7 Tesla MRI Bolus CR Studies of Human BBB Permeability

7 人体 BBB 渗透性的特斯拉 MRI Bolus CR 研究

• 批准号: 8431800
• 负责人: WILLIAM D ROONEY
• 金额: $ 31.28万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-04-15 至 2016-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8431800
• 关键词: A-factor (Streptomyces); Accounting; Acute; Affect; Agreement; Area; Biological Markers; Biophysics; Blood; Blood - brain barrier anatomy; Blood Vessels; Blood Volume; Blood capillaries; Bolus Infusion; Brain; Brain Pathology; Brain region; Breast Cancer Detection; Cardiomyopathies; Cell Volumes; Cerebrum; Chronic; Complement 3d Receptors; Data; Dependence; Detection; Development; Diagnostic; Dose; Drug Kinetics; Equilibrium; Exhibits; Extravasation; Generations; Goals; Gold; Grant; Health; Histocompatibility Testing; Hour; Human; Image; Influentials; Injection of therapeutic agent; Kinetics; Knowledge; Laboratories; Lesion; Magnetic Resonance Imaging; Malignant Neoplasms; Maps; Measurement; Measures; Methods; Modeling; Molecular; Monitor; Multiple Sclerosis; Multiple Sclerosis Lesions; Myocardium; Noise; Pathology; Pathway interactions; Permeability; Physical Chemistry; Physics; Physiologic pulse; Physiology; Property; Reagent; Relaxation; Resolution; Rodent; Signal Transduction; Specificity; Speed; Stroke; Surface; Syringes; Techniques; Time; Tissues; Variant; Water; Weight; Work; capillary; disease phenotype; falls; gray matter; improved; in vivo; instrument; interest; interstitial; magnetic field; molecular mass; novel; pharmacokinetic model; radiotracer; research study; spatiotemporal; white matter

DESCRIPTION (provided by applicant): The long-term goal of this project is absolute quantification of (Dynamic-Contrast-Enhanced) DCE-MRI, the high spatiotemporal resolution recording of contrast reagent (CR) passage following bolus injection, via its effect on the tissue 1H2O MR signal longitudinal relaxation time constant (T1). Though applied to all tissues, the approved, low-MW Gd(III) chelate CRs are particularly sensitive probes of blood-brain-barrier (BBB) integrity. Even slight compromises of the para(endothelial)cellular pathway mainly defining BBB tightness are detected. In particular, this work exploits two recent developments - the increased availability of ultra-high magnetic field [BB0 e 7 Tesla (T)] whole-body MRI, and the introduction of the "Shutter-Speed" DCE-MRI pharmacokinetic model (SSM). The former is important because it has recently been shown that CR detectability increases with BB0: i.e., the detection threshold CR concentration decreases with increasing BB0. One consequence is that, at least by 4T, it is possible to detect monomeric Gd(III) chelate extravasation across even the normal BBB. This is contrary to conventional wisdom only because it is not easily detectable at BB0 values [d 3T] currently used clinically: it occurs in all diagnostic CR MRI examinations. The SSM corrects a significant systematic error in the almost universally used Standard DCE-MRI pharmacokinetic Model (SM). SSM incorporates the effects of equilibrium intercompartmental water exchange kinetics, which are crucial since CR detection is indirect - via its effect on 1H2O. Large systematic errors in DCE-MRI pharmacokinetic parameters, Ktrans (volume-weighted CR trans-BBB rate constant), vb (blood volume fraction), and ve (interstitial volume fraction) can occur if shutter-speed effects are ignored. [For example, such SM errors negate very high (so far perfect) specificity in SSM DCE-MRI breast cancer screening.] The SSM recognizes that DCE-MRI is an intrinsically dual probe (CR and water) technique. It is proposed here that, at high BB0 (7T), SSM will allow high-resolution mapping of the permeability coefficient capillary surface area products for CR and water (PCRS and PWS) for the whole brain. Since S is an extensive property, it increases with vb. Thus, PS maps usually show greater intensity in gray matter (GM) than white matter because of the larger GM vb value. However, it is proposed that the ratio PCRS/PWS measures the intensive property PCR/PW. This new imaging biomarker has a very large dynamic range [>10-2 (musculature) to 10-5 (normal brain)], and should be exquisitely sensitive to normal brain anatomical variations and to BBB compromise, from subtle to major. The three specific aims are to: 1.) optimize DCE-MRI at 7T, and map PCR/PW in the entire 2.) normal brain, and in the entire 3.) normal-appearing, acute lesion-containing, and chronic lesion multiple sclerosis (MS) brain. [Comparison of neutral CR0 and anionic CR2- in the normal brain will probe the PCR molecular mechanism.] This work involves aspects of physics, physical chemistry, biophysics, physiology, and relates to a number of pathologies including MS, stroke, cancer, and myocardial disease.

描述（由申请人提供）：该项目的长期目标是（动态对比增强）DCE-MRI 的绝对量化，即通过其对组织 1H2O MR 信号纵向弛豫时间常数 (T1) 的影响，对推注后造影剂 (CR) 通道进行高时空分辨率记录。尽管适用于所有组织，但已批准的低分子量 Gd(III) 螯合物 CR 是血脑屏障 (BBB) 完整性特别敏感的探针。甚至可以检测到主要定义 BBB 紧密性的（内皮）细胞旁通路的轻微损害。特别是，这项工作利用了两项最新进展 - 超高磁场 [BB0 e 7 Tesla (T)] 全身 MRI 可用性的增加，以及“快门速度”DCE-MRI 药代动力学模型 (SSM) 的引入。前者很重要，因为最近表明 CR 可检测性随着 BB0 的增加而增加：即检测阈值 CR 浓度随着 BB0 的增加而降低。结果之一是，至少在 4T 时，甚至可以检测到正常 BBB 中的单体 Gd(III) 螯合物外渗。这与传统观点相反，只是因为它在目前临床使用的 BB0 值 [d 3T] 下不容易检测到：它出现在所有诊断性 CR MRI 检查中。 SSM 纠正了几乎普遍使用的标准 DC​​E-MRI 药代动力学模型 (SM) 中的显着系统误差。 SSM 结合了平衡室间水交换动力学的影响，这一点至关重要，因为 CR 检测是间接的 - 通过其对 1H2O 的影响。如果忽略快门速度影响，DCE-MRI 药代动力学参数、Ktrans（体积加权 CR trans-BBB 速率常数）、vb（血液体积分数）和 ve（间质体积分数）可能会出现较大的系统误差。 [例如，此类 SM 错误否定了 SSM DCE-MRI 乳腺癌筛查中非常高（迄今为止完美）的特异性。]SSM 认识到 DCE-MRI 本质上是一种双探针（CR 和水）技术。这里建议，在高 BB0 (7T) 下，SSM 将允许对全脑 CR 和水（PCRS 和 PWS）的渗透系数毛细血管表面积产品进行高分辨率绘图。由于 S 是一个广泛的属性，因此它随着 vb 的增加而增加。因此，PS 图通常显示灰质 (GM) 的强度高于白质，因为 GM vb 值较大。然而，建议比率PCRS/PWS衡量强度属性PCR/PW。这种新的成像生物标志物具有非常大的动态范围[>10-2（肌肉组织）至10-5（正常大脑）]，并且应该对正常大脑解剖变化和BBB妥协（从细微到主要）极其敏感。这三个具体目标是：1.) 在 7T 下优化 DCE-MRI，并在整个 2.) 正常大脑和整个 3.) 正常外观、包含急性病变和慢性病变多发性硬化 (MS) 大脑中绘制 PCR/PW。 【比较正常大脑中的中性CR0和阴离子CR2-，探讨PCR分子机制。】这项工作涉及物理学、物理化学、生物物理学、生理学等方面，涉及多发性硬化症、中风、癌症、心肌疾病等多种病理学。

项目成果

Gray matter blood-brain barrier water exchange dynamics are reduced in progressive multiple sclerosis.

• DOI: 10.1111/jon.12912
• 发表时间: 2021-11
• 期刊: JOURNAL OF NEUROIMAGING
• 影响因子: 2.4
• 作者: Tagge, Ian J.;Anderson, Valerie C.;Springer, Charles S.;Sammi, Manoj K.;Bourdette, Dennis M.;Spain, Rebecca, I;Rooney, William D.
• 通讯作者: Rooney, William D.

Signal-to-noise ratio, contrast-to-noise ratio and pharmacokinetic modeling considerations in dynamic contrast-enhanced magnetic resonance imaging.

• DOI: 10.1016/j.mri.2012.05.005
• 发表时间: 2012-11
• 期刊: MAGNETIC RESONANCE IMAGING
• 影响因子: 2.5
• 作者: Li, Xin;Huang, Wei;Rooney, William D.
• 通讯作者: Rooney, William D.

Human whole-blood (1)H2O longitudinal relaxation with normal and high-relaxivity contrast reagents: influence of trans-cell-membrane water exchange.

• DOI: 10.1002/mrm.25064
• 发表时间: 2014-12
• 期刊: MAGNETIC RESONANCE IN MEDICINE
• 影响因子: 3.3
• 作者: Wilson, Gregory J.;Woods, Mark;Springer, Charles S.;Bastawrous, Sarah;Bhargava, Puneet;Maki, Jeffrey H.
• 通讯作者: Maki, Jeffrey H.

Discrimination of intra- and extracellular 23Na+ signals in yeast cell suspensions using longitudinal magnetic resonance relaxography.

使用纵向磁共振松弛成像技术区分酵母细胞悬浮液中的细胞内和细胞外 23Na 信号。

• DOI: 10.1016/j.jmr.2010.03.018
• 发表时间: 2010
• 期刊: Journal of magnetic resonance (San Diego, Calif. : 1997)
• 作者: Zhang,Yajie;Poirer-Quinot,Marie;SpringerJr,CharlesS;Balschi,JamesA
• 通讯作者: Balschi,JamesA

Cell membrane water exchange effects in prostate DCE-MRI.

• DOI: 10.1016/j.jmr.2012.03.019
• 发表时间: 2012-05
• 期刊: JOURNAL OF MAGNETIC RESONANCE
• 影响因子: 2.2
• 作者: Li, Xin;Priest, Ryan A.;Woodward, William J.;Siddiqui, Faisal;Beer, Tomasz M.;Garzotto, Mark G.;Rooney, William D.;Springer, Charles S., Jr.
• 通讯作者: Springer, Charles S., Jr.