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1.
Magn Reson Med ; 87(2): 837-849, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34590729

RESUMO

PURPOSE: Chemical exchange saturation transfer signals from amines are sensitive to pH, and detection of these signals can serve as an alternative pH imaging method to amide proton transfer (APT). However, conflicting results regarding amine CEST imaging at 2 ppm in ischemic stroke have been reported. Here, we correlated amine CEST with APT in animal stroke models to evaluate its specificity to pH, and investigated the reason for the different results through simulations and sample studies. METHODS: A three-point quantification method was used to quantify APT. A polynomial fit method and a multiple-pool Lorentzian fit method were used to quantify amine CEST. Samples of creatine and glutamate were prepared to study the different CEST effects from arginine amine and fast exchanging pools. Samples of tissue homogenates with different pH were prepared to study the variation in CEST signals due only to changes in pH. RESULTS: The polynomial fit of amine CEST at 2 ppm had a significant correlation with APT, whereas the Lorentzian fit did not. Further studies showed that arginine amine contributed to the polynomial fit, whereas both the arginine amine and the fast exchanging pools contributed to the Lorentzian fit with their CEST effects varying in opposite directions after stroke. The CEST signal from the fast exchanging pool decreased, probably due to the reduced pool concentration but not pH. CONCLUSION: The variation in opposite directions led to an insignificant correlation of the Lorentzian fit of amine CEST with APT and the different results in different experimental conditions.

2.
Magn Reson Med ; 87(1): 409-416, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34480767

RESUMO

PURPOSE: A relayed nuclear Overhauser enhancement (rNOE) saturation transfer effect at around -1.6 ppm from water, termed NOE(-1.6), was previously reported in rat and human brain, and some publications suggest that it may be related to blood. Here, we studied whether the NOE(-1.6) arises from blood through in vivo and ex vivo experiments. METHODS: To evaluate the contribution from in vivo blood to NOE(-1.6), intravascular signals in rat brain were suppressed by two approaches: (1) signal acquisition with a diffusion-weighting of b = 400 s/mm2 ; (2) intravascular injection of 5 mg/kg monocrystalline iron oxide nanoparticle (MION). Ex vivo blood sample was also prepared. The signals were acquired using a chemical exchange saturation transfer (CEST) pulse sequence. Multiple-pool Lorentzian fitting of CEST Z-spectra was performed to quantify the NOE(-1.6) signal. RESULTS: There are no significant variations in the fitted in vivo NOE(-1.6) signals when measured with or without diffusion-weighting, but significant signal decease does occur after injection of MION. The NOE(-1.6) signal from ex vivo blood is weaker than that from in vivo tissues. CONCLUSION: Considering the relatively small volume of blood in brain, the in vivo experiments with diffusion weighting and the ex vivo experiments both suggest that the NOE(-1.6) is not mainly from blood. The mechanism for the in vivo experiments with MION are less clear. MION not only suppresses MR signals from intravascular space, but changes the susceptibility in the perivascular space. This result suggests that although the NOE(-1.6) is not mainly from blood, it may be vasculature dependent.

3.
NMR Biomed ; : e4610, 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34636458

RESUMO

Chemical exchange saturation transfer (CEST) methods measure the effect of magnetization exchange between solutes and water. While CEST methods are often implemented using a train of off-resonant shaped RF pulses, they are typically analyzed as if the irradiation were continuous. This approximation does not account for exchange of rotated magnetization, unique to pulsed irradiation and exploited by chemical exchange rotation transfer methods. In this work, we derive and test an analytic solution for the steady-state water signal under pulsed irradiation by extending a previous work to include the effects of pulse shape. The solution is largely accurate at all offsets, but this accuracy diminishes at higher exchange rates and when applying pulse shapes with large root-mean-squared to mean ratios (such as multi-lobe sinc pulses).

4.
Magn Reson Imaging ; 84: 1-11, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34052306

RESUMO

Measurements of the variations of spin-locking relaxation rates (R1ρ) with locking field amplitude allow the derivation of quantitative parameters that describe different dynamic processes, such as slow molecular motions, chemical exchange and diffusion. In some samples, changes in R1ρ values between locking frequency 0 and 200 Hz may be dominated mainly by diffusion of water in intrinsic field gradients, while those at higher locking fields are due to exchange processes. The exchange and diffusion effects act independently of each other, as confirmed by simulation and experimentally. In tissues, the relevant intrinsic field gradients may arise from the magnetic inhomogeneities caused by microvascular blood so that R1ρ dispersion over weak locking field amplitudes (≤ 200 Hz) is affected by changes in capillary density and geometry. Here we first review the theoretical and experimental background to the interpretation of R1ρ dispersions caused by intrinsic magnetic susceptibility variations within the tissue. We then provide new empirical results of R1ρ dispersion imaging of the human brain and skeletal muscle at low locking field amplitudes for the first time and identify potential applications of R1ρ dispersion imaging in clinical studies.

5.
Neuroimage Clin ; 30: 102633, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33780866

RESUMO

PURPOSE: The sensitivity and accuracy of chemical exchange saturation transfer (CEST) and nuclear Overhauser enhancement (NOE) effects for assessing injury-associated changes in cervical spinal cords were evaluated in squirrel monkeys. Multiple interacting pools of protons, including one identified by an NOE at -1.6 ppm relative to water (NOE(-1.6)), were derived and quantified from fitting proton Z-spectra. The effects of down-sampled data acquisitions and corrections for non-specific factors including T1, semi-solid magnetization transfer, and direct saturation of free water (DS), were investigated. The overall goal is to develop a protocol for rapid data acquisition for assessing the molecular signatures of the injured spinal cord and its surrounding regions. METHODS: MRI scans were recorded of anesthetized squirrel monkeys at 9.4 T, before and after a unilateral dorsal column sectioning of the cervical spinal cord. Z-spectral images at 51 different RF offsets were acquired. The amplitudes of CEST and NOE effects from multiple proton pools were quantified using a six-pool Lorenzian fitting of each Z-spectrum (MTRmfit). In addition, down-sampled data using reduced selections of RF offsets were analyzed and compared. An apparent exchange-dependent relaxation (AREXmfit) method was also used to correct for non-specific factors in quantifying regional spectra around lesion sites. RESULTS: The parametric maps from multi-pool fitting using the complete sampling data (P51e) detected unilateral changes at and around the injury. The maps derived from selected twofold down-sampled data with appropriate interpolation (P26sI51) revealed quite similar spatial distributions of different pools as those obtained using P51e at each resonance shift. Across 10 subjects, both data acquisition schemes detected significant decreases in NOE(-3.5) and NOE(-1.6) and increases in DS(0.0) and CEST(3.5) at the lesion site relative to measures of the normal tissues before injury. AREXmfit of cysts and other abnormal tissues at and around the lesion site also exhibited significant changes, especially at 3.5, -1.6 and -3.5 ppm RF offsets. CONCLUSION: These results confirm that a reduced set of RF offsets and down sampling are adequate for CEST imaging of injured spinal cord and allow shorter imaging times and/or permit additional signal averaging. AREXmfit correction improved the accuracy of CEST and NOE measures. The results provide a rapid (~13 mins), sensitive, and accurate protocol for deriving multiple NOE and CEST effects simultaneously in spinal cord imaging at high field.


Assuntos
Medula Cervical , Interpretação de Imagem Assistida por Computador , Algoritmos , Medula Cervical/diagnóstico por imagem , Imageamento por Ressonância Magnética , Prótons , Sensibilidade e Especificidade
6.
NMR Biomed ; 34(2): e4437, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33283945

RESUMO

In chemical exchange saturation transfer (CEST) imaging, the signal at 2.6 ppm from the water resonance in muscle has been assigned to phosphocreatine (PCr). However, this signal has limited specificity for PCr since the signal is also sensitive to exchange with protein and macromolecular protons when using some conventional quantification methods, and will vary with changes in the water longitudinal relaxation rate. Correcting for these effects while maintaining reasonable acquisition times is challenging. As an alternative approach to overcome these problems, here we evaluate chemical exchange rotation transfer (CERT) imaging of PCr in muscle at 9.4 T. Specifically, the CERT metric, AREXdouble,cpw at 2.6 ppm, was measured in solutions containing the main muscle metabolites, in tissue homogenates with controlled PCr content, and in vivo in rat leg muscles. PCr dominates CERT metrics around 2.6 ppm (although with nontrivial confounding baseline contributions), indicating that CERT is well-suited to PCr specific imaging, and has the added benefit of requiring a relatively small number of acquisitions.


Assuntos
Músculo Esquelético/química , Ressonância Magnética Nuclear Biomolecular/métodos , Fosfocreatina/análise , Espectroscopia de Prótons por Ressonância Magnética/métodos , Trifosfato de Adenosina/análise , Animais , Creatina/análise , Glicogênio/análise , Membro Posterior , Lactatos/análise , Músculo Esquelético/diagnóstico por imagem , Ratos , Rotação , Extratos de Tecidos/química
7.
Magn Reson Med ; 85(2): 748-761, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32936478

RESUMO

PURPOSE: This report introduces and validates a new diffusion MRI-based method, termed MRI-cytometry, which can noninvasively map intravoxel, nonparametric cell size distributions in tissues. METHODS: MRI was used to acquire diffusion MRI signals with a range of diffusion times and gradient factors, and a model was fit to these data to derive estimates of cell size distributions. We implemented a 2-step fitting method to avoid noise-induced artificial peaks and provide reliable estimates of tumor cell size distributions. Computer simulations in silico, experimental measurements on cultured cells in vitro, and animal xenografts in vivo were used to validate the accuracy and precision of the method. Tumors in 7 patients with breast cancer were also imaged and analyzed using this MRI-cytometry approach on a clinical 3 Tesla MRI scanner. RESULTS: Simulations and experimental results confirm that MRI-cytometry can reliably map intravoxel, nonparametric cell size distributions and has the potential to discriminate smaller and larger cells. The application in breast cancer patients demonstrates the feasibility of direct translation of MRI-cytometry to clinical applications. CONCLUSION: The proposed MRI-cytometry method can characterize nonparametric cell size distributions in human tumors, which potentially provides a practical imaging approach to derive specific histopathological information on biological tissues.


Assuntos
Imagem de Difusão por Ressonância Magnética , Imageamento por Ressonância Magnética , Animais , Tamanho Celular , Simulação por Computador , Difusão , Humanos
8.
PLoS One ; 15(10): e0240513, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33064765

RESUMO

OBJECTIVE: In vivo functional changes in white matter during the progression of Alzheimer's disease (AD) have not been previously reported. Our objectives are to measure changes in white matter functional connectivity (FC) in an elderly population undergoing cognitive decline as AD develops, to establish their relationship to neuropsychological scores of cognitive abilities, and to assess the performance in prediction of AD using white matter FC measures as features. METHODS: Analyses were conducted using resting state functional MRI and neuropsychological data from 383 ADNI participants, including 136 cognitive normal (CN) controls, 46 with significant memory concern, 83 with early mild cognitive impairment (MCI), 37 with MCI, 46 with late MCI, and 35 with AD dementia. FC metrics between segregated white matter tracts and discrete gray matter volumes or between white matter tracts were quantitatively analyzed and characterized, along with their relationships to 6 cognitive measures. Finally, supervised machine learning was implemented on white matter FCs to classify the participants and performance of the classification was evaluated. RESULTS: Significant decreases in FC measures were found in white matter with prominent, specific, regional deficits appearing in late MCI and AD dementia patients from CN. These changes significantly correlated with neuropsychological measurements of impairments in cognition and memory. The sensitivity and specificity of distinguishing AD dementia and CN using white matter FCs were 0.83 and 0.81 respectively. CONCLUSIONS AND RELEVANCE: The white matter FC decreased in late MCI and AD dementia patients compared to CN participants, and this decrease was correlated with cognitive measures. White matter FC is valuable in the prediction of AD. All these findings suggest that white matter FC may be a promising avenue for understanding functional impairments in white matter tracts during AD progression.


Assuntos
Doença de Alzheimer/psicologia , Disfunção Cognitiva/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Substância Branca/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico por imagem , Estudos de Casos e Controles , Disfunção Cognitiva/fisiopatologia , Progressão da Doença , Feminino , Humanos , Masculino , Testes Neuropsicológicos , Sensibilidade e Especificidade , Aprendizado de Máquina Supervisionado , Substância Branca/diagnóstico por imagem
9.
MAGMA ; 33(6): 809-818, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32462557

RESUMO

PURPOSE: The purpose of this study was to characterize the individual contribution of multiple fat peaks to the measured chemical exchange saturation transfer (CEST) signal when using water-selective binomial-pulse excitation and to determine the effects of multiple fat peaks in the presence of B0 inhomogeneity. METHODS: The excitation profiles of multiple binomial pulses were simulated. A CEST sequence with binomial-pulse excitation and modified point-resolved spectroscopy localization was then applied to the in vivo lumbar spinal vertebrae to determine the signal contributions of three distinct groups of lipid resonances. These confounding signal contributions were measured as a function of the irradiation frequency offset to determine the effect of the multi-peak nature of the fat signal on CEST imaging of exchange sites (at 1.0, 2.0 and 3.5 ppm) and robustness in the presence of B0 inhomogeneity. RESULTS: Numerical simulations and in vivo experiments showed that water excitation (WE) using a 1-3-3-1 (WE-4) pulse provided the broadest signal suppression, which provided partial robustness against B0 inhomogeneity effects. Confounding fat signal contributions to the CEST contrasts at 1.0, 2.0 and 3.5 ppm were unavoidable due to the multi-peak nature of the fat signal. However, these CEST sites only suffer from small lipid artifacts with ∆B0 spanning roughly from - 50 to 50 Hz. Especially for the CEST site at 3.5 ppm, the lipid artifacts are smaller than 1% with ∆B0 in this range. CONCLUSION: In WE-4-based CEST magnetic resonance imaging, B0 inhomogeneity is the limiting factor for fat suppression. The CEST sites at 1.0, 2.0 ppm and 3.5 ppm unavoidably suffer from lipid artifacts. However, when the ∆B0 is confined to a limited range, these CEST sites are only affected by small lipid artifacts, which may be ignorable in some cases of clinical applications.


Assuntos
Imageamento por Ressonância Magnética , Água , Artefatos , Imagens de Fantasmas
10.
Magn Reson Med ; 84(4): 1961-1976, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32243662

RESUMO

PURPOSE: Phospholipids are key constituents of cell membranes and serve vital functions in the regulation of cellular processes; thus, a method for in vivo detection and characterization could be valuable for detecting changes in cell membranes that are consequences of either normal or pathological processes. Here, we describe a new method to map the distribution of partially restricted phospholipids in tissues. METHODS: The phospholipids were measured by signal changes caused by relayed nuclear Overhauser enhancement-mediated CEST between the phospholipid Cho headgroup methyl protons and water at around -1.6 ppm from the water resonance. The biophysical basis of this effect was examined by controlled manipulation of head group, chain length, temperature, degree of saturation, and presence of cholesterol. Additional experiments were performed on animal tumor models to evaluate potential applications of this novel signal while correcting for confounding contributions. RESULTS: Negative relayed nuclear Overhauser dips in Z-spectra were measured from reconstituted Cho phospholipids with cholesterol but not for other Cho-containing metabolites or proteins. Significant contrast was found between tumor and contralateral normal tissue signals in animals when comparing both the measured saturation transfer signal and a more specific imaging metric. CONCLUSION: We demonstrated specific relayed nuclear Overhauser effects in partially restricted phospholipid phantoms and similar effects in solid brain tumors after correcting for confounding signal contributions, suggesting possible translational applications of this novel molecular imaging method, which we name restricted phospholipid transfer.


Assuntos
Interpretação de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Algoritmos , Animais , Encéfalo , Fosfolipídeos
11.
Magn Reson Med ; 84(4): 2074-2087, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32141646

RESUMO

PURPOSE: To develop and evaluate a reliable non-invasive means for assessing the severity and progression of fibrosis in kidneys. We used spin-lock MR imaging with different locking fields to detect and characterize progressive renal fibrosis in an hHB-EGFTg/Tg mouse model. METHODS: Male hHB-EGFTg/Tg mice, a well-established model of progressive fibrosis, and age-matched normal wild type (WT) mice, were imaged at 7T at ages 5-7, 11-13, and 30-40 weeks. Spin-lock relaxation rates R1 ρ were measured at different locking fields (frequencies) and the resultant dispersion curves were fit to a model of exchanging water pools. The obtained MRI parameters were evaluated as potential indicators of tubulointerstitial fibrosis in kidney. Histological examinations of renal fibrosis were also carried out post-mortem after MRI. RESULTS: Histology detected extensive fibrosis in the hHB-EGFTg/Tg mice, in which collagen deposition and reductions in capillary density were observed in the fibrotic regions of kidneys. R2 and R1 ρ values at different spin-lock powers clearly dropped in the fibrotic region as fibrosis progressed. There was less variation in the asymptotic locking field relaxation rate R 1 ρ ∞ between the groups. The exchange parameter Sρ and the inflection frequency ωinfl changed by larger factors. CONCLUSION: Both Sρ and ωinfl depend primarily on the average exchange rate between water and other chemically shifted resonances such as hydroxyls and amides. Spin-lock relaxation rate dispersion, rather than single measurements of relaxation rates, provides more comprehensive and specific information on spatiotemporal changes associated with tubulointerstitial fibrosis in murine kidney.


Assuntos
Rim , Imageamento por Ressonância Magnética , Amidas , Animais , Modelos Animais de Doenças , Fibrose , Rim/diagnóstico por imagem , Masculino , Camundongos
12.
Magn Reson Med ; 83(4): 1405-1417, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31691367

RESUMO

PURPOSE: Chemical exchange saturation transfer (CEST) signals at 3 ppm acquired with high irradiation powers, termed GluCEST, have been suggested as an indicator of glutamate in neural systems. However, amines in proteins may also contribute to the GluCEST signal, but they have been ignored in previous studies. This study aims to investigate the molecular origins and specificity of GluCEST signal in rat brain. METHODS: Dialysis was used to selectively remove small molecules, such as glutamate and other metabolites, from tissue homogenates prepared from rat brain. This approach allowed the specific influence of proteins on GluCEST to be measured. Clean CEST effects were also quantified by a 2-step analysis, which first used a fitting approach to quantify the asymmetric magnetization transfer effect and an inverse subtraction to remove it, and then combined an apparent exchange-dependent relaxation method with asymmetric analysis to remove the direct water saturation and T1 weighting. RESULTS: The removal of glutamate and other small metabolites by dialysis decreases the GluCEST signal by approximately 24%, indicating that a major contributor to GluCEST in the brain is amines in proteins under our experimental conditions. CONCLUSION: Data from in vivo GluCEST measurements should be interpreted with caution, especially in disorders in which changes in the content or conformation of proteins are expected.


Assuntos
Ácido Glutâmico , Imageamento por Ressonância Magnética , Animais , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Imagem Molecular , Proteínas , Ratos
13.
Magn Reson Med ; 83(5): 1587-1595, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31883149

RESUMO

PURPOSE: Previous studies have shown that diffusion of water through intrinsic susceptibility gradients produces a dispersion of the spin-lattice relaxation rate in the rotating frame (R1 ρ ) over a low range of spin-locking amplitudes (0 < ω1 < 100 Hz), whereas at higher ω1 and high magnetic fields, a second dispersion arises due to chemical exchange. Here, we separated these different effects and evaluated their contributions in tumors. METHODS: Maps of R1 ρ and its changes with locking field were acquired on intracranial 9-L tumor models. The R1 ρ changes due to diffusion ( R 1 ρ Diff ) were calculated by subtracting maps of R1 ρ at 100 Hz (R1 ρ [100 Hz]) from those at 0 Hz (R1 ρ [0 Hz]). The R1 ρ changes due to exchange ( R 1 ρ Ex ) were calculated by subtracting maps of R1 ρ at 5620 Hz (R1 ρ [5620 Hz]) from those of R1 ρ at 100 Hz (R1 ρ [100 Hz]). Measurements of vascular dimensions and spacing were performed ex vivo using 3D confocal microscopy. RESULTS: The R1 ρ changes at low ω1 in tumors (5.24 ± 1.78 s-1 ) are substantially (p = 3.76 ) greater than those in normal tissues (1.36 ± 0.70 s-1 ), which we suggest are due to greater contributions from diffusion through susceptibility gradients. Tumor vessels were larger and spaced less closely compared with normal brain, which may be 1 factor contributing the susceptibility within 9-L tumors. The contrast between tumor and normal tissues for R 1 ρ Diff is larger than for R 1 ρ Ex and for the apparent R2w . CONCLUSION: Images that are sensitive to the variations of spin-lock relaxation rates at low ω1 provide a novel form of contrast that reflects the heterogeneous nature of intrinsic variations within tumors.


Assuntos
Neoplasias Encefálicas , Imageamento por Ressonância Magnética , Encéfalo/diagnóstico por imagem , Neoplasias Encefálicas/diagnóstico por imagem , Difusão , Humanos , Campos Magnéticos
14.
Magn Reson Med ; 81(1): 208-219, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30058128

RESUMO

PURPOSE: Recently, a new relayed nuclear Overhauser enhancement (NOE) saturation transfer effect at around -1.6 parts per million, termed NOE(-1.6), and its potential applications in tumor and stroke were reported by several institutes. However, there is a concern of the reproducibility of NOE(-1.6) measurements because it is not reported by many other publications. This paper aims to study the influence of typically overlooked experimental settings on the NOE(-1.6) signal and to build a framework for more reliable measurements of NOE(-1.6) at 9.4T. METHODS: Z-spectra were obtained in rat brains. A fitting approach was performed to quantify all known saturation transfer effects except NOE(-1.6). Residual signals were obtained by removing these confounding effects from Z-spectra and were then used to quantify NOE(-1.6). Multislice imaging was performed to study the NOE(-1.6) dependence on brain regions. The influences of euthanasia, anesthesia, breathing gases, and RF irradiation power were also evaluated. RESULTS: Results demonstrate that the NOE(-1.6) signal contributions are often not clearly observable in raw Z-spectra at relatively high irradiation powers due to, for example, the direct water saturation effect, but they can be visualized after removing other nonspecific effects. In addition, the NOE(-1.6) effect depends on brain region, decreases postmortem, shifts after long-duration anesthesia, and may be enhanced by increasing O2 and N2 O breathing air concentrations. CONCLUSION: Because the NOE(-1.6) effect is more susceptible to the direct water saturation effect and more sensitive to physiological conditions than are other CEST effects, incorporating known sensitivities into the experimental design and data analysis is necessary to ensure more reliable NOE(-1.6) results.


Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Glioma/diagnóstico por imagem , Algoritmos , Anestesia , Animais , Neoplasias Encefálicas/patologia , Meios de Contraste , Gases , Glioma/patologia , Interpretação de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética , Prótons , Ratos , Reprodutibilidade dos Testes , Respiração , Sensibilidade e Especificidade
15.
NMR Biomed ; 31(12): e4017, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30334295

RESUMO

Recently, a new nuclear Overhauser enhancement (NOE)-mediated saturation transfer effect at around -1.6 ppm from water, termed NOE(-1.6), was reported to show hypointense signals in brain tumors. Similar to chemical exchange saturation transfer or magnetization transfer (MT) effects, which depend on the solute pool concentration, the exchange/coupling rate, the solute transverse relaxation rate, etc., the NOE(-1.6) effect should also depend on these factors. Since the exchange rate is relevant to tissue pH, and the coupling rate and the solute transverse relaxation rate are relevant to the motional property of the coupled molecules, further studies to quantify the contribution from only the exchange/coupling rate and the solute transverse relaxation rate are always interesting. The purpose of this paper is to apply a ratiometric approach to the NOE(-1.6) effect to obtain a metric that is more specific to the NOE coupling rate and the solute transverse relaxation rate than the NOE(-1.6) signal amplitude. Simulations indicate that the ratiometric approach allows us to rule out nearly all of the non-specific factors including the solute pool concentration, solute and water longitudinal relaxation rates, direct water saturation, and semi-solid MT effects, and provides a more specific NOE coupling rate- and solute transverse relaxation rate-weighted signal. Animal studies show that the ratiometric NOE(-1.6) decreases dramatically in brain tumors, which suggests that the change in the NOE(-1.6) coupling rate and/or the solute transverse relaxation rate are major contributors to the previously observed hypointense NOE(-1.6) signal in tumors.


Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Imageamento por Ressonância Magnética , Animais , Simulação por Computador , Modelos Animais de Doenças , Ratos
16.
Phys Med Biol ; 63(15): 15NT03, 2018 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-29978838

RESUMO

The response to radiation of polymer gel dosimeters has previously been measured by magnetic resonance imaging (MRI) in terms of changes in the water transverse relaxation rate (R 2w) or magnetization transfer (MT) parameters. Here we report a new MRI approach, based on detecting nuclear Overhauser enhancement (NOE) mediated saturation transfer effects, which can also be used to detect radiation and measure dose distributions in MAGIC-f (Methacrylic and Ascorbic Acid and Gelatin Initiated by Copper Solution with formaldehyde) polymer gels. Results show that the NOE effects produced by low powered radiofrequency (RF) irradiation at specific frequencies offset from water may be quantified by appropriate measurements and over a useful range depend linearly on the radiation dose. The NOE effect likely arises from the polymerization of methacrylic acid monomers which become less mobile, facilitating dipolar through-space cross-relaxation and/or relayed magnetization exchange between polymer and water protons. Our study suggests a potential new MRI method for polymer gel dosimetry.


Assuntos
Imageamento por Ressonância Magnética/métodos , Dosímetros de Radiação , Ácido Ascórbico , Sulfato de Cobre , Gelatina , Hidroquinonas , Imageamento por Ressonância Magnética/instrumentação , Metacrilatos , Polímeros , Radiometria/instrumentação , Radiometria/métodos
17.
Magn Reson Med ; 80(6): 2609-2617, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-29802641

RESUMO

PURPOSE: To test the ability of a novel pulse sequence applied in vivo at 3 Tesla to separate the contributions to the water signal from amide proton transfer (APT) and relayed nuclear Overhauser enhancement (rNOE) from background direct water saturation and semisolid magnetization transfer (MT). The lack of such signal source isolation has confounded conventional chemical exchange saturation transfer (CEST) imaging. METHODS: We quantified APT and rNOE signals using a chemical exchange rotation transfer (CERT) metric, MTRdouble . A range of duty cycles and average irradiation powers were applied, and results were compared with conventional CEST analyses using asymmetry (MTRasym ) and extrapolated magnetization transfer (EMR). RESULTS: Our results indicate that MTRdouble is more specific than MTRasym and, because it requires as few as 3 data points, is more rapid than methods requiring a complete Z-spectrum, such as EMR. In white matter, APT (1.5 ± 0.5%) and rNOE (2.1 ± 0.7%) were quantified by using MTRdouble with a 30% duty cycle and a 0.5-µT average power. In addition, our results suggest that MTRdouble is insensitive to B0 inhomogeneity, further magnifying its speed advantage over CEST metrics that require a separate B0 measurement. However, MTRdouble still has nontrivial sensitivity to B1 inhomogeneities. CONCLUSION: We demonstrated that MTRdouble is an alternative metric to evaluate APT and rNOE, which is fast, robust to B0 inhomogeneity, and easy to process.


Assuntos
Mapeamento Encefálico , Neoplasias Encefálicas/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Imageamento por Ressonância Magnética , Adulto , Algoritmos , Simulação por Computador , Feminino , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Prótons , Rotação
18.
NMR Biomed ; 31(7): e3934, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29806717

RESUMO

Amide proton transfer (APT) imaging is a variation of chemical exchange saturation transfer MRI that has shown promise in diagnosing tumors, ischemic stroke, multiple sclerosis, traumatic brain injury, etc. Specific quantification of the APT effect is crucial for the interpretation of APT contrast in pathologies. Conventionally, magnetization transfer ratio with asymmetric analysis (MTRasym ) has been used to quantify the APT effect. However, some studies indicate that MTRasym is contaminated by water longitudinal relaxation time (T1w ), and thus it is necessary to normalize T1w in MTRasym to obtain specific quantification of the APT effect. So far, whether to use MTRasym or the T1w -normalized MTRasym is still under debate in the field. In this paper, the influence of T1w on the quantification of APT was evaluated through theoretical analysis, numerical simulations, and phantom studies for different experimental conditions. Results indicate that there are two types of T1w effect (T1w recovery and T1w -related saturation), which have inverse influences on the steady-state MTRasym . In situations with no or weak direct water saturation (DS) effect, there is only the T1w recovery effect, and MTRasym linearly depends on T1w . In contrast, in situations with significant DS effects, the dependence of MTRasym on T1w is complex, and is dictated by the competition of these two T1w effects. Therefore, by choosing appropriate irradiation powers, MTRasym could be roughly insensitive to T1w . Moreover, in non-steady-state acquisitions with very short irradiation time, MTRasym is also roughly insensitive to T1w . Therefore, for steady-state APT imaging at high fields or with very low irradiation powers, where there are no significant DS effects, it is necessary to normalize T1w to improve the specificity of MTRasym . However, in clinical MRI systems (usually low fields or non-steady-state acquisitions), T1w normalization may not be necessary when appropriate sequence parameters are chosen.


Assuntos
Amidas , Imageamento por Ressonância Magnética , Prótons , Simulação por Computador , Análise Numérica Assistida por Computador , Água/química
20.
NMR Biomed ; 31(4): e3893, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29424463

RESUMO

We have previously reported that the dispersion of spin-lattice relaxation rates in the rotating frame (R1ρ ) of tissue water protons at high field can be dominated by chemical exchange contributions. Ischemia in brain causes changes in tissue pH, which in turn may affect proton exchange rates. Amide proton transfer (APT, a form of chemical exchange saturation transfer) has been shown to be sensitive to chemical exchange rates and able to detect pH changes non-invasively following ischemic stroke. However, the specificity of APT to pH changes is decreased because of the influence of several other factors that affect magnetization transfer. R1ρ is less influenced by such confounding factors and thus may be more specific for detecting variations in pH. Here, we applied a spin-locking sequence to detect ischemic stroke in animal models. Although R1ρ images acquired with a single spin-locking amplitude (ω1 ) have previously been used to assess stroke, here we use ΔR1ρ , which is the difference in R1ρ values acquired with two different locking fields to emphasize selectively the contribution of chemical exchange effects. Numerical simulations with different exchange rates and measurements of tissue homogenates with different pH were performed to evaluate the specificity of ΔR1ρ to detect tissue acidosis. Spin-lock and APT data were acquired on five rat brains after ischemic strokes induced via middle cerebral artery occlusions. Correlations between these data were analyzed at different time points after the onset of stroke. The results show that ΔR1ρ (but not R1ρ acquired with a single ω1 ) was significantly correlated with APT metrics consistent with ΔR1ρ varying with pH.


Assuntos
Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/metabolismo , Imageamento por Ressonância Magnética , Marcadores de Spin , Animais , Simulação por Computador , Concentração de Íons de Hidrogênio , Análise Numérica Assistida por Computador , Especificidade de Órgãos , Ratos
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