Amide proton transfer CEST of the cervical spinal cord in multiple sclerosis patients at 3T

By, Samantha; Barry, Robert; Smith, Alex K.; Lyttle, Bailey D.; Box, Bailey A.; Bagnato, Francesca; Pawate, Siddharama; Smith, Seth A.

doi:10.1002/mrm.26736

Cited by 47 publications

(59 citation statements)

References 43 publications

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“…Unfortunately, neither of these methods allows validation of the MT effect with existing qMT literature; there is either no parameter to investigate the MT effect (MTR asym ) or the parameter describing the MT effect is derived using different methodologies (AREX), meaning it has a different parameter range than what has already been established in the literature. By harmonizing the estimates derived from a CEST analysis with established methods in the qMT literature, we can better correlate the structural (qMT) and chemical (CEST) environments, particularly in pathologies such as multiple sclerosis, and cancer …”

Section: Discussionmentioning

confidence: 99%

“…Importantly, the magnitude of the attenuation of the water signal is related to both the chemical exchange rate, which has been correlated with pH, and the concentration of the exchanging solute. CEST imaging is thus a unique imaging technique which can be used to investigate how pathology perturbs the underlying biochemistry and pH balance in the body and has been used to study pathologies such as stroke, cancer, and multiple sclerosis …”

Section: Introductionmentioning

confidence: 99%

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

Smith

Ray

Larkin

et al. 2020

Magnetic Resonance in Med

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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

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Smith

Ray

Larkin

et al. 2020

Magnetic Resonance in Med

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“…Chemical exchange saturation transfer imaging is an important molecular MRI method that can generate contrast on free bulk water protons in tissue that originates from and reflects labile protons in low‐concentration (mM range) solute molecules such as metabolites. Amide proton transfer (APT) imaging, a variant of the CEST‐based molecular MRI technique, is based on the chemical exchange between free bulk water protons and the amide protons (‐NH) of endogenous mobile proteins and peptides in tissue . An abundance of preclinical and clinical data suggests that APT‐weighted (APTw) MRI enables the noninvasive identification and differentiation of brain tumors from peritumoral edema or normal tissue, high‐grade from low‐grade tumors, or radiation necrosis from tumor recurrence .…”

Section: Introductionmentioning

confidence: 99%

Prospective acceleration of parallel RF transmission‐based 3D chemical exchange saturation transfer imaging with compressed sensing

Heo

Jiang

et al. 2019

Magnetic Resonance in Med

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Purpose: To develop prospectively accelerated 3D CEST imaging using compressed sensing (CS), combined with a saturation scheme based on time-interleaved parallel transmission. Methods: A variable density pseudo-random sampling pattern with a centric elliptical k-space ordering was used for CS acceleration in 3D. Retrospective CS studies were performed with CEST phantoms to test the reconstruction scheme.Prospectively CS-accelerated 3D-CEST images were acquired in 10 healthy volunteers and 6 brain tumor patients with an acceleration factor (R CS ) of 4 and compared with conventional SENSE reconstructed images. Amide proton transfer weighted (APTw) signals under varied RF saturation powers were compared with varied acceleration factors. Results: The APTw signals obtained from the CS with acceleration factor of 4 were well-preserved as compared with the reference image (SENSE R = 2) both in retrospective phantom and prospective healthy volunteer studies. In the patient study, the APTw signals were significantly higher in the tumor region (gadolinium [Gd]enhancing tumor core) than in the normal tissue (p < .001). There was no significant APTw difference between the CS-accelerated images and the reference image. The scan time of CS-accelerated 3D APTw imaging was dramatically reduced to 2:10 minutes (in-plane spatial resolution of 1.8 × 1.8 mm 2 ; 15 slices with 4-mm slice thickness) as compared with SENSE (4:07 minutes).

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“…Recently, CEST MRI has been performed on MS patients at 7.0 T . Amide proton transfer (APT) CEST (with S sat /S 0 set at 3.5 ppm), which is sensitive to proteins and peptides, was demonstrated to be a potential imaging biomarker of WM pathology . Glutamate (Glu)‐sensitive CEST MRI (with S sat /S 0 set at 3.0 ppm) was reported to have utility as an imaging biomarker for GM pathology .…”

Section: Introductionmentioning

confidence: 99%

CEST MRI with distribution‐based analysis for assessment of early stage disease activity in a mouse model of multiple sclerosis: An initial study

et al. 2019

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Imaging biomarkers that can detect pathological changes at an early stage of multiple sclerosis (MS) may allow earlier therapeutic intervention with an improved outcome. Using a mouse model of MS, termed as experimental autoimmune encephalomyelitis (EAE), we performed chemical exchange saturation transfer (CEST) MRI at a very early stage before symptom onset (6 days post‐induction) for assessment of changes in tissues that appear “normal” with conventional MRI. The collected CEST Z‐spectra signals (Ssat/S0) were analyzed using a histogram‐guided method to determine the contributions from various offset frequencies. Histogram analysis showed that EAE mice exhibit a more heterogeneous distribution with lower peak heights in the hindbrain compared with naïve mice at saturation offsets of 1 and 2 ppm. At these two offsets, both the mean Ssat/S0 and the mean MTRasym values in the cerebellum and brain stem are significantly different between EAE and naïve mice (P < 0.05). Immunofluorescent staining validated the presence of neuroinflammation, with IBA1‐positive cells detected throughout the hindbrain including the cerebellum and brain stem. Follow‐up MRI at the symptom onset (score = 1.5–2.5, 13 days post‐induction) confirmed gadolinium‐enhanced periventricular lesions. CEST Z‐spectra signals also changed by this time. The proposed three‐level histogram‐oriented analysis is simple to execute and robust for detecting subtle changes in Z‐spectra signals, which does not require a priori knowledge of damage locations or contributing offset components. CEST MRI signals at 1 and 2 ppm were sensitive to the subtle pathological changes at an early stage in EAE mice, and have potential as novel imaging biomarkers complementary to functional and physiological MRI measures.

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Amide proton transfer CEST of the cervical spinal cord in multiple sclerosis patients at 3T

Abstract: Respiration correction in the spinal cord is necessary to accurately quantify APT CEST, which can provide unique biochemical information regarding disease processes within the spinal cord. Magn Reson Med 79:806-814, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Cited by 47 publications

References 43 publications

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

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

Prospective acceleration of parallel RF transmission‐based 3D chemical exchange saturation transfer imaging with compressed sensing

CEST MRI with distribution‐based analysis for assessment of early stage disease activity in a mouse model of multiple sclerosis: An initial study

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