Inter-Vendor Reproducibility of Myelin Water Imaging Using a 3D Gradient and Spin Echo Sequence

Myelin water imaging can be achieved using multicomponent T2 relaxation analysis to quantify in vivo measurement of myelin content, termed the myelin water fraction (MWF). Therefore, myelin water imaging can be a valuable tool to better understand the underlying white matter pathology in demyelinating diseases, such as multiple sclerosis. To apply myelin water imaging in multisite studies and clinical applications, it must be acquired in a clinically feasible scan time (less than 15 min) and be reproducible across sites and scanner vendors. Here, we assessed the reproducibility of MWF measurements in regional and global white matter in 10 healthy human brains across two sites with two different 3 T magnetic resonance imaging scanner vendors (Philips and Siemens), using a 32-echo gradient and spin echo (GRASE) sequence. A strong correlation was found between the MWF measurements in the global white matter (Pearson’s r = 0.91; p < 0.001) for all participants across the two sites. The mean intersite MWF coefficient of variation across participants was 2.77% in the global white matter and ranged from 4.47% (splenium of the corpus callosum) to 17.89% (genu of the corpus callosum) in white matter regions of interest. Bland-Altman analysis showed a good agreement in MWF measurements between the two sites with small bias of 0.002. Overall, MWF estimates were in good agreement across the two sites and scanner vendors. Our findings support the use of quantitative multi-echo T2 relaxation metrics, such as the MWF, in multicenter studies and clinical trials to gain deeper understanding about the pathological processes resulting from the underlying disease progression in neurodegenerative diseases

Applicability of multiple quantitative magnetic resonance methods in genetic brain white matter disorders

Background and purpose: Magnetic resonance imaging (MRI) measures of tissue microstructure are important for monitoring brain white matter (WM) disorders like leukodystrophies and multiple sclerosis. They should be sensitive to underlying pathological changes. Three whole-brain isotropic quantitative methods were applied and compared within a cohort of controls and leukodystrophy patients: two novel myelin water imaging (MWI) techniques (multi-compartment relaxometry diffusion-informed MWI: MCR-DIMWI, and multi-echo T2 relaxation imaging with compressed sensing: METRICS) and neurite orientation dispersion and density imaging (NODDI).// Methods: For 9 patients with different leukodystrophies (age range 0.4-62.4 years) and 15 control subjects (2.3-61.3 years), T1-weighted MRI, fluid-attenuated inversion recovery, multi-echo gradient echo with variable flip angles, METRICS, and multi-shell diffusion-weighted imaging were acquired on 3 Tesla. MCR-DIMWI, METRICS, NODDI, and quality control measures were extracted to evaluate differences between patients and controls in WM and deep gray matter (GM) regions of interest (ROIs). Pearson correlations, effect size calculations, and multi-level analyses were performed.// Results: MCR-DIMWI and METRICS-derived myelin water fractions (MWFs) were lower and relaxation times were higher in patients than in controls. Effect sizes of MWF values and relaxation times were large for both techniques. Differences between patients and controls were more pronounced in WM ROIs than in deep GM. MCR-DIMWI-MWFs were more homogeneous within ROIs and more bilaterally symmetrical than METRICS-MWFs. The neurite density index was more sensitive in detecting differences between patients and controls than fractional anisotropy. Most measures obtained from MCR-DIMWI, METRICS, NODDI, and diffusion tensor imaging correlated strongly with each other.// Conclusion: This proof-of-concept study shows that MCR-DIMWI, METRICS, and NODDI are sensitive techniques to detect changes in tissue microstructure in WM disorders

Multi-modal characterization of rapid anterior hippocampal volume increase associated with aerobic exercise.

The hippocampus has been shown to demonstrate a remarkable degree of plasticity in response to a variety of tasks and experiences. For example, the size of the human hippocampus has been shown to increase in response to aerobic exercise. However, it is currently unknown what underlies these changes. Here we scanned sedentary, young to middle-aged human adults before and after a six-week exercise intervention using nine different neuroimaging measures of brain structure, vasculature, and diffusion. We then tested two different hypotheses regarding the nature of the underlying changes in the tissue. Surprisingly, we found no evidence of a vascular change as has been previously reported. Rather, the pattern of changes is better explained by an increase in myelination. Finally, we show hippocampal volume increase is temporary, returning to baseline after an additional six weeks without aerobic exercise. This is the first demonstration of a change in hippocampal volume in early to middle adulthood suggesting that hippocampal volume is modulated by aerobic exercise throughout the lifespan rather than only in the presence of age related atrophy. It is also the first demonstration of hippocampal volume change over a period of only six weeks, suggesting gross morphometric hippocampal plasticity occurs faster than previously thought

Quantitative evaluation of metal artifact reduction techniques in MRI

Several techniques for metal artifact reduction in MRI were studied in order to determine their effectiveness. The noise and blur introduced by the techniques were also investigated. To this end, non-metallic replicas of two metal implants (stainless steel and titanium/chromium-cobalt femoral prostheses) were fabricated from wax, and MR images were obtained of each component immersed in water. The difference between the images of each metal prosthesis and its wax replica was measured in terms of energy. The difference energy attributed to noise and blur were isolated, resulting in a measure of the metal artifact. This new "gold standard" method was successfully demonstrated to provide a quantitative means of measuring metal artifact. Several pulse sequences were evaluated in terms of metal artifact reduction capability, as well as signal-to-noise ratio and blur. The analysis revealed that increasing the image bandwidth from ±16 kHz to ±64 kHz reduced metal artifact by an average of 60%, while employing View Angle Tilting (VAT) was only slightly more efficient, reducing metal artifact by an average of 63%. The metal artifact reduction sequence (MARS), which combines the increased image bandwidth with VAT as well as an increased slice-select bandwidth, resulted in the least amount of image distortion, reducing the artifact by an average of 79%. The signal-to-noise ratio was lower for MARS, but blurring was found to be significantly improved.Science, Faculty ofPhysics and Astronomy, Department ofGraduat

Myelin water imaging : development at 3.0T, application to the study of multiple sclerosis, and comparison to diffusion tensor imaging

T2 relaxation imaging can be used to measure signal from water trapped between myelin bilayers; the ratio of myelin water signal to total water is termed the myelin water fraction (MWF). First, results from multi-component T2 relaxation and diffusion tensor imaging (DTI) were compared for 19 multiple sclerosis (MS) subjects at 1.5 T to better understand how each measure is affected by pathology. In particular, it was determined that the detection of a long-T2 signal within an MS lesion may be indicative of a different underlying pathology than is present in lesions without long-T2 signal. Next, the single-slice T2 relaxation measurement was implemented, refined, and validated at 3.0 T. Scan parameters were varied for phantoms and in-vivo brain, and changes in multi-exponential fit residuals and T2 distribution-derived parameters such as MWF were monitored to determine which scan parameters minimized artifacts. Measurements were compared between 1.5 T and 3.0 T for 10 healthy volunteers. MWF maps were qualitatively similar between field strengths. MWFs were significantly higher at 3.0 T than at 1.5 T, but with a strong correlation between measurements at the different field strengths. Due to long acquisition times, multi-component T2 relaxation has thus far been clinically infeasible. The next study aimed to validate a new 3D multi-component T2 relaxation imaging technique against the 2D single-slice technique most commonly used. Ten healthy volunteers were scanned with both the 2D single-slice and 3D techniques. MWF maps were qualitatively similar between scans. MWF values were highly correlated between the acquisition methods. Although MWF values were generally lower using the 3D technique, they were only significantly so for peripheral brain structures, likely due to increased sensitivity of slab-selective refocusing pulses used for the 3D approach. The 3D T2 relaxation sequence was then applied to the study of MS to take advantage of the increased brain coverage. Thirteen MS subjects and 11 controls underwent T2 relaxation and DTI examinations to produce histograms of MWF and several DTI-derived metrics. MS MWF histograms differed considerably from those of controls, and differences in MS MWF histograms did not mirror differences in DTI histograms relative to matched controls.Science, Faculty ofPhysics and Astronomy, Department ofGraduat

Rapid Three-Dimensional Multicomponent Relaxation Imaging of the Cervical Spinal Cord

Currently, little is known about the pathology of myelin in spinal cord disease due to the technical challenges of specifically measuring myelin content noninvasively. Multicomponent relaxometry allows estimation of the myelin water fraction, which is related to myelin content. However, conventional multiple-echo spin-echo-based multicomponent relaxometry techniques require prohibitively long acquisition times, lack spatial coverage, and are sensitive to artifacts common in spinal cord imaging. Multicomponent driven equilibrium single pulse observation of T-1 and T-2 (mcDESPOT) offers a promising alternative to conventional multicomponent relaxometry techniques. The goal of this pilot study was to assess the efficacy of mcDESPOT for obtaining high spatial resolution spinal cord myelin water fraction data covering the entire cervical spinal cord. Myelin water fraction values were found to be highly reproducible between subjects and over time but varied considerably along the length of the cord. Other relaxation characteristics that relate to tissue structure and health were also reliably measured. Magn Reson Med 65:551-556, 2011. (C) 2010 Wiley-Liss, Inc

dGEMRIC and metal artifact at 3T

Objective. To evaluate the effect of metal artifact reduction techniques on dGEMRIC T₁ calculation with surgical hardware present. Materials and Methods. We examined the effect of stainless steel and titanium hardware on dGEMRIC T₁ 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 hardware. T₁ 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 T₁ (+151% IR ROIartifact) and decreased mean inversion efficiency (f; 0.45 ROIartifact, versus 2 for perfect inversion)) compared to the SR maps (ROIartifact: +13% T1 SR, 0.95 versus 1 for perfect excitation), however SR produced noisier T₁ 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, SRMARS may allow dGEMRIC measurements. The position and size of the IR artifact is variable, and must be assessed for each implant/imaging set-up.Applied Science, Faculty ofMedicine, Faculty ofScience, Faculty ofOther UBCNon UBCMechanical Engineering, Department ofOrthopaedic Surgery, Department ofPhysics and Astronomy, Department ofReviewedFacultyGraduat

Non-negative least squares computation for in vivo myelin mapping using simulated multi-echo spin-echo T2 decay data

Multi‐compartment T2 mapping has gained particular relevance for the study of myelin water in the brain. As a facilitator of rapid saltatory axonal signal transmission, myelin is a cornerstone indicator of white matter development and function. Regularized non‐negative least squares fitting of multi‐echo T2 data has been widely employed for the computation of the myelin water fraction (MWF), and the obtained MWF maps have been histopathologically validated. MWF measurements depend upon the quality of the data acquisition, B1+ homogeneity and a range of fitting parameters. In this special issue article, we discuss the relevance of these factors for the accurate computation of multi‐compartment T2 and MWF maps. We generated multi‐echo spin‐echo T2 decay curves following the Carr‐Purcell‐Meiboom‐Gill approach for various myelin concentrations and myelin T2 scenarios by simulating the evolution of the magnetization vector between echoes based on the Bloch equations. We demonstrated that noise and imperfect refocusing flip angles yield systematic underestimations in MWF and intra−/extracellular water geometric mean T2 (gmT2). MWF estimates were more stable than myelin water gmT2 time across different settings of the T2 analysis. We observed that the lower limit of the T2 distribution grid should be slightly shorter than TE1. Both TE1 and the acquisition echo spacing also have to be sufficiently short to capture the rapidly decaying myelin water T2 signal. Among all parameters of interest, the estimated MWF and intra−/extracellular water gmT2 differed by approximately 0.13–4 percentage points and 3–4 ms, respectively, from the true values, with larger deviations observed in the presence of greater B1+ inhomogeneities and at lower signal‐to‐noise ratio. Tailoring acquisition strategies may allow us to better characterize the T2 distribution, including the myelin water, in vivo

Myelin Water Fraction Is Transiently Reduced after a Single Mild Traumatic Brain Injury--A Prospective Cohort Study in Collegiate Hockey Players.

Impact-related mild traumatic brain injuries (mTBI) are a major public health concern, and remain as one of the most poorly understood injuries in the field of neuroscience. Currently, the diagnosis and management of such injuries are based largely on patient-reported symptoms. An improved understanding of the underlying pathophysiology of mTBI is urgently needed in order to develop better diagnostic and management protocols. Specifically, dynamic post-injury changes to the myelin sheath in the human brain have not been examined, despite 'compromised white matter integrity' often being described as a consequence of mTBI. In this preliminary cohort study, myelin water imaging was used to prospectively evaluate changes in myelin water fraction, derived from the T2 decay signal, in two varsity hockey teams (45 players) over one season of athletic competition. 11 players sustained a concussion during competition, and were scanned at 72 hours, 2 weeks, and 2 months post-injury. Results demonstrated a reduction in myelin water fraction at 2 weeks post-injury in several brain areas relative to preseason scans, including the splenium of the corpus callosum, right posterior thalamic radiation, left superior corona radiata, left superior longitudinal fasciculus, and left posterior limb of the internal capsule. Myelin water fraction recovered to pre-season values by 2 months post-injury. These results may indicate transient myelin disruption following a single mTBI, with subsequent remyelination of affected neurons. Myelin disruption was not apparent in the athletes who did not experience a concussion, despite exposure to repetitive subconcussive trauma over a season of collegiate hockey. These findings may help to explain many of the metabolic and neurological deficits observed clinically following mTBI