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1.
Magn Reson Med ; 87(2): 1074-1092, 2022 02.
Article in English | MEDLINE | ID: mdl-34632626

ABSTRACT

PURPOSE: To test an integrated "AC/DC" array approach at 7T, where B0 inhomogeneity poses an obstacle for functional imaging, diffusion-weighted MRI, MR spectroscopy, and other applications. METHODS: A close-fitting 7T 31-channel (31-ch) brain array was constructed and tested using combined Rx and ΔB0 shim channels driven by a set of rapidly switchable current amplifiers. The coil was compared to a shape-matched 31-ch reference receive-only array for RF safety, signal-to-noise ratio (SNR), and inter-element noise correlation. We characterize the coil array's ability to provide global and dynamic (slice-optimized) shimming using ΔB0 field maps and echo planar imaging (EPI) acquisitions. RESULTS: The SNR and average noise correlation were similar to the 31-ch reference array. Global and slice-optimized shimming provide 11% and 40% improvements respectively compared to baseline second-order spherical harmonic shimming. Birdcage transmit coil efficiency was similar for the reference and AC/DC array setups. CONCLUSION: Adding ΔB0 shim capability to a 31-ch 7T receive array can significantly boost 7T brain B0 homogeneity without sacrificing the array's rdiofrequency performance, potentially improving ultra-high field neuroimaging applications that are vulnerable to off-resonance effects.


Subject(s)
Image Processing, Computer-Assisted , Magnetic Resonance Imaging , Brain/diagnostic imaging , Echo-Planar Imaging , Phantoms, Imaging , Radio Waves , Signal-To-Noise Ratio
2.
Magn Reson Med ; 85(1): 429-443, 2021 01.
Article in English | MEDLINE | ID: mdl-32643152

ABSTRACT

PURPOSE: We propose a fast, patient-specific workflow for on-line specific absorption rate (SAR) supervision. An individualized electromagnetic model is created while the subject is on the table, followed by rapid SAR estimates for that individual. Our goal is an improved correspondence between the patient and model, reducing reliance on general anatomical body models. METHODS: A 3D fat-water 3T acquisition (~2 minutes) is automatically segmented using a computer vision algorithm (~1 minute) into what we found to be the most important electromagnetic tissue classes: air, bone, fat, and soft tissues. We then compute the individual's EM field exposure and global and local SAR matrices using a fast electromagnetic integral equation solver. We assess the approach in 10 volunteers and compare to the SAR seen in a standard generic body model (Duke). RESULTS: The on-the-table workflow averaged 7'44″. Simulation of the simplified Duke models confirmed that only air, bone, fat, and soft tissue classes are needed to estimate global and local SAR with an error of 6.7% and 2.7%, respectively, compared to the full model. In contrast, our volunteers showed a 16.0% and 20.3% population variability in global and local SAR, respectively, which was mostly underestimated by the Duke model. CONCLUSION: Timely construction and deployment of a patient-specific model is computationally feasible. The benefit of resolving the population heterogeneity compared favorably to the modest modeling error incurred. This suggests that individualized SAR estimates can improve electromagnetic safety in MRI and possibly reduce conservative safety margins that account for patient-model mismatch, especially in non-standard patients.


Subject(s)
Algorithms , Magnetic Resonance Imaging , Computer Simulation , Computers , Electromagnetic Fields , Humans
3.
Magn Reson Med ; 81(2): 839-851, 2019 02.
Article in English | MEDLINE | ID: mdl-30277268

ABSTRACT

PURPOSE: Acquisition timing and B1 calibration are two key factors that affect the quality and accuracy of hyperpolarized 13 C MRI. The goal of this project was to develop a new approach using regional bolus tracking to trigger Bloch-Siegert B1 mapping and real-time B1 calibration based on regional B1 measurements, followed by dynamic imaging of hyperpolarized 13 C metabolites in vivo. METHODS: The proposed approach was implemented on a system which allows real-time data processing and real-time control on the sequence. Real-time center frequency calibration upon the bolus arrival was also added. The feasibility of applying the proposed framework for in vivo hyperpolarized 13 C imaging was tested on healthy rats, tumor-bearing mice and a healthy volunteer on a clinical 3T scanner following hyperpolarized [1-13 C]pyruvate injection. Multichannel receive coils were used in the human study. RESULTS: Automatic acquisition timing based on either regional bolus peak or bolus arrival was achieved with the proposed framework. Reduced blurring artifacts in real-time reconstructed images were observed with real-time center frequency calibration. Real-time computed B1 scaling factors agreed with real-time acquired B1 maps. Flip angle correction using B1 maps results in a more consistent quantification of metabolic activity (i.e, pyruvate-to-lactate conversion, kPL ). Experiment recordings are provided to demonstrate the real-time actions during the experiment. CONCLUSIONS: The proposed method was successfully demonstrated on animals and a human volunteer, and is anticipated to improve the efficient use of the hyperpolarized signal as well as the accuracy and robustness of hyperpolarized 13 C imaging.


Subject(s)
Carbon Isotopes/chemistry , Image Processing, Computer-Assisted/methods , Magnetic Resonance Imaging , Adult , Algorithms , Animals , Brain Mapping , Calibration , Disease Models, Animal , Healthy Volunteers , Humans , Male , Mice , Neoplasm Transplantation , Normal Distribution , Pattern Recognition, Automated , Prostatic Neoplasms/diagnostic imaging , Pyruvic Acid , Rats
4.
Magn Reson Med ; 81(4): 2702-2709, 2019 04.
Article in English | MEDLINE | ID: mdl-30375043

ABSTRACT

PURPOSE: To develop and translate a metabolite-specific imaging sequence using a symmetric echo planar readout for clinical hyperpolarized (HP) Carbon-13 (13 C) applications. METHODS: Initial data were acquired from patients with prostate cancer (N = 3) and high-grade brain tumors (N = 3) on a 3T scanner. Samples of [1-13 C]pyruvate were polarized for at least 2 h using a 5T SPINlab system operating at 0.8 K. Following injection of the HP substrate, pyruvate, lactate, and bicarbonate (for brain studies) were sequentially excited with a singleband spectral-spatial RF pulse and signal was rapidly encoded with a single-shot echo planar readout on a slice-by-slice basis. Data were acquired dynamically with a temporal resolution of 2 s for prostate studies and 3 s for brain studies. RESULTS: High pyruvate signal was seen throughout the prostate and brain, with conversion to lactate being shown across studies, whereas bicarbonate production was also detected in the brain. No Nyquist ghost artifacts or obvious geometric distortion from the echo planar readout were observed. The average error in center frequency was 1.2 ± 17.0 and 4.5 ± 1.4 Hz for prostate and brain studies, respectively, below the threshold for spatial shift because of bulk off-resonance. CONCLUSION: This study demonstrated the feasibility of symmetric EPI to acquire HP 13 C metabolite maps in a clinical setting. As an advance over prior single-slice dynamic or single time point volumetric spectroscopic imaging approaches, this metabolite-specific EPI acquisition provided robust whole-organ coverage for brain and prostate studies while retaining high SNR, spatial resolution, and dynamic temporal resolution.


Subject(s)
Brain Neoplasms/diagnostic imaging , Carbon Isotopes , Carbon-13 Magnetic Resonance Spectroscopy , Echo-Planar Imaging , Prostatic Neoplasms/diagnostic imaging , Artifacts , Bicarbonates/analysis , Brain/diagnostic imaging , Calibration , Humans , Image Enhancement/methods , Image Processing, Computer-Assisted/methods , Lactic Acid/analysis , Male , Molecular Imaging , Phantoms, Imaging , Prostate/diagnostic imaging , Pyruvic Acid/analysis , Signal-To-Noise Ratio
5.
NMR Biomed ; 32(3): e4052, 2019 03.
Article in English | MEDLINE | ID: mdl-30664305

ABSTRACT

Hyperpolarized 13 C MRI takes advantage of the unprecedented 50 000-fold signal-to-noise ratio enhancement to interrogate cancer metabolism in patients and animals. It can measure the pyruvate-to-lactate conversion rate, kPL , a metabolic biomarker of cancer aggressiveness and progression. Therefore, it is crucial to evaluate kPL reliably. In this study, three sequence components and parameters that modulate kPL estimation were identified and investigated in model simulations and through in vivo animal studies using several specifically designed pulse sequences. These factors included a magnetization spoiling effect due to RF pulses, a crusher gradient-induced flow suppression, and intrinsic image weightings due to relaxation. Simulation showed that the RF-induced magnetization spoiling can be substantially improved using an inputless kPL fitting. In vivo studies found a significantly higher apparent kPL with an additional gradient that leads to flow suppression (kPL,FID-Delay,Crush /kPL,FID-Delay  = 1.37 ± 0.33, P < 0.01, N = 6), which agrees with simulation outcomes (12.5% kPL error with Δv = 40 cm/s), indicating that the gradients predominantly suppressed flowing pyruvate spins. Significantly lower kPL was found using a delayed free induction decay (FID) acquisition versus a minimum-TE version (kPL,FID-Delay /kPL,FID  = 0.67 ± 0.09, P < 0.01, N = 5), and the lactate peak had broader linewidth than pyruvate (Δωlactate /Δωpyruvate  = 1.32 ± 0.07, P < 0.000 01, N = 13). This illustrated that lactate's T2 *, shorter than that of pyruvate, can affect calculated kPL values. We also found that an FID sequence yielded significantly lower kPL versus a double spin-echo sequence that includes spin-echo spoiling, flow suppression from crusher gradients, and more T2 weighting (kPL,DSE /kPL,FID  = 2.40 ± 0.98, P < 0.0001, N = 7). In summary, the pulse sequence, as well as its interaction with pharmacokinetics and the tissue microenvironment, can impact and be optimized for the measurement of kPL . The data acquisition and analysis pipelines can work synergistically to provide more robust and reproducible kPL measures for future preclinical and clinical studies.


Subject(s)
Carbon Isotopes/metabolism , Lactic Acid/metabolism , Magnetic Resonance Imaging , Pyruvic Acid/metabolism , Animals , Computer Simulation , Image Processing, Computer-Assisted , Mice, Inbred C57BL , Models, Theoretical
6.
Magn Reson Med ; 78(3): 1087-1092, 2017 09.
Article in English | MEDLINE | ID: mdl-27735082

ABSTRACT

PURPOSE: The purpose of this work was to explore the impact of slice profile effects on apparent diffusion coefficient (ADC) mapping of hyperpolarized (HP) substrates. METHODS: Slice profile effects were simulated using a Gaussian radiofrequency (RF) pulse with a variety of flip angle schedules and b-value ordering schemes. A long T1 water phantom was used to validate the simulation results, and ADC mapping of HP [13 C,15 N2 ]urea was performed on the murine liver to assess these effects in vivo. RESULTS: Slice profile effects result in excess signal after repeated RF pulses, causing bias in HP measurements. The largest error occurs for metabolites with small ADCs, resulting in up to 10-fold overestimation for metabolites that are in more-restricted environments. A mixed b-value scheme substantially reduces this bias, whereas scaling the slice-select gradient can mitigate it completely. In vivo, the liver ADC of hyperpolarized [13 C,15 N2 ]urea is nearly 70% lower (0.99 ± 0.22 vs 1.69 ± 0.21 × 10-3 mm2 /s) when slice-select gradient scaling is used. CONCLUSION: Slice profile effects can lead to bias in HP ADC measurements. A mixed b-value ordering scheme can reduce this bias compared to sequential b-value ordering. Slice-select gradient scaling can also correct for this deviation, minimizing bias and providing more-precise ADC measurements of HP substrates. Magn Reson Med 78:1087-1092, 2017. © 2016 International Society for Magnetic Resonance in Medicine.


Subject(s)
Diffusion Magnetic Resonance Imaging/methods , Image Processing, Computer-Assisted/methods , Algorithms , Animals , Computer Simulation , Liver/diagnostic imaging , Mice , Phantoms, Imaging
7.
Magn Reson Med ; 78(3): 963-975, 2017 09.
Article in English | MEDLINE | ID: mdl-27770458

ABSTRACT

PURPOSE: Balanced steady-state free precession (bSSFP) sequences can provide superior signal-to-noise ratio efficiency for hyperpolarized (HP) carbon-13 (13 C) magnetic resonance imaging by efficiently utilizing the nonrecoverable magnetization, but managing their spectral response is challenging in the context of metabolic imaging. A new spectrally selective bSSFP sequence was developed for fast imaging of multiple HP 13 C metabolites with high spatiotemporal resolution. THEORY AND METHODS: This novel approach for bSSFP spectral selectivity incorporates optimized short-duration spectrally selective radiofrequency pulses within a bSSFP pulse train and a carefully chosen repetition time to avoid banding artifacts. RESULTS: The sequence enabled subsecond 3D dynamic spectrally selective imaging of 13 C metabolites of copolarized [1-13 C]pyruvate and [13 C]urea at 2-mm isotropic resolution, with excellent spectral selectivity (∼100:1). The sequence was successfully tested in phantom studies and in vivo studies with normal mice. CONCLUSION: This sequence is expected to benefit applications requiring dynamic volumetric imaging of metabolically active 13 C compounds at high spatiotemporal resolution, including preclinical studies at high field and, potentially, clinical studies. Magn Reson Med 78:963-975, 2017. © 2016 International Society for Magnetic Resonance in Medicine.


Subject(s)
Carbon Isotopes/metabolism , Imaging, Three-Dimensional/methods , Magnetic Resonance Imaging/methods , Animals , Artifacts , Carbon Isotopes/analysis , Carbon Isotopes/chemistry , Computer Simulation , Lactates/analysis , Lactates/chemistry , Lactates/metabolism , Mice , Phantoms, Imaging , Pyruvic Acid/analysis , Pyruvic Acid/chemistry , Pyruvic Acid/metabolism
8.
Magn Reson Med ; 77(1): 65-73, 2017 01.
Article in English | MEDLINE | ID: mdl-27859575

ABSTRACT

PURPOSE: To investigate acute changes in glucose metabolism in liver and kidneys in vivo after a bolus injection of either fructose or glucose, using hyperpolarized [2-13 C]dihydroxyacetone. METHODS: Spatially registered, dynamic, multislice MR spectroscopy was acquired for the metabolic products of [2-13 C]dihydroxyacetone in liver and kidneys. Metabolism was probed in 13 fasted rats at three time points: 0, 70, and 140 min. At 60 min, rats were injected intravenously with fructose (n = 5) or glucose (n = 4) at 0.8 g/kg to initiate acute response. Controls (n = 4) did not receive a carbohydrate challenge. RESULTS: Ten minutes after fructose infusion, levels of [2-13 C]phosphoenolpyruvate and [2-13 C]glycerol-3-phosphate halved in liver: 51% (P = 0.0010) and 47% (P = 0.0001) of baseline, respectively. Seventy minutes later, levels returned to baseline. The glucose challenge did not alter the signals significantly, nor did repeated administration of the dihydroxyacetone imaging bolus. In kidneys, no statistically significant changes were detected after sugar infusion other than a 20% increase of the glycerol-3-phosphate signal between 10 and 80 min after fructose injection (P = 0.0028). CONCLUSION: Hyperpolarized [2-13 C]dihydroxyacetone detects a real-time, transient metabolic response of the liver to an acute fructose challenge. Observed effects possibly include ATP depletion and changes in the unlabeled pool sizes of glycolytic intermediates. Magn Reson Med 77:65-73, 2017. © 2016 International Society for Magnetic Resonance in Medicine.


Subject(s)
Carbon Isotopes/metabolism , Dihydroxyacetone/metabolism , Fructose/metabolism , Glucose/metabolism , Kidney/metabolism , Liver/metabolism , Animals , Blood Glucose/metabolism , Carbon Isotopes/chemistry , Dihydroxyacetone/chemistry , Fructose/analysis , Fructose/chemistry , Glucose/analysis , Glucose/chemistry , Image Processing, Computer-Assisted , Kidney/chemistry , Kidney/diagnostic imaging , Liver/chemistry , Liver/diagnostic imaging , Magnetic Resonance Imaging , Rats , Rats, Sprague-Dawley
9.
Magn Reson Med ; 75(2): 917-22, 2016 Feb.
Article in English | MEDLINE | ID: mdl-25765516

ABSTRACT

PURPOSE: Hyperpolarization of carbon-13 ((13) C) nuclei by dissolution dynamic nuclear polarization increases signal-to-noise ratio (SNR) by >10,000-fold for metabolic imaging, but care must be taken when transferring hyperpolarized (HP) samples from polarizer to MR scanner. Some (13) C substrates relax rapidly in low ambient magnetic fields. A handheld electromagnet carrier was designed and constructed to preserve polarization by maintaining a sufficient field during sample transfer. METHODS: The device was constructed with a solenoidal electromagnet, powered by a nonmagnetic battery, holding the HP sample during transfer. A specially designed switch automated deactivation of the field once transfer was complete. Phantom and rat experiments were performed to compare MR signal enhancement with or without the device for HP [(13) C]urea and [1-(13) C]pyruvate. RESULTS: The magnetic field generated by this device was tested to be >50 G over a 6-cm central section. In phantom and rat experiments, [(13) C]urea transported via the device showed SNR improvement by a factor of 1.8-1.9 over samples transferred through the background field. CONCLUSION: A device was designed and built to provide a suitably high yet safe magnetic field to preserve hyperpolarization during sample transfer. Comparative testing demonstrated SNR improvements of approximately two-fold for [(13) C]urea while maintaining SNR for [1-(13) C]pyruvate.


Subject(s)
Electromagnetic Fields , Magnetic Resonance Imaging , Animals , Carbon Isotopes , Equipment Design , Phantoms, Imaging , Rats , Signal-To-Noise Ratio
10.
Biochem Biophys Res Commun ; 450(1): 723-8, 2014 Jul 18.
Article in English | MEDLINE | ID: mdl-24950408

ABSTRACT

Site-directed spin labeling (SDSL) electron paramagnetic resonance (EPR) spectroscopy is a powerful tool for characterizing conformational sampling and dynamics in biological macromolecules. Here we demonstrate that nitroxide spectra collected at frequencies higher than X-band (∼9.5 GHz) have sensitivity to the timescale of motion sampled by highly dynamic intrinsically disordered proteins (IDPs). The 68 amino acid protein IA3, was spin-labeled at two distinct sites and a comparison of X-band, Q-band (35 GHz) and W-band (95 GHz) spectra are shown for this protein as it undergoes the helical transition chemically induced by tri-fluoroethanol. Experimental spectra at W-band showed pronounced line shape dispersion corresponding to a change in correlation time from ∼0.3 ns (unstructured) to ∼0.6 ns (α-helical) as indicated by comparison with simulations. Experimental and simulated spectra at X- and Q-bands showed minimal dispersion over this range, illustrating the utility of SDSL EPR at higher frequencies for characterizing structural transitions and dynamics in IDPs.


Subject(s)
Algorithms , Electron Spin Resonance Spectroscopy/methods , Proteins/chemistry , Proteins/ultrastructure , Protein Conformation , Staining and Labeling/methods
12.
J Phys Chem B ; 127(45): 9734-9746, 2023 Nov 16.
Article in English | MEDLINE | ID: mdl-37936402

ABSTRACT

IA3 is a 68 amino acid natural peptide/protein inhibitor of yeast aspartic proteinase A (YPRA) that is intrinsically disordered in solution with induced N-terminal helicity when in the protein complex with YPRA. Based on the intrinsically disordered protein (IDP) parameters of fractional net charge (FNC), net charge density per residue (NCPR), and charge patterning (κ), the two domains of IA3 are defined to occupy different domains within conformationally based subclasses of IDPs, thus making IA3 a bimodal domain IDP. Site-directed spin labeling (SDSL) electron paramagnetic resonance (EPR) spectroscopy and low-field Overhauser dynamic nuclear polarization (ODNP) spectroscopy results show that these two domains possess different degrees of compaction and hydration diffusivity behavior. This work suggests that SDSL EPR line shapes, analyzed in terms of their local tumbling volume (VL), provide insights into the compaction of the unstructured IDP ensemble in solution and that protein sequence and net charge distribution patterns within a conformational subclass can impact bound water hydration dynamics, thus possibly offering an alternative thermodynamic property that can encode conformational binding and behavior of IDPs and liquid-liquid phase separations.


Subject(s)
Intrinsically Disordered Proteins , Saccharomyces cerevisiae , Electron Spin Resonance Spectroscopy/methods , Protein Conformation , Spin Labels , Amino Acid Sequence , Intrinsically Disordered Proteins/chemistry
13.
IEEE Trans Biomed Eng ; 70(5): 1575-1586, 2023 05.
Article in English | MEDLINE | ID: mdl-36383593

ABSTRACT

High static field MR scanners can produce human tissue images of astounding clarity, but rely on high frequency electromagnetic radiation that generates complicated in-tissue field patterns that are patient-specific and potentially harmful. Many such scanners use parallel transmitters to better control field patterns, but then adjust the transmitters based on general guidelines rather than optimizing for the specific patient, mostly because computing patient-specific fields was presumed far too slow. It was recently demonstrated that the combination of fast low-resolution tissue mapping and fast voxel-based field simulation can be used to perform a patient-specific MR safety check in minutes. However, the field simulation required several of those minutes, making it too slow to perform the dozens of simulations that would be needed for patient-specific optimization. In this paper we describe a compressed-perturbation-matrix technique that nearly eliminates the computational cost of including complex coils (or coils and shields) in voxel-based field simulation of tissue, thereby reducing simulation time from minutes to seconds. The approach is demonstrated on a wide variety of head+coil and head+coil+shield configurations, using the implementation in MARIE 2.0, the latest version of the open-source MR field simulator MARIE.


Subject(s)
Magnetic Resonance Imaging , Humans , Magnetic Resonance Imaging/methods , Computer Simulation , Phantoms, Imaging
14.
J Magn Reson ; 312: 106691, 2020 03.
Article in English | MEDLINE | ID: mdl-32058912

ABSTRACT

As in conventional 1H MRI, T1 and T2 relaxation times of hyperpolarized (HP) 13C nuclei can provide important biomedical information. Two new approaches were developed for simultaneous T1 and T2 mapping of HP 13C probes based on balanced steady state free precession (bSSFP) acquisitions: a method based on sequential T1 and T2 mapping modules, and a model-based joint T1/T2 approach analogous to MR fingerprinting. These new methods were tested in simulations, HP 13C phantoms, and in vivo in normal Sprague-Dawley rats. Non-localized T1 values, low flip angle EPI T1 maps, bSSFP T2 maps, and Bloch-Siegert B1 maps were also acquired for comparison. T1 and T2 maps acquired using both approaches were in good agreement with both literature values and data from comparative acquisitions. Multiple HP 13C compounds were successfully mapped, with their relaxation time parameters measured within heart, liver, kidneys, and vasculature in one acquisition for the first time.


Subject(s)
Carbon-13 Magnetic Resonance Spectroscopy , Heart/diagnostic imaging , Kidney/diagnostic imaging , Liver/diagnostic imaging , Animals , Female , Phantoms, Imaging , Pyruvic Acid/chemistry , Rats , Rats, Sprague-Dawley , Urea/chemistry
15.
J Magn Reson ; 290: 46-59, 2018 05.
Article in English | MEDLINE | ID: mdl-29567434

ABSTRACT

Acceleration of dynamic 2D (T2 Mapping) and 3D hyperpolarized 13C MRI acquisitions using the balanced steady-state free precession sequence was achieved with a specialized reconstruction method, based on the combination of low rank plus sparse and local low rank reconstructions. Methods were validated using both retrospectively and prospectively undersampled in vivo data from normal rats and tumor-bearing mice. Four-fold acceleration of 1-2 mm isotropic 3D dynamic acquisitions with 2-5 s temporal resolution and two-fold acceleration of 0.25-1 mm2 2D dynamic acquisitions was achieved. This enabled visualization of the biodistribution of [2-13C]pyruvate, [1-13C]lactate, [13C, 15N2]urea, and HP001 within heart, kidneys, vasculature, and tumor, as well as calculation of high resolution T2 maps.


Subject(s)
Image Processing, Computer-Assisted/methods , Magnetic Resonance Imaging/methods , Algorithms , Animals , Computer Simulation , Lactic Acid/pharmacokinetics , Mice , Neoplasms, Experimental/diagnostic imaging , Pyruvic Acid/pharmacokinetics , Rats , Rats, Sprague-Dawley , Reproducibility of Results , Tissue Distribution , Urea/pharmacokinetics
16.
IEEE Trans Med Imaging ; 37(12): 2603-2612, 2018 12.
Article in English | MEDLINE | ID: mdl-29994332

ABSTRACT

We present a method of generating spatial maps of kinetic parameters from dynamic sequences of images collected in hyperpolarized carbon-13 magnetic resonance imaging (MRI) experiments. The technique exploits spatial correlations in the dynamic traces via regularization in the space of parameter maps. Similar techniques have proven successful in other dynamic imaging problems, such as dynamic contrast enhanced MRI. In this paper, we apply these techniques for the first time to hyperpolarized MRI problems, which are particularly challenging due to limited signal-to-noise ratio (SNR). We formulate the reconstruction as an optimization problem and present an efficient iterative algorithm for solving it based on the alternation direction method of multipliers. We demonstrate that this technique improves the qualitative appearance of parameter maps estimated from low SNR dynamic image sequences, first in simulation then on a number of data sets collected in vivo. The improvement this method provides is particularly pronounced at low SNR levels.


Subject(s)
Carbon Isotopes/chemistry , Image Processing, Computer-Assisted/methods , Magnetic Resonance Imaging/methods , Molecular Imaging/methods , Algorithms , Animals , Humans , Kidney/diagnostic imaging , Male , Prostate/diagnostic imaging , Prostatic Neoplasms/diagnostic imaging , Rats , Rats, Sprague-Dawley , Signal-To-Noise Ratio
17.
Sci Rep ; 8(1): 2088, 2018 02 01.
Article in English | MEDLINE | ID: mdl-29391429

ABSTRACT

The type 2 diabetic phenotype results from mixed effects of insulin deficiency and insulin resistance, but the relative contributions of these two distinct factors remain poorly characterized, as do the respective roles of the gluconeogenic organs. The purpose of this study was to investigate localized in vivo metabolic changes in liver and kidneys of contrasting models of diabetes mellitus (DM): streptozotocin (STZ)-treated wild-type Zucker rats (T1DM) and Zucker diabetic fatty (ZDF) rats (T2DM). Intermediary metabolism was probed using hyperpolarized (HP) [1-13C]pyruvate MRI of the liver and kidneys. These data were correlated with gene expression data for key mediators, assessed using rtPCR. Increased HP [1-13C]lactate was detected in both models, in association with elevated gluconeogenesis as reflected by increased expression of phosphoenolpyruvate carboxykinase. In contrast, HP [1-13C]alanine diverged between the two models, increasing in ZDF rats, while decreasing in the STZ-treated rats. The differences in liver alanine paralleled differences in key lipogenic mediators. Thus, HP [1-13C]alanine is a marker that can identify phenotypic differences in kidneys and liver of rats with T1DM vs. T2DM, non-invasively in vivo. This approach could provide a powerful diagnostic tool for characterizing tissue metabolic defects and responses to treatment in diabetic patients with ambiguous systemic manifestations.


Subject(s)
Diabetes Mellitus, Experimental/metabolism , Gluconeogenesis , Insulin Resistance , Insulin/deficiency , Lipogenesis , Magnetic Resonance Imaging/methods , Alanine/pharmacokinetics , Animals , Diabetes Mellitus, Experimental/diagnostic imaging , Kidney/diagnostic imaging , Kidney/metabolism , Lactic Acid/pharmacokinetics , Liver/diagnostic imaging , Liver/metabolism , Male , Pyruvates/pharmacokinetics , Rats , Rats, Zucker
18.
Magn Reson Imaging ; 38: 152-162, 2017 05.
Article in English | MEDLINE | ID: mdl-28077268

ABSTRACT

The goal of this project was to develop and apply techniques for T2 mapping and 3D high resolution (1.5mm isotropic; 0.003cm3) 13C imaging of hyperpolarized (HP) probes [1-13C]lactate, [1-13C]pyruvate, [2-13C]pyruvate, and [13C,15N2]urea in vivo. A specialized 2D bSSFP sequence was implemented on a clinical 3T scanner and used to obtain the first high resolution T2 maps of these different hyperpolarized compounds in both rats and tumor-bearing mice. These maps were first used to optimize timings for highest SNR for single time-point 3D bSSFP acquisitions with a 1.5mm isotropic spatial resolution of normal rats. This 3D acquisition approach was extended to serial dynamic imaging with 2-fold compressed sensing acceleration without changing spatial resolution. The T2 mapping experiments yielded measurements of T2 values of >1s for all compounds within rat kidneys/vasculature and TRAMP tumors, except for [2-13C]pyruvate which was ~730ms and ~320ms, respectively. The high resolution 3D imaging enabled visualization the biodistribution of [1-13C]lactate, [1-13C]pyruvate, and [2-13C]pyruvate within different kidney compartments as well as in the vasculature. While the mouse anatomy is smaller, the resolution was also sufficient to image the distribution of all compounds within kidney, vasculature, and tumor. The development of the specialized 3D sequence with compressed sensing provided improved structural and functional assessments at a high (0.003cm3) spatial and 2s temporal resolution in vivo utilizing HP 13C substrates by exploiting their long T2 values. This 1.5mm isotropic resolution is comparable to 1H imaging and application of this approach could be extended to future studies of uptake, metabolism, and perfusion in cancer and other disease models and may ultimately be of value for clinical imaging.


Subject(s)
Carbon Isotopes/chemistry , Imaging, Three-Dimensional , Magnetic Resonance Imaging , Molecular Imaging , Animals , Female , Image Processing, Computer-Assisted , Kidney/diagnostic imaging , Male , Mice , Mice, Transgenic , Monte Carlo Method , Neoplasm Transplantation , Pyruvic Acid/metabolism , Rats , Tissue Distribution , Urea/chemistry
19.
Protein Sci ; 20(1): 150-9, 2011 Jan.
Article in English | MEDLINE | ID: mdl-21080428

ABSTRACT

Electron paramagnetic resonance (EPR) spectroscopy coupled with site-directed spin labeling (SDSL) is a valuable tool for characterizing the mobility and conformational changes of proteins but has seldom been applied to intrinsically disordered proteins (IDPs). Here, IA3 is used as a model system demonstrating SDSL-EPR characterization of conformational changes in small IDP systems. IA3 has 68 amino acids, is unstructured in solution, and becomes α-helical upon addition of the secondary structural stabilizer 2,2,2-trifluoroethanol (TFE). Two single cysteine substitutions, one in the N-terminus (S14C) and one in the C-terminus (N58C), were generated and labeled with three different nitroxide spin labels. The resultant EPR line shapes of each of the labels were compared and each reported changes in mobility upon addition of TFE. Specifically, the spectral line shape parameters h((+1))/h(0), the local tumbling volume (V(L)), and the percent change of the h(₋1) intensity were utilized to quantitatively monitor TFE-induced conformational changes. The values of h((+1)/)h(0) as a function of TFE titration varied in a sigmoidal manner and were fit to a two-state Boltzmann model that provided values for the midpoint of the transition, thus, reporting on the global conformational change of IA3. The other parameters provide site-specific information and show that S14C-SL undergoes a conformational change resulting in more restricted motion than N58C-SL, which is consistent with previously published results obtained by studies using NMR and circular dichroism spectroscopy indicating a higher degree of α-helical propensity of the N-terminal segment of IA3. Overall, the results provide a framework for data analyzes that can be used to study induced unstructured-to-helical conformations in IDPs by SDSL.


Subject(s)
Saccharomyces cerevisiae Proteins/chemistry , Electron Spin Resonance Spectroscopy , Nitrogen Oxides/chemistry , Protein Structure, Secondary , Spin Labels
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