Correcting partial volume artifacts of the arterial input function in quantitative cerebral perfusion MRI.

To quantify cerebral perfusion with dynamic susceptibility contrast MRI (DSC-MRI), one needs to measure the arterial input function (AIF). Conventionally, one derives the contrast concentration from the DSC sequence by monitoring changes in either the amplitude or the phase signal on the assumption that the signal arises completely from blood. In practice, partial volume artifacts are inevitable because a compromise has to be reached between the temporal and spatial resolution of the DSC acquisition. As the concentration of the contrast agent increases, the vector of the complex blood signal follows a spiral-like trajectory. In the case of a partial-volume voxel, the spiral is located around the static contribution of the surrounding tissue. If the static contribution of the background tissue is disregarded, estimations of the contrast concentration will be incorrect. By optimizing the correspondence between phase information and amplitude information one can estimate the origin of the spiral, and thereupon correct for partial volume artifacts. This correction is shown to be accurate at low spatial resolutions for phantom data and to improve the AIF determination in a clinical example. Magn Reson Med 45:477-485, 2001.     

Effects of tracer arrival time on flow estimates in MR perfusion-weighted imaging.

A common technique for calculating cerebral blood flow (CBF) and mean transit time (MTT) is to track a bolus of contrast agent using perfusion-weighted MRI (PWI) and to deconvolve the change in concentration with an arterial input function (AIF) using singular value decomposition (SVD). This method has been shown to often overestimate the volume of tissue that infarcts and in cases of severe vasculopathy to produce CBF maps that are inconsistent with clinical presentation. This study examines the effects of tracer arrival time differences between tissue and a user-selected global AIF on flow estimates. CBF and MTT were calculated in both numerically simulated and clinically acquired PWI data where the AIF and tissue signals were shifted backward and forward in time with respect to one another. Results show that when the AIF leads the tissue, CBF is underestimated independent of extent of delay, but dependent on MTT. When the AIF lags the tissue, flow may be over- or underestimated depending on MTT and extent of timing differences. These conditions may occur in practice due to the application of a user-selected AIF that is not the "true AIF" and therefore caution must be taken in interpreting CBF and MTT estimates.     

Analysis of partial volume effects on arterial input functions using gradient echo: A simulation study

Absolute blood flow and blood volume measurements using perfusion weighted MRI require an accurately measured arterial input function (AIF). Because of limited spatial resolution of MR images, AIF voxels cannot be placed completely within a feeding artery. We present a two‐compartment model of an AIF voxel including the relaxation properties of blood and tissue. Artery orientations parallel and perpendicular to the main magnetic field were investigated and AIF voxels were modeled to either include or be situated close to a large artery. The impact of partial volume effects on quantitative perfusion metrics was investigated for the gradient echo pulse sequence at 1.5 T and 3.0 T. It is shown that the tissue contribution broadens and introduces fluctuations in the AIF. Furthermore, partial volume effects bias perfusion metrics in a nonlinear fashion, compromising quantitative perfusion estimates and profoundly effecting local AIF selection. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.     

Phase‐based arterial input function measurements for dynamic susceptibility contrast MRI

In dynamic susceptibility contrast perfusion MRI, arterial input function (AIF) measurements using the phase of the MR signal are traditionally performed inside an artery. However, phase‐based AIF selection is also feasible in tissue surrounding an artery such as the middle cerebral artery, which runs approximately perpendicular to B₀ since contrast agents also induce local field changes in tissue surrounding the artery. The aim of this study was to investigate whether phase‐based AIF selection is better performed in tissue just outside the middle cerebral artery than inside the artery. Additionally, phase‐based AIF selection was compared to magnitude‐based AIF selection. Both issues were studied theoretically and using numerical simulations, producing results that were validated using phantom experiments. Finally, an in vivo experiment was performed to illustrate the feasibility of phase‐based AIF selection. Three main findings are presented: first, phase‐based AIF selections are better made in tissue outside the middle cerebral artery, rather than within the middle cerebral artery, since in the latter approach partial‐volume effects affect the shape of the estimated AIF. Second, optimal locations for phase‐based AIF selection are similar for different clinical dynamic susceptibility contrast MRI sequences. Third, phase‐based AIF selection allows more locations in tissue to be chosen that show the correct AIF than does magnitude‐based AIF selection. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

New criterion to aid manual and automatic selection of the arterial input function in dynamic susceptibility contrast MRI

Dynamic susceptibility contrast‐MRI requires an arterial input function (AIF) to obtain cerebral blood flow, cerebral blood volume, and mean transit time. The current AIF selection criteria discriminate venous, capillary, and arterial profiles based on shape and timing characteristics of the first passage. Unfortunately, partial volume effects can lead to shape errors in the bolus passage, including a narrower and higher peak, which might be selected as a “correct” AIF. In this study, a new criterion is proposed that detects shape errors based on tracer kinetic principles for computing cerebral blood volume. This criterion uses the ratio of the steady‐state value to the area‐under‐the‐curve of the first passage, which should result in an equal value for tissue and arterial responses. By using a reference value from tissue, partial volume effects–induced shape errors of the AIF measurement can be detected. Different factors affecting the ratio were investigated using simulations. These showed that the new criterion should only be used in studies with T₁‐insensitive acquisition. In vivo data were used to evaluate the proposed approach. The data showed that the new criterion enables detection of shape errors, although false positives do occur, which could be easily avoided when combined with current AIF selection criteria. Magn Reson Med, 2011. © 2010 Wiley‐Liss, Inc.     

ΔR2* gadolinium‐diethylenetriaminepentacetic acid relaxivity in venous blood

The accuracy of perfusion measurements using dynamic, susceptibility‐weighted, contrast‐enhanced MRI depends on estimating contrast agent concentration in an artery, i.e., the arterial input function. One of the difficulties associated with obtaining an arterial input function are partial volume effects when both blood and brain parenchyma occupy the same pixel. Previous studies have attempted to correct arterial input functions which suffer from partial volume effects using contrast concentration in venous blood. However, the relationship between relaxation and concentration (C) in venous blood has not been determined in vivo. In this note, a previously employed fitting approach is used to determine venous relaxivity in vivo. In vivo relaxivity is compared with venous relaxivity measured in vitro in bulk blood. The results show that the fitting approach produces relaxivity calibration curves which give excellent agreement with arterial measurements. Magn Reson Med 69:1104–1108, 2013. © 2012 Wiley Periodicals, Inc.     

Contrast agent influences MRI phase‐contrast flow measurements in small vessels

Contrast‐enhanced MR angiography is often combined with phase contrast (PC) flow measurement to answer a particular clinical question. The contrast agent that is administered during contrast‐enhanced MR angiography may still be present in the blood during the consecutive PC flow measurement. The aim of this work was to evaluate the influence of contrast agent on PC flow measurements in small vessels. For that purpose, both in vivo measurements and computer simulations were performed. The dependence of the PC flow quantification on the signal amplitude difference between blood and stationary background tissue for various vessel sizes was characterized. Results show that the partial‐volume effect strongly affects the accuracy of the PC flow quantification when the imaged vessel is small compared to the spatial resolution. A higher blood‐to‐background‐contrast level during imaging significantly increases the partial‐volume effect and thereby reduces the accuracy of the flow quantification. On the other hand, a higher blood‐to‐background‐contrast level facilitated the segmentation of the vessel for flow rate determination. PC flow measurements should therefore be performed after contrast agent administration in large vessels, but before contrast agent administration in small vessels. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

Measuring the arterial input function with gradient echo sequences.

The measurement of the arterial input function by use of gradient echo sequences was investigated by in vitro and in vivo experiments. First, calibration curves representing the influence of the concentration of Gd-DTPA on both the phase and the amplitude of the MR signal were measured in human blood by means of a slow-infusion experiment. The results showed a linear increase in the phase velocity and a quadratic increase in DeltaR(*) (2) as a function of the Gd-DTPA concentration. Next, the resultant calibration curves were incorporated in a partial volume correction algorithm for the arterial input function determination. The algorithm was tested in a phantom experiment and was found to substantially improve the accuracy of the concentration measurement. Finally, the reproducibility of the arterial input function measurement was estimated in 16 patients by considering the input function of the left and the right sides as replicate measurements. This in vivo study showed that the reproducibility of the arterial input function determination using gradient echo sequences is improved by employing a partial volume correction algorithm based on the calibration curve for the contrast agent used.     

Comparison of errors associated with single- and multi-bolus injection protocols in low-temporal-resolution dynamic contrast-enhanced tracer kinetic analysis.

Accurate sampling of the arterial input function (AIF) in low-temporal-resolution quantitative dynamic contrast-enhanced MRI (DCE-MRI) studies is crucial for accurate and reproducible parameter estimation. However, when conventional AIFs are sampled at low temporal resolution, they introduce an unpredictable degree of error. An alternative double contrast agent (CA) bolus injection protocol designed to compensate for temporal mis-sampling of the AIF and tissue uptake curve was simulated in addition to a commonly used single CA bolus injection protocol. A range of tissue uptake curves for each AIF form were generated using a distributed parameter model, and Monte Carlo simulation studies were performed over a range of offset times (to mimic temporal mis-sampling), temporal resolutions and SNR in order to compare the performance of both AIF forms in compartmental modeling. Insufficient data sampling of the single bolus AIF at temporal resolutions in excess of 9 s leads to large errors, which can be reduced by employing an additional, appropriately administered, second CA bolus injection.     

Blind estimation of the arterial input function in dynamic contrast‐enhanced MRI using purity maximization

Uncertainty in arterial input function (AIF) estimation is one of the major errors in the quantification of dynamic contrast‐enhanced MRI. A blind source separation algorithm was proposed to determine the AIF by selecting the voxel time course with maximum purity, which represents a minimal contamination from partial volume effects. Simulations were performed to assess the partial volume effect on the purity of AIF, the estimation accuracy of the AIF, and the influence of purity on the derived kinetic parameters. In vivo data were acquired from six patients with hypopharyngeal cancer and eight rats with brain tumor. Results showed that in simulation the AIF with the highest purity is closest to the true AIF. In patients, the manually selection had reduced purity, which could lead to underestimations of K^trans and V_e and an overestimation of V_p when compared with those obtained by the proposed blind source separation algorithm. The derived kinetic parameters in the tumor were more susceptible to the changes in purity when compared with those in the muscle. The animal experiment demonstrated good reproducibility in blind source separation‐AIF derived parameters. In conclusion, the blind source separation method is feasible and reproducible to identify the voxel with the tracer concentration time course closest to the true AIF. Magn Reson Med, 2012. © 2012 Wiley Periodicals, Inc.     

Prebolus quantitative MR heart perfusion imaging.

The purpose of this study was to present the prebolus technique for quantitative multislice myocardial perfusion imaging. In quantitative MR perfusion studies the maximum contrast agent dose is limited by the requirement to determine the arterial input function (AIF). The prebolus technique consists of two consecutive contrast agent administrations. The AIF is determined from a first low-dose bolus, while a second, high-dose bolus allows the measurement of the myocardium with improved signal increase. The results of the prebolus technique using a multislice saturation recovery trueFISP sequence in healthy volunteers are presented. In comparison to a standard dose of 3 ml Gd-DTPA, perfusion values are maintained while the signal increase in the concentration time courses was considerably improved, accompanied by reduced standard deviations of the obtained perfusion values (0.72 +/- 0.13 ml/g/min for 1 ml/8 ml and 0.67 +/- 0.10 ml/g/min for 1 ml/12 ml Gd-DTPA, respectively).     

The impact of partial-volume effects in dynamic susceptibility contrast magnetic resonance perfusion imaging

PURPOSE: To demonstrate the degree of the cerebral blood flow (CBF) estimation bias that could arise from distortion of the arterial input function (AIF) as a result of partial-volume effects (PVEs) in dynamic susceptibility contrast (DSC) magnetic resonance imaging (MRI). MATERIALS AND METHODS: A model of the volume fraction an artery occupies in a voxel was devised, and a mathematical relationship between the amount of PVE and the measured baseline MR signal intensity was derived. Based on this model, simulation studies were performed to assess the impact of PVE on CBF. Furthermore, the effectiveness of linear PVE compensation approaches on the concentration function was investigated. RESULTS: Simulation results showed a nonlinear relationship between PVE and the resulting CBF measurement error. In addition to AIF underestimation, PVE also causes distortions of AIF frequency characteristics, leading to CBF errors varying with mean transit time (MTT). An uncorrected AIF measured at a voxel with a partial-volume fraction of 相似文献   

Estimating the arterial input function using two reference tissues in dynamic contrast-enhanced MRI studies: fundamental concepts and simulations.

In dynamic contrast-enhanced MRI (DCE-MRI) studies, an accurate knowledge of the arterial contrast agent concentration as a function of time is crucial for the estimation of kinetic parameters. In this work, a novel method for estimating the arterial input function (AIF) based on the contrast agent concentration-vs.-time curves in two different reference tissues is described. It is assumed that the AIFs of the two tissues have the same shape, and that simple models with two or more compartments, and unknown kinetic parameters, can describe their tracer concentration-vs.-time curves. Based on the principle of self-consistency, one can relate the two tracer concentration-vs.-time curves to estimate their common underlining AIF, together with the kinetic parameters of the two tissues. In practice, the measured concentration-vs.-time curves have noise, and the AIFs of the two tissues are not exactly the same due to different dispersion effects. These factors will produce errors in the AIF estimate. Simulation studies show that despite the two error sources, the double-reference-tissue method provides reliable estimates of the AIF.     

Dual-bolus approach to quantitative measurement of pulmonary perfusion by contrast-enhanced MRI

PURPOSE: To evaluate a dual-bolus approach to pulmonary perfusion MRI. MATERIALS AND METHODS: The dual-bolus approach uses a separate low-dose measurement for the arterial input function (AIF) to ensure linearity. The measured AIF is constructed according to a subsequent higher dose used for the tissue concentration curves in the lung. In this study a prebolus of 0.01 mmol/kg followed by doses of 0.04 mmol/kg and 0.08 mmol/kg was used. Measurements were performed using time-resolved two-dimensional fast low-angle shot (2D FLASH) MRI (TE/TR = 0.73 msec/1.73 msec; flip angle = 40 degrees ; generalized autocalibrating partially parallel acquisitions (GRAPPA) factor = 3; temporal resolution = 400 msec) in end-inspiratory breath-hold. RESULTS: The combination of prebolus/0.04 mmol/kg resulted in a pulmonary blood flow (PBF) of 211 +/- 77 mL/min/100 mL, and a pulmonary blood volume (PBV) of 20 +/- 3 mL/100 mL. The combination of prebolus/0.08 mmol/kg resulted in approximately 50% lower perfusion values, most likely due to saturation effects in the lung tissue. CONCLUSION: A dual-bolus approach to pulmonary perfusion MRI is feasible and may reduce the problem of lacking linear relationship between the contrast-agent concentration and signal intensity.     

Partial volume effect (PVE) on the arterial input function (AIF) in T1‐weighted perfusion imaging and limitations of the multiplicative rescaling approach

The partial volume effect (PVE) on the arterial input function (AIF) remains a major obstacle to absolute quantification of cerebral blood flow (CBF) using MRI. This study evaluates the validity and performance of a commonly used multiplicative rescaling of the AIF to correct for the PVE. In a group of six patients, perfusion imaging was performed using a T₁‐weighted approach that minimizes confounding susceptibility artifacts. Various degrees of PVE were induced on the AIF and subsequently corrected using four different schemes of multiplicative AIF rescaling. Our results show that a multiplicative rescaling is not always applicable and can introduce a CBF bias. An easily measurable quantity denoted the tissue signal fraction (TSF) is proposed as a measure of the applicability of a multiplicative rescaling. For the present CBF quantification method, a TSF of <0.4 results in a CBF bias <15% after AIF rescaling. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.     

Quantitative contrast‐enhanced perfusion measurements of the human lung using the prebolus approach

Purpose

To investigate dynamic contrast‐enhanced MRI (DCE‐MRI) for quantification of pulmonary blood flow (PBF) and blood volume (PBV) using the prebolus approach and to compare the results to the global lung perfusion (GLP).

Materials and Methods

Eleven volunteers were examined by applying different contrast agent doses (0.5, 1.0, 2.0, and 3.0 mL gadolinium diethylene triamine pentaacetic acid [Gd‐DTPA]), using a saturation‐recovery (SR) true fast imaging with steady precession (TrueFISP) sequence. PBF and PBV were determined for single bolus and prebolus. Region of interest (ROI) evaluation was performed and parameter maps were calculated. Additionally, cardiac output (CO) and lung volume were determined and GLP was calculated as a contrast agent–independent reference value.

Results

The prebolus results showed good agreement with low‐dose single‐bolus and GLP: PBF (mean ± SD in units of mL/minute/100 mL) = single bolus 190 ± 73 (0.5‐mL dose) and 193 ± 63 (1.0‐mL dose); prebolus 192 ± 70 (1.0–2.0‐mL dose) and 165 ± 52 (1.0–3.0‐mL dose); GLP (mL/minute/100 mL) = 187 ± 34. Higher single‐bolus resulted in overestimated values due to arterial input function (AIF) saturation.

Conclusion

The prebolus approach enables independent determination of appropriate doses for AIF and tissue signal. Using this technique, the signal‐to‐noise ratio (SNR) from lung parenchyma can be increased, resulting in improved PBF and PBV quantification, which is especially useful for the generation of parameter maps. J. Magn. Reson. Imaging 2009;30:104–111. © 2009 Wiley‐Liss, Inc.     

Carboxymethyldextran-A2-Gd-DOTA enhancement patterns in the abdomen and pelvis in an animal model

The aim of this study was to assess MR signal enhancement patterns of carboxymethyldextran (CMD)-A2-Gd-DOTA, a new macromolecular contrast agent, in the abdomen and pelvis of New Zealand white rabbits. Nine New Zealand white rabbits underwent MRI before and following injection of 0.05 mmol/kg body weight (bw) CMD-A2-Gd-DOTA (52.1 kDa), using turbo FLASH-, dynamic FLASH 60 degrees-, T1- and T2-weighted spin-echo and turbo spin-echo sequences up to 10 days p.i. Changes in blood and tissue signal intensities (deltaSI) and relaxation rates (deltaR1) were calculated. Differences between pre- and post-contrast MRI data were compared using the Scheffé test. CMD-A2-Gd-DOTA demonstrated significant blood-pool enhancement and significant tissue enhancement on T1-weighted images, whereas no significant signal changes were observed on T2-weighted images (P < 0.05). Kidney parenchyma, pelvis and bladder demonstrated a subsequent enhancement, resembling renal elimination of the majority of the contrast agent. Liver parenchyma demonstrated a slow, delayed decay of the contrast enhancement due to storage and biodegradation of larger subfractions of the contrast agent. All tissue signal intensities were back to baseline 10 days p.i. CMD-A2-Gd-DOTA is a new macromolecular contrast agent with blood-pool effect, significant signal enhancement of abdominal organs and pelvic bone marrow, partial storage in the liver and baseline tissue signal intensities by 10 days p.i.     

Inflow effect correction in fast gradient-echo perfusion imaging.

The purposes of this study were to assess the extent of the inflow effect on signal intensity (SI) for fast gradient-recalled-echo (GRE) sequences used to observe first-pass perfusion, and to develop and validate a correction method for this effect. A phantom experiment with a flow apparatus was performed to determine SI as a function of Gd-DTPA concentration for various velocities. Subsequently a flow-sensitive calibration method was developed, and validated on bolus injections into an open-circuit flow apparatus and in vivo. It is shown that calibration methods based on static phantoms are not appropriate for accurate signal-to-concentration conversion in images affected by high flow. The flow-corrected calibration method presented here can be used to improve the accuracy and robustness of the arterial input function (AIF) determination for tissue perfusion quantification using MRI and contrast media.     

Arterial input functions for dynamic susceptibility contrast MRI: requirements and signal options

Cerebral perfusion imaging using dynamic susceptibility contrast (DSC) has been the subject of considerable research and shows promise for basic science and clinical use. In DSC, the MRI signals in brain tissue and feeding arteries are monitored dynamically in response to a bolus injection of paramagnetic agents, such as gadolinium (Gd) chelates. DSC has the potential to allow quantitative imaging of parameters such as cerebral blood flow (CBF) with a high signal-to-noise ratio (SNR) in a short scan time; however, quantitation depends critically on accurate and precise measurement of the arterial input function (AIF). We discuss many requirements and factors that make it difficult to measure the AIF. The AIF signal should be linear with respect to Gd concentration, convertible to the same concentration scale as the tissue signal, and independent of hematocrit. Complicated relationships between signal and concentration can violate these requirements. The additional requirements of a high SNR and high spatial/temporal resolution are technically challenging. AIF measurements can also be affected by signal saturation and aliasing, as well as dispersion/delay between the AIF sampling site and the tissue. We present new in vivo preliminary results for magnitude-based (DeltaR2*) and phase-based (Deltaphi) AIF measurements that show a linearity advantage of phase, and a disparity in the scaling of Deltaphi AIFs, DeltaR2* AIFs, and DeltaR2* tissue curves. Finally, we discuss issues related to the choice of AIF signal for quantitative perfusion imaging.     

Contrast-agent phase effects: An experimental system for analysis of susceptibility,concentration, and bolus input function kinetics

A system is presented for experimental arterial input function (AIF) simulation and for accurate measurement of the concentration, susceptibility effects, and magnetic moment of paramagnetic MR contrast agents. Signal effects of contrast agents are evaluated with a stable, well-characterized, and precise experimental setup. A cylindrical phantom and a closed-loop circulating flow system were designed for AIF simulation, assessment of the physical determinants of contrast-agent phase effects, and measurement of contrast agent properties under controlled conditions. A mathematical model of the AIF dynamics is proposed. From the experimental phase shift (Δ?), either the concentration or molar susceptibility, x_M, is determined. The linear dependence of Δ? on concentration and echo time (TE), the orientation dependence, and the lack of dependence on T₁, T₂, and diffusion time are proven precisely for water solutions under a wide variety of conditions. The measured effective magnetic moment of Gd⁺³, μ_eff, was 7.924 ± 0.015 Bohr magnetons in agreement with the theoretical value of 7.937.