Spiller M, Brown R D, Koenig S H, Wolf G L
IBM Research Division, T. J. Watson Research Center, Yorktown Heights, New York 10598.
Magn Reson Med. 1988 Nov;8(3):293-313. doi: 10.1002/mrm.1910080307.
The factors that determine the field-dependent increase in 1/T1 of tissue water protons were investigated for MnCl2 and Mn2+ (PDTA) (1,3-propylenediamine-N,N',N'',N'''-tetraacetic acid) introduced intravenously into rabbits. Mn2+ was used in preference to other paramagnetic ions in part because of the distinct NMRD profiles (magnetic field dependence of 1/T1) of free Mn2+ ions, their small chelate complexes, and their macromolecular conjugates, and in part because the relatively low toxicity of Mn2+ is favorable for animal studies. Tissue content of Mn2+ was determined in all samples by inductively coupled plasma analyses the state of Mn2+ in excised tissues was determined from the form of the 1/T1 NMRD profile of water protons; and distribution of contrast agent within tissue and access of water on a T1 time scale were determined by double-exponential analyses of proton relaxation behavior in intact doped tissue, as well as by the change of single-exponential relaxation rates and proton signal intensity upon gentle disruption of the tissue. MnCl2 is found in all tissues, except fat and skeletal muscle, but liver is most avid at low dose, and Mn2+ accumulates in spleen after high doses. Chelation targets Mn2+ to liver and kidney, saturating the liver chemically at relatively low dose. We suggest that pronounced increase in tissue relaxivity results from irrotationally bound Mn2+, ostensibly associated with the polar head groups of cell membranes. Compartmentalization of contrast agent and restricted diffusion of tissue water influences the maximum relaxation rates attainable, so that there is an optimal dose of these contrast agents which is rather low.
研究了静脉注射到兔子体内的氯化锰（MnCl₂）和锰（PDTA）（1,3 - 丙二胺 - N,N',N'',N'''- 四乙酸）时，决定组织水质子1/T₁场依赖性增加的因素。优先使用Mn²⁺而非其他顺磁性离子，部分原因是游离Mn²⁺离子、其小螯合物及其大分子缀合物具有独特的NMRD谱（1/T₁的磁场依赖性），部分原因是Mn²⁺相对较低的毒性有利于动物研究。通过电感耦合等离子体分析测定所有样品中Mn²⁺的组织含量；从水质子的1/T₁ NMRD谱形式确定切除组织中Mn²⁺的状态；通过对完整掺杂组织中质子弛豫行为的双指数分析，以及在轻轻破坏组织后单指数弛豫率和质子信号强度的变化，确定造影剂在组织内的分布以及T₁时间尺度上的水的可及性。除脂肪和骨骼肌外，在所有组织中均发现有MnCl₂，但肝脏在低剂量时摄取最 avid，高剂量时Mn²⁺在脾脏中积累。螯合作用将Mn²⁺靶向肝脏和肾脏，在相对低剂量时化学性地饱和肝脏。我们认为组织弛豫率的显著增加是由于非旋转结合的Mn²⁺，表面上与细胞膜的极性头部基团相关。造影剂的区室化和组织水的受限扩散影响可达到的最大弛豫率，因此这些造影剂存在一个相当低的最佳剂量。
