The most frequent malignant tumors of the central nervous system are adult-type diffuse gliomas. T1 weighted, T2 weighted, and gadolinium-enhanced sequences of magnetic resonance imaging (MRI) play essential roles in the diagnosis, surveillance, and therapeutic monitoring of gliomas. Compared to CT, such conventional MRI techniques offer significantly better tissue characterization and high resolution multiplanar structural information. Despite the availability of high-resolution morphological imaging with conventional MRI, the diagnosis of gliomas remains inadequate. Gadolinium enhancement is typically linked to more aggressive lesions. However, because up to one-third of non-enhancing gliomas are malignant, contrast enhancement is not a reliable indicator of high-grade from low-grade gliomas [1]. Multiple imaging modalities, including positron emission tomography (PET) and advanced MRI are used together to obtain precise information and metabolic data to improve diagnostic accuracy.

Diffusion-weighted MRI (DWI) is based on the Brownian motion of water molecules and can provide in vivo contrast images of biological tissues [2]. The most significant parameter assessed using DWI, the apparent diffusion coefficient (ADC), has been widely used for pre- and postoperative glioma characterization. However, ADC is intrinsically overestimated and may not accurately reflect water molecule diffusion in vivo because it is produced by a monoexponential DWI model, which also includes capillary blood microcirculation known as perfusion. Le Bihan et al. suggested intravoxel incoherent motion (IVIM) imaging to visualize the microscopic motion of water and differentiate water molecular diffusion from local microvascular perfusion in a single acquisition approach [3]. IVIM imaging with various b values has been utilized to evaluate malignancies, including pancreatic, prostate, breast, and white matter lesions; brain tumors; and strokes [2]. IVIM imaging has been extensively used to investigate the relationship between IVIM parameters and the histological grade of gliomas [4].

PET is a functional molecular approach that allows early detection of pathophysiological alterations in gliomas that typically occur before morphostructural changes are visible on structural imaging [5]. Obtaining information on amino-acid transport using PET to quantify the biological tumor volume for treatment planning, therapy monitoring, and recurrence evaluation has emerged as a crucial and complementary technique to traditional MRI [6]. In contrast to 18F-fluorodeoxyglucose (18F-FDG), amino acid PET tracers such as 11C-methionine (11C-MET) and 18F-fluoroethyltyrosine (18F-FET), do not excessively accumulate in healty brain tissues. PET with 11C-MET has been widely used to detect brain tumors and grade gliomas [7].

Chemical exchange saturation transfer (CEST), a novel MRI contrast mechanism, is an effective and advanced MRI method [8]. CEST is based on the chemical exchange of protons between solutes and water molecules. Amide proton transfer (APT) is the most widely used CEST type for amide protons in mobile proteins and peptides in glioma detection and grading [9]. APT imaging is typically evaluated based on the magnetization transfer ratio asymmetry (MTRasym) at an offset of 3.5 ppm [10]. However, MTRasym is semi-quantitative and has limitations, such as being affected by pH, T1 value of the tissue, magnetization transfer (MT) effect, and nuclear Overhauser enhancement (NOE) [[10], [11], [12]]. APT imaging using multi-pool models (MPMs), such as Lorentzian-based and Bayesian model-based methods, has been developed to overcome these limitations [13,14]. A possible explanation is that MPM reduces the NOE and MT effects by separating their signals. Particularly, the Lorentzian-based MPM shows promise for evaluating glioma grades as an alternative to MTRasym [15]. We developed a multi-pool fitting approach; however, the underlying mechanism of MPM-induced APT signal intensity (SI) in gliomas remains unclear [16]. Investigating the relationship of APT imaging using MPMs with other imaging methods can help elucidate this mechanism. Therefore, this study aimed to evaluate the relationship of APT imaging with MPM, IVIM, and 11C-MET uptake on PET/CT to clarify the clinical significance of APT imaging of gliomas using MPM.