Enhanced CEST MRI Using the Residual of Inversed Z-Spectra for Ischemia Detection

Chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) had shown potential in sensing pH changes that occurs early in ischemic stroke. However, detection of mild acidosis is still challenging. To enhance CEST detection for ischemia, we proposed a quantification approach using the residual of inversed Z-spectra, i.e. <inline-formula> <tex-math notation="LaTeX">$MTR_{Rex}^{VOPVP} =1/{Z}_{exp} -1/{Z}_{ref}$ </tex-math></inline-formula>, where the reference Z-spectra <inline-formula> <tex-math notation="LaTeX">${Z}_{ref}$ </tex-math></inline-formula> was calculated using our previously developed Voxel-wise Optimization of Pseudo Voigt Profile (VOPVP). Simulations were performed at two different exchange rates of amide, representing different pH values. Among all tested quantification methods, including <italic>MTR</italic><sub>asym</sub>, Lorentzian Difference (LD), VOPVP residual (<inline-formula> <tex-math notation="LaTeX">$Z_{residual}^{VOPVP}$ </tex-math></inline-formula>), the analytical solution and <inline-formula> <tex-math notation="LaTeX">$MTR_{Rex}^{VOPVP} $ </tex-math></inline-formula>, <inline-formula> <tex-math notation="LaTeX">$MTR_{Rex}^{VOPVP} $ </tex-math></inline-formula> exhibited the largest difference between the two exchange rates. In <italic>vivo</italic> CEST-MRI was performed at 7 Tesla in rat brain, at 2 hours after transient ischemia by middle cerebral artery occlusion. Firstly, Z-spectra images were assessed at multiple offsets using histogram analysis, with 3.5 and −3.5 ppm exhibiting significant changes between normal rats and stroke rats (n = 5 each). For all stroke rats, <inline-formula> <tex-math notation="LaTeX">$MTR_{Rex}^{VOPVP} $ </tex-math></inline-formula> images (3.5 ppm) exhibited a large area of hypointensity in the lesion hemisphere. In contrast, <inline-formula> <tex-math notation="LaTeX">${MTR}_{asym}$ </tex-math></inline-formula> and the three-offsets method failed in detecting such changes, particularly for rats with little changes on T<sub>2</sub>w and DWI images. Among all tested methods, <inline-formula> <tex-math notation="LaTeX">$MTR_{Rex}^{VOPVP} $ </tex-math></inline-formula> achieved the highest contrast-to-noise ratio between lesion striatum and the contralateral. For amide, amine and NOE, <inline-formula> <tex-math notation="LaTeX">$Z_{residual}^{VOPVP} \mathbf {}$ </tex-math></inline-formula> and <inline-formula> <tex-math notation="LaTeX">$MTR_{Rex}^{VOPVP} $ </tex-math></inline-formula> showed significant reduced signals in lesions compared to the contralateral, indicating lower pH with slower exchange. But Z-spectra and <inline-formula> <tex-math notation="LaTeX">${MTR}_{asym}$ </tex-math></inline-formula> signal did not show such difference. At later time points (6 hrs and 24 hrs), all methods displayed contrast between two hemispheres and <inline-formula> <tex-math notation="LaTeX">$MTR_{Rex}^{VOPVP} $ </tex-math></inline-formula> still show the largest contrast between the two hemisphere. Histology confirmed the edema and other damage in the ipsilateral hemisphere at 2 hours post transient ischemia. In summary, <inline-formula> <tex-math notation="LaTeX">$MTR_{Rex}^{VOPVP} $ </tex-math></inline-formula> may enhance CEST detection for ischemia.