Macromolecular Proton Fraction Research Articles

Automatic Brain Tissue and Lesion Segmentation and Multi-Parametric Mapping of Contrast-Enhancing Gliomas without the Injection of Contrast Agents: A Preliminary Study.

This study aimed to develop a rapid, 1 mm3 isotropic resolution, whole-brain MRI technique for automatic lesion segmentation and multi-parametric mapping without using contrast by continuously applying balanced steady-state free precession with inversion pulses throughout incomplete inversion recovery in a single 6 min scan. Modified k-means clustering was performed for automatic brain tissue and lesion segmentation using distinct signal evolutions that contained mixed T1/T2/magnetization transfer properties. Multi-compartment modeling was used to derive quantitative multi-parametric maps for tissue characterization. Fourteen patients with contrast-enhancing gliomas were scanned with this sequence prior to the injection of a contrast agent, and their segmented lesions were compared to conventionally defined manual segmentations of T2-hyperintense and contrast-enhancing lesions. Simultaneous T1, T2, and macromolecular proton fraction maps were generated and compared to conventional 2D T1 and T2 mapping and myelination water fraction mapping acquired with MAGiC. The lesion volumes defined with the new method were comparable to the manual segmentations (r = 0.70, p < 0.01; t-test p > 0.05). The T1, T2, and macromolecular proton fraction mapping values of the whole brain were comparable to the reference values and could distinguish different brain tissues and lesion types (p < 0.05), including infiltrating tumor regions within the T2-lesion. Highly efficient, whole-brain, multi-contrast imaging facilitated automatic lesion segmentation and quantitative multi-parametric mapping without contrast, highlighting its potential value in the clinic when gadolinium is contraindicated.

Multiparametric Quantitative MRI Evaluation of Changes in Brain Myelin Content after the First Course of Chemotherapy

Objective. Quantitative assessment of changes in brain myelin content after the first course of chemotherapyMaterials and Methods. T1 and T2 maps as well as myelin water fraction (MWF) and macromolecular proton fraction (MPF) maps, reflecting myelin content, were acquired in 6 patients (mean age — 13.7 ± 2.4 years) before and after the first course of chemotherapy. The study was carried out using on 3T MRI scanner. Statistical data processing was carried out using the GraphPad Prism.Results. MPF and T2 values showed an increase in the thalamus and white matter of the occipital lobes of the brain, while MWF values showed an increase in the cerebellum and a decline in the white matter of the frontal lobes. Significant changes were not found for T1 values.Discussion. According to MWF the structures of the brain which are primarily affected by treatment with toxic drugs — the white matter of the frontal lobes and the cerebellum, were revealed. MWF values decreasing in the white matter of the frontal lobes may indicate the process of demyelination in this area, while increased MWF values in the cerebellum could be caused either by remyelination processes or by incomplete cleansing of myelin residues accumulation by macrophages at the site of degeneration. Conclusion. The results obtained demonstrated high potential of MWF values serve as early changes biomarker of neurotoxicity after the chemotherapy treatment. Along with this, the MPF index, which is more sensitive to cerebral edema, may be a predictor of demyelination.

Ultrasound attenuation of cortical bone correlates with biomechanical, microstructural, and compositional properties

BackgroundWe investigated the relationship of two commonly used quantitative ultrasound (QUS) parameters, speed of sound (SoS) and attenuation coefficient (α), with water and macromolecular contents of bovine cortical bone strips as measured with ultrashort echo time (UTE) magnetic resonance imaging (MRI).MethodsSoS and α were measured in 36 bovine cortical bone strips utilizing a single-element transducer with nominal 5 MHz center frequency based on the time of flight principles after accommodating for reflection losses. Specimens were then scanned using UTE MRI to measure total, bound, and pore water proton density (TWPD, BWPD, and PWPD) as well as macromolecular proton fraction and macromolecular transverse relaxation time (T2-MM). Specimens were also scanned using microcomputed tomography (μCT) at 9-μm isometric voxel size to measure bone mineral density (BMD), porosity, and pore size. The elastic modulus (E) of each specimen was measured using a 4-point bending test.Resultsα demonstrated significant positive Spearman correlations with E (R = 0.69) and BMD (R = 0.44) while showing significant negative correlations with porosity (R = -0.41), T2-MM (R = -0.47), TWPD (R = -0.68), BWPD (R = -0.67), and PWPD (R = -0.45).ConclusionsThe negative correlation between α and T2-MM is likely indicating the relationship between QUS and collagen matrix organization. The higher correlations of α with BWPD than with PWPD may indicate that water organized in finer structure (bound to matrix) provides lower acoustic impedance than water in larger pores, which is yet to be investigated thoroughly.Relevance statementThis study highlights the importance of future investigations exploring the relationship between QUS measures and all major components of the bone, including the collagenous matrix and water. Investigating the full potential of QUS and its validation facilitates a more affordable and accessible tool for bone health monitoring in clinics.Key points• Ultrasound attenuation demonstrated significant positive correlations with bone mechanics and mineral density.• Ultrasound attenuation demonstrated significant negative correlations with porosity and bone water contents.• This study highlights the importance of future investigations exploring the relationship between QUS measures and all major components of the bone.Graphical

Age-Related Decline in Brain Myelination: Quantitative Macromolecular Proton Fraction Mapping, T2-FLAIR Hyperintensity Volume, and Anti-Myelin Antibodies Seven Years Apart.

Age-related myelination decrease is considered one of the likely mechanisms of cognitive decline. The present preliminary study is based on the longitudinal assessment of global and regional myelination of the normal adult human brain using fast macromolecular fraction (MPF) mapping. Additional markers were age-related changes in white matter (WM) hyperintensities on FLAIR-MRI and the levels of anti-myelin autoantibodies in serum. Eleven healthy subjects (33-60 years in the first study) were scanned twice, seven years apart. An age-related decrease in MPF was found in global WM, grey matter (GM), and mixed WM-GM, as well as in 48 out of 82 examined WM and GM regions. The greatest decrease in MPF was observed for the frontal WM (2-5%), genu of the corpus callosum (CC) (4.0%), and caudate nucleus (5.9%). The age-related decrease in MPF significantly correlated with an increase in the level of antibodies against myelin basic protein (MBP) in serum (r = 0.69 and r = 0.63 for global WM and mixed WM-GM, correspondingly). The volume of FLAIR hyperintensities increased with age but did not correlate with MPF changes and the levels of anti-myelin antibodies. MPF mapping showed high sensitivity to age-related changes in brain myelination, providing the feasibility of this method in clinics.

Achilles tendon and enthesis assessment using ultrashort echo time magnetic resonance imaging (UTE-MRI) T1 and magnetization transfer (MT) modeling in psoriatic arthritis.

The purpose of this study is to investigate the use of ultrashort echo time (UTE) magnetic resonance imaging (MRI) techniques (T1 and magnetization transfer [MT] modeling) for imaging of the Achilles tendons and entheses in patients with psoriatic arthritis (PsA) compared with asymptomatic volunteers. The heels of twenty-sixPsA patients (age 59 ± 15 years, 41% female) and twenty-seven asymptomatic volunteers (age 33 ± 11 years, 47% female) were scanned in the sagittal plane with UTE-T1 and UTE-MT modeling sequences on a 3-T clinical scanner. UTE-T1 and macromolecular proton fraction (MMF; the main outcome of MT modeling) were calculated in the tensile portions of the Achilles tendon and at the enthesis (close to the calcaneus bone). Mann-Whitney-U tests were used to examine statistically significant differences between the two cohorts. UTE-T1 in the entheses was significantly higher for the PsA group compared with the asymptomatic group (967 ± 145 vs. 872 ± 133 ms, p< 0.01). UTE-T1 in the tendons was also significantly higher for the PsA group (950 ± 145 vs. 850 ± 138 ms, p< 0.01). MMF in the entheses was significantly lower in the PsA group compared with the asymptomatic group (15% ± 3% vs. 18% ± 3%, p< 0.01). MMF in the tendons was also significantly lower in the PsA group compared with the asymptomatic group (17% ± 4% vs. 20% ± 5%, p< 0.01). Percentage differences in MMF between the asymptomatic and PsA groups (-16.6% and -15.0% for the enthesis and tendon, respectively) were higher than the T1 differences (10.8% and 11.7% for the enthesis and tendon, respectively). The results suggest higher T1 and lower MMF in the Achilles tendons and entheses in PsA patients compared with the asymptomatic group. This study highlights the potential of UTE-T1 and UTE-MT modeling for quantitative evaluation of entheses and tendons in PsA patients.

B1 inhomogeneity-corrected T1 mapping and quantitative magnetization transfer imaging via simultaneously estimating Bloch-Siegert shift and magnetization transfereffects.

To introduce a method of inducing Bloch-Siegert shift and magnetization Transfer Simultaneously (BTS) and demonstrate its utilization for measuring binary spin-bath model parameters free pool spin-lattice relaxation ( ), macromolecular fraction ( ), magnetization exchange rate ( ) and local transmit field ( ). Bloch-Siegert shift and magnetization transfer is simultaneously induced through the application of off-resonance irradiation in between excitation and acquisition of an RF-spoiled gradient-echo scheme. Applying the binary spin-bath model, an analytical signal equation is derived and verified through Bloch simulations. Monte Carlo simulations were performed to analyze the method's performance. The estimation of the binary spin-bath parameters with compensation was further investigated through experiments, both ex vivo and in vivo. Comparing BTS with existing methods, simulations showed that existing methods can significantly bias estimation when not accounting for transmit heterogeneity and MT effects that are present. Phantom experiments further showed that the degree of this bias increases with increasing macromolecular proton fraction. Multi-parameter fit results from an in vivo brain study generated values in agreement with previous literature. Based on these studies, we confirmed that BTS is a robust method for estimating the binary spin-bath parameters in macromolecule-rich environments, even in the presence of inhomogeneity. A method of estimating Bloch-Siegert shift and magnetization transfer effect has been developed and validated. Both simulations and experiments confirmed that BTS can estimate spin-bath parameters ( , , ) that are free from bias.

Quantitative magnetization transfer MRI unbiased by on-resonance saturation and dipolar order contributions.

To demonstrate the bias in quantitative MT (qMT) measures introduced by the presence of dipolar order and on-resonance saturation (ONRS) effects using magnetization transfer (MT) spoiled gradient-recalled (SPGR) acquisitions, and propose changes to the acquisition and analysis strategies to remove these biases. The proposed framework consists of SPGR sequences prepared with simultaneous dual-offset frequency-saturation pulses to cancel out dipolar order and associated relaxation (T1D ) effects in Z-spectrum acquisitions, and a matched quantitative MT (qMT) mathematical model that includes ONRS effects of readout pulses. Variable flip angle and MT data were fitted jointly to simultaneously estimate qMT parameters (macromolecular proton fraction [MPF], T2,f , T2,b , R, and free pool T1 ). This framework is compared with standard qMT and investigated in terms of reproducibility, and then further developed to follow a joint single-point qMT methodology for combined estimation of MPF and T1 . Bland-Altman analyses demonstrated a systematic underestimation of MPF (-2.5% and -1.3%, on average, in white and gray matter, respectively) and overestimation of T1 (47.1 ms and 38.6 ms, on average, in white and gray matter, respectively) if both ONRS and dipolar order effects are ignored. Reproducibility of the proposed framework is excellent (ΔMPF = -0.03% and ΔT1 = -19.0 ms). The single-point methodology yielded consistent MPF and T1 values with respective maximum relative average bias of -0.15% and -3.5 ms found in white matter. The influence of acquisition strategy and matched mathematical model with regard to ONRS and dipolar order effects in qMT-SPGR frameworks has been investigated. The proposed framework holds promise for improved accuracy with reproducibility.

Developmental and regional dependence of macromolecular proton fraction and fractional anisotropy in fixed brain tissue.

An important advantage of imaging fixed tissue is a gain in signal-to-noise ratio and in resolution due to unlimited scan time. However, the fidelity of quantitative MRI parameters in fixed brain tissue, particularly in developmental settings, requires validation. Macromolecular proton fraction (MPF) and fractional anisotropy (FA) indices are quantitative markers of myelination and axonal integrity relevant to preclinical and clinical research. The goal of this study was to assert the correspondence of MR-derived markers of brain development MPF and FA between in vivo and fixed tissue measures. MPF and FA were compared in several white and gray matter structures of the normal mouse brain at 2, 4, and 12 weeks of age. At each developmental stage, in vivo imaging was performed, followed by paraformaldehyde fixation and a second imaging session. MPF maps were acquired from three source images (magnetization transfer weighted, proton density weighted, and T1 weighted), and FA was obtained from diffusion tensor imaging. The MPF and FA values, measured in the cortex, striatum, and major fiber tracts, were compared before and after fixation using Bland-Altman plots, regression analysis, and analysis of variance. MPF values of the fixed tissue were consistently greater than those from in vivo measurements. Importantly, this bias varied significantly with brain region and the developmental stage of the tissue. At the same time, FA values were preserved after fixation, across tissue types and developmental stages. The results of this study suggest that MPF and FA in fixed brain tissue can be used as a proxy for in vivo measurements, but additional considerations should be made to correct for the bias in MPF.

Temporal trajectories of normal myelination and axonal development assessed by quantitative macromolecular and diffusion MRI: Ultrastructural and immunochemical validation in a rabbit model

IntroductionQuantitative and non-invasive measures of brain myelination and maturation during development are of great importance to both clinical and translational research communities. While the metrics derived from diffusion tensor imaging, are sensitive to developmental changes and some pathologies, they remain difficult to relate to the actual microstructure of the brain tissue. The advent of advanced model-based microstructural metrics requires histological validation. The purpose of the study was to validate novel, model-based MRI techniques, such as macromolecular proton fraction mapping (MPF) and neurite orientation and dispersion indexing (NODDI), against histologically derived indexes of myelination and microstructural maturation at various stages of development. MethodsNew Zealand White rabbit kits underwent serial in-vivo MRI examination at postnatal days 1, 5, 11, 18, and 25, and as adults. Multi-shell, diffusion-weighted experiments were processed to fit NODDI model to obtain estimates, intracellular volume fraction (ICVF) and orientation dispersion index (ODI). Macromolecular proton fraction (MPF) maps were obtained from three source (MT-, PD-, and T1-weighted) images. After MRI sessions, a subset of animals was euthanized and regional samples of gray and white matter were taken for western blot analysis, to determine myelin basic protein (MBP), and electron microscopy, to estimate axonal, myelin fractions and g-ratio. ResultsMPF of white matter regions showed a period of fast growth between P5 and P11 in the internal capsule, with a later onset in the corpus callosum. This MPF trajectory was in agreement with levels of myelination in the corresponding brain region, as assessed by western blot and electron microscopy. In the cortex, the greatest increase of MPF occurred between P18 and P26. In contrast, myelin, according to MBP western blot, saw the largest hike between P5 and P11 in the sensorimotor cortex and between P11 and P18 in the frontal cortex, which then seemingly plateaued after P11 and P18 respectively.G-ratio by MRI markers decreased with age in the white matter. However, electron microscopy suggest a relatively stable g-ratio throughout development. ConclusionDevelopmental trajectories of MPF accurately reflected regional differences of myelination rate in different cortical regions and white matter tracts. MRI-derived estimation of g-ratio was inaccurate during early development, likely due to the overestimation of axonal volume fraction by NODDI due to the presence of a large proportion of unmyelinated axons.

Detecting Early‐Stage Liver Fibrosis Using Macromolecular Proton Fraction Mapping Based on Spin‐Lock MRI: Preliminary Observations

Macromolecular proton fraction (MPF) and T1rho maps for two representative patients with F0 and F2 stage fibrosis as confirmed by liver histology. (A) MPF maps from a patient with F0 stage fibrosis, (B) MPF maps from a patient with F2 stage fibrosis, (C) T1rho maps from the same patient with F0 stage fibrosis, and (D) T1rho maps from the same patient with F2 stage fibrosis. by Jian Hou et al. (485–492). image

Inhomogeneous Magnetization Transfer (ihMT) imaging in the acute cuprizone mouse model of demyelination/remyelination

To investigate the association of ihMT (inhom signals with the demyelination and remyelination phases of the acute cuprizone mouse model in comparison with histology, and to assess the extent of tissue damage and repair from MRI data. Acute demyelination by feeding 0.2% cuprizone for five weeks, followed by a four-week remyelination period was applied on genetically modified plp-GFP mice. Animals were scanned at different time points of the demyelination and remyelination phases of the cuprizone model using a multimodal MRI protocol, including ihMT T1D-filters, MPF (Macromolecular Proton Fraction) and R1 (longitudinal relaxation rate). For histology, plp-GFP (proteolipid protein - Green Fluorescent Protein) microscopy and LFB (Luxol Fast Blue) staining were employed as references for the myelin content. Comparison of MRI with histology was performed in the medial corpus callosum (mCC) and cerebral cortex (CTX) at two brain levels whereas ROI-wise and voxel-based analyses of the MRI metrics allowed investigating in vivo the spatial extent of myelin alterations. IhMT high-pass T1D-filters, targeted toward long T1D components, showed significant temporal variations in the mCC consistent with the effects induced by the cuprizone toxin. In addition, the corresponding signals correlated strongly and significantly with the myelin content assessed by GFP fluorescence and LFB staining over the demyelination and the remyelination phases. The signal of the band-pass T1D-filter, which isolates short T1D components, showed changes over time that were poorly correlated with histology, hence suggesting a sensitivity to pathological processes possibly not related to myelin. Although MPF was also highly correlated to histology, ihMT high-pass T1D-filters showed better capability to characterize the spatial-temporal patterns during the demyelination and remyelination phases of the acute cuprizone model (e.g., rostro-caudal gradient of demyelination in the mCC previously described in the literature). IhMT sequences selective for long T1D components are specific and sensitive in vivo markers of demyelination and remyelination and have successfully captured the spatially heterogeneous pattern of the demyelination and remyelination mechanisms in the cuprizone model. Interestingly, differences in signal variations between the ihMT high-pass and band-pass T1D-filter, suggest a sensitivity of the ihMT sequences targeted to short T1Ds to alterations other than those of myelin. Future studies will need to further address these differences by examining more closely the origin of the short T1D components and the variation of each T1D component in pathology.

Language input in late infancy scaffolds emergent literacy skills and predicts reading related white matter development.

Longitudinal studies provide the unique opportunity to test whether early language provides a scaffolding for the acquisition of the ability to read. This study tests the hypothesis that parental language input during the first 2 years of life predicts emergent literacy skills at 5 years of age, and that white matter development observed early in the 3rd year (at 26 months) may help to account for these effects. We collected naturalistic recordings of parent and child language at 6, 10, 14, 18, and 24 months using the Language ENvironment Analysis system (LENA) in a group of typically developing infants. We then examined the relationship between language measures during infancy and follow-up measures of reading related skills at age 5 years, in the same group of participants (N = 53). A subset of these children also completed diffusion and quantitative MRI scans at age 2 years (N = 20). Within this subgroup, diffusion tractography was used to identify white matter pathways that are considered critical to language and reading development, namely, the arcuate fasciculus (AF), superior and inferior longitudinal fasciculi, and inferior occipital-frontal fasciculus. Quantitative macromolecular proton fraction (MPF) mapping was used to characterize myelin density within these separately defined regions of interest. The longitudinal data were then used to test correlations between early language input and output, white matter measures at age 2 years, and pre-literacy skills at age 5 years. Parental language input, child speech output, and parent-child conversational turns correlated with pre-literacy skills, as well as myelin density estimates within the left arcuate and superior longitudinal fasciculus. Mediation analyses indicated that the left AF accounted for longitudinal relationships between infant home language measures and 5-year letter identification and letter-sound knowledge, suggesting that the left AF myelination at 2 years may serve as a mechanism by which early language experience supports emergent literacy.

Development of executive function-relevant skills is related to both neural structure and function in infants.

The development of skills related to executive function (EF) in infancy, including their emergence, underlying neural mechanisms, and interconnections to other cognitive skills, is an area of increasing research interest. Here, we report on findings from a multidimensional dataset demonstrating that infants' behavioral performance on a flexible learning task improved across development and that the task performance is highly correlated with both neural structure and neural function. The flexible learning task probed infants' ability to learn two different associations, concurrently, over 16 trials, requiring multiple skills relevant to EF. We examined infants' neural structure by measuring myelin density in the brain, using a novel macromolecular proton fraction (MPF) mapping method. We further examined an important neural function of speech processing by characterizing the mismatch response (MMR) to speech contrasts using magnetoencephalography (MEG). All measurements were performed longitudinally in monolingual English-learning infants at 7- and 11-months of age. At the group level, 11-month-olds, but not 7-month-olds, demonstrated evidence of learning both associations in the behavioral task. Myelin density in the prefrontal region at 7 months of age was found to be highly predictive of behavioral task performance at 11 months of age, suggesting that myelination may support the development of these skills. Furthermore, a machine-learning regression analysis revealed that individual differences in the behavioral task are predicted by concurrent neural speech processing at both ages, suggesting that these skills do not develop in isolation. Together, these cross-modality results revealed novel insights into EF-related skills. HIGHLIGHT: Monolingual infants demonstrated flexible learning on a task requiring executive function skills at 11 months, but not at 7 months. Infants' myelin density at 7 months is highly predictive of their behavioral performance in the flexible learning task at 11 months of age. Individual differences in the flexible learning task performance are also correlated with concurrent neural processing of speech at both ages.

Brain myelination at 7 months of age predicts later language development

Between 6 and 12 months of age there are dramatic changes in infants’ processing of language. The neurostructural underpinnings of these changes are virtually unknown. The objectives of this study were to (1) examine changes in brain myelination during this developmental period and (2) examine the relationship between myelination during this period and later language development. Macromolecular proton fraction (MPF) was used as a marker of myelination. Whole-brain MPF maps were obtained with 1.25 mm3 isotropic spatial resolution from typically developing children at 7 and 11 months of age. Effective myelin density was calculated from MPF based on a linear relationship known from the literature. Voxel-based analyses were used to identify longitudinal changes in myelin density and to calculate correlations between myelin density at these ages and later language development. Increases in myelin density were more predominant in white matter than in gray matter. A strong predictive relationship was found between myelin density at 7 months of age, language production at 24 and 30 months of age, and rate of language growth. No relationships were found between myelin density at 11 months, or change in myelin density between 7 and 11 months of age, and later language measures. Our findings suggest that critical changes in brain structure may precede periods of pronounced change in early language skills.

Decreased basal ganglia and thalamic iron in early psychotic spectrum disorders are associated with increased psychotic and schizotypal symptoms.

Iron deficits have been reported as a risk factor for psychotic spectrum disorders (PSD). However, examinations of brain iron in PSD remain limited. The current study employed quantitative MRI to examine iron content in several iron-rich subcortical structures in 49 young adult individuals with PSD (15 schizophrenia, 17 schizoaffective disorder, and 17 bipolar disorder with psychotic features) compared with 35 age-matched healthy controls (HC). A parametric approach based on a two-pool magnetization transfer model was applied to estimate longitudinal relaxation rate (R1), which reflects both iron and myelin, and macromolecular proton fraction (MPF), which is specific to myelin. To describe iron content, a synthetic effective transverse relaxation rate(R2*) was modeled using a linear fitting of R1 and MPF. PSD patients compared to HC showed significantly reduced R1 and synthetic R2*across examined regions including the pallidum, ventral diencephalon, thalamus, and putamen areas. This finding was primarily driven by decreases in the subgroup with schizophrenia, followed by schizoaffective disorder. No significant group differences were noted for MPF between PSD and HC while for regional volume, significant reductions in patients were only observed in bilateral caudate, suggesting that R1 and synthetic R2*reductions in schizophrenia and schizoaffective patients likely reflect iron deficits that either occur independently or precede structural and myelin changes. Subcortical R1 and synthetic R2*were also found to be inversely related to positive symptoms within the PSD group and to schizotypal traits across the whole sample. These findings that decreased iron in subcortical regions are associated with PSD risk and symptomatology suggest that brain iron deficiencies may play a role in PSD pathology and warrant further study.

Inhomogeneous liver fibrosis distribution revealed by macromolecular proton fraction quantification based on spin-lock MRI.

Inhomogeneous liver fibrosis distribution revealed by macromolecular proton fraction quantification based on spin-lock MRI.

The effect of corpus callosum abnormalities on myelin development in the fetal brain using the fast macromolecular proton fraction mapping

INTRODUCTION: There is evidence, indicate early compensatory axonal remodeling connections in the prenatal period, providing a favorable neurological outcome in isolated anomalies of the corpus callosum (CC). Mapping of the macromolecular proton fraction (MPF) is proven method of quantitative determination of myelin, which has been adapted for prenatal studies.OBJECTIVE: To investigate the relationship between CC anomalies and prenatal myelination of the brain using the fast macromolecular proton fraction (MPF) mapping.MATERIALS AND METHODS: Fetal MR imaging were performed on a 1.5 scanner (Achieva, Philips) using a 16-channel body coil. Of 66 fetal brains MRI, 12 studies were selected with MT abnormalities (22.8±2.8, 19–28.5 WG) and 21 without brain pathology (23.1±2.3, 20–29.5 WG). The images were analyzed according to structural MRI data (T2-Ssh and T1-GE, EPI, DWI, MYUR, T2-BFE-DYN) by two experienced radiologists. Fast-3D-MPF scan protocol with the MPF maps reconstruction was carried out according to a specialized protocol (open-source software: https://www.macroatomicmri.org /). Quantitative data were obtained by choosing the region of interest (ROI) in numerous brain structures bilateral (bridge, medulla oblongata, thalamus, cerebellum, and cerebral hemispheres). Statistics: distinctions between the groups and structures were assessed using repeated-measures analysis of covariance (ANCOVA), Pearson correlation analysis.RESULTS: MPF was significantly increased in the CC anomalies group as compared to controls in the medulla (3.26±0.63% vs. 2.75±0.59%, р=0.001) and cerebellum (2.02±0.55% vs. 1.76±0.34%, р=0.006). In hemispheres significant correlation with GA was observed in CC anomalies group (r=0.81, р=0.002), but was absent in controls (r=0.32, р=0.16).CONCLUSION: Primary observed MPF increase in the medulla and cerebellum as well as the dependence of the large hemispheres myelination on gestational age indicates that fetal cerebral matter undergoes early compensatory axonal remodeling in the cases of the interhemispheric connections’ reduction.

Detecting Early-Stage Liver Fibrosis Using Macromolecular Proton Fraction Mapping Based on Spin-Lock MRI: Preliminary Observations.

Liver fibrosis is characterized by macromolecule depositions. Recently, a novel technology termed macromolecular proton fraction quantification based on spin-lock magnetic resonance imaging (MPF-SL) is reported to measure macromolecule levels. MPF-SL can detect early-stage liver fibrosis by measuring macromolecule levels in the liver. Retrospective. Fifty-five participants, including 22 with no fibrosis (F0) and 33 with early-stage fibrosis (F1-2), were recruited. 3 T; two-dimensional (2D) MPF-SL turbo spin-echo sequence, 2D spin-lock T1rho turbo spin-echo sequence, and multi-slice 2D gradient echo sequence. Macromolecular proton fraction (MPF), T1rho, liver iron concentration (LIC), and fat fraction (FF) biomarkers were quantified within regions of interest. Group comparison of the biomarkers using Mann-Whitney U tests; correlation between the biomarkers assessed using Spearman's rank correlation coefficient and linear regression with goodness-of-fit; fibrosis stage differentiation using receiver operating characteristic curve (ROC) analysis. P-value < 0.05 was considered statistically significant. Average T1rho was 41.76 ± 2.94 msec for F0 and 41.15 ± 3.73 msec for F1-2 (P=0.60). T1rho showed nonsignificant correlation with either liver fibrosis (ρ=-0.07; P=0.61) or FF (ρ=-0.14; P=0.35) but indicated a negative correlation with LIC (ρ=-0.66). MPF was 4.73 ± 0.45% and 5.65 ± 0.81% for F0 and F1-2 participants, respectively. MPF showed a positive correlation with liver fibrosis (ρ=0.59), and no significant correlations with LIC (ρ=0.02; P=0.89) or FF (ρ=0.05; P=0.72). The area under the ROC curve was 0.85 (95% confidence interval [CI] 0.75-0.95) and 0.55 (95% CI 0.39-0.71; P=0.55) for MPF and T1rho to discriminate between F0 and F1-2 fibrosis, respectively. MPF-SL has the potential to diagnose early-stage liver fibrosis and does not appear to be confounded by either LIC or FF. 3 TECHNICAL EFFICACY STAGE: 3.

Macromolecular Proton Fraction as a Myelin Biomarker: Principles, Validation, and Applications.

Macromolecular proton fraction (MPF) is a quantitative MRI parameter describing the magnetization transfer (MT) effect and defined as a relative amount of protons bound to biological macromolecules with restricted molecular motion, which participate in magnetic cross-relaxation with water protons. MPF attracted significant interest during past decade as a biomarker of myelin. The purpose of this mini review is to provide a brief but comprehensive summary of MPF mapping methods, histological validation studies, and MPF applications in neuroscience. Technically, MPF maps can be obtained using a variety of quantitative MT methods. Some of them enable clinically reasonable scan time and resolution. Recent studies demonstrated the feasibility of MPF mapping using standard clinical MRI pulse sequences, thus substantially enhancing the method availability. A number of studies in animal models demonstrated strong correlations between MPF and histological markers of myelin with a minor influence of potential confounders. Histological studies validated the capability of MPF to monitor both demyelination and re-myelination. Clinical applications of MPF have been mainly focused on multiple sclerosis where this method provided new insights into both white and gray matter pathology. Besides, several studies used MPF to investigate myelin role in other neurological and psychiatric conditions. Another promising area of MPF applications is the brain development studies. MPF demonstrated the capabilities to quantitatively characterize the earliest stage of myelination during prenatal brain maturation and protracted myelin development in adolescence. In summary, MPF mapping provides a technically mature and comprehensively validated myelin imaging technology for various preclinical and clinical neuroscience applications.

T1D -weighted ihMT imaging - Part II. Investigating the long- and short-T1D components correlation with myelin content. Comparison with R1 and the macromolecular proton fraction.

To investigate the long- and short-T1D components correlation with myelin content using inhomogeneous magnetization transfer (ihMT) high-pass and band-pass T1D -filters and to compare ihMT, R1 , and the macromolecular proton fraction (MPF) for myelin specific imaging. The 3D ihMT rapid gradient echo (ihMTRAGE) sequences with increasing switching times (Δt) were used to derive ihMT high-pass T1D -filters with increasing T1D cutoff values and an ihMT band-pass T1D -filter for components in the 100 µs to 1 ms range. 3D spoiled gradient echo quantitative MT (SPGR-qMT) protocols were used to derive R1 and MPF maps. The specificity of R1 , MPF, and ihMT T1D -filters was evaluated by comparison with two histological reference techniques for myelin imaging. The higher contribution of long-T1D s as compared to the short components as Δt got longer led to an increase in the specificity to myelination. In contrast, focusing on the signal originating from a narrow range of short-T1D s (< 1 ms) as isolated by the band-pass T1D -filter led to lower specificity. In addition, the significantly lower r2 correlation coefficient of the band-pass T1D -filter suggests that the origin of short-T1D components is mostly associated with non-myelin protons. Also, the important contribution of short-T1D s to the estimated MPF, explains its low specificity to myelination as compared to the ihMT high-pass T1D -filters. Long-T1D components imaging by means of ihMT high-pass T1D -filters is proposed as an MRI biomarker for myelin content. Future studies should enable the investigation of the sensitivity of ihMT T1D -filters for demyelinating processes.