Dynamic susceptibility contrast (DSC) MR perfusion imaging can provide valuable perfusion metrics, including cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT). DSC is typically performed with a single-band single-echo EPI sequence, which has limited spatial and temporal resolution, and is prone to measurement errors due to contrast agent (CA) extravasation in cases of blood brain barrier (BBB) breakdown such as in brain tumors¹. In the present study, we proposed a novel multi-band multi-echo EPI (M2-EPI) DSC method for perfusion imaging with leakage correction, which can also provide additional vascular permeability parameters K^tran and v_e. Simulations were performed to study the effects of improved temporal resolution afforded by multi-band acquisition on the accuracy of perfusion parameter estimation.

DSC was performed with a Siemens Tim Trio 3T scanner equipped with a 32 channel head coil using a novel M2-EPI pulse sequence²: TR = 800 ms, TE = 18 / 41 /65 ms, FOV = 240 x 240 mm², matrix = 100 x 100, slice thickness/gap = 4/1 mm, 24 slices multiband-factor = 3, GRAPPA factor = 3. Gadobenate Dimeglumine (MultiHance, Bracco, Milan, Italy) was injected at 4 ml/s 10 seconds following initiation of the M2-EPI sequence. T₁-weighted MPRAGE imaging was also acquired after the contrast agent injection. Three patients with known brain tumors underwent MRI scans with the above sequences. The temporal signal following contrast injection can be expressed as the following equation:$$S(t,TE)=S_{0}(t)e^{-TE\cdot R_2^*(t)}+\sigma$$ $$S_{0}(t)=M_{0}\frac{1-e^{-TR\cdot R_{1}(t)}}{1-e^{-TR\cdot R_{1}(t)}\cos\theta}\sin\theta$$

where TE denotes the echo time, TR the repetition time, θ the flip angle, M₀ the equilibrium longitudinal magnetization, σ the noise, and R₁(t) the longitudinal relaxivity which is a function of CA leaked into the extravascular-extracellular space (ESS), R₂^*(t) the transverse relaxivity which is approximately a linear function of CA concentration in the intravascular space. CA leakage primarily causes a change in S₀(t). The acquisition of multi-echo images using M2-EPI allows the isolation of this effect by estimating S₀(t) and R₂^*(t) at each time point. The obtained R₂^*(t) dynamic volumes was subject to DSC modeling using a regularized deconvolution technique following automatic identification of the arterial input function to produce the CBF, CBV, MTT and Tmax images³. DSC processing was also performed on the second echo without leakage correction for comparison. The volume transfer constant K^trans and the EES volume fraction v_e were estimated from S₀(t) using the adiabatic approximation to the tissue homogeneity model¹. Simulations were performed to study the accuracy of permeability and perfusion estimations by varying temporal resolution (TR) and perfusion/permeability parameters. Gaussian noise was added based on SNR measurement of experimental data. Simulations were repeated 100 times to calculate the mean values and SD of the perfusion parameters. TR was varied from 400 to 3200 ms, CBF from 20 to 100 ml/100g/min, K^trans from 0.00 to 0.12 min^-1. MTT was set to 5 second and v_e to 0.25.

Figure 1 shows signal time courses of the DSC acquisition as well as calculated S₀(t) from voxels in healthy tissue and tumor. Increased S₀(t) following contrast injection can be observed in the tumor region due to extravasation of the contrast agent into the ESS caused by BBB breakdown. Figure 2 shows CBV and MTT maps calculated from the second echo without leakage correction, as well as from all three echoes with leakage correction in a patient with a brain tumor. CBV map without leakage correction underestimates the blood volume in the tumor, while leakage-corrected CBV map showed high blood volume in the tumor. Additional vascular permeability measures including the volume transfer constant K^trans and the EES volume fraction v_e maps were also obtained. Elevated permeability parameters K^trans and v_e in tumor suggest substantial leakage of contrast agent in this region. Multi-echo based leakage correction were successfully performed in all three patients with brain tumors and provided improved stimulation of the CBV in regions of brain tumor (Figure 3). Simulation showed that shorter TR is associated with more accurate estimation of CBF and MTT while differences in TR have minimal effects on the estimation of K^trans, v_e, and CBV (Figure 4).Perfusion and vascular permeability parameters can be simultaneously assessed through the multi-band multi-echo DSC perfusion imaging method. Multi-echo data acquisitions improve perfusion measurements by reducing or eliminating T₁-shortening effects due to CA extravasation, with additional permeability determination. Multi-band data acquisitions provide high temporal resolution, allowing more accurate perfusion quantification. In conclusion, M2-EPI DSC could facilitate accurate perfusion/permeability evaluation in brain tumor and thus can be used as a valuable diagnosis tool.