Магнитно-резонансная трактография: возможности и ограничения метода, современный подход к обработке данных

Purpose: systematization of the knowledge about diffusion tensor magnetic resonance tomography; analysis of literature related to current limitations of this method and possibilities of overcoming these limitations.Materials and methods. We have analyzed 74 publications (6 Проанализировано 74 публикации (6 Russian, 68 foreign), published in the time period from 1986 to 2021years.  More, than half of these articles were published in the last ten years, 19 studies-in the time period from 2016 to 2021years.Results. In this article we  represent the physical basis of diffusion weighted techniques of magnetic resonance tomography, principles of obtaining diffusion weighted images and diffusion tensor, cover the specific features of the probabilistic and deterministic approaches of the diffusion tensor MRI data processing, describe methods of evaluation of the diffusion characteristics of tissues in clinical practice. Article provides a thorough introduction to the reasons of existing limitations of diffusion tensor MRI and systematization the main developed approaches of overcoming these limitations, such as multi-tensor model, high angular resolution diffusion imaging, diffusion kurtosis visualization. The article consistently reviews the stages of data processing of diffusion tensor magnetic resonance tomography (preprocessing, processing and post processing). We also describe the special aspects of the main approaches to the quantitative data analysis of diffusion tensor magnetic resonance tomography (such as analysis of the region of interest, analysis of the total data amount, quantitative tractography).Conclusion. Magnetic resonance tractography is a unique technique for noninvasive in vivo visualization of brain white matter tracts and assessment of the structural integrity of their constituent axons. In the meantime this technique, which has found applications in numerous pathologies of central nervous system, has a number of significant limitations, and the main of them are the inability to adequately visualize the crossing fibers and the relatively low reproducibility of the results. Standardization of the data postprocessing algorithms, further upgrading of the magnetic resonance scanners and implementation of the alternative tractography methods have the potential of partially reducing of the current limitations.Цель исследования. Систематизация знаний о диффузионной тензорной магнитно-резонансной томографии; анализ литературы, касающейся существующих на сегодняшний момент ограничений метода и возможностей их преодоления.Материал и методы. Проанализировано 74 публикации (6 отечественных, 68 зарубежных), вышедших в свет в период с 1986 по 2021 год. Более половины работ было опубликовано в последнее десятилетие, 19 работ – в период с 2016 по 2021 год.Результаты. В статье изложены физические основы диффузионных методик магнитно-резонансной томографии, принципы получения диффузионно-взвешенных изображений и диффузионного тензора, отражены особенности вероятностного и детерминистского подходов к обработке данных диффузионной тензорной МРТ, а также методы оценки диффузионных характеристик тканей в клинической практике. Подробно рассмотрены причины имеющихся ограничений диффузионной тензорной МРТ, а также систематизированы основные разработанные приемы преодоления этих ограничений, таких как мультитензорная модель, диффузионная визуализация высокого углового разрешения, диффузионная спектральная визуализация, диффузионная куртозисная визуализация. Последовательно рассмотрены этапы обработки данных диффузионной тензорной магнитно-резонансной томографии (препроцессинг, процессинг и постпроцессинг). Отражены особенности основных подходов к количественному анализу данных диффузионной тензорной магнитно-резонансной томографии (таких как анализ области интереса, анализ всего объема данных, количественная трактография).Заключение. Магнитно-резонансная трактография – уникальная методика неинвазивной прижизненной визуализации проводящих путей головного мозга и оценки структурной целостности составляющих их аксонов, нашедшая применение при многих заболеваниях центральной нервной системы. В то же время эта методика имеет ряд существенных ограничений, основными из которых являются невозможность адекватной визуализации перекрещивающихся волокон и относительно низкая воспроизводимость результатов. Стандартизация алгоритмов постпроцессинга данных, дальнейшее совершенствование магнитнорезонансных томографов и внедрение альтернативных методов трактографии потенциально способны частично нивелировать имеющиеся в настоящее время недостатки

Терапевтическая эффективность внутриартериального введения нейральных прогениторных клеток, полученных из индуцированных плюрипотентных стволовых клеток, при остром экспериментальном ишемическом инсульте у крыс

Aim. Neural progenitor cells (NPC) are used for the development of cell therapies of neurological diseases. Their stereotaxic transplantation in the middle cerebral artery occlusion (MCAO) model imitating ischemic stroke results in symptom aleviation. However, exploration of less invasive transplantation options is essential, because stereotaxic transplantation is a complex procedure and can be applied to humans only by vital indications in a specialized neurological ward. The aim of the present study was to evaluate the efficacy of cell therapy of the experimental ischemic stroke by the intra-arterial transplantation of NPC.Materials and methods. NPC for transplantation (IPSC-NPC) were derived by two-stage differentiation of cells of a stable line of human induced pluripotent stem cells. Stroke modeling in rats was carried out by transitory 90 min endovascular MCAO by a silicon-tipped filament. NPC were transplanted 24 hours after MCAO. Repetitive magnetic resonance tomography of experimental animals was made with the Bruker BioSpin ClinScan tomograph with 7 Tl magnetic field induction. Animal survival rate and neurological deficit (using mNSS standard stroke severity scale) were evaluated at the 1st (before IPSC-NPC transplantation), 7th and 14th day after transplantation. Histological studies were carried out following standard protocols.Results. Intra-arterial transplantation of 7 × 105 IPSC-NPC in 1 ml at a constant 100 l/min rate in case of secured blood flow through the internal carotid artery did not cause brain capillary embolism, additional cytotoxic brain tissue edemas or other complications, while inducing increase of animal survival rate and enhanced revert of the neurological deficit. IPSC-NPC accumulation in brain after intra-arterial infusion was demonstrated. Some cells interacted with the capillary endothelium and probably penetrated through the blood-brain barrier.Conclusion. Therapeutic efficacy of the systemic, intra-arterial administration of NPC in ischemic stroke has been experimentally proven. A method of secure intra-arterial infusion of cell material into the internal carotid artery middle in rats has been developed and tested.Цель. Нейральные прогениторные клетки (НПК) используются при разработке технологий клеточной терапии неврологических заболеваний. Их стереотаксическое введение в мозг крыс после имитирующей ишемический инсульт операции окклюзии средней мозговой артерии (ОСМА) приводит к облегчению симптоматики. Однако стереотаксическое введение является сложной процедурой и для лечения болезней человека может быть применено только в специализированной клинике по жизненным показаниям, что делает необходимым исследование возможности менее травматичных способов трансплантации. Цель настоящей работы – исследование возможности проведения клеточной терапии экспериментального инсульта путем внутриартериального введения НПК.Материалы и методы. НПК для трансплантации (ИПСК-НПК) получали путем двухступенчатой дифференцировки клеток стабильной линии индуцированных плюрипотентных стволовых клеток человека. Моделирование инсульта у крыс производилось методом транзиторной (90 мин) эндоваскулярной ОСМА филаментом с силиконовым наконечником. Внутриартериальная трансплантация НПК выполнялась через 24 часа после ОСМА. Магнитно-резонансная томография экспериментальных животных в динамике проводилась на МР-томографе ClinScan фирмы Bruker BioSpin с индукцией магнитного поля 7 Тл. На 1 (до введения ИПСК-НПК), 7 и 14-е сутки после трансплантации оценивались выживаемость животных и неврологический дефицит с использованием стандартной шкалы оценки тяжести инсульта mNSS для грызунов. Гистологические исследования проводили, пользуясь стандартными методами.Результаты. Внутриартериальная трансплантация ИПСК-НПК в дозе 7 × 105 НПК в 1 мл с равномерной скоростью100 мкл/мин и поддержанием кровотока по внутренней сонной артерии не вызывала эмболии капилляров мозга, появления новых зон цитотоксического отека вещества головного мозга или других осложнений и приводила к достоверному повышению выживаемости животных и более быстрому восстановлению неврологического статуса. Продемонстрировано накопление ИПСК-НПК в мозге после их внутриартериальной инфузии. Часть клеток взаимодействовала с эндотелием капилляров и, вероятно, способна проникать через ГЭБ.Заключение. Получено экспериментальное подтверждение терапевтической эффективности НПК при ишемическом инсульте при системной, внутриартериальной трансплантации. Отработан и протестирован метод безопасной внутриартериальной инфузии клеточного материала в бассейн внутренней сонной артерии у крыс

Combined Cell Therapy in the Treatment of Neurological Disorders

Cell therapy of neurological diseases is gaining momentum. Various types of stem/progenitor cells and their derivatives have shown positive therapeutic results in animal models of neurological disorders and in clinical trials. Each tested cell type proved to have its advantages and flaws and unique cellular and molecular mechanism of action, prompting the idea to test combined transplantation of two or more types of cells (combined cell therapy). This review summarizes the results of combined cell therapy of neurological pathologies reported up to this point. The number of papers describing experimental studies or clinical trials addressing this subject is still limited. However, its successful application to the treatment of neurological pathologies including stroke, spinal cord injury, neurodegenerative diseases, Duchenne muscular dystrophy, and retinal degeneration has been reported in both experimental and clinical studies. The advantages of combined cell therapy can be realized by simple summation of beneficial effects of different cells. Alternatively, one kind of cells can support the survival and functioning of the other by enhancing the formation of optimum environment or immunomodulation. No significant adverse events were reported. Combined cell therapy is a promising approach for the treatment of neurological disorders, but further research needs to be conducted

On the proton radiography of magnetic fields in targets irradiated by intense picosecond laser pulses

Proton radiography is a common diagnostic technique in laser-driven magnetic field generation studies. It is based on measuring proton beam deflection in electromagnetic fields induced around the target with the help of radiochromic film stacks. Unraveling information recorded in experimental radiographs and extracting the field profiles is not always a straightforward task. In this paper, some aspects of data analysis by reproducing experimental radiographs in numerical simulations are described. The approach allows determining the field strength and structure in the target area for various target geometries

The Impact of Cerebral Perfusion on Mesenchymal Stem Cells Distribution after Intra-Arterial Transplantation: A Quantitative MR Study

Intra-arterial (IA) mesenchymal stem cells (MSCs) transplantation providing targeted cell delivery to brain tissue is a promising approach to the treatment of neurological disorders, including stroke. Factors determining cell distribution after IA administration have not been fully elucidated. Their decoding may contribute to the improvement of a transplantation technique and facilitate translation of stroke cell therapy into clinical practice. The goal of this work was to quantitatively assess the impact of brain tissue perfusion on the distribution of IA transplanted MSCs in rat brains. We performed a selective MR-perfusion study with bolus IA injection of gadolinium-based contrast agent and subsequent IA transplantation of MSCs in intact rats and rats with experimental stroke and evaluated the correlation between different perfusion parameters and cell distribution estimated by susceptibility weighted imaging (SWI) immediately after cell transplantation. The obtained results revealed a certain correlation between the distribution of IA transplanted MSCs and brain perfusion in both intact rats and rats with experimental stroke with the coefficient of determination up to 30%. It can be concluded that the distribution of MSCs after IA injection can be partially predicted based on cerebral perfusion data, but other factors requiring further investigation also have a significant impact on the fate of transplanted cells

Therapeutic efficacy of intra-arterial administration of induced pluripotent stem cells-derived neural progenitor cells in acute experimental ischemic stroke in rats

Aim. Neural progenitor cells (NPC) are used for the development of cell therapies of neurological diseases. Their stereotaxic transplantation in the middle cerebral artery occlusion (MCAO) model imitating ischemic stroke results in symptom aleviation. However, exploration of less invasive transplantation options is essential, because stereotaxic transplantation is a complex procedure and can be applied to humans only by vital indications in a specialized neurological ward. The aim of the present study was to evaluate the efficacy of cell therapy of the experimental ischemic stroke by the intra-arterial transplantation of NPC.Materials and methods. NPC for transplantation (IPSC-NPC) were derived by two-stage differentiation of cells of a stable line of human induced pluripotent stem cells. Stroke modeling in rats was carried out by transitory 90 min endovascular MCAO by a silicon-tipped filament. NPC were transplanted 24 hours after MCAO. Repetitive magnetic resonance tomography of experimental animals was made with the Bruker BioSpin ClinScan tomograph with 7 Tl magnetic field induction. Animal survival rate and neurological deficit (using mNSS standard stroke severity scale) were evaluated at the 1st (before IPSC-NPC transplantation), 7th and 14th day after transplantation. Histological studies were carried out following standard protocols.Results. Intra-arterial transplantation of 7 × 105 IPSC-NPC in 1 ml at a constant 100 l/min rate in case of secured blood flow through the internal carotid artery did not cause brain capillary embolism, additional cytotoxic brain tissue edemas or other complications, while inducing increase of animal survival rate and enhanced revert of the neurological deficit. IPSC-NPC accumulation in brain after intra-arterial infusion was demonstrated. Some cells interacted with the capillary endothelium and probably penetrated through the blood-brain barrier.Conclusion. Therapeutic efficacy of the systemic, intra-arterial administration of NPC in ischemic stroke has been experimentally proven. A method of secure intra-arterial infusion of cell material into the internal carotid artery middle in rats has been developed and tested

Dynamic MRI of the Mesenchymal Stem Cells Distribution during Intravenous Transplantation in a Rat Model of Ischemic Stroke

Systemic transplantation of mesenchymal stem cells (MSCs) is a promising approach for the treatment of ischemia-associated disorders, including stroke. However, exact mechanisms underlying its beneficial effects are still debated. In this respect, studies of the transplanted cells distribution and homing are indispensable. We proposed an MRI protocol which allowed us to estimate the dynamic distribution of single superparamagnetic iron oxide labeled MSCs in live ischemic rat brain during intravenous transplantation after the transient middle cerebral artery occlusion. Additionally, we evaluated therapeutic efficacy of cell therapy in this rat stroke model. According to the dynamic MRI data, limited numbers of MSCs accumulated diffusely in the brain vessels starting at the 7th minute from the onset of infusion, reached its maximum by 29 min, and gradually eliminated from cerebral circulation during 24 h. Despite low numbers of cells entering brain blood flow and their short-term engraftment, MSCs transplantation induced long lasting improvement of the neurological deficit, but without acceleration of the stroke volume reduction compared to the control animals during 14 post-transplantation days. Taken together, these findings indicate that MSCs convey their positive action by triggering certain paracrine mechanisms or cell–cell interactions or invoking direct long-lasting effects on brain vessels