紫杉醇治疗小鼠S180肉瘤的体内31P MRS研究

为了研究紫杉醇治疗小鼠S180肉瘤的³¹P MRS参数的变化及这些参数的变化是否早于常规观察的瘤体积的变化.方法:利用表面线圈³¹P NMR方法,研究小鼠皮下接种的S180肉瘤.结果:用药48h后给药组的PCr/Pi、β-NTP/Pi、PME/β-NTP比值与对照组有显著性差别(P<0.05),而肿瘤体积在给药组和对照组之间无显著性差别,³¹P MRS参数的变化早于瘤体积变化.结论:小鼠S180肉瘤³¹P MRS不仅可以给出定量的结果,而且可以较早地显示出治疗的效果.     

急性低氧大鼠脑31P核磁共振波谱研究

³¹P磁共振波谱是目前唯一可以用作在体无损伤的检测细胞水平能量代谢变化的非侵入性技术,可测得脑内多种能量代谢产物.目的：急性低氧大鼠脑组织的³¹P MRS检测.方法：(1)20只成年SD大鼠分为4组：低氧0min(对照),5min,10min,15min后,迅速液氮冷冻;(2)将脑组织研碎后,加入高氯酸(PCA),冷冻干燥;(3)将提取物用0.5mL D\-2O溶解后进行MRS检测.结果：(1)急性低氧早期即引起³¹P MRS中PCr和ATP峰降低,ADP和Pi峰增高,PCr/Pi和ATP/Pi降低,而ADP/ATP增高.可交换磷池(EPP)中PCr的正常值为42.4%,低氧5min后降到28.9%, ATP从33.8%降到19.2%,Pi从17.7%升到42.0%.(2)急性低氧时³¹P MRS中脑内磷酯分解代谢产物GPC、GPE含量增加,说明低氧早期脑内即有膜磷酯的分解增加.结论：³¹P磁共振波谱可用于脑低氧性疾病的诊断,我们波谱中最敏感的指标是PCr/Pi和ATP/Pi,尤其早期降低更为显著.     

一种脑代谢研究的有效方法——高分辨率磁共振波谱分析

介绍了一种脑代谢研究的有效方法.成年大鼠脑经漏斗法液氮冷冻,制备脑组织高氯酸提取物并冷冻干燥,所得固体溶于D2O后用¹H和³¹P磁共振波谱(MRS)检测.结果表明：脑高氯酸提取物的磁共振波谱有着极好的分辨率,³¹P MRS可以分辨出ATP、ADP、磷酸肌酸(PCr)、无机磷以及多种磷酯和糖磷;¹H MRS可以分辨出乳酸(Lac)、N-乙酰天冬氨酸(NAA)、胆碱(Cho)、肌酸(Cr)、GABA、肌醇(Ino)、琥珀酸(Suc)以及多种氨基酸.各波峰积分后得到各种物质的相对含量,而这些代谢中间产物的相对含量变化可以反应脑内的代谢状况和脑受损伤情况.     

高场磁共振成像1H/31P双调谐射频线圈研究进展

在众多可产生磁共振现象的原子核中,¹H核凭借其在生物体中含量高、磁共振信号强的优势,成为磁共振成像的主要研究对象．但其它杂核在生命科学相关研究中同样具有不可替代的独特性,如³¹P核广泛参与了生物体内的能量代谢过程,是非质子成像研究领域的重要内容．MRI向更高场强的发展使得杂核成像逐渐普及,其核心部件是高质量的¹H/³¹P双调谐射频线圈．本文总结了与¹H/³¹P双调谐射频线圈相关的研究与应用,展示了9.4 T下小鼠脑的质子磁共振成像及磁共振磷谱,并讨论了高场¹H/³¹P双调谐射频线圈的潜在应用价值．     

人淋巴瘤白血病细胞系Molt-4的31P核磁共振研究

用³¹P核磁共振(NMR)观察了人淋巴瘤白血病细胞系Molt-4的³¹P谱.NMR测试温度为37℃、20℃和4℃时,随着测试时间增长,细胞³¹P谱中ATP峰降低,无机磷峰升高,细胞³¹P谱的变化随测试温度降低依次减缓.实验温度为4℃,从收集细胞至开始NMR累加在30min内,NMR累加在60min内,获得活细胞的稳定的³¹P谱.根据细胞内无机磷的化学位移数值,对细胞内pH值进行了测定.     

金属核的磁共振研究*Ⅱ含磷配体铂(Ⅱ)络合物的195Pt和31P-NMR谱

本文测定了12个含苯基环戊基磷、亚磷酸、卤素等配体的铂(Ⅱ)络合物的¹⁹⁵Pt、³¹P-NMR谱,考察了溶剂、浓度、温度对¹⁹⁵Pt谱的影响,研究了¹⁹⁵Pt、³¹P化学位移、偶合常数与络合物几何构型的关系及对卤素的依赖关系。讨论1,2-丙二胺溶液中络合物³¹P谱的变化,以及各种含亚磷酸配体的铂络合物¹⁹⁵Pt和³¹P谱的变化。     

大鼠急性缺血心肌31P磁共振波谱的基础研究

利用³¹P磁共振波谱（MRS）检测了急性缺血心肌组织提取物中高能磷酸化合物的变化. 方法：成年SD大鼠在心肌梗塞后0、5、 20、45 min后进行取材,梗塞区、边缘区及正常区的心肌组织经高氯酸萃取后进行高分辨MRS检测. 结果：梗塞区,缺血5 min PCr/Pi比值下降到对照组的12 ％;20 min ATP/Pi 比值下降至0.05,Pi/EPP比值上升至0.8;45 min 梗塞区PDE/ATP上升至1.93,与45 min心肌的不可逆损伤超微结构相吻合. 边缘区各代谢产物出现改变的程度要小于梗塞区,大于正常区. 正常区也有能量代谢的改变. 结论：心肌组织的³¹P MRS能够反映心肌缺血后心肌不同部位的动态能量代谢改变. PDE/ATP是判断心肌不可拟性损伤的可靠指标.     

S-烷基-O-(邻烷氧基羰基苯基)-硫(赶)代磷酰胺的NMR研究

本工作记录了六种通式为H₂N RS P=O-O-COOR'(R=Me,Et,i-Pr,n-Pr;R'=Me,Et,i-Pr)的有机磷农药的¹H、¹³C、³¹P NMR谱及¹³C,¹H异核化学位移相关谱。确定了各¹H、¹³C、³¹P的化学位移值和¹H-¹H、³¹P-¹H、³¹P-¹³C的偶合常数。讨论了核磁参数与分子结构和运动以及³¹P化学位移与生物活性之间的关系。     

体内31P NMR表面线圈探头的研制

报道一种为进行活体小动物核磁共振实验而研制的体内³¹P NMK表面线圈探头.该探头工作频率为161.83MHz,无载Q值为300,可无损伤地研究生命体内各部位的性质.本文给出了用该探头所测得的小鼠体内肝脏、大腿肌肉、大脑以及大脑缺氧状态下³¹P NMR谱图实例.     

双环磷酸酯类化合物NMR结构效应研究

用现有理论说明不了双环磷酸酯类化合物³¹P NMR化学位移的变化。本文在我们提出的核外电子云球对称效应原理基础上,用量子化学和分子力学计算的参数,表达了这类化合物³¹P化学位移变化的规律,同时还研究了它们的¹³C NMR化学位移和偶合常数的取代基效应。     

Effect of melanin on phosphorus T1s in human melanoma xenografts studied by 31P MRS

³¹P MRS resonance ratios of tumors depend on the T₁s of the phosphorus compounds. The objective of the ³¹P MRS study reported here was to investigate whether the phosphorus T₁s of melanomas are influenced by the presence of melanin. One amelanotic (COX-t) and one melanotic (ROX-t) human melanoma xenograft line were studied at two different tumor volumes: 200 and 1000 mm³. ³¹P MRS was performed in nonanaesthetized mice at 4.7 T. The T₁s were measured by using the superfast inversion recovery technique. Fraction of necrotic tissue in the tumors was determined by histological examination. The ROX-t tumors showed shorter T₁s than the COX-t tumors at a volume of 200 mm³, where the fraction of necrotic tissue in the tumors was insignificant. The difference was similar in magnitude for all resonances. The T₁s were not significantly different for COX-t and ROX-t at a volume of 1000 mm³, where the tumors of both lines had developed significant necrosis. The phosphorus T₁s of melanomas without necrosis can be shortened significantly by the presence of melanin. The magnitude of the T₁ shortening is similar for all major compounds. ³¹P MRS resonance ratios of melanomas are not altered significantly by correcting for effects of partial saturation.     

Radio-frequency probe for 1H decoupled 31P MRS of the head and neck region.

For optimal performance of 31P MRS at 1.5 Tesla, the use of a double resonant probe is essential to enable the application of 1H decoupling and Nuclear Overhauser Enhancement. This note describes the design, evaluation and safety validation of a versatile and compact probe optimized for 1H decoupled 31P MRS studies of tumors close to the surface of the body, in particular the head and neck region.     

Quality assessment in in vivo NMR spectroscopy: V. Multicentre evaluation of prototype test objects and protocols for performance assessment in small bore MRS equipment

This paper reports the results of multicentre studies aimed at designing, constructing, and evaluating prototype test objects for performance assessment in small-bore MRS systems, by utilizing the test protocols already proposed by the EEC COMAC-BME Concerted Action for clinical MRS equipment. Three classes of test objects were considered: (1) a multicompartment test object for ³¹P MRS measurements performed with slice-selective sequences; (2) a two-compartment test object for volume-selection ¹H MRS; and (3) two-compartment test objects for assessing the performance of experimental systems using ISIS as volume localization sequence in ³¹P MRS. The results suggested the interest of adopting some of these prototypes for improving the comparison of spectroscopy data obtained from different sites, for providing useful means of quality assurance in experimental MRS, and facilitating the validation of new localization sequences.     

Point-wise measurements of MRS volume selection performance are insensitive to magnetic susceptibility effects of phantom materials

The purpose was to analyse magnetic susceptibility effects on accuracy of point-wise measurements of signal profiles in the assessment of MRS volume selection performance. An existing phantom design consisting of a sphere with a movable signal source was used for the investigation. The influence from the phantom on magnetic field homogeneity was measured with phase sensitive 1H imaging and 31P spectroscopy on a 1.5 T whole body MR system. The susceptibility effects for such a phantom design can be separated in 1/ A variation in the background magnetic field, which is caused by the stationary structures and has a significant influence on spatial accuracy. 2/ A magnetic field distortion, which is caused by the movable signal source and has very little influence on accuracy. The spatial inaccuracy due to susceptibility effects in this phantom, was 0.03 mm for positions of the signal source covering a 40-mm VOI. Susceptibility effects from the movable signal source were substantial but had very little influence on spatial accuracy. Still, improvements of this phantom design are possible. Point-wise measurements using a phantom with a movable signal source is inherently insensitive to susceptibility effects from the signal source and permits accurate signal profile measurements of high spatial (sub-mm) resolution.     

Quality assessment in in vivo NMR spectroscopy: III. Clinical test objects: Design,construction, and solutions

Based on the requirements of test protocols developed to evaluate clinical MRS single slice and volume localisation sequences, two clinical test objects, STO1 and STO2 have been developed. The properties of a range of potential construction materials have been assessed, demonstrating that the water/Perspex interface produced minimum susceptibility effects. The design of the objects has been evaluated in trials on different magnetic resonance instruments, with size and loading being adjusted to allow use on currently available equipment. Appropriate test solutions for ³¹P and ¹H measurements have been developed and their properties evaluated.     

On neglecting chemical exchange effects when correcting in vivo (31)P MRS data for partial saturation

Signal acquisition in most MRS experiments requires a correction for partial saturation that is commonly based on a single exponential model for T(1) that ignores effects of chemical exchange. We evaluated the errors in (31)P MRS measurements introduced by this approximation in two-, three-, and four-site chemical exchange models under a range of flip-angles and pulse sequence repetition times (T(R)) that provide near-optimum signal-to-noise ratio (SNR). In two-site exchange, such as the creatine-kinase reaction involving phosphocreatine (PCr) and gamma-ATP in human skeletal and cardiac muscle, errors in saturation factors were determined for the progressive saturation method and the dual-angle method of measuring T(1). The analysis shows that these errors are negligible for the progressive saturation method if the observed T(1) is derived from a three-parameter fit of the data. When T(1) is measured with the dual-angle method, errors in saturation factors are less than 5% for all conceivable values of the chemical exchange rate and flip-angles that deliver useful SNR per unit time over the range T(1)/5 < or = T(R) < or = 2T(1). Errors are also less than 5% for three- and four-site exchange when T(R) > or = T(1)(*)/2, the so-called "intrinsic" T(1)'s of the metabolites. The effect of changing metabolite concentrations and chemical exchange rates on observed T(1)'s and saturation corrections was also examined with a three-site chemical exchange model involving ATP, PCr, and inorganic phosphate in skeletal muscle undergoing up to 95% PCr depletion. Although the observed T(1)'s were dependent on metabolite concentrations, errors in saturation corrections for T(R) = 2 s could be kept within 5% for all exchanging metabolites using a simple interpolation of two dual-angle T(1) measurements performed at the start and end of the experiment. Thus, the single-exponential model appears to be reasonably accurate for correcting (31)P MRS data for partial saturation in the presence of chemical exchange. Even in systems where metabolite concentrations change, accurate saturation corrections are possible without much loss in SNR.     

Impact of hyperthermic regional perfusion therapy on cell metabolism of malignant melanoma monitored by 31P MR spectroscopy

For the first time, the influence of hyperthermic regional perfusion therapy on tumor cell metabolism has been monitored by means of 31P MR spectroscopy. Shortly after treatment, a complete depletion of high energy phosphates, a significant increase of inorganic phosphate, phosphomono- and phosphodiester resonances and a decrease of pH have been observed. Healthy muscle tissue showed only minor effects caused by this aggressive therapy. The time course of the transient variation of phosphate metabolite concentrations is explained in the framework of a simple pathophysiological model. The results demonstrate that the imediate effect of chemotherapy on tumor tissue can be detected by 31P MRS before any clinical signs of tumor response are visible.     

IRIS-HSVD algorithm for automatic quantitation of in vivo 31P MRS

The rapid development of (31)P magnetic resonance spectroscopy (MRS) has enhanced non-invasive measurement of brain metabolites, which is important for biomedical research. The accuracy and efficiency of data post processing and quantification is paramount for MRS applications. One of the difficulties with in vivo(31)P MRS data quantification is the separation of broad line-width resonances from chemical compounds' resonances under a low signal-to-noise ratio condition. Furthermore, the chemical shift of some compounds caused by pH and Mg(2+) concentration can be troublesome. This work aims to develop an automatic algorithm using a state-space based quantification approach to solve the above mentioned problems. To achieve this aim, we utilized an HSVD based adaptive optimizing prior knowledge algorithm, which uses so called "interference" signals to optimize prior knowledge iteratively for parameter optimization. We termed this algorithm IRIS-HSVD, which stands for Iterative Reduction of Interference Signal HSVD. The Monte Carlo evaluations of the algorithm were conducted with simulated data using in vivo parameters commonly obtained from a 4T scanner. The performance of this algorithm using simulated data was compared to those of other automatic methods including HSVD and HTLS-PK. Examples of in vivo(31)P data obtained from brains of healthy subjects on a 4T MRI scanner were also presented, which demonstrated the superiority of the new method. The results were compared with those using AMARES.     

Quantitative multivoxel proton chemical shift imaging of the breast

The study of focal pathology by single-voxel magnetic resonance spectroscopy (MRS) is hampered by the impossibility to study tissue heterogeneity or compare the metabolite signals in breast lesion directly to those in unaffected tissue. Multivoxel MRS studies, while potentially allowing for truly quantitative tissue characterization, have up to now also been far from quantitative with, for example, the signal-to-noise ratio of the choline (Cho) signal serving as measure of tumor activity. Shown in this study is that in a standard clinical setting with a regular 1.5-T magnetic resonance scanner, it is possible to perform quantitative multivoxel MRS. With the use of literature values for the T1 and T2 relaxation times of Cho and water in fibroglandular breast tissue and tumors, one can determine the concentrations of Cho in different tumor compartments and surrounding tissues in two brief multivoxel MRS measurements. This opens excellent perspectives to quantitative diagnostic and follow-up studies of focal pathology such as lesions suspected of breast cancer.     

In situ 19F MRS measurement of RIF-1 tumor blood volume: Corroboration by radioisotope-labeled [125I]-albumin and correlation to tumor size

Tumor blood volume (TBV) is an important factor in the metabolism of a tumor and in its response to therapy. Until recently, the only methods to determine TBV were highly invasive and many involved radioisotopes. In this study, a perfluorocarbon (PFC) emulsion, Oxypherol, was monitored by ¹⁹F magnetic resonance spectroscopy (MRS). TBVs, as determined by ¹⁹F MRS of in situ and excised radiation-induced fibrosarcoma (RIF-1) tumors (n = 9), were strongly correlated with the TBV measured by a radioisotope labeled albumin method (slopes of 1.1 and 0.8 with R = 0.86 and 0.91, respectively, by linear regression). In general, the TBV as calculated from the in situ MRS measurements (n = 24) decreased from 28 to 5 ml/100 g tumor mass for tumors ranging in mass from 0.15 to 2 g. However, there was an indication of an initial increase of TBV in tumors smaller than 0.5 g.