Partial volume effects on arterial input functions: shape and amplitude distortions and their correction

For quantification of perfusion values from a bolus-tracking MRI experiment, the measurement of an arterial input function (AIF) is necessary. Gradient-echo (GE) sequences are commonly used for this type of experiment because they offer a high signal-to-noise ratio (SNR) and the potential to quantify the concentration of contrast agent. Measurements of calibration curves for Gd-DTPA in human blood have shown a quadratic relation between the DeltaR(2)* and the concentration of contrast agent, and a linear relationship between phase changes and the concentration of contrast agent. However, for in vivo studies the spatial resolution is usually limited, which leads to partial volume effects. Partial volume effects result in a complex sum of signal arising from the tissue outside the vessel and a contrast agent concentration-dependent blood signal. Ignoring the presence of partial volume effects can lead to an overestimation or underestimation of the contrast agent concentration, depending on the experimental conditions. Correction for partial volume effects is feasible in arteries that are parallel to the main magnetic field by estimation and subtraction of the static signal of the surrounding tissue. Patient studies showed a large variation due to the AIF measurements, but it has also been shown that this influence can be minimized by correction for partial volume effects.     

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.     

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.     

Evaluation of an AIF correction algorithm for dynamic susceptibility contrast-enhanced perfusion MRI

For longitudinal studies in patients suffering from cerebrovascular diseases the poor reproducibility of perfusion measurements via dynamic susceptibility-weighted contrast-enhanced MRI (DSC-MRI) is a relevant concern. We evaluate a novel algorithm capable of overcoming limitations in DSC-MRI caused by partial volume and saturation issues in the arterial input function (AIF) by a blood flow stimulation-study. In 21 subjects, perfusion parameters before and after administration of blood flow stimulating L-arginine were calculated utilizing a block-circulant singular value decomposition (cSVD). A total of two different raters and three different rater conditions were employed to select AIFs: Besides 1) an AIF selection by an experienced rater, a beginner rater applied a steady state-oriented strategy, returning; 2) raw; and 3) corrected AIFs. Highly significant changes in regional cerebral blood flow (rCBF) by 9.0% (P < 0.01) could only be found when the AIF correction was performed. To further test for improved reproducibility, in a subgroup of seven subjects the baseline measurement was repeated 6 weeks after the first examination. In this group as well, using the correction algorithm decreased the SD of the difference between the two baseline measurements by 42%.     

Combined T2* and T1 measurements for improved perfusion and permeability studies in high field using dynamic contrast enhancement

This study analyzed the T2* effect of extracellularly distributed gadolinium contrast agents in arterial blood during tumor studies using T1-weighted sequences at high field strength. A saturation-prepared dual echo sequence with echo times of 1.5 and 3.5 ms was employed at 3 T to simultaneously characterize T1 and T2* of arterial blood during bolus administration of Gd-DTPA in 28 patients with body tumors. T2* effect and T1 effect of Gd-DTPA on image intensity of whole blood were calibrated in human blood samples with different concentrations of contrast agent. T2* was used to estimate concentration near the peak of the bolus. T1 was used to measure lower concentrations when T2* was not significant. T2* was measurable on calibration curves for Gd-DTPA concentrations higher than 4 mM. This concentration was exceeded in 18 patients. The mean signal intensity reduction because of T2* effect was estimated at 22±14% of the T2* compensated signal. Using T2* measurements reduced underestimations of peak arterial Gd-DTPA concentration (59±38%) and overestimation of permeability K^trans (58%). The T2* effect of gadolinium contrast agents should therefore be accounted for when performing tumors study with T1-weighted sequences at high field strength.     

Effects of inflow and radiofrequency spoiling on the arterial input function in dynamic contrast‐enhanced MRI: A combined phantom and simulation study

The arterial input function is crucial in pharmacokinetic analysis of dynamic contrast‐enhanced MRI data. Among other artifacts in arterial input function quantification, the blood inflow effect and nonideal radiofrequency spoiling can induce large measurement errors with subsequent reduction of accuracy in the pharmacokinetic parameters. These errors were investigated for a 3D spoiled gradient‐echo sequence using a pulsatile flow phantom and a total of 144 typical imaging settings. In the presence of large inflow effects, results showed poor average accuracy and large spread between imaging settings, when the standard spoiled gradient‐echo signal equation was used in the analysis. For example, one of the investigated inflow conditions resulted in a mean error of about 40% and a spread, given by the coefficient of variation, of 20% for K^trans. Minimizing inflow effects by appropriate slice placement, combined with compensation for nonideal radiofrequency spoiling, significantly improved the results, but they remained poorer than without flow (e.g., 3–4 times larger coefficient of variation for K^trans). It was concluded that the 3D spoiled gradient‐echo sequence is not optimal for accurate arterial input function quantification and that correction for nonideal radiofrequency spoiling in combination with inflow minimizing slice placement should be used to reduce the errors. Magn Reson Med, 2011. © 2011 Wiley‐Liss, Inc.     

T1 measurement of flowing blood and arterial input function determination for quantitative 3D T1-weighted DCE-MRI

PURPOSE: To propose a simple, accurate method for measuring T(1) in flowing blood and the arterial input function (AIF), and to evaluate the impact on dynamic contrast-enhanced MRI (DCE-MRI) quantification of pharmacokinetic parameters. MATERIALS AND METHODS: A total of 10 rabbits were scanned at 1.5 Tesla and administered a bolus of Gadomer. Preinjection T(1) and AIF measurements were acquired in the iliac arteries using a rapid three-dimensional (3D) spoiled gradient recalled echo (SPGR) approach. Correction was made for imperfect B(1) fields, in-flow, and partial volume effects. DCE-MRI parameters blood volume (v(b)) and endothelial transfer constant (K(trans)) in resting skeletal muscle were estimated from pharmacokinetic analysis using individually measured AIFs. Literature comparisons were made to assess accuracy. RESULTS: Blood T(1) was more accurate and precise after correction for B(1) and partial volume errors (1267 +/- 72 msec). Measured AIFs followed reported biexponential decay characteristics for Gadomer clearance in rabbits. Parameters v(b) (2.47 +/- 0.65%) and K(trans) (3.6 +/- 1.0 x 10(-3) minute(-1)) derived from AIFs based on corrected blood T(1)s were more reproducible and in better agreement with literature values. CONCLUSION: The proposed method enables accurate in vivo blood T(1) and AIF measurements and can be easily implemented in a range of DCE-MRI applications to improve both the accuracy and reproducibility of pharmacokinetic parameters.     

Measurement of the arterial concentration of Gd-DTPA using MRI: A step toward quantitative perfusion imaging

A noninvasive method using an inversion recovery turbo-FLASH for dynamic measurement of the arterial input function represented by the bolus passage of Gd-DTPA in the descending aorta is presented, and the results are compared with the input function obtained by arterial blood samples. A good accordance between the two input functions was found, indicating that it is possible to measure the input function to the myocardium using MRI. A variation between the two concentration curves of 5% at upslope, 2.7% at peak point, and <7% at downslope was found. The study also indicates that a short inversion time <250 ms has to be used to ensure correct measurement of peak concentration.     

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.     

Measurement and correction of transmitter and receiver induced nonuniformities in vivo.

Signal intensity nonuniformities in high field MR imaging limit the ability of MRI to provide quantitative information and can negatively impact diagnostic scan quality. In this paper, a simple method is described for correcting these effects based on in vivo measurement of the transmission field B1+ and reception sensitivity maps. These maps can be obtained in vivo with either gradient echo (GE) or spin echo (SE) imaging sequences, but the SE approach exhibits an advantage over the GE approach for correcting images over a range of flip angles. In a uniform phantom, this approach reduced the ratio of the signal SD to its mean from around 30% before correction to approximately 6% for the SE approach and 9% for the GE approach after correction. The application of the SE approach for correcting intensity nonuniformities is demonstrated in vivo with human brain images obtained using a conventional spin echo sequence at 3.0 T. Furthermore, it is also shown that this in vivo B1+ and reception sensitivity mapping can be performed using segmented echo planar imaging sequences providing acquisition times of less than 2 min. Although the correction presented here is demonstrated with a simultaneous transmit and receive volume coil, it can be extended to the case of separate transmission and reception coils, including surface and phase array coils.     

Absolute quantification of cerebral blood flow in neurologically normal volunteers: Dynamic‐susceptibility contrast MRI‐perfusion compared with computed tomography (CT)‐perfusion

To improve the reproducibility of arterial input function (AIF) registration and absolute cerebral blood flow (CBF) quantification in dynamic‐susceptibility MRI‐perfusion (MRP) at 1.5T, we rescaled the AIF by use of a venous output function (VOF). We compared CBF estimates of 20 healthy, elderly volunteers, obtained by computed tomography (CT)‐perfusion (CTP) and MRP on two consecutive days. MRP, calculated without the AIF correction, did not result in any significant correlation with CTP. The rescaled MRP showed fair to moderate correlation with CTP for the central gray matter (GM) and the whole brain. Our results indicate that the method used for correction of partial volume effects (PVEs) improves MRP experiments by reducing AIF‐introduced variance at 1.5T. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.     

Method for quantitation of dynamic MRI contrast agent uptake in colorectal liver metastases

PURPOSE: To investigate the reproducibility of dynamic contrast-enhanced MRI (DCE-MRI) in colorectal liver metastases using a vascular normalization function (VNF) from pixels in the spleen and to compare this with a technique using an arterial input function (AIF) from pixels in the aorta. MATERIALS AND METHODS: DCE-MRI with gadolinium-DTPA (Gd-DTPA) was performed in patients with colorectal liver metastases. The VNF and AIF were determined using an automated algorithm. The average Gd-DTPA uptake rate (k(ep)) was calculated for the metastases using a physiological pharmacokinetic model. The protocol was repeated on a second day to calculate the repeatability coefficient of the measurements of k(ep). RESULTS: Using the VNF from the spleen the overall mean k(ep) of the two sessions for 11 patients was 0.033 per second and the repeatability coefficient was 0.009 per second. Using the AIF from the aorta these values were 0.031 per second and 0.028 per second, respectively. CONCLUSION: The mean Gd-DTPA uptake rate using a VNF taken from the spleen can be determined with adequate reproducibility in colorectal liver metastases. The use of a VNF from pixels in the spleen is better than an AIF from pixels in the aorta in terms of reproducibility, and is recommended when this DCE-MRI technique is used for prediction and monitoring of therapy outcome in colorectal liver metastases.     

The effect of blood inflow and B1‐field inhomogeneity on measurement of the arterial input function in axial 3D spoiled gradient echo dynamic contrast‐enhanced MRI

A major potential confound in axial 3D dynamic contrast‐enhanced magnetic resonance imaging studies is the blood inflow effect; therefore, the choice of slice location for arterial input function measurement within the imaging volume must be considered carefully. The objective of this study was to use computer simulations, flow phantom, and in vivo studies to describe and understand the effect of blood inflow on the measurement of the arterial input function. All experiments were done at 1.5 T using a typical 3D dynamic contrast‐enhanced magnetic resonance imaging sequence, and arterial input functions were extracted for each slice in the imaging volume. We simulated a set of arterial input functions based on the same imaging parameters and accounted for blood inflow and radiofrequency field inhomogeneities. Measured arterial input functions along the vessel length from both in vivo and the flow phantom agreed with simulated arterial input functions and show large overestimations in the arterial input function in the first 30 mm of the vessel, whereas arterial input functions measured more centrally achieve accurate contrast agent concentrations. Use of inflow‐affected arterial input functions in tracer kinetic modeling shows potential errors of up to 80% in tissue microvascular parameters. These errors emphasize the importance of careful placement of the arterial input function definition location to avoid the effects of blood inflow. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

Method for the quantitative assessment of contrast agent uptake in dynamic contrast-enhanced MRI

In previous papers relative signal intensity increase was used as a quantitative assessment parameter for contrast uptake in contrastenhanced MRI. However, relative signal intensity increase does not only reflect contrast uptake but depends also on tissue parameters (native T₁ relaxation time) and sequence parameters (repetition time and flip angle); thus, the contrast uptake cannot be assessed accurately using relative signal intensity increase. Based on an analysis of the contrast behavior of spoiled gradient echo sequences, a method is described in this paper that overcomes the limitations of relative signal intensity increase measurement. A parameter, called “enhancement factor” (EF) is introduced that approximates differential T₁ relaxation rate. The enhancement factor scales linearly with contrast uptake and is independent of tissue and sequence parameters. The additional measurement time involved in determining the enhancement factor is less than 1 min and computation is straightforward. The practicality of the new method was confirmed by phantom measurements using T₁-weighted and proton density-weighted spoiled gradient echo sequences (FLASH-2D). Enhancing tissues were simulated by water phantoms doped with increasing concentrations of Gd-DTPA.     

First order correction for T2*‐relaxation in determining contrast agent concentration from spoiled gradient echo pulse sequence signal intensity

Purpose:

To investigate the accuracy of a method neglecting T₂*‐relaxation, for the conversion of spoiled gradient echo pulse sequence signal intensity to contrast agent (CA) concentration, in dynamic contrast enhanced MRI studies. In addition a new closed form conversion expression is proposed that accounts for a first order approximation of T₂*‐relaxation.

Materials and Methods:

The accuracy of both conversion methods is compared theoretically by means of simulations for four pulse sequences from literature. Both methods are tested in vivo against the numerical conversion method for measuring the arterial input function in mice.

Results:

Simulations show that the T₂*‐neglecting method underestimates typical tissue CA concentrations (0 mM to 2 mM) up to 6%, while the errors for arterial concentrations (0 mM to 10 mM) range up to 43%. The results from our first order method are numerically indistinguishable from the simulation input values in tumor tissue, while for arterial concentrations the error is reduced up to a factor 10. In vivo, peak Gd‐DOTA concentration is underestimated up to 14% with the T₂*‐neglecting method and up to 0.9% with our first order method.

Conclusion:

Our conversion method reduces the underestimation of CA concentration severely in a broad physiological concentration range and is easy to perform in any clinical setting. J. Magn. Reson. Imaging 2011;. © 2011 Wiley‐Liss, 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).     

Improving dynamic susceptibility contrast MRI measurement of quantitative cerebral blood flow using corrections for partial volume and nonlinear contrast relaxivity: A xenon computed tomographic comparative study

Purpose

To test whether dynamic susceptibility contrast MRI‐based CBF measurements are improved with arterial input function (AIF) partial volume (PV) and nonlinear contrast relaxivity correction, using a gold‐standard CBF method, xenon computed tomography (xeCT).

Materials and Methods

Eighteen patients with cerebrovascular disease underwent xeCT and MRI within 36 h. PV was measured as the ratio of the area under the AIF and the venous output function (VOF) concentration curves. A correction was applied to account for the nonlinear relaxivity of bulk blood (BB). Mean CBF was measured with both techniques and regression analyses both within and between patients were performed.

Results

Mean xeCT CBF was 43.3 ± 13.7 mL/100g/min (mean ± SD). BB correction decreased CBF by a factor of 4.7 ± 0.4, but did not affect precision. The least‐biased CBF measurement was with BB but without PV correction (45.8 ± 17.2 mL/100 g/min, coefficient of variation [COV] = 32%). Precision improved with PV correction, although absolute CBF was mildly underestimated (34.3 ± 10.8 mL/100 g/min, COV = 27%). Between patients correlation was moderate even with both corrections (R = 0.53).

Conclusion

Corrections for AIF PV and nonlinear BB relaxivity improve bolus MRI‐based CBF maps. However, there remain challenges given the moderate between‐patient correlation, which limit diagnostic confidence of such measurements in individual patients. J. Magn. Reson. Imaging 2009;30:743–752. © 2009 Wiley‐Liss, Inc.     

Automatic selection of arterial input function using cluster analysis.

Quantification of cerebral blood flow (CBF) using dynamic susceptibility contrast MRI requires determination of the arterial input function (AIF) representing the delivery of intravascular tracer to tissue. This is typically accomplished manually by inspection of concentration time curves (CTCs) in regions containing the ICA, VA, and MCA. This is, however, a time consuming and operator dependent procedure. We suggest a completely automatic procedure for establishing the AIF based on a cluster analysis algorithm. In 20 normal subjects CBF maps calculated in 2 slices by the automatic procedure were compared to maps obtained with AIFs selected individually by 7 experienced operators. The average manual to automatic CBF ratio was 1.03+/-0.15 in the lower slice and 1.05+/-0.12 in the upper slice, demonstrating excellent agreement between the manual and automatic method. The algorithm provides means for objectively assessing AIF candidates in local AIF search algorithms designed to reduce bias due to delay and dispersion. Given the reproducibility and speed (10 s) of the automatic method, we speculate that it will greatly improve the accuracy of perfusion images and facilitate their use in clinical diagnosis and decision-making, particularly in acute stroke but also in cerebrovascular disease in general.     

Quantification of myocardial perfusion with FAST sequence and Gd bolus in patients with normal cardiac function

The present study reports on a new calibration of the magnetic resonance imaging (MRI) signal intensity of a fast gradient-echo sequence used for in vivo myocardial perfusion quantification in patients. The signal from a FAST sequence preceded by a arrhythmia-insensitive magnetization preparation was calibrated in vitro using tubes filled with various gadolinium (Gd) solutions. Single short-axis views of the heart were obtained in patients (n = 10) with normal cardiac function. Myocardial and blood signal intensity were converted to concentration of Gd according to the in vitro calibration curve and fitted by a one-compartment model. K1 [first-order transfer constant from the blood to the myocardium for the gadolinium-diethylenetriamine-pentaacetic acid (Gd-DTPA)] and Vd (distribution volume of Gd-DTPA in myocardium) obtained from the fit of the MRI-derived perfusion curves were 0.72+/-0.22 (mL/min/g) and 15.3+/-5.22%. These results were in agreement with previous observations on animals and demonstrated that a reliable measurement of myocardial perfusion can be obtained by MRI in patients with an in vitro calibration procedure.     

High magnetic susceptibility coatings for visualisation of optical fibres on a specialised interventional MRI system

The aim of this study was to develop methods of visualising optical fibres on MRI scans for monitoring interstitial laser therapy. Scans were performed on a specialised MRI extremity scanner at 0.17 T. Optical fibres of 0.4 mm diameter used for delivering laser energy were coated with iron particles from a superferromagnetic contrast agent. MR images of the fibres were acquired using gradient echo sequences (TR/TE = 300/10, 1 mm in-plane, 3 mm slice) and assessed for fibre visibility. Coated fibres could be resolved as lines 2 ± 1 mm wide using the gradient echo sequence. Uncoated fibres were invisible on the sequences used for in vivo therapy monitoring due to partial volume averaging. It is concluded that optical fibre visualisation by MRI may be improved by coating with ferromagnetic particles. Biocompatibility requires further assessment, but direct coating appears to be a promising method for fibre visualisation in MR-guided laser therapy.