Combined spin- and gradient-echo perfusion MRI [electronic resource]
Keywords: Bioengineering.

Dynamic susceptibility-contrast perfusion-weighted imaging (DSC PWI) is a magnetic resonance imaging (MRI) technique that measures the delivery of arterial blood to the tissue capillary bed using a contrast agent. DSC PWI can reveal important information in stroke patients by assessing hypoperfused brain tissue, while in tumor patients it is used to evaluate the tumor vasculature. For clinical applications, DSC PWI relies on both accurate and rapid image formation. Gradient-echo echo-planar imaging (EPI) is the most commonly used MRI pulse sequence for DSC PWI, mainly due to its fast image acquisition capability, a relatively high contrast-to-noise ratio, and its availability on most clinical MRI systems. However, quantification of perfusion parameters with gradient-echo EPI remains challenging. Gradient-echo EPI is most sensitive to larger vessels, including arteries and veins. These measurements do not provide specific information about true perfusion within the microvasculature, the site of oxygen and nutrient extraction to brain tissue. To acquire perfusion measurements that are more confined to the microvasculature, spin-echo EPI acquisition techniques have been proposed. Spin-echo EPI is most sensitive to smaller vessels, providing a clear advantage over gradient-echo EPI. Unfortunately, spin-echo EPI suffers from lower sensitivity to the contrast agent passage, and the determination of arterial contrast agent concentrations required for quantitative perfusion MRI remains an unsolved problem when using spin-echo EPI data. In the first part of this dissertation, a combined approach for simultaneous spin- and gradient-echo (SAGE) perfusion MRI is presented. The proposed imaging technique combines the advantages of higher overall sensitivity to contrast agent passage of gradient-echo EPI with superior microvascular selectivity of spin-echo EPI, resulting in complementary perfusion information. The combined method enabled improved detection of abnormal brain perfusion compared to conventionally processed DSC PWI data, as illustrated in cases of stroke and brain tumors. Specifically, reduced sensitivity to larger blood vessels of spin-echo data generated from SAGE perfusion MRI measurements improved the visibility of hypoperfused tissue. In the second part, the gradient-echo and spin-echo signal contributions to the proposed SAGE perfusion MRI acquisition technique are analyzed in detail. The development of an optimized pair of MRI excitation and refocusing pulses enhanced the contrast-to-noise ratio of the spin-echo signal. Moreover, augmented perfusion parameter estimation improved the accuracy of both gradient-echo and spin-echo signals to reduce perfusion quantification errors. In the last part, implications of contrast agent leakage from the brain vasculature are discussed. Considerable contrast agent extravasation, caused by blood-brain barrier leakage commonly observed in brain tumors and subacute strokes, results in additional quantification errors of brain perfusion parameters. To mitigate these errors, pharmacokinetic modeling of contrast agent distribution was applied to SAGE perfusion MRI data. Intravascular contrast agent concentrations could then be separated from extravascular concentrations, resulting in leakage-corrected perfusion data. Moreover, the applied pharmacokinetic modeling approach facilitated the extraction of permeability parameters. The combined evaluation of perfusion and permeability parameters, derived from SAGE perfusion MRI data, showed potential utility in brain tumor imaging with the goal of improving the diagnostic value of perfusion MRI in the assessment of brain tumor progression.