Characterizing biophysical properties of the Central Nervous System tissue with quantitative Magnetic Resonance Imaging

通过定量磁共振成像表征中枢神经系统组织的生物物理特性

基本信息

  • 批准号:
    RGPIN-2014-04849
  • 负责人:
  • 金额:
    $ 2.62万
  • 依托单位:
  • 依托单位国家:
    加拿大
  • 项目类别:
    Discovery Grants Program - Individual
  • 财政年份:
    2014
  • 资助国家:
    加拿大
  • 起止时间:
    2014-01-01 至 2015-12-31
  • 项目状态:
    已结题

项目摘要

Magnetic Resonance Imaging (MRI) is one of the most versatile imaging techniques for studying fundamental properties of tissue. Since MRI signal is predominantly generated by protons in the water molecules, MRI can be used to study the water behaviour in different environments in different types of tissue, thus allowing characterization of biophysical properties of these tissues. Thanks to MRI’s intrinsically non-invasive character, such studies can be carried out in living organisms, making MRI one of the most powerful techniques to non-invasively study basic biology and physiology. Quantitative T2 MRI has been successfully applied to characterize Central Nervous System (CNS) tissue in human brain. My laboratory has developed similar technology to study rodent spinal cord tissue. In the current application we propose to further develop and validate quantitative MRI techniques to characterize biophysical properties of the rodent CNS tissue. Long term objective of the proposed research programme is the development, validation and application of quantitative MRI techniques to study biophysical properties of CNS tissue in animals. Short term objectives of the proposed research are: 1. To develop 3D MWI of rat spinal cord in vivo. We will extend our 2D Compressed Sensing Myelin Water Imaging (CS MWI) technique to three dimensions. The CS algorithm will take advantage of the data sparsity in the slice dimension, in addition to the two in-plane dimensions and the time dimension used in our 2D CS algorithm. 2. To study fundamental characteristics and limitations of MWI in rodent CNS tissue We will study whether potential exchange of water molecules between the myelin compartment (i.e. the space in between the myelin bi-layers) and the intra-/extra-axonal compartment has any significant effect on Myelin Water Fraction values acquired with our MWI technique from rat spinal cords. We will establish the dependence of MWF values in excised rat spinal cords on the cord temperature. We will also study the effect of tissue fixation on MWF and T2 values by varying the fixation time and phosphate buffer concentration. Finally, we will study the effect of myelin compaction on MWI. We will carry out MWI measurements in PLP-null transgenic mouse model characterized by widening and irregularities of the spaces in between the myelin sheaths: similar pattern to myelin debris. We will compare the MWF values and T2 distributions from the PLP-null cords to the ones obtained from the control cords and cords with myelin debris present. 3. To characterize differences between functional myelin and myelin debris. We will study correlation between ultra-structure of myelin bi-layers measured with electron microscopy (EM) and MWI. Specifically we will compare T2 distributions in functional myelin vs. myelin debris and study how they correspond to morphological features measured with EM. 4. To compare phase MRI and MWI in characterizing biophysical properties of rodent CNS tissue We will compare phase MRI and MWI in their respective abilities to distinguish between myelin debris and functional myelin. Since phase MRI is sensitive to presence of both myelin and axons, its ability to distinguish between functional myelin and myelin debris may be superior to that of the MWI technique. We will verify this through a number of in vivo and ex vivo experiments involving normal and abnormal rat spinal cords. Significance of the proposed research: The proposed program will further expand research capabilities in the area of non-invasive studies of CNS tissue and will help to broaden our understanding of animal CNS biology and physiology. This programme will also provide excellent opportunities for training graduate students in an interdisciplinary environment.
磁共振成像(MRI)是研究组织基本特性的最通用的成像技术之一。由于MRI信号主要由水分子中的质子产生,因此MRI可用于研究不同类型组织中不同环境中的水行为,从而允许表征这些组织的生物物理特性。由于MRI固有的非侵入性特征,这些研究可以在活生物体中进行,使MRI成为非侵入性研究基础生物学和生理学的最强大技术之一。定量T2 MRI已成功应用于表征人脑中的中枢神经系统(CNS)组织。我的实验室已经开发出类似的技术来研究啮齿动物的脊髓组织。在本申请中,我们提出进一步开发和验证定量MRI技术,以表征啮齿动物CNS组织的生物物理特性。拟议研究计划的长期目标是开发、验证和应用定量MRI技术,以研究动物中枢神经系统组织的生物物理特性。本研究的近期目标为:1.建立大鼠在体脊髓三维磁共振成像。我们将扩展我们的二维压缩传感髓鞘水成像(CS MWI)技术到三维。CS算法将利用切片维度中的数据稀疏性,除了我们的2D CS算法中使用的两个平面内维度和时间维度之外。2.为了研究啮齿动物CNS组织中MWI的基本特征和局限性,我们将研究髓磷脂隔室(即髓磷脂双层之间的空间)和轴突内/外隔室之间的水分子的潜在交换是否对用我们的MWI技术从大鼠脊髓获得的髓磷脂水分数值具有任何显著影响。我们将建立在离体大鼠脊髓的MWF值对脊髓温度的依赖性。我们还将通过改变固定时间和磷酸盐缓冲液浓度来研究组织固定对MWF和T2值的影响。最后,我们将研究髓鞘致密化对MWI的影响。我们将在PLP缺失转基因小鼠模型中进行MWI测量,其特征在于髓鞘之间的空间变宽和不规则:与髓鞘碎片相似的模式。我们将比较来自PLP-空索的MWF值和T2分布与从对照索和存在髓磷脂碎片的索获得的MWF值和T2分布。3.表征功能性髓鞘和髓鞘碎片之间的差异。我们将研究电镜(EM)测量的髓鞘双层超微结构与MWI之间的相关性。具体来说,我们将比较T2分布在功能性髓鞘与髓鞘碎片,并研究它们如何对应于与EM测量的形态学特征。4.为了比较相位MRI和MWI在表征啮齿动物CNS组织的生物物理特性方面的作用,我们将比较相位MRI和MWI在区分髓鞘碎片和功能性髓鞘方面的各自能力。由于相位MRI对髓鞘和轴突的存在敏感,因此其区分功能性髓鞘和髓鞘碎片的能力可能上级MWI技术。我们将通过一些涉及正常和异常大鼠脊髓的体内和体外实验来验证这一点。拟议研究的意义:拟议的计划将进一步扩大在中枢神经系统组织的非侵入性研究领域的研究能力,并将有助于扩大我们对动物中枢神经系统生物学和生理学的理解。该计划还将为在跨学科环境中培养研究生提供极好的机会。

项目成果

期刊论文数量(0)
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Kozlowski, Piotr其他文献

Spinal Perineural Cysts among European Patients
Identification of 54 large deletions/duplications in TSC1 and TSC2 using MLPA, and genotype-phenotype correlations
  • DOI:
    10.1007/s00439-006-0308-9
  • 发表时间:
    2007-05-01
  • 期刊:
  • 影响因子:
    5.3
  • 作者:
    Kozlowski, Piotr;Roberts, Penelope;Kwiatkowski, David J.
  • 通讯作者:
    Kwiatkowski, David J.
Identification of Amino Acid Residues of ERH Required for Its Recruitment to Nuclear Speckles and Replication Foci in HeLa Cells
  • DOI:
    10.1371/journal.pone.0074885
  • 发表时间:
    2013-08-28
  • 期刊:
  • 影响因子:
    3.7
  • 作者:
    Banko, Monika I.;Krzyzanowski, Marek K.;Kozlowski, Piotr
  • 通讯作者:
    Kozlowski, Piotr
Assessment of the need for DCE MRI in the detection of dominant lesions in the whole gland: Correlation between histology and MRI of prostate cancer
  • DOI:
    10.1002/nbm.3882
  • 发表时间:
    2018-03-01
  • 期刊:
  • 影响因子:
    2.9
  • 作者:
    Kozlowski, Piotr;Chang, Silvia D.;Goldenberg, S. Larry
  • 通讯作者:
    Goldenberg, S. Larry
Unpredictable changes of selected miRNA in expression profile of HNSCC
  • DOI:
    10.3233/cbm-150540
  • 发表时间:
    2016-01-01
  • 期刊:
  • 影响因子:
    3.1
  • 作者:
    Lamperska, Katarzyna M.;Kozlowski, Piotr;Golusinski, Wojciech
  • 通讯作者:
    Golusinski, Wojciech

Kozlowski, Piotr的其他文献

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{{ truncateString('Kozlowski, Piotr', 18)}}的其他基金

Development and validation of quantitative MRI techniques for CNS tissue
CNS 组织定量 MRI 技术的开发和验证
  • 批准号:
    RGPIN-2019-04505
  • 财政年份:
    2022
  • 资助金额:
    $ 2.62万
  • 项目类别:
    Discovery Grants Program - Individual
Development and validation of quantitative MRI techniques for CNS tissue
CNS 组织定量 MRI 技术的开发和验证
  • 批准号:
    RGPIN-2019-04505
  • 财政年份:
    2021
  • 资助金额:
    $ 2.62万
  • 项目类别:
    Discovery Grants Program - Individual
Development and validation of quantitative MRI techniques for CNS tissue
CNS 组织定量 MRI 技术的开发和验证
  • 批准号:
    RGPIN-2019-04505
  • 财政年份:
    2020
  • 资助金额:
    $ 2.62万
  • 项目类别:
    Discovery Grants Program - Individual
Development and validation of quantitative MRI techniques for CNS tissue
CNS 组织定量 MRI 技术的开发和验证
  • 批准号:
    RGPIN-2019-04505
  • 财政年份:
    2019
  • 资助金额:
    $ 2.62万
  • 项目类别:
    Discovery Grants Program - Individual
Characterizing biophysical properties of the Central Nervous System tissue with quantitative Magnetic Resonance Imaging
通过定量磁共振成像表征中枢神经系统组织的生物物理特性
  • 批准号:
    RGPIN-2014-04849
  • 财政年份:
    2018
  • 资助金额:
    $ 2.62万
  • 项目类别:
    Discovery Grants Program - Individual
Characterizing biophysical properties of the Central Nervous System tissue with quantitative Magnetic Resonance Imaging
通过定量磁共振成像表征中枢神经系统组织的生物物理特性
  • 批准号:
    RGPIN-2014-04849
  • 财政年份:
    2017
  • 资助金额:
    $ 2.62万
  • 项目类别:
    Discovery Grants Program - Individual
Characterizing biophysical properties of the Central Nervous System tissue with quantitative Magnetic Resonance Imaging
通过定量磁共振成像表征中枢神经系统组织的生物物理特性
  • 批准号:
    RGPIN-2014-04849
  • 财政年份:
    2016
  • 资助金额:
    $ 2.62万
  • 项目类别:
    Discovery Grants Program - Individual
Characterizing biophysical properties of the Central Nervous System tissue with quantitative Magnetic Resonance Imaging
通过定量磁共振成像表征中枢神经系统组织的生物物理特性
  • 批准号:
    RGPIN-2014-04849
  • 财政年份:
    2015
  • 资助金额:
    $ 2.62万
  • 项目类别:
    Discovery Grants Program - Individual
Development of quantitative MRI and PET techniques for biological applications
开发用于生物应用的定量 MRI 和 PET 技术
  • 批准号:
    327525-2007
  • 财政年份:
    2013
  • 资助金额:
    $ 2.62万
  • 项目类别:
    Discovery Grants Program - Individual
Development of quantitative MRI and PET techniques for biological applications
开发用于生物应用的定量 MRI 和 PET 技术
  • 批准号:
    327525-2007
  • 财政年份:
    2010
  • 资助金额:
    $ 2.62万
  • 项目类别:
    Discovery Grants Program - Individual

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通过定量磁共振成像表征中枢神经系统组织的生物物理特性
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Characterizing biophysical properties of the Central Nervous System tissue with quantitative Magnetic Resonance Imaging
通过定量磁共振成像表征中枢神经系统组织的生物物理特性
  • 批准号:
    RGPIN-2014-04849
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    $ 2.62万
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