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. MTR
_Rex
^VOPVP
= 1/Z
_exp
-1/Z
_ref
, where the reference Z-spectra Z
_ref
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 MTR
_asym
, Lorentzian Difference (LD), VOPVP residual (ZVOPVP residual), the analytical solution and MTR
_Rex
^OPVP
, MTR
_Rex
^VOPVP
exhibited the largest difference between the two exchange rates. In vivo 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, MTR
_Rex
^VOPVP
images (3.5 ppm) exhibited a large area of hypointensity in the lesion hemisphere. In contrast, MTR
_asym
and the three-offsets method failed in detecting such changes, particularly for rats with little changes on T
_2w
and DWI images. Among all tested methods, MTR
_Rex
^VOPVP
achieved the highest contrast-to-noise ratio between lesion striatum and the contralateral. For amide, amine and NOE, Z
_residual
^VOPVP
and MTR
_Rex
^VOPVP
showed significant reduced signals in lesions compared to the contralateral, indicating lower pH with slower exchange. But Z-spectra and MTRasym signal did not show such difference. At later time points (6 hrs and 24 hrs), all methods displayed contrast between two hemispheres and MTR
_Rex
^VOPVP
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, MTR
_Rex
^VOPVP
may enhance CEST detection for ischemia.