Enhanced tissue differentiation in the developing mouse brain using magnetic resonance micro‐histology

Purpose: Worldwide efforts to understand developmental processes demand new high‐resolution 3D imaging methods to detect the consequences of gene function in embryo development and diseases. Encouragingly, recent studies have shown that MRI contrast agents can highlight specific tissue structures in ex vivo adult mouse brains. MR imaging of mouse embryos is currently limited by a lack of tissue staining capabilities that would provide the flexibility and specificity offered by histological stains conventionally used for mouse embryo phenotyping. Methods: The MRI staining properties of two readily available contrast agents, Mn‐DPDP and Gd‐DTPA, were investigated in mid‐gestation mouse embryos. Results: Brain tissue substructures not normally visible using MRI were detected. Mn‐DPDP and Gd‐DTPA provided spatially distinct tissue staining patterns. An initial assessment indicated that these agents utilized independent contrast enhancement mechanisms. Mn‐DPDP was identified as a potential MRI contrast agent for enhancement of mouse embryonic cellular density and enabled identification of regions containing populations of neural stem and progenitor cells within the intact embryo brain. Conclusions: Different contrast agents may be used to provide tissue‐specific contrast enhancement, suggesting that a host of specialized MRI stains may be available for probing the developing mouse brain and investigating developmental and disease mechanisms. Magn Reson Med 70:1380–1388, 2013. © 2012 Wiley Periodicals, Inc.     

Delayed contrast-enhanced MRI: use in myocardial viability assessment and other cardiac pathology

As in other organs, tissue characterization is important for many cardiac diseases. For example, in ischemic heart disease, differentiation between reversibly and irreversibly damaged myocardium in patients with a prior myocardial infarction is crucial in determining disease severity, functional recovery and patient outcome. With the recent advent of the single inversion-recovery contrast-enhanced magnetic resonance imaging (MRI) sequence (delayed contrast-enhanced MRI), contrast between normal and abnormal tissues could be significantly enhanced compared with the conventional cardiac MRI sequences, enabling even subtle abnormalities to be visualized. Together with other advances in cardiac MRI (e.g. functional imaging, coronary artery imaging), MRI has become one of the preferred non-invasive modalities to study cardiac diseases. In this paper an overview of the versatility of delayed contrast-enhanced MRI for investigating cardiac diseases is given.     

Vaskuläre und parenchymale Erkrankungen der Nieren

Diseases of the kidney often progress to end-stage renal failure over a period of several years and might lead to life-long dialysis. To avoid loss of renal function, kidney disease should be diagnosed as early as possible in order to initiate therapeutic measures in time. Several invasive and non-invasive radiological imaging techniques for the detection and characterization of renal disease are available. Particularly, non-invasive computed tomography (CT) and magnetic resonance imaging (MRI) have seen substantial technical advances in recent years. Today, both modalities offer a comprehensive diagnostic evaluation of renal diseases in a single examination, comprising detailed information of the parenchyma as well as of arterial and venous vasculature. This review article describes the most important vascular and parenchymal kidney diseases and their radiological characteristics with a focus on MRI and CT.     

Early changes in the apparent diffusion coefficient (ADC) in a mouse model of Sandhoff's disease occur prior to disease symptoms and behavioral deficits

Sandhoff's disease is a lysosomal storage disease in which the ganglioside GM2 accumulates in lysosomes. It has been reported that MRI cannot detect abnormalities in spin echo images in clinically presymptomatic Sandhoff's disease patients. Because one of the results of GM2 accumulation is cell swelling and lysosomal distension, our goal was to determine if changes in the diffusion of water is perturbed. We utilized the MRI imaging modality diffusion‐weighted imaging to measure the apparent diffusion coefficient in a mouse models of Sandhoff's disease, the hexb?/? mouse, and determined if diffusion‐weighted imaging could be utilized to detect early changes prior to behavioral or overt disease symptom onset. Here we report for the first time a comprehensive behavioral characterization of the hexb?/? mouse in conjunction with the apparent diffusion coefficient measurement. Our data indicate that the apparent diffusion coefficient decreases in the hexb?/? mouse in many but not all brain regions prior to disease symptoms (<3.5 to 4 months of age) and behavioral deficits (3 months of age). The magnitude of the decrease ranged from 4‐18%. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.     

Accelerated cardiac magnetic resonance imaging in the mouse using an eight‐channel array at 9.4 Tesla

MRI has become an important tool to noninvasively assess global and regional cardiac function, infarct size, or myocardial blood flow in surgically or genetically modified mouse models of human heart disease. Constraints on scan time due to sensitivity to general anesthesia in hemodynamically compromised mice frequently limit the number of parameters available in one imaging session. Parallel imaging techniques to reduce acquisition times require coil arrays, which are technically challenging to design at ultrahigh magnetic field strengths. This work validates the use of an eight‐channel volume phased‐array coil for cardiac MRI in mice at 9.4 T. Two‐ and three‐dimensional sequences were combined with parallel imaging techniques and used to quantify global cardiac function, T₁‐relaxation times and infarct sizes. Furthermore, the rapid acquisition of functional cine‐data allowed for the first time in mice measurement of left‐ventricular peak filling and ejection rates under intravenous infusion of dobutamine. The results demonstrate that a threefold accelerated data acquisition is generally feasible without compromising the accuracy of the results. This strategy may eventually pave the way for routine, multiparametric phenotyping of mouse hearts in vivo within one imaging session of tolerable duration. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

Magnetic resonance imaging of amyloid plaques in transgenic mouse models of Alzheimer's disease

A major objective in the treatment of Alzheimer's disease is amyloid plaque reduction. Transgenic mouse models of Alzheimer's disease provide a controlled and consistent environment for studying amyloid plaque deposition in Alzheimer's disease. Magnetic resonance imaging is an attractive tool for longitudinal studies because it offers non-invasive monitoring of amyloid plaques. Recent studies have demonstrated the ability of magnetic resonance imaging to detect individual plaques in living mice. This review discusses the mouse models, MR pulse sequences, and parameters that have been used to image plaques and how they can be optimized for future studies.     

Imaging of adrenal masses.

Adrenal pathology may be discussed based on hormonal functionality of the adrenals, appearances on imaging modality, or pathological determination. There are three main categories of adrenal function. Hyperfunctional states include Conn's or Cushing's syndrome. Lesions with normal function may be detected incidentally. Hypofunctional states may occur from idiopathic Addison's disease or some bilateral adrenal pathology. The most common modalities for characterization of adrenal pathology are non-enhanced CT, often followed by contrast CT or chemical shift MRI. The common appearance on non-enhanced CT is a well-defined homogeneous lesion with low-density due to the microscopic fat present and adrenal adenomas. When density criteria are not met, many of these may be characterized as adenomas by washed out of contrast or signal decrease using in phase and out-of-phase MRI sequences. Other non-invasive modalities may incidentally discover adrenal lesions, but are not typically used in the work-up. NP-59 is an uncommonly used nuclear medicine technique which is very specific for adenoma when correlated with pathology on other imaging studies. In the rare cases where non-invasive imaging is non-specific, fine needle aspiration or core biopsies may be necessary. However, biopsies have associated risks including infection and hemorrhage. The imaging appearance of an adrenal lesion is often specific such that further imaging is not necessary. These lesions include adrenal adenoma, pheochromocytoma, myelolipoma, adrenal cyst, and some large adrenocortical carcinomas. However, the findings in lesions such as metastasis, smaller primary adrenal carcinomas, lymphoma, granulomatous disease, and many adenomas are not as specific. In the proper clinical situation, follow-up imaging may be necessary, or biopsy may be warranted.     

Indications for body MRI Part I. Upper abdomen and renal imaging

The lack of ionizing radiation use in MRI makes the high spatial resolution technique very appealing. Also, the easy access to multiplanar imaging and the fact that gadolinium-DTPA is well tolerated and not nephrotoxic makes MRI a robust alternative in the healthy as well as the renal compromised patient. Furthermore, MRI adds advanced possibility for tissue characterization and pathology detection and dynamic imaging can be performed. Specific contrast agents specific to the hepatobiliary or the reticuloendothelial system can help with additional information in problem cases. The role of MRI for different organs is discussed and a review of the literature is given. We concluded that MRI is considered a useful and non-invasive diagnostic tool for the detection of hepatic iron concentration, to correct misdiagnosis (pseudolesions) from US and CT in focal steatosis and to help with focal lesion detection and characterization, in the healthy and especially in the cirrhotic liver, where MRI is superior to CT. Moreover, MRCP is excellent for identifying the presence and the level of biliary obstruction in malignant invasion and is considered in the literature as a non-invasive screening tool for common bile duct stones, appropriately selecting candidates for preoperative ERCP and sparing others the need for an endoscopic procedure with its associated complications. MRI is the first choice modality for adrenal evaluation in contemporary medical imaging. It is a useful examination in renal as well as splenic pathology and best assesses loco-regional staging, i.e. arterial involvement in pancreatic cancer.     

Molekulare und parametrische Bildgebung mit Eisenoxiden

Superparamagnetic iron oxide (SPIO) contrast agents, clinically established for high resolution magnetic resonance imaging of reticuloendothelial system containing anatomical structures, can additionally be exploited for the non-invasive characterization and quantification of pathology down to the molecular level. In this context, SPIOs can be applied for non-invasive cell tracking, quantification of tissue perfusion and target specific imaging, as well as for the detection of gene expression.This article provides an overview of new applications for clinically approved iron oxides as well of new, modified SPIO contrast agents for parametric and molecular imaging.     

Lung MRI for experimental drug research

Current techniques to evaluate the efficacy of potential treatments for airways diseases in preclinical models are generally invasive and terminal. In the past few years, the flexibility of magnetic resonance imaging (MRI) to obtain anatomical and functional information of the lung has been explored with the scope of developing a non-invasive approach for the routine testing of drugs in models of airways diseases in small rodents. With MRI, the disease progression can be followed in the same animal. Thus, a significant reduction in the number of animals used for experimentation is achieved, as well as minimal interference with their well-being and physiological status. In addition, under certain circumstances the duration of the observation period after disease onset can be shortened since the technique is able to detect changes before these are reflected in parameters of inflammation determined using invasive procedures. The objective of this article is to briefly address MRI techniques that are being used in experimental lung research, with special emphasis on applications. Following an introduction on proton techniques and MRI of hyperpolarized gases, the attention is shifted to the MRI analysis of several aspects of lung disease models, including inflammation, ventilation, emphysema, fibrosis and sensory nerve activation. The next subject concerns the use of MRI in pharmacological studies within the context of experimental lung research. A final discussion points towards advantages and limitations of MRI in this area.     

Stellenwert der multiparametrischen Magnetresonanztomographie beim Prostatakarzinom

Prostate cancer is biologically and clinically a heterogeneous disease which makes imaging evaluation challenging. Magnetic resonance imaging (MRI) has considerable potential to improve prostate cancer detection and characterization. Until recently morphologic MRI has not been routinely incorporated into clinical care because of its limitation to detect, localize and characterize prostate cancer. Performing prostate gland MRI using functional techniques has the potential to provide unique information regarding tumor behavior, including treatment response. In order for multiparametric MRI data to have an impact on patient management, the collected data need to be relayed to clinicians in a standardized way for image construction, analysis and interpretation. This will ensure that patients are treated effectively and in the most appropriate way. Scoring systems similar to those employed successfully for breast imaging need to be developed.     

Lung MRI for experimental drug research

Current techniques to evaluate the efficacy of potential treatments for airways diseases in preclinical models are generally invasive and terminal. In the past few years, the flexibility of magnetic resonance imaging (MRI) to obtain anatomical and functional information of the lung has been explored with the scope of developing a non-invasive approach for the routine testing of drugs in models of airways diseases in small rodents. With MRI, the disease progression can be followed in the same animal. Thus, a significant reduction in the number of animals used for experimentation is achieved, as well as minimal interference with their well-being and physiological status. In addition, under certain circumstances the duration of the observation period after disease onset can be shortened since the technique is able to detect changes before these are reflected in parameters of inflammation determined using invasive procedures. The objective of this article is to briefly address MRI techniques that are being used in experimental lung research, with special emphasis on applications. Following an introduction on proton techniques and MRI of hyperpolarized gases, the attention is shifted to the MRI analysis of several aspects of lung disease models, including inflammation, ventilation, emphysema, fibrosis and sensory nerve activation. The next subject concerns the use of MRI in pharmacological studies within the context of experimental lung research. A final discussion points towards advantages and limitations of MRI in this area.     

MRI of the peritoneum: spectrum of abnormalities

OBJECTIVE: Our objective was to detail peritoneal anatomy, techniques for optimizing peritoneal MRI, and the MRI characteristics of several disease processes that frequently involve the peritoneum. CONCLUSION: Homogeneous fat suppression and dynamic contrast-enhanced imaging, including delayed imaging, are critical technical factors for successful lesion detection and characterization on peritoneal MRI.     

Segmentation propagation using a 3D embryo atlas for high‐throughput MRI phenotyping: Comparison and validation with manual segmentation

Effective methods for high‐throughput screening and morphometric analysis are crucial for phenotyping the increasing number of mouse mutants that are being generated. Automated segmentation propagation for embryo phenotyping is an emerging application that enables noninvasive and rapid quantification of substructure volumetric data for morphometric analysis. We present a study to assess and validate the accuracy of brain and kidney volumes generated via segmentation propagation in an ex vivo mouse embryo MRI atlas comprising three different groups against the current “gold standard”—manual segmentation. Morphometric assessment showed good agreement between automatically and manually segmented volumes, demonstrating that it is possible to assess volumes for phenotyping a population of embryos using segmentation propagation with the same variation as manual segmentation. As part of this study, we have made our average atlas and segmented volumes freely available to the community for use in mouse embryo phenotyping studies. These MRI datasets and automated methods of analyses will be essential for meeting the challenge of high‐throughput, automated embryo phenotyping. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc.     

Cross-sectional imaging work-up of adrenal masses

Advances in medical imaging with current cross-section modalities enable non-invasive characterization of adrenal lesions. Computed tomography (CT) provides characterization with its non-contrast and wash-out features. Magnetic resonance imaging (MRI) is helpful in further characterization using chemical shift imaging (CSI) and MR spectroscopy. For differentiating between benign and malignant masses, positron emission tomography (PET) imaging is useful with its qualitative analysis, as well as its ability to detect the presence of extra-adrenal metastases in cancer patients. The work-up for an indeterminate adrenal mass includes evaluation with a non-contrast CT. If a lesion is less than 10 Hounsfield Units on a non-contrast CT, it is a benign lipid-rich adenoma and no further work-up is required. For the indeterminate adrenal masses, a lipid-poor adenoma can be differentiated from a metastasis utilizing CT wash-out features. Also, MRI is beneficial with CSI and MR spectroscopy. If a mass remains indeterminate, PET imaging may be of use, in which benign lesions demonstrate low or no fluorodeoxyglucose activity. In the few cases in which adrenal lesions remain indeterminate, surgical sampling such as percutaneous biopsy can be performed.     

Diagnostic and prognostic value of non-invasive imaging in known or suspected coronary artery disease

The role of non-invasive imaging techniques in the evaluation of patients with suspected or known coronary artery disease (CAD) has increased exponentially over the past decade. The traditionally available imaging modalities, including nuclear imaging, stress echocardiography and magnetic resonance imaging (MRI), have relied on detection of CAD by visualisation of its functional consequences (i.e. ischaemia). However, extensive research is being invested in the development of non-invasive anatomical imaging using computed tomography or MRI to allow detection of (significant) atherosclerosis, eventually at a preclinical stage. In addition to establishing the presence of or excluding CAD, identification of patients at high risk for cardiac events is of paramount importance to determine post-test management, and the majority of non-invasive imaging tests can also be used for this purpose. The aim of this review is to provide an overview of the available non-invasive imaging modalities and their merits for the diagnostic and prognostic work-up in patients with suspected or known CAD.     

Clinical decision support systems for brain tumor characterization using advanced magnetic resonance imaging techniques

In recent years, advanced magnetic resonance imaging (MRI) techniques, such as magnetic resonance spectroscopy, diffusion weighted imaging, diffusion tensor imaging and perfusion weighted imaging have been used in order to resolve demanding diagnostic problems such as brain tumor characterization and grading, as these techniques offer a more detailed and non-invasive evaluation of the area under study. In the last decade a great effort has been made to import and utilize intelligent systems in the so-called clinical decision support systems (CDSS) for automatic processing, classification, evaluation and representation of MRI data in order for advanced MRI techniques to become a part of the clinical routine, since the amount of data from the aforementioned techniques has gradually increased. Hence, the purpose of the current review article is two-fold. The first is to review and evaluate the progress that has been made towards the utilization of CDSS based on data from advanced MRI techniques. The second is to analyze and propose the future work that has to be done, based on the existing problems and challenges, especially taking into account the new imaging techniques and parameters that can be introduced into intelligent systems to significantly improve their diagnostic specificity and clinical application.     

多模态影像技术在僵直少动型帕金森病的脑机制及TMS治疗中的研究进展

僵直少动型帕金森病(AR-PD)病人更易出现运动障碍且预后较差。多模态影像技术为评估PD病人大脑结构及功能改变提供了无创手段。经颅磁刺激(TMS)作为一种无创的治疗方法,可以通过改变刺激脑区的兴奋性达到改善PD运动症状的效果。总结AR-PD的临床特征,并就基于磁敏感加权成像、结构MRI、血氧水平依赖功能MRI和扩散张量成像等多模态MRI以及核医学技术对AR-PD的脑机制及其在AR-PD TMS治疗中的研究进展予以综述。     

Multiple-mouse MRI.

Several theoretical parallel-imaging approaches are evaluated that seek to improve the efficiency of an MRI experiment involving multiple small samples, such as mice. The best method for our mouse phenotyping application is chosen in terms of efficiency and ease of implementation, and the approach is demonstrated at 1.5 T on a clinical scanner with an array of four shielded birdcage coils with four parallel receivers. Electronic interactions between the receiver channels in the system are quantified and a novel sensitivity-encoding (SENSE)-like postprocessing method is described to remove the resulting image ghosts. In parallel imaging with a four-coil array, the time required for three-dimensional (3D) high-resolution imaging of four mice is reduced to one-fourth the time that it would take to image the mice sequentially.