A physiological model of increased plasma nonesterified fatty acid (NEFA) levels result in myocardial triglyceride (TG) accumulation, which is related to cardiac dysfunction. A pathophysiological model of increased plasma NEFA levels result in hepatic steatosis, which has been linked to abnormal myocardial energy metabolism. Hepatic steatosis is accompanied by hepatic inflammation, reflected by plasma cholesteryl ester transfer protein (CETP) levels. The current study aimed to investigate effects of these models via different nutritional interventions on right ventricular (RV) function.
Fifteen men (age 25.0±6.6 years) were included and underwent magnetic resonance imaging and spectroscopy in this prospective crossover intervention study. RV function, myocardial and hepatic TG content, and CETP levels were assessed on three occasions: after normal diet, very low-calorie diet (VLCD, physiological model) and high-fat high-energy (HFHE, pathophysiological model) diet (all 3-days diets, randomly ordered, washout phase at least 14 days).
VLCD induced a decrease in mean E deceleration by 27%. Myocardial TG content increased by 55%, whereas hepatic TG content decreased by 32%. Plasma CETP levels decreased by 14% (all P<0.05). HFHE diet induced a decrease in E/A by 19% (P<0.05). Myocardial TG content did not change, whereas hepatic TG content increased by 112% (P<0.01). Plasma CETP levels increased by 14% (P<0.05).
These findings show that RV diastolic function is impaired after short-term VLCD and HFHE diet in healthy men, respectively a physiological and a pathophysiological model of increased plasma NEFA levels. After short-term VLCD, myocardial lipotoxicity may be of importance in decreased RV diastolic function. RV diastolic dysfunction is accompanied by increased hepatic TG content and plasma CETP levels after short-term HFHE diet, suggesting that systemic inflammation reflecting local macrophage infiltration in the heart may be involved in RV dysfunction.
Black-blood fast spin-echo imaging is a powerful technique for the evaluation of cardiac anatomy. To avoid fold-over artifacts, using a sufficiently large field of view in phase-encoding direction is mandatory. The related oversampling affects scanning time and respiratory chest motion artifacts are commonly observed. The excitation of a volume that exclusively includes the heart without its surrounding structures may help to improve scan efficiency and minimize motion artifacts. Therefore, and by building on previously reported inner-volume approach, the combination of a black-blood FSE sequence with a two-dimensionally selective radiofrequency pulse is proposed for selective “local excitation” small-FOV imaging of the heart. This local excitation technique has been developed, implemented, and tested in phantoms and in vivo. With this method, small-FOV imaging of a user-specified region in the human thorax is feasible, scanning becomes more time efficient, motion artifacts can be minimized and additional flexibility in the choice of imaging parameters can be exploited.
2D-selective RF Pulses; Black-Blood; local excitation
Measurement of microvascular perfusion with Intravoxel Incoherent Motion (IVIM) MRI is gaining interest. Yet, the physiological influences on the IVIM perfusion parameters (“pseudo-diffusion” coefficient D*, perfusion fraction f, and flow related parameter fD*) remain insufficiently characterized. In this article, we hypothesize that D* and fD*, which depend on blood speed, should vary during the cardiac cycle. We extended the IVIM model to include time dependence of D* = D*(t), and demonstrate in the healthy human brain that both parameters D* and fD* are significantly larger during systole than diastole, while the diffusion coefficient D and f do not vary significantly. The results non-invasively demonstrate the pulsatility of the brain’s microvasculature.
Outcome in sepsis is mainly defined by the degree of organ failure, for which endothelial dysfunction at the macro- and microvascular level is an important determinant. In this study we evaluated endothelial function in patients with severe sepsis using cellular endothelial markers and in vivo assessment of reactive hyperaemia.
Materials and Methods
Patients with severe sepsis (n = 30) and 15 age- and gender- matched healthy volunteers were included in this study. Using flow cytometry, CD34+/KDR+ endothelial progenitor cells (EPC), CD31+ T-cells, and CD31+/CD42b- endothelial microparticles (EMP) were enumerated. Migratory capacity of cultured circulating angiogenic cells (CAC) was assessed in vitro. Endothelial function was determined using peripheral arterial tonometry at the fingertip.
In patients with severe sepsis, a lower number of EPC, CD31+ T-cells and a decreased migratory capacity of CAC coincided with a blunted reactive hyperaemia response compared to healthy subjects. The number of EMP, on the other hand, did not differ. The presence of organ failure at admission (SOFA score) was inversely related with the number of CD31+ T-cells. Furthermore, the number of EPC at admission was decreased in patients with progressive organ failure within the first week.
In patients with severe sepsis, in vivo measured endothelial dysfunction coincides with lower numbers and reduced function of circulating cells implicated in endothelial repair. Our results suggest that cellular markers of endothelial repair might be valuable in the assessment and evolution of organ dysfunction.
The purpose of this study was to (1) develop a high resolution 3T MRA technique with in-plane resolution approximate to that of MDCT and a voxel size of 0.35 × 0.35 × 1.5 mm3 and to (2) investigate the image quality of this technique in healthy subjects and preliminarily in patients with known coronary artery disease (CAD).
Materials and Methods
A 3T coronary MRA technique optimized for an image acquisition voxel as small as 0.35 × 0.35 × 1.5mm3 (HRC) was implemented and the coronary arteries of twenty two subjects were imaged. These included 11 healthy subjects (average age 28.5 years old, five males) and 11 subjects (average age 52.9 years old, five females) with CAD as identified on multidetector coronary computed tomography (MDCT). Additionally, the 11 healthy subjects were imaged using a method with a more common spatial resolution of 0.7×1×3 mm3 (RRC). Qualitative and quantitative comparisons were made between the two MRA techniques.
Normal vessels and CAD lesions were successfully depicted at 350×350μm2 in-plane resolution with adequate signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR). The CAD findings were consistent among MDCT and HRC. The HRC showed a 47% improvement in sharpness despite a reduction in SNR (reduced by 72%) and CNR (reduced by 86%) compared to the RRC.
This study, as a first step towards substantial improvement in the resolution of coronary MRA, demonstrates the feasibility of obtaining at 3T a spatial resolution that approximates that of MDCT. The acquisition in-plane pixel dimensions are as small as 350μm × 350μm with a 1.5 mm slice thickness. While SNR is lower, the images have improved sharpness resulting in image quality that allowed qualitative identification of disease sites on MRA consistent with MDCT.
Coronary endothelial function (endoFx) is abnormal in patients with established coronary artery disease (CAD) and was recently shown by MRI to relate to the severity of luminal stenosis. Recent advances in MRI now allow the non-invasive assessment of both anatomic and functional (endoFx) changes that previously required invasive studies. We tested the hypothesis that abnormal coronary endoFx is related to measures of early atherosclerosis such as increased coronary wall thickness (CWT).
Methods and Results
Seventeen arteries in fourteen healthy adults and seventeen arteries in fourteen patients with non-obstructive CAD were studied. To measure endoFx, coronary MRI was performed before and during isometric handgrip exercise, an endothelial-dependent stressor and changes in coronary cross-sectional area (CSA) and flow were measured. Black blood imaging was performed to quantify CWT and other indices of arterial remodeling. The mean stress-induced change in CSA was significantly higher in healthy adults (13.5%±12.8%, mean±SD, n=17) than in those with mildly diseased arteries (-2.2±6.8%, p<0.0001, n=17). Mean CWT was lower in healthy subjects (0.9±0.2mm) than in CAD patients (1.4±0.3mm, p<0.0001). In contrast to healthy subjects, stress-induced changes in CSA, a measure of coronary endoFx, correlated inversely with CWT in CAD patients (r= -0.73, p=0.0008).
There is an inverse relationship between coronary endothelial function and local CWT in CAD patients but not in healthy adults. These findings demonstrate that local endothelial-dependent functional changes are related to the extent of early anatomic atherosclerosis in mildly diseased arteries. This combined MRI approach enables the anatomic and functional investigation of early coronary disease.
coronary disease; endothelium; magnetic resonance imaging
Background and Purpose
Time-of-flight (TOF) angiography detects embolic occlusion of arteries in patients with acute ischemic stroke due to the absence of blood flow in the occluded vessel. In contrast, susceptibility weighted imaging (SWI) directly enables intravascular clot visualization due to hypointense susceptibility vessel signs (SVS) in the occluded vessel. The aim of this study was to compare the diagnostic accuracy of both methods to determine vessel occlusion in patients with acute stroke.
94 patients were included who presented with clinical symptoms for acute stroke and displayed a delay on the time-to-peak perfusion map in the territory of the anterior (ACA), middle (M1, M1/M2, M2/M3) or posterior (PCA) cerebral artery. The frequency of SVS on SWI and vessel occlusion or stenosis on TOF-angiography was compared using the McNemar-Test.
87 of 94 patients displayed a clearly definable SVS on SWI. In 72 patients the SVS was associated with occlusion or stenosis on TOF-angiography. Fifteen patients exclusively displayed SVS on SWI (14 M2/M3, 1 M1), whereas no patient revealed exclusively occlusion or stenosis on TOF-angiography. Sensitivity for detection of embolic occlusion within major vessel segments (M1, M1/M2, ACA, and PCA) did not show any significant difference between both techniques (97% for SWI versus 96% for TOF-angiography) while the sensitivity for detection of embolic occlusion within M2/M3 was significantly different (84% for SWI versus 39% for TOF-angiography, p<0.00012).
SWI and TOF-angiography provide similar sensitivity for central thrombi while SWI is superior for the detection of peripheral thrombi in small arterial vessel segments.
As Doppler ultrasound has been proven to be an effective tool to predict and compress the optimal pulsing windows, we evaluated the effective dose and diagnostic accuracy of coronary CT angiography (CTA) incorporating Doppler-guided prospective electrocardiograph (ECG) gating, which presets pulsing windows according to Doppler analysis, in patients with a heart rate >65 bpm.
Materials and Methods
119 patients with a heart rate >65 bpm who were scheduled for invasive coronary angiography were prospectively studied, and patients were randomly divided into traditional prospective (n = 61) and Doppler-guided prospective (n = 58) ECG gating groups. The exposure window of traditional prospective ECG gating was set at 30%–80% of the cardiac cycle. For the Doppler group, the length of diastasis was analyzed by Doppler. For lengths greater than 90 ms, the pulsing window was preset during diastole (during 60%–80%); otherwise, the optimal pulsing intervals were moved from diastole to systole (during 30%–50%).
The mean heart rates of the traditional ECG and the Doppler-guided group during CT scanning were 75.0±7.7 bpm (range, 66–96 bpm) and 76.5±5.4 bpm (range: 66–105 bpm), respectively. The results indicated that whereas the image quality showed no significant difference between the traditional and Doppler groups (P = 0.42), the radiation dose of the Doppler group was significantly lower than that of the traditional group (5.2±3.4mSv vs. 9.3±4.5mSv, P<0.001). The sensitivities of CTA applying traditional and Doppler-guided prospective ECG gating to diagnose stenosis on a segment level were 95.5% and 94.3%, respectively; specificities 98.0% and 97.1%, respectively; positive predictive values 90.7% and 88.2%, respectively; negative predictive values 99.0% and 98.7%, respectively. There was no statistical difference in concordance between the traditional and Doppler groups (P = 0.22).
Doppler-guided prospective ECG gating represents an improved method in patients with a high heart rate to reduce effective radiation doses, while maintaining high diagnostic accuracy.
Our objective is to test the hypothesis that coronary endothelial function (CorEndoFx) does not change with repeated isometric handgrip (IHG) stress in CAD patients or healthy subjects.
Coronary responses to endothelial-dependent stressors are important measures of vascular risk that can change in response to environmental stimuli or pharmacologic interventions. The evaluation of the effect of an acute intervention on endothelial response is only valid if the measurement does not change significantly in the short term under normal conditions. Using 3.0 Tesla (T) MRI, we non-invasively compared two coronary artery endothelial function measurements separated by a ten minute interval in healthy subjects and patients with coronary artery disease (CAD).
Twenty healthy adult subjects and 12 CAD patients were studied on a commercial 3.0 T whole-body MR imaging system. Coronary cross-sectional area (CSA), peak diastolic coronary flow velocity (PDFV) and blood-flow were quantified before and during continuous IHG stress, an endothelial-dependent stressor. The IHG exercise with imaging was repeated after a 10 minute recovery period.
In healthy adults, coronary artery CSA changes and blood-flow increases did not differ between the first and second stresses (mean % change ±SEM, first vs. second stress CSA: 14.8%±3.3% vs. 17.8%±3.6%, p = 0.24; PDFV: 27.5%±4.9% vs. 24.2%±4.5%, p = 0.54; blood-flow: 44.3%±8.3 vs. 44.8%±8.1, p = 0.84). The coronary vasoreactive responses in the CAD patients also did not differ between the first and second stresses (mean % change ±SEM, first stress vs. second stress: CSA: −6.4%±2.0% vs. −5.0%±2.4%, p = 0.22; PDFV: −4.0%±4.6% vs. −4.2%±5.3%, p = 0.83; blood-flow: −9.7%±5.1% vs. −8.7%±6.3%, p = 0.38).
MRI measures of CorEndoFx are unchanged during repeated isometric handgrip exercise tests in CAD patients and healthy adults. These findings demonstrate the repeatability of noninvasive 3T MRI assessment of CorEndoFx and support its use in future studies designed to determine the effects of acute interventions on coronary vasoreactivity.
Animal studies suggest that renal tissue hypoxia plays an important role in the development of renal damage in hypertension and renal diseases, yet human data were scarce due to the lack of noninvasive methods. Over the last decade, blood oxygenation level-dependent magnetic resonance imaging (BOLD-MRI), detecting deoxyhemoglobin in hypoxic renal tissue, has become a powerful tool to assess kidney oxygenation noninvasively in humans. This paper provides an overview of BOLD-MRI studies performed in patients suffering from essential hypertension or chronic kidney disease (CKD). In line with animal studies, acute changes in cortical and medullary oxygenation have been observed after the administration of medication (furosemide, blockers of the renin-angiotensin system) or alterations in sodium intake in these patient groups, underlining the important role of renal sodium handling in kidney oxygenation. In contrast, no BOLD-MRI studies have convincingly demonstrated that renal oxygenation is chronically reduced in essential hypertension or in CKD or chronically altered after long-term medication intake. More studies are required to clarify this discrepancy and to further unravel the role of renal oxygenation in the development and progression of essential hypertension and CKD in humans.
Takayasu arteritis (TA) is a rare form of chronic inflammatory granulomatous arteritis of the aorta and its major branches. Late gadolinium enhancement (LGE) with magnetic resonance imaging (MRI) has demonstrated its value for the detection of vessel wall alterations in TA. The aim of this study was to assess LGE of the coronary artery wall in patients with TA compared to patients with stable CAD.
We enrolled 9 patients (8 female, average age 46±13 years) with proven TA. In the CAD group 9 patients participated (8 male, average age 65±10 years). Studies were performed on a commercial 3T whole-body MR imaging system (Achieva; Philips, Best, The Netherlands) using a 3D inversion prepared navigator gated spoiled gradient-echo sequence, which was repeated 34–45 minutes after low-dose gadolinium administration.
No coronary vessel wall enhancement was observed prior to contrast in either group. Post contrast, coronary LGE on IR scans was detected in 28 of 50 segments (56%) seen on T2-Prep scans in TA and in 25 of 57 segments (44%) in CAD patients. LGE quantitative assessment of coronary artery vessel wall CNR post contrast revealed no significant differences between the two groups (CNR in TA: 6.0±2.4 and 7.3±2.5 in CAD; p = 0.474).
Our findings suggest that LGE of the coronary artery wall seems to be common in patients with TA and similarly pronounced as in CAD patients. The observed coronary LGE seems to be rather unspecific, and differentiation between coronary vessel wall fibrosis and inflammation still remains unclear.
Four different techniques for 3T whole-heart coronary MRA using free-breathing 3D segmented parallel imaging and adiabatic T2-Prep were assessed. Coronary MRA at 3T is improved by shortening the acquisition window more than employing the highest spatial resolution. Double oblique whole-heart acquisitions result in better overall image quality and allow for better delineation of the LAD. It is possible to attain shorter acquisition windows and a smaller voxel size at 3T than previously reported at 1.5T.
Magnetic resonance angiography (MRA) provides a noninvasive means to detect the presence, location and severity of atherosclerosis throughout the vascular system. In such studies, and especially those in the coronary arteries, the vessel luminal area is typically measured at multiple cross-sectional locations along the course of the artery. The advent of fast volumetric imaging techniques covering proximal to mid segments of coronary arteries necessitates automatic analysis tools requiring minimal manual interactions to robustly measure cross-sectional area along the three-dimensional track of the arteries in under-sampled and non-isotropic datasets. In this work, we present a modular approach based on level set methods to track the vessel centerline, segment the vessel boundaries, and measure transversal area using two user-selected endpoints in each coronary of interest. Arterial area and vessel length are measured using our method and compared to the standard Soap-Bubble reformatting and analysis tool in in-vivo non-contrast enhanced coronary MRA images.
3D Centerline Tracking; 3D Segmentation; Level Set Methods; Non-contrast enhanced Magnetic Resonance Angiography; Coronary Arteries
Coronary vessel distensibility is reduced with atherosclerosis and normal aging but direct measurements have historically required invasive measurements at cardiac catheterization. Therefore, we sought to assess coronary artery distensibility non-invasively with 3.0T coronary magnetic resonance imaging (MRI) and to test the hypothesis that this non-invasive technique can detect differences in coronary distensibility between healthy and coronary artery disease (CAD) subjects. Thirty-eight healthy, adult subjects (23 men, mean age 31±10 years) and 21 patients with CAD defined on X-ray angiography (11 men, mean age 57±6 years) were studied on a commercial whole-body MR imaging system (Achieva 3.0 T; Philips, Best, The Netherlands). In each subject, the proximal segment of a coronary artery was imaged for cross-sectional area measurements using cine spiral MRI. Distensibility (mmHg−1*103) was determined as: (end-systolic lumen area–end-diastolic lumen area) / (pulse pressure multiplied by the end-diastolic lumen area). Pulse pressure was calculated as the difference between the systolic and diastolic brachial blood pressures. Thirty-four healthy subjects and nineteen patients had adequate image quality for coronary area measurements. Coronary artery distensibility was significantly higher in healthy subjects, than in the CAD patients (mean ± 1 SD: 2.4 ± 1.7 mmHg−1*103 vs. 1.1 ± 1.1 mmHg−1*103 respectively, p=0.007); (median: 2.2 vs. 0.9 mmHg−1*103). In a subgroup of 10 CAD patients we found a significant correlation between coronary artery distensibility measurements assessed with MRI and X-ray coronary angiography (R=0.65; p=0.003). In a group of 10 healthy subjects repeated distensibility measurements demonstrated a significant correlation (R=0.80; p=0.006). In conclusion, 3.0T MRI, a reproducible non-invasive means to assess human coronary artery vessel wall distensibility, is able to detect significant differences in distensibility between healthy subjects and CAD patients.
coronary artery distensibility; non-invasive; cardiac magnetic resonance; 3.0 Tesla
To implement and characterize a fluorine-19 (19F) magnetic resonance imaging (MRI) technique and to test the hypothesis that the 19F 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 T1 and T2 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 1H and 19F 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 19F and 1H images, which was followed by vessel tracking to determine the vessel conspicuity for both modalities.
In vitro, the detection limit was ∼400 µM, while the 19F T1 and T2 were 1350±40 and 25±2 ms. The 19F MR angiograms selectively visualized the vasculature (and the liver parenchyma over time) while precisely coregistering with the 1H images. Due to the lower SNR of 19F compared to 1H (17±8 vs. 83±49, p<0.001), the 19F CNR was also lower at 15±8 vs. 52±35 (p<0.001). Vessel tracking demonstrated a significantly higher vessel sharpness in the 19F images (66±11 vs. 56±12, p = 0.002).
19F magnetic resonance angiography of intravenously administered perfluorocarbon emulsions is feasible for a selective and exclusive visualization of the vasculature in vivo.
To develop and evaluate a practical method for the quantification of signal-to-noise ratio (SNR) on coronary magnetic resonance angiograms (MRA) acquired with parallel imaging.
Materials and Methods
To quantify the spatially varying noise due to parallel imaging reconstruction, a new method has been implemented incorporating image data acquisition followed by a fast noise scan during which radiofrequency pulses, cardiac triggering and navigator gating are disabled. The performance of this method was evaluated in a phantom study where SNR measurements were compared to those of a reference standard (multiple repetitions). Subsequently, SNR of myocardium and posterior skeletal muscle was determined on in vivo human coronary MRA.
In a phantom, the SNR measured using the proposed method deviated less than 10.1% from the reference method for small geometry factors (<=2). In-vivo, the noise scan for a 10 minutes coronary MRA acquisition was acquired in 30s. Higher signal and lower SNR, due to spatially varying noise, were found in myocardium compared to posterior skeletal muscle.
SNR quantification based on a fast noise scan is a validated and easy-to-use method when applied to 3D coronary MRA obtained with parallel imaging as long as the geometry factor remains low.
SNR measurement; parallel imaging; coronary MRA; phased array coils; image noise
Cell therapy has the potential to treat or cure a wide variety of diseases. Non-invasive cell tracking techniques are, however, necessary to translate this approach to the clinical setting. This protocol details methods to create microcapsules that are visible by X-ray, ultrasound (US ) or magnetic resonance (MR) for the encapsulation and immunoisolation of cellular therapeutics. Three steps are generally used to encapsulate cellular therapeutics in an alginate matrix: (i) droplets of cell-containing liquid alginate are extruded, using an electrostatic generator, through a needle tip into a solution containing a dissolved divalent cation salt to form a solid gel; (ii) the resulting gelled spheres are coated with polycations as a cross-linker; and (iii) these complexes are then incubated in a second solution of alginate to form a semipermeable membrane composed of an inner and an outer layer of alginate. The microcapsules can be rendered visible during the first step by adding contrast agents to the primary alginate layer. Such contrast agents include superparamagnetic iron oxide for detection by 1H MR imaging (MRI); the radiopaque agents barium or bismuth sulfate for detection by X-ray modalities; or perfluorocarbon emulsions for multimodal detection by 19F MRI, X-ray and US imaging. The entire synthesis can be completed within 2 h.