Clinical translation of amide proton transfer (APT) MRI for ischemic stroke: a systematic review (2003–2020)

Abstract

Amide proton transfer (APT) magnetic resonance imaging (MRI) is a pH-sensitive imaging technique that can potentially complement existing clinical imaging protocol for the assessment of ischemic stroke. This review aims to summarize the developments in the clinical research of APT imaging of ischemic stroke after 17 years of progress since its first preclinical study in 2003. Three electronic databases: PubMed, Scopus, and Cochrane Library were systematically searched for articles reporting clinical studies on APT imaging of ischemic stroke. Only articles in English published between 2003 to 2020 that involved patients presenting ischemic stroke-like symptoms that underwent APT MRI were included. Of 1,093 articles screened, 14 articles met the inclusion criteria with a total of 282 patients that had been scanned using APT imaging. Generally, the clinical studies agreed APT effect to be hypointense in ischemic tissue compared to healthy tissue, allowing for the detection of ischemic stroke. Other uses of APT imaging have also been investigated in the studies, including penumbra identification, predicting long term clinical outcome, and serving as a biomarker for supportive treatment monitoring. The published results demonstrated the potential of APT imaging in these applications, but further investigations and larger trials are needed for conclusive evidence. Future studies are recommended to report the result of asymmetry analysis at 3.5 ppm along with the findings of the study to reduce this contribution to the heterogeneity of experimental methods observed and to facilitate effective comparison of results between studies and centers. In addition, it is important to focus on the development of fast 3D imaging for full volumetric ischemic tissue assessment for clinical translation.

Review and consensus recommendations on clinical APT‐weighted imaging approaches at 3T: Application to brain tumors

“…The basics of APTw imaging have been explained in several previous review articles. [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21] Briefly, APTw imaging is generally obtained by RF saturation labeling of the water-exchangeable backbone amide proton pool of proteins and peptides, followed by a physical transfer (chemical exchange) of these saturated amide protons to bulk water protons, resulting in a decrease in their magnetization. Theoretically, the CEST effect of amide protons can be expressed in terms of a so-called amide proton transfer ratio (APTR), a formulation that describes the different parameters on which the CEST effect depends.…”

“…The basics of APTw imaging have been explained in several previous review articles 4–21 . Briefly, APTw imaging is generally obtained by RF saturation labeling of the water‐exchangeable backbone amide proton pool of proteins and peptides, followed by a physical transfer (chemical exchange) of these saturated amide protons to bulk water protons, resulting in a decrease in their magnetization.…”

Magnetic Resonance pH Imaging in Stroke – Combining the Old With the New

“…Although the use of this in ischemic stroke may be limited due to the nature of the disease, the potential of measuring both the intra-and extra-cellular pH using a single imaging sequence with clinically approved contrast agents can lead to a shorter development time and thus faster translation. The better image resolution, higher SNR and lower technological barrier to entry have led to a high interest in using CEST for clinical stroke imaging (Foo et al, 2021a), competing with 31 P MRS.…”

“…When CEST is used in higher field strength clinical scanners (7 T), the magnetic field inhomogeneity is found to be higher and it is harder to maintain homogenous radiofrequency pulses across the whole brain. Nevertheless, this is less of an issue at the moment because the majority of clinical scanners are 3 T and below, and so far all the published studies assessing APT in ischemic stroke patients up to 31st December 2020 used 3 T scanners and most of them used single slice acquisition (Foo et al, 2021a).…”

Ratiometric chemical exchange saturation transfer pH mapping using two iodinated agents with nonequivalent amide protons and a single low saturation power

“…Chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) has emerged as one of the most promising noninvasive techniques for pH quantification (14)(15)(16). Following selective radiofrequency (RF) irradiation, labile protons are saturated, and the saturated protons successively exchange with the surrounding water protons, resulting in a significant loss of the water MRI signal (17)(18)(19).…”