Fluorine-19 magnetic resonance angiography of the mouse.

PURPOSE: To implement and characterize a fluorine-19 ((19)F) magnetic resonance imaging (MRI) technique and to test the hypothesis that the (19)F MRI signal in steady state after intravenous injection of a perfluoro-15-crown-5 ether (PCE) emulsion may be exploited for angiography in a pre-clinical in vivo animal study. MATERIALS AND METHODS: In vitro at 9.4T, the detection limit of the PCE emulsion at a scan time of 10 min/slice was determined, after which the T(1) and T(2) of PCE in venous blood were measured. Permission from the local animal use committee was obtained for all animal experiments. 12 µl/g of PCE emulsion was intravenously injected in 11 mice. Gradient echo (1)H and (19)F images were obtained at identical anatomical levels. Signal-to-noise (SNR) and contrast-to-noise (CNR) ratios were determined for 33 vessels in both the (19)F and (1)H images, which was followed by vessel tracking to determine the vessel conspicuity for both modalities. RESULTS: In vitro, the detection limit was ∼400 µM, while the (19)F T(1) and T(2) were 1350±40 and 25±2 ms. The (19)F MR angiograms selectively visualized the vasculature (and the liver parenchyma over time) while precisely coregistering with the (1)H images. Due to the lower SNR of (19)F compared to (1)H (17±8 vs. 83±49, p<0.001), the (19)F CNR was also lower at 15±8 vs. 52±35 (p<0.001). Vessel tracking demonstrated a significantly higher vessel sharpness in the (19)F images (66±11 vs. 56±12, p = 0.002). CONCLUSION: (19)F magnetic resonance angiography of intravenously administered perfluorocarbon emulsions is feasible for a selective and exclusive visualization of the vasculature in vivo

Fluorine MR Imaging of Inflammation in Atherosclerotic Plaque in Vivo.

PURPOSE: To preliminarily test the hypothesis that fluorine 19 ((19)F) magnetic resonance (MR) imaging enables the noninvasive in vivo identification of plaque inflammation in a mouse model of atherosclerosis, with histologic findings as the reference standard. MATERIALS AND METHODS: The animal studies were approved by the local animal ethics committee. Perfluorocarbon (PFC) emulsions were injected intravenously in a mouse model of atherosclerosis (n = 13), after which (19)F and anatomic MR imaging were performed at the level of the thoracic aorta and its branches at 9.4 T. Four of these animals were imaged repeatedly (at 2-14 days) to determine the optimal detection time. Repeated-measures analysis of variance with a Tukey test was applied to determine if there was a significant change in (19)F signal-to-noise ratio (SNR) of the plaques and liver between the time points. Six animals were injected with a PFC emulsion that also contained a fluorophore. As a control against false-positive results, wild-type mice (n = 3) were injected with a PFC emulsion, and atherosclerotic mice were injected with a saline solution (n = 2). The animals were sacrificed after the last MR imaging examination, after which high-spatial-resolution ex vivo MR imaging and bright-field and immunofluorescent histologic examination were performed. RESULTS: (19)F MR signal was detected in vivo in plaques in the aortic arch and its branches. The SNR was found to significantly increase up to day 6 (P < .001), and the SNR of all mice at this time point was 13.4 ± 3.3. The presence of PFC and plaque in the excised vessels was then confirmed both through ex vivo (19)F MR imaging and histologic examination, while no signal was detected in the control animals. Immunofluorescent histologic findings confirmed the presence of PFC in plaque macrophages. CONCLUSION: (19)F MR imaging allows the noninvasive in vivo detection of inflammation in atherosclerotic plaques in a mouse model of atherosclerosis and opens up new avenues for both the early detection of vulnerable atherosclerosis and the elucidation of inflammation mechanisms in atherosclerosis

Coronary reserve in patients with aortic valve disease before and after successful aortic valve replacement

In patients with aortic valve disease and normal coronary angiograms coronary reserve was determined by the coronary sinus thermodilution technique. Three groups of patients were studied: 37 preoperative patients; 18 different patients 12.52 months after aortic valve replacement and seven control subjects with no cardiac disease. Coronary flow ratio (dipyridamole/rest) was diminished in preoperative compared with postoperative patients (1.66±0.44 vs 2.22±0.85; P<0.05) as well as with controls (2.80±0.84; P<0.01), and corresponding coronary resistance ratio (dipyridamolej rest) was higher in preoperative patients than in both other groups (0.61±0.17 vs 0.48±0.14; P<0.05 vs 0.37±0.10; P<0.01). Differences in the flow ratio, but not in the resistance ratio, were significant (P<0.05) in patients after aortic valve replacement compared with controls. Total coronary sinus blood flow at rest was elevated in preoperative compared with both postoperative patients and controls (252±99 vs 169±63; P<0.01; vs 170±35 ml.min−1, P<0.05), whereas flows after maximal vasodilation did not differ among the three groups (416± 184 vs 361 ± 150 vs 488± 235 ml.min−1). Postoperative patients showed a distinct, though not total regression of left ventricular angiographic muscle mass index and wall thickness. Nine of the 18 postoperative patients showed a normal coronary flow reserve and nine showed subnormal response. These two subgroups did not differ with respect to preoperative macroscopic and microscopic measures of hypertrophy. Thus in aortic valve disease, the reduced coronary vasodilator capacity is mainly due to an elevated coronary flow at rest, while the maximal coronary blood flow achieved is identical to that of postoperative patients and controls. With regression of left ventricular hypertrophy, flow at rest decreases and this leads to a distinct improvement of coronary flow reserv

Feasibility of perfusion cardiovascular magnetic resonance in paediatric patients

AIMS: As coronary artery disease may also occur during childhood in some specific conditions, we sought to assess the feasibility and accuracy of perfusion cardiovascular magnetic resonance (CMR) in paediatric patients. METHODS AND RESULTS: First-pass perfusion CMR studies were performed under pharmacological stress with adenosine and by using a hybrid echo-planar pulse sequence with slice-selective saturation recovery preparation. Fifty-six perfusion CMR examinations were performed in 47 patients. The median age was 12 years (1 month-18 years), and weight 42.8 kg (2.6-82 kg). General anaesthesia was required in 18 patients. Mean examination time was 67 +/- 19 min. Diagnostic image quality was obtained in 54/56 examinations. In 23 cases the acquisition parameters were adapted to patient's size. Perfusion CMR was abnormal in 16 examinations. The perfusion defects affected the territory of the left anterior descending coronary artery in 11, of the right coronary artery in 3, and of the circumflex coronary artery in 2 cases. Compared to coronary angiography, perfusion CMR showed a sensitivity of 87% (CI 52-97%) and a specificity of 95% (CI 79-99%). CONCLUSION: In children, perfusion CMR is feasible and accurate. In very young children (less than 1 year old), diagnostic image quality may be limited

Characterization of perfluorocarbon relaxation times and their influence on the optimization of fluorine-19 MRI at 3 tesla.

To characterize and optimize javax.xml.bind.JAXBElement@7524a985 F MRI for different perfluorocarbons (PFCs) at 3T and quantify the loss of acquisition efficiency as a function of different temperature and cellular conditions. The T javax.xml.bind.JAXBElement@1ef4ca84 and T javax.xml.bind.JAXBElement@295b7e6f relaxation times of the commonly used PFCs perfluoropolyether (PFPE), perfluoro-15-crown-5-ether (PFCE), and perfluorooctyl bromide (PFOB) were measured in phantoms and in several different conditions (cell types, presence of fixation agent, and temperatures). These relaxation times were used to optimize pulse sequences through numerical simulations. The acquisition efficiency in each cellular condition was then determined as the ratio of the signal after optimization with the reference relaxation times and after optimization with its proper relaxation times. Finally, PFC detection limits were determined. The loss of acquisition efficiency due to parameter settings optimized for the wrong temperature and cellular condition was limited to 13%. The detection limits of all PFCs were lower at 24 °C than at 37 °C and varied from 11.8 ± 3.0 mM for PFCE at 24 °C to 379.9 ± 51.8 mM for PFOB at 37 °C. Optimizing javax.xml.bind.JAXBElement@30187e57 F pulse sequences with a known phantom only leads to moderate loss in acquisition efficiency in cellular conditions that might be encountered in in vivo and in vitro experiments. Magn Reson Med 77:2263-2271, 2017. © 2016 International Society for Magnetic Resonance in Medicine

Impact of bileaflet mitral valve prolapse on quantification of mitral regurgitation with cardiac magnetic resonance: a single-center study.

To quantify mitral regurgitation (MR) with CMR, the regurgitant volume can be calculated as the difference between the left ventricular (LV) stroke volume (SV) measured with the Simpson's method and the reference SV, i.e. the right ventricular SV (RVSV) in patients without tricuspid regurgitation. However, for patients with prominent mitral valve prolapse (MVP), the Simpson's method may underestimate the LV end-systolic volume (LVESV) as it only considers the volume located between the apex and the mitral annulus, and neglects the ventricular volume that is displaced into the left atrium but contained within the prolapsed mitral leaflets at end systole. This may lead to an underestimation of LVESV, and resulting an over-estimation of LVSV, and an over-estimation of mitral regurgitation. The aim of the present study was to assess the impact of prominent MVP on MR quantification by CMR. In patients with MVP (and no more than trace tricuspid regurgitation) MR was quantified by calculating the regurgitant volume as the difference between LVSV and RVSV. LVSV &lt;sub&gt;uncorr&lt;/sub&gt; was calculated conventionally as LV end-diastolic (LVEDV) minus LVESV. A corrected LVESV &lt;sub&gt;corr&lt;/sub&gt; was calculated as the LVESV plus the prolapsed volume, i.e. the volume between the mitral annulus and the prolapsing mitral leaflets. The 2 methods were compared with respect to the MR grading. MR grades were defined as absent or trace, mild (5-29% regurgitant fraction (RF)), moderate (30-49% RF), or severe (≥50% RF). In 35 patients (44.0 ± 23.0y, 14 males, 20 patients with MR) the prolapsed volume was 16.5 ± 8.7 ml. The 2 methods were concordant in only 12 (34%) patients, as the uncorrected method indicated a 1-grade higher MR severity in 23 (66%) patients. For the uncorrected/corrected method, the distribution of the MR grades as absent-trace (0 vs 11, respectively), mild (20 vs 18, respectively), moderate (11 vs 5, respectively), and severe (4 vs 1, respectively) was significantly different (p &lt; 0.001). In the subgroup without MR, LVSV &lt;sub&gt;corr&lt;/sub&gt; was not significantly different from RVSV (difference: 2.5 ± 4.7 ml, p = 0.11 vs 0) while a systematic overestimation was observed with LVSV &lt;sub&gt;uncorr&lt;/sub&gt; (difference: 16.9 ± 9.1 ml, p = 0.0007 vs 0). Also, RVSV was highly correlated with aortic forward flow (n = 24, R &lt;sup&gt;2&lt;/sup&gt;  = 0.97, p &lt; 0.001). For patients with severe bileaflet prolapse, the correction of the LVSV for the prolapse volume is suggested as it modified the assessment of MR severity by one grade in a large portion of patients

Detection of coronary artery disease by magnetic resonance myocardial perfusion imaging with various contrast medium doses: first european multi-centre experience

Aims Magnetic resonance (MR) first-pass myocardial perfusion imaging during hyperaemia detects coronary artery stenoses in humans with test sensitivity depending on contrast medium (CM)-induced signal change in myocardium. In this prospective multi-centre study, the effect of CM dose on myocardial signal change and on diagnostic performance was evaluated using a stress-only approach. Methods and results Ninety-four patients with known or suspected coronary artery disease (CAD) were randomised to 0.05,0.10, or 0.15 mmol/kg body weight of an extravascular CM (Gd-DTPA) and X-ray coronary angiography was performed within 30 days prior/after the MR examination. A multi-slice MR technique with identical hardware and software in all centres was used during hyperaemia (adenosine 0.14 mg/kg/min) to monitor myocardial CM wash-in kinetics and data were analysed semi-automatically in a core laboratory. Protocol violations resulted in 80 complete studies with CAD (defined as ⩾1 vessel with diameter stenosis ⩾50% on quantitative coronary angiography) present in 19/29, 13/24, and 20/27 patients for doses 1, 2, and 3, respectively. In normal myocardium, the upslope increased with CM dose (overall-p<0.0001, ANOVA). For CAD detection the area under the receiver operator characteristics curve for subendocardial data (3 slices with quality score<4 representing 86% of cases) was 0.91±0.07 and 0.86±0.08 for doses 2 and 3, respectively, and was lower for dose 1 (0.53±0.13, p<0.01 and p<0.02 vs. doses 2 and 3, respectively). Corresponding sensitivities/specificities (95% confidence intervals) for pooled doses 2/3 were 93% (77-99%; ns vs. dose 1) and 75% (48-92%;p<0.05 vs. dose 1), respectively. Conclusions With increasing doses of CM, a higher signal response in the myocardium was achieved and consequently this stress-only protocol, with CM doses of 0.10-0.15 mmol/kg combined with a semi-automatic analysis, yielded a high diagnostic performance for the detection of CA

Four-dimensional trapped ion mobility spectrometry lipidomics for high throughput clinical profiling of human blood samples

Lipidomics encompassing automated lipid extraction, a four-dimensional (4D) feature selection strategy for confident lipid annotation as well as reproducible and cross-validated quantification can expedite clinical profiling. Here, we determine 4D descriptors (mass to charge, retention time, collision cross section, and fragmentation spectra) of 200 lipid standards and 493 lipids from reference plasma via trapped ion mobility mass spectrometry to enable the implementation of stringent criteria for lipid annotation. We use 4D lipidomics to confidently annotate 370 lipids in reference plasma samples and 364 lipids in serum samples, and reproducibly quantify 359 lipids using level-3 internal standards. We show the utility of our 4D lipidomics workflow for high-throughput applications by reliable profiling of intra-individual lipidome phenotypes in plasma, serum, whole blood, venous and finger-prick dried blood spots

Three-Dimensional Self-Navigated T2 Mapping for the Detection of Acute Cellular Rejection After Orthotopic Heart Transplantation.

T2 mapping is a magnetic resonance imaging technique measuring T2 relaxation time, which increases with the myocardial tissue water content. Myocardial edema is a component of acute cellular rejection (ACR) after heart transplantation. This pilot study compares in heart transplantation recipients a novel high resolution 3-dimensional (3D) T2-mapping technique with standard 2-dimensional (2D) T2-mapping for ACR detection. Consecutive asymptomatic patients (n = 26) underwent both 3D T2 mapping and reference 2D T2 mapping magnetic resonance imaging on the day of endomyocardial biopsy (EMB). 3D T2 maps were obtained at an isotropic spatial resolution of 1.72 mm (voxel volume 5.1 mm(3)). 2D and 3D maps were matched anatomically, and maximum segmental T2 values were compared blinded to EMB results. In addition, all 3D T2 maps were rendered as 3D images and inspected for foci of T2 elevation. T2 values of segments from 2D and reformatted 3D T2 maps agreed (p &gt; 0.5). The highest 2D segmental T2 values were 49.9 ± 4.0 ms (no ACR = 0R, n = 18), 48.9 ± 0.8 ms (mild ACR = 1R, n = 3), and 65.0 ms (moderate ACR = 2R). Rendered 3D T2 maps of cases with 1R showed foci with significantly elevated T2 signal (T2 = 58.2 ± 3.6 ms); 5 cases (28%) in the 0R group showed foci with increased T2 values (&gt;2 SD above adjacent tissue) that were not visible on the 2D T2 maps. This pilot study in a small cohort suggests equivalency of standard segmental analysis between 3D and 2D T2-mapping. 3D T2 mapping provides a spatial resolution that permits detection of foci with elevated T2 in patients with mild ACR