Does the magnetization transfer effect bias chemical exchange saturation transfer effects? Quantifying chemical exchange saturation transfer in the presence of magnetization transfer

Abstract

Purpose: Chemical exchange saturation transfer (CEST) is an MRI technique sensitive to the presence of low-concentration solute protons exchanging with water. However, magnetization transfer (MT) effects also arise when large semisolid molecules interact with water, which biases CEST parameter estimates if quantitative models do not account for macromolecular effects. This study establishes under what conditions this bias is significant and demonstrates how using an appropriate model provides more accurate quantitative CEST measurements. Methods: CEST and MT data were acquired in phantoms containing bovine serum albumin and agarose. Several quantitative CEST and MT models were used with the phantom data to demonstrate how underfitting can influence estimates of the CEST effect. CEST and MT data were acquired in healthy volunteers, and a twopool model was fit in vivo and in vitro, whereas removing increasing amounts of CEST data to show biases in the CEST analysis also corrupts MT parameter estimates. Results: When all significant CEST/MT effects were included, the derived parameter estimates for each CEST/MT pool significantly correlated (P < .05) with bovine serum albumin/agarose concentration; minimal or negative correlations were found with underfitted data. Additionally, a bootstrap analysis demonstrated that significant biases occur in MT parameter estimates (P < .001) when unmodeled CEST data are included in the analysis. Conclusions: These results indicate that current practices of simultaneously fitting both CEST and MT effects in model-based analyses can lead to significant bias in all 1360 | SMITH eT al. | THEORYSimilar to the analytical solution for a two-pool model described in the various papers by Yarnykh et al 36,37 and Zhou et al,4,38 we parameter estimates unless a sufficiently detailed model is utilized. Therefore, care must be taken when quantifying CEST and MT effects in vivo by properly modeling data to minimize these biases. K E Y W O R D S amide, CEST, MT, NOE, qMT, quantitative 1366 | SMITH eT al. F I G U R E 3 Semisolid (PSR), and amide and NOE (MTR*) maps for the variable agarose phantom experiment. The top row illustrates the full, four-pool model estimation, the middle displays the fixed-qMT estimation, and the bottom row shows the same fit assuming the NOE and MT pools are a single pool, similar to Tee et al 34 F I G U R E 4 Semisolid (PSR), and amide and NOE (MTR*) maps for the variable BSA phantom experiment. The top row illustrates the full, four-pool model estimation, the middle displays the fixed-qMT estimation, and the bottom row shows the same fit assuming the NOE and MT pools are a single pool, similar to similar to Tee et al 34

Relaxation-Compensated Chemical Exchange Saturation Transfer MRI in the Brain at 7T: Application in Relapsing-Remitting Multiple Sclerosis

“…In terms of glutamate-weighted CEST signal quantification, we chose to use −3.0 ppm as the reference frequency for the signal at 3.0 ppm, which could potentially be affected by rNOE effects as described above despite the sequence being optimized for sensitivity to glutamate CEST effects. We used a relatively simple two-pool Lorentzian model to fit the broad MT baseline in our CEST data and it performed well, but future studies could also employ higher spectral resolution for z-spectra and acquire offset frequencies outside the typical CEST window of −5.0–5.0 ppm to take advantage of other strategies for fitting CEST z-spectrum components ( 30 , 61 ) and modeling the macromolecular MT effects that confound CEST quantification ( 22 ). Future work may also benefit from using an 8-channel parallel transmit system at 7.0 T to improve the homogeneity of the B 1 + field for CEST saturation pulses.…”

“…CEST is sensitive to the choice of saturation parameters (saturation pulse power and duration), field strength, direct water saturation (spillover effect), and T 1 relaxation time of the free water pool. The semisolid macromolecular components in tissues participate in magnetization transfer (MT) which imparts a broad, asymmetric baseline convolved on the measured CEST spectrum ( 12 , 22 ). Of note, the MT asymmetry is substantially larger than the CEST effect, which can diminish the detection of small changes in the CEST spectrum.…”

Quantitative chemical exchange saturation transfer imaging of nuclear overhauser effects in acute ischemic stroke

“…We observed that l MTR* was decreased in all pathological ROIs relative to the contralateral normal tissue. There is some ambiguity in interpreting this observation, as the way in which we modeled semisolid effects is approximate compared to modeling used in the quantitative MT literature 58 . The multipool formalism describes each pool using a single transverse relaxation time, which analytically yields a Lorentzian absorption line shape 59 .…”

“…There is some ambiguity in interpreting this observation, as the way in which we modeled semisolid effects is approximate compared to modeling used in the quantitative MT literature. 58 The multipool formalism describes each pool using a single transverse relaxation time, which analytically yields a Lorentzian absorption line shape. 59 The Lorentzian line shape is suitable for mobile populations which can be described using a single T 2 .…”

“…14,23 Our construction of the semisolid pool therefore plays more of a correctional role that improves quantitation of CEST effects, rather than being interpreted as an accurate representation of quantitative MT in its own right. The model fitting function used in this study has been developed further by Smith et al 58 to include a super-Lorentzian line shape, rendering it suitable for making quantitative MT measures simultaneously with CEST in future studies.…”