Novel gradient echo sequence-based amide proton transfer magnetic resonance imaging in hyperacute cerebral infarction

In the progression of ischemia, pH is important and is essential in elucidating the association between metabolic disruption, lactate formation, acidosis and tissue damage. Chemical exchange-dependent saturation transfer (CEST) imaging can be used to detect tissue pH and, in particular, a specific form of CEST magnetic resonance imaging (MRI), termed amide proton transfer (APT) MRI, which is sensitive to pH and can detect ischemic lesions, even prior to diffusion abnormalities. The critical parameter governing the ability of CEST to detect pH is the sequence. In the present study, a novel strategy was used, based on the gradient echo sequence (GRE), which involved the insertion of a magnetization transfer pulse in each repetition time (TR) and minimizing the TR for in vivo APT imaging. The proposed GRE-APT MRI method was initially verified using a tissue-like pH phantom and optimized MRI parameters for APT imaging. In order to assess the range of acute cerebral infarction, rats (n=4) were subjected to middle cerebral artery occlusion (MCAO) and MRI scanning at 7 telsa (T). Hyperacute ischemic tissue damage was characterized using multiparametric imaging techniques, including diffusion, APT and T(2)-Weighted MRI. By using a magnetization transfer pulse and minimizing TR, GRE-APT provided high spatial resolution and a homogeneous signal, with clearly distinguished cerebral anatomy. The GRE-APT and diffusion MRI were significantly correlated with lactate content and the area of cerebral infarction in the APT and apparent diffusion coefficient (ADC) maps matched consistently during the hyperacute period. In addition, compared with the infarction area observed on the ADC MRI map, the APT map contained tissue, which had not yet been irreversibly damaged. Therefore, GRE-APT MRI waa able to detect ischemic lactic acidosis with sensitivity and spatiotemporal resolution, suggesting the potential use of pH MRI as a surrogate imaging marker of impaired tissue metabolism for the diagnosis and prognosis of hyperacute stroke.