tissue with impaired BBB. With a sensitivity and specificity as high as 86% and 80%, respectively, quantitative T1-relaxometry allows for detecting contrast-enhancing areas without the use of GBCA. This method could make it unnecessary to subject patients to the risk of adverse events associated with the use of GBCA. Nonetheless, a large-scale analysis is needed to confirm our findings. ABSTRACT Background: Gadolinium-based contrast agents (GBCA) are crucial for magnetic resonance imaging (MRI)-based evaluation of tumor burden in glioblastoma (GBM). Serious adverse events of GBCA, even though uncommon, and gadolinium deposition in brain tissue could be avoided by novel imaging techniques not requiring GBCA. Altered tissue composition in areas with impaired blood-brain-barrier also alters the quantified T1 relaxation time (qT1), so that qT1 analysis could replace GBCA-based MRI for the analysis of tumor burden and response. www.impactjournals.com/oncotarget/ Methods: As a part of a prospective pilot MRI-relaxometry trial, patients with newly-diagnosed GBM who relapsed under standard radiochemotherapy were selected for this study. At recurrence, subtraction of qT1 maps pre and post-GBCA application (ΔqT1 maps) was used to determine areas of contrast-enhancement. With the contrast-enhancement on ΔqT1 maps as reference, ROC analysis served to detect an optimal qT1 cut-off on qT1 maps prior to GBCA to distinguish between contrastenhancing tissue and its surroundings. Results: Ten patients were included. A qT1 value >2051ms predicted contrastenhancing tumor tissue with a sensitivity of 86% and specificity of 80% (AUC, 0.92; p<0.0001). Interestingly, qT1 prolongation >2051 ms that did not overlap with contrast-enhancing area transformed into contrast-enhancement later on (n=4). Conclusion: T1-relaxometry may be a useful technique to assess tissue properties equivalent to contrast-enhancement without the need for GBCA application. It may also provide information on sites with future tumor progression. Nonetheless, largescale studies are needed to confirm these findings.
doi:10.18632/oncotarget.18612 pmid:28881830 pmcid:PMC5581129 fatcat:esyb2ctxz5apzjofhwzcjrjqsu

A pilot study of magnetic resonance fingerprinting in Parkinson's disease

Vera Catharina Keil, Stilyana Peteva Bakoeva, Alina Jurcoane, Mariya Doneva, Thomas Amthor, Peter Koken, Burkhard Mädler, Guido Lüchters, Wolfgang Block, Ullrich Wüllner, Elke Hattingen
2020 NMR in Biomedicine  
Parkinson's disease (PD) affects more than six million people, but reliable MRI biomarkers with which to diagnose patients have not been established. Magnetic resonance fingerprinting (MRF) is a recent quantitative technique that can provide relaxometric maps from a single sequence. The purpose of this study is to assess the potential of MRF to identify PD in patients and their disease severity, as well as to evaluate comfort during MRF. Twenty-five PD patients and 25 matching controls
more » ... 3 T MRI, including an axial 2D spoiled gradient echo MRF sequence. T1 and T2 maps were generated by voxel-wise matching the measured MRF signal to a precomputed dictionary. All participants also received standard inversion recovery T1 and multi-echo T2 mapping. An ROI-based analysis of relaxation times was performed. Differences between patients and controls as well as techniques were determined by logistic regression, Spearman correlation and t-test. Patients were asked to estimate the subjective comfort of the MRF sequence. Both MRF-based T1 and T2 mapping discriminated patients from controls: T1 relaxation times differed most in cortical grey matter (PD 1337 ± 38 vs. control 1386 ± 37 ms; mean ± SD; P = .0001) and, in combination with normal-appearing white matter, enabled correct discrimination in 85.7% of cases (sensitivity 83.3%; specificity 88.0%; receiver-operating characteristic [ROC]) area under the curve [AUC] 0.87), while for T2 mapping the left putamen was the strongest classifier (40.54 ± 6.28 vs. 34.17 ± 4.96 ms; P = .0001), enabling differentiation of groups in 84.0% of all cases (sensitivity 80.0%; specificity 88.0%; ROC AUC 0.87). Relaxation time differences were not associated with disease severity. Standard mapping techniques generated significantly different relaxation time values and identified other structures as different between groups other than MRF. Twenty-three out of 25 PD patients preferred the MRF examination instead of a standard MRI. MRF-based mapping can identify PD patients with good comfort but needs further assessment regarding disease severity identification and its potential for comparability with standard mapping technique results.
doi:10.1002/nbm.4389 pmid:32783321 fatcat:lbo5kw377rcilfq2hibzqn5pmu

Exploiting the chemical shift displacement effect in the detection of glutamate and glutamine (Glx) with PRESS

Atiyah Yahya, Burkhard Mädler, B. Gino Fallone
2008 Journal of magnetic resonance (San Diego, Calif. 1997 : Print)  
doi:10.1016/j.jmr.2007.12.007 pmid:18249017 fatcat:uxehdejhgfdyti4dwpqpvnzw4m

Age-related microstructural differences quantified using myelin water imaging and advanced diffusion MRI

Thibo Billiet, Mathieu Vandenbulcke, Burkhard Mädler, Ronald Peeters, Thijs Dhollander, Hui Zhang, Sabine Deprez, Bea R.H. Van den Bergh, Stefan Sunaert, Louise Emsell
2015 Neurobiology of Aging  
2014 ,Madler,! et! al.,! 2008 (Coutu,!et!al.,!2014 ,Gong,!et!al.,!2014 ,Latt,!et!al.,!2013 .!Age%related!differences!in! AK! were! only! reported! in! (Coutu,! et! al.,!  ... 
doi:10.1016/j.neurobiolaging.2015.02.029 pmid:25840837 fatcat:yegd6kqdijfmfenkzovrf64mbe

Myelin Water Imaging Demonstrates Lower Brain Myelination in Children and Adolescents With Poor Reading Ability

Christian Beaulieu, Eugene Yip, Pauline B. Low, Burkhard Mädler, Catherine A. Lebel, Linda Siegel, Alex L. Mackay, Cornelia Laule
2020 Frontiers in Human Neuroscience  
Magnetic resonance imaging (MRI) provides a means to non-invasively investigate the neurological links with dyslexia, a learning disability that affects one's ability to read. Most previous brain MRI studies of dyslexia and reading skill have used structural or diffusion imaging to reveal regional brain abnormalities. However, volumetric and diffusion MRI lack specificity in their interpretation at the microstructural level. Myelin is a critical neural component for brain function and
more » ... , and as such, deficits in myelin may impact reading ability. MRI can estimate myelin using myelin water fraction (MWF) imaging, which is based on evaluation of the proportion of short T2 myelin-associated water from multi-exponential T2 relaxation analysis, but has not yet been applied to the study of reading or dyslexia. In this study, MWF MRI, intelligence, and reading assessments were acquired in 20 participants aged 10-18 years with a wide range of reading ability to investigate the relationship between reading ability and myelination. Group comparisons showed markedly lower MWF by 16-69% in poor readers relative to good readers in the left and right thalamus, as well as the left posterior limb of the internal capsule, left/right anterior limb of the internal capsule, left/right centrum semiovale, and splenium of the corpus callosum. MWF over the entire group also correlated positively with three different reading scores in the bilateral thalamus as well as white matter, including the splenium of the corpus callosum, left posterior limb of the internal capsule, left anterior limb of the internal capsule, and left centrum semiovale. MWF imaging from T2 relaxation suggests that myelination, particularly in the bilateral thalamus, splenium, and left hemisphere white matter, plays a role in reading abilities. Myelin water imaging thus provides a potentially valuable in vivo imaging tool for the study of dyslexia and its remediation.
doi:10.3389/fnhum.2020.568395 pmid:33192398 pmcid:PMC7596275 fatcat:ba7tixou5zdmfpgx2sthrhxdla

Tractography-assisted deep brain stimulation of the superolateral branch of the medial forebrain bundle (slMFB DBS) in major depression

Volker A. Coenen, Bastian Sajonz, Marco Reisert, Jan Bostroem, Bettina Bewernick, Horst Urbach, Carolin Jenkner, Peter C. Reinacher, Thomas E. Schlaepfer, Burkhard Mädler
2018 NeuroImage: Clinical  
Deep brain stimulation (DBS) of the superolateral branch of the medial forebrain bundle (slMFB) emerges as a -yet experimental -treatment for major depressive disorder (MDD) and other treatment refractory psychiatric diseases. First experiences have been reported from two open label pilot trials in major depression (MDD) and long-term effectiveness for MDD (50 months) has been reported. Objective: To give a detailed description of the surgical technique for DBS of the superolateral branch of
more » ... medial forebrain bundle (slMFB) in MDD. Methods: Surgical experience from bilateral implantation procedures in n = 24 patients with MDD is reported. The detailed procedure of tractography-assisted targeting together with detailed electrophysiology in 144 trajectories in the target region (recording and stimulation) is described. Achieved electrode positions were evaluated based on postoperative helical CT and fused to preoperative high resolution anatomical magnetic resonance imaging (MRI; Philips Medical Systems, Best, Netherlands), including the pre-operative diffusion tensor imaging (DTI) tractographic information (StealthViz DTI, Medtronic, USA; Framelink 5.0, Medtronic, USA). Midcommissural point (MCP) coordinates of effective contact (EC) location, together with angles of entry into the target region were evaluated. To investigate incidental stimulation of surrounding nuclei (subthalamic nucleus, STN; substantia nigra, SNr; and red nucleus, RN) as a possible mechanism, a therapeutic triangle (TT) was defined, located between these structures (based on MRI criteria in T2) and evaluated with respect to EC locations. Results: Bilateral slMFB DBS was performed in all patients. We identified an electrophysiological environment (defined by autonomic reaction, passive microelectrode recording, acute effects and oculomotor effects) that helps to identify the proper target site on the operation table. Postoperative MCP-evaluation of effective contacts (EC) shows a significant variability with respect to localization. Evaluation of the TT shows that responders will typically have their active contacts inside the triangle and that surrounding nuclei (STN, SNr, RN) are not directly hit by EC, indicating a predominant white matter stimulation. The individual EC position within the triangle cannot be predicted and is based on individual slMFB (tractography) geometry. There was one intracranial bleeding (FORESEE I study) during a first implantation attempt in a patient who later received full https://doi.T bilateral implantation. Typical oculomotor side effects are idiosyncratic for the target region and at inferior contacts. Conclusion: The detailed surgical procedure of slMFB DBS implantation has not been described before. The slMFB emerges as an interesting region for the treatment of major depression (and other psychiatric diseases) with DBS. So far it has only been successfully researched in open label clinical case series and in 15 patients published. Stimulation probably achieves its effect through direct white-matter modulation of slMFB fibers. The surgical implantation comprises a standardized protocol combining tractographic imaging based on DTI, targeting and electrophysiological evaluation of the target region. To this end, slMFB DBS surgery is in technical aspects comparable to typical movement disorder surgery. In our view, slMFB DBS should only be performed under tractographic assistance.
doi:10.1016/j.nicl.2018.08.020 pmid:30186762 pmcid:PMC6120598 fatcat:jhiysbgmmvb4fpmlf6u3qsuny4

Using the dGEMRIC technique to evaluate cartilage health in the presence of surgical hardware at 3T: comparison of inversion recovery and saturation recovery approaches

Agnes G. d'Entremont, Shannon H. Kolind, Burkhard Mädler, David R. Wilson, Alexander L. MacKay
2013 Skeletal Radiology  
Objective. To evaluate the effect of metal artifact reduction techniques on dGEMRIC T 1 calculation with surgical hardware present. Materials and Methods. We examined the effect of stainless steel and titanium hardware on dGEMRIC T 1 maps. We tested two strategies to reduce metal artifact in dGEMRIC: 1) saturation recovery (SR) instead of inversion recovery (IR) and 2) applying the Metal Artifact Reduction Sequence (MARS), in a gadolinium-doped agarose gel phantom and in vivo with titanium
more » ... are. T 1 maps were obtained using custom curve-fitting software and phantom ROIs were defined to compare conditions (metal, MARS, IR, SR). Results. A large area of artifact appeared in phantom IR images with metal when TI≤700ms. IR maps with metal had additional artifact both in vivo and in the phantom (shifted null points, increased mean T 1 (+151% IR ROIartifact) and decreased mean inversion efficiency (f; 0.45 ROIartifact, versus 2 for perfect inversion)) compared to the SR maps (ROIartifact: +13% T 1 SR, 0.95 versus 1 for perfect excitation), however SR produced noisier T 1 maps than IR (phantom SNR: 118 SR, 212 IR). MARS subtly reduced the extent of artifact in the phantom (IR and SR). Conclusion. dGEMRIC measurement in the presence of surgical hardware at 3T is possible with appropriately applied strategies. Measurements may work best in the presence of titanium and are severely limited with stainless steel. For regions near hardware where IR produces large artifacts making dGEMRIC analysis impossible, SR-MARS may allow dGEMRIC measurements. The position and size of the IR artifact is variable, and must be assessed for each implant/imaging set-up.
doi:10.1007/s00256-013-1777-2 pmid:24357123 fatcat:2z65qcxe5vf45dq2kmgusf2qty

Short-term stability of T 1 and T 2 relaxation measures in multiple sclerosis normal appearing white matter

Alice L. W. Liang, Irene M. Vavasour, Burkhard Mädler, Anthony L. Traboulsee, Donna J. Lang, David K. B. Li, Alex L. MacKay, Cornelia Laule
2011 Journal of Neurology  
INTRODUCTION Substantial evidence exists for the presence of diffuse and widespread abnormalities within the 'normal appearing' white matter (NAWM) of multiple sclerosis (MS) brain 1 . T 1 histogram analysis reveals increased T 1 in segmented NAWM 2 , while quantitative assessment of T 2 relaxation measures demonstrates decreased myelin water fraction (MWF, related to myelin content 3, 4 ) 5, 6 and increased geometric mean T 2 (GMT 2 ) of the intra/extracellular water pool 7 . Longitudinal
more » ... es have found NAWM T 1 changes over time 8, 9 , however longitudinal changes in MWF and GMT 2 of segmented NAWM have not been examined. Elucidation of MWF and GMT 2 evolution in NAWM is warranted for the characterization of MS natural history, therefore we sought to examine the short-term evolution of MWF, GMT 2 and mean T 1 in MS NAWM based on monthly scanning over 6 months. METHODS Subjects & MR Experiments: Eighteen subjects with relapsing-remitting MS (13F/5M; median EDSS = 2.5 (range 1.0-6.0); mean age = 40yrs (range 28-57yrs); mean disease duration = 9.1yrs (range 0.5-27yrs)) were scanned at months 0, 1, 2, 3, 4, 5 and 6 on a Philips Achieva 3.0T system. The MR examination was centered on a transverse slab superior to the ventricles, and included a 3D T 2 relaxation sequence (utilizing a 90º excitation pulse followed by 32 slab-selective refocusing pulses, 7 slices, 32 echoes, 10ms echo spacing, TR=1200ms) 10 and a T 1 inversion recovery experiment (5 TIs (150 -3500ms), 13 slices) 11 . Additional scans included a 3DT 1 turbo field echo (TFE) for segmentation (120 slices, TR = 10 ms, TE = 6 ms, matrix = 192 x 163, slice thickness = 1.1 mm) and an axial FLAIR for lesion detection (28 slices, TR = 10000 ms, TE = 125 ms, TI = 2800 ms, matrix = 256 x 203, slice thickness = 5 mm). Analysis: All T 1 and T 2 data was registered to the baseline TI=1500ms T1 data using FSL 12 (ver 3.3). Lesion masks for each time point were created through segmentation of a combination of the FLAIR and 3DT 1 with FSL 12 followed by manual editing. A global lesion mask was then made by adding all lesions masks together. A white matter mask was created for each subject at baseline through segmentation of a combination of the TI=150ms, 400ms, 1500ms and 3DT 1 with FSL 12 . Finally, a NAWM mask was created by subtracting the global lesion mask from the white matter mask. T 2 distributions were calculated for every voxel in the T 2 relaxation data set using a regularized non-negative least squares (NNLS) algorithm 13 . MWF was the area under the T 2 distribution from 0-40ms divided by the total area. GMT 2 was calculated as the mean on a logarithmic scale from 40ms<T 2 <200ms. T 1 was calculated using a mono-exponential fit for each voxel in the image. NAWM masks were applied to MWF, GMT 2 and T 1 maps. Histograms were created of all NAWM pixels and the following metrics were compared over time for each subject and as a group using a regression analysis: mean, median, 1 st quartile, 3 rd quartile, peak height and peak location. Bonferroni correction was applied to account for multiple comparisons (p-level set at <0.00014). Figure 1 shows the average histograms across all MS subjects for each study time point. On average, no change over time was observed for any MR histogram metric. Figure 1 insets demonstrate histograms from 2 subjects, highlighting that while MR measures remained stable over 6 months, clear inter-subject variability existed. Examining MR histogram metrics for individual subjects, no significant change over time was observed for any MR histogram metric. However, for individual subjects there were trends indicating change over time of several T 1 and MWF parameters including T 1 peak height and location and median MWF. RESULTS DISCUSSION & CONCLUSION Histogram metrics derived from quantitative assessment of T 1 and T 2 relaxation in MS NAWM demonstrated short-term (6 month) stability of mean T 1 , myelin water fraction and geometric mean T 2 . As previous studies have observed changes in NAWM T 1 over a longer period of time (14-22 months 8 ; 3 and 5 years 9 ) it is probable that a change in NAWM T 1 would also be expected with an extended follow-up period for our subjects. While the longitudinal evolution of mean T2 and myelin water fraction in NAWM is still unknown, because loss of myelin has been observed to varying degrees in MS NAWM 5, 6, 14 it is reasonable to hypothesize that diffuse progressive myelin loss will also occur given a longer follow-up period. Longitudinal follow-up on the order of years will be needed to assess the rate of global demyelination in NAWM. ACKNOWLEDGMENTS: MS volunteers, MRI technologists and MS Society of Canada.
doi:10.1007/s00415-011-6318-0 pmid:22119771 fatcat:lrkcee64izdvpgkwdh2ph5emxi
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