Table of contents

A.V. Naumova ^1,2, M.Yu. Khodanovich^1,2, V.L. Yarnykh^1,2

¹ Department of Radiology, University of Washington, Seattle, WA, USA

² Research Institute of Biology and Biophysics, Tomsk State University, Tomsk, Russia

Abstract

The Third International Conference and Young Scientist School "Magnetic Resonance Imaging in Biomedical Research" was held in Novosibirsk, Russia, on November 24-26, 2016. The Conference was held within the framework of the International Congress on Clinical and Translational Neuroimaging organized by the International Tomography Center of the SB RAS, Institute of Medicine and Psychology at Novosibirsk State University (NSU), Institute of Cytology and Genetics of the SB RAS, and Tomsk State University (TSU).

The Conference focused on magnetic resonance imaging (MRI) applications for biomedical research. The main goal was to bring together major scientists, clinical researchers and developers of new MRI techniques to bridge the gap between clinical/research needs and advanced technological solutions. The Conference encouraged research and development in basic and clinical MR science and its application in health care. It also had an educational purpose to promote understanding of cutting-edge MR developments. The Conference provided an opportunity for researchers and clinicians to present their recent theoretical developments, practical applications, and to discuss acute problems.

The program of the Conference was divided into three main topics. The first day of the Conference was devoted to educational lectures on the fundamentals of MRI physics and image acquisition/reconstruction techniques including recent developments in quantitative MRI. The second day focused on developments and applications of new contrast agents. Multinuclear and spectroscopic acquisitions as well as functional MRI were presented on the third day of the Conference.

We would like to highlight the main developments presented at the Conference and introduce the prominent speakers. The keynote speaker of the conference Dr. Vasily Yarnykh (University of Washington, Seattle, USA) demonstrated a method of macromolecular proton fraction and its application in clinical and preclinical studies. Professor Yury Pirogov (Lomonosov Moscow State University) presented development of multinuclear magnetic resonance imaging in biomedical experiments. Dr. Marina Khodanovich (Tomsk State University) described histological validation of macromolecular proton fraction mapping on the model of cuprizone-induced demyelination.

We express our thanks to the scientific committee, the local organizing committee and Tomsk State University for giving the opportunity to share scientific ideas and up-to-date developments at the Conference, and the Russian Science Foundation (project № 14-45-00040) and Biovitrum Ltd. for financial support.

All papers published in this volume of Journal of Physics: Conference Series have been peer reviewed through processes administered by the proceedings Editors. Reviews were conducted by expert referees to the professional and scientific standards expected of a proceedings journal published by IOP Publishing.

This paper presents a method for optimizing the parameters of the scanning pulse sequences for MRI in relation to objects with a wide NMR spectrum. In this case, a broadband excitation of the spin system is difficult because of hardware limitations. It is proposed to apply the selective excitation, the optimum parameters of which are calculated by an algorithm that uses information concerning the NMR spectrum. The method is especially useful for ¹⁹F MRI of fluorocarbons.

Stroke studies employ experimental models of cerebral ischemic and reperfusion injury in rodents. MRI provides valuable supravital data of cerebral blood flow and brain tissue damage. This paper presents MRI applications for cerebral blood flow research in mice lines with impaired nitric oxide production by endothelial nitric oxide synthase. Our data demonstrates that specific modifications of MRI methodology in transgenic mouse models help to evaluate the role of eNOS in the brain-blood barrier function.

Enzymatic oxidation of L-arginine catalyzed by inducible nitric oxide synthase gives nitric oxide as the main product and superoxide anion as a side reaction product. Recombination of these radicals gives a very reactive species – peroxynitrite, which is involved in many biochemical processes. In the current work it was shown that such a system can be a usable model system for investigating the influence of magnetic field on enzymatic peroxynitrite formation. Using a selective fluorescent probe for peroxynitrite - coumarin boronic acid and an adopted for the experimental purpose incubation mixture, magnetic field experiments have been done at 11.7T. The averaged magnetic field effect is equal to 2.8±0.9%.

The study aims to evaluate the effect of insulin-like growth factor 1 (IGF-1) on the demyelination and astrogliosis using the cuprizone murine model. Demyelination was induced in 14 adult male mice by 0.3% cuprizone in drinking water. Five animals from the cuprizone-treated group received subcutaneous injections of IGF-1. Seven animals were used as a control group. The extent of demyelination was evaluated as a decrease in the size of the corpus callosum on T2-weighted images that were received using an 11.7T animal MRI scanner. Brain sections were immunohistochemically stained for glial fibrillary acidic protein (GFAP), a marker of astrocytes. It was revealed that the cuprizone caused extensive demyelination and astroglyosis. IGF-1 treatment restored the size of the corpus callosum and the number of astrocytes in the corpus callosum and the anterior commissure to the control level.

The detection of nuclei other than protons can significantly enhance the opportunities of MRI method. Thereby one of the most promising nuclei in this field is fluorine-19. We showed that it is possible to visualize lungs, gastrointestinal tract and inflammation regions by 19F MRI without complicated and expensive specific technics. Moreover, the use of other nuclei in multinuclear applications is also possible and it is a promising direction in this field.

The study aimed to assess the neural activity of different brain regions in patients with fragile X syndrome (FXS) and the healthy volunteers by resting-state functional magnetic resonance imaging (fMRI) on a 1.5 T MRI Achieva scanner (Philips). Results: The fMRI study showed a DMN of brain function in patients with FXS, as well as in the healthy volunteers. Furthermore, it was found that a default mode network of the brain in patients with FXS and healthy volunteers does not have statistically significant differences (p>0.05), which may indicate that the basal activity of neurons in patients with FXS is not reduced. In addition, we have found a significant (p<0.001) increase in the FC within the right inferior parietal and right angular gyrus in the resting state in patients with FXS. Conclusion: New data of functional status of the brain in patients with FXS were received. The significant increase in the resting state functional connectivity within the right inferior parietal and right angular gyrus (p<0.001) in patients with FXS was found.

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.

Astrocytes are the most abundant cell class in the CNS. Astrocytic therapies have a huge potential for neuronal repair after stroke. The majority of brain stroke studies address the damage to neurons. Modern studies turn to the usage of morphological and functional changes in astroglial cells after stroke in regenerative medicine. Our study is focused on the changes in the number of astrocytes in the hippocampus (where new glia cells divide) after brain ischemia. Ischemia was modeled by occlusion of tr. brachiocephalicus, a. subclavia sin., a. carotis communis sin. Astrocytes were determined using immunohistochemical labeling with anti GFAP antibody. We found out that the number of astrocytes increased on the 10^th and 30^th days after stroke in the CA1, CA2 fields, the granular layer of dentate gyrus (GrDG) and hilus. The morphology of astrocytes became reactive in these regions. Therefore, our results revealed long-term reactive astrogliosis in the hippocampus region after total ischemia in rats.

Macromolecular proton fraction (MPF) is a biophysical parameter describing the amount of macromolecular protons involved into magnetization exchange with water protons in tissues. MPF represents a significant interest as a magnetic resonance imaging (MRI) biomarker of myelin for clinical applications. A recent fast MPF mapping method enabled clinical translation of MPF measurements due to time-efficient acquisition based on the single-point constrained fit algorithm. However, previous MPF mapping applications utilized only 3 Tesla MRI scanners and modified pulse sequences, which are not commonly available. This study aimed to test the feasibility of MPF mapping implementation on a 1.5 Tesla clinical scanner using standard manufacturer's sequences and compare the performance of this method between 1.5 and 3 Tesla scanners. MPF mapping was implemented on 1.5 and 3 Tesla MRI units of one manufacturer with either optimized custom-written or standard product pulse sequences. Whole-brain three-dimensional MPF maps obtained from a single volunteer were compared between field strengths and implementation options. MPF maps demonstrated similar quality at both field strengths. MPF values in segmented brain tissues and specific anatomic regions appeared in close agreement. This experiment demonstrates the feasibility of fast MPF mapping using standard sequences on 1.5 T and 3 T clinical scanners.

Chronic disorders of consciousness are clinically challenging conditions, and advanced methods of imaging for better understanding of diagnosis and prognosis are needed. Recent functional neuroradiological studies utilizing PET and fMRI demonstrated that besides widespread neuronal loss disruption of interconnection between certain cortical networks after the injury may also play the leading role in the development of behaviourally assessed unresponsiveness. Functional and structural connectivity, evaluated by neuroimaging approaches, may correlate with clinical status and may also play prognostic role. Integration of data from various diagnostic modalities is needed for further progress in this area.

Intra-arterial transplantation of mesenchymal stem cells (MSCs) is an effective delivery route for treatment of ischemic brain injury. Despite significant therapeutic effects and targeted cells delivery to the brain infraction, serious adverse events such as cerebral embolism have been reported and may restrict potential clinical applications of this method. In current study, we evaluate potential complications of intra-arterial MSCs administration and determine the optimum parameters for cell transplantation. We injected SPIO-labeled human MSCs via internal carotid artery with different infusion parameters and cell dose in intact rats and in rats with the middle cerebral occlusion stroke model. Cerebrovascular complications and labeled cells were visualized in vivo using MRI. We have shown that the incidence of cerebral embolic events depends on such parameters as cell dose, infusion rate and maintenance of blood flow in the internal carotid artery (ICA). Optimal parameters were considered to be 5×10⁵ hMSC in 1 ml of PBS by syringe pump with velocity 100 μ/min and maintenance of blood flow in the ICA. Obtained data should be considered before planning experiments in rats and, potentially, can help in planning clinical trials in stroke patients.

In this research, a cuprizone model of multiple sclerosis (MS) was used to study oligodendrogenesis and neurogenesis in remyelination. It has been shown that, with the administration of cuprizone, the amount of myelin in a number of structures of white and gray matter and the level of neurogenesis decrease, while the level of oligodendrogenesis increases. The withdrawal of cuprizone leads to the restoration of myelin content, the reduction of the excessive production of oligodendrocytes and to the restoration of the number of neurons to control values. The negative correlation between the number of oligodendrocyte precursors (OPCs) and the degree of demyelination of the corpus callosum indicates migration of OLG precursors from the subventricular zone (SVZ) to the structure during demyelination.

Cerebral hyperperfusion syndrome (CHS) after revascularization is a rare phenomenon associated with post-ischemic (reactive) hyperemia and acute pathological hyperperfusion. First described on perfusion CT as a very often moderate CBF increase, MTT/TTP decrease within 30% like a temporary effect, according to a short-time deterioration of neurological symptoms (vestibular ataxia - 58%, vegetative dysfunction - 100%, asthenic syndrome - 100%) in early postoperative period in patients with cardiac ischemia who had undergone coronary artery bypass surgery. The acute pathological hyperperfusion carotid revascularization is a casuistic phenomenon with two- or three-fold CBV and MTT/TTP increase and high hemorrhage risk. Besides, we detected similar exchanges via perfusion CT called benign hyperemia, which marks extension of MTT/TTP and an increase of CBV from 27% to 48% (average 30%), but with normal CBF-parameters, indicating that venous stasis in acute venous ischemic stroke due cerebral venous sinus-trombosis (68%), only 6% in cardioembolic stroke and appears never in arterial stroke. Territorial coincidence registered for perifocal of necrosis zones of benign hyperemia and vasogenic edema accompanied on MRI (DWI, ADC). Secondary hemorrhagic transformation registered for primary non-hemorrhagic venous stroke in 27%, only in 9% for arterial stroke and in 60% for cardioembolic stroke. Probably, congestion is an increasingly predisposing factor secondary hemorrhaging than necrosis.

Non-invasive molecular imaging techniques can enhance diagnosis of neurological diseases to achieve their successful treatment. Positron emission tomography (PET) imaging can identify activated microglia and provide detailed functional information based on molecular biology. This imaging modality is based on detection of isotope labeled tracers, which emit positrons. The review summarizes the developments of various radiolabeled ligands for PET imaging of neuroinflammation.

The blood realizes the transport of substances, which are necessary for livelihoods, throughout the body. The assumption about the relationship some disease and structure of vasculature (in particular of brain) is natural. In the paper we consider models of Willis' circle for two groups of laboratory mice – one control group and another with diabetes. Vascular net obtained as a result of preprocessing MRI data. The purpose of the work is to determine the effect of type 1 diabetes on the properties of the laboratory mice vasculature.