Abdominal fat radiodensity, quantity and cardiometabolic risk: The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND AND AIMS: Fat radiodensity, as measured by fat attenuation on computed tomography (CT), has emerged as a potential biomarker of "fat quality." We sought to characterize the relationship between fat radiodensity and quantity in subcutaneous, visceral, and intermuscular fat depots, and its role in inflammation, insulin resistance, and metabolic syndrome (MetS). METHODS AND RESULTS: We studied 1511 individuals from the Multi-Ethnic Study of Atherosclerosis who underwent CT for measurement of regional fat distribution and radiodensity, along with biomarker assessments and adjudication of incident metabolic syndrome (MetS). Linear, logistic and Cox regression analyses were used to measure association between fat radiodensity and (1) fat quantity, (2) biomarkers of cardiometabolic dysfunction, and (3) both prevalent and incident MetS. In each fat depot, radiodensity was strongly and inversely associated with quantity (e.g., visceral fat radiodensity vs. quantity: ρ = -0.82, P < 0.01). After adjustment for age, sex and race, lower visceral fat radiodensity was associated with greater C-reactive protein, leptin and insulin, but lower adiponectin (P < 0.01 for all). After full adjustment for cardiovascular disease risk factors, visceral (but not subcutaneous or intermuscular) fat radiodensity was associated with prevalent MetS (OR = 0.96, 95% CI = 0.93-0.99, P = 0.01). Moreover, lower visceral fat radiodensity was associated with incident MetS after the same adjustment (HR = 0.95, 95% CI 0.93-0.98, P < 0.01). However, this association became non-significant after further adjustment for visceral fat quantity. CONCLUSION: Fat radiodensity is strongly correlated with fat quantity and relevant inflammatory biomarkers. Fat radiodensity (especially for visceral fat) may be a complementary, easily assessed marker of cardiometabolic risk.

Diet and adipose tissue distributions: The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND AND AIMS: Dietary quality affects cardiometabolic risk, yet its pathways of influence on regional adipose tissue depots involved in metabolic and diabetes risk are not well established. We aimed to investigate the relationship between dietary quality and regional adiposity. METHODS AND RESULTS: We investigated 5079 individuals in the Multi-Ethnic Study of Atherosclerosis (MESA) who had food-frequency questionnaires and measurement of pericardial fat and hepatic attenuation at the baseline study visit in MESA, as well as a subgroup with imaging for visceral and subcutaneous fat (N = 1390). A dietary quality score (DietQuality) was constructed to include established food group constituents of a Mediterranean-type diet. Linear models estimated associations of dietary score as well as its constituents with regional adiposity. Baseline mean age was 61 (± 10) years, and approximately half of the participants (47%) were male. Those with a higher DietQuality score were generally older, female, with a lower body mass index, C-reactive protein, and markers of insulin resistance. After adjustment, a higher DietQuality score was associated with lower visceral fat (lowest vs. highest dietary score quartile: 523.6 vs. 460.5 cm(2)/m; P < 0.01 for trend), pericardial fat (47.5 vs. 41.3 cm(3)/m; P < 0.01 for trend), lesser hepatic steatosis (by hepatic attenuation; 58.6 vs. 60.7 Hounsfield units; P < 0.01 for trend), but not subcutaneous fat (P = 0.39). Greater fruits, vegetables, whole grains, seeds/nuts and yogurt intake were associated with decreased adiposity, while red/processed meats were associated with greater regional adiposity. CONCLUSION: A higher quality diet pattern is associated with less regional adiposity, suggesting a potential mechanism of beneficial dietary effects on diabetes, metabolic, and cardiovascular risk.

Visceral adiposity and left ventricular remodeling: The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND AND AIMS: Visceral fat (VF) is a source of pro-inflammatory adipokines implicated in cardiac remodeling. We sought to determine the impact of visceral fat and subcutaneous fat (SQ) depots on left ventricular (LV) structure, function, and geometry in the Multi-Ethnic Study of Atherosclerosis (MESA). METHODS AND RESULTS: We performed a post-hoc analysis on 1151 participants from MESA with cardiac magnetic resonance quantification of LV mass and LV mass-to-volume ratio (LVMV, an index of concentricity) and computed tomographic-derived SQ and VF area. Multivariable regression models to estimate association between height-indexed SQ and VF area (per cm(2)/m) with height-indexed LV mass (per height(2.7)) and LVMV were constructed, adjusted for clinical, biochemical, and demographic covariates. We found that both VF and SQ area were associated with height-indexed LV mass (ρ = 0.36 and 0.12, P < 0.0001, respectively), while only VF area was associated with LVMV (ρ = 0.28, P < 0.0001). Individuals with above-median VF had lower LV ejection fraction, greater indexed LV volumes and mass, and higher LVMV (all P < 0.001). In multivariable models adjusted for weight, VF (but not SQ) area was associated with LV concentricity and LV mass index, across both sexes. CONCLUSION: Visceral adiposity is independently associated with LV concentricity, a precursor to heart failure. Further study into the role of VF in LV remodeling as a potential therapeutic target is warranted.

[Cardiovascular magnetic resonance imaging in childhood - clinical indications and case studies]. / Kardiovaskuläre Magnetresonanztomografie im Kindesalter - klinische Indikationen und Beispiele.

In today's clinical practice cardiovascular magnetic resonance (CMR) imaging is increasingly used for assessment of congenital and acquired heart disease in children. CMR complements echocardiography and provides a noninvasive alternative to diagnostic cardiac catheterization. In contrast to echocardiography, CMR is not limited by acoustic windows, and unlike cardiac catheterization, CMR lacks ionizing radiation. Contiguous three and four dimensional data sets allow to display cardiac and thoracic vessel anatomy in any desired imaging plane. These characteristics provide unique images for the complete depiction of the pathological anatomy in particular in congenital heart disease. Furthermore CMR is also used for assessment of cardiac function, blood-flow measurements, tissue characterization, and, more recently, for evaluation of myocardial perfusion and viability. The following article reviews CMR indications in pediatric cardiology by means of clinical examples.

[3 tesla magnetic resonance imaging in children and adults with congenital heart disease]. / 3-Tesla-Magnetresonanztomographie zur Untersuchung von Kindern und Erwachsenen mit angeborenen Herzfehlern.

Cardiovascular magnetic resonance imaging (CMR) has become a routinely used imaging modality for congenital heart disease. A CMR examination allows the assessment of thoracic anatomy, global and regional cardiac function, blood flow in the great vessels and myocardial viability and perfusion. In the clinical routine cardiovascular MRI is mostly performed at field strengths of 1.5 Tesla (T). Recently, magnetic resonance systems operating at a field strengths of 3 T became clinically available and can also be used for cardiovascular MRI. The main advantage of CMR at 3 T is the gain in the signal-to-noise ratio resulting in improved image quality and/or allowing higher acquisition speed. Several further differences compared to MRI systems with lower field strengths have to be considered for practical applications. This article describes the impact of CMR at 3 T in patients with congenital heart disease by meanings of methodical considerations and case studies.

Magnetic resonance quantification of the myocardial perfusion reserve with a Fermi function model for constrained deconvolution.

The myocardial perfusion reserve, defined as the ratio of hyperemic and basal myocardial blood flow, is a useful indicator of the functional significance of a coronary artery lesion. Rapid magnetic resonance (MR) imaging for the noninvasive detection of a bolus-injected contrast agent as a MR tracer is applied to the measurement of regional tissue perfusion during rest and hyperemia, in patients with microvascular dysfunction. A Fermi function model for the distribution of tracer residence times in the myocardium is used to fit the MR signal curves. The myocardial perfusion reserve is calculated from the impulse response amplitudes for rest and hyperemia. The assumptions of the model are tested with Monte Carlo simulations, using a multiple path, axially distributed mathematical model of blood tissue exchange, which allows for systematic variation of blood flow, vascular volume, and capillary permeability. For a contrast-to-noise ratio of 6:1, and over a range of flows from 0.5 to 4.0 ml/min per g of tissue, the ratio of the impulse response amplitudes for hyperemic and basal flows is linearly proportional to the ratio of model blood flows, if the mean transit time of the input function is shorter than approximately 9 s. The uncertainty in the blood flow reserve estimates grows both at low (< 1.0 ml/min/g) and high (> 3-4 ml/min/g) flows. The predictions of the Monte Carlo simulations agree with the results of MR first pass studies in patients without significant coronary artery lesions and microvascular dysfunction, where the perfusion reserve in the territory of the left anterior descending coronary artery (LAD) correlates linearly with the intracoronary Doppler ultrasound flow reserve in the LAD (r = 0.84), in agreement with previous PET studies.

Myocardial viability.

This article reviews various means to assess myocardial viability by imaging, and provides recommendations for current clinical practice. This article also discusses future directions in assessing myocardial viability.

Assessing myocardial perfusion in coronary artery disease with magnetic resonance first-pass imaging.

MRFP perfusion imaging can now be used clinically on most MR scanner systems (1.0 to 1.5 T). The current experimental data demonstrate that MRFP imaging allows the quantitative assessment of myocardial blood flow changes and accurate measurements of collateral flow, including changes in the collateral dependent zones. Certain protocols, however, as outlined here have to be followed to obtain all the possible diagnostic information. Based on the current data on MRFP imaging, it is realistic to anticipate that MRFP imaging in combination with cine or tagging MR imaging will provide clinicians with better methods to distinguish stunned and hibernating, from nonviable myocardium and obtain better outcome data. Dedicated MR scanners are now being designed to meet the needs for MR imaging of patients with coronary artery disease. These scanners, small in size and with better patient access, make placement near the coronary care unit or catheterization laboratory feasible. This is a major step toward enhancing the utility of this new technique by providing the necessary infrastructure for scanning large numbers of patients. The main obstacle to wider use of these new diagnostic tools to assess perfusion is the lack of a large clinical database because there have not yet been major multicenter trials. With the development of novel intravascular contrast agents, however, larger trials are planned that should provide the clinical data mandatory for full integration of MRFP imaging into clinical practice. In particular, the development of dedicated and user-friendly perfusion analysis software will create the means to evaluate MR perfusion data accurately in large patient populations. These studies need to be conducted in a collaborative fashion by cardiologists, heart surgeons, and radiologists to be fully accepted by health care providers in an increasingly cost-averse and competitive health care environment.

Combined proton T1N and CPMG T2N studies of water saturated sandstone core plugs.

Diffusion dynamics for water in a series of sandstone core plugs with a broad range of permeabilities was studied using both the Carr-Purcell-Meiboom-Gill (CPMG) and inversion recovery experiments. Both the transverse and longitudinal magnetization curves were found to fit well to stretched exponential relaxation kinetics. At short times, the transverse magnetization is well described by an expression for free diffusion averaged over a distribution of pore sizes. The stretch exponents for the transverse and longitudinal magnetization are shown to be simply related to the width of the pore size distribution. A cross over from free to restricted diffusion is evident in the dependence of T2 with increasing diffusion time set by the interpulse spacing tau in the CPMG experiment. The T2(tau) data is fit to a model which interpolates between the limits of free and restricted diffusion. A length derived from this model is shown to provide a simple estimate of the absolute fluid flow permeability.

Functional MRI of brain during breath holding at 4 T.

Both theoretical considerations and animal experiments predict increased signal intensity in brain cortex on T2*-weighted images that develops over a breath hold period. This has not been observed in recent human studies performed at 1.0 and 1.5 T. To clarify this inconsistency, we undertook a study in normal volunteers at 4.0 T. Unlike the earlier studies, we observed a 3-10% signal intensity increase in the gray matter. Possible reasons for the discrepant results are discussed. We conclude that regional cerebral hemodynamics are observable by fMRI in man and this may have clinical applications.

Variability in the cardiac EIT image as a function of electrode position, lung volume and body position.

A study was conducted using the Sheffield electrical impedance tomography (EIT) portable system DAS-01 P to determine the change in the cardiac image with electrode position, lung volume and body position. Sixteen electrodes were positioned in three transverse planes around the thorax at the level of the second intercostal space, at the level of the xiphisternal joint, and midway between upper and lower locations. Data were collected at each electrode level with the breath held at end expiration and after inspiring 0.5, 1 and 1.5 l of air with the subject in both the supine and sitting position. These data were analysed using a Matlab developed program that calculates the average resistivity change in the cardiac region from automatically determined borders. Results show significant individual variability with electrode position and air volume. The middle electrode most consistently shows an increase in impedance in the region of the heart during systole. In some subjects the change in the ventricular-volume-like curve showed a greater than 50% change as a function of lung volume. The pattern of variability with electrode position was not consistent among subjects. In one subject MRI images were obtained to compare actual structures with those seen in the EIT image. The results suggest that using these electrode locations reliable and consistent data, which could be used in clinical applications, cannot be obtained.

Magnetic resonance first-pass perfusion imaging: overview and perspectives.

The data from clinical studies with quantitative MR first-pass perfusion imaging suggests that this technique outperforms SPECT--widely available clinical imaging tool--in sensitivity and specificity. Moreover, MRFP imaging may be combined with the assessment of global and segmental function of the heart and regional wall thickening, and in addition, performed with pharmacological stress agents. The inter- and intra-observer reproducibility of quantitative MRFP is comparable with clinically used nuclear medicine techniques. MRFP measurements can discern collateral myocardium and are able to identify small changes in myocardial blood flow and myocardial perfusion reserve (the ratio of stress blood flow over resting). MRFP imaging has been mainly used in context of coronary artery disease but many other exciting areas in clinical cardiology are awaiting of new insights that can be accomplished with this technique. Trials are needed to obtain the approval of the contrast agent (Gd-DTPA) and perfusion sequences by the Food and Drug Administration and to establish reimbursement procedures with the third-party insurance companies and health maintenance organizations.

Fully automated registration of first-pass myocardial perfusion MRI using independent component analysis.

This paper presents a novel method for registration of cardiac perfusion MRI. The presented method successfully corrects for breathing motion without any manual interaction using Independent Component Analysis to extract physiologically relevant features together with their time-intensity behavior. A time-varying reference image mimicking intensity changes in the data of interest is computed based on the results of ICA, and used to compute the displacement caused by breathing for each frame. Qualitative and quantitative validation of the method is carried out using 46 clinical quality, short-axis, perfusion MR datasets comprising 100 images each. Validation experiments showed a reduction of the average LV motion from 1.26+/-0.87 to 0.64+/-0.46 pixels. Time-intensity curves are also improved after registration with an average error reduced from 2.65+/-7.89% to 0.87+/-3.88% between registered data and manual gold standard. We conclude that this fully automatic ICA-based method shows an excellent accuracy, robustness and computation speed, adequate for use in a clinical environment.

The delay of contrast arrival in magnetic resonance first-pass perfusion imaging: a novel non-invasive parameter detecting collateral-dependent myocardium.

AIM: To establish the regional delay of contrast arrival in magnetic resonance perfusion imaging (MRPI) for the detection of collateral-dependent myocardium in patients with coronary artery disease. DESIGN AND SETTING: Observational study, case series; single centre, university hospital. PATIENTS: 30 patients with coronary artery disease and collateral-dependent myocardium and 17 healthy volunteers. METHODS: Resting and hyperaemic (adenosine) MRPI was used to determine the delay time (Deltat(d)) of contrast arrival between the left ventricle and collateral-dependent or antegradely perfused myocardium, and myocardial perfusion (MP, ml/min/g). RESULTS: In healthy volunteers, mean (SD) Deltat(d) at rest and during hyperaemia were 0.8 (0.4) and 0.3 (0.3) s, and MP was 1.14 (0.21) and 4.23 (1.12) ml/min/g. In patients Deltat(d) in antegradely perfused vs collateral-dependent myocardium was 0.9 (0.7) vs 1.7 (1.0) s at rest (p<0.001), and 0.4 (0.3) vs 1.1 (0.6) s (p<0.001) during hyperaemia. MP was 1.12 (0.11) and 0.98 (0.28) ml/min/g (p = NS) at rest and 2.46 (0.85) vs 1.86 (0.91) ml/min/g (p<0.01) during hyperaemia. Receiver operating characteristics analysis showed the best sensitivity and specificity of 90% and 83% for hyperaemic Deltat(d) of >0.6 s (area under the curve (AUC) = 0.89) to detect collateral-dependent myocardium, while resting Deltat(d) (AUC = 0.77) and perfusion (AUC = 0.69 at rest or 0.70 during hyperaemia) were less accurate. CONCLUSIONS: MRPI-derived hyperaemic delay of contrast arrival detects collateral-dependent myocardium with high sensitivity and specificity. Perfusion was less sensitive, emphasising the clinical role of Deltat(d) in non-invasive detection of collateral-dependent myocardium.

MR first pass imaging: quantitative assessment of transmural perfusion and collateral flow.

Recent advances with fast switching gradient coils, and the optimization of magnetic resonance techniques for multislice imaging have made it possible to apply models of contrast agent transit for the quantification of myocardial perfusion, and determination of the transmural distribution of blood flow. This article summarizes some of these recent developments and presents examples of quantitative, multi-slice myocardial perfusion imaging studies in patients and animal models. Multi-slice, true first pass imaging, with high temporal resolution, and T1-weighted, arrhythmia insensitive contrast enhancement is used for the quantification of perfusion changes accompanying mild to severe ischemia. The first pass imaging technique and the modeling approach are sufficiently robust for fitting of tissue residue curves corresponding to a wide, physiologically realistic range of myocardial blood flows. In animals this was validated by comparison to blood flow measurements with radiolabeled microspheres as gold standard. It is demonstrated that with the proposed modeling approach one can determine the myocardial perfusion reserve from two consecutive MR first pass measurements under resting and hyperemic conditions. In patients with microvascular dysfunction the MR studies show for the first time that the myocardial perfusion reserve correlates with Doppler flow measurements (linear regression with slope of 1.02 +/- 0.09; r = 0.80). Since perfusion limitations usually begin in the subendocardium as coronary flow is gradually reduced, first pass imaging with the prerequisitie spatial and temporal resolution allows early detection of a mild coronary stenosis.

Use of an intravascular T1 contrast agent to improve MR cine myocardial-blood pool definition in man.

The feasibility of improving myocardial/blood pool contrast in MR cine images through use of an intravascular contrast agent (Ferumoxtran, Advanced Magnetics, Inc., Cambridge, MA) was tested in four subjects. The contrast-to-noise ratio (CNR) demonstrated a trend toward improvement in the short axis and improved significantly in the long axis cine by an average of 128% (P < .05). Image intensity gradients at the myocardial/blood pool interface increased significantly in both the short and long axis (P < .01). It is expected that larger image intensity gradients at the endocardial border should improve the capabilities of automated segmentation algorithms, reducing the uncertainty and need for manual editing.

Motional phase artifacts in Fourier transform MRI.

Most magnetic resonance imaging (MRI) techniques are subject to a "motional blurring" arising from the acquisition of data in the presence of a frequency-encoding gradient. The Fourier transform of the signal from a spin moving along a magnetic field gradient obeys an equation analogous to the free space Schrödinger equation. Computer simulations of the Bloch equations illustrate the implications of this motional blurring in MRI.