In vitro pharmacokinetic phantom for two-compartment modeling in DCE-MRI

\u3cp\u3eDynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is an established minimally-invasive method for assessment of extravascular leakage, hemodynamics, and tissue viability. However, differences in acquisition protocols, variety of pharmacokinetic models, and uncertainty on physical sources of MR signal hamper the reliability and widespread use of DCE-MRI in clinical practice. Measurements performed in a controlled in vitro setup could be used as a basis for standardization of the acquisition procedure, as well as objective evaluation and comparison of pharmacokinetic models. In this paper, we present a novel flow phantom that mimics a two-compartmental (blood plasma and extravascular extracellular space/EES) vascular bed, enabling systemic validation of acquisition protocols. The phantom consisted of a hemodialysis filter with two compartments, separated by hollow fiber membranes. The aim of this phantom was to vary the extravasation rate by adjusting the flow in the two compartments. Contrast agent transport kinetics within the phantom was interpreted using two-compartmental pharmacokinetic models. Boluses of gadolinium-based contrast-agent were injected in a tube network connected to the hollow fiber phantom; time-intensity curves (TICs) were obtained from image series, acquired using a T1-weighted DCE-MRI sequence. Under the assumption of a linear dilution system, the TICs obtained from the input and output of the system were then analyzed by a system identification approach to estimate the trans-membrane extravasation rates in different flow conditions. To this end, model-based deconvolution was employed to determine (identify) the impulse response of the investigated dilution system. The flow rates in the EES compartment significantly and consistently influenced the estimated extravasation rates, in line with the expected trends based on simulation results. The proposed phantom can therefore be used to model a two-compartmental vascular bed and can be employed to test and optimize DCE-MRI acquisition sequences in order to determine a standardized acquisition procedure leading to consistent quantification results.\u3c/p\u3

Monitoring thoracic fluid content using bioelectrical impedance spectroscopy and Cole modeling

Heart failure is a chronic disease marked by frequenthospitalizations due to pulmonary fluid congestion. Monitoringthe thoracic fluid status may favor the detection of fluidcongestion in an early stage and enable targeted preventivemeasures. Bioelectrical impedance spectroscopy (BIS) has beenused in combination with the Cole model for monitoring bodycomposition including fluid status. The model parameters reflectintracellular and extracellular fluid volume as well as cell sizes,types and interactions. Transthoracic BIS may be a suitableapproach to monitoring variations in thoracic fluid content.The aim of this study was to identify BIS measures, which canbe derived based on the Cole model, that are sensitive to earlystages of thoracic fluid accumulation. We simulated this medicalcondition in healthy subjects by shifting a part of the whole bloodfrom the periphery towards the thorax. The redistribution ofblood was achieved non-invasively through leg compression usinginflatable leg sleeves. We acquired BIS data before, during andafter compression of the legs and examined the effect of thoracicfluid variations on parameters derived based on the Cole modeland on geometrical properties of the impedance arc. Indicatordilution measurements obtained through cardiac magneticresonance imaging were used as a reference for the changes inpulmonary fluid volume.Eight healthy subjects were included in the study. The Colemodel parameters of the study group at baseline were: R0 = 51.4 ±6.7 Ω, R∞ = 25.0 ± 7.0 Ω, fc = 49.0 ± 10.5 kHz, α = 0.687 ± 0.027, theresistances of individual fluid compartments were RE = 51.4 ± 6.7Ω, RI = 50.5 ± 22.9 Ω, the fluid distribution ratio was K = 1.1 ± 0.3,and the radius, area and depression of the arc’s center were: R =15.7 ± 1.3 Ω, XC = −8.5 ± 1.5 Ω, A = 134.0 ± 15.6 Ω2. The effect ofleg compression was a relatively small, reversible increase inpulmonary blood volume of 90 ± 57 mL. We observed significantchanges in parameters associated with intracellular, extracellularand total fluid volume (R0: -1.5 ± 0.9 %, p < 0.01; R∞: −2.1 ± 1.1, p <0.01; RI: −2.6 ± 1.6 %, p < 0.01), and in the arc’s geometricalproperties (R: -1.6 ± 1.3 %, p < 0.05; XC: −1.7 ± 1.5 %, p < 0.05, A:−2.9 ± 1.2 %, p < 0.01). K and the parameters associated withtissue structure fc and α remained stable.Transthoracic BIS is sensitive to small variations in intrathoracicblood volume, in particular the resistances of fluidcompartments and the geometric properties of the impedancearc. Taken together with previous studies, our findings suggestthat R0 may be a suitable parameter to monitor congestion. Use ofadditional parameters such as RI, K, XC, fc and α may enable thediscrimination between different types and stages of thoracic fluidaccumulation and should be the focus of future research

Pulmonary blood volume measured by contrast enhanced ultrasound : a comparison with transpulmonary thermodilution

Background Blood volume quantification is essential for haemodynamic evaluation guiding fluid management in anaesthesia and intensive care practice. Ultrasound contrast agent (UCA)-dilution measured by contrast enhanced ultrasound (CEUS) can provide the UCA mean transit time (MTT) between the right and left heart, enabling the assessment of the intrathoracic blood volume (ITBVUCA). The purpose of the present study was to investigate the agreement between UCA-dilution using CEUS and transpulmonary thermodilution (TPTD) in vitro and in vivo. Methods In an in vitro setup, with variable flows and volumes, we injected a double indicator, ice-cold saline with SonoVue®, and performed volume measurements using transesophageal echo and thermodilution by PiCCO®. In a pilot study, we assigned 17 patients undergoing elective cardiac surgery for pulmonary blood volume (PBV) measurement using TPTD by PiCCO® and ITBV by UCA-dilution. Correlation coefficients and Bland-Altman analysis were performed for all volume measurements. Results In vitro, 73 experimental MTT's were obtained using PiCCO® and UCA-dilution. The volumes by PiCCO® and UCA-dilution correlated with true volumes; rs=0.96 (95% CI, 0.93–0.97; P<0.0001) and rs=0.97 (95% CI, 0.95–0.98; P<0.0001), respectively. The bias of PBV by PiCCO® and ITBVUCA were −380 ml and −42 ml, respectively. In 16 patients, 86 measurements were performed. The correlation between PBV by PiCCO® and ITBVUCA was rs=0.69 (95% CI 0.55–0.79; P<0.0001). Bland-Altman analysis revealed a bias of −323 ml. Conclusions ITBV assessment with CEUS seems a promising technique for blood volume measurement, which is minimally-invasive and bedside applicable

Maximum-likelihood estimation for indicator dilution analysis

Indicator-dilution methods are widely used by many medical imaging techniques and by dye-, lithium-, and thermodilution measurements. The measured indicator dilution curves are typically fitted by a mathematical model to estimate the hemodynamic parameters of interest. This paper presents a new maximum-likelihood algorithm for parameter estimation, where indicator dilution curves are considered as the histogram of underlying transit-time distribution. Apart from a general description of the algorithm, semi-analytical solutions are provided for three well-known indicator dilution models. An adaptation of the algorithm is also introduced to cope with indicator recirculation. In simulations as well as in experimental data obtained by dynamic contrast-enhanced ultrasound imaging, the proposed algorithm shows a superior parameter estimation accuracy over nonlinear least-squares regression. The feasibility of the algorithm for use in vivo is evaluated using dynamic contrastenhanced ultrasound recordings obtained with the purpose of prostate cancer detection. The proposed algorithm shows an improved ability (increase in receiver-operating-characteristic curve area of up to 0.13) with respect to existing methods to differentiate between healthy tissue and cancer

Noninvasive pulmonary transit time:a new parameter for general cardiac performance

\u3cp\u3eIntroduction: Pulmonary transit time (PTT) assessed with contrast-enhanced ultrasound (CEUS) is a novel tool to evaluate cardiac function. PTT represents the time for a bolus of contrast to pass from the right to the left ventricle, measured according to the indicator dilution principles using CEUS. We investigated the hypothesis that PTT is a measure of general cardiac performance in patient populations eligible for cardiac resynchronization therapy (CRT). Methods: The study population consisted of heart failure patients referred for CRT with NYHA class II–IV, left ventricular ejection fraction (LVEF)≤35% and QRS≥120 ms. CEUS, ECG, and blood were analyzed, and participants completed a quality of life questionnaire at baseline and 3 months after CRT implantation. Normalized PTT (nPTT) was calculated to compensate for the heart rate. Correlations were assessed with Pearson's or Spearman's coefficients and stratified for rhythm and NYHA class. Results: The study population consisted of 94 patients (67 men) with a mean age of 70±8.9 years. (n)PTT was significantly correlated with left ventricular parameters (r\u3csub\u3es\u3c/sub\u3e=−.487, P<.001), right ventricular parameters (r=−.282, P=.004), N-terminal pro-B-type natriuretic peptide (NT-proBNP) (r\u3csub\u3es\u3c/sub\u3e=.475, P<.001), and quality of life (r\u3csub\u3es\u3c/sub\u3e=.364, P<.001). Stronger significant correlations were found in patients in sinus rhythm. Conclusion: CEUS-derived PTT and nPTT correlate to a fair degree with measures of systolic and diastolic function, NT-pro-BNP, and quality of life. As CEUS-derived PTT can be obtained easily, noninvasively and at the bedside, it is a promising future measure of general cardiac performance.\u3c/p\u3

Model-based characterization of the transpulmonary circulation by dynamic contrast-enhanced MRI in heart failure and healthy volunteers

Objectives: Novel quantitative measures of the trans-pulmonary circulation status may allow improvement of heart failure (HF) patient management. In this work, we propose a method for the assessment of the trans-pulmonary circulation using measurements from indicator time-intensity curves, derived from dynamic contrast-enhanced magnetic resonance (DCE-MRI) image series. The derived indicator dilution parameters in healthy volunteers (HV) and HF patients were compared, and repeatability was assessed. Furthermore, we compared the parameters derived using the proposed method with standard measures of cardiovascular function (such as left ventricular volumes and ejection fraction).Materials and methodsIn all, 19 HVs and 33 HF patients underwent a DCE-MRI scan on a 1.5 T MRI scanner using a T1-weigthed spoiled gradient echo sequence. Image loops with one heart-beat temporal resolution were acquired in four-chamber view during ventricular late diastole, after the injection of a 0.1 mmol gadoteriol bolus. On a subset of the patients (8 HF, 2 HV), a second injection of a 0.3 mmol gadoteriol bolus was performed with same imaging settings. The study was approved by the local institutional review board. Indicator dilution curves (IDCs) were derived averaging the MR signal within regions of interest in the right and left ventricle; parametric deconvolution was performed between right and left ventricular (LV) IDCs to identify the impulse response of the trans-pulmonary dilution system. The local density random walk model was used to parametrize the impulse response; pulmonary transit time (PTT) was defined as the mean transit time of the indicator; λ, related to the Peclet number (ratio between convection and diffusion) for the dilution process, was also estimated. Results PTT was significantly prolonged in HF patients (8.70 ± 1.87 s vs. 6.68 ± 1.89 s in HV, p<0.005), even stronger when normalized to subject heart rate (normalized PTT, 9.90 ± 2.16 vs. 7.11 ± 2.17 in HV, dimensionless, p<0.001). λ was significantly smaller in HF patients (8.59 ± 4.24 in HF vs. 12.50 ± 17.09 in HV, dimensionless, p<0.005), indicating a longer tail for the impulse response. PTT correlated well with established cardiovascular parameters (left ventricular end-diastolic volume index, r=0.61, p<0.0001; left ventricular ejection fraction r=-0.62, p<0.0001). We consider the measurement of indicator dilution parameters this way repeatable (correlation between estimates based on the two repetitions for PTT: r=0.94, p<0.001, difference between two repetitions 0.01 ± 0.60 s, for λ: r=0.74, p<0.01, difference 0.69 ± 4.39).ConclusionsCharacterization of the trans-pulmonary circulation by DCE-MRI is feasible in heart failure patients and healthy volunteers. Significant differences are observed between indicator dilution parameters measured in healthy volunteers and heart failure patients; preliminary results suggest good repeatability for the proposed parameters

Comparison of cardiac magnetic resonance imaging and bio-impedance spectroscopy for the assessment of fluid displacement induced by external leg compression

\u3cp\u3eHeart failure is marked by frequent hospital admissions, often as a consequence of pulmonary congestion. Current gold standard techniques for thoracic fluid measurement require invasive heamodynamic access and therefore they are not suitable for continuous monitoring. Changes in thoracic impedance (TI) may enable non-invasive early detection of congestion and prevention of unplanned hospitalizations. However, the usefulness of TI to assess thoracic fluid status is limited by inter-subject variability and by the lack of reliable normalization methods. Indicator dilution methods allow absolute fluid volume estimation; cardiac magnetic resonance (CMR) has been recently proposed to apply indicator dilution methods in a minimally-invasive manner. In this study, we aim to compare bio-impedance spectroscopy (BIS) and CMR for the assessment of thoracic fluid status, and to determine their ability to detect fluid displacement induced by a leg compression procedure in healthy volunteers. A pressure gradient was applied across each subject's legs for 5 min (100-60 mmHg, distal to proximal). Each subject underwent a continuous TI-BIS measurement during the procedure, and repeated CMR-based indicator dilution measurements on a 1.5 T scanner at baseline, during compression, and after pressure release. The Cole-Cole and the local density random walk models were used for parameter extraction from TI-BIS and indicator dilution measurements, respectively. Intra-thoracic blood volume index (ITBI) derived from CMR, and extracellular fluid resistance (R \u3csub\u3eE\u3c/sub\u3e) from TI-BIS, were considered as thoracic fluid status measures. Eight healthy volunteers were included in this study. An increase in ITBI of 45.2 47.2 ml m\u3csup\u3e-2\u3c/sup\u3e was observed after the leg inflation (13.1 15.1% w.r.t. baseline, p < 0.05), while a decrease of -0.84 0.39 Ω in R \u3csub\u3eE\u3c/sub\u3e (-1.7 0.9% w.r.t. baseline, p < 0.05) was observed. ITBV and R \u3csub\u3eE\u3c/sub\u3e normalized by body mass index were strongly inversely correlated (r = -0.93, p < 0.05). In conclusion, an acute fluid displacement to the thoracic circulation was induced in healthy volunteers. Significant changes were observed in the considered thoracic fluid measures derived from BIS and CMR. Good correlation was observed between the two measurement techniques. Further clinical studies will be necessary to prospectively evaluate the value of a combination of the two techniques for prediction of re-hospitalizations after admission for heart failure.\u3c/p\u3

The hemodynamic effects of different pacing modalities after cardiopulmonary bypass in patients with reduced left ventricular function

\u3cp\u3eObjectives: Patients with decreased left ventricular function undergoing cardiac surgery have a greater chance of difficult weaning from cardiopulmonary bypass and a poorer clinical outcome. Directly after weaning, interventricular dyssynchrony, paradoxical septal motion, and even temporary bundle-branch block might be observed. In this study, the authors measured arterial dP/dt\u3csub\u3emax\u3c/sub\u3e, mean arterial pressure (MAP), and cardiac index using transpulmonary thermodilution, pulse contour analysis, and femoral artery catheter and compared the effects between right ventricular (A-RV) and biventricular (A-BiV) pacing on these parameters. Design: Prospective study. Setting: Single-center study. Participants: The study comprised 17 patients with a normal or prolonged QRS duration and a left ventricular ejection fraction ≤35% who underwent coronary artery bypass grafting with or without valve replacement. Interventions: Temporary pacing wires were placed on the right atrium and both ventricles. Different pacing modalities were used in a standardized order. Measurements and Main Results: A-BiV pacing compared with A-RV pacing demonstrated higher arterial dP/dt\u3csub\u3emax\u3c/sub\u3e values (846 ± 646 mmHg/s v 800 ± 587 mmHg/s, p = 0.023) and higher MAP values (77 ± 19 mmHg v 71 ± 18 mmHg, p = 0.036). Conclusion: In patients with preoperative decreased left ventricular function undergoing coronary artery bypass grafting, A-BiV pacing improve the arterial dP/dt\u3csub\u3emax\u3c/sub\u3e and MAP in patients with both normal and prolonged QRS duration compared with standard A-RV pacing. In addition, arterial dP/dt\u3csub\u3emax\u3c/sub\u3e and MAP can be used to evaluate the effect of intraoperative pacing. In contrast to previous studies using more invasive techniques, transpulmonary thermodilution is easy to apply in the perioperative clinical setting.\u3c/p\u3