SPICE (simultaneous perfusion imaging with consecutive echoes) is a method that permits simultaneous estimation of DSC- and DCE-MRI parameters, in one acquisition, using a single dose of contrast agent. Conventional algorithms are used to obtain the perfusion and permeability parameters corrected for confounding recirculation and leakage effects. The proposed method does not require administration of a loading dose of contrast agent (traditionally employed for DSC), and pre-contrast spin density and native T1 calibration scans (traditionally required for DCE) have been eliminated.
Brain tumors are the second- and fifth- most common cause of death in males and females under 40, respectively. Prognosis is dismal, even after decades of research, as reflected in the five-year survival rate of only 33%. The two most common contrast-agent perfusion techniques, dynamic susceptibility contrast (DSC) MRI and dynamic contrast enhanced (DCE) MRI, are used to probe the angiogenic character of brain tumors, which provide estimates of vascularity and vascular permeability. With the DSC-MRI method, the administration of a gadolinium-based contrast agent (GBCA) is used during image acquisition to generate parameters such as RCBV (relative cerebral blood volume), CBF (cerebral blood flow) and MTT (mean transit time), with RCBV being used most often for the evaluation of brain tumors. The resulting RCBV maps have demonstrated the ability to predict tumor grade (1-6) and survival (7), distinguish post-treatment radiation effects (PTRE) from recurrent tumor (8) and predict response to anti-angiogenic therapies (9-12). With DCE-MRI, the T1 effect of GBCA is exploited. Pharmacokinetic analysis of DCE-MRI data provides insight into the underlying tissue pathophysiology through estimation of the blood-brain volume transfer constant (Ktrans), fractional volume of the extravascular, extracellular space (EES) (Ve), plasma volume fraction (Vp) and the efflux rate constant from EES to plasma (kep) (13). While less common for brain tumors, DCE-MRI has also demonstrated promise to predict tumor grade (14) and response to treatment (15-17).
Despite its acknowledged potential, DSC-MRI has not achieved widespread clinical adoption. Many cite the lack of standardized approaches to acquire and post-process the data. For instance, preload dosing schemes of GBCA, which diminish contrast leakage effects and aid in the post-processing leakage correction, have (and are) being evaluated for quality purposes. The preload dose has been shown to improve accuracy and repeatability for predicting survival and monitoring treatment response (13-14) in single-echo DSC imaging. The challenges for conventional DCE imaging result in part for the need to obtain a precontrast T1 measurement and the collection of dynamic data with sufficiently high temporal resolution. Current fast gradient echo-echo planar imaging (GRE-EPI) methods are not capable of this temporal resolution. Also, the precontrast T1 measurement can be confounded by B1 inhomogeneities, requiring additional steps of B1 field mapping to correct (18-20). These additional steps increase scanner time as well as the potential for error, such as inter-series motion. Moreover, due to the increased concerns of nephrogenic systemic fibrosis (NSF) (21) and the
more recent concerns about GBCA deposits in the brain (22), the general use and administration of GBCA's have received additional scrutiny. The approach presented here, termed SPICE, accounts for multiple MR scanner and post-processing limitations that plague conventional DSC and DCE imaging, and has demonstrated the ability to simultaneously generate both sets of parameters from a single MR acquisition using a single, standard dose of GBCA. SPICE encodes two echoes simultaneously enabling both T1-weighted (short TE) and T2*-weighted (longer TE) to be obtained with a temporal resolution of about one second, and eliminates the need to acquire separate precontrast S0 and T1 calibrations scans, historically required for DCE-MRI. This, in turn, eliminates extra scanning at multiple flip angles which, in turn, saves time and can reduce variability due to inter-scan motion and B1 field inhomogeneities. Finally, SPICE DSC parameters are implicitly corrected for T1 leakage effects, and both DSC and DCE parameters can be corrected for residual susceptibility effects and T2/T2* effects arising from GBCA recirculation.
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