Role of T1 mapping as a complementary tool to T2* for non-invasive cardiac iron overload assessment.

BACKGROUND: Iron overload-related heart failure is the principal cause of death in transfusion dependent patients, including those with Thalassemia Major. Linking cardiac siderosis measured by T2* to therapy improves outcomes. T1 mapping can also measure iron; preliminary data suggests it may have higher sensitivity for iron, particularly for early overload (the conventional cut-point for no iron by T2* is 20ms, but this is believed insensitive). We compared T1 mapping to T2* in cardiac iron overload. METHODS: In a prospectively large single centre study of 138 Thalassemia Major patients and 32 healthy controls, we compared T1 mapping to dark blood and bright blood T2* acquired at 1.5T. Linear regression analysis was used to assess the association of T2* and T1. A "moving window" approach was taken to understand the strength of the association at different levels of iron overload. RESULTS: The relationship between T2* (here dark blood) and T1 is described by a log-log linear regression, which can be split in three different slopes: 1) T2* low, <20ms, r2 = 0.92; 2) T2* = 20-30ms, r2 = 0.48; 3) T2*>30ms, weak relationship. All subjects with T2*<20ms had low T1; among those with T2*>20ms, 38% had low T1 with most of the subjects in the T2* range 20-30ms having a low T1. CONCLUSIONS: In established cardiac iron overload, T1 and T2* are concordant. However, in the 20-30ms T2* range, T1 mapping appears to detect iron. These data support previous suggestions that T1 detects missed iron in 1 out of 3 subjects with normal T2*, and that T1 mapping is complementary to T2*. The clinical significance of a low T1 with normal T2* should be further investigated.

Effect of red cell clustering and anisotropy on ultrasound blood backscatter: a Monte Carlo study.

When flowing at a low shear rate, blood appears hyperechogenic on ultrasound B-scans. The formation of red blood cell (RBC) aggregates that also alters blood viscosity is the microscopic mechanism explaining this acoustical phenomenon. In this study, Monte Carlo simulations were performed to predict how RBC clustering increases ultrasound scattering by blood. A bidimensional Gibbs-Markov random point process parameterized by the adhesion energy epsilon and an anisotropy index nu was used to describe RBC positions for a hematocrit H = 40%. The frequency dependence of the backscattering coefficient chi(f) was computed using Born approximation. The backscattering coefficient chi0 at 5 MHz and the spectral slopes n(x) and n(y) (chi alpha f(nx) or f(ny)) measured, respectively, when the insonification is parallel and perpendicular with the RBC cluster axis were then extracted. Under isotropic conditions, chi0 increased up to 7 dB with epsilon and n(x) = n(y) decreased from 4.2 to 3.4. Under anisotropic conditions, the backscattering was stronger perpendicularly to aggregate axis, resulting in n(x) < n(y). The anisotropy in scattering appeared more pronounced when epsilon or nu increased. These two dimensional results generally predict that low-frequency blood backscatter is related to cluster dimension, and higher-frequency properties are affected by finer morphological features as anisotropy. This numerically establishes that ultrasound backscatter spectroscopy on a large frequency range is pertinent to characterize in situ hemorheology.

Sonorheometry: a noncontact method for the dynamic assessment of thrombosis.

Inappropriate blood coagulation plays a central role in the onset of myocardial infarction, stroke, pulmonary embolism, and other thrombotic disorders. The ability to screen for an increased propensity to clot could prevent the onset of such events by appropriately identifying those at risk and enabling prophylactic treatment. Similarly, the ability to characterize the mechanical properties of clots in vivo might improve patient outcomes by better informing treatment strategies. We have developed a technique called sonorheometry. Unlike existing methods, sonorheometry is able to assess mechanical properties of coagulation with minimal disturbance to the delicate structure of a forming thrombus. Sonorheometry uses acoustic radiation force to produce small, localized displacements within the sample. Time delay estimation is performed on returned ultrasound echoes to determine sample deformation. Mechanical modeling and parametric fitting to experimental data yield maps of mechanical properties. Sonorheometry is well suited to both in vitro and in vivo applications. A control experiment was performed to verify that sonorheometry provides mechanical characterization in agreement with that from a conventional rheometer. We also examined thrombosis in blood samples taken from four subjects. This data suggests that sonorheometry may offer a novel and valuable method for assessing the thrombogenicity of blood samples.

Whole body [O-15]water pharmacokinetics measured in blood.

A simple pharmacokinetic model to explain the time course of [O-15] water in human whole blood after bolus injection is described. The model has been derived from measurements in twelve healthy volunteers who were measured repeatedly, resulting in 67 datasets, made in the context of PET blood flow studies. In contrast to traditional volume of distribution estimates of total body water (TBW) which rely on measurements after many hours, the model and data provide insights into the fast uptake components in the distribution of water in the body. Data fitting shows that the volume of distribution of fast exchanging tissues is 21 l. TBW was calculated to be 37 l. Monte Carlo simulation showed that the expected inaccuracy of determination of parameters due to unsystematic sources in the measurement data was around 5% for most parameters. Our data show that water extraction to tissue is somewhat higher than would be predicted from the tabulated values, probably because skeletal blood flow is sensitive to physiological status and environmental conditions. The study provides valuable reference data on the distribution and kinetics of water in man. Using the parameters and model from this study, reference input time-activity curves can be calculated, e.g. for the Monte Carlo study of error propagation in PET studies.

Towards a quantitative in vivo evaluation of venous blood echogenicity: image processing versus subjective assessment.

PURPOSE: Spontaneous blood echogenicity in vein ultrasound images may be a marker for an increased erythrocyte aggregability, but a reliable quantitative evaluation method is a prerequisite for its use in clinical studies. We compared a simple scoring system of blood echogenicity intensity and pattern, with automatic image analysis. MATERIAL AND METHODS: 157 femoral and popliteal vein digitized ultrasound sequences were reviewed by two independent observers who chose an image, delimited an area of interest (ROI), and graded blood echogenicity intensity and pattern, using a four class score. Each observer reviewed the images selected by the other, without and with ROI. The computer calculated first and second order parameters describing echo intensity and spatial organization. RESULTS: Inter-observer reproducibility of subjective assessment was poor (Kappa<0.5), whereas the automatically calculated ROI average gray level intensity relatively to the whole image (tau(1)) effectively separated all grades of intensity. No parameter effectively separated patterns. CONCLUSION: Tau(1) is a simple parameter for the in vivo evaluation of blood echogenicity intensity. It should be evaluated in standardized conditions for clinical hemorheology studies in correlation with in vitro erythrocyte aggregation measurements.

Assessment of arterial stenosis in a flow model with power Doppler angiography: accuracy and observations on blood echogenicity.

The objective of the project was to study the influence of various hemodynamic and rheologic factors on the accuracy of 3-D power Doppler angiography (PDA) for quantifying the percentage of area reduction of a stenotic artery along its longitudinal axis. The study was performed with a 3-D power Doppler ultrasound (US) imaging system and an in vitro mock flow model containing a simulated artery with a stenosis of 80% area reduction. Measurements were performed under steady and pulsatile flow conditions by circulating, at different flow rates, four types of fluid (porcine whole blood, porcine whole blood with a US contrast agent, porcine blood cell suspension and porcine blood cell suspension with a US contrast agent). A total of 120 measurements were performed. Computational simulations of the fluid dynamics in the vicinity of the axisymmetrical stenosis were performed with finite-element modeling (FEM) to locate and identify the PDA signal loss due to the wall filter of the US instrument. The performance of three segmentation algorithms used to delineate the vessel lumen on the PDA images was assessed and compared. It is shown that the type of fluid flowing in the phantom affects the echoicity of PDA images and the accuracy of the segmentation algorithms. The type of flow (steady or pulsatile) and the flow rate can also influence the PDA image accuracy, whereas the use of US contrast agent has no significant effect. For the conditions that would correspond to a US scan of a common femoral artery (whole blood flowing at a mean pulsatile flow rate of 450 mL min(-1)), the errors in the percentages of area reduction were 4.3 +/- 1.2% before the stenosis, -2.0 +/- 1.0% in the stenosis, 11.5 +/- 3.1% in the recirculation zone, and 2.8 +/- 1.7% after the stenosis, respectively. Based on the simulated blood flow patterns obtained with FEM, the lower accuracy in the recirculation zone can be attributed to the effect of the wall filter that removes low flow velocities. In conclusion, the small errors reported in vitro may support the clinical use of this technique.

Assessment of blood echogenicity as an alternative measure to erythrocyte sedimentation rate.

OBJECTIVE: To determine the relation between erythrocyte sedimentation rate and blood echogenicity and whether measurement of erythrocyte sedimentation rate could be replaced by measurement of blood echogenicity in monitoring acute phase reactions. DESIGN: Simultaneous measurement of echogenicity of flowing blood and erythrocyte sedimentation rate in blood samples and comparison of results. SETTING: A radiological department in a university hospital. SUBJECTS: 83 patients with a suspected venous thrombosis and 36 healthy volunteers. MAIN OUTCOME MEASURES: Correlations between the erythrocyte sedimentation rate, packed cell volume, and echogenicity of flowing blood. RESULTS: Blood echogenicity correlated poorly with the packed cell volume, but strongly correlated with the erythrocyte sedimentation rate (when the packed cell volume was within reference limits) (correlation coefficient = 0.73). Blood samples with a greatly raised erythrocyte sedimentation rate were highly echogenic. Only one of the 30 samples with an erythrocyte sedimentation rate below 10 mm in first hour had a higher echogenicity than the least echogenic sample of the 19 with a sedimentation rate above 30 mm in first hour. CONCLUSIONS: Echogenicity of flowing blood correlates with the erythrocyte sedimentation rate and its measurement may compete with conventional methods for evaluating the long term changes in acute phase reactions. Also, it has the added advantage that non-invasive in vivo measurements of blood echogenicity may become possible.

Left and right ventricular function after streptokinase reperfusion: assessment by gated blood pool scans.

Twenty-three patients with acute anterior or inferior myocardial infarction (AMI, IMI) were investigated by gated blood pool scans at a mean 4.9 h after reperfusion and 10 days later. Eighteen (78%) successful reperfusion cases were divided into two groups; reperfusion in less than 4 h (Rp less than 4 h, n = 9) and reperfusion in more than 4 h (Rp greater than 4 h, n = 9) from the onset of chest pain. As control group, gated blood pool scans were also performed in the early hours following infarction in an additional 42 patients who received conventional treatments. Rp less than 4 h demonstrated significant improvement of mean LVEF in AMI (from 39.5 +/- 3.3 to 50.3 +/- 3.1%, p less than 0.01) and IMI (from 54.6 +/- 4.3 to 60.4 +/- 5.8%, p less than 0.01). Improvement of initially abnormal segments was noticed in 68% of AMI and 65% of IMI by quantitative wall motion analysis, while Rp greater than 4 h showed only slight improvement of LVEF and regional wall motion compared to Rp less than 4 h. On the other hand, the control group showed no significant change in left ventricular performance and regional wall motion. In patients with AMI, RVEF remained within normal range. In IMI, whether reperfused or not, the RVEF showed moderate improvement. In conclusion, these studies indicated that the time of reperfusion and location of infarction may influence functional recovery after streptokinase reperfusion.