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1.
PLoS One ; 15(11): e0242483, 2020.
Article in English | MEDLINE | ID: mdl-33216786

ABSTRACT

For decades, traditional correlation analysis and regression models have been used in social science research. However, the development of machine learning algorithms makes it possible to apply machine learning techniques for social science research and social issues, which may outperform standard regression methods in some cases. Under the circumstances, this article proposes a methodological workflow for data analysis by machine learning techniques that have the possibility to be widely applied in social issues. Specifically, the workflow tries to uncover the natural mechanisms behind the social issues through a data-driven perspective from feature selection to model building. The advantage of data-driven techniques in feature selection is that the workflow can be built without so much restriction of related knowledge and theory in social science. The advantage of using machine learning techniques in modelling is to uncover non-linear and complex relationships behind social issues. The main purpose of our methodological workflow is to find important fields relevant to the target and provide appropriate predictions. However, to explain the result still needs theory and knowledge from social science. In this paper, we trained a methodological workflow with left-behind children as the social issue case, and all steps and full results are included.


Subject(s)
Child, Abandoned/statistics & numerical data , Machine Learning , Models, Theoretical , Social Sciences/methods , Workflow , Algorithms , Child , China , Data Analysis , Education/statistics & numerical data , Humans , Neural Networks, Computer , Parents
2.
Article in English | MEDLINE | ID: mdl-33167348

ABSTRACT

Mental health is the foundation of health and happiness as well as the basis for an individual's meaningful life. The environmental and social health of a city can measure the mental state of people living in a certain areas, and exploring urban dwellers' mental states is an important factor in understanding and better managing cities. New dynamic and granular urban data provide us with a way to determine the environmental factors that affect the mental states of urban dwellers. The characteristics of the maximal information coefficient can identify the linear and nonlinear relationships so that we can fully identify the physical and social environmental factors that affect urban dwellers' mental states and further test these relationships through linear and nonlinear modeling. Taking the Greater London as an example, we used data from the London Datastore to discover the environmental factors that had the highest correlation with urban mental health from 2015 to 2017 and to prove that they had a high nonlinear correlation through neural network modeling. This paper aimed to use a data-driven approach to find environmental factors that had not yet received enough attention and to provide a starting point for research by establishing hypotheses for further exploration of the impact of environmental factors on mental health.


Subject(s)
Mental Health , Urban Health , Urban Population , Cities , Humans , London
3.
Sensors (Basel) ; 20(19)2020 Sep 28.
Article in English | MEDLINE | ID: mdl-32998427

ABSTRACT

Road surface monitoring and maintenance are essential for driving comfort, transport safety and preserving infrastructure integrity. Traditional road condition monitoring is regularly conducted by specially designed instrumented vehicles, which requires time and money and is only able to cover a limited proportion of the road network. In light of the ubiquitous use of smartphones, this paper proposes an automatic pothole detection system utilizing the built-in vibration sensors and global positioning system receivers in smartphones. We collected road condition data in a city using dedicated vehicles and smartphones with a purpose-built mobile application designed for this study. A series of processing methods were applied to the collected data, and features from different frequency domains were extracted, along with various machine-learning classifiers. The results indicated that features from the time and frequency domains outperformed other features for identifying potholes. Among the classifiers tested, the Random Forest method exhibited the best classification performance for potholes, with a precision of 88.5% and recall of 75%. Finally, we validated the proposed method using datasets generated from different road types and examined its universality and robustness.

4.
Build Environ ; 186: 107323, 2020 Dec.
Article in English | MEDLINE | ID: mdl-33041458

ABSTRACT

It is crucial to accurately and efficiently predict transient particle transport in indoor environments to improve air distribution design and reduce health risks. For steady-state indoor airflow, fast fluid dynamics (FFD) + Markov chain model increased the calculation speed by around seven times compared to computational fluid dynamics (CFD) + Eulerian model and CFD + Lagrangian model, while achieving the same level of accuracy. However, the indoor airflow could be transient, if there were human behaviors involved like coughing or sneezing and air was supplied periodically. Therefore, this study developed an FFD + Markov chain model solver for predicting transient particle transport in transient indoor airflow. This investigation used two cases, transient particle transport in a ventilated two-zone chamber and a chamber with periodic air supplies, for validation. Case 1 had experimental data for validation and the results showed that the predicted particle concentration by FFD + Markov chain model matched well with the experimental data. Besides, it had similar accuracy as the CFD + Eulerian model. In the second case, the prediction by large eddy simulation (LES) was used for validating the FFD. The simulated particle concentrations by the Markov chain model and the Eulerian model were similar. The simulated particle concentrations by the Markov chain model and the Eulerian model were similar. The computational time of the FFD + Markov chain model was 7.8 times less than that of the CFD + Eulerian model.

5.
Magn Reson Med ; 71(1): 1-11, 2014 Jan.
Article in English | MEDLINE | ID: mdl-23412881

ABSTRACT

PURPOSE: Magnetic resonance spectroscopy of hyperpolarized substrates allows for the observation of label exchange catalyzed by enzymes providing a powerful tool to investigate tissue metabolism and potentially kinetics in vivo. However, the accuracy of current methods to calculate kinetic parameters has been limited by T1 relaxation effects, extracellular signal contributions, and reduced precision at lower signal-to-noise ratio. THEORY AND METHODS: To address these challenges, we investigated a new modeling technique using metabolic activity decomposition-stimulated echo acquisition mode. The metabolic activity decomposition-stimulated echo acquisition mode technique separates exchanging from nonexchanging metabolites providing twice the information as conventional techniques. RESULTS: This allowed for accurate measurements of rates of conversion and of multiple T1 values simultaneously using a single acquisition. CONCLUSION: The additional measurement of T1 values for the reaction metabolites provides further biological information about the cellular environment of the metabolites. The new technique was investigated through simulations and in vivo studies of transgenic mouse models of cancer demonstrating improved assessments of kinetic rate constants and new T1 relaxation value measurements for hyperpolarized (13) C-pyruvate, (13) C-lactate, and (13) C-alanine.


Subject(s)
Alanine/chemistry , Biomarkers, Tumor/metabolism , Lactic Acid/metabolism , Liver Neoplasms/metabolism , Magnetic Resonance Spectroscopy/methods , Models, Biological , Pyruvic Acid/metabolism , Algorithms , Animals , Carbon Isotopes/pharmacokinetics , Computer Simulation , Mice , Mice, Transgenic , Reproducibility of Results , Sensitivity and Specificity
6.
J Magn Reson Imaging ; 38(3): 701-13, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23293097

ABSTRACT

PURPOSE: To implement and evaluate combined parallel magnetic resonance imaging (MRI) and partial Fourier acquisition and reconstruction for rapid hyperpolarized carbon-13 ((13) C) spectroscopic imaging. Short acquisition times mitigate hyperpolarized signal losses that occur due to T1 decay, metabolism, and radiofrequency (RF) saturation. Human applications additionally require rapid imaging to permit breath-holding and to minimize the effects of physiologic motion. MATERIALS AND METHODS: Numerical simulations were employed to validate and characterize the reconstruction. In vivo MR spectroscopic images were obtained from a rat following injection of hyperpolarized (13) C pyruvate using an 8-channel array of carbon-tuned receive elements. RESULTS: For small spectroscopic matrix sizes, combined parallel imaging and partial Fourier undersampling resulted primarily in decreased spatial resolution, with relatively less visible spatial aliasing. Parallel reconstruction qualitatively restored lost image detail, although some pixel spectra had persistent numerical error. With this technique, a 30 × 10 × 16 matrix of 4800 3D MR spectroscopy imaging voxels from a whole rat with isotropic 8 mm(3) resolution was acquired within 11 seconds. CONCLUSION: Parallel MRI and partial Fourier acquisitions can provide the shorter imaging times and wider spatial coverage that will be necessary as hyperpolarized (13) C techniques move toward human clinical applications.


Subject(s)
Algorithms , Carbon Isotopes/pharmacokinetics , Carbon/metabolism , Magnetic Resonance Spectroscopy/methods , Molecular Imaging/methods , Animals , Fourier Analysis , Humans , Male , Rats, Sprague-Dawley , Reproducibility of Results , Sensitivity and Specificity
7.
Magn Reson Med ; 70(1): 33-9, 2013 Jul.
Article in English | MEDLINE | ID: mdl-22851374

ABSTRACT

High resolution compressed sensing hyperpolarized (13)C magnetic resonance spectroscopic imaging was applied in orthotopic human glioblastoma xenografts for quantitative assessment of spatial variations in (13)C metabolic profiles and comparison with histopathology. A new compressed sensing sampling design with a factor of 3.72 acceleration was implemented to enable a factor of 4 increase in spatial resolution. Compressed sensing 3D (13)C magnetic resonance spectroscopic imaging data were acquired from a phantom and 10 tumor-bearing rats following injection of hyperpolarized [1-(13)C]-pyruvate using a 3T scanner. The (13)C metabolic profiles were compared with hematoxylin and eosin staining and carbonic anhydrase 9 staining. The high-resolution compressed sensing (13)C magnetic resonance spectroscopic imaging data enabled the differentiation of distinct (13)C metabolite patterns within abnormal tissues with high specificity in similar scan times compared to the fully sampled method. The results from pathology confirmed the different characteristics of (13)C metabolic profiles between viable, non-necrotic, nonhypoxic tumor, and necrotic, hypoxic tissue.


Subject(s)
Biomarkers, Tumor/metabolism , Brain Neoplasms/metabolism , Data Compression/methods , Glioblastoma/metabolism , Magnetic Resonance Imaging/methods , Magnetic Resonance Spectroscopy/methods , Neoplasm Proteins/metabolism , Animals , Carbon Isotopes , Cell Line, Tumor , Humans , Imaging, Three-Dimensional/methods , Male , Molecular Imaging/methods , Rats , Rats, Nude , Reproducibility of Results , Sensitivity and Specificity , Tissue Distribution
8.
Magn Reson Imaging ; 31(4): 490-6, 2013 May.
Article in English | MEDLINE | ID: mdl-23107275

ABSTRACT

The development of hyperpolarized technology utilizing dynamic nuclear polarization (DNP) has enabled the rapid measurement of (13)C metabolism in vivo with very high SNR. However, with traditional DNP equipment, consecutive injections of a hyperpolarized compound in an animal have been subject to a practical minimum time between injections governed by the polarization build-up time, which is on the order of an hour for [1-(13)C]pyruvate. This has precluded the monitoring of metabolic changes occurring on a faster time scale. In this study, we demonstrated the ability to acquire in vivo dynamic magnetic resonance spectroscopy (MRS) and 3D magnetic resonance spectroscopic imaging (MRSI) data in normal rats with a 5 min interval between injections of hyperpolarized [1-(13)C]pyruvate using a prototype, sub-Kelvin dynamic nuclear polarizer with the capability to simultaneously polarize up to 4 samples and dissolve them in rapid succession. There were minimal perturbations in the hyperpolarized spectra as a result of the multiple injections, suggesting that such an approach would not confound the investigation of metabolism occurring on this time scale. As an initial demonstration of the application of this technology and approach for monitoring rapid changes in metabolism as a result of a physiological intervention, we investigated the pharmacodynamics of the anti-cancer agent dichloroacetate (DCA), collecting hyperpolarized data before administration of DCA, 1 min after administration, and 6 min after administration. Dramatic increases in (13)C-bicarbonate were detected just 1 min (as well as 6 min) after DCA administration.


Subject(s)
Dichloroacetic Acid/pharmacokinetics , Image Enhancement/methods , Magnetic Resonance Imaging/methods , Magnetic Resonance Spectroscopy/methods , Molecular Imaging/methods , Pyruvic Acid/administration & dosage , Pyruvic Acid/pharmacokinetics , Animals , Carbon Isotopes/administration & dosage , Carbon Isotopes/pharmacokinetics , Male , Metabolic Clearance Rate , Organ Specificity , Rats , Rats, Sprague-Dawley , Reproducibility of Results , Sensitivity and Specificity , Tissue Distribution
9.
Magn Reson Imaging ; 30(10): 1367-72, 2012 Dec.
Article in English | MEDLINE | ID: mdl-22819176

ABSTRACT

Development of hyperpolarized technology utilizing dynamic nuclear polarization has enabled the measurement of (13)C metabolism in vivo at very high signal-to-noise ratio (SNR). In vivo mitochondrial metabolism can, in principle, be monitored with pyruvate, which is catalyzed to acetyl-CoA via pyruvate dehydrogenase (PDH). The purpose of this work was to determine whether the compound sodium dichloroacetate (DCA) could aid the study of mitochondrial metabolism with hyperpolarized pyruvate. DCA stimulates PDH by inhibiting its inhibitor, pyruvate dehydrogenase kinase. In this work, hyperpolarized [1-(13)C]pyruvate and [2-(13)C]pyruvate were used to probe mitochondrial metabolism in normal rats. Increased conversion to bicarbonate (+181±69%, P=.025) was measured when [1-(13)C]pyruvate was injected after DCA administration, and increased glutamate (+74±23%, P=.004), acetoacetate (+504±281%, P=.009) and acetylcarnitine (+377±157%, P=.003) were detected when [2-(13)C]pyruvate was used.


Subject(s)
Antineoplastic Agents/pharmacology , Carbon Isotopes/metabolism , Dichloroacetic Acid/pharmacology , Magnetic Resonance Spectroscopy/methods , Mitochondria/metabolism , Pyruvic Acid/metabolism , Acetoacetates/chemistry , Acetylcarnitine/chemistry , Animals , Catalysis , Glutamic Acid/chemistry , Male , Mitochondria/drug effects , Models, Biological , Pyruvate Dehydrogenase Complex/metabolism , Pyruvic Acid/chemistry , Rats , Rats, Sprague-Dawley
10.
Magn Reson Imaging ; 30(3): 305-11, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22169407

ABSTRACT

The metabolically inactive hyperpolarized agents HP001 (bis-1,1-(hydroxymethyl)-[1-(13)C]cyclopropane-d(8)) and urea enable a new type of perfusion magnetic resonance imaging based on a direct signal source that is background-free. The addition of perfusion information to metabolic information obtained by spectroscopic imaging of hyperpolarized [1-(13)C]pyruvate would be of great value in exploring the relationship between perfusion and metabolism in cancer. In preclinical normal murine and cancer model studies, we performed both dynamic multislice imaging of the specialized hyperpolarized perfusion compound HP001 (T(1)=95 s ex vivo, 32 s in vivo at 3 T) using a pulse sequence with balanced steady-state free precession and ramped flip angle over time for efficient utilization of the hyperpolarized magnetization and three-dimensional echo-planar spectroscopic imaging of urea copolarized with [1-(13)C]pyruvate, with compressed sensing for resolution enhancement. For the dynamic data, peak signal maps and blood flow maps derived from perfusion modeling were generated. The spatial heterogeneity of perfusion was increased 2.9-fold in tumor tissues (P=.05), and slower washout was observed in the dynamic data. The results of separate dynamic HP001 imaging and copolarized pyruvate/urea imaging were compared. A strong and significant correlation (R=0.73, P=.02) detected between the urea and HP001 data confirmed the value of copolarizing urea with pyruvate for simultaneous assessment of perfusion and metabolism.


Subject(s)
Carbon Isotopes/metabolism , Contrast Media/metabolism , Cyclopropanes/metabolism , Imaging, Three-Dimensional/methods , Liver Neoplasms, Experimental/blood supply , Liver Neoplasms, Experimental/metabolism , Magnetic Resonance Spectroscopy/methods , Neoplasms, Experimental/blood supply , Neoplasms, Experimental/metabolism , Prostatic Neoplasms/blood supply , Prostatic Neoplasms/metabolism , Pyruvic Acid/metabolism , Urea/metabolism , Animals , Disease Models, Animal , Male , Mice , Mice, Transgenic , Rats , Rats, Sprague-Dawley
11.
Magn Reson Imaging ; 29(8): 1035-40, 2011 Oct.
Article in English | MEDLINE | ID: mdl-21855243

ABSTRACT

Hyperpolarized technology utilizing dynamic nuclear polarization has enabled rapid and high-sensitivity measurements of (13)C metabolism in vivo. The most commonly used in vivo agent for hyperpolarized (13)C metabolic imaging thus far has been [1-(13)C]pyruvate. In preclinical studies, not only is its uptake detected, but also its intracellular enzymatic conversion to metabolic products including [1-(13)C]lactate and [1-(13)C]alanine. However, the ratio of (13)C-lactate/(13)C-pyruvate measured in this data does not accurately reflect cellular values since much of the [1-(13)C]pyruvate is extracellular depending on timing, vascular properties, and extracellular space and monocarboxylate transporter activity. In order to measure the relative levels of intracellular pyruvate and lactate, in this project we hyperpolarized [1-(13)C]alanine and monitored the in vivo conversion to [1-(13)C]pyruvate and then the subsequent conversion to [1-(13)C]lactate. The intracellular lactate-to-pyruvate ratio of normal rat tissue measured with hyperpolarized [1-(13)C]alanine was 4.89±0.61 (mean±S.E.) as opposed to a ratio of 0.41±0.03 when hyperpolarized [1-(13)C]pyruvate was injected.


Subject(s)
Alanine/metabolism , Carbon Isotopes/metabolism , Lactic Acid/metabolism , Pyruvic Acid/metabolism , Animals , Image Processing, Computer-Assisted/methods , Kinetics , Magnetic Resonance Spectroscopy/methods , Male , Monocarboxylic Acid Transporters/metabolism , Rats , Rats, Sprague-Dawley , Signal-To-Noise Ratio
12.
Cell Metab ; 14(1): 131-42, 2011 Jul 06.
Article in English | MEDLINE | ID: mdl-21723511

ABSTRACT

Tumor cells have an altered metabolic phenotype characterized by increased glycolysis and diminished oxidative phosphorylation. Despite the suspected importance of glycolysis in tumorigenesis, the temporal relationship between oncogene signaling, in vivo tumor formation, and glycolytic pathway activity is poorly understood. Moreover, how glycolytic pathways are altered as tumors regress remains unknown. Here, we use a switchable model of Myc-driven liver cancer, along with hyperpolarized (13)C-pyruvate magnetic resonance spectroscopic imaging (MRSI) to visualize glycolysis in de novo tumor formation and regression. LDHA abundance and activity in tumors is tightly correlated to in vivo pyruvate conversion to lactate and is rapidly inhibited as tumors begin to regress, as are numerous glycolysis pathway genes. Conversion of pyruvate to alanine predominates in precancerous tissues prior to observable morphologic or histological changes. These results demonstrate that metabolic changes precede tumor formation and regression and are directly linked to the activity of a single oncogene.


Subject(s)
Liver Neoplasms/metabolism , Proto-Oncogene Proteins c-myc/metabolism , Pyruvic Acid/metabolism , Alanine/metabolism , Animals , Carbon Isotopes/chemistry , Citric Acid Cycle/genetics , Disease Models, Animal , Gene Expression Profiling , Glycolysis/genetics , L-Lactate Dehydrogenase/metabolism , Liver Neoplasms/pathology , Magnetic Resonance Imaging , Mice , Mice, Transgenic , Pyruvic Acid/chemistry , Signal Transduction
13.
J Magn Reson ; 211(2): 109-13, 2011 Aug.
Article in English | MEDLINE | ID: mdl-21596601

ABSTRACT

A new method was developed for simultaneous spatial localization and spectral separation of multiple compounds based on a single echo, by designing the acquisition to place individual compounds in separate frequency encoding bands. This method was specially designed for rapid and robust metabolic imaging of hyperpolarized (13)C substrates and their metabolic products, and was investigated in phantom studies and studies in normal mice and transgenic models of prostate cancer to provide rapid metabolic imaging of hyperpolarized [1-(13)C]pyruvate and its metabolic products [1-(13)C]lactate and [1-(13)C]alanine at spatial resolutions up to 3mm in-plane. Elevated pyruvate and lactate signals in the vicinity of prostatic tissues were observed in transgenic tumor mice. The multi-band frequency encoding technique enabled rapid metabolic imaging of hyperpolarized (13)C compounds with important advantages over prior approaches, including less complicated acquisition and reconstruction methods.


Subject(s)
Magnetic Resonance Imaging/methods , Pyruvic Acid , Alanine/metabolism , Algorithms , Animals , Carbon Isotopes , Computer Simulation , Image Processing, Computer-Assisted , Kidney/anatomy & histology , Kidney/metabolism , Lactic Acid/metabolism , Liver/anatomy & histology , Liver/metabolism , Male , Metabolism , Mice , Mice, Transgenic , Phantoms, Imaging , Prostatic Neoplasms/pathology
14.
J Magn Reson Imaging ; 33(3): 692-7, 2011 Mar.
Article in English | MEDLINE | ID: mdl-21563254

ABSTRACT

PURPOSE: To demonstrate dynamic imaging of a diffusible perfusion tracer, hyperpolarized [(13)C]urea, for regional measurement of blood flow in preclinical cancer models. MATERIALS AND METHODS: A pulse sequence using balanced steady state free precession (bSSFP) was developed, with progressively increasing flip angles for efficient sampling of the hyperpolarized magnetization. This allowed temporal and volumetric imaging of the [(13)C]urea signal. Regional signal dynamics were quantified for kidneys and liver, and estimates of relative blood flows were derived from the data. Detailed perfusion simulations were performed to validate the methodology. RESULTS: Significant differences were observed in the signal patterns between normal and cancerous murine hepatic tissues. In particular, a 19% reduction in mean blood flow was observed in tumors, with 26% elevation in the tumor rim. The blood flow maps were also compared with metabolic imaging results with hyperpolarized [1-(13)C]pyruvate. CONCLUSION: Regional assessment of perfusion is possible by imaging of hyperpolarized [(13)C]urea, which is significant for the imaging of cancer.


Subject(s)
Carbon Isotopes/pharmacology , Neoplasms/blood supply , Neoplasms/diagnosis , Algorithms , Animals , Blood Flow Velocity , Diffusion , Disease Models, Animal , Humans , Kidney/pathology , Liver/pathology , Male , Mice , Neoplasm Transplantation , Rats , Rats, Sprague-Dawley
15.
Magn Reson Med ; 65(3): 610-9, 2011 Mar.
Article in English | MEDLINE | ID: mdl-20939089

ABSTRACT

Hyperpolarized 13C MR spectroscopic imaging can detect not only the uptake of the pre-polarized molecule but also its metabolic products in vivo, thus providing a powerful new method to study cellular metabolism. Imaging the dynamic perfusion and conversion of these metabolites provides additional tissue information but requires methods for efficient hyperpolarization usage and rapid acquisitions. In this work, we have developed a time-resolved 3D MR spectroscopic imaging method for acquiring hyperpolarized 13C data by combining compressed sensing methods for acceleration and multiband excitation pulses to efficiently use the magnetization. This method achieved a 2 sec temporal resolution with full volumetric coverage of a mouse, and metabolites were observed for up to 60 sec following injection of hyperpolarized [1-(13)C]-pyruvate. The compressed sensing acquisition used random phase encode gradient blips to create a novel random undersampling pattern tailored to dynamic MR spectroscopic imaging with sampling incoherency in four (time, frequency, and two spatial) dimensions. The reconstruction was also tailored to dynamic MR spectroscopic imaging by applying a temporal wavelet sparsifying transform to exploit the inherent temporal sparsity. Customized multiband excitation pulses were designed with a lower flip angle for the [1-(13)C]-pyruvate substrate given its higher concentration than its metabolic products ([1-(13)C]-lactate and [1-(13)C]-alanine), thus using less hyperpolarization per excitation. This approach has enabled the monitoring of perfusion and uptake of the pyruvate, and the conversion dynamics to lactate and alanine throughout a volume with high spatial and temporal resolution.


Subject(s)
Data Compression/methods , Imaging, Three-Dimensional/methods , Magnetic Resonance Imaging/methods , Magnetic Resonance Spectroscopy/methods , Neoplasms, Experimental/metabolism , Neoplasms, Experimental/pathology , Pyruvic Acid/pharmacokinetics , Algorithms , Animals , Carbon Isotopes/pharmacokinetics , Mice , Mice, Transgenic , Radiopharmaceuticals/pharmacokinetics
16.
J Magn Reson ; 208(1): 171-7, 2011 Jan.
Article in English | MEDLINE | ID: mdl-21130012

ABSTRACT

We report metabolic images of (13)C, following injection of a bolus of hyperpolarized [1-(13)C] pyruvate in a live rat. The data were acquired on a clinical scanner, using custom coils for volume transmission and array reception. Proton blocking of all carbon resonators enabled proton anatomic imaging with the system body coil, to allow for registration of anatomic and metabolic images, for which good correlation was achieved, with some anatomic features (kidney and heart) clearly visible in a carbon image, without reference to the corresponding proton image. Parallel imaging with sensitivity encoding was used to increase the spatial resolution in the SI direction of the rat. The signal to noise ratio in was in some instances unexpectedly high in the parallel images; variability of the polarization among different trials, plus partial volume effects, are noted as a possible cause of this.


Subject(s)
Algorithms , Magnetic Resonance Imaging/instrumentation , Magnetic Resonance Imaging/veterinary , Magnetic Resonance Spectroscopy/instrumentation , Magnetics/instrumentation , Pyruvic Acid/metabolism , Animals , Carbon Radioisotopes/analysis , Carbon Radioisotopes/chemistry , Equipment Design , Equipment Failure Analysis , Male , Pyruvic Acid/analysis , Rats , Rats, Sprague-Dawley , Tissue Distribution , Whole Body Imaging/instrumentation , Whole Body Imaging/veterinary
17.
Cancer Res ; 70(19): 7400-10, 2010 Oct 01.
Article in English | MEDLINE | ID: mdl-20858719

ABSTRACT

The recent development of hyperpolarized (13)C magnetic resonance spectroscopic imaging provides a novel method for in vivo metabolic imaging with potential applications for detection of cancer and response to treatment. Chemotherapy-induced apoptosis was shown to decrease the flux of hyperpolarized (13)C label from pyruvate to lactate due to depletion of NADH, the coenzyme of lactate dehydrogenase. In contrast, we show here that in PC-3MM2 tumors, inhibition of platelet-derived growth factor receptor with imatinib reduces the conversion of hyperpolarized pyruvate to lactate by lowering the expression of lactate dehydrogenase itself. This was accompanied by reduced expression of vascular endothelial growth factor and glutaminase, and is likely mediated by reduced expression of their transcriptional factors hypoxia-inducible factor-1 and c-Myc. Our results indicate that hyperpolarized (13)C MRSI could potentially detect the molecular effect of various cell signaling inhibitors, thus providing a radiation-free method to predict tumor response.


Subject(s)
Hypoxia-Inducible Factor 1/metabolism , Prostatic Neoplasms/metabolism , Proto-Oncogene Proteins c-myc/metabolism , Receptors, Platelet-Derived Growth Factor/metabolism , Animals , Benzamides , Capillary Permeability/drug effects , Carbon Isotopes , Humans , Imatinib Mesylate , L-Lactate Dehydrogenase/biosynthesis , L-Lactate Dehydrogenase/metabolism , Lactic Acid/metabolism , Magnetic Resonance Spectroscopy/methods , Male , Mice , Mice, Nude , Neovascularization, Pathologic/metabolism , Paclitaxel/pharmacology , Piperazines/pharmacology , Prostatic Neoplasms/blood supply , Pyrimidines/pharmacology , Receptors, Platelet-Derived Growth Factor/antagonists & inhibitors , Signal Transduction/drug effects , Vascular Endothelial Growth Factor A/biosynthesis
18.
J Magn Reson ; 205(1): 141-7, 2010 Jul.
Article in English | MEDLINE | ID: mdl-20478721

ABSTRACT

Methods for the simultaneous polarization of multiple 13C-enriched metabolites were developed to probe several enzymatic pathways and other physiologic properties in vivo, using a single intravenous bolus. A new method for polarization of 13C sodium bicarbonate suitable for use in patients was developed, and the co-polarization of 13C sodium bicarbonate and [1-(13)C] pyruvate in the same sample was achieved, resulting in high solution-state polarizations (15.7% and 17.6%, respectively) and long spin-lattice relaxation times (T1) (46.7 s and 47.7 s respectively at 3 T). Consistent with chemical shift anisotropy dominating the T1 relaxation of carbonyls, T1 values for 13C bicarbonate and [1-(13)C] pyruvate were even longer at 3 T (49.7s and 67.3s, respectively). Co-polarized 13C bicarbonate and [1-(13)C] pyruvate were injected into normal mice and a murine prostate tumor model at 3T. Rapid equilibration of injected hyperpolarized 13C sodium bicarbonate with 13C CO2 allowed calculation of pH on a voxel by voxel basis, and simultaneous assessment of pyruvate metabolism with cellular uptake and conversion of [1-(13)C] pyruvate to its metabolic products. Initial studies in a Transgenic Adenocarcinoma of Mouse Prostate (TRAMP) model demonstrated higher levels of hyperpolarized lactate and lower pH within tumor, relative to surrounding benign tissues and to the abdominal viscera of normal controls. There was no significant difference observed in the tumor lactate/pyruvate ratio obtained after the injection of co-polarized 13C bicarbonate and [1-(13)C] pyruvate or polarized [1-(13)C] pyruvate alone. The technique was extended to polarize four 13C labelled substrates potentially providing information on pH, metabolism, necrosis and perfusion, namely [1-(13)C]pyruvic acid, 13C sodium bicarbonate, [1,4-(13)C]fumaric acid, and 13C urea with high levels of solution polarization (17.5%, 10.3%, 15.6% and 11.6%, respectively) and spin-lattice relaxation values similar to those recorded for the individual metabolites. These studies demonstrated the feasibility of simultaneously measuring in vivo pH and tumor metabolism using nontoxic, endogenous species, and the potential to extend the multi-polarization approach to include up to four hyperpolarized probes providing multiple metabolic and physiologic measures in a single MR acquisition.


Subject(s)
Enzymes/chemistry , Enzymes/metabolism , Magnetic Resonance Spectroscopy/methods , Animals , Biomarkers, Tumor/analysis , Fumarates/pharmacokinetics , Gadolinium , Hydrogen-Ion Concentration , Indicators and Reagents , Injections, Intravenous , Isotope Labeling , Male , Mice , Necrosis , Neoplasm Transplantation , Prostatic Neoplasms/chemistry , Prostatic Neoplasms/metabolism , Pyruvic Acid/administration & dosage , Pyruvic Acid/chemistry , Pyruvic Acid/pharmacokinetics , Sodium Bicarbonate/administration & dosage , Sodium Bicarbonate/chemistry , Sodium Bicarbonate/pharmacokinetics , Solubility , Urea/pharmacokinetics
19.
Magn Reson Med ; 63(3): 582-91, 2010 Mar.
Article in English | MEDLINE | ID: mdl-20187172

ABSTRACT

Hyperpolarized [1-(13)C]-pyruvate is an exciting new agent for the in vivo study of cellular metabolism and a potential cancer biomarker. The nature of the hyperpolarized signal poses unique challenges because of its short duration and the loss of magnetization with every excitation. In this study, we applied a novel and efficient time-resolved MR spectroscopic imaging (MRSI) method to investigate in a prostate cancer model the localized temporal dynamics of the uptake of [1-(13)C]-pyruvate and its conversion to metabolic products, specifically [1-(13)C]-lactate. This hyperpolarized (13)C method used multiband excitation pulses for efficient use of the magnetization. This study demonstrated that regions of tumor were differentially characterized from normal tissue by the lactate dynamics, where tumors showed later lactate detection and longer lactate duration that was statistically significant (P < 0.001). Compared to late-pathologic-stage tumors, early- to intermediate-stage tumors demonstrated significantly (P < 0.01) lower lactate total signal-to-noise ratio (SNR), with similar temporal dynamic parameters. Hyperpolarized pyruvate dynamics provided uptake, perfusion, and vascularization information on tumors and normal tissue. Large, heterogeneous tumors demonstrated spatially variable uptake of pyruvate and metabolic conversion that was consistent with cellularity and necrosis identified by histology. The results of this study demonstrated the potential of this new hyperpolarized MR dynamic method for improved cancer detection and characterization.


Subject(s)
Echo-Planar Imaging/methods , Magnetic Resonance Spectroscopy/methods , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/metabolism , Pyruvic Acid/analysis , Animals , Carbon Isotopes , Male , Mice , Mice, Transgenic , Reproducibility of Results , Sensitivity and Specificity
20.
Neuro Oncol ; 12(2): 133-44, 2010 Feb.
Article in English | MEDLINE | ID: mdl-20150380

ABSTRACT

In order to compare in vivo metabolism between malignant gliomas and normal brain, (13)C magnetic resonance (MR) spectroscopic imaging data were acquired from rats with human glioblastoma xenografts (U-251 MG and U-87 MG) and normal rats, following injection of hyperpolarized [1-(13)C]-pyruvate. The median signal-to-noise ratio (SNR) of lactate, pyruvate, and total observed carbon-13 resonances, as well as their relative ratios, were calculated from voxels containing Gadolinium-enhanced tissue in T(1) postcontrast images for rats with tumors and from normal brain tissue for control rats. [1-(13)C]-labeled pyruvate and its metabolic product, [1-(13)C]-lactate, demonstrated significantly higher SNR in the tumor compared with normal brain tissue. Statistical tests showed significant differences in all parameters (P < .0004) between the malignant glioma tissue and normal brain. The SNR of lactate, pyruvate, and total carbon was observed to be different between the U-251 MG and U-87 MG models, which is consistent with inherent differences in the molecular characteristics of these tumors. These results suggest that hyperpolarized MR metabolic imaging may be valuable for assessing prognosis and monitoring response to therapy for patients with brain tumors.


Subject(s)
Brain Neoplasms/diagnosis , Brain Neoplasms/metabolism , Carbon Radioisotopes , Magnetic Resonance Spectroscopy/methods , Radiopharmaceuticals , Animals , Humans , Immunohistochemistry , Male , Neoplasms, Experimental/diagnosis , Neoplasms, Experimental/metabolism , Rats , Rats, Nude , Transplantation, Heterologous
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