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).     

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.     

Arterial input functions determined from MR signal magnitude and phase for quantitative dynamic contrast‐enhanced MRI in the human pelvis

Dynamic contrast‐enhanced (DCE) MRI is often used to measure the transfer constant (K^trans) and distribution volume (v_e) in pelvic tumors. For optimal accuracy and reproducibility, one must quantify the arterial input function (AIF). Unfortunately, this is challenging due to inflow and signal saturation. A potential solution is to use MR signal phase (?), which is relatively unaffected by these factors. We hypothesized that phase‐derived AIFs (AIF_?) would provide more reproducible K^trans and v_e values than magnitude‐derived AIFs (AIF_|S|). We tested this in 27 prostate dynamic contrast‐enhanced MRI studies (echo time = 2.56 ms, temporal resolution = 13.5 s), using muscle as a standard. AIF_? peak amplitude varied much less as a function of measurement location (inferior–superior) than AIF_|S| (5.6 ± 0.6 mM vs. 2.6 ± 1.5 mM), likely as a result of ? inflow insensitivity. However, our main hypothesis was not confirmed. The best AIF_|S| provided similar reproducibility versus AIF_? (interpatient muscle K^trans = 0.039 ± 0.021 min^?1 vs. 0.037 ± 0.025 min^?1, v_e = 0.090 ± 0.041 vs. 0.062 ± 0.022, respectively). Magn Reson Med, 2011. © 2011 Wiley‐Liss, Inc.     

Contrast agents in functional MR imaging

Contrast agents have greatly expanded the role of MR imaging (MRI) to allow assessment of physiologic, or “functional,” parameters. Although activation mapping generally does not require contrast agents, other forms of functional MRI, including mapping of cerebral hemodynamics (eg, perfusion imaging), are best done with the use of contrast agents. Serial echo planar images are obtained after bolus injection of lanthanide chelates. Application of susceptibility contrast physics and standard tracer kinetic principles permits generation of relative cerebral blood volume maps. Deconvolution of cerebral blood flow and mean transit time parameters is also possible within technical limitations. By using diffusion and perfusion pulse sequences, an imaging correlate to the ischemic penumbra can be identified. Functional MRI perfusion imaging of intraaxial tumors is analogous to positron emission tomography for delineation of metabolic activity, yet may be even more sensitive to neovascularity and possesses improved image quality. Clinical applications include biopsy site selection and postirradiation follow-up. Further improvements in data analysis and map generation techniques may improve diagnostic accuracy and utility.     

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.     

Arterial input function measurements for bolus tracking perfusion imaging in the brain

Imaging of cerebral perfusion by tracking the first passage of an exogenous paramagnetic contrast agent (termed dynamic susceptibility contrast, MRI) has been used in the clinical practice for about a decade. However, the primary goal of dynamic susceptibility contrast MRI to directly quantify the local cerebral blood flow remains elusive. The major challenge of dynamic susceptibility contrast MRI is to measure the contrast inflow to the brain, i.e., the arterial input function. The measurement is complicated by the limited dynamic range of MRI pulse sequences that are optimized for a good contrast in brain tissue but are suboptimal for a much higher tracer concentration in arterial blood. In this work, we suggest a novel method for direct arterial input function quantification. The arterial input function is measured in the carotid arteries with a dedicated plug‐in to the conventional pulse sequence to enable resolution of T₂ on the order of a millisecond. The new technique is compatible with the clinical measurement protocols. Applied to the pig model (N = 13), the method demonstrates robustness of the arterial input function measurement. The cardiac output and cerebral blood volume, obtained without adjustable parameters, agree well with positron emission tomography measurements and values found in the literature. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc.     

Pitfalls in MR measurement of tissue blood flow with intravascular tracers: Which mean transit time?

Measuring tissue blood flow with NMR imaging of intravascular tracers is more difficult than measurements of tissue blood volume. One major obstacle to the application of the Central Volume Principle is the direct measurement of the mean transit time. In this note, we demonstrate that mean transit time (MTT), which relates tissue blood volume to blood flow via the Central Volume Principle, is not the first moment of the concentration-time curve for MR or CT imaging of purely intravascular tracers. However, while first moment methods cannot be used by themselves to determine absolute flow, we show that transit curves may provide a useful relative measure of flow, for example, by considering ratios of the first moments.     

Magnetic resonance brain perfusion imaging with voxel-specific arterial input functions

PURPOSE: To propose an automatic method for estimating voxel-specific arterial input functions (AIFs) in dynamic contrast brain perfusion imaging. MATERIALS AND METHODS: Voxel-specific AIFs were estimated blindly using the theory of homomorphic transformations and complex cepstrum analysis. Wiener filtering was used in the subsequent deconvolution. The method was verified using simulated data and evaluated in 10 healthy adults. RESULTS: Computer simulations accurately estimated differently shaped, normalized AIFs. Simple Wiener filtering resulted in underestimation of flow values. Preliminary in vivo results showed comparable cerebral flow value ratios between gray matter (GM) and white matter (WM) when using blindly estimated voxel-specific AIFs or a single manually selected AIF. Significant differences (P < or = 0.0125) in mean transit time (MTT) and time-to-peak (TTP) in GM compared to WM was seen with the new method. CONCLUSION: Initial results suggest that the proposed method can replace the tedious and difficult task of manually selecting an AIF, while simultaneously providing better differentiation between time-dependent hemodynamic parameters.     

MR imaging contrast agents — what's in a name?

The purpose of this brief review is to reduce the confusion surrounding the nomenclature of MRI contrast agents. There are several different categories of contrast agents for potential use in human diagnosis and several alternative names for each contrast agent, an array of choices that actually changes over time. This review describes the general process by which these various agents are named, presents one general categorization by which these agents can be considered, and provides a concise table to which readers can refer to identify the proper name to use for each of the agents that has thus far been administered to humans.     

Comparison of different contrast agents and doses for quantitative MR myocardial perfusion imaging

PURPOSE: To investigate three different contrast agents at different injection volumes for repetitive quantitative multislice myocardial perfusion imaging using the prebolus technique. MATERIALS AND METHODS: Two consecutive prebolus perfusion measurements were performed on a 1.5 T scanner using identical injection volumes for the first and second examination to test the reproducibility for possible rest and stress examination in normal volunteers. Either 1-8 mL, 1-12 mL Gd-DTPA, 1-4 mL, 1-6 mL, 1-9 mL Gd-BOPTA, or 1-4 mL, 1-6 mL gadobutrol were applied. RESULTS: In cases where injection volumes were sufficiently small, there was no indication of significant differences in quantitative perfusion values with respect to the different contrast agents. Increasing the bolus volume improved the contrast-to-noise ratio (CNR) but led to saturation effects and underestimation of the true perfusion. The highest CNR was measured for gadobutrol (6 mL, p < 0.0005 compared to 8 mL Gd-DTPA). The smallest difference of perfusion values between the first and the second prebolus examination was found for Gd-BOPTA (p < or = 0.006 compared Gd-DTPA). CONCLUSION: Prebolus examinations for quantitative myocardial perfusion imaging are possible with all three contrast agents for sufficient small injection volumes. Gd-BOPTA was found to be advantageous for a combined quantitative rest and stress examination.     

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.     

Fast mapping of myocardial blood flow with MR first-pass perfusion imaging.

Accurate and fast quantification of myocardial blood flow (MBF) with MR first-pass perfusion imaging techniques on a pixel-by-pixel basis remains difficult due to relatively long calculation times and noise-sensitive algorithms. In this study, Zierler's central volume principle was used to develop an algorithm for the calculation of MBF with few assumptions on the shapes of residue curves. Simulation was performed to evaluate the accuracy of this algorithm in the determination of MBF. To examine our algorithm in vivo, studies were performed in nine normal dogs. Two first-pass perfusion imaging sessions were performed with the administration of the intravascular contrast agent Gadomer at rest and during dipyridamole-induced vasodilation. Radiolabeled microspheres were injected to measure MBF at the same time. MBF measurements in dogs using MR methods correlated well with the microsphere measurements (R2=0.96, slope=0.9), demonstrating a fair accuracy in the perfusion measurements at rest and during the vasodilation stress. In addition to its accuracy, this method can also be optimized to run relatively fast, providing potential for fast and accurate myocardial perfusion mapping in a clinical setting.     

Estimation of absolute myocardial blood flow during first-pass MR perfusion imaging using a dual-bolus injection technique: comparison to single-bolus injection method

PURPOSE: To compare the dual-bolus to single-bolus quantitative first-pass magnetic resonance myocardial perfusion imaging for estimation of absolute myocardial blood flow (MBF). MATERIALS AND METHODS: Dogs had local hyperemia of MBF in the left anterior descending (LAD) coronary artery (intracoronary adenosine). Animals (n = 6) had sequential single- and dual-bolus perfusion studies with microsphere determination of absolute MBF. Perfusion imaging was performed using a saturation-recovery gradient-echo sequence. Absolute MBF was by Fermi function deconvolution and compared to transmural, endocardial, and epicardial microsphere values in the same region of interest (ROI). RESULTS: Signal and contrast were significantly higher for the dual-bolus perfusion images. The correlation with MBF by microspheres was r = 0.94 for the dual-bolus method and r = 0.91 for the single-bolus method. There was no significant difference between MRI and microsphere MBF values for control or hyperemic zones for transmural segments for either technique. When the ROI was reduced to define endocardial and epicardial zones, single-bolus MR first-pass imaging significantly overestimated MBF and had a significantly larger absolute error vs. microspheres when compared to dual-bolus perfusion. CONCLUSION: Both single-bolus and dual-bolus perfusion methods correlate closely with MBF but the signal and contrast of the dual-bolus images are greater. With smaller nontransmural ROIs where signal is reduced, the dual-bolus method appeared to provide slightly more accurate results.     

Evaluation of tissue perfusion in a rat model of hind-limb muscle ischemia using dynamic contrast-enhanced magnetic resonance imaging

PURPOSE: To evaluate the feasibility of using dynamic contrast-enhanced magnetic resonance imaging (MRI) for assessment of muscle perfusion in a rat model of hind-limb ischemia. MATERIALS AND METHODS: The acute alteration and chronic recovery in muscle perfusion and perfusion reserve after femoral artery ligation were quantified using the maximum Gd-DTPA uptake rate obtained by a T(1)-weighted gradient-recalled echo sequence. Radionuclide-labeled microsphere blood flow measurements were performed for comparison with the MR perfusion measurement on a separate set of animals. RESULTS: After femoral artery ligation, a significant reduction in resting muscle perfusion was only observed at 1 hour post-ligation during the 28-day follow-up period. Muscle perfusion reserve was severely diminished following the ligation. Despite significant recovery over time, perfusion reserve to the ligated limb reached only 63% of the perfusion capacity in the unaffected limb by 42 days post ligation. A strong correlation (r = 0.86) between MR perfusion and microsphere blood flow measurements was observed for evaluation of relative changes in muscle perfusion. CONCLUSION: Dynamic contrast-enhanced MRI with Gd-DTPA is useful to assess time-dependent changes in muscle perfusion and perfusion reserve in this hind-limb ischemia model.     

Cepstral estimation of arterial input functions in brain perfusion imaging

PURPOSE: To investigate voxel-specific arterial input functions (AIFs) obtained through blind deconvolution using complex cepstrum liftering. Blindly estimated AIFs have the potential of reducing dispersion effects in perfusion maps and are completely user-independent. MATERIALS AND METHODS: The separability of AIFs and tissue residue functions (TRFs) in the cepstrum domain is exemplified using synthetic data, wherein the AIFs are modeled as gamma variate functions and the TRFs are modeled as exponential or linear functions. A novel separation filter is suggested. Initial results of different blind methods are illustrated using data from a stroke patient. RESULTS: The AIFs and the TRFs partly overlap in the complex cepstrum. The AIFs, obtained using the new separation filter, are closer to those obtained using noncepstral blind separation. CONCLUSION: The overlap of AIFs and TRFs in the complex cepstrum makes reliable separation of the two functions more difficult than previously described. Comparison to noncepstral blind methods suggests that similar optima are found using the new separation filter.     

Detection of liver metastases using gadoxetic-enhanced dynamic and 10- and 20-minute delayed phase MR imaging

Purpose:

To assess the incremental value of hepatobiliary phase images in gadoxetate disodium‐enhanced magnetic resonance imaging (MRI), and to compare diagnostic accuracy and lesion conspicuity on 10‐ and 20‐minute delayed images for preoperative detection of hepatic metastases with subgroup analysis according to size and history of chemotherapy.

Materials and Methods:

Forty‐six patients with 107 metastases who underwent surgery after gadoxetate disodium‐enhanced MRI were evaluated. Four observers independently interpreted three sets: dynamic set comprising precontrast T1‐, T2‐weighted, and dynamic images; 10‐minute set comprising dynamic set and 10‐minute delayed; 20‐minute set comprising 10‐minute set and 20‐minute delayed. Diagnostic accuracy was compared with subgroup analysis. Liver‐to‐lesion signal ratio (SR) was calculated using the region of interest method and compared.

Results:

Mean A_z and sensitivities were significantly higher for 10‐ (A_z = 0.894, sensitivity = 95.6%) and 20‐minute (0.910, 97.2%) than dynamic set (0.813, 79.9%) (P < 0.001), with no significant difference between 10‐ and 20‐minute sets (P = 0.140). In patients with small (≤1 cm) metastases and a history of chemotherapy, sensitivities were significantly higher with 10‐ (88.2%) and 20‐minute (91.6%) sets than dynamic set (48.6%) (P < 0.001). SR was significantly higher for 10‐ and 20‐minute delayed than precontrast and dynamic, with significantly higher SR on 20‐ than 10‐minute delayed.

Conclusion:

Regardless of size or prior chemotherapy, detection of hepatic metastases was significantly improved by adding hepatobiliary phase images without significant differences between 10‐ and 20‐minute delayed. J. Magn. Reson. Imaging 2012;35:635‐643. © 2011 Wiley Periodicals, Inc.