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Magnetic resonance imaging (MRI) and MR cholangiopancreatography (MRCP) have emerged as non-invasive diagnostic techniques for the diagnosis of pancreatic and pancreatic duct disorders in humans. The number of studies focused on MR and MRCP for pancreatic disease in small animals is very limited. MR has been described for the evaluation of insulinoma in dogs and to investigate pancreatitis in cats. The studies were based on a standard protocol with T2 weighted (w) fast recovery fast spin-echo (FRFSE) with and without fat suppression, T1w FSE pre-contrast and T1w FSE post-contrast with and without fat suppression. MRCP after secretin stimulation has been described in cats to assess the pancreatic ductal system, taking advantage of pulse sequences heavily T2w as rapid acquisition with rapid enhancement (RARE), fast-recovery fast spin-echo (FRFSE) sequences and single-shot fast spin-echo (SSFSE) sequences. In addition to the standard protocol, fast spoiled gradient recalled echo pulse sequences (fSPGR) and volume interpolated 3D gradient-echo T1w pulse sequences pre and post-contrast have also been used in cats, reaching the goal of assessing the biliary tree and the pancreatic duct with the same sequence and in multiple planes. Despite the small amount of data, the results show potential, and the most recent technical innovations, in particular, focused on diffusion MRI and fast acquisition, further support the need for continued evaluation of MRI as an effective instrument for the investigation of pancreatic disease.
Diffusional Kurtosis Magnetic Resonance Imaging (DKI) quantifies the extent of non-Gaussian water diffusion, which has been shown to be a sensitive biomarker for microstructure in health and disease. However, DKI is not specific to any microstructural property per se since kurtosis may emerge from several different sources. Q-space trajectory encoding schemes have been proposed for decoupling kurtosis arising from the variance of mean diffusivities (isotropic kurtosis) from kurtosis driven by microscopic anisotropy (anisotropic kurtosis). Still, these methods assume that the system is comprised of multiple Gaussian diffusion components with vanishing intra-compartmental kurtosis (associated with restricted diffusion). Here, we develop a more general framework for resolving the underlying kurtosis sources without relying on the multiple Gaussian diffusion approximation. We introduce Correlation Tensor MRI (CTI) - an approach harnessing the versatility of double diffusion encoding (DDE) and its sensitivity to displacement correlation tensors capable of explicitly decoupling isotropic and anisotropic kurtosis components from intra-compartmental kurtosis effects arising from restricted (and time-dependent) diffusion. Additionally, we show that, by subtracting these isotropic and anisotropic kurtosis components from the total diffusional kurtosis, CTI provides an index that is potentially sensitive to intra-compartmental kurtosis. The theoretical foundations of CTI, as well as the first proof-of-concept CTI experiments in ex vivo mouse brains at ultrahigh field of 16.4 T, are presented. We find that anisotropic and isotropic kurtosis can decouple microscopic anisotropy from substantial partial volume effects between tissue and free water. Our intra-compartmental kurtosis index exhibited positive values in both white and grey matter tissues. Simulations in different synthetic microenvironments show, however, that our current CTI protocol for estimating intra-compartmental kurtosis is limited by higher order terms that were not taken into account in this study. CTI measurements were then extended to in vivo settings and used to map heathy rat brains at 9.4 T. These in vivo CTI results were found to be consistent with our ex vivo findings. Although future studies are still required to assess and mitigate the higher order effects on the intra-compartmental kurtosis index, our results show that CTI's more general estimates of anisotropic and isotropic kurtosis contributions are already ripe for future in vivo studies, which can have significant impact our understanding of the mechanisms underlying diffusion metrics extracted in health and disease.
Glutamate, a major neurotransmitter in the brain, shows a pH- and concentration-dependent chemical exchange saturation transfer effect (GluCEST) between its amine group and bulk water, with potential for in vivo imaging by nuclear magnetic resonance. GluCEST asymmetry is observed ∼3 p.p.m. downfield from bulk water. Middle cerebral artery occlusion in the rat brain resulted in an ∼100% elevation of GluCEST in the ipsilateral side compared with the contralateral side, predominantly owing to pH changes. In a rat brain tumor model with blood-brain barrier disruption, intravenous glutamate injection resulted in a clear elevation of GluCEST and a similar increase in the proton magnetic resonance spectroscopy signal of glutamate. GluCEST maps from healthy human brain were also obtained. These results demonstrate the feasibility of using GluCEST for mapping relative changes in glutamate concentration, as well as pH, in vivo. Contributions from other brain metabolites to the GluCEST effect are also discussed.
Dynamic MR biomarkers (T2*-weighted or susceptibility-based and T1-weighted or relaxivity-enhanced) have been applied to assess tumor perfusion and its response to therapies. A significant challenge in the development of reliable biomarkers is a rigorous assessment and optimization of reproducibility. The purpose of this study was to determine the measurement reproducibility of T1-weighted dynamic contrast-enhanced (DCE)-MRI and T2*-weighted dynamic susceptibility contrast (DSC)-MRI with two contrast agents (CA) of different molecular weight (MW): gadopentetate (Gd-DTPA, 0.5 kDa) and Gadomelitol (P792, 6.5 kDa). Each contrast agent was tested with eight mice that had subcutaneous MDA-MB-231 breast xenograft tumors. Each mouse was imaged with a combined DSC-DCE protocol three times within one week to achieve measures of reproducibility. DSC-MRI results were evaluated with a contrast to noise ratio (CNR) efficiency threshold. There was a clear signal drop (>95% probability threshold) in the DSC of normal tissue, while signal changes were minimal or non-existent (<95% probability threshold) in tumors. Mean within-subject coefficient of variation (wCV) of relative blood volume (rBV) in normal tissue was 11.78% for Gd-DTPA and 6.64% for P792. The intra-class correlation coefficient (ICC) of rBV in normal tissue was 0.940 for Gd-DTPA and 0.978 for P792. The inter-subject correlation coefficient was 0.092. Calculated K(trans) from DCE-MRI showed comparable reproducibility (mean wCV, 5.13% for Gd-DTPA, 8.06% for P792). ICC of K(trans) showed high intra-subject reproducibility (ICC = 0.999/0.995) and inter-subject heterogeneity (ICC = 0.774). Histograms of K(trans) distributions for three measurements had high degrees of overlap (sum of difference of the normalized histograms <0.01). These results represent homogeneous intra-subject measurement and heterogeneous inter-subject character of biological population, suggesting that perfusion MRI could be an imaging biomarker to monitor or predict response of disease.
MRI of the spine is an accurate, noninvasive sensitive imaging modality for the spine capable of demonstrating many pathologic conditions. Its ability to demonstrate long segments of the spine as well as its multiplanar imaging capability offer a unique anatomic perspective. It has superior contrast resolution without the use of iodinated contrast material and uses no ionizing radiation. By manipulating pulse sequences (TR and TE), differences in T1 and T2 relaxation rates can be made manifest, allowing differentiation of anatomic structures and in many cases pathologic conditions. Imminent and future improvements in slice thickness, spatial resolution, and signal-to-noise ratio are likely to improve further its sensitivity and accuracy as an imaging modality.
Determination of progesterone receptor (PR) status in hormone-dependent diseases is essential in ascertaining disease prognosis and monitoring treatment response. The development of a noninvasive means of monitoring these processes would have significant impact on early detection, cost, repeated measurements, and personalized treatment options. Magnetic resonance imaging (MRI) is widely recognized as a technique that can produce longitudinal studies, and PR-targeted MR probes may address a clinical problem by providing contrast enhancement that reports on PR status without biopsy. Commercially available MR contrast agents are typically delivered via intravenous injection, whereas steroids are administered subcutaneously. Whether the route of delivery is important for tissue accumulation of steroid-modified MRI contrast agents to PR-rich tissues is not known. To address this question, modification of the chemistry linking progesterone with the gadolinium chelate led to MR probes with increased water solubility and lower cellular toxicity and enabled administration through the blood. This attribute came at a cost through lower affinity for PR and decreased ability to cross the cell membrane, and ultimately it did not improve delivery of the PR-targeted MR probe to PR-rich tissues or tumors in vivo. Overall, these studies are important, as they demonstrate that targeted contrast agents require optimization of delivery and receptor binding of the steroid and the gadolinium chelate for optimal translation in vivo.
Noradrenaline is a neurotransmitter involved in general arousal, selective attention, memory, inflammation, and neurodegeneration. The purpose of this work was to delineate noradrenergic neurons in vivo by T1-weighted MRI with magnetization transfer (MT). In the brainstem of human and mice, MRI identified the locus coeruleus, dorsal motor vagus nucleus, and nucleus tractus solitarius. Given (1) the long T1 and low magnetization transfer ratio for the noradrenergic cell groups compared to other gray matter, (2) significant correlation between MT MRI signal intensity and proton density, and (3) no correlation between magnetization transfer ratio (or R1) and iron, copper, or manganese in human brain, the high MRI signal of the noradrenergic neurons must be attributed to abundant water protons interacting with any T1-shortening paramagnetic ions in active cells rather than to specific T1-shortening molecules. The absence of a high MRI signal from the locus coeruleus of Ear2(-/-) mice lacking noradrenergic neurons confirms that cell bodies of noradrenergic neurons are the source of the bright MRI appearance. The observation of this high signal in DBH(-/-) mice, in 3-week-old mice, and in mice under hyperoxia/hypercapnia/hypoxia together with the general absence of neuromelanin (NM) in noradrenergic neurons of young rodents further excludes that it is due to NM, dopamine β-hydroxylase, their binding to paramagnetic ions, blood inflow, or hemoglobin. Instead, these findings indicate a high density of water protons whose T1 is shortened by paramagnetic ions as the relevant source of the high MRI signal. In the brain of APP/PS1/Ear2(-/-) mice, a transgenic model of Alzheimer's disease, MRI detected noradrenergic neuron loss in the locus coeruleus. Proton magnetic resonance spectroscopy revealed that a 60-75% reduction of noradrenaline is responsible for a reduction of N-acetylaspartate and glutamate in the hippocampus as well as for a shortening of the water proton T2 in the frontal cortex. These results suggest that a concurrent shortage of noradrenaline in Alzheimer's disease accelerates pathologic processes such as inflammation and neuron loss.
Since the introduction of 4 T human systems in three academic laboratories circa 1990, rapid progress in imaging and spectroscopy studies in humans at 4 T and animal model systems at 9.4 T have led to the introduction of 7 T and higher magnetic fields for human investigation at about the turn of the century. Work conducted on these platforms has demonstrated the existence of significant advantages in SNR and biological information content at these ultrahigh fields, as well as the presence of numerous challenges. Primary difference from lower fields is the deviation from the near field regime; at the frequencies corresponding to hydrogen resonance conditions at ultrahigh fields, the RF is characterized by attenuated traveling waves in the human body, which leads to image nonuniformities for a given sample-coil configuration because of interferences. These nonuniformities were considered detrimental to the progress of imaging at high field strengths. However, they are advantageous for parallel imaging for signal reception and parallel transmission, two critical technologies that account, to a large extend, for the success of ultrahigh fields. With these technologies, and improvements in instrumentation and imaging methods, ultrahigh fields have provided unprecedented gains in imaging of brain function and anatomy, and started to make inroads into investigation of the human torso and extremities. As extensive as they are, these gains still constitute a prelude to what is to come given the increasingly larger effort committed to ultrahigh field research and development of ever better instrumentation and techniques.
Oxygen loaded microbubbles are being investigated as a means of reducing tumour hypoxia in order to improve response to cancer therapy. To optimise this approach, it is desirable to be able to measure changes in tissue oxygenation in real-time during treatment. In this study, the feasibility of using magnetic resonance imaging (MRI) for this purpose was investigated. Longitudinal relaxation time (T1) measurements were made in simple hydrogel phantoms containing two different concentrations of oxygen microbubbles. T1 was found to be unaffected by the presence of oxygen microbubbles at either concentration. Upon application of ultrasound to destroy the microbubbles, however, a statistically significant reduction in T1 was seen for the higher microbubble concentration. Further work is needed to assess the influence of physiological conditions upon the measurements, but these preliminary results suggest that MRI could provide a method for quantifying the changes in tissue oxygenation produced by microbubbles during therapy.
19F-magnetic resonance imaging (MRI) is a promising technique that may allow us to measure the concentration of exogenous fluorinated imaging probes quantitatively in vivo. Here, we describe the synthesis and characterisation of a novel geminal bisphosphonate (19F-BP) that contains chemically-equivalent fluorine atoms that show a single and narrow 19F resonance and a bisphosphonate group that may be used for labelling inorganic materials based in calcium phosphates and metal oxides. The potential of 19F-BP to provide contrast was analysed in vitro and in vivo using 19F-MRI. In vitro studies demonstrated the potential of 19F-BP as an MRI contrast agent in the millimolar concentration range with signal-to-noise ratios (SNR) comparable to previously reported fluorinated probes. The preliminary in vivo MRI study reported here allowed us to visualise the biodistribution of 19F-BP, showing uptake in the liver and in the bladder/urinary system areas. However, bone uptake was not observed. In addition, 19F-BP showed undesirable toxicity effects in mice that prevent further studies with this compound at the required concentrations for MRI contrast. This study highlights the importance of developing 19F MRI probes with the highest signal intensity achievable.
In its almost 25 years of clinical use, cardiac magnetic resonance imaging (CMR) has been developed for a wide range of indications due to the development of robust techniques and their comprehensive validation. CMR-based assessment of cardiac volumes and systolic ventricular function as well as the characterization of focal myocardial scars belongs today to standard cardiac imaging. More recently, the introduction of accelerated acquisition techniques, quantitative myocardial T1- and T2-mapping methods and 4‑dimensional (4D) flow measurements as well as new postprocessing techniques such as myocardial feature tracking have attracted attention.
Patients in ICUs often require neuroimaging to rule out a wide variety of intracranial problems. CT may be available in the ICU itself, but MRI has greater sensitivity for many conditions that affect the brain. However, transporting patients who are on ventilators and other life-sustaining devices is a labor-intensive process and involves placing the patient at risk for adverse events. This is a report of portable MRI in a clinical setting.
Previous studies have documented a spectrum of brain magnetic resonance imaging (MRI) abnormalities in patients with cerebral malaria, but little is known about the prevalence of such abnormalities in patients with non-cerebral malaria. The aim of this study was to assess the frequency of brain MRI findings in returning travellers with non-cerebral malaria.
Postmortem magnetic resonance imaging (MRI) has been used to investigate the cause of death, but due to time constraints, it is not widely applied to the heart. Therefore, MRI analysis of the heart after formalin fixation was previously performed. However, the changes in MRI signal values based on the fixation time of formalin were not investigated. The objective was to investigate changes over time in the T1- and T2-values of MRI signals in normal areas of hearts removed during autopsy, hearts subsequently fixed in formalin, and heart specimens sliced for the preparation of pathological specimens.
The Lisfranc joint has complex structures, and articular surfaces overlap on conventional X-ray radiographs. Hence, there is no available auxiliary examination for diagnosing related injuries. At present, few studies on the imaging of Lisfranc ligaments have been reported, and related imaging data are rare. Therefore, no imaging reference can be used for related diagnosis and repair operations. This study aims to observe and describe the morphology and structure of Lisfranc ligaments using magnetic resonance imaging (MRI), in order to provide imaging reference for the diagnosis and repair of Lisfranc joint injuries.
In the central nervous system of vertebrates, cell bodies of neurons are often assembled as nuclei or cellular layers that play specific roles as functional units. The purpose of this work was to selectively highlight such cell assemblies by magnetic resonance imaging using signals from water protons that are associated with intracellular paramagnetic ions, while saturating lipid-associated water protons as well as extracellular free water protons. Given the significant correlation between image signal intensity and water proton density, the high signal intensities observed for such cell assemblies must be attributed to their abundant paramagnetic-ion-associated water protons. In the hippocampal formation, the technique visualized cell assemblies that were so far not depicted in human in vivo. In the brainstem, the technique delineated noradrenergic neuron groups such as the locus coeruleus in human and mice in vivo. Their reduced magnetization-transfer ratios together with their prolonged relaxation times compared to other gray matter indicate that the source of their high signal intensity is not the presence of T1-shortening molecules, e.g., neuromelanin, but their high water content. Given the general absence of neuromelanin in noradrenergic neurons of rodents, their high signal intensity in mice in vivo further supports this view.
Functional magnetic resonance imaging (fMRI) non-invasively measures the activity of the human brain and provides a unique technological tool for investigating aspects of the human brain including cognition, development, and disorders. As one of the main funding agencies for basic research in China, the National Natural Scientific Foundation of China (NSFC) has initiated various research programs during the last two decades that are related to fMRI research. In this review, we collected and analyzed the metadata of the projects and published studies in research fields using fMRI that were funded by the NSFC. We observed a trend of increasing funding amounts from the NSFC for fMRI research, typically from the General Program and Key Program. Leading research institutes from economically developed municipalities and provinces received the most support and formed close collaboration relationships. Finally, we reviewed several representative achievements from research institutions in china, involving data analysis methods, brain connectomes, and computational platforms in addition to their applications in brain disorders.
While computed tomography and other imaging techniques are measured in absolute units with physical meaning, magnetic resonance images are expressed in arbitrary units that are difficult to interpret and differ between study visits and subjects. Much work in the image processing literature on intensity normalization has focused on histogram matching and other histogram mapping techniques, with little emphasis on normalizing images to have biologically interpretable units. Furthermore, there are no formalized principles or goals for the crucial comparability of image intensities within and across subjects. To address this, we propose a set of criteria necessary for the normalization of images. We further propose simple and robust biologically motivated normalization techniques for multisequence brain imaging that have the same interpretation across acquisitions and satisfy the proposed criteria. We compare the performance of different normalization methods in thousands of images of patients with Alzheimer's disease, hundreds of patients with multiple sclerosis, and hundreds of healthy subjects obtained in several different studies at dozens of imaging centers.
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