Data-driven retrospective correction of B1 field inhomogeneity in fast macromolecular proton fraction and R1 mapping

Correction of B1 field non-uniformity is critical for many quantitative MRI methods including variable flip angle (VFA) T1 mapping and single-point macromolecular proton fraction (MPF) mapping. The latter method showed promising results as a fast and robust quantitative myelin imaging approach and involves VFA-based R1 = 1/T1 map reconstruction as an intermediate processing step. The need for B1 correction restricts applications of the above methods, since B1 mapping sequences increase the examination time and are not commonly available in clinics. A new algorithm was developed to enable retrospective data-driven simultaneous B1 correction in VFA R1 and single-point MPF mapping. The principle of the algorithm is based on different mathematical dependences of B1-related errors in R1 and MPF allowing extraction of a surrogate B1 field map from uncorrected R1 and MPF maps. To validate the method, whole-brain R1 and MPF maps with isotropic 1.25 mm3 resolution were obtained on a 3 T MRI scanner from 11 volunteers. Mean parameter values in segmented brain tissues were compared between three reconstruction options including the absence of correction, actual B1 correction, and surrogate B1 correction. Surrogate B1 maps closely reproduced actual patterns of B1 inhomogeneity. Without correction, B1 non-uniformity caused highly significant biases in R1 and MPF (P < 0.001). Surrogate B1 field correction reduced the biases in both R1 and MPF to a non-significant level (0.1 ≤ P ≤ 0.8). The described algorithm obviates the use of dedicated B1 mapping sequences in fast single-point MPF mapping and provides an alternative solution for correction of B1 non-uniformities in VFA R1 mapping

Mathematical modeling of the magnetization transfer effect in tissues

The term magnetization transfer (MT) describes a group of molecular processes causing incoherent exchange of magnetic energy between water and macromolecules in biological objects. Magnetic resonance imaging (MRI) can be sensitized to the MT effect using various magnetization preparation techniques. Since its introduction in early 90s, MT MRI has been used in various applications as a tool for quantitative or semi-quantitative tissue characterization and modification of tissue contrast. This review article provides an overview of biophysical mechanisms of MT in tissues, in-depth mathematical consideration of the widely used two-pool model of MT, and a summary of experimental methods used to study MT phenomena

High‐Resolution Multi‐Contrast MRI of the Carotid Artery Wall for Evaluation of Atherosclerotic Plaques

Carotid atherosclerosis is an important medical condition associated with a high potential risk of stroke. In addition to the degree of artery stenosis, the size and tissue composition of the atherosclerotic plaque are thought to be important factors for disease management and prognosis. This unit presents a protocol for high‐resolution multi‐contrast MRI of the carotid artery wall. The protocol employs a combination of bright‐blood magnetic resonance angiography and black‐blood imaging with different contrast weightings (T1, T2, and proton‐density contrasts) in order to provide comprehensive characterization of the atherosclerotic lesion. The images obtained with the protocol presented here can be used to identify basic tissue components of the atherosclerotic plaque (fibrous matrix, lipid core, calcificates, and hemorrhage) and to conduct morphological measurements of plaque size and distribution.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/145403/1/cpmia0104.pd

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

Dynamics of myelin content decrease in the rat stroke model

The majority of studies were usually focused on neuronal death after brain ischemia; however, stroke affects all cell types including oligodendrocytes that form myelin sheath in the CNS. Our study is focused on the changes of myelin content in the ischemic core and neighbor structures in early terms (1, 3 and 10 days) after stroke. Stroke was modeled with middle cerebral artery occlusion (MCAo) in 15 male rats that were divided into three groups by time points after operation. Brain sections were histologically stained with Luxol Fast Blue (LFB) for myelin quantification. The significant demyelination was found in the ischemic core, corpus callosum, anterior commissure, whereas myelin content was increased in caudoputamen, internal capsule and piriform cortex compared with the contralateral hemisphere. The motor cortex showed a significant increase of myelin content on the 1st day and a significant decrease on the 3rd and 10th days after MCAo. These results suggest that stroke influences myelination not only in the ischemic core but also in distant structures

MR histology of advanced atherosclerotic lesions of ApoE- knockout mice

The purposes of this study were to examine the feasibility of determining the composition of advanced atherosclerotic plaques in fixed ApoE-knockout mice and to develop a time-efficient microimaging protocol for MR histological imaging on mice. Five formalin-fixed transgenic ApoE-knockout mice were imaged at the 9.4T Bruker BioSpec MR scanner using 3D spoiled gradient-echo sequence with an isotropic field of view of 24 mm3; TR 20.8 ms; TE 2.6 ms; flip angle 20°, resulted voxel size 47 × 63 × 94 pm3. MRI examination has shown that advanced atherosclerotic lesions of aorta, innominate and carotid arteries in ApoE-knockout mice are characterized by high calcification and presence of the large fibrofatty nodules. MRI quantification of atherosclerotic lesion components corresponded to histological assessment of plaque composition with a correlation coefficient of 0.98

MRI study of the cuprizone-induced mouse model of multiple sclerosis: demyelination is not found after co-treatment with polyprenols (long-chain isoprenoid alcohols)

Multiple sclerosis is a neurological disorder with poorly understood pathogenic mechanisms and a lack of effective therapies. Therefore, the search for new MS treatments remains very important. This study was performed on a commonly used cuprizone animal model of multiple sclerosis. It evaluated the effect of a plant-derived substance called Ropren® (containing approximately 95% polyprenols or long-chain isoprenoid alcohols) on cuprizone- induced demyelination. The study was performed on 27 eight-week old male CD-1 mice. To induce demyelination mice were fed 0.5% cuprizone in the standard diet for 10 weeks. Ropren® was administered in one daily intraperitoneal injection (12mg/kg), beginning on the 6th week of the experiment. On the 11th week, the corpus callosum in the brain was evaluated in all animals using magnetic resonance imaging with an 11.7 T animal scanner using T2- weighted sequence. Cuprizone treatment successfully induced the model of demyelination with a significant decrease in the size of the corpus callosum compared with the control group (p<0.01). Mice treated with both cuprizone and Ropren® did not exhibit demyelination in the corpus callosum (p<0.01). This shows the positive effect of polyprenols on cuprizone-induced demyelination in mice

Demyelination of subcortical nuclei in multiple sclerosis

Myelin containing in basal ganglia in multiple sclerosis patients was evaluated using new noninvasive quantitative MRI method fast whole brain macromolecular proton fraction mapping. Myelin level in globus pallidus and putamen significantly decreased in multiple sclerosis patients as compared with healthy control subjects but not in substantia nigra and caudate nucleus

Plant polyprenols reduce demyelination and recover impaired oligodendrogenesis and neurogenesis in the cuprizone murine model of multiple sclerosis

Recent studies showed hepatoprotective, neuroprotective, and immunomodulatory properties of polyprenols isolated from the green verdure of Picea abies (L.) Karst. This study aimed to investigate effects of polyprenols on oligodendrogenesis, neurogenesis, and myelin content in the cuprizone demyelination model. Demyelination was induced by 0.5% cuprizone in CD-1 mice during 10 weeks. Nine cuprizone-treated animals received daily injections of polyprenols intraperitoneally at a dose of 12-mg/kg body weight during Weeks 6-10. Nine control animals and other nine cuprizone-treated received sham oil injections. At Week 10, brain sections were stained for myelin basic protein, neuro-glial antigen-2, and doublecortin to evaluate demyelination, oligodendrogenesis, and neurogenesis. Cuprizone administration caused a decrease in myelin basic protein in the corpus callosum, cortex, hippocampus, and the caudate putamen compared with the controls. Oligodendrogenesis was increased, and neurogenesis in the subventricular zone and the dentate gyrus of the hippocampus was decreased in the cuprizone-treated group compared with the controls. Mice treated with cuprizone and polyprenols did not show significant demyelination and differences in oligodendrogenesis and neurogenesis as compared with the controls. Our results suggest that polyprenols can halt demyelination, restore impaired neurogenesis, and mitigate reactive overproduction of oligodendrocytes caused by cuprizone neurotoxicity