In vivo quantification of contrast agent concentration using the induced magnetic field for time‐resolved arterial input function measurement with MRI

Abstract

For pharmacokinetic modeling of tissue physiology, there is great interest in measuring the arterial input function (AIF) from dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) using paramagnetic contrast agents. Due to relaxation effects, the measured signal is a nonlinear function of the injected contrast agent concentration and depends on sequence parameters, system calibration, and time-of-flight effects, making it difficult to accurately measure the AIF during the first pass. Paramagnetic contrast agents also affect susceptibility and modify the magnetic field in proportion to their concentration. This information is contained in the MR signal phase which is discarded in a typical image reconstruction. However, quantifying AIF through contrast agent susceptibility induced phase changes is made difficult by the fact that the induced magnetic field is nonlocal and depends upon the contrast agent spatial distribution and thus on organ and vessel shapes. In this article, the contrast agent susceptibility was quantified through inversion of magnetic field shifts using a piece-wise constant model. Its feasibility is demonstrated by a determination of the AIF from the susceptibility-induced field changes of an intravenous bolus. After in vitro validation, a time-resolved two-dimensional (2D) gradient echo scan, triggered to diastole, was performed in vivo on the aortic arch during a bolus injection of 0.1 mmol/kg Gd-DTPA. An approximate geometrical model of the aortic arch constructed from the magnitude images was used to calculate the spatial variation of the field associated with the bolus. In 14 subjects, Gd concentration curves were measured dynamically (one measurement per heart beat) and indirectly validated by independent 2D cine phase contrast flow rate measurements. Flow rate measurements using indicator conservation with this novel quantitative susceptibility imaging technique were found to be in good agreement with those obtained from the cine phase contrast measurements in all subjects. Contrary to techniques that rely on intensity, the accuracy of this signal phase based method is insensitive to factors influencing signal intensity such as flip angle, coil sensitivity, relaxation changes, and time-of-flight effects extending the range of pulse sequences and contrast doses for which quantitative DCE-MRI can be applied.

Comparison of the Diagnostic Accuracy of DSC- and Dynamic Contrast-Enhanced MRI in the Preoperative Grading of Astrocytomas

“…This limitation can be overcome by using phase images to derive the VIF. [9][10][11][12][13] Phase measurements are less biased by intensity changes from inflow and relaxation effects. Magnitude-derived vascular input functions can underestimate the contrast concentration measurement during the first pass (if Ͼ5 mmol/L), especially when a high-relaxivity agent is used.…”

“…Magnitude-derived vascular input functions can underestimate the contrast concentration measurement during the first pass (if Ͼ5 mmol/L), especially when a high-relaxivity agent is used. 9 One limitation of our study is the estimation of the precontrast T1 map by using a variable flip angle technique with only 2 flip angles. This approach is sensitive to B1 variation and could introduce errors in the conversion of DCE signal to concentration.…”

“…7,8 Recently, some au-thors have suggested that measuring changes in the phase of the MR signal rather than its magnitude following gadolinium injection might provide a more accurate VIF because phase change inside the vessel is linearly related to the concentration of contrast agent. [9][10][11][12] While measurement of precontrast tissue T1 is typically included in DCE-MR imaging studies, an additional measurement of tissue T1 postinjection ("bookend" method) might also improve the reproducibility of perfusion values in gliomas. 13,14 To our knowledge, there have been few comparative studies between DCE and DSC imaging in patients with gliomas.…”

Phase-based arterial input functions in humans applied to dynamic contrast-enhanced MRI: potential usefulness and limitations

“…6b. The imaging site was selected to ensure good agreement with the infinite cylinder assumption, but the use of advanced mathematical models to compensate for geometric effects should be considered [18]. A final potential source of low-frequency errors were partial volume effects, but these were most likely of less importance due to the inflow effects, ensuring much higher intensity in the arterial ROI compared with the surrounding background [16].…”

“…A favourable SNR has also been demonstrated [9], and the accuracy of phase AIFs has been evaluated by cross validation against external monitoring of a radioactive tracer [10]. However, in spite of numerous encouraging results, the phase-based AIF approach has mainly been demonstrated by phantom experiments, in animal models and in human in vivo examples [5,6,[8][9][10][11][12][13][14][15][16][17], while large-scale systematic evaluations of typical patient materials have been limited [7,18,19]. Furthermore, phase AIFs have mainly been introduced in connection with DSC-MRI, while applications to AIFs and venous output functions (VOFs) in DCE-MRI have been very sparse [14,16,19].…”