Publications by authors named "Albert P Chen"

Article Synopsis
  • * The study involved six female cervical cancer patients, using hyperpolarized [1-C]-pyruvate MRI/MRS to analyze splenic metabolism before and after radiotherapy, aiming to assess tumor response.
  • * Results showed that responders had significantly lower baseline splenic HP [1-C]-lactate ratios compared to non-responders, and an increase in neutrophil counts post-treatment indicated heightened immune activity.
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Article Synopsis
  • - MRI with hyperpolarized (HP) C agents allows for the measurement of altered metabolism in various diseases, including cancers and organ diseases, and has seen increased application in human studies over the last decade due to improved preparation methods of HP agents.
  • - This paper focuses on the use of [1-C]pyruvate, the most popular HP agent, and is organized into four main sections: agent preparation, MRI system setup, data collection, and analysis, highlighting essential components for effective studies.
  • - The findings come from the "HP C MRI Consensus Group" and aim to provide a comprehensive guide for best practices, addressing both successful studies and existing gaps, while fostering future advancements in metabolic imaging.
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Hyperpolarized- C magnetic resonance imaging (HP- C MRI) was used to image changes in C-lactate signal during a visual stimulus condition in comparison to an eyes-closed control condition. Whole-brain C-pyruvate, C-lactate and C-bicarbonate production was imaged in healthy volunteers (N=6, ages 24-33) for the two conditions using two separate hyperpolarized C-pyruvate injections. BOLD-fMRI scans were used to delineate regions of functional activation.

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Purpose: To test the hypothesis that lactate oxidation contributes to the C-bicarbonate signal observed in the awake human brain using hyperpolarized C MRI.

Methods: Healthy human volunteers (N = 6) were scanned twice using hyperpolarized C-MRI, with increased radiofrequency saturation of C-lactate on one set of scans. C-lactate, C-bicarbonate, and C-pyruvate signals for 132 brain regions across each set of scans were compared using a clustered Wilcoxon signed-rank test.

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MRI with hyperpolarized (HP) C agents, also known as HP C MRI, can measure processes such as localized metabolism that is altered in numerous cancers, liver, heart, kidney diseases, and more. It has been translated into human studies during the past 10 years, with recent rapid growth in studies largely based on increasing availability of hyperpolarized agent preparation methods suitable for use in humans. This paper aims to capture the current successful practices for HP MRI human studies with [1-C]pyruvate - by far the most commonly used agent, which sits at a key metabolic junction in glycolysis.

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In this study, hyperpolarized C MRI (HP- C MRI) was used to investigate changes in the uptake and metabolism of pyruvate with age. Hyperpolarized C-pyruvate was administered to healthy aging individuals (N = 35, ages 21-77) and whole-brain spatial distributions of C-lactate and C-bicarbonate production were measured. Linear mixed-effects regressions were performed to compute the regional percentage change per decade, showing a significant reduction in both normalized C-lactate and normalized C-bicarbonate production with age: per decade for C-lactate and per decade for C-bicarbonate.

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Article Synopsis
  • This study explores time-resolved carbon-13 magnetic resonance spectroscopy (MRS) as a method for assessing how pyruvate metabolizes in the human brain, using hyperpolarized [1-C]pyruvate instead of traditional imaging techniques.
  • Researchers conducted MRS on healthy participants, measuring the production rates of lactate and other metabolites from pyruvate, and analyzed the relationship between the concentration of these signals and brain tissue types.
  • The findings suggest that using dynamic MRS with multichannel radiofrequency coils is a cost-effective and reliable method for investigating brain metabolism, with good reproducibility between sessions.
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Alterations in metabolism following radiotherapy affect therapeutic efficacy, although the mechanism underlying such alterations is unclear. A new imaging technique-named dynamic nuclear polarization (DNP) carbon-13 magnetic resonance imaging (MRI)-probes the glycolytic flux in a real-time, dynamic manner. The [1-C]pyruvate is transported by the monocarboxylate transporter (MCT) into cells and converted into [1-C]lactate by lactate dehydrogenase (LDH).

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Hyperpolarized (HP) [1- C]lactate is an attractive alternative to [1- C]pyruvate as a substrate to investigate cardiac metabolism in vivo: it can be administered safely at a higher dose and can be polarized to a degree similar to pyruvate via dynamic nuclear polarization. While C cardiac experiments using HP lactate have been performed in small animal models, they have not been demonstrated in large animal models or humans. Utilizing the same hardware and data acquisition methods as the first human HP C cardiac study, C metabolic images were acquired following injections of HP [1- C]lactate in porcine hearts.

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Background: Stereotactic radiosurgery (SRS) is used to manage intracranial metastases in a significant fraction of patients. Local progression after SRS can often only be detected with increased volume of enhancement on serial MRI scans which may lag true progression by weeks or months.

Methods: Patients with intracranial metastases (N = 11) were scanned using hyperpolarized [Formula: see text]C MRI prior to treatment with stereotactic radiosurgery (SRS).

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Article Synopsis
  • The study aimed to explore how regional differences affect the image quality of hyperpolarized carbon-13 (C) cardiac imaging and to find ways to improve this.
  • Researchers tested field map correction techniques in healthy participants by comparing different spiral readout durations and assessing their impact on image quality and performance.
  • Results showed that while shorter readouts maintained consistent image clarity, longer readouts improved signal-to-noise ratio but introduced more artifacts; however, these could be partially corrected using the new MFI method.
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  • This study aimed to explore the potential of hyperpolarized [N]carnitine as a new MRI probe with a long signal lifespan for in vivo imaging.
  • L-[N]carnitine-d was hyperpolarized using dynamic nuclear polarization and tested in a rat study, showing significant signal lifetimes of 210 seconds in solution and 160 seconds in vivo.
  • Results indicated that hyperpolarized [N]carnitine could be effectively detected in the rat abdomen for up to 5 minutes post-injection, demonstrating its feasibility for assessing biodistribution without detecting any metabolites.
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  • The study aims to enhance human hyperpolarized carbon MR spectroscopic imaging by employing new methods like Tensor Rank truncation-Image enhancement (TRI) and optimal receiver combination (ORC) to improve clinical diagnostic information extraction.
  • A data-driven processing framework was created using patient data from various body regions, testing TRI and two ORC techniques which resulted in significant gains in signal-to-noise ratio (SNR) for effective imaging.
  • Results showed TRI and ORC together led to a 63-fold increase in SNR for receiver arrays and improvements in detecting otherwise indiscernible signals, demonstrating the potential of this approach for cancer diagnostics and future research in HP carbon MRI.
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Hyperpolarized (HP) MRI provides the means to monitor lactate metabolism noninvasively in tumours. Since -lactate signal levels obtained from HP imaging depend on multiple factors, such as the rate of substrate delivery via the vasculature, the expression level of monocarboxylate transporters (MCTs) and lactate dehydrogenase (LDH), and the local lactate pool size, the interpretation of HP metabolic images remains challenging. In this study, ex vivo tissue extract measurements (i.

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Dynamic nuclear polarization (DNP) provides the opportunity to boost liquid state magnetic resonance (MR) signals from selected nuclear spins by several orders of magnitude. A cryostat running at a temperature of ~ 1 K and a superconducting magnet set to between 3 and 10 T are required to efficiently hyperpolarize nuclear spins. Several DNP polarizers have been implemented for the purpose of hyperpolarized MR and recent systems have been designed to avoid the need for user input of liquid cryogens.

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Purpose: Asymmetric in-plane k-space sampling of EPI can reduce the minimum achievable TE in hyperpolarized with spectral-spatial radio frequency pulses, thereby reducing weighting and signal-losses. Partial Fourier image reconstruction exploits the approximate Hermitian symmetry of k-space data and can be applied to asymmetric data sets to synthesize unmeasured data. Here we tested whether the application of partial Fourier image reconstruction would improve spatial resolution from hyperpolarized [1- ]pyruvate scans in the human brain.

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Metabolic imaging using hyperpolarized magnetic resonance can increase the sensitivity of MRI, though its ability to inform on relevant changes to biochemistry in humans remains unclear. In this work, we image pyruvate metabolism in patients, assessing the reproducibility of delivery and conversion in the setting of primary prostate cancer. We show that the time to max of pyruvate does not vary significantly within patients undergoing two separate injections or across patients.

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Lactate is now recognized as an important intermediate in brain metabolism, but its role is still under investigation. In this work we mapped the distribution of lactate and bicarbonate produced from intravenously injected C-pyruvate over the whole brain using a new imaging method, hyperpolarized C MRI (N = 14, ages 23 to 77). Segmenting the C-lactate images into brain atlas regions revealed a pattern of lactate that was preserved across individuals.

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Article Synopsis
  • Metabolic variations within and among tumors significantly influence cancer treatment outcomes, but non-invasive methods to assess these differences are limited.
  • The study focuses on pancreatic ductal adenocarcinoma, showing that tumors with the same genetic makeup can be differentiated by their rates of 13C labeled glucose metabolism using advanced imaging techniques.
  • This imaging approach reveals unique metabolic profiles and regions of lactate production in tumors, highlighting tumor heterogeneity that conventional methods like FDG-PET may fail to detect.
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Article Synopsis
  • * C magnetic resonance spectroscopy (MRS) offers potential advantages for detecting metabolism changes but struggles with low sensitivity, mainly used in single voxel measurements, unless enhanced by complex methods like dDNP.
  • * A new method using MRI chemical shift imaging (CSI) with advanced post-processing via tensor decomposition significantly boosts signal-to-noise ratio, allowing effective imaging of glucose metabolism and the Warburg effect without needing hyperpolarization, achieving great spatial and temporal resolution.
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Article Synopsis
  • Hyperpolarized MRI using [1-13C] pyruvate is a new technique that helps scientists study energy use in the brain and brain tumors.
  • The first pictures from this method show how tumors change the way they produce energy differently from the normal brain.
  • The findings suggest that this imaging method can help doctors see how well tumors are responding to treatments.
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  • This study aimed to explore the possibility of C->H hyperpolarization transfer to enhance the detection of hyperpolarized carbon probes in clinical MRI scanning.
  • A custom RF transmit channel for C was developed and tested alongside a standard H channel, allowing for successful pulse sequence integration and effective polarization transfer in various experiments, including in vivo tests.
  • The findings confirmed that the custom RF system enabled effective C->H hyperpolarization transfer in a clinical MRI environment, suggesting promising applications for detecting metabolic processes in vivo.
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Purpose: To investigate the feasibility of performing large FOV hyperpolarized C metabolic imaging using simultaneous multislice excitation.

Methods: A spectral-spatial multislice excitation pulse was constructed by cosine modulation and incorporated into a C spiral imaging sequence. Phantom and in vivo pig experiments were performed to test the feasibility of simultaneous multislice data acquisition and image reconstruction.

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Purpose: Although H spin coupling is generally avoided in probes for hyperpolarized (HP) C MRI, enzymatic transformations of biological interest can introduce large C- H couplings in vivo. The purpose of this study was to develop and investigate the application of H decoupling for enhancing the sensitivity for detection of affected HP C metabolic products.

Methods: A standalone H decoupler system and custom concentric C/ H paddle coil setup were integrated with a clinical 3T MRI scanner for in vivo C MR studies using HP [2- C]dihydroxyacetone, a novel sensor of hepatic energy status.

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