In vivo nuclear magnetic resonance imaging of lithium

Magnetic resonance imaging techniques have previously been applied to 1H, 23Na, 31P, and 19F nuclei. This is the first report of application of these techniques to 7Li. Lithium images of both aqueous phantoms and a rat abdomen are presented. Applications of this technique to humans are discussed.     

In vivo imaging of gene expression:

With the ability to readily engineer genes, create knock-in and knock-out models of human disease, and replace and insert genes in clinical trials of gene therapy, it has become clear that imaging will play a critical role in these fields. Imaging is particularly helpful in recording temporal and spatial resolution of gene expression in vivo, determining vector distribution, and, ultimately, understanding endogenous gene expression during disease development. While endeavors are under way to image targets ranging from DNA to entire phenotypes in vivo, this short review focuses on in vivo imaging of gene expression with magnetic resonance and optical techniques.     

In vivo proton nuclear magnetic resonance imaging and spectroscopy studies of halocarbon-induced liver damage

Proton magnetic resonance imaging and localized NMR spectroscopy were used to study the rat liver in situ. Respiratory gating was used in both the imaging and the localized spectroscopy studies to control for the movement of the upper abdomen of the rat during breathing. After administration of carbon tetrachloride, bromotrichloromethane, or halothane, localized regions of high proton signal intensity were observed in the NMR images of the liver. Localized (VOSY) proton NMR spectra from within these regions indicated that the increase in a signal intensity was due to a longer T2 relaxation time for the water resonance, indicating acute edema in the region of tissue damage.     

In vivo 19F NMR imaging

In vitro and in vivo 19F spectra and images were obtained using various clinically safe fluorinated compounds. Standard and chemical shift images were acquired in solutions of fluorinated anesthetics with the chemical shift images clearly separating signals arising from a mixture of halothane and methoxyflurane. The 19F images of halothane in rats were unsuccessful at anesthetic concentration. In vivo 19F nuclear magnetic resonance (NMR) images were acquired at 57.9 MHz in rats receiving chronic injections of 14% perfluorodecalin, 6% perfluorotripropylamine (Fluosol-DA). The liver accumulates Fluosol-DA in the reticuloendothelial cells to concentrations that allow images to be obtained in less than 30 min. Image intensity from the perfluorochemicals reflects reticuloendothelial cell activity and thus is a functional image. Conventional proton NMR images at corresponding levels confirmed that the 19F signal arose from the liver and not muscle or fat. The 19F NMR images of the large bowel and stomach in rats were obtained by filling the lumen with concentrated Fluosol-DA. High contrast anatomical images showing gross structure of the gastrointestinal tract were acquired in as little as 12 min. These data suggest that 19F NMR may have a potential role in clinical imaging.     

In vivo intravascular MR imaging: transvenous technique for arterial wall imaging

PURPOSE: To determine, in vivo, the potential for transvenous magnetic resonance (MR) imaging of the arterial wall and to assess appropriate MR pulse sequences for this method. MATERIALS AND METHODS: MR imaging was performed on 19 vessels (right renal artery, N = 9; left renal artery N = 2; external iliac artery, N = 4; abdominal aorta, N = 4) in nine swine. The animals were either low-density lipoprotein receptor knockout (N = 5) or Yucatan mini-pigs fed an atherogenic diet for 6 to 11 weeks (N = 4). The intravascular MR coil/guide wire (IVMRG) (Surgi-Vision, Gaithersburg, MD) was introduced via the external iliac vein into the inferior vena cava (IVC). The following electrocardiograph-gated MR pulse sequences were obtained: T1-weighted precontrast with and without fat saturation and T1-weighted postcontrast with fat saturation. Two observers scored wall signal and conspicuity and classified the vessel as normal, abnormal, or stented. Images were compared with histopathologic findings. RESULTS: The T1-weighted precontrast without fat saturation, T1-weighted precontrast with fat saturation, and T1-weighted postcontrast images correlated with histopathologic findings in 12 of 15 vessels, eight of 10 vessels, and 14 of 16 vessels, respectively. Abnormal histopathologic findings included: arterial wall thickening (N = 3), arterial dissection (N = 2), focal fibrous plaque (N = 2), adherent thrombus (N = 1). The T1-weighted postcontrast images were not compromised by artifacts and had the highest score for vessel wall signal and conspicuity. T1-weighted precontrast images were compromised by chemical shift artifact and poor blood suppression. Negligible artifacts were created by the platinum stent. CONCLUSION: The T1-weighted fat saturated postcontrast pulse sequence was superior to other sequences for transvenous MR imaging of the arterial wall.     

In vivo magnetic resonance imaging of single cells in mouse brain with optical validation.

In the current work we demonstrate, for the first time, that single cells can be detected in mouse brain in vivo using magnetic resonance imaging (MRI). Cells were labeled with superparamagnetic iron oxide nanoparticles and injected into the circulation of mice. Individual cells trapped within the microcirculation of the brain could be visualized with high-resolution MRI using optimized MR hardware and the fast imaging employing steady state acquisition (FIESTA) pulse sequence on a 1.5 T clinical MRI scanner. Single cells appear as discrete signal voids on MR images. Direct optical validation was provided by coregistering signal voids on MRI with single cells visualized using high-resolution confocal microscopy. This work demonstrates the sensitivity of MRI for detecting single cells in small animals for a wide range of application from stem cell to cancer cell tracking.     

In vivo MR tractography using diffusion imaging

Diffusion in structured tissue, such as white matter or muscle, is anisotropic. MR diffusion tensor imaging (DTI) measures anisotropy per pixel and provides the directional information relevant for MR tractography or fiber tracking in vivo. MR tractography is non-invasive, relatively fast, and can be repeated multiple times without destructing important tissue. Moreover, the combination with other MR images is relatively simple. In this paper, the basic principles of tractography are presented. Different tracking methods with varying degrees of complexity are introduced and their potential strengths and weaknesses are discussed. Clinical applications and different strategies for evaluating the fidelity of tracking results are reviewed.     

In vivo validation of MR velocity imaging

Calculations of left ventricular stroke volume obtained by summing the areas of multiple contiguous transverse magnetic resonance (MR) slices in systole and diastole using a spin echo sequence have been compared in 10 healthy volunteers with the stroke output derived from velocity maps in the ascending aorta using a field even-echo rephasing sequence. The results gave a correlation coefficient of 0.97 (p less than 0.001) and a standard error of estimate of 3.2 ml. Velocity maps have also been obtained in the pulmonary artery, the descending aorta, and the superior vena cava. The accuracy of this technique and the theoretical limitations of MR measurements have implications for the earlier detection of atheroma in the coronary and other arteries.     

脑卒中细胞凋亡的活体成像进展

脑卒中是全球第二大常见死因,是我国第一大死亡和致残原因.缺血脑卒中急性期及迟发性神经元死亡期均存在神经元细胞的凋亡,凋亡决定了脑卒中最终的梗死体积.应用活体成像技术能够无创地检测脑内的细胞凋亡信息,为脑卒中的早期诊断、病程及治疗效果监测提供了新的方向.     

In vivo sodium chemical shift imaging.

The shift reagents thulium(III) 1,4,7,10-tetraazacyclododecane N,N',N",N"'tetramethylenephosphonate (TmDOTP5-), and dysprosium(III)triethylenetetramine-hexaacetate (DyTTHA3-) are compared in this work for their uses in sodium chemical shift imaging (NaCSI). In a series of experiments using phantoms we evaluated the relative contributions of bulk magnetic susceptibility (BMS) effects and hyperfine shifts to the induced 23Na chemical shift for these two shift reagents. The ratios of BMS effects to hyperfine shifts suggest that TmDOTP5- should be a more effective shift reagent than DyTTHA3- for 23Na NMR spectroscopy as well as NaCSI. The dependence on pH and free Ca2+ concentration of the 23Na NMR frequency shift induced by TmDOTP5- was evaluated. It was found that TmDOTP5- produces good spectral resolution under physiologic conditions. Examples presented from in vivo NaCSI experiments using TmDOTP5- to study diffusion in the posterior chamber of the rabbit eye and to monitor the rate of clearance of aqueous fluid from the anterior chamber demonstrate the effectiveness of this new shift reagent and of the NaCSI technique for in vivo studies.     

In vivo and ex vivo MR imaging of slowly cycling melanoma cells

Slowly cycling cells are believed to play a critical role in tumor progression and metastatic dissemination. The goal of this study was to develop a method for in vivo detection of slowly cycling cells. To distinguish these cells from more rapidly proliferating cells that constitute the vast majority of cells in tumors, we used the well‐known effect of label dilution due to division of cells with normal cycle and retention of contrast agent in slowly dividing cells. To detect slowly cycling cells, melanoma cells were labeled with iron oxide particles. After labeling, we observed dilution of contrast agent in parallel with cell proliferation in the vast majority of normally cycling cells. A small and distinct subpopulation of iron‐retaining cells was detected by flow cytometry after 20 days of in vitro proliferation. These iron‐retaining cells exhibited high expression of a biological marker of slowly cycling cells, JARID1B. After implantation of labeled cells as xenografts into immunocompromised mice, iron‐retaining cells were detected in vivo and ex vivo by magnetic resonance imaging that was confirmed by Prussian Blue staining. Magnetic resonance imaging detects not only iron retaining melanoma cells but also iron positive macrophages. Proposed method opens up opportunities to image subpopulation of melanoma cells, which is critical for continuous tumor growth. Magn Reson Med, 2011. © 2011 Wiley Periodicals, Inc.     

In vivo fluorine-19 MR imaging: Relaxation enhancement with Gd-DTPA

The lack of a naturally occurring background signal from fluorine in magnetic resonance (MR) imaging makes fluorinated compounds potentially attractive candidates for tissue-specific MR contrast agents. Problems associated with the in vivo use of fluorinated compounds are toxicity, which limits the amount of agent that can be used; multiple resonance lines; and an excessively long T1, which leads to long sequence TRs and consequently long imaging times. Many fluorinated agents also possess complex MR spectra that result in chemical shift artifacts if not corrected. The authors demonstrate the use of an extracellular fluorinated agent with a single MR peak for selective imaging of a brain abscess in an animal model and show that the image signal per unit of acquisition time can be enhanced through the use of a T1 relaxation agent, gadolinium diethylenetriamine-pentaacetic acid (DTPA). Trifluoromethylsulfonate was administered at a fluorine-19 dose of 4 mmol/kg, and fluorine images of the induced abscess were acquired before and after the injection of a standard dose of Gd-DTPA (0.1 mmol/kg); non—section-selected projection images were used. Typical imaging times were less than 5 minutes. The signal enhancement factor achieved was approximately four (4.0 ± 0.8) with use of a 500/12 (TR msec/TE msec) spinecho sequence.     

In vivo nuclear magnetic resonance spectroscopy applied to medicine

The author describes the medical diagnostic and research context into which in vivo nuclear magnetic resonance (NMR) spectroscopy promises to fit. The different constraints and possibilities of in vivo NMR are contrasted with those of conventional in vitro NMR spectroscopy. To illustrate the discussion, examples are given of the roles that phosphorus-31 spectroscopy plays in the evaluation of energy metabolism, that the editing of proton (1H) spectra plays in the observation of individual metabolites such as lactate, and that natural-abundance carbon-13 spectroscopy might play in the investigation of fat metabolism.