Assessment of a simplified spin and gradient echo (sSAGE) approach for human brain tumor perfusion imaging.

The goal of this study was to validate a simplified spin- and gradient-echo (sSAGE) approach to obtain T1-corrected dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) data in a clinical brain tumor population. A five-echo SAGE sequence was used to acquire DSC-MRI data (n=8 patients, 3 primary glioma, and 5 brain metastases). The ΔR2⁎ and ΔR2 time series obtained from a nonlinear fit of all echoes (SAGE) were compared to ΔR2⁎ and ΔR2 time series obtained analytically (sSAGE) using three echoes (two GEs and one SE). Through the use of multiple echoes, both methods removed T1 leakage effects from the ΔR2⁎ and ΔR2 time series, and the sSAGE ΔR2⁎ and ΔR2 time series were highly correlated with those from SAGE, with average correlations of 0.9. The resulting hemodynamic parameters included GE and SE cerebral blood volume (CBV), cerebral blood flow (CBF), mean vessel diameter (mVD), volume transfer constant (Ktrans), and volume fraction of the extravascular extracellular space (ve). For each metric, there was good correlation (>0.86) between sSAGE and SAGE, with no significant differences. The sSAGE method provides T1-corrected GE and SE DSC-MRI parameters in an efficient and clinically feasible manner.

Assessing tumor cytoarchitecture using multiecho DSC-MRI derived measures of the transverse relaxivity at tracer equilibrium (TRATE).

PURPOSE: In brain tumor dynamic susceptibility contrast (DSC)-MRI studies, multiecho acquisition methods are used to quantify the dynamic changes in T1 and T2 * that occur when contrast agent (CA) extravasates. Such methods also enable the estimation of the effective tissue CA transverse relaxivity. The goal of this study was to evaluate the sensitivity of the transverse relaxivity at tracer equilibrium (TRATE) to tumor cytoarchitecture. METHODS: Computational and in vitro studies were used to evaluate the biophysical basis of TRATE. In 9L, C6, and human brain tumors, TRATE, the apparent diffusion coefficient (ADC), the CA transfer constant (K(trans) ), the extravascular extracellular volume fraction (ve ), and histological data were compared. RESULTS: Simulations and in vitro results indicate that TRATE is highly sensitive to variations in cellular properties such as cell size and density. The histologic cell density and TRATE values were significantly higher in 9L tumors as compared to C6 tumors. In animal and human tumors, a voxel-wise comparison of TRATE with ADC, ve , and K(trans) maps showed low spatial correlation. CONCLUSION: The assessment of TRATE is clinically feasible and its sensitivity to tissue cytoarchitectural features not present in other imaging methods indicate that it could potentially serve as a unique structural signature or "trait" of cancer.

Assessment of a combined spin- and gradient-echo (SAGE) DSC-MRI method for preclinical neuroimaging.

The goal of this study was to optimize and validate a combined spin- and gradient-echo (SAGE) sequence for dynamic susceptibility-contrast magnetic resonance imaging to obtain hemodynamic parameters in a preclinical setting. The SAGE EPI sequence was applied in phantoms and in vivo rat brain (normal, tumor, and stroke tissue). Partial and full Fourier encoding schemes were implemented and characterized. Maps of cerebral blood volume (CBV), cerebral blood flow (CBF), mean transit time (MTT), vessel size index (VSI), volume transfer constant (K(trans)), and volume fraction of the extravascular extracellular space (ve) were obtained. Partial Fourier encoding provided shortened echo times with acceptable signal-to-noise ratio and temporal stability, thus enabling reliable characterization of T2, T2(*) and T1 in both phantoms and rat brain. The hemodynamic parameters CBV, CBF, and MTT for gradient-echo and spin-echo contrast were determined in tumor and stroke; VSI, K(trans), and ve were also computed in tumor tissue. The SAGE EPI sequence allows the acquisition of multiple gradient- and spin-echoes, from which measures of perfusion, permeability, and vessel size can be obtained in a preclinical setting. Partial Fourier encoding can be used to minimize SAGE echo times and reliably quantify dynamic T2 and T2(*) changes. This acquisition provides a more comprehensive assessment of hemodynamic status in brain tissue with vascular and perfusion abnormalities.

Evaluation of a multiple spin- and gradient-echo (SAGE) EPI acquisition with SENSE acceleration: applications for perfusion imaging in and outside the brain.

Perfusion-based changes in MR signal intensity can occur in response to the introduction of exogenous contrast agents and endogenous tissue properties (e.g. blood oxygenation). MR measurements aimed at capturing these changes often implement single-shot echo planar imaging (ssEPI). In recent years ssEPI readouts have been combined with parallel imaging (PI) to allow fast dynamic multi-slice imaging as well as the incorporation of multiple echoes. A multiple spin- and gradient-echo (SAGE) EPI acquisition has recently been developed to allow measurement of transverse relaxation rate (R2 and R2(*)) changes in dynamic susceptibility contrast (DSC)-MRI experiments in the brain. With SAGE EPI, the use of PI can influence image quality, temporal resolution, and achievable echo times. The effect of PI on dynamic SAGE measurements, however, has not been evaluated. In this work, a SAGE EPI acquisition utilizing SENSE PI and partial Fourier (PF) acceleration was developed and evaluated. Voxel-wise measures of R2 and R2(*) in healthy brain were compared using SAGE EPI and conventional non-EPI multiple echo acquisitions with varying SENSE and PF acceleration. A conservative SENSE factor of 2 with PF factor of 0.73 was found to provide accurate measures of R2 and R2(*) in white (WM) (rR2=[0.55-0.79], rR2*=[0.47-0.71]) and gray (GM) matter (rR2=[0.26-0.59], rR2*=[0.39-0.74]) across subjects. The combined use of SENSE and PF allowed the first dynamic SAGE EPI measurements in muscle, with a SENSE factor of 3 and PF factor of 0.6 providing reliable relaxation rate estimates when compared to multi-echo methods. Application of the optimized SAGE protocol in DSC-MRI of high-grade glioma patients provided T1 leakage-corrected estimates of CBV and CBF as well as mean vessel diameter (mVD) and simultaneous measures of DCE-MRI parameters K(trans) and ve. Likewise, application of SAGE in a muscle reperfusion model allowed dynamic measures of R2', a parameter that has been shown to correlate with muscle oxy-hemoglobin saturation.

A comparison of individual and population-derived vascular input functions for quantitative DCE-MRI in rats.

Dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) can quantitatively and qualitatively assess physiological characteristics of tissue. Quantitative DCE-MRI requires an estimate of the time rate of change of the concentration of the contrast agent in the blood plasma, the vascular input function (VIF). Measuring the VIF in small animals is notoriously difficult as it requires high temporal resolution images limiting the achievable number of slices, field-of-view, spatial resolution, and signal-to-noise. Alternatively, a population-averaged VIF could be used to mitigate the acquisition demands in studies aimed to investigate, for example, tumor vascular characteristics. Thus, the overall goal of this manuscript is to determine how the kinetic parameters estimated by a population based VIF differ from those estimated by an individual VIF. Eight rats bearing gliomas were imaged before, during, and after an injection of Gd-DTPA. K(trans), ve, and vp were extracted from signal-time curves of tumor tissue using both individual and population-averaged VIFs. Extended model voxel estimates of K(trans) and ve in all animals had concordance correlation coefficients (CCC) ranging from 0.69 to 0.98 and Pearson correlation coefficients (PCC) ranging from 0.70 to 0.99. Additionally, standard model estimates resulted in CCCs ranging from 0.81 to 0.99 and PCCs ranging from 0.98 to 1.00, supporting the use of a population based VIF if an individual VIF is not available.

Comparison of dynamic contrast-enhanced MRI and quantitative SPECT in a rat glioma model.

Pharmacokinetic modeling of dynamic contrast-enhanced (DCE) MRI data provides measures of the extracellular-extravascular volume fraction (v(e) ) and the volume transfer constant (K(trans) ) in a given tissue. These parameter estimates may be biased, however, by confounding issues such as contrast agent and tissue water dynamics, or assumptions of vascularization and perfusion made by the commonly used model. In contrast to MRI, radiotracer imaging with SPECT is insensitive to water dynamics. A quantitative dual-isotope SPECT technique was developed to obtain an estimate of v(e) in a rat glioma model for comparison with the corresponding estimates obtained using DCE-MRI with a vascular input function and reference region model. Both DCE-MRI methods produced consistently larger estimates of v(e) in comparison to the SPECT estimates, and several experimental sources were postulated to contribute to these differences.