Chemical exchange saturation transfer (CEST) is a contrast mechanism exploiting exchange-based magnetization transfer (MT) between solute and water protons. CEST effects compete with direct water saturation and conventional MT processes and generally can only be quantified through an asymmetry analysis of the water saturation spectrum (Z-spectrum) with respect to the water frequency, a process that is exquisitely sensitive to magnetic field inhomogeneities. Here, it is shown that direct water saturation imaging allows measurement of the absolute water frequency in each voxel, allowing proper centering of Z-spectra on a voxel-by-voxel basis independent of spatial B 0 field variations. Optimal acquisition parameters for this "water saturation shift referencing" or "WASSR" approach were estimated using Monte Carlo simulations and later confirmed experimentally. The optimal ratio of the WASSR sweep width to the linewidth of the direct saturation curve was found to be 3.3-4.0, requiring a sampling of 16-32 points. The frequency error was smaller than 1 Hz at signal to noise ratios of 40 or higher. The WASSR method was applied to study glycogen, where the chemical shift difference between the hydroxyl (OH) protons and bulk water protons at 3T is so small (0.75-1.25 ppm) that the CEST spectrum is inconclusive without proper referencing.

Amide proton transfer (APT) imaging is a type of chemical exchange-dependent saturation transfer (CEST) magnetic resonance imaging (MRI) in which amide protons of endogenous mobile proteins and peptides in tissue are detected. Initial studies have shown promising results for distinguishing tumor from surrounding brain in patients, but these data were hampered by magnetic field inhomogeneity and a low signal-to-noise ratio (SNR). Here a practical six-offset APT data acquisition scheme is presented that, together with a separately acquired CEST spectrum, can provide B 0 -inhomogeneity corrected human brain APT images of sufficient SNR within a clinically relevant time frame. Data from nine brain tumor patients at 3T shows that APT intensities were significantly higher in the tumor core, as assigned by gadolinium-enhancement, than in contralateral normal-appearing white matter ( Recent progress in the field of proteomics (1-3) has shown that the biological characteristics of human gliomas and other cancers are defined by numerous proteins, and that the pathologic distinctions between normal and malignant tissues can be identified at the level of protein expression. Using in vivo proton MRS, Howe et al. (4) showed that the MRS-detectable mobile macromolecular proton concentration is higher in human brain tumors than in normal white matter (WM), and increases with tumor grade. These advances have prompted much interest in visualizing the protein content of tumors in vivo in MRI.Chemical exchange-dependent saturation transfer (CEST) has recently emerged as a new contrast mechanism for MRI (5-7) in the field of cellular and molecular imaging. This technique, which is a type of magnetization transfer (MT)imaging (8), has now evolved into several different variants as new CEST contrast agents (diamagnetic and paramagnetic) and approaches have been designed (9 -22). In one of these, dubbed amide proton transfer (APT) imaging (9 -13,23-25), endogenous cytosolic proteins and peptides are detected through saturation of the amide protons in the peptide bonds. Similar to the results of Howe et al. (4), this unique amide proton-based MRI contrast mechanism has shown promise for imaging the increase in protein and peptide content in brain tumors in animals (11), as well as in an initial study in human brain tumor patients (23). However, these preliminary human studies were confounded by a low signal-to-noise ratio (SNR; the APT effect is only a few percent of the water signal) and by local field inhomogeneity. The high sensitivity of APT to field inhomogeneity is due to the inherent approach in CEST-type imaging, where water saturation is measured as a function of transmitter frequency, producing the "z-spectra" (26) or CEST spectra (5). Such spectra are dominated by large direct water saturation around the water frequency at about 4.7 ppm in the proton spectrum and other saturation effects, such as conventional MT based on semisolid tissue structures (8). The effects of the saturation transfer of exchangeable protons to water ...

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Recent studies have proposed that glycosaminoglycan chemical exchange saturation transfer (gagCEST) is associated with a loss of glycosaminoglycans (GAGs), which may be an initiating factor in intervertebral disc (IVD) degeneration. Despite its promising potential, this application has not been reported in human in vivo IVD studies because of the challenges of B(0) magnetic field inhomogeneity in gagCEST. This study aimed to evaluate the feasibility of quantifying CEST values in IVDs of healthy volunteers using a clinical 3 T scanner. A single-slice turbo spin echo sequence was used to quantify the CEST effect in various GAG phantoms and in IVDs of 12 volunteers. The phantom results indicated high correlation between gagCEST and GAG concentrations (R(2)  = 0.95). With optimal B(0) inhomogeneity correction, in vivo CEST maps of IVDs showed robust contrast between the nucleus pulposus (NP) and the annulus fibrosus (AF) (p < 0.01), as well as higher signal in the central relative to the peripheral NP. In addition, a trend of decreasing CEST values from upper to lower disc levels was evident in NP. Our results demonstrate that in vivo gagCEST quantification in human lumbar IVDs is feasible at 3 T in combination with successful B(0) inhomogeneity correction, but without significant hardware modifications. Our initial findings suggest that it would be worthwhile to perform direct correlation studies between CEST and GAGs using cadaver samples, and to extend this novel technique to studies on patients with degenerative discs to better understand its distinct imaging features relative to conventional techniques.

Purpose: To investigate whether quantitative MRI measures of cervical spinal cord white matter (WM) using diffusion tensor imaging (DTI) in neuromyelitis optica (NMO) differed from controls and correlated with clinical disability. Materials and Methods:Ten referred patients and 12 healthy volunteers were imaged on a 3 Tesla scanner and patients were clinically assessed on the Expanded Disability Status Scale (EDSS). Two raters quantified DTIderived indices from all participants, including fractional anisotropy (FA), mean diffusivity (MD), parallel diffusivity (lambda [parallel]) and perpendicular diffusivity (lambda[-perpendicular]) at C1-C6 for lateral and dorsal columns. After the inter-rater reliability test, univariate correlations between DTI measures and disability were assessed using the Spearman's rho correlation coefficient. Multiple regression analysis was performed to investigate which DTI measures independently correlated with the clinical score.Results: Statistical test results indicated high reliability of all DTI measurements between two raters. NMO patients showed reduced FA, increased MD and lambda[-perpendicular] compared with controls while lambda [parallel] did not show any significant difference. The former three DTI metrics also showed significant correlations with disability scores, and especially FA was found to be sensitive to mild NMO (EDSS 3) Conclusion: FA is a potentially useful quantitative biomarker of otherwise normal appearing WM damage in NMO. Such damage is associated with clinical disability.

Background: The aim of this study was to translate dynamic glucose enhancement (DGE) body magnetic resonance imaging (MRI) based on the glucose chemical exchange saturation transfer (glucoCEST) signal to a 3 T clinical field strength. Methods: An infusion protocol for intravenous (i.v.) glucose was optimised using a hyperglycaemic clamp to maximise the chances of detecting exchange-sensitive MRI signal. Numerical simulations were performed to define the optimum parameters for glucoCEST measurements with consideration to physiological conditions. DGE images were acquired for patients with lymphomas and prostate cancer injected i.v. with 20% glucose. Results: The optimised hyperglycaemic clamp infusion based on the DeFronzo method demonstrated higher efficiency and stability of glucose delivery as compared to manual determination of glucose infusion rates. DGE signal sensitivity was found to be dependent on T 2 , B 1 saturation power and integration range. Our results show that motion correction and B 0 field inhomogeneity correction are crucial to avoid mistaking signal changes for a glucose response while field drift is a substantial contributor. However, after B 0 field drift correction, no significant glucoCEST signal enhancement was observed in tumour regions of all patients in vivo. Conclusions: Based on our simulated and experimental results, we conclude that glucose-related signal remains elusive at 3 T in body regions, where physiological movements and strong effects of B 1 + and B 0 render the originally small glucoCEST signal difficult to detect.

Our study demonstrates the feasibility of using UTE MRI in humans in vivo to assess the integrity of the CEP. A statistically significant association was found to exist between the presence of CEP defects and IVD degeneration. In the lower lumbar region, more severe degeneration was found to occur in the IVDs with CEP defects than in those without defects.

Arterial spin labeling (ASL) MRI is becoming a popular method for measuring perfusion due to its ability of generating perfusion maps non-invasively. This allows for frequent repeat scanning, which is especially useful for follow-up studies. However, limited information is available regarding the reliability and reproducibility of ASL perfusion measurements. Here, the reliability and reproducibility of pulsed ASL (PASL) was investigated in an elderly population to determine the variation in perfusion among cognitively normal individuals in different brain structures. Intra-class correlation coefficients (ICC) and within-subject variation coefficients (wsCV) were used to estimate reliability and reproducibility over a period of one year. Twelve cognitively normal subjects (75.5±5.3 years old, six male and six female) were scanned four times (at 0, 3, 6 and 12 months). No significant difference in cerebral blood flow (CBF) was found over this period. CBF values ranged from 46–53 ml/100g/min in the medial frontal gyrus (MFG) and from 40–44 ml/100g/min over all gray matter regions in the superior part of the brain. Data obtained from the first two scans were processed by two readers and showed high reliability (ICC>0.97) and reproducibility (wsCV <6%). However, over the total period of one year, reliability reduced to a moderate level (ICC = 0.63–0.74) with wsCVs of gray matter, left MFG, right MFG of13.5%, 12.3% , and 15.4%, respectively. In conclusion, measurement of CBF with pulsed ASL provided good agreement between inter-raters. A moderate level of reliability was obtained over a one-year period, which was attributed to variance in slice positioning and coregistration. As such pulsed ASL has the potential to be used for CBF comparison in longitudinal studies.