Magnetization Transfer Values Research Articles

Voxel-Based quantitative MRI reveals spatial patterns of grey matter alteration in multiple sclerosis.

Despite robust postmortem evidence and potential clinical importance of gray matter (GM) pathology in multiple sclerosis (MS), assessing GM damage by conventional magnetic resonance imaging (MRI) remains challenging. This prospective cross‐sectional study aimed at characterizing the topography of GM microstructural and volumetric alteration in MS using, in addition to brain atrophy measures, three quantitative MRI (qMRI) parameters—magnetization transfer (MT) saturation, longitudinal (R1), and effective transverse (R2*) relaxation rates, derived from data acquired during a single scanning session. Our study involved 35 MS patients (14 relapsing–remitting MS; 21 primary or secondary progressive MS) and 36 age‐matched healthy controls (HC). The qMRI maps were computed and segmented in different tissue classes. Voxel‐based quantification (VBQ) and voxel‐based morphometry (VBM) statistical analyses were carried out using multiple linear regression models. In MS patients compared with HC, three configurations of GM microstructural/volumetric alterations were identified. (a) Co‐localization of GM atrophy with significant reduction of MT, R1, and/or R2*, usually observed in primary cortices. (b) Microstructural modifications without significant GM loss: hippocampus and paralimbic cortices, showing reduced MT and/or R1 values without significant atrophy. (c) Atrophy without significant change in microstructure, identified in deep GM nuclei. In conclusion, this quantitative multiparametric voxel‐based approach reveals three different spatially‐segregated combinations of GM microstructural/volumetric alterations in MS that might be associated with different neuropathology.

Edaravone reduces astrogliosis and apoptosis in young rats with kaolin-induced hydrocephalus.

We investigated the possible neuroprotective effects of the free radical scavenger edaravone in experimental hydrocephalus. Seven-day-old Wistar rats were divided into three groups: control group (C), untreated hydrocephalic (H), and hydrocephalic treated with edaravone (EH). The H and EH groups were subjected to hydrocephalus induction by 20% kaolin intracisternal injection. The edaravone (20mg/kg) was administered daily for 14days from the induction of hydrocephalus. All animals were daily weighed and submitted to behavioral test and assessment by magnetic resonance imaging. After 14days, the animals were sacrificed and the brain was removed for histological, immunohistochemical, and biochemical studies. The gain weight was similar between groups from the ninth post-induction day. The open field test performance of EH group was better (p<0.05) as compared to untreated hydrocephalic animals. Hydrocephalic animals (H and EH) showed ventricular ratio values were higher (p<0.05), whereas magnetization transfer values were lower (p<0.05), as compared to control animals. Astrocyte activity (glial fibrillary acidic protein) and apoptotic cells (caspase-3) of EH group were decreased on the corpus callosum (p>0.01), germinal matrix (p>0.05), and cerebral cortex (p>0.05), as compared to H group. We have demonstrated that administration of edaravone for 14 consecutive days after induction of hydrocephalus reduced astrocyte activity and that it has some beneficial effects over apoptotic cell death.

Associations between brain white matter integrity and disease severity in obstructive sleep apnea.

Obstructive sleep apnea (OSA) is characterized by recurrent upper airway blockage, with continued diaphragmatic efforts to breathe during sleep. Brain structural changes in OSA appear in various regions, including white matter sites that mediate autonomic, mood, cognitive, and respiratory control. However, the relationships between brain white matter changes and disease severity in OSA are unclear. This study examines associations between an index of tissue integrity, magnetization transfer (MT) ratio values (which show MT between free and proton pools associated with tissue membranes and macromolecules), and disease severity (apnea-hypopnea index [AHI]) in OSA subjects. We collected whole-brain MT imaging data from 19 newly diagnosed, treatment-naïve OSA subjects (50.4 ± 8.6 years of age, 13 males, AHI 39.7 ± 24.3 events/hr], using a 3.0-Tesla MRI scanner. With these data, whole-brain MT ratio maps were calculated, normalized to common space, smoothed, and correlated with AHI scores by using partial correlation analyses (covariates, age and gender; P < 0.005). Multiple brain sites in OSA subjects, including superior and inferior frontal regions, ventral medial prefrontal cortex and nearby white matter, midfrontal white matter, insula, cingulate and cingulum bundle, internal and external capsules, caudate nuclei and putamen, basal forebrain, hypothalamus, corpus callosum, and temporal regions, showed principally lateralized negative correlations (P < 0.005). These regions showed significant correlations even with correction for multiple comparisons (cluster-level, family-wise error, P < 0.05), except for a few superior frontal areas. Predominantly negative correlations emerged between local MT values and OSA disease severity, indicating potential usefulness of MT imaging for examining the OSA condition. These findings indicate that OSA severity plays a significant role in white matter injury. © 2016 Wiley Periodicals, Inc.

Magnetization Transfer MR Imaging to Monitor Muscle Tissue Formation during Myogenic in Vivo Differentiation of Muscle Precursor Cells.

Purpose To determine whether magnetization transfer (MT) magnetic resonance (MR) imaging may serve as a quantitative measure of the degree of fiber formation during differentiation of muscle precursor cells into engineered muscle tissue as a potential noninvasive monitoring tool in mice. Materials and Methods The study was approved by the local ethics committee (no. StV 01/2008) and the local Veterinary Office (license no. 99/2013). Human muscle progenitor cells (hMPCs) derived from rectus abdominis muscles were subcutaneously injected into CD-1 nude mice (CD-1 nude mice, Crl:CD1-Foxn1nu; Charles River Laboratories, Wilmington, Mass) for development of muscle tissue. The mice underwent MR imaging examinations at 4.7 T at days 1, 3, 7, 14, 21, and 28 after cell transplantation by using a gradient-echo sequence with an MT prepulse and systematic variation of the off-resonance frequency (50-37 500 Hz) at an amplitude of 800°. Direct saturation was estimated from a Bloch equation simulation. The MT ratio (MTR) was correlated to immunohistochemistry findings, Western blot results, and results of myography. Data were analyzed by using one-way or two-way analysis of variance with the Sidak or Tukey multiple comparisons test. Results In the reference skeletal muscle, highest MT was found for 2500 Hz off-resonance frequency with an MTR ± standard deviation of 57.5% ± 3.5. The developing muscle tissue exhibited increasing MT values during the 28 days of myogenic in vivo differentiation and did not reach the values of native skeletal muscle. Mean values of MTR (2500 Hz) for hMPCs were 27.6% ± 6.3 (day 1), 24.7% ± 8.7 (day 3), 28.2% ± 5.7 (day 7), 35.9% ± 5.0 (day 14), 37.0% ± 7.9 (day 21), and 39.9% ± 8.1 (day 28). The results from MT MR imaging correlated qualitatively well with muscle tissue expression of specific skeletal markers, as well as muscle contractility. Conclusion MT MR imaging may be used to noninvasively monitor the process of myogenic in vivo differentiation of hMPCs as a biomarker of the quantity and quality of muscle fiber formation. © RSNA, 2016 Online supplemental material is available for this article.

Pre- and Postshunting Magnetization Transfer Ratios Are in Accordance with Neurological and Behavioral Changes in Hydrocephalic Immature Rats

Hydrocephalus is a common neurological condition in children characterized by an imbalance between the production and absorption of cerebrospinal fluid (CSF), causing abnormal fluid accumulation in the brain cavities. Shunt systems have been used to drain excess CSF and to prevent progressive ventricular enlargement. However, despite improvements in these systems, neurological and structural changes cannot always be reversed. Our aim was to evaluate the magnetization transfer ratio as a biomarker for the effectiveness of a CSF shunt system to treat neurological and behavioral disorders observed in experimental hydrocephalus. Seven-day-old Wistar rats were used in this study. The pups were subjected to hydrocephalus induction via 20% kaolin intracisternal injection. After confirmation of ventriculomegaly by magnetic resonance imaging (MRI), a group of animals underwent placement of a ventriculosubcutaneous shunt (VSS). The reduction in ventricular size in hydrocephalic rats operated with functional VSS was observed as a decrease in ventricular ratio values and preservation of the corpus callosum thickness. Magnetization transfer values were significantly increased and matched to the recovery process of axonal myelination observed based on more-intense blue staining by solochrome cyanin. The histopathological analysis revealed a reduction in reactive astrocytes by means of GFAP immunostaining. The hydrocephalic rats operated with functional VSS also showed significant progress in motor and exploratory activities, similar to the control animals, at the end of the experiment. In conclusion, the VSS system employed 7 days after hydrocephalus induction was able to prevent structural damage and restore the axonal myelination process in periventricular structures by stabilizing and reducing the ventricular enlargement, and the results are in accordance with the magnetization transfer ratio in MRI.

Effects of formalin fixation and collagen cross‐linking on T2 and magnetization transfer in bovine nasal cartilage

Endogenous collagen cross-links influence cartilage biomechanical properties and resistance to degradation. Formalin fixation modifies collagen residues and forms new cross-links in a dose-dependent manner. We tested the hypothesis that magnetization transfer (MT) effects and T(2) depend on collagen cross-linking in cartilage. These parameters were measured in bovine nasal cartilage (BNC) prior to fixation, after 9 weeks of immersion in formalin solutions ranging in concentration from 0% to 10%, and after NaBH(3)CN reduction and washing. T(2) decreased by 59.4% +/- 1.1% upon fixation in 10% formalin, and was 32.2% +/- 5.2% shorter than initial values after washing. The apparent MT rate increased 25.9% +/- 3.7% and 52.8% +/- 7.1% over baseline under these conditions. Biochemical assays showed no significant differences in water, proteoglycan, natural cross-link, or collagen content between the 0% and 10% formalin-treated samples, while amino acid analysis demonstrated losses in (hydroxy)lysine and tyrosine, and new peaks consistent with methylene cross-links in fixed samples only. We conclude that formalin fixation of cartilage results in significant decreases in T(2) and increases in MT parameters that persist after removal of unreacted formaldehyde. The collagen cross-links thus created are associated with large changes in MT and T(2), indicating that interpretation of T(2) and MT values in terms of cartilage macromolecular content must be made with caution.

Characterization of Intimal Changes in Coronary Artery Specimens with MR Microscopy

To determine if magnetic resonance (MR) microscopy can yield images sufficient for discriminating early progressive atherosclerotic lesions from nonprogressive atherosclerotic lesions in human coronary arteries. Institutional review board approval and informed consent were not required. Seventeen coronary artery segments (mean diameter, 2.8 mm +/- 1.0 [standard deviation]) were collected within 36 hours after death from 11 cadavers (six men, five women; age range at death, 33-65 years). Quantitative T1, T2, intensity-weighted (IW), and magnetization transfer (MT) maps were acquired with a 9.4-T vertical-bore magnet. Coronary artery lesions were classified as adaptive intimal thickening (AIT), pathologic intimal thickening (PIT), or intimal xanthoma (IXA). Internal anatomic fiducial landmarks and stains were applied to proximal and epicardial vessel surfaces and used to register histologic sections with MR images and thus enable comparison of MR images and Movat pentachrome-stained histologic specimens. Unique 0.0012-0.0287-cm(2) regions of interest were visually identified on quantitative T1, T2, MT, and IW maps of AIT, IXA, and PIT lesions. Distributions of T1, T2, MT, and IW values were compared with Student t and Wilcoxon two-sample tests. MR microscopic images of nonprogressive AIT and IXA lesions revealed two intimal layers. The luminal intima had higher T1 and T2 values and lower MT values than did the medial intima; these findings were consistent with compositional differences observed in histologic sections. In the IXA lesion, T2 values of both intimal layers were markedly reduced when compared with T2 values of AIT lesions because of the accumulation of lipid-laden macrophages in both layers. Progressive PIT lesions had a typical multilayered appearance or foci with a short T2 relaxation time and low IW values; these features were not observed in AIT or IXA lesions. MR microscopy enabled identification of morphologic arterial wall features that enable discrimination of progressive PIT lesions from nonprogressive AIT or IXA lesions.

Histomorphometry of the embryonic avian growth plate by proton nuclear magnetic resonance microscopy.

Quantitative nuclear magnetic resonance (NMR) microscopy was used to characterize the biochemical and morphological properties of the different zones within the growth plate of an embryonic chick femur. For precalcified tissue, water proton transverse relaxation times (T2) and magnetization transfer values (MT) were directly and inversely dependent, respectively, on tissue cellularity, defined as the intracellular area per unit area on histological sections. T2 values extrapolated for intra- and extracellular water were 96 ms and 46 ms, respectively. The extracellular T2 was comparable with that measured for mature cartilage. The MT values extrapolated for intra- and extracellular compartments were 0.32 and 0.85, respectively. These values were comparable with those values reported in the literature for cell pellets and for mature cartilage tissue. Thus, cellularity dominated the NMR properties of this immature cartilage tissue. Mineral deposits within calcified cartilage and periosteal bone invoked NMR relaxation processes that were dependent on the inorganic mineral phase. Additionally, collagen molecules present in mineralized zones gave rise to a significant MT effect. These results show the utility of water proton NMR microscopy for assessing both the organic and inorganic phases within mineralized tissues.

Post-Gadolinium Evaluation of Intracranial Tumours: A Comparative Study of Spin Echo, Fast Spin Echo, Gradient Echo T1-Weighted Sequences, with and without Magnetization Transfer

This study compares the use of six different post-gadolinium T1-weighted sequences on intracranial tumours with the aim of evaluating their efficacy in terms of lesion and edema contrast resolution and cortex visualization. Forty-eight intracranial neoplastic lesions were evaluated after contrast media administration by means of the following T1-weighted sequences: Fast Spin-Echo (FSE), Spin-Echo (SE) and Gradient-Echo (GE) with and without Magnetization Transfer (MT) pulse. For each technique tumour/background contrast resolution (T/B CR), oedema/background contrast resolution (E/B CR) and white matter/grey matter contrast resolution (WM/GM CR) were calculated. GE sequences, with and without MT, showed the lowest contrast resolution values for all parameters. FSE MT sequences showed the highest T/B CR values. SE sequences, instead, showed the best E/B and WM/GM CR values. FSE and SE MT values were intermediate between FSE MT and SE sequences. No sequence had high values for all contrast resolution parameters. The sequence with the best T/B CR was the FSE MT, but that with the best anatomic peritumoural edema and cortex definition was SE. Both FSE MT and SE T1-weighted sequences may be acquired to obtain accurate post-gadolinium tumour evaluation.

Measuringin VivoMyelination of Human White Matter Fiber Tracts with Magnetization Transfer MR

Precise characterization of white matter pathways is important for the understanding of structural–functional relationships in the human brain. While it is known from postmortem studies that the connectivity of cortical areas is conveyed by projection, commissural, and association fibers, most clinical studies disregard useful information about specific fiber tracts. Magnetization transfer (MT) MR detects the relative proportion of free mobile protons and immobile protons bound to macromolecules. MT values correlate with histopathology and it has been proposed that in the white matter, the amount of magnetization transfer correlates with the degree of myelination. Thus, MT-MR provides measures that may reflect more accurately the physiology and natural course of diseases involving the white matter. We applied this quantitativein vivomethod to five children at different ages to determine whether the maturational changes of distinct fiber tracts could be measured. All regions of interest were localized by means of Brodmann's original descriptions and the additional use of reconstructed 3D-matched data from 10 myelin-stained human brain specimens. With this atlas-guided approach we localized and measured 26 supratentorial white matter fiber tracts in each hemisphere, connecting to primary as well as association cortices. All fiber tracts showed consistent age-related MT changes and the strongest effects were found in those tracts projecting to the primary cortical areas. These results suggest that our method is suitable forin vivoMT measurements in specific fiber tracts. It can provide data that relate to myelination during ontogenesis or myelination delays in myelin disorders. In the clinical domain, the focus on specific fiber tracts appears to be advantageous over standard approaches, because such system of parcellation is based on the functional anatomy of the white matter. Consequently, it may be especially useful for topical analysis in neurology allowing the assessment of the functional consequences of white matter damage as well as the effectiveness of treatments in patients with any lesion that can be visualized by MRI.