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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.
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Imageamento por Ressonância Magnética , Prótons , Humanos , Imageamento por Ressonância Magnética/métodos , Imagens de Fantasmas , Interpretação de Imagem Assistida por Computador/métodos , AlgoritmosRESUMO
BACKGROUND: High radiation doses of stereotactic radiosurgery (SRS) for brain metastases (BM) can increase the likelihood of radiation necrosis (RN). Advanced MRI sequences can improve the differentiation between RN and tumor progression (TP). PURPOSE: To use saturation transfer MRI methods including chemical exchange saturation transfer (CEST) and magnetization transfer (MT) to distinguish RN from TP. STUDY TYPE: Prospective cohort study. SUBJECTS: Seventy patients (median age 60; 73% females) with BM (75 lesions) post-SRS. FIELD STRENGTH/SEQUENCE: 3-T, CEST imaging using low/high-power (saturation B1 = 0.52 and 2.0 µT), quantitative MT imaging using B1 = 1.5, 3.0, and 5.0 µT, WAter Saturation Shift Referencing (WASSR), WAter Shift And B1 (WASABI), T1 , and T2 mapping. All used gradient echoes except T2 mapping (gradient and spin echo). ASSESSMENT: Voxel-wise metrics included: magnetization transfer ratio (MTR); apparent exchange-dependent relaxation (AREX); MTR asymmetry; normalized MT exchange rate and pool size product; direct water saturation peak width; and the observed T1 and T2 . Regions of interests (ROIs) were manually contoured on the post-Gd T1 w. The mean (of median ROI values) was compared between groups. Clinical outcomes were determined by clinical and radiologic follow-up or histopathology. STATISTICAL TESTS: t-Test, univariable and multivariable logistic regression, receiver operating characteristic, and area under the curve (AUC) with sensitivity/specificity values with the optimal cut point using the Youden index, Akaike information criterion (AIC), Cohen's d. P < 0.05 with Bonferroni correction was considered significant. RESULTS: Seven metrics showed significant differences between RN and TP. The high-power MTR showed the highest AUC of 0.88, followed by low-power MTR (AUC = 0.87). The combination of low-power CEST scans improved the separation compared to individual parameters (with an AIC of 70.3 for low-power MTR/AREX). Cohen's d effect size showed that the MTR provided the largest effect sizes among all metrics. DATA CONCLUSION: Significant differences between RN and TP were observed based on saturation transfer MRI. EVIDENCE LEVEL: 3 Technical Efficacy: Stage 2.
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Neoplasias Encefálicas , Lesões por Radiação , Feminino , Humanos , Pessoa de Meia-Idade , Masculino , Estudos Prospectivos , Imageamento por Ressonância Magnética/métodos , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/patologia , Lesões por Radiação/diagnóstico por imagem , Água , Necrose , Encéfalo/diagnóstico por imagem , Encéfalo/patologiaRESUMO
Alteration in brain metabolism predates clinical onset of Alzheimer's Disease (AD). Realizing its potential as an early diagnostic marker, however, requires understanding how early AD metabolic dysregulation manifests on non-invasive brain imaging. We presently utilized magnetic resonance imaging and spectroscopy to map glucose and ketone metabolic profiles and image cerebrovascular function in a rat model of early stage AD - 9-month-old TgF344-AD (TgAD) rats - and their age-matched non-transgenic (nTg) littermates. Compared to the nTg rats, TgAD rats displayed attenuation in global cerebral and hippocampal vasoreactivity to hypercapnia, by 49 ± 17% and 58 ± 19%, respectively, while their functional hyperemia to somatosensory stimulation diminished by 69 ± 5%. To assess brain glucose uptake, rats were fasted overnight and then challenged with an intravenous infusion of 2-deoxy-D-glucose (2DG). Compared to their non-transgenic littermates, TgAD rats exhibited 99 ± 10% and 52 ± 5% smaller glucose uptake in the entorhinal cortex and the hippocampus, respectively. Moreover, hippocampal glucose uptake reduction in male TgAD rats compared to the nTg was 54 ± 36% greater than the reduction seen in female TgAD rats. TgAD rats also showed a 59 ± 42% increase in total choline level in the hippocampus, suggesting increased membrane turnover. In combination with our earlier findings of impaired electrophysiological metrics at this early stage of AD pathology progression, our findings suggest that subtle neuronal function alterations that would be difficult to assess in a clinical population may be accompanied by MRI-detectable changes in brain glucose metabolism and cerebrovascular function.
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Doença de Alzheimer , Doença de Alzheimer/metabolismo , Animais , Encéfalo/metabolismo , Modelos Animais de Doenças , Feminino , Glucose/metabolismo , Masculino , Ratos , Ratos TransgênicosRESUMO
PURPOSE: Target localization, for stereotactic radiosurgery (SRS) treatment with Gamma Knife, has become increasingly reliant on the co-registration between the planning MRI and the stereotactic cone-beam computed tomography (CBCT). Validating image registration between modalities would be particularly beneficial when considering the emergence of novel functional and metabolic MRI pulse sequences for target delineation. This study aimed to develop a phantom-based methodology to quantitatively compare the co-registration accuracy of the standard clinical imaging protocol to a representative MRI sequence that was likely to fail co-registration. The comparative methodology presented in this study may serve as a useful tool to evaluate the clinical translatability of novel MRI sequences. METHODS: A realistic human skull phantom with fiducial marker columns was designed and manufactured to fit into a typical MRI head coil and the Gamma Knife patient positioning system. A series of "optimized" 3D MRI sequences-T1 -weighted Dixon, T1 -weighted fast field echo (FFE), and T2 -weighted fluid-attenuated inversion recovery (FLAIR)-were acquired and co-registered to the CBCT. The same sequences were "compromised" by reconstructing without geometric distortion correction and re-collecting with lower signal-to-noise-ratio (SNR) to simulate a novel MRI sequence with poor co-registration accuracy. Image similarity metrics-structural similarity (SSIM) index, mean squared error (MSE), and peak SNR (PSNR)-were used to quantitatively compare the co-registration of the optimized and compromised MR images. RESULTS: The ground truth fiducial positions were compared to positions measured from each optimized image volume revealing a maximum median geometric uncertainty of 0.39 mm (LR), 0.92 mm (AP), and 0.13 mm (SI) between the CT and CBCT, 0.60 mm (LR), 0.36 mm (AP), and 0.07 mm (SI) between the CT and T1 -weighted Dixon, 0.42 mm (LR), 0.23 mm (AP), and 0.08 mm (SI) between the CT and T1 -weighted FFE, and 0.45 mm (LR), 0.19 mm (AP), and 1.04 mm (SI) between the CT and T2 -weighted FLAIR. Qualitatively, pairs of optimized and compromised image slices were compared using a fusion image where separable colors were used to differentiate between images. Quantitatively, MSE was the most predictive and SSIM the second most predictive metric for evaluating co-registration similarity. A clinically relevant threshold of MSE, SSIM, and/or PSNR may be defined beyond which point an MRI sequence should be rejected for target delineation based on its dissimilarity to an optimized sequence co-registration. All dissimilarity thresholds calculated using correlation coefficients with in-plane geometric uncertainty would need to be defined on a sequence-by-sequence basis and validated with patient data. CONCLUSION: This study utilized a realistic skull phantom and image similarity metrics to develop a methodology capable of quantitatively assessing whether a modern research-based MRI sequence can be co-registered to the Gamma Knife CBCT with equal or less than equal accuracy when compared to a clinically accepted protocol.
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Radiocirurgia , Humanos , CrânioRESUMO
Chemical exchange saturation transfer (CEST) MRI was performed for the evaluation of cerebral metabolic changes in a rat model of depressive-like disease induced by chronic unpredictable mild stress (CUMS). CEST Z-spectra were acquired on a 7 T MRI with two saturation B1 amplitudes (0.5 and 0.75 µT) to measure the magnetization transfer ratio (MTR), CEST and relayed nuclear Overhauser effect (rNOE). Cerebral cortex and hippocampus were examined in two groups of animals: healthy control (n = 10) and stressed (n = 14), the latter of which was exposed to eight weeks of the CUMS protocol. The stressed group Z-spectrum parameters, primarily MTRs, were significantly lower than in controls, at all selected frequency offsets (3.5, 3.0, 2.0, - 3.2, - 3.6 ppm) in the cortex (the largest difference of ~ 3.5% at - 3.6 ppm, p = 0.0005) and the hippocampus (MTRs measured with a B1 = 0.5 µT). The hippocampal rNOE contributions decreased significantly in the stressed brains. Glutamate concentration (assessed using ELISA) and MTR at 3 ppm correlated positively in both brain regions. GABA concentration also correlated positively with CEST contributions in both cerebral areas, while such correlation with MTR was positive in hippocampus, and nonsignificant in cortex. Results indicate that CEST is sensitive to neurometabolic changes following chronic stress exposure.
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Córtex Cerebral/diagnóstico por imagem , Depressão/diagnóstico por imagem , Depressão/patologia , Hipocampo/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Estresse Psicológico/complicações , 5-Metiltetra-Hidrofolato-Homocisteína S-Metiltransferase/metabolismo , Animais , Córtex Cerebral/metabolismo , Córtex Cerebral/patologia , Doença Crônica , Depressão/etiologia , Depressão/metabolismo , Modelos Animais de Doenças , Glutamatos/metabolismo , Hipocampo/metabolismo , Hipocampo/patologia , Ratos , Ácido gama-Aminobutírico/metabolismoRESUMO
MRI phantom studies often fail to mimic the temperature of the human body, which can negatively impact accuracy. An artifact induced by increasing temperature in liquid phantoms was observed, presenting a significant challenge to temperature-controlled experiments. In this study we characterize and provide a solution to eliminate this temperature-induced MRI artifact. Low concentration (0.5-2.5 mM) agar phantoms were prepared. Utilizing a temperature-controlled phantom holder, T1 - and T2 -weighted structural images were acquired at 7 T along with quantitative B0 , B1 , T1 , T2 and ADC maps at both 25 and 37°C. Additionally, computer simulations were conducted to demonstrate the fluid flow and thermal flux patterns in water to provide an insight into the origins of the artifact. Evidence from computer simulation and quantitative MRI strongly suggest the artifact was caused by heat transfer in the form of natural convection leading to structured patterns of signal loss in MR images. The artifact was present up to agar concentrations of 1.5 mM (T1 = 3068 ± 16 ms, T2 = 1052 ± 20 ms, ADC = 2.29 ± 0.36 × 10-3 mm2 /s at 25°C; T1 = 3928 ± 44 ms, T2 = 1122 ± 24 ms, ADC = 2.64 ± 0.49 × 10-3 mm2 /s at 37°C), above which point increased sample viscosity no longer allows for convection currents, thereby eliminating the artifact. The methodology described in this work simplifies quantitative MR acquisition of liquid phantoms at physiological temperature by suppressing convection currents with relatively small changes to intrinsic MR parameters (T1 increased by 1.4% and T2 decreased by 17% for 1.5 mM agar at 25°C).
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Artefatos , Convecção , Imageamento por Ressonância Magnética , Imagens de Fantasmas , Temperatura , Simulação por Computador , DifusãoRESUMO
Histopathology is currently the most reliable tool in assessing the aggressiveness and prognosis of solid tumours. However, developing non-invasive modalities for tumour evaluation remains crucial due to the side effects and complications caused by biopsy procedures. In this study, saturation transfer MRI was used to investigate the microstructural and metabolic properties of tumour xenografts in mice derived from the prostate cancer cell lines 22Rv1 and DU145, which express different aggressiveness. The magnetization transfer (MT) and chemical exchange saturation transfer (CEST) effects, which are associated with the microstructural and metabolic properties in biological tissue, respectively, were analyzed quantitatively and compared amongst different tumour types and regions. Histopathological staining was performed as a reference. Higher cellular density and metabolism expressed in more aggressive tumours (22Rv1) were associated with larger MT and CEST effects. High collagen content in the necrotic regions might explain their higher MT effects compared to tumour regions.
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Adenocarcinoma/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Transplante de Neoplasias/diagnóstico por imagem , Neoplasias da Próstata/diagnóstico por imagem , Animais , Linhagem Celular Tumoral , Feminino , Masculino , Camundongos NusRESUMO
Saturation transfer MRI can be useful in the characterization of different tumour types. It is sensitive to tumour metabolism, microstructure, and microenvironment. This study aimed to use saturation transfer to differentiate between intratumoural regions, demarcate tumour boundaries, and reduce data acquisition times by identifying the imaging scheme with the most impact on segmentation accuracy. Saturation transfer-weighted images were acquired over a wide range of saturation amplitudes and frequency offsets along with T1 and T2 maps for 34 tumour xenografts in mice. Independent component analysis and Gaussian mixture modelling were used to segment the images and identify intratumoural regions. Comparison between the segmented regions and histopathology indicated five distinct clusters: three corresponding to intratumoural regions (active tumour, necrosis/apoptosis, and blood/edema) and two extratumoural (muscle and a mix of muscle and connective tissue). The fraction of tumour voxels segmented as necrosis/apoptosis quantitatively matched those calculated from TUNEL histopathological assays. An optimal protocol was identified providing reasonable qualitative agreement between MRI and histopathology and consisting of T1 and T2 maps and 22 magnetization transfer (MT)-weighted images. A three-image subset was identified that resulted in a greater than 90% match in positive and negative predictive value of tumour voxels compared to those found using the entire 24-image dataset. The proposed algorithm can potentially be used to develop a robust intratumoural segmentation method.
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Adenocarcinoma/patologia , Algoritmos , Processamento de Imagem Assistida por Computador/métodos , Aprendizado de Máquina , Imageamento por Ressonância Magnética/métodos , Neoplasias da Próstata/patologia , Animais , Apoptose , Automação , Proliferação de Células , Feminino , Humanos , Masculino , Camundongos , Camundongos Nus , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
PURPOSE: The diagnosis of monoamine-related psychiatric disorders is based on the phenomenological evaluation of symptoms and behavior by trained clinicians. The CEST technique can be sensitive to monoamines such as serotonin. This study quantifies the CEST properties of the compounds in the serotonin biosynthesis pathway with the goal of developing noninvasive techniques aimed at advancing the diagnostic assessment of serotonin dysfunction. METHODS: Saturation transfer-weighted images of L-tryptophan, 5-hydroxytryptophan, serotonin, 5-hydroxyindoleacetic acid, and melatonin phantoms were acquired over a range of saturation amplitudes and frequency offsets along with observed T1 , T2 , and B1 efficiency maps at physiological temperature and pH of 5.5, 6.7, and 7.4. The CEST and MT data were fitted to a three-pool Bloch-McConnell model of exchange to estimate the model parameters. RESULTS: At a pH of 5.5, tryptophan, 5-hydroxytryptophan and serotonin exhibited significant CEST contrast at resonance frequency offset, Δω between 2.64 ppm and 2.71 ppm, and magnetization transfer ratio asymmetry amplitudes up to 20% per 30 mM. At a pH of 7.4, all molecules exhibited significant CEST contrast between 5.11 ppm and 5.47 ppm, and magnetization transfer ratio asymmetry amplitudes up to 9.5% per 30 mM. At a pH of 6.7, all studied compounds except melatonin exhibited a CEST peak from each of the preceding two pHs. CONCLUSION: At a pH of 5.5, tryptophan, 5-hydroxytryptophan, and serotonin CEST contrast originates from the NH3+ side chain, whereas at a pH of 7.4, CEST contrast is due to the chemical exchange between water and the NH proton on the indole ring. The data in this study could be used to inform future investigations aimed at detecting and measuring in vivo serotonin.
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Imageamento por Ressonância Magnética , Serotonina , Humanos , Concentração de Íons de Hidrogênio , Imagens de Fantasmas , PrótonsRESUMO
Accurate characterization of the craniomaxillofacial (CMF) skeleton using finite element (FE) modeling requires representation of complex geometries, heterogeneous material distributions, and physiological loading. Musculature in CMF FE models are often modeled with simple link elements that do not account for fiber bundles (FBs) and their differential activation. Magnetic resonance (MR) diffusion-tensor imaging (DTI) enables reconstruction of the three-dimensional (3D) FB arrangement within a muscle. However, 3D quantitative validation of DTI-generated FBs is limited. This study compares 3D FB arrangement in terms of pennation angle (PA) and fiber bundle length (FBL) generated through DTI in a human masseter to manual digitization. CT, MR-proton density, and MR-DTI images were acquired from a single cadaveric specimen. Bone and masseter surfaces were reconstructed from CT and MR-proton density images, respectively. PA and FBL were estimated from FBs reconstructed from MR-DTI images using a streamline tracking (STT) algorithm (n = 193) and FBs identified through manual digitization (n = 181) and compared using the Mann-Whitney test. DTI-derived PAs did not differ from the digitized data (p = 0.411), suggesting that MR-DTI can be used to simulate FB orientation and the directionality of transmitted forces. Conversely, a significant difference was observed in FBL (p < 0.01) which may have resulted due to the tractography stopping criterion leading to early tract termination and greater length variability. Overall, this study demonstrated that DTI can yield muscle FB orientation data suitable to representative directionality of physiologic muscle loading in patient-specific CMF FE modeling.
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Imagem de Tensor de Difusão , Processamento de Imagem Assistida por Computador/métodos , Músculo Masseter/diagnóstico por imagem , Feminino , Humanos , Lactente , Tomografia Computadorizada por Raios XRESUMO
PURPOSE: Detecting cell death and predicting tumor response early in a course of chemotherapy could help optimize treatment regimens and improve clinical outcomes. Chemical exchange saturation transfer (CEST) MRI was investigated in vivo to study properties that may be able to detect cancer death. RESULTS: Using a magnetization transfer ratio (MTR) cutoff of 0.12 at 1.8 ppm was able to differentiate between viable tumor and cell death regions. Comparison of MTR values at this frequency showed significant differences (p < 0.0001) between viable tumor and cell death regions, matching patterns seen on histology. Using this cutoff, the mean increase in cell death index (± standard error of the mean) after chemotherapy was 4 ± 4%, 10% ± 7%, 10 ± 8%, and 4 ± 9% at 4, 8, 12, and 24 h, respectively. CONCLUSIONS: CEST MRI can detect cell death in MDA-231 xenografts but further work is needed to characterize the clinical applications of this finding. Maximum response to chemotherapy occurred at 8-12 h after chemotherapy injection in this in vivo tumor model. MATERIALS AND METHODS: Breast cancer xenografts (MDA-MB-231) were scanned using 7 T MRI before and after chemotherapy. As a measure of CEST effect at 0.5 µT saturation amplitude, MTR values at frequency offsets of 1.8 and -3.3 ppm were evaluated. CEST signals after chemotherapy treatment were compared to cell-death histopathology of tumors.
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The ability of MRI to differentiate between normal and radioresistant cancer was investigated in prostate tumour xenografts in mice. Specifically, the process of magnetization exchange between water and other molecules was studied. It was found that magnetization transfer from semisolid macromolecules (MT) and chemical exchange saturation transfer (CEST) combined were significantly different between groups (p < 0.01). Further, the T2 relaxation of the semisolid macromolecular pool (T2,B), a parameter specific to MT, was found to be significantly different (p < 0.01). Also significantly different were the rNOE contributions associated with methine groups at -0.9 ppm with a saturation B1 of 0.5 µT (p < 0.01) and with other aliphatic groups at -3.3 ppm with 0.5 and 2 µT (both p < 0.05). Independently, using a live-cell metabolic assay, normal cells were found to have a greater metabolic rate than radioresistant ones. Thus, MRI provides a novel, in vivo method to quantify the metabolic rate of tumours and predict their radiosensitivity.
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Imageamento por Ressonância Magnética/métodos , Neoplasias da Próstata/diagnóstico , Tolerância a Radiação , Animais , Metabolismo Basal , Linhagem Celular , Diagnóstico Diferencial , Xenoenxertos , Humanos , Magnetismo , Masculino , Camundongos , Consumo de Oxigênio , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/fisiopatologiaRESUMO
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 300â MHz 1 Hâ NMR, 3â T and 7â 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.
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PURPOSE: The objective was to investigate (with quantitative MRI) whether the normal appearing white matter (NAWM) of glioblastoma (GBM) patients on the contralateral side (cNAWM) was different from NAWM of healthy controls. METHODS: Thirteen patients with newly diagnosed GBM and nine healthy age-matched controls were MRI-scanned with quantitative magnetization transfer (qMT), chemical exchange saturation transfer (CEST), and transverse relaxation time (T2)-mapping. MRI scans were performed after surgery and before chemo-radiation treatment. Comprehensive qMT, CEST, T2 data were acquired. A two-pool MT model was fit to qMT data in transient state, to calculate MT model parameters [Formula: see text]. CEST signal was isolated by removing the contributions from the MT and direct water saturation, and CEST signal was calculated for Amide (CESTAmide), Amine (CESTAmine) and nuclear overhauser effect, NOE (CESTNOE). RESULTS: There was no difference between GBM patients and normal controls in the qMT properties of the macromolecular pool [Formula: see text]. However, their free water pool spectrum was different (1/RaT2a,patient = 28.1 ± 3.9, 1/RaT2a,control = 25.0 ± 1.1, p = 0.03). This difference could be attributed to the difference in their T2 time ([Formula: see text] = 83 ± 4, [Formula: see text] = 88 ± 1, p = 0.004). CEST signals were statistically significantly different with the CESTAmide having the largest difference between the two cohorts (CESTAmide,patient = 2.8 ± 0.4, CESTAmide,control = 3.4 ± 0.5, p = 0.009). CONCLUSIONS: CEST in cNAWM of GBM patients was lower than healthy controls which could be caused by modified brain metabolism due to tumor cell infiltration. There was no difference in MT properties of the patients and controls, however, the differences in free water pool properties were mainly due to reduced T2 in cNAWM of the patients (resulting from structural changes and increased cellularity).
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Neoplasias Encefálicas/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Glioblastoma/diagnóstico por imagem , Imageamento por Ressonância Magnética , Substância Branca/diagnóstico por imagem , Neoplasias Encefálicas/terapia , Feminino , Lateralidade Funcional , Glioblastoma/terapia , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-IdadeRESUMO
Magnetization Transfer Contrast (MTC) and Chemical Exchange Saturation Transfer (CEST) experiments measure the transfer of magnetization from molecular protons to the solvent water protons, an effect that becomes apparent as an MRI signal loss ("saturation"). This allows molecular information to be accessed with the enhanced sensitivity of MRI. In analogy to Magnetic Resonance Spectroscopy (MRS), these saturation data are presented as a function of the chemical shift of participating proton groups, e.g. OH, NH, NH2, which is called a Z-spectrum. In tissue, these Z-spectra contain the convolution of multiple saturation transfer effects, including nuclear Overhauser enhancements (NOEs) and chemical exchange contributions from protons in semi-solid and mobile macromolecules or tissue metabolites. As a consequence, their appearance depends on the magnetic field strength (B0) and pulse sequence parameters such as B1 strength, pulse shape and length, and interpulse delay, which presents a major problem for quantification and reproducibility of MTC and CEST effects. The use of higher B0 can bring several advantages. In addition to higher detection sensitivity (signal-to-noise ratio, SNR), both MTC and CEST studies benefit from longer water T1 allowing the saturation transferred to water to be retained longer. While MTC studies are non-specific at any field strength, CEST specificity is expected to increase at higher field because of a larger chemical shift dispersion of the resonances of interest (similar to MRS). In addition, shifting to a slower exchange regime at higher B0 facilitates improved detection of the guanidinium protons of creatine and the inherently broad resonances of the amine protons in glutamate and the hydroxyl protons in myoinositol, glycogen, and glucosaminoglycans. Finally, due to the higher mobility of the contributing protons in CEST versus MTC, many new pulse sequences can be designed to more specifically edit for CEST signals and to remove MTC contributions.
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Química Encefálica , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Fenômenos Magnéticos , Imageamento por Ressonância Magnética/métodos , Espectroscopia de Ressonância Magnética/métodos , HumanosRESUMO
PURPOSE: To demonstrate how reference data affect the quantification of the apparent diffusion coefficient (ADC) in long diffusion time measurements with diffusion-weighted stimulated echo acquisition mode (DW-STEAM) measurements, and to present a modification to avoid contribution from crusher gradients in DW-STEAM. METHODS: For DW-STEAM, reference measurements at long diffusion times have significant b0 value, because b = 0 cannot be achieved in practice as a result of the need for signal spoiling. Two strategies for acquiring reference data over a range of diffusion times were considered: constant diffusion weighting (fixed-b0 ) and constant gradient area (fixed-q0 ). Fixed-b0 and fixed-q0 were compared using signal calculations for systems with one and two diffusion coefficients, and experimentally using data from postmortem human corpus callosum samples. RESULTS: Calculations of biexponential diffusion decay show that the ADC is underestimated for reference images with b > 0, which can induce an apparent time-dependence for fixed-q0 . Restricted systems were also found to be affected. Experimentally, the exaggeration of the diffusion time-dependent effect under fixed-q0 versus fixed-b0 was in a range predicted theoretically, accounting for 62% (longitudinal) and 35% (radial) of the time dependence observed in white matter. CONCLUSIONS: Variation in the b-value of reference measurements in DW-STEAM can induce artificial diffusion time dependence in ADC, even in the absence of restriction. Magn Reson Med 79:952-959, 2018. © 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
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Imagem de Difusão por Ressonância Magnética/métodos , Corpo Caloso/diagnóstico por imagem , Humanos , Processamento de Sinais Assistido por ComputadorRESUMO
PURPOSE: In the brain, there is growing interest in using the temporal diffusion spectrum to characterize axonal geometry in white matter because of the potential to be more sensitive to small pores compared to conventional time-dependent diffusion. However, analytical expressions for the diffusion spectrum of particles have only been derived for simple, restricting geometries such as cylinders, which are often used as a model for intra-axonal diffusion. The extra-axonal space is more complex, but the diffusion spectrum has largely not been modeled. We propose a model for the extra-axonal space, which can be used for interpretation of experimental data. THEORY AND METHODS: An empirical model describing the extra-axonal space diffusion spectrum was compared with simulated spectra. Spectra were simulated using Monte Carlo methods for idealized, regularly and randomly packed axons over a wide range of packing densities and spatial scales. The model parameters are related to the microstructural properties of tortuosity, axonal radius, and separation for regularly packed axons and pore size for randomly packed axons. RESULTS: Forward model predictions closely matched simulations. The model fitted the simulated spectra well and accurately estimated microstructural properties. CONCLUSIONS: This simple model provides expressions that relate the diffusion spectrum to biologically relevant microstructural properties.
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Axônios , Imagem de Difusão por Ressonância Magnética/métodos , Substância Branca/anatomia & histologia , Processamento de Imagem Assistida por Computador , Modelos Teóricos , Método de Monte CarloRESUMO
PURPOSE: To design and demonstrate a new susceptibility-based tracking device with an artifact that can be mechanically turned on and off, thus permitting tracking and imaging at the device tip with limited artifact. METHODS: The magnetic susceptibilities of readily obtainable grades of titanium and graphite were measured. Using numerical optimization, layer thicknesses for three concentric cylinders were found where the field from the graphite layer maximally cancelled the fields from titanium layers. The tracking elements were fabricated for an outer diameter of 3 mm and attached to a catheter to show feasibility of detection in phantoms and in vivo. RESULTS: The device was successfully integrated into a 9F catheter, and its use with conventional guidewires under fluoroscopy was demonstrated by guiding the catheter through the bifurcation into the carotid artery. MR images including the catheter tip were acquired with the device in both the "on" and "off" positions. CONCLUSION: A new passive tracking device with a susceptibility effect that can be enabled and disabled by sliding one of the components was designed, fabricated, and demonstrated in phantoms and in vivo. The device may also be integrated into many different interventional MR devices such as needles, ultrasound transducers for prostate biopsy, or any catheter-based devices.
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Catéteres , Imageamento por Ressonância Magnética/instrumentação , Animais , Artefatos , Desenho de Equipamento , Fluoroscopia , Grafite/química , Imageamento Tridimensional/instrumentação , Monitorização Fisiológica , Imagens de Fantasmas , Politetrafluoretileno , Suínos , Titânio/químicaRESUMO
(13)C MR spectroscopy studies performed on hearts ex vivo and in vivo following perfusion of prepolarized [1-(13)C]pyruvate have shown that changes in pyruvate dehydrogenase (PDH) flux may be monitored non-invasively. However, to allow investigation of Krebs cycle metabolism, the (13)C label must be placed on the C2 position of pyruvate. Thus, the utilization of either C1 or C2 labeled prepolarized pyruvate as a tracer can only afford a partial view of cardiac pyruvate metabolism in health and disease. If the prepolarized pyruvate molecules were labeled at both C1 and C2 positions, then it would be possible to observe the downstream metabolites that were the results of both PDH flux ((13)CO(2) and H(13)CO(3)(-)) and Krebs cycle flux ([5-(13)C]glutamate) with a single dose of the agent. Cardiac pH could also be monitored in the same experiment, but adequate SNR of the (13)CO(2) resonance may be difficult to obtain in vivo. Using an interleaved selective RF pulse acquisition scheme to improve (13)CO(2) detection, the feasibility of using dual-labeled hyperpolarized [1,2-(13)C(2)]pyruvate as a substrate for dynamic cardiac metabolic MRS studies to allow simultaneous investigation of PDH flux, Krebs cycle flux and pH, was demonstrated in vivo.
Assuntos
Ciclo do Ácido Cítrico , Miocárdio/enzimologia , Complexo Piruvato Desidrogenase/metabolismo , Ácido Pirúvico/metabolismo , Animais , Bicarbonatos/metabolismo , Dióxido de Carbono/metabolismo , Isótopos de Carbono , Concentração de Íons de Hidrogênio , Imagens de Fantasmas , Sus scrofaRESUMO
Lung ventilation was mapped in five healthy Brown Norway rats (210-377 g) using both hyperpolarized (3)He MRI and Xe-enhanced computed tomography (Xe-CT) under similar ventilator conditions. Whole-lung measurements of ventilation r obtained with (3)He MRI were not significantly different from those obtained from Xe-CT (p = 0.1875 by Wilcoxon matched pairs test). The ventilation parameter r is defined as the fraction of refreshed gas per unit volume per breath. Regional ventilation was also measured in four regions of the lung using both methods. A two-tailed paired t-test was performed for each region, yielding p > 0.05 for all but the upper portion of the right lung. The distribution of regional ventilation was evaluated by calculating ventilation gradients in the superior/inferior (S/I) direction. The average S/I gradient obtained using the (3)He MRI method was found to be 0.17 ± 0.04 cm(-1) , whereas the average S/I gradient obtained using the Xe-CT method was found to be 0.016 ± 0.005 cm(-1) . In general, S/I ventilation gradients obtained from both methods were significantly different from each other (p = 0.0019 by two-tailed paired t-test). These regional differences in ventilation measurements may be caused by the manner in which the gas contrast agents distribute physiologically and/or by the imaging modality.