Optimized dualCEST-MRI for imaging of endogenous bulk mobile proteins in the human brain.

Published on May 1, 2020in NMR in Biomedicine3.221
· DOI :10.1002/NBM.4262
Johannes Breitling5
Estimated H-index: 5
Jan Eric Meissner10
Estimated H-index: 10
(DKFZ: German Cancer Research Center)
+ 4 AuthorsSteffen Goerke14
Estimated H-index: 14
(DKFZ: German Cancer Research Center)
: Dual-frequency irradiation chemical exchange saturation transfer (dualCEST) allows imaging of endogenous bulk mobile proteins by selectively measuring the intramolecular spin diffusion. The resulting specificity to changes in the concentration, molecular size, and folding state of mobile proteins is of particular interest as a marker for neurodegenerative diseases and cancer. Until now, application of dualCEST in clinical trials was prevented by the inherently small signal-to-noise ratio and the resulting comparatively long examination time. In this study, we present an optimized acquisition protocol allowing 3D dualCEST-MRI examinations in a clinically relevant time frame. The optimization comprised the extension of the image readout to 3D, allowing a retrospective co-registration and application of denoising strategies. In addition, cosine-modulated dual-frequency presaturation pulses were implemented with a weighted acquisition scheme of the necessary frequency offsets. The optimization resulted in a signal-to-noise ratio gain by a factor of approximately 8. In particular, the application of denoising and the motion correction were the most crucial improvement steps. In vitro experiments verified the preservation of specificity of the dualCEST signal to proteins. Good-to-excellent intra-session and good inter-session repeatability was achieved, allowing reliable detection of relative signal differences of about 16% or higher. Applicability in a clinical setting was demonstrated by examining a patient with glioblastoma. The optimized acquisition protocol for dualCEST-MRI at 3 T enables selective imaging of endogenous bulk mobile proteins under clinically relevant conditions.
#1Jan Eric Meissner (DKFZ: German Cancer Research Center)H-Index: 10
#2Andreas Korzowski (DKFZ: German Cancer Research Center)H-Index: 7
Last. Daniel Paech (DKFZ: German Cancer Research Center)H-Index: 20
view all 12 authors...
BACKGROUND: Patients with newly diagnosed inoperable glioma receive chemoradiotherapy (CRT). Standard Response Assessment in Neuro-Oncology (RANO) takes a minimum of 4 weeks after the end of treatment. PURPOSE/HYPOTHESIS: To investigate whether chemical exchange saturation transfer (CEST) MRI enables earlier assessment of response to CRT in glioma patients. STUDY TYPE: Longitudinal prospective study. POPULATION: Twelve brain tumor patients who underwent definitive CRT were included in this study...
22 CitationsSource
#1Steffen Goerke (DKFZ: German Cancer Research Center)H-Index: 14
#2Yannick Soehngen (DKFZ: German Cancer Research Center)H-Index: 1
Last. Mark E. Ladd (DKFZ: German Cancer Research Center)H-Index: 57
view all 13 authors...
PURPOSE: Relaxation-compensated CEST-MRI (i.e., the inverse metrics magnetization transfer ratio and apparent exchange-dependent relaxation) has already been shown to provide valuable information for brain tumor diagnosis at ultrahigh magnetic field strengths. This study aims at translating the established acquisition protocol at 7 T to a clinically relevant magnetic field strength of 3 T. METHODS: Protein model solutions were analyzed at multiple magnetic field strengths to assess the spectral ...
21 CitationsSource
#1Johannes Breitling (DKFZ: German Cancer Research Center)H-Index: 5
#2Anagha Deshmane (MPG: Max Planck Society)H-Index: 12
Last. Moritz Zaiss (MPG: Max Planck Society)H-Index: 28
view all 9 authors...
: High image signal-to-noise ratio (SNR) is required to reliably detect the inherently small chemical exchange saturation transfer (CEST) effects in vivo. In this study, it was demonstrated that identifying spectral redundancies of CEST data by principal component analysis (PCA) in combination with an appropriate data-driven extraction of relevant information can be used for an effective and robust denoising of CEST spectra. The relationship between the number of relevant principal components an...
18 CitationsSource
#1Pramodh Vallurupalli (TIFR: Tata Institute of Fundamental Research)H-Index: 24
#2Ved Prakash Tiwari (TIFR: Tata Institute of Fundamental Research)H-Index: 2
Last. Shamasree Ghosh (TIFR: Tata Institute of Fundamental Research)H-Index: 3
view all 3 authors...
Despite the importance of protein dynamics to function, studying exchange between multiple conformational states remains a challenge because sparsely populated states are invisible to conventional techniques. CEST NMR experiments can detect minor states with lifetimes between 5 and 200 ms populated to a level of just ∼1%. However, CEST often cannot provide the exchange mechanism for processes involving three or more states, leaving the role of the detected minor states unknown. Here a double-res...
4 CitationsSource
#2Zhiliang Wei (JHUSOM: Johns Hopkins University School of Medicine)H-Index: 9
#3Kannie W.Y. Chan (CityU: City University of Hong Kong)H-Index: 23
Last. Jiadi Xu (JHUSOM: Johns Hopkins University School of Medicine)H-Index: 34
view all 10 authors...
Abstract The goal of this study was to develop a molecular biomarker for the detection of protein aggregation involved in Alzheimer's disease (AD) by exploiting the features of the water saturation transfer spectrum (Z-spectrum), the CEST signal of which is sensitive to the molecular configuration of proteins. A radial-sampling steady-state sequence based ultrashort echo time (UTE) readout was implemented to image the Z-spectrum in the mouse brain, especially the contributions from mobile protei...
17 CitationsSource
#1Vincent Evans (UCL: University College London)H-Index: 2
#2F. J. Torrealdea (UCL: University College London)H-Index: 9
Last. David Atkinson (UCL: University College London)H-Index: 68
view all 11 authors...
BACKGROUND: Chemical exchange saturation transfer (CEST) can potentially support cancer imaging with metabolically derived information. Multiparametric prostate MRI has improved diagnosis but may benefit from additional information to reduce the need for biopsies. PURPOSE: To optimize an acquisition and postprocessing protocol for 3.0 T multipool CEST analysis of prostate data and evaluate the repeatability of the technique. STUDY TYPE: Prospective. SUBJECTS: Five healthy volunteers (age range: ...
8 CitationsSource
#1Jinyuan Zhou (Johns Hopkins University)H-Index: 54
#2Hye Young Heo (Johns Hopkins University)H-Index: 20
Last. Shanshan Jiang (Johns Hopkins University)H-Index: 20
view all 5 authors...
Amide proton transfer‐weighted (APTw) imaging is a molecular MRI technique that generates image contrast based predominantly on the amide protons in mobile cellular proteins and peptides that are endogenous in tissue. This technique, the most studied type of chemical exchange saturation transfer imaging, has been used successfully for imaging of protein content and pH, the latter being possible due to the strong dependence of the amide proton exchange rate on pH. In this article we briefly revie...
82 CitationsSource
PURPOSE: To investigate the reproducibility of gray and white matter glutamate contrast of a brain slice among a small group of healthy volunteers by using the 2D single-slice glutamate CEST (GluCEST) imaging technique. METHODS: Six healthy volunteers were scanned multiple times for within-day and between-day reproducibility. One more volunteer was scanned for within-day reproducibility at 7T MRI. Glutamate CEST contrast measurements were calculated for within subjects and among the subjects and...
17 CitationsSource
#1Steffen Goerke (DKFZ: German Cancer Research Center)H-Index: 14
#2Johannes Breitling (DKFZ: German Cancer Research Center)H-Index: 5
Last. Mark E. Ladd (DKFZ: German Cancer Research Center)H-Index: 57
view all 11 authors...
: A novel MRI contrast is proposed which enables the selective detection of endogenous bulk mobile proteins in vivo. Such a non-invasive imaging technique may be of particular interest for many diseases associated with pathological alterations of protein expression, such as cancer and neurodegenerative disorders. Specificity to mobile proteins was achieved by the selective measurement of intramolecular spin diffusion and the removal of semi-solid macromolecular signal components by a correction ...
13 CitationsSource
PURPOSE: To introduce and evaluate an image registration technique for robust quantification of CEST acquisitions corrupted by motion. METHODS: The proposed iterative algorithm exploits a low-rank approximation of the z-spectrum (LRAZ), to gradually separate the contrast variation due to saturation at different off-resonance frequencies and accompanying motion. This registration method was first tested in a creatine CEST analysis of a phantom with simulated rigid motion. Subsequently, creatine C...
10 CitationsSource
Cited By1
#1Steffen Goerke (DKFZ: German Cancer Research Center)H-Index: 14
#2Johannes Breitling (DKFZ: German Cancer Research Center)H-Index: 5
Last. P Bachert (Heidelberg University)
view all 8 authors...
PURPOSE The value of relaxation-compensated amide proton transfer (APT) and relayed nuclear Overhauser effect (rNOE) chemical exchange saturation transfer (CEST)-MRI has already been demonstrated in various neuro-oncological clinical applications. Recently, we translated the approach from 7T to a clinically relevant magnetic field strength of 3T. However, the overall acquisition time was still too long for a broad application in the clinical setting. The aim of this study was to establish a shor...
1 CitationsSource