Chemical exchange saturation transfer imaging for epilepsy secondary to tuberous sclerosis complex at 3 T: Optimization and analysis

Abstract

The homeostasis of various metabolites is impaired in epilepsy secondary to the tuberous sclerosis complex (TSC). Chemical exchange saturation transfer (CEST) imaging is an emerging molecular MRI technique that can detect various metabolites and proteins in vivo. However, the role of CEST imaging for TSC‐associated epilepsy has not been assessed. Here, we aim to investigate the feasibility of applying CEST imaging to TSC‐associated epilepsy, optimize the CEST acquisition parameters, and provide an analysis method for exploring the dominant molecular contributors to the CEST signal measured. Nine TSC epilepsy patients were scanned on a 3‐T MRI system. The CEST saturation frequencies were swept from −6 to 6 ppm with 12 different combinations of saturation power (4, 3, 2 and 1 μT) and duration (1000, 700 and 400 ms). Furthermore, a two‐stage simulation method based on the seven‐pool Bloch‐McConnell model was proposed to assess the contribution of each exchangeable pool to the CEST signal in normal‐appearing white matter and cortical tubers, which avoided the complexity and uncertainty of full Bloch‐McConnell fitting. The results showed that under the optimal saturation duration of 1000 ms, the greatest contrast between tubers and normal tissues occurred around 3, 2.5, 1.75 and 3.5 ppm for B1 of 4, 3, 2 and 1 μT, respectively. At the optimal frequency offsets, the CEST values of tubers were significantly higher than those in the normal brain tissues (P < 0.01). Furthermore, the two‐stage analysis suggested that the amine pool played a dominant role in yielding the contrast between cortical tubers and normal tissues. These results indicate that CEST MRI may serve as a potentially useful tool for identifying tubers in TSC, and the two‐stage analysis method may provide a route for investigating the molecular contributions to the CEST contrast in biological tissues.

Joint K‐space and Image‐space Parallel Imaging (KIPI) for accelerated chemical exchange saturation transfer acquisition

“…Here, the 3.5 ppm frame is selected as the calibration one because it is critical for APTw imaging and contributes a major part of the SNR in the asymmetry analysis result. But the calibration frame does not have to be at 3.5 ppm, and the KIPI method can be easily adapted for other CEST imaging applications by using calibration frames at different frequency offsets, such as for glutamate 13,14 or glucose 7,8 imaging. However, it should be noted that the calibration frame must have sufficient SNR for calculating the sensitivity maps, and the best calibration frequency needs to be investigated in future studies.…”

Progress of clinical research studies on tuberous sclerosis complex‐related epilepsy in China

“…Furthermore, the amine pool plays a dominant role in the contrast between the cortical tubers and normal tissues. These results indicate that CEST MRI may serve as a potentially useful tool for identifying epileptogenic tubers in TSC 37 . Magnetoencephalography and ictal single‐photon emission computed tomography (SPECT) have also been used for the preoperative evaluation of TSC‐related DRE 38,39 .…”

“…These results indicate that CEST MRI may serve as a potentially useful tool for identifying epileptogenic tubers in TSC. 37 Magnetoencephalography and ictal single-photon emission computed tomography (SPECT) have also been used for the preoperative evaluation of TSC-related DRE. 38,39 The epileptogenic tuber was defined in the same brain region on scalp EEG.…”

Lateralization of temporal lobe epileptic foci with automated chemical exchange saturation transfer measurements at 3 Tesla

“…A latest study demonstrated successful detection of tubers in patients with epilepsy secondary to the tuberous sclerosis complex using 3 T CEST and suggested that amine protons might be the major contributor to the elevated CEST signal in tubers. 18 Thus, we hypothesize that CEST MRI can predict seizure laterality of TLE at 3 T.…”

“…Chemical exchange saturation transfer (CEST) imaging is an emerging MRI technique that can detect proteins and metabolites noninvasively through the exchange of protons between biomolecules and free water. 14 , 15 The exchange rate of amine protons in glutamate is in the slow to intermediate exchange regime (∼2000–∼5000 s −1 ) 15 , 16 , 17 , 18 with respect to its chemical shift at 7 T (∼5600 rad/s), making glutamate an ideal target metabolite for CEST detection at 7 T or higher field strength. Notably, glutamate plays a crucial role in the generation and maintenance of seizures, as demonstrated by both human 19 and animal 20 studies.…”