Lorentzian-Corrected Apparent Exchange-Dependent Relaxation (LAREX) Ω-Plot Analysis—An Adaptation for qCEST in a Multi-Pool System: Comprehensive In Silico, In Situ, and In Vivo Studies

Abstract

Based on in silico, in situ, and in vivo studies, this study aims to develop a new method for the quantitative chemical exchange saturation transfer (qCEST) technique considering multi-pool systems. To this end, we extended the state-of-the-art apparent exchange-dependent relaxation (AREX) method with a Lorentzian correction (LAREX). We then validated this new method with in situ and in vivo experiments on human intervertebral discs (IVDs) using the Kendall-Tau correlation coefficient. In the in silico experiments, we observed significant deviations of the AREX method as a function of the underlying exchange rate (kba) and fractional concentration (fb) compared to the ground truth due to the influence of other exchange pools. In comparison to AREX, the LAREX-based Ω-plot approach yielded a substantial improvement. In the subsequent in situ and in vivo experiments on human IVDs, no correlation to the histological reference standard or Pfirrmann classification could be found for the fb (in situ: τ = −0.17 p = 0.51; in vivo: τ = 0.13 p = 0.30) and kba (in situ: τ = 0.042 p = 0.87; in vivo: τ = −0.26 p = 0.04) of Glycosaminoglycan (GAG) with AREX. In contrast, the influence of interfering pools could be corrected by LAREX, and a moderate to strong correlation was observed for the fractional concentration of GAG for both in situ (τ = −0.71 p = 0.005) and in vivo (τ = −0.49 p < 0.001) experiments. The study presented here is the first to introduce a new qCEST method that enables qCEST imaging in systems with multiple proton pools.

Comparison of compositional MRI techniques to quantify the regenerative potential of articular cartilage: a preclinical minipig model after osteochondral defect treatments with autologous mesenchymal stromal cells and unseeded scaffolds

“…Compared to morphological sequences like T 2 -weighted (T 2w ) or proton density-weighted (PD) sequences, compositional MR sequences provide more detailed information about the structure and composition of cartilage tissue ( 10 ). Moreover, compared to other biosensitive sequences such as chemical exchange saturation transfer (CEST) ( 12 , 13 ), quantitative susceptibility mapping (QSM) ( 14 ), and 23 Na ( 15 ) imaging, the MRI techniques do not require specific hardware, are less susceptible to noise, require simpler post-processing, and are more commonly used and validated, making them suitable for our focus on more straightforward clinical translation.…”

Deep Learning-Based Denoising of CEST MR Data: A Feasibility Study on Applying Synthetic Phantoms in Medical Imaging

“…It allows for the comprehensive analysis of tissue biomolecule concentrations without the need for exogenous contrast agents [3]. Although CEST imaging can provide valuable information about solutes at low concentrations, a high signal-to-noise ratio (SNR) is essential for accurately detecting subtle CEST effects [4,5]. Achieving a high SNR ensures that the CEST effects, no matter how subtle, are distinctly discernible against the background noise.…”

“…While conventional methodologies, including Magnetization Transfer Ratio Asymmetry (MTR asym ) and Lorentzian analyses, are effective metrics for CEST imaging [6,7], they do exhibit susceptibility to image noise [5,8]. Mathematically, MTR asym is defined as the difference between the signals at positive and negative frequency offsets with respect to the water resonance.…”

“…This susceptibility inherently lowers the precision, complicating the shift to quantitative concentration estimations by CEST in the in vivo analyses [5]. However, one must acknowledge the omnipresence of noise across all image-processing modalities.…”

Highlights in Pathophysiology of the Musculoskeletal System

“…For instance, the study by Kamp et al [ 30 ] evaluated and reported on the apparent tissue sodium content (aTSC) and sodium relaxation times for the Achilles tendons (ATs) by using sodium magnetic resonance imaging (MRI) to serve as a better comparable parameter between different studies regarding the examinations of diseased ATs with sodium MRI. Still, based on in silico, in situ, and in vivo studies, the study by Radke et al [ 31 ] developed and reported a new method for the quantitative chemical exchange saturation transfer (qCEST) technique, a promising bio-sensitive MRI technique, in systems with multiple proton pools, to assess the biochemical composition of the intervertebral discs, allowing for the timely diagnosis of degenerative diseases. Moreover, the validity of the dual innervation technique for the facial paralysis treatment has been reported in a study by Watanabe et al [ 32 ].…”