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Chemical exchange saturation transfer (CEST) is a relatively novel magnetic resonance imaging (MRI) technique with an image contrast designed for in vivo measurement of certain endogenous molecules with protons that are exchangeable with water protons, such as amide proton transfer commonly used for neuro-oncology applications. Recent technological advances have made it feasible to implement CEST on clinical grade scanners within practical acquisition times, creating new opportunities to integrate CEST in clinical workflow. In addition, the majority of CEST applications used in neuro-oncology are performed without the use gadolinium-based contrast agents which are another appealing feature of this technique. This review is written for clinicians involved in neuro-oncologic care (nonphysicists) as the target audience explaining what they need to know as CEST makes its way into practice. The purpose of this article is to (1) review the basic physics and technical principles of CEST MRI, and (2) review the practical applications of CEST in neuro-oncology. [ABSTRACT FROM AUTHOR]

Objectives: 1. Determine the feasibility and efficiency of local magnetic targeting delivery of gadolinium (Gad) contrast to the inner ear in rodents. 2. Assess any potential ototoxicity of magnetic targeting delivery of Gad in the inner ear. 3. Study the utility of magnetic targeting delivery of Gad to visualize and quantify endolymphatic hydrops (EH) in a transgenic mouse model. Study Design: Controlled in vivo animal model study. Methods: Paramagnetic Gad was locally delivered to the inner ear using the magnetic targeting technique in both rat and mouse models. Efficiency of contrast delivery was assessed using magnetic resonance imaging (MRI). Ototoxicity of Gad was examined with histology of the cochlea and functional audiological tests. The Phex mouse model was used to study EH, hearing loss, and balance dysfunction. Magnetic targeting delivery of Gad contrast was used in the Phex mouse model to visualize the effects of EH using MRI. Results: Magnetic targeting improved the delivery of Gad to the inner ear and the technique was reproducible in both rat and mouse models. The delivery method did not result in microstructural damage or any significant hearing loss in a normal animal. Magnetic targeting of Gad in the Phex mouse model allowed detailed visualization and quantification of EH. Conclusion: This study provided the first evidence of the effectiveness and efficiency of the local magnetic targeting delivery of gadolinium contrast to the inner ear and its application to the visualization and quantification of EH. Laryngoscope, 133:914–923, 2023 [ABSTRACT FROM AUTHOR]

A model of dysmyelination, the Long Evans Shaker ( les) rat, was used to study the contribution of myelin to MR tissue properties in white matter. A large region of white matter was identified in the deep cerebellum and was used for measurements of the MR relaxation rate constants, R1 = 1/ T1 and R2 = 1/ T2, at 7 T. In this study, R1 of the les deep cerebellar white matter was found to be 0.55 ± 0.08 s -1 and R2 was found to be 15 ± 1 s-1, revealing significantly lower R1 and R2 in les white matter relative to wild-type ( wt: R1 = 0.69 ± 0.05 s-1 and R2 = 18 ± 1 s-1). These deviated from the expected Δ R1 and Δ R2 values, given a complete lack of myelin in the les white matter, derived from the literature using values of myelin relaxivity, and we suspect that metals could play a significant role. The absolute concentrations of the paramagnetic transition metals iron (Fe) and manganese (Mn) were measured by a micro-synchrotron radiation X-ray fluorescence (μSRXRF) technique, with significantly greater Fe and Mn in les white matter than in wt (in units of μg [metal]/g [wet weight tissue]: les: Fe concentration,19 ± 1; Mn concentration, 0.71 ± 0.04; wt: Fe concentration,10 ± 1; Mn concentration, 0.47 ± 0.04). These changes in Fe and Mn could explain the deviations in R1 and R2 from the expected values in white matter. Although it was found that the influence of myelin still dominates R1 and R2 in wt rats, there were non-negligible changes in the contribution of the metals to relaxation. Although there are already problems with the estimation of myelin from R1 and R2 changes in disease models with pathology that also affects the relaxation rate constants, this study points to a specific pitfall in the estimation of changes in myelin in diseases or models with disrupted concentrations of paramagnetic transition metals. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Carr-Purcell-Meiboom-Gill-based sequences are often assumed to be insensitive to diffusion. However, imaging gradients always contribute some degree of diffusion weighting which increases with resolution. This may cause an apparent decrease in T2 when using a multi-echo sequence, such as quantitative T2 (qT2) at high resolution. This study investigated the impact of diffusion on the qT2 sequence. An equation was developed relating the diffusion factor associated with each echo ( bqT2) to the underestimation of T2, which was strongly dependent on both the actual T2 and the apparent diffusion coefficient of the tissue. The diffusion dependence of the measured T2 was demonstrated in rat spinal cord. The measured T2 was independent of the imaging plane in gray matter, where diffusion was isotropic, and orientation dependent in white matter, where diffusion was strongly anisotropic. The dependence of the measured T2 on the actual T2 value was also demonstrated in MnCl2 phantoms. The relationship between the resolution and underestimation of T2 was investigated both theoretically and experimentally for the original readout and a fully refocused readout. The fully refocused readout increased the resolution at which diffusion effects could be neglected whilst measuring T2. To avoid the misidentification of cerebrospinal fluid when applying qT2 in the brain or spinal cord, a minimum in-plane voxel dimension of 0.2 mm was suggested for the standard qT2 sequence and 0.1 mm for the refocused readout. Simulations of myelin water fraction measurement indicated that signal-to-noise ratio requirements were increased in the presence of diffusion. Finally, the use of decreasing spoiler gradients to attenuate stimulated echoes should be avoided, as it was found to distort the T2 distribution when the slice thickness was less than 1 mm. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is one of the most common causes of dementia and difficult to study as the pool of subjects is highly heterogeneous. Saturation transfer (ST) magnetic resonance imaging (MRI) methods are quantitative modalities with potential for non-invasive identification and tracking of various aspects of AD pathology. In this review we cover ST-MRI studies in both humans and animal models of AD over the past 20 years. A number of magnetization transfer (MT) studies have shown promising results in human brain. Increased computing power enables more quantitative MT studies, while access to higher magnetic fields improves the specificity of chemical exchange saturation transfer (CEST) techniques. While much work remains to be done, results so far are very encouraging. MT is sensitive to patterns of AD-related pathological changes, improving differential diagnosis, and CEST is sensitive to particular pathological processes which could greatly assist in the development and monitoring of therapeutic treatments of this currently incurable disease. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To measure possible positional and diurnal physiological effects on brain metabolites in single-voxel proton magnetic resonance spectroscopy (1H-MRS) measurements of the right and left striatum. Methods: 1H-MRS measurements were performed in 10 healthy adult volunteers using a short echo PRESS sequence (TE=30 ms, TR=3000 ms). Each individual was scanned during both morning and afternoon hours. Regions of interest were right and left striatum. To control for systematic drift in scanner performance, 1H-MRS measurements of a standard phantom solution were also acquired. Statistical analysis was performed using a repeated measures analysis of variance that included three within-subject factors: metabolite (N-acetyl-aspartate [NAA] or creatine [Cr]), laterality (left or right caudate) and time (morning or afternoon). Results: A significant interaction (P<.016) between time of day and metabolite levels was observed. Further exploration of this finding revealed a significant difference between morning and afternoon levels of NAA (P<.044) but not Cr. In addition, no significant morning-to-afternoon differences were observed for the 1H-MRS phantom measurements. Conclusions: Systematic variation due to scanner performance does not account for the changes observed in repeated measurements of striatal NAA levels. This difference may be accounted for by either repositioning effects or circadian physiological effects. Further studies are required to learn whether time of day standardization of 1H-MRS acquisitions may contribute to improved reproducibility of measurements. [Copyright &y& Elsevier]

The rapid formation of hydrazones under physiological conditions was exploited for the detection of aldehydes through chemical exchange saturation transfer magnetic resonance imaging (CEST-MRI). A metal-free, diamagnetic contrast agent derived from N-amino anthranilic acid was introduced, which selectively "turned-on" upon hydrazone formation through an effect termed Hydrazo-CEST. While the hydrazine form of the probe produced no CEST-MRI signal enhancement, the formation of the aryl hydrazone resulted in >20 % intensity decrease in the bulk water signal through the CEST effect, as measured by 300 MHz 1 H NMR, 3 T and 7 T MRI. Both the electronic contributions of the N-amino anthranilate and the aldehyde binding partner were shown to directly impact the exchange rate of the proton on the ring-proximal nitrogen, and thus the imaging signal. Additionally, the presence of the carboxylic acid moiety ortho to the hydrazine was necessary not only for contrast production, but also for rapid hydrazone formation and prolonged hydrazone product stability under physiological conditions. This work provided the first example of an MRI-based contrast agent capable of a "turn on" response upon reaction with bioactive aldehydes, and outlined both the structural and electronic requirements to expand on Hydrazo-CEST, a novel, hydrazone-dependent subtype of diamagnetic CEST-MRI., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A model of dysmyelination, the Long Evans Shaker (les) rat, was used to study the contribution of myelin to MR tissue properties in white matter. A large region of white matter was identified in the deep cerebellum and was used for measurements of the MR relaxation rate constants, R1  = 1/T1 and R2  = 1/T2 , at 7 T. In this study, R1 of the les deep cerebellar white matter was found to be 0.55 ± 0.08 s (-1) and R2 was found to be 15 ± 1 s(-1) , revealing significantly lower R1 and R2 in les white matter relative to wild-type (wt: R1  = 0.69 ± 0.05 s(-1) and R2  = 18 ± 1 s(-1) ). These deviated from the expected ΔR1 and ΔR2 values, given a complete lack of myelin in the les white matter, derived from the literature using values of myelin relaxivity, and we suspect that metals could play a significant role. The absolute concentrations of the paramagnetic transition metals iron (Fe) and manganese (Mn) were measured by a micro-synchrotron radiation X-ray fluorescence (μSRXRF) technique, with significantly greater Fe and Mn in les white matter than in wt (in units of μg [metal]/g [wet weight tissue]: les: Fe concentration,19 ± 1; Mn concentration, 0.71 ± 0.04; wt: Fe concentration,10 ± 1; Mn concentration, 0.47 ± 0.04). These changes in Fe and Mn could explain the deviations in R1 and R2 from the expected values in white matter. Although it was found that the influence of myelin still dominates R1 and R2 in wt rats, there were non-negligible changes in the contribution of the metals to relaxation. Although there are already problems with the estimation of myelin from R1 and R2 changes in disease models with pathology that also affects the relaxation rate constants, this study points to a specific pitfall in the estimation of changes in myelin in diseases or models with disrupted concentrations of paramagnetic transition metals. Copyright © 2016 John Wiley & Sons, Ltd., (Copyright © 2016 John Wiley & Sons, Ltd.)

Objective: Our objective was to analyze MRI contrast-enhancement patterns in arthritic and nonarthritic knees and the relationship of those patterns with clinical, laboratory, and histologic synovium markers., Materials and Methods: Dynamic contrast-enhanced MRI was performed in nine arthritic and three nonarthritic knees of juvenile rabbits. A two-compartment pharmacokinetic model of signal intensity-time data was implemented to generate parametric maps of signal slope, maximal percentage of signal change, capillary permeability, leakage space volume, and time-to-peak. MRI values were compared with clinical, laboratory, and histologic markers for evaluation of synovial changes during the progression of arthritis., Results: Parametric maps of capillary permeability and signal slope depicted significant differences between arthritic and nonarthritic knees. Arthritic knees showed increased capillary permeability (p = 0.006) and signal slope (p = 0.01) with time after onset of disease as opposed to nonarthritic knees (permeability, p = 0.65; slope, p = 0.56). Significant correlations were found between temporal changes in capillary permeability (p = 0.002), signal slope (p = 0.003), and serum concentrations of amyloid A. No relationship was noted between any MRI parameters and histologic scores. The discriminative power of MRI indexes varied according to the stage of arthritis: time-to-peak was most accurate for differentiation of presence versus absence of arthritis in early arthritis (day 1, p = 0.0002), and signal slope was most accurate in midterm arthritis (day 14, p = 0.001)., Conclusion: In vivo capillary permeability and signal slope have distinctive dynamic MRI properties. The accuracy of MRI parameters for diagnostic evaluation of experimental arthritis differs according to the stage of disease.

Background and Purpose: MR examination of infants with kernicterus shows abnormal changes in signal intensity in various parts of the brain, including the globus pallidus and subthalamic regions. The purpose of this study was to retrospectively analyze proton ((1)H) MR spectroscopic data to see if the MR spectroscopic profiles of infants with hyperbilirubinemia and symptoms of kernicterus provide new insights into the pathophysiology of bilirubin neurotoxicity., Methods: Six patients aged 3 days to 3 weeks, with hyperbilirubinemia and symptoms of kernicterus underwent MR imaging and MR spectroscopy with a single-voxel point-resolved spectroscopic sequence. The voxel of interest was centered in the basal ganglia with CSF excluded. Quantitative analysis was done by using LCModel. Between-subject comparisons were based on metabolite ratios relative to creatine., Results: Ratios of taurine, glutamate and glutamine, and myoinositol relative to creatine were significantly elevated (P < .001), whereas the ratio of choline to creatine was significantly decreased (P < .001) compared with normal values published for this age group. Lactate levels were not significantly elevated., Conclusion: Kernicterus has a characteristic signature that is detectable on (1)H-MR spectroscopy. Our results are generally in agreement with what is known about bilirubin pathology, and the finding of increased glutamate and glutamine and decreased choline ratios indicates a possible link between hepatic encephalopathy and kernicterus. This observation may help in elucidating the pathophysiology of bilirubin neurotoxicity.