Intravascular MR imaging and intravascular MR-guided interventions

Intravascular MR technology, using an intravascularly placed MR receiver probe to acquire high-resolution angiographic MR images (i.e. intravascular MR imaging) and to guide cardiovascular interventional therapies (i.e. intravascular MR-guided interventions), is a new, very attractive development in the field of MR imaging. The new technology offers unique advantages for cardiovascular imaging and interventions, including superior contrast capability and multiplanar imaging capabilities without the use of contrast agents and with no risk of ionizing radiation. Thecombination of intravascular MR techniques with other advanced MR imaging techniques, such as functional MR imaging, will open new avenues for the future comprehensive management of cardiovascular atherosclerotic disease. Further improvements in intravascular MR fluoroscopy with true real-time display, analogous to X-ray fluoroscopy, will dramatically establish the role of intravascular MR technology in modern medicine.     

磁共振胰胆管成像（MRCP）检查胆道系统结石的方法探讨

目的探讨磁共振胰胆管成像（MRCP）时不同扫描方法对胆道系统结石的发现率,以期确定合理的检查方法。材料和方法50例接受MRCP检查者,GE1．5T MRI扫描仪,分别采用常规薄层MRCP、厚层单次激发、薄层单次激发的MRCP,并同时行冠状面FIESTA扫描。分析不同方法对胆道系统结石的发现率。结果不同方法对胆道系统结石都有一定的漏诊。以薄层MRCP结合原始图像最少,而薄层单次激发MRCP结合冠状面FIESTA可以达到最佳的诊断效果。结论MRCP检查胆道系统结石时,采用单次激发MRCP结合冠状面FIESTA可以达到最佳的效果。     

Localization of chloride conductance to mitochondria-rich cells in frog skin epithelium

Summary Cell volume determinations and electrophysiological measurements have been made in an attempt to determine if mitochondria-rich (MR) cells are localized pathways for conductive movements of Cl across frog skin epithelium. Determinations of cell volume with video microscope techniques during transepithelial passage of current showed that most MR cells swell when the tissue is voltage clamped to serosa-positive voltages. Voltage-induced cell swelling was eliminated when Cl was removed from the mucosal bath solution. Using a modified vibrating probe technique, it was possible to electrically localize a conductance specifically to some MR cells in some tissues. These data are evidence supporting the idea that MR cells are pathways for conductive movements of Cl through frog skin epithelium.     

New concepts in characterization of ischemically injured myocardium by MRI

New concepts regarding the assessment of ischemic myocardial injuries have been addressed in this Minireview using magnetic resonance imaging (MRI). MRI, with its different techniques, brings not only anatomic, but also physiologic, information on ischemic heart disease. It has the ability to measure identical parameters in preclinical and clinical studies. MRI techniques provide the ideal package for repeated and noninvasive assessment of myocardial anatomy, viability, perfusion, and function. MR contrast agents can be applied in a variety of ways to improve MRI sensitivity for detecting and assessing ischemically injured myocardium. With MR contrast agents protocol, it becomes possible to identify ischemic, acutely infarcted, and peri-infarcted myocardium in occlusive and reperfused infarctions. Necrosis specific and nonspecific extracellular contrast-enhanced MRI has been used to assess myocardial viability. Contrast-enhanced perfusion MRI can explore the disturbances in large (angiography) and small coronary arteries (myocardial perfusion) as the underlying cause of myocardial dysfunction. Perfusion MRI has been used to measure myocardial perfusion (ml/min/g) and to demonstrate the difference in transmural myocardial blood flow. Information on no-reflow phenomenon is derived from dynamic changes in regional signal intensity after bolus injection of MR contrast agents. Another development is the near future availability of blood pool MR contrast agents. These agents are able to assess microvascular permeability and integrity and are advantageous in MR angiography (MRA) due to their persistence in the blood. Noncontrast-enhanced MRI such as cine MRI at rest/stress, sodium MRI, and MR spectroscopy also have the potential to noninvasively assess myocardial viability in patients. Futuristic applications for MRI in the heart will focus on identifying coronary artery disease at an early stage and the beneficial effects of new therapeutic agents such as intra-arterial gene therapy. MR techniques will have great future in the drug discovery process and in testing the effects of drugs on myocardial biochemistry, physiology, and morphology. Molecular imaging is going to bloom in this decade.     

Use of magnetic resonance to measure molecular diffusion within the brain extracellular space

Ion-selective microelectrode measurements of molecular diffusion have provided unique information about the structural characteristics of the extracellular compartment of brain tissue. Magnetic resonance (MR) techniques can also be used to perform diffusion measurements in living tissue in situ. In MR applications, the challenge to study a particular physiological compartment lies in achieving the appropriate specificity in the experimentally-observed MR signal, and many strategies have been used to provide measurements that reflect molecular diffusion within the extracellular space. This review describes how magnetic resonance and microelectrode diffusion measurements are performed, and applications using the MR technique are summarized. Comparisons of experimental results obtained from the two techniques indicate that their use in combination may further augment what is known about extracellular space structure.     

In vivo assessment of nodularin-induced hepatotoxicity in the rat using magnetic resonance techniques (MRI, MRS and EPR oximetry)

Acute nodularin-induced hepatotoxicity was assessed in vivo, in rats using magnetic resonance (MR) techniques, including MR imaging (MRI), MR spectroscopy (MRS), and electron paramagnetic resonance (EPR) oximetry. Nodularin is a cyclic hepatotoxin isolated from the cyanobacterium Nodularia spumigena. Three hours following the intraperitoneal (i.p.) administration of nodularin (LD50), a region of 'damage', characterized by an increase in signal intensity, was observed proximal to the porta hepatis (PH) region in T2-weighted MR images of rat liver. Image analysis of these regions of apparent 'damage' indicated a statistically significant increase in signal intensity around the PH region following nodularin administration, in comparison with controls and regions peripheral to the PH region. An increase in signal intensity was also observed proximal to the PH region in water chemical shift selective images (CSSI) of nodularin-treated rat livers, indicating that the increased signal observed by MRI is an oedematous response to the toxin. Microscopic assessment (histology and electron microscopy) and serum liver enzyme function tests (aminotransferase (ALT) and aspartate ALT (AST)) confirmed the nodularin-induced tissue injury observed by MRI. In vivo and in vitro MRS was used to detect alterations in metabolites, such as lipids, Glu+Gln, and choline, during the hepatotoxic response (2-3 h post-exposure). Biochemical assessment of perchloric acid extracts of nodularin-treated rat livers were used to confirm the MRS results. In vivo EPR oximetry was used to monitor decreasing hepatic pO2 (approximately 2-fold from controls) 2-3 h following nodularin exposure. In vivo MR techniques (MRI, MRS and EPR oximetry) are able to highlight effects that may not have been evident in single end point studies, and are ideal methods to follow tissue injury progression in longitudinally, increasing the power of a study through repeated measures, and decreasing the number of animals to perform a similar study using histological or biochemical techniques.     

磁共振功能成像在监测乳腺癌新辅助化疗中的应用和进展

近年来,新辅助化疗在原发乳腺癌治疗中运用越来越广泛。影像学手段在评价新辅助化疗疗效、指导临床治疗方案的制定中发挥重要作用。磁共振功能成像的引入,可以加深对恶性乳腺肿瘤的病理生理活动及分子生物学特性的了解,监测化疗疗效,提高早期预测的准确性。本文总结功能学MRI(磁共振成像)探测乳腺癌患者生物标志物的研究现状及发展情况,描述各种生物学标志物特性,评价其潜在的临床应用价值和局限性。以下将对动态增强磁共振成像、弥散加权成像、血氧水平依赖成像以及波谱成像等几种磁共振功能学成像方法的原理进行描述,重点对其在监测乳腺癌新辅助化疗中的应用进行综述。     

A noncontact,nondestructive method for quantifying intratissue deformations and strains

The function of soft connective tissues is frequently characterized by quantifying tissue strain (e.g., during joint motion). Conventional techniques for quantifying tendon and ligament strain typically provide surface measures, using markers, stain lines or instrumentation that may influence the tissue. An alternative approach is to quantify intratendinous strain by applying texture correlation analysis to magnetic resonance (MR) images. This paper reports the accuracy and reproducibility of this approach by (1) assessing the reproducibility of MR images, (2) assessing texture correlation accuracy using simulated displacements, and (3) comparing texture correlation measures of displacement and strain from MR images to conventional techniques.     

Brain Magnetic Resonance in the Diagnostic Evaluation of Mitochondrial Encephalopathies

Brain MR imaging techniques are important ancillary tests in the diagnosis of a suspected mitochondrial encephalopathy since they provide details on brain structural and metabolic abnormalities. This is particularly true in children where non-specific neurologic symptoms are common, biochemical findings can be marginal and genetic defects may be not discovered. MR imaging modalities include conventional, or structural, imaging (MRI) and functional, or ultrastructural, imaging (spectroscopy, MRS; diffusion, DWI-ADC; perfusion, DSCI––ASL). Among them MRI and MRS are the main tools for diagnosis and work up of MD, and this review will focus mainly on them. The MRI findings of MD are very heterogeneous, as they depend on the metabolic brain defects, age of the patient, stage and severity of the disease. No correlation has been found between genetic defects and neuroimaging picture; however, some relationships between MR findings and clinical phenotypes may be identified. Different combinations of MRI signal abnormalities are often encountered but the most common findings may be summarized into three main MR patterns: (i) non-specific; (ii) specific; (iii) leukodystrophic-like. Regarding the functional MR techniques, only proton MRS plays an important role in demonstrating an oxidative metabolism impairment in the brain since it can show the accumulation of lactate, present as a doublet peak at 1.33 ppm. Assessment of lactate should be always performed on brain tissue and on the ventricular cerebral spinal fluid. As for MRI, metabolic MRS abnormalities can be of different types, and two distinct patterns can be recognized: non-specific and specific. The specific metabolic profiles, although not frequent to find, are highly pathognomonic of MD. The un-specific metabolic profiles add value to structural images in allowing to define the lesion load and to monitor the response to therapy trials.     

Abdominal magnetic resonance imaging in small rodents using a clinical 1.5 T MR scanner

Because of superior soft-tissue contrast compared to other imaging techniques, non-invasive abdominal magnetic resonance imaging (MRI) is ideal for monitoring organ regeneration, tissue repair, cancer stage, and treatment effects in a wide variety of experimental animal models. Currently, sophisticated MR protocols, including technically demanding procedures for motion artefact compensation, achieve an MRI resolution limit of < 100 microm under ideal conditions. However, such a high spatial resolution is not required for most experimental rodent studies. This article describes both a detailed imaging protocol for MR data acquisition in a ubiquitously and commercially available 1.5 T MR unit and 3-dimensional volumetry of organs, tissue components, or tumors. Future developments in MR technology will allow in vivo investigation of physiological and pathological processes at the cellular and even the molecular levels. Experimental MRI is crucial for non-invasive monitoring of a broad range of biological processes and will further our general understanding of physiology and disease.     

MRI strain imaging of the carotid artery: Present limitations and future challenges

Rupture of atherosclerotic plaques in the carotid artery is a main cause of stroke. Current diagnostics are not sufficient to identify all rupture-prone plaques, and studies have shown that biomechanical factors improve current plaque risk assessment. Strain imaging may be a valuable contribution to this risk assessment. MRI is a versatile imaging technique that offers various methods that are capable of measuring tissue strain. In this review, MR imaging techniques with displacement (DENSE), velocity (PC MRI), or strain (SENC) encoding protocols are discussed, together with post-processing techniques based on time-resolved MRI data. Although several MRI techniques are being developed to improve time-resolved MR imaging, current technical limitations related to spatial and temporal resolutions render MRI strain imaging currently unfit for carotid plaque strain evaluation.     

Investigations of back muscle fatigue by simultaneous 31P MRS and surface EMG measurements.

Investigations of back muscle fatigue are important for understanding the role of muscle strain in the development of low back pain. The aim of this contribution is to review the two main techniques used for in vivo investigations of metabolic and electrophysiological changes, namely magnetic resonance phosphorous spectroscopy ((31)P MRS) and surface electromyography (SEMG), and to report some of our recent results on simultaneous measurements using these techniques during isometric back-muscle contraction in volunteers. Since it appears that electrophysiological and metabolic factors are simultaneously involved in the processes of fatigue and muscle recovery during load application, simultaneous acquisition of complete information is quite promising for obtaining new insights into the metabolic origin of electrophysiological changes or vice versa. Performing these measurements simultaneously, however, is more intricate owing to the occurrence of signal artifacts caused by mutual signal interferences of both techniques. Besides these mutual disturbances, further experimental difficulties are related to spatial limitations within the bore of clinical whole-body high-field magnetic resonance (MR) systems (1.5 T) and the sensitivity of MR measurements to motion-induced artifacts. Our own experimental results are presented, and problems that occur using both techniques simultaneously, as well as possibilities to resolve them, are discussed. The results shed light on the interrelation of electrophysiological and metabolic changes during fatigue of the back muscle while performing an exercise.     

FRAXA screening in Brazilian institutionalized individuals with nonspecific severe mental retardation

Individuals with mental disabilities are a heterogeneous group, mainly when we consider the etiology of mental retardation (MR). Recent advances in molecular genetics techniques have enabled us to unveil more about the molecular basis of several genetic syndromes associated with MR. In this study, we surveyed 85 institutionalized individuals with severe MR, 38 males and 47 females, by two molecular techniques, to detect CGG amplifications in the FMR1 gene. No FRAXA mutations were found in the FMR1 gene, reinforcing the low prevalence of Fragile X syndrome among institutionalized individuals with severe MR. We considered the PCR protocol used adequate for screening males with mental retardation of unknown etiology. The use of the Southern blot is still necessary for the decisive diagnosis of the Fragile X syndrome. To exclude chromosomal abnormalities associated with MR as a possible cause of the phenotype in these individuals, G-banded chromosome analysis was performed in all patients and 7.3% of chromosomal aberrations were found. Our results are similar to those reported previously and point to the necessity of expanding the molecular investigation toward other causes of MR, such as subtle chromosomal rearrangements, as suggested recent by a combination of fluorescence in situ hybridization (FISH) and PCR studies.     

Rapid MR imaging of cryoprotectant permeation in an engineered dermal replacement

Magnetic resonance (MR) imaging is a powerful technique for monitoring the permeation of cryoprotective agents (CPAs) inside tissues. However, the techniques published until now suffer from inherently long imaging times, limiting the application of these techniques to slow diffusion processes and large CPA concentrations. In this study, we present a rapid MR imaging technique based on a CHESS-FLASH scheme combined with Keyhole image acquisition. This technique can image the fast permeation of Me(2)SO solutions into freeze-dried artificial dermal replacements for concentrations down to 10% v/v. Special attention is given to evaluating the technique for quantitative analysis.     

PTSD样大鼠蓝斑核盐皮质激素受体表达变化的研究

目的探讨PTSD样大鼠蓝斑（locus ceruleus,LC）神经元盐皮质激素受体（mineralocorticoid receptors,MR）表达的变化。方法使用连续单一应激（SPS）方法建立PTSD大鼠模型,随机分为SPS处理后24h、4d、7d、14d和28d组,非SPS刺激大鼠作为对照,应用免疫组化、免疫印迹方法分别进行各组蓝斑神经元MR表达变化的观察及检测,进行图像分析和统计学处理。结果蓝斑神经元MR的表达呈现24h急剧下调,4d、7d,14d和28d恢复性上调。结论PTSD样大鼠蓝斑神经元MR的表达变化可能直接参与了PTSD持续性精神行为障碍的发生发展过程。     

An Objective Method to Optimize the MR Sequence Set for Plaque Classification in Carotid Vessel Wall Images Using Automated Image Segmentation

A typical MR imaging protocol to study the status of atherosclerosis in the carotid artery consists of the application of multiple MR sequences. Since scanner time is limited, a balance has to be reached between the duration of the applied MR protocol and the quantity and quality of the resulting images which are needed to assess the disease. In this study an objective method to optimize the MR sequence set for classification of soft plaque in vessel wall images of the carotid artery using automated image segmentation was developed. The automated method employs statistical pattern recognition techniques and was developed based on an extensive set of MR contrast weightings and corresponding manual segmentations of the vessel wall and soft plaque components, which were validated by histological sections. Evaluation of the results from nine contrast weightings showed the tradeoff between scan duration and automated image segmentation performance. For our dataset the best segmentation performance was achieved by selecting five contrast weightings. Similar performance was achieved with a set of three contrast weightings, which resulted in a reduction of scan time by more than 60%. The presented approach can help others to optimize MR imaging protocols by investigating the tradeoff between scan duration and automated image segmentation performance possibly leading to shorter scanning times and better image interpretation. This approach can potentially also be applied to other research fields focusing on different diseases and anatomical regions.     

Subcellular in vivo 1H MR spectroscopy of Xenopus laevis oocytes

In vivo magnetic resonance (MR) spectra are typically obtained from voxels whose spatial dimensions far exceed those of the cells they contain. This study was designed to evaluate the potential of localized MR spectroscopy to investigate subcellular phenomena. Using a high magnetic field and a home-built microscopy probe with large gradient field strengths, we achieved voxel sizes of (180 microm)3. In the large oocytes of the frog Xenopus laevis, this was small enough to allow the recording of the first compartment-selective in vivo MR spectra from the animal and vegetal cytoplasm as well as the nucleus. The two cytoplasmic regions differed in their lipid contents and NMR lineshape characteristics-differences that are not detectable with whole-cell NMR techniques. In the nucleus, the signal appeared to be dominated by water, whereas other contributions were negligible. We also used localized spectroscopy to monitor the uptake of diminazene acturate, an antitrypanosomal agent, into compartments of a single living oocyte. The resulting spectra from the nucleus and cytoplasm revealed different uptake kinetics for the two components of the drug and demonstrate that MR technology is on the verge of becoming a tool for cell biology.     

Homologues of archaeal rhodopsins in plants, animals and fungi: structural and functional predications for a putative fungal chaperone protein

The microbial rhodopsins (MR) are homologous to putative chaperone and retinal-binding proteins of fungi. These proteins comprise a coherent family that we have termed the MR family. We have used modeling techniques to predict the structure of one of the putative yeast chaperone proteins, YRO2, based on homology with bacteriorhodopsins (BR). Availability of the structure allowed depiction of conserved residues that are likely to be of functional significance. The results lead us to predict an extracellular protein folding function and a transmembrane proton transport pathway. We suggest that protein folding is energized by a novel mechanism involving the proton motive force. We further show that MR family proteins are distantly related to a family of fungal, animal and plant proteins that include the human lysosomal cystine transporter (LCT) of man (cystinosin), mutations in which cause cystinosis. Sequence and phylogenetic analyses of both the MR family and the LCT family are reported. Proteins in both families are of the same approximate size, exhibit seven putative transmembrane alpha-helical spanners (TMSs) and show limited sequence similarity. We show that the LCT family arose by an internal gene duplication event and that TMSs 1-3 are homologous to TMSs 5-7. Although the same could not be demonstrated statistically for MR family members, homology with the LCT family suggests (but does not prove) a common evolutionary pathway. Thus, TMSs 1-3 and 5-7 in both LCT and MR family members may share a common origin, accounting for their shared structural features.     

Partial least squares regression as an alternative to current regression methods used in ecology

This paper briefly presents the aims, requirements and results of partial least squares regression analysis (PLSR), and its potential utility in ecological studies. This statistical technique is particularly well suited to analyzing a large array of related predictor variables (i.e. not truly independent), with a sample size not large enough compared to the number of independent variables, and in cases in which an attempt is made to approach complex phenomena or syndromes that must be defined as a combination of several variables obtained independently. A simulation experiment is carried out to compare this technique with multiple regression (MR) and with a combination of principal component analysis and multiple regression (PCA+MR), varying the number of predictor variables and sample sizes. PLSR models explained a similar amount of variance to those results obtained by MR and PCA+MR. However, PLSR was more reliable than other techniques when identifying relevant variables and their magnitudes of influence, especially in cases of small sample size and low tolerance. Finally, we present one example of PLSR to illustrate its application and interpretation in ecology.