Search results
Found 12764 matches for
Hyperpolarized 13 C magnetic resonance imaging for noninvasive assessment of tissue inflammation.
Inflammation is a central mechanism underlying numerous diseases and incorporates multiple known and potential future therapeutic targets. However, progress in developing novel immunomodulatory therapies has been slowed by a need for improvement in noninvasive biomarkers to accurately monitor the initiation, development and resolution of immune responses as well as their response to therapies. Hyperpolarized magnetic resonance imaging (MRI) is an emerging molecular imaging technique with the potential to assess immune cell responses by exploiting characteristic metabolic reprogramming in activated immune cells to support their function. Using specific metabolic tracers, hyperpolarized MRI can be used to produce detailed images of tissues producing lactate, a key metabolic signature in activated immune cells. This method has the potential to further our understanding of inflammatory processes across different diseases in human subjects as well as in preclinical models. This review discusses the application of hyperpolarized MRI to the imaging of inflammation, as well as the progress made towards the clinical translation of this emerging technique.
Quantifying the effect of dobutamine stress on myocardial Pi and pH in healthy volunteers: A 31 P MRS study at 7T.
PURPOSE: Phosphorus spectroscopy (31 P-MRS) is a proven method to probe cardiac energetics. Studies typically report the phosphocreatine (PCr) to adenosine triphosphate (ATP) ratio. We focus on another 31 P signal: inorganic phosphate (Pi), whose chemical shift allows computation of myocardial pH, with Pi/PCr providing additional insight into cardiac energetics. Pi is often obscured by signals from blood 2,3-diphosphoglycerate (2,3-DPG). We introduce a method to quantify Pi in 14 min without hindrance from 2,3-DPG. METHODS: Using a 31 P stimulated echo acquisition mode (STEAM) sequence at 7 Tesla that inherently suppresses signal from 2,3-DPG, the Pi peak was cleanly resolved. Resting state UTE-chemical shift imaging (PCr/ATP) and STEAM 31 P-MRS (Pi/PCr, pH) were undertaken in 23 healthy controls; pH and Pi/PCr were subsequently recorded during dobutamine infusion. RESULTS: We achieved a clean Pi signal both at rest and stress with good 2,3-DPG suppression. Repeatability coefficient (8 subjects) for Pi/PCr was 0.036 and 0.12 for pH. We report myocardial Pi/PCr and pH at rest and during catecholamine stress in healthy controls. Pi/PCr was maintained during stress (0.098 ± 0.031 [rest] vs. 0.098 ± 0.031 [stress] P = .95); similarly, pH did not change (7.09 ± 0.07 [rest] vs. 7.08 ± 0.11 [stress] P = .81). Feasibility for patient studies was subsequently successfully demonstrated in a patient with cardiomyopathy. CONCLUSION: We introduced a method that can resolve Pi using 7 Tesla STEAM 31 P-MRS. We demonstrate the stability of Pi/PCr and myocardial pH in volunteers at rest and during catecholamine stress. This protocol is feasible in patients and potentially of use for studying pathological myocardial energetics.
Cardiac MRS studies in rodents and other animals
© 2015 John Wiley & Sons, Ltd. We describe MR spectroscopy techniques that have been used over the past 40 years, first in the isolated, beating rodent heart and, more recently, the in situ heart. Initially, 31P MRS was used to follow changes in myocardial phosphocreatine, ATP, and Pi during ischemia. From the spectra, changes in intra- and extracellular pH (pHi and pHo) could be calculated, as could the concentration of free magnesium, ADP and AMP, the cytosolic phosphorylation potential, and the free energy of ATP hydrolysis. Subsequently, attempts were made to use 2-deoxyglucose to measure pHi and glucose uptake, while magnetization transfer was used to measure myocardial creatine kinase flux. Making the same measurements in vivo has proved difficult, yet 31P and 1H MRS of the in vivo mouse heart have been achieved by several groups, who have measured myocardial energetics, creatine, and lipids. 13C MRS has been used to follow cardiac glycogen, lipids, and TCA cycle flux and, more recently, hyperpolarized 13C MRS has been used to measure pyruvate dehydrogenase flux, pHi, and short-chain fatty acid and ketone metabolism in vivo. Finally, MRS has been used to measure the intra- and extracellular cation concentrations and thereby trans-sarcolemmal cation fluxes in the rodent heart.
Hyperpolarised magnetic resonance for in vivo real-time metabolic imaging.
Although non-invasive perfusion and viability imaging often provide the gateway to coronary revascularisation, current non-invasive imaging methods only report the surrogate markers of inducible hypoperfusion and presence or absence of myocardial scar, rather than actually visualising areas of ischaemia and/or viable myocardium. This may lead to suboptimal revascularisation decisions. Normally respiring (viable) cardiomyocytes convert pyruvate to acetyl-CoA and CO2/bicarbonate (via pyruvate dehydrogenase), but under ischaemic conditions characteristically shift this conversion to lactate (by lactate dehydrogenase). Imaging pyruvate metabolism thus has the potential to improve upon current imaging techniques. Using the novel hyperpolarisation technique of dynamic nuclear polarisation (DNP), the magnetic resonance signal of injected [1-13C]pyruvate can be transiently magnified >10 000 times over that seen in conventional MR spectroscopy, allowing the characteristic metabolic signatures of ischaemia (lactate production) and viability (CO2/bicarbonate production) to be directly imaged. As such DNP imaging of the downstream metabolism of [1-13C]pyruvate could surpass the diagnostic capabilities of contemporary ischaemia and viability testing. Here we review the technique, and with brief reference to the salient biochemistry, discuss its potential applications within cardiology. These include ischaemia and viability testing, and further characterisation of the altered metabolism seen at different stages during the natural history of heart failure.
CINE-MR imaging of the normal and infarcted rat heart using an 11.7 T vertical bore MR system.
MR imaging is uniquely placed to non-invasively study rodent cardiac structure and function. High-field MR scanners commonly have a vertical bore, and the purpose of this work was to demonstrate CINE-MR imaging in normal and infarcted rat hearts after determining hemodynamic stability when positioned vertically for imaging. Optimisation of imaging parameters was carried out prior to assessment of cardiac function in a group of normal and infarcted rat hearts. Rat hemodynamics were unaltered when vertical for 90 minutes, compared with horizontal measurements and rat cardiac parameters were measured accurately and reproducibly with our optimized CINE-MR protocol. A flip angle of 17.5 degrees was shown to provide optimal contrast for the assessment of structure and function, and, in contrast to our findings in mice, respiratory gating was not found to be essential. Hence, we conclude that vertical bore MR systems can be used to measure in vivo cardiac function in normal and infarcted rat hearts.
Cardiac cine MR-imaging at 3T: FLASH vs SSFP.
The implications of an increase in field strength, from 1.5 T to 3 T, for routine functional cardiac examinations have been systematically investigated. Flip angle optimization was carried out for identical SSFP and FLASH cine imaging sequences at 1.5 T and 3 T, which supported the use of 20 degrees (FLASH 1.5 T and 3 T) and >60 degrees (SSFP 1.5 T and 3 T). The optimized sequences were applied in a study of cardiac function in a group of ten normal volunteers. Both SSFP and FLASH sequences showed significant SNR increases in the myocardium and blood at 3 T compared with 1.5 T, increases of 48% and 30% (myocardium and blood, respectively) for the SSFP sequence and 19% and 13% for the FLASH sequence. The SSFP sequence also showed a significant increase in CNR (22%). Image quality assessment revealed that the SSFP acquisitions were superior to FLASH at both field strengths. Although SSFP contained more artifacts at 3 T, they would not prevent its clinical use. We conclude that cardiac functional examinations at 3 T should use SSFP sequences.
High-resolution, multicontrast three-dimensional-MRI characterizes atherosclerotic plaque composition in ApoE-/- mice ex vivo.
PURPOSE: To systematically investigate intrinsic MR contrast mechanisms that would facilitate plaque characterization and quantification in the aortic root and brachiocephalic artery of ApoE-/- mice ex vivo. MATERIALS AND METHODS: To establish unambiguous MR parameters for routinely analyzing atherosclerotic plaque ex vivo at 11.7 T, relaxation times of plaque components were quantitatively assessed. Magnetization transfer and lipid-proton three-dimensional MR imaging was investigated for visualization of collagen- and lipid-rich plaque regions, respectively. A three-dimensional multiecho sequence with a spatial resolution of 47 x 47 x 63 microm was implemented providing a variable degree of T2-weighting. RESULTS: Relaxation time measurements showed clear tissue heterogeneity between atherosclerotic plaque components in the T2-values, but similar T1-values at 11.7 T (T1/T2 mean +/- SD; cellular plaque component: 1.2 +/- 0.3 seconds/26.3 +/- 0.4 msec; fibrofatty plaque component: 1.1 +/- 0.2 seconds/13.7 +/- 2.0 msec). The three-dimensional multiecho sequence allowed the calculation of the intrinsic proton density and T2-maps. The sum of the multiecho data provided strong T2-weighting that facilitated quantification of various components of atherosclerotic plaque in the mouse aortic root and correlated well with histology (P < 0.0001). CONCLUSION: High-resolution MRI allows for accurate classification and quantification of atherosclerotic plaque components in the aortic root of mice.
Fast, high-resolution in vivo cine magnetic resonance imaging in normal and failing mouse hearts on a vertical 11.7 T system.
PURPOSE: To establish fast, high-resolution in vivo cine magnetic resonance imaging (cine-MRI) on a vertical 11.7-T MR system and to investigate the stability of normal and failing mouse hearts in the vertical position. MATERIALS AND METHODS: To optimize the method on a high-field system, various MR-related parameters, such as relaxation times and the need for respiratory gating, were quantitatively investigated. High-resolution cine-MRI was applied to normal mice and to a murine heart failure model. Cardiac functional parameters were compared to matched mice imaged previously on a horizontal MR system. RESULTS: A T(1) of 1.10 +/- 0.27 seconds and a T(2) of 18.5 +/- 3.9 msec were measured for murine myocardial tissue. A quantitative analysis also proved respiratory gating to be essential for obtaining artifact-free cine images in the vertical position at this field strength. Cardiac functional parameters of mice, obtained within one hour, agreed well with those from previous studies of mice in the horizontal position. CONCLUSION: This work shows that MR systems with a vertical bore design can be used to accurately measure cardiac function in both normal and chronically failing mouse hearts within one hour. The increased signal-to-noise ratio (SNR) due to the higher field strength could be exploited to obtain higher temporal and spatial resolution compared to previous studies that were performed on horizontal systems with lower field strengths.
In vivo cardiac 1H-MRS in the mouse.
The mouse is the predominant animal model to study the effect of gene manipulations. Imaging techniques to define functional effects on the heart caused by genomic alterations are becoming increasingly routine in mice, yet methods for in vivo investigation of metabolic phenotypes in the mouse heart are lacking. In this work, cardiac 1H-MRS was developed and applied in mouse hearts in vivo using a single-voxel technique (PRESS). In normal C57Bl/6J mice, stability and reproducibility achieved by dedicated cardiac and respiratory gating was demonstrated by measuring amplitude and zero-order phase changes of the unsuppressed water signal. Various cardiac metabolites, such as creatine, taurine, carnitine, or intramyocardial lipids were successfully detected and quantified relative to the total water content in voxels as small as 2 microl, positioned in the interventricular septum. The method was applied to a murine model of guanidinoacetate N-methyltransferase (GAMT) deficiency, which is characterized by substantially decreased myocardial creatine levels. Creatine deficiency was confirmed noninvasively in myocardium of anesthetized GAMT-/- mice. This is the first study to report the application of cardiac 1H-MRS in mice in vivo.
Fat emulsification measured using NMR transverse relaxation.
This paper presents a novel method of measuring the droplet size in oil-in-water emulsions. It is based on changes in the NMR transverse relaxation rate due to the effect of microscopic magnetic susceptibility differences between fat droplets and the surrounding water. The longitudinal and transverse relaxation rates of a series of emulsions with constant oil volume fraction and five different mean droplet sizes, in the range 0.4-20.9 microm, were measured in vitro at 37 degrees C using EPI. While the longitudinal relaxation rate 1/T(1) did not change significantly, 1/T(2) was observed to increase with mean droplet size. The measured changes in 1/T(2) were found to be in good agreement with results predicted from proton random walk simulations, and were also consistent with analytical solutions based on an outer sphere relaxation model. Measurements of 1/T(2) on emulsions with a higher oil volume fraction, and on emulsions of a fixed size where the water phase was doped with gadolinium to modulate the susceptibility difference between the phases, also showed the predicted behavior. As part of this study the susceptibility difference between olive oil and water was measured to be 1.55 ppm.
Myometrial and placental artery reactivity alone cannot explain reduced placental perfusion in pre-eclampsia and intrauterine growth restriction.
OBJECTIVES: (1) To investigate a possible association between myometrial and placental artery vasoreactivity and perfusion at the basal and chorionic plates, respectively. (2) To confirm that myometrial arteries from women with pre-eclampsia and intrauterine growth restriction exhibit an attenuated endothelium-dependent vasodilatory response. METHODS: Women with normal pregnancy, pre-eclampsia and intrauterine growth restriction had a magnetic resonance scan to assess placental perfusion using a technique called intravoxel incoherent motion. At delivery, myometrial and chorionic plate placental arteries were assessed on a wire myograph. Vessels were pre-constricted with the thromboxane mimetic U46619 and dilated with incremental doses of bradykinin. RESULTS: Pre-constricted myometrial arteries from women with pre-eclampsia or intrauterine growth restriction exhibited an attenuated vasodilatory response to bradykinin, compared with normal pregnancy (P < 0.0001). Pre-constricted placental arteries exhibited a minimal vasodilatory response in all three groups of women (P = 0.10). Maximal constrictor and vasodilatory responses of myometrial arteries were not associated with the perfusing fraction at the basal plate. Maximal constrictor and vasodilatory responses of chorionic plate placental arteries were not associated with the perfusing fraction at the chorionic plate. CONCLUSION: We confirm that myometrial arteries from women with pre-eclampsia or intrauterine growth restriction exhibit an attenuated endothelium-dependent vasodilatory response. Apart from vasoreactivity of small arteries, other factors may be involved in the control of placental perfusion.
Echo-planar magnetic resonance imaging of Gaviscon alginate rafts in-vivo.
Liquid Gaviscon and Gaviscon Advance are established reflux suppressant formulations. This study describes the use of echo-planar magnetic resonance imaging (EPI) to visualise non-invasively intragastric alginate rafts of Liquid Gaviscon and Gaviscon Advance in healthy subjects. Secondly, the feasibility of using relaxation rate (T2(-1)) measurements to monitor changes in the physicochemical properties of the rafts in-vivo is evaluated. Six subjects ingested 500 mL of a liquid meal and received a single dose of 20 mL Liquid Gaviscon or 10 mL Gaviscon Advance on 2 separate visits each and were imaged every 15 min. An alginate raft was observed in the stomach for all subjects and both treatments. The raft was observed to consist of a few large fragments on the majority of the scans for both products. At t = 60 min a raft was still present in all cases. Three-dimensional volume reconstructions showed, for the first time, the spatial distribution of the rafts within the gastric lumen. The T2(-1) data showed potential for assessment of dynamic changes in the physicochemical properties of the alginate rafts in-vivo. We conclude that EPI shows great potential in assessing alginate rafts formation in-vivo.