Publications by authors named "Galen D Reed"

30 Publications

  • Page 1 of 1

The Effect of Transmit B Inhomogeneity on Hyperpolarized [1- C]-Pyruvate Metabolic MR Imaging Biomarkers.

Med Phys 2021 Jul 20. Epub 2021 Jul 20.

Department of Imaging Physics, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, 77030, USA.

Purpose: A specialized Helmholtz-style C volume transmit "clamshell" coil is currently being utilized for C excitation in pre-clinical and clinical hyperpolarized C MRI studies aimed at probing metabolic activity of tumors in various target anatomy. Due to widespread use of this C clamshell coil design, it is important that the effects of the C clamshell coil B profile on HP signal evolution and quantification are well understood. The goal of this study was to characterize the B field of the C clamshell coil and assess the impact of inhomogeneities on semi-quantitative and quantitative hyperpolarized MR imaging biomarkers of metabolism.

Methods: The B field of the C clamshell coil was mapped by hand using a network analyzer equipped with a S-parameter test set. Pharmacokinetic models were used to simulate signal evolution as a function of position dependent local excitation angles, for various nominal excitation angles, which were assumed to be accurately calibrated at isocenter. These signals were then quantified according to the normalized lactate ratio (nLac) and the apparent rate constant for the conversion of pyruvate to lactate (k ). The percent difference between these metabolic imaging biomarker maps and the reference value observed at isocenter of the clamshell coil was calculated to estimate the potential for error due to position within the clamshell coil. Finally, regions were identified within the clamshell coil where deviations in B field inhomogeneity or imaging biomarker errors imparted by the B field were within ±10% of the value at isocenter.

Results: The B field maps show that a limited volume encompassed by a region measuring approximately 12.9 x 11.5 x 13.4 cm (X-direction, Y-direction, Z-direction) centered in the C clamshell coil will produce deviations in the B field within ±10% of that at isocenter. For the metabolic imaging biomarkers that we evaluated, the case when the pyruvate excitation angle (θ ) and lactate excitation angle (θ ) were equal to 10° produced the largest volumetric region with deviations within ±10% of the value at isocenter. Higher excitation angles yielded higher signal and SNR, but the size of the region in which uniform measurements could be collected near the isocenter of the coil was reduced at higher excitation angles. The tradeoff between the size of the homogenous region at isocenter and signal intensity must be weighed carefully depending on the particular imaging application.

Conclusion: This work identifies regions and optimal excitation angles (θ and θ ) within the C clamshell coil where deviations in B field inhomogeneity or imaging biomarker errors imparted by the B field were within ±10% of the respective value at isocenter, and thus where excitation angles are reproducible and well calibrated. Semi-quantitative and quantitative metabolic imaging biomarkers can vary with position in the clamshell coil as a result of B field inhomogeneity, necessitating care in patient positioning and the selection of an excitation angle set that balances reproducibility and SNR performance over the target imaging volume.
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http://dx.doi.org/10.1002/mp.15107DOI Listing
July 2021

Hyperpolarized C MR Spectroscopy Depicts in Vivo Effect of Exercise on Pyruvate Metabolism in Human Skeletal Muscle.

Radiology 2021 Jun 22:204500. Epub 2021 Jun 22.

From the Advanced Imaging Research Center (J.M.P., C.E.H., J.M., J.C., J.R., J.L., G.D.R., A.C., C.R.M.), Department of Radiology (J.M.P., A.C., C.R.M.), Department of Neurology and Neurotherapeutics (R.G.H.), and Department of Internal Medicine (C.R.M.), University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390-8568; Department of Electrical and Computer Engineering, University of Texas at Dallas, Dallas, Tex (J.M.P.); Department of Diagnostic Imaging and Radiology, Developing Brain Institute, Children's National Hospital, Washington, DC (Z.Z.); Department of Pediatrics and Radiology, George Washington University, Washington, DC (Z.Z.); GE Healthcare, Dallas, Tex (G.D.R.); Department of Biochemistry and Molecular Medicine, University of California, Davis, Davis, Calif (T.J.); and Veterans Affairs North Texas Healthcare System, Dallas, Tex (C.R.M.).

Background Pyruvate dehydrogenase (PDH) and lactate dehydrogenase are essential for adenosine triphosphate production in skeletal muscle. At the onset of exercise, oxidation of glucose and glycogen is quickly enabled by dephosphorylation of PDH. However, direct measurement of PDH flux in exercising human muscle is daunting, and the net effect of covalent modification and other control mechanisms on PDH flux has not been assessed. Purpose To demonstrate the feasibility of assessing PDH activation and changes in pyruvate metabolism in human skeletal muscle after the onset of exercise using carbon 13 (C) MRI with hyperpolarized (HP) [1-C]-pyruvate. Materials and Methods For this prospective study, sedentary adults in good general health (mean age, 42 years ± 18 [standard deviation]; six men) were recruited from August 2019 to September 2020. Subgroups of the participants were injected with HP [1-C]-pyruvate at resting, during plantar flexion exercise, or 5 minutes after exercise during recovery. In parallel, hydrogen 1 arterial spin labeling MRI was performed to estimate muscle tissue perfusion. An unpaired test was used for comparing C data among the states. Results At rest, HP [1-C]-lactate and [1-C]-alanine were detected in calf muscle, but [C]-bicarbonate was negligible. During moderate flexion-extension exercise, total HP C signals (tC) increased 2.8-fold because of increased muscle perfusion ( = .005), and HP [1-C]-lactate-to-tC ratio increased 1.7-fold ( = .04). HP [C]-bicarbonate-to-tC ratio increased 8.4-fold ( = .002) and returned to the resting level 5 minutes after exercise, whereas the lactate-to-tC ratio continued to increase to 2.3-fold as compared with resting ( = .008). Conclusion Lactate and bicarbonate production from hyperpolarized (HP) [1-carbon 13 {C}]-pyruvate in skeletal muscle rapidly reflected the onset and the termination of exercise. These results demonstrate the feasibility of imaging skeletal muscle metabolism using HP [1-C]-pyruvate MRI and the sensitivity of in vivo pyruvate metabolism to exercise states. © RSNA, 2021
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http://dx.doi.org/10.1148/radiol.2021204500DOI Listing
June 2021

Cardiac measurement of hyperpolarized C metabolites using metabolite-selective multi-echo spiral imaging.

Magn Reson Med 2021 09 6;86(3):1494-1504. Epub 2021 Apr 6.

Advanced Imaging Research Center, The University of Texas Southwestern Medical Center, Dallas, Texas, USA.

Purpose: Noninvasive imaging with hyperpolarized (HP) pyruvate can capture in vivo cardiac metabolism. For proper quantification of the metabolites and optimization of imaging parameters, understanding MR characteristics such as s of the HP signals is critical. This study is to measure in vivo cardiac s of HP [1- C]pyruvate and the products in rodents and humans.

Methods: A dynamic C multi-echo spiral imaging sequence that acquires [ C]bicarbonate, [1- C]lactate, and [1- C]pyruvate images in an interleaved manner was implemented for a clinical 3 Tesla system. of each metabolite was calculated from the multi-echo images by fitting the signal decay of each region of interest mono-exponentially. The performance of measuring using the sequence was first validated using a C phantom and then with rodents following a bolus injection of HP [1- C]pyruvate. In humans, of each metabolite was calculated for left ventricle, right ventricle, and myocardium.

Results: Cardiac s of HP [1- C]pyruvate, [1- C]lactate, and [ C]bicarbonate in rodents were measured as 24.9 ± 5.0, 16.4 ± 4.7, and 16.9 ± 3.4 ms, respectively. In humans, of [1- C]pyruvate was 108.7 ± 22.6 ms in left ventricle and 129.4 ± 8.9 ms in right ventricle. of [1- C]lactate was 40.9 ± 8.3, 44.2 ± 5.5, and 43.7 ± 9.0 ms in left ventricle, right ventricle, and myocardium, respectively. of [ C]bicarbonate in myocardium was 64.4 ± 2.5 ms. The measurements were reproducible and consistent over time after the pyruvate injection.

Conclusion: The proposed metabolite-selective multi-echo spiral imaging sequence reliably measures in vivo cardiac s of HP [1- C]pyruvate and products.
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http://dx.doi.org/10.1002/mrm.28796DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8212421PMC
September 2021

Characterization and compensation of inhomogeneity artifact in spiral hyperpolarized C imaging of the human heart.

Magn Reson Med 2021 07 5;86(1):157-166. Epub 2021 Feb 5.

Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX, USA.

Purpose: This study aimed to investigate the role of regional inhomogeneity in spiral hyperpolarized C image quality and to develop measures to alleviate these effects.

Methods: Field map correction of hyperpolarized C cardiac imaging using spiral readouts was evaluated in healthy subjects. Spiral readouts with differing duration (26 and 45 ms) but similar resolution were compared with respect to off-resonance performance and image quality. An map-based image correction based on the multifrequency interpolation (MFI) method was implemented and compared to correction using a global frequency shift alone. Estimation of an unknown frequency shift was performed by maximizing a sharpness objective based on the Sobel variance. The apparent full width half at maximum (FWHM) of the myocardial wall on [ C]bicarbonate was used to estimate blur.

Results: Mean myocardial wall FWHM measurements were unchanged with the short readout pre-correction (14.1 ± 2.9 mm) and post-MFI correction (14.1 ± 3.4 mm), but significantly decreased in the long waveform (20.6 ± 6.6 mm uncorrected, 17.7 ± 7.0 corrected, P = .007). Bicarbonate signal-to-noise ratio (SNR) of the images acquired with the long waveform were increased by 1.4 ± 0.3 compared to those acquired with the short waveform (predicted 1.32). Improvement of image quality was observed for all metabolites with correction.

Conclusions: -map correction reduced blur and recovered signal from dropouts, particularly along the posterior myocardial wall. The low image SNR of [ C]bicarbonate can be compensated with longer duration readouts but at the expense of increased artifacts, which can be partially corrected for with the proposed methods.
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http://dx.doi.org/10.1002/mrm.28691DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8049085PMC
July 2021

Analysis Methods for Hyperpolarized Carbon (C) MRI of the Kidney.

Methods Mol Biol 2021 ;2216:697-710

Department of Radiology, Washington University, St. Louis, MO, USA.

Hyperpolarized C MR is a novel medical imaging modality with substantially different signal dynamics as compared to conventional H MR, thus requiring new methods for processing the data in order to access and quantify the embedded metabolic and functional information. Here we describe step-by-step analysis protocols for functional renal hyperpolarized C imaging. These methods are useful for investigating renal blood flow and function as well as metabolic status of rodents in vivo under various experimental physiological conditions.This chapter is based upon work from the COST Action PARENCHIMA, a community-driven network funded by the European Cooperation in Science and Technology (COST) program of the European Union, which aims to improve the reproducibility and standardization of renal MRI biomarkers. This analysis protocol chapter is complemented by two separate chapters describing the basic concept and experimental procedure.
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http://dx.doi.org/10.1007/978-1-0716-0978-1_42DOI Listing
March 2021

Hyperpolarized Carbon (C) MRI of the Kidney: Experimental Protocol.

Methods Mol Biol 2021 ;2216:481-493

GE Healthcare, Dallas, TX, USA.

Alterations in renal metabolism are associated with both physiological and pathophysiologic events. The existing noninvasive analytic tools including medical imaging have limited capability for investigating these processes, which potentially limits current understanding of kidney disease and the precision of its clinical diagnosis. Hyperpolarized C MRI is a new medical imaging modality that can capture changes in the metabolic processing of certain rapidly metabolized substrates, as well as changes in kidney function. Here we describe experimental protocols for renal metabolic [1-C]pyruvate and functional C-urea imaging step-by-step. These methods and protocols are useful for investigating renal blood flow and function as well as the renal metabolic status of rodents in vivo under various experimental (patho)physiological conditions.This chapter is based upon work from the COST Action PARENCHIMA, a community-driven network funded by the European Cooperation in Science and Technology (COST) program of the European Union, which aims to improve the reproducibility and standardization of renal MRI biomarkers. This experimental protocol is complemented by two separate chapters describing the basic concept and data analysis.
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http://dx.doi.org/10.1007/978-1-0716-0978-1_29DOI Listing
March 2021

Hyperpolarized Carbon (C) MRI of the Kidneys: Basic Concept.

Methods Mol Biol 2021 ;2216:267-278

Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.

Existing clinical markers for renal disease are limited. Hyperpolarized (HP) C MRI is based on the technology of dissolution dynamic nuclear polarization (DNP) and provides new avenues for imaging kidney structure, function, and most notably, renal metabolism, addressing some of these prior limitations. Changes in kidney structure and function associated with kidney disease can be evaluated using [C]urea, a metabolically inert tracer. Metabolic changes can be assessed using [1-C]pyruvate and a range of other rapidly metabolized small molecules, which mainly probe central carbon metabolism. Results from numerous preclinical studies using a variety of these probes demonstrated that this approach holds great potential for monitoring renal disease, although more work is needed to bridge intelligently into clinical studies. Here we introduce the general concept of HP C MRI and review the most relevant probes and applications to renal disease, including kidney cancer, diabetic nephropathy and ischemic kidney injury.This chapter is based upon work from the PARENCHIMA COST Action, a community-driven network funded by the European Cooperation in Science and Technology (COST) program of the European Union, which aims to improve the reproducibility and standardization of renal MRI biomarkers. This introduction chapter is complemented by two separate chapters describing the experimental procedure and data analysis.
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http://dx.doi.org/10.1007/978-1-0716-0978-1_16DOI Listing
March 2021

Imaging Acute Metabolic Changes in Patients with Mild Traumatic Brain Injury Using Hyperpolarized [1-C]Pyruvate.

iScience 2020 Dec 30;23(12):101885. Epub 2020 Nov 30.

Advanced Imaging Research Center, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

Traumatic brain injury (TBI) involves complex secondary injury processes following the primary injury. The secondary injury is often associated with rapid metabolic shifts and impaired brain function immediately after the initial tissue damage. Magnetic resonance spectroscopic imaging (MRSI) coupled with hyperpolarization of C-labeled substrates provides a unique opportunity to map the metabolic changes in the brain after traumatic injury in real-time without invasive procedures. In this report, we investigated two patients with acute mild TBI (Glasgow coma scale 15) but no anatomical brain injury or hemorrhage. Patients were imaged with hyperpolarized [1-C]pyruvate MRSI 1 or 6 days after head trauma. Both patients showed significantly reduced bicarbonate (HCO ) production, and one showed hyperintense lactate production at the injured sites. This study reports the feasibility of imaging altered metabolism using hyperpolarized pyruvate in patients with TBI, demonstrating the translatability and sensitivity of the technology to cerebral metabolic changes after mild TBI.
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http://dx.doi.org/10.1016/j.isci.2020.101885DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7736977PMC
December 2020

Comparison of hyperpolarized C and non-hyperpolarized deuterium MRI approaches for imaging cerebral glucose metabolism at 4.7 T.

Magn Reson Med 2021 04 28;85(4):1795-1804. Epub 2020 Nov 28.

Mallinckrodt Institute of Radiology, Washington University, St. Louis, Missouri, USA.

Purpose: The purpose of this study was to directly compare two isotopic metabolic imaging approaches, hyperpolarized (HP) C MRI and deuterium metabolic imaging (DMI), for imaging specific closely related segments of cerebral glucose metabolism at 4.7 T.

Methods: Comparative HP- C and DMI neuroimaging experiments were conducted consecutively in normal rats during the same scanning session. Localized conversions of [1- C]pyruvate and [6,6- H ]glucose to their respective downstream metabolic products were measured by spectroscopic imaging, using an identical 2D-CSI sequence with parameters optimized for the respective experiments. To facilitate direct comparison, a pair of substantially equivalent 2.5-cm double-tuned X/ H RF surface coils was developed. For improved results, multidimensional low-rank reconstruction was applied to denoise the raw DMI data.

Results: Localized conversion of HP [1- C]pyruvate to [1- C]lactate, and [6,6- H ]glucose to [3,3- H ]lactate and Glx-d (glutamate and glutamine), was detected in rat brain by spectroscopic imaging at 4.7 T. The SNR and spatial resolution of HP- C MRI was superior to DMI but limited to a short time window, whereas the lengthy DMI acquisition yielded maps of not only lactate, but also Glx production, albeit with relatively poor spectral discrimination between metabolites at this field strength. Across the individual rats, there was an apparent inverse correlation between cerebral production of HP [1- C]lactate and Glx-d, along with a trend toward increased [3,3- H ]lactate.

Conclusion: The HP- C MRI and DMI methods are both feasible at 4.7 T and have significant potential for metabolic imaging of specific segments of glucose metabolism.
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http://dx.doi.org/10.1002/mrm.28612DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8018714PMC
April 2021

N-carnitine, a novel endogenous hyperpolarized MRI probe with long signal lifetime.

Magn Reson Med 2021 04 12;85(4):1814-1820. Epub 2020 Nov 12.

Department of Biochemistry, University of Florida, Gainesville, Florida, USA.

Purpose: The purpose of this study was to investigate hyperpolarization and in vivo imaging of [ N]carnitine, a novel endogenous MRI probe with long signal lifetime.

Methods: L-[ N]carnitine-d was hyperpolarized by the method of dynamic nuclear polarization followed by rapid dissolution. The T signal lifetimes were estimated in aqueous solution and in vivo following intravenous injection in rats, using a custom-built dual-tuned N/ H RF coil at 4.7 T. N chemical shift imaging and N fast spin-echo images of rat abdomen were acquired 3 minutes after [ N]carnitine injection.

Results: Estimated T times of [ N]carnitine at 4.7 T were 210 seconds (in H O) and 160 seconds (in vivo), with an estimated polarization level of 10%. Remarkably, the [ N]carnitine coherence was detectable in rat abdomen for 5 minutes after injection for the nonlocalized acquisition. No downstream metabolites were detected on localized or nonlocalized N spectra. Diffuse liver enhancement was detected on N fast spin-echo imaging 3 minutes after injection, with mean hepatic SNR of 18 ± 5 at a spatial resolution of 4 × 4 mm.

Conclusion: This study showed the feasibility of hyperpolarizing and imaging the biodistribution of HP [ N]carnitine.
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http://dx.doi.org/10.1002/mrm.28578DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7856872PMC
April 2021

Tensor image enhancement and optimal multichannel receiver combination analyses for human hyperpolarized C MRSI.

Magn Reson Med 2020 12 5;84(6):3351-3365. Epub 2020 Jun 5.

Department of Radiology and Biomedical Imaging, University of California, San Francisco, California, USA.

Purpose: With the initiation of human hyperpolarized C (HP- C) trials at multiple sites and the development of improved acquisition methods, there is an imminent need to maximally extract diagnostic information to facilitate clinical interpretation. This study aims to improve human HP- C MR spectroscopic imaging through means of Tensor Rank truncation-Image enhancement (TRI) and optimal receiver combination (ORC).

Methods: A data-driven processing framework for dynamic HP C MR spectroscopic imaging (MRSI) was developed. Using patient data sets acquired with both multichannel arrays and single-element receivers from the brain, abdomen, and pelvis, we examined the theory and application of TRI, as well as 2 ORC techniques: whitened singular value decomposition (WSVD) and first-point phasing. Optimal conditions for TRI were derived based on bias-variance trade-off.

Results: TRI and ORC techniques together provided a 63-fold mean apparent signal-to-noise ratio (aSNR) gain for receiver arrays and a 31-fold gain for single-element configurations, which particularly improved quantification of the lower-SNR-[ C]bicarbonate and [1- C]alanine signals that were otherwise not detectable in many cases. Substantial SNR enhancements were observed for data sets that were acquired even with suboptimal experimental conditions, including delayed (114 s) injection (8× aSNR gain solely by TRI), or from challenging anatomy or geometry, as in the case of a pediatric patient with brainstem tumor (597× using combined TRI and WSVD). Improved correlation between elevated pyruvate-to-lactate conversion, biopsy-confirmed cancer, and mp-MRI lesions demonstrated that TRI recovered quantitative diagnostic information.

Conclusion: Overall, this combined approach was effective across imaging targets and receiver configurations and could greatly benefit ongoing and future HP C MRI research through major aSNR improvements.
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http://dx.doi.org/10.1002/mrm.28328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7718428PMC
December 2020

Simultaneous T and T mapping of hyperpolarized C compounds using the bSSFP sequence.

J Magn Reson 2020 03 1;312:106691. Epub 2020 Feb 1.

Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA.

As in conventional H MRI, T and T relaxation times of hyperpolarized (HP) C nuclei can provide important biomedical information. Two new approaches were developed for simultaneous T and T mapping of HP C probes based on balanced steady state free precession (bSSFP) acquisitions: a method based on sequential T and T mapping modules, and a model-based joint T/T approach analogous to MR fingerprinting. These new methods were tested in simulations, HP C phantoms, and in vivo in normal Sprague-Dawley rats. Non-localized T values, low flip angle EPI T maps, bSSFP T maps, and Bloch-Siegert B maps were also acquired for comparison. T and T maps acquired using both approaches were in good agreement with both literature values and data from comparative acquisitions. Multiple HP C compounds were successfully mapped, with their relaxation time parameters measured within heart, liver, kidneys, and vasculature in one acquisition for the first time.
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http://dx.doi.org/10.1016/j.jmr.2020.106691DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7227792PMC
March 2020

Using a local low rank plus sparse reconstruction to accelerate dynamic hyperpolarized C imaging using the bSSFP sequence.

J Magn Reson 2018 05 11;290:46-59. Epub 2018 Mar 11.

Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA; UC Berkeley-UCSF Graduate Program in Bioengineering, University of California, San Francisco, Berkeley, CA, USA. Electronic address:

Acceleration of dynamic 2D (T Mapping) and 3D hyperpolarized C 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 mm 2D dynamic acquisitions was achieved. This enabled visualization of the biodistribution of [2-C]pyruvate, [1-C]lactate, [C, N]urea, and HP001 within heart, kidneys, vasculature, and tumor, as well as calculation of high resolution T maps.
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http://dx.doi.org/10.1016/j.jmr.2018.03.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6054792PMC
May 2018

In vivo hyperpolarization transfer in a clinical MRI scanner.

Magn Reson Med 2018 08 27;80(2):480-487. Epub 2018 Feb 27.

Department of Biochemistry, University of Florida, Gainesville, Florida.

Purpose: The purpose of this study was to investigate the feasibility of in vivo C-> H hyperpolarization transfer, which has significant potential advantages for detecting the distribution and metabolism of hyperpolarized C probes in a clinical MRI scanner.

Methods: A standalone pulsed C RF transmit channel was developed for operation in conjunction with the standard H channel of a clinical 3T MRI scanner. Pulse sequences for C power calibration and polarization transfer were programmed on the external hardware and integrated with a customized water-suppressed H MRS acquisition running in parallel on the scanner. The newly developed RF system was tested in both phantom and in vivo polarization transfer experiments in J -coupled systems: phantom experiments in thermally polarized and hyperpolarized [2- C]glycerol, and H detection of [2- C]lactate generated from hyperpolarized [2- C]pyruvate in rat liver in vivo.

Results: Operation of the custom pulsed C RF channel resulted in effective C-> H hyperpolarization transfer, as confirmed by the characteristic antiphase appearance of H-detected, J -coupled doublets. In conjunction with a pulse sequence providing 190-fold water suppression in vivo, H detection of hyperpolarized [2- C]lactate generated in vivo was achieved in a rat liver slice.

Conclusion: The results show clear feasibility for effective C-> H hyperpolarization transfer in a clinical MRI scanner with customized heteronuclear RF system.
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http://dx.doi.org/10.1002/mrm.27154DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5910192PMC
August 2018

Development of high resolution 3D hyperpolarized carbon-13 MR molecular imaging techniques.

Magn Reson Imaging 2017 05 7;38:152-162. Epub 2017 Jan 7.

Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA; UC Berkeley-UCSF Graduate Program in Bioengineering, University of California, San Francisco and University of California, Berkeley, CA, USA. Electronic address:

The goal of this project was to develop and apply techniques for T mapping and 3D high resolution (1.5mm isotropic; 0.003cm) C imaging of hyperpolarized (HP) probes [1-C]lactate, [1-C]pyruvate, [2-C]pyruvate, and [C,N]urea in vivo. A specialized 2D bSSFP sequence was implemented on a clinical 3T scanner and used to obtain the first high resolution T 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 T mapping experiments yielded measurements of T values of >1s for all compounds within rat kidneys/vasculature and TRAMP tumors, except for [2-C]pyruvate which was ~730ms and ~320ms, respectively. The high resolution 3D imaging enabled visualization the biodistribution of [1-C]lactate, [1-C]pyruvate, and [2-C]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 (0.003cm) spatial and 2s temporal resolution in vivo utilizing HP C substrates by exploiting their long T values. This 1.5mm isotropic resolution is comparable to H 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.
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http://dx.doi.org/10.1016/j.mri.2017.01.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5360530PMC
May 2017

Spectrally selective three-dimensional dynamic balanced steady-state free precession for hyperpolarized C-13 metabolic imaging with spectrally selective radiofrequency pulses.

Magn Reson Med 2017 09 21;78(3):963-975. Epub 2016 Oct 21.

Department of Radiology and Biomedical Imaging, University of California, San Francisco, California, USA.

Purpose: Balanced steady-state free precession (bSSFP) sequences can provide superior signal-to-noise ratio efficiency for hyperpolarized (HP) carbon-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 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 C metabolites of copolarized [1- C]pyruvate and [ 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 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.
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http://dx.doi.org/10.1002/mrm.26480DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5400740PMC
September 2017

Imaging Renal Urea Handling in Rats at Millimeter Resolution using Hyperpolarized Magnetic Resonance Relaxometry.

Tomography 2016 Jun;2(2):125-135

Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, California, USA; Graduate Group in Bioengineering University of California San Francisco, San Francisco, California, USA, and University of California Berkeley, Berkeley, California, USA.

spin spin relaxation time () heterogeneity of hyperpolarized [C,N]urea in the rat kidney was investigated. Selective quenching of the vascular hyperpolarized C signal with a macromolecular relaxation agent revealed that a long- component of the [C,N]urea signal originated from the renal extravascular space, thus allowing the vascular and renal filtrate contrast agent pools of the [C,N]urea to be distinguished via multi-exponential analysis. The response to induced diuresis and antidiuresis was performed with two imaging agents: hyperpolarized [C,N]urea and a control agent hyperpolarized bis-1,1-(hydroxymethyl)-1-C-cyclopropane-H. Large increases in the inner-medullar and papilla were observed with the former agent and not the latter during antidiuresis. Therefore, [C,N]urea relaxometry is sensitive to two steps of the renal urea handling process: glomerular filtration and the inner-medullary urea transporter (UT)-A1 and UT-A3 mediated urea concentrating process. Simple motion correction and subspace denoising algorithms are presented to aid in the multi exponential data analysis. Furthermore, a -edited, ultra long echo time sequence was developed for sub-2 mm resolution 3D encoding of urea by exploiting relaxation differences in the vascular and filtrate pools.
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http://dx.doi.org/10.18383/j.tom.2016.00127DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4996281PMC
June 2016

Screen-printed flexible MRI receive coils.

Nat Commun 2016 Mar 10;7:10839. Epub 2016 Mar 10.

Department of Electrical Engineering and Computer Sciences, University of California, Berkeley, California 94720, USA.

Magnetic resonance imaging is an inherently signal-to-noise-starved technique that limits the spatial resolution, diagnostic image quality and results in typically long acquisition times that are prone to motion artefacts. This limitation is exacerbated when receive coils have poor fit due to lack of flexibility or need for padding for patient comfort. Here, we report a new approach that uses printing for fabricating receive coils. Our approach enables highly flexible, extremely lightweight conforming devices. We show that these devices exhibit similar to higher signal-to-noise ratio than conventional ones, in clinical scenarios when coils could be displaced more than 18 mm away from the body. In addition, we provide detailed material properties and components performance analysis. Prototype arrays are incorporated within infant blankets for in vivo studies. This work presents the first fully functional, printed coils for 1.5- and 3-T clinical scanners.
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http://dx.doi.org/10.1038/ncomms10839DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5553354PMC
March 2016

Chemical shift separation with controlled aliasing for hyperpolarized (13) C metabolic imaging.

Magn Reson Med 2015 Oct 8;74(4):978-89. Epub 2014 Oct 8.

Department of Radiology and Biomedical Imaging, University of California at San Francisco, San Francisco, California, USA.

Purpose: A chemical shift separation technique for hyperpolarized (13) C metabolic imaging with high spatial and temporal resolution was developed. Specifically, a fast three-dimensional pulse sequence and a reconstruction method were implemented to acquire signals from multiple (13) C species simultaneously with subsequent separation into individual images.

Theory And Methods: A stack of flyback echo-planar imaging readouts and a set of multiband excitation radiofrequency pulses were designed to spatially modulate aliasing patterns of the acquired metabolite images, which translated the chemical shift separation problem into parallel imaging reconstruction problem. An eight-channel coil array was used for data acquisition and a parallel imaging method based on nonlinear inversion was developed to separate the aliased images.

Results: Simultaneous acquisitions of pyruvate and lactate in a phantom study and in vivo rat experiments were performed. The results demonstrated successful separation of the metabolite distributions into individual images having high spatial resolution.

Conclusion: This method demonstrated the ability to provide accelerated metabolite imaging in hyperpolarized (13) C MR using multichannel coils, tailored readout, and specialized RF pulses.
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http://dx.doi.org/10.1002/mrm.25473DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4390401PMC
October 2015

Rapid in vivo apparent diffusion coefficient mapping of hyperpolarized (13) C metabolites.

Magn Reson Med 2015 Sep 11;74(3):622-633. Epub 2014 Sep 11.

Department of Radiology and Biomedical Imaging, University of California, San Francisco, California, USA.

Purpose: Hyperpolarized (13) C magnetic resonance allows for the study of real-time metabolism in vivo, including significant hyperpolarized (13) C lactate production in many tumors. Other studies have shown that aggressive and highly metastatic tumors rapidly transport lactate out of cells. Thus, the ability to not only measure the production of hyperpolarized (13) C lactate but also understand its compartmentalization using diffusion-weighted MR will provide unique information for improved tumor characterization.

Methods: We used a bipolar, pulsed-gradient, double spin echo imaging sequence to rapidly generate diffusion-weighted images of hyperpolarized (13) C metabolites. Our methodology included a simultaneously acquired B1 map to improve apparent diffusion coefficient (ADC) accuracy and a diffusion-compensated variable flip angle scheme to improve ADC precision.

Results: We validated this sequence and methodology in hyperpolarized (13) C phantoms. Next, we generated ADC maps of several hyperpolarized (13) C metabolites in a normal rat, rat brain tumor, and prostate cancer mouse model using both preclinical and clinical trial-ready hardware.

Conclusion: ADC maps of hyperpolarized (13) C metabolites provide information about the localization of these molecules in the tissue microenvironment. The methodology presented here allows for further studies to investigate ADC changes due to disease state that may provide unique information about cancer aggressiveness and metastatic potential.
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http://dx.doi.org/10.1002/mrm.25422DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4362805PMC
September 2015

Directly detected (55)Mn MRI: application to phantoms for human hyperpolarized (13)C MRI development.

Magn Reson Imaging 2014 Dec 29;32(10):1165-70. Epub 2014 Aug 29.

Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA; UC Berkeley-UCSF Graduate Program in Bioengineering, University of California, San Francisco and University of California, Berkeley, CA.

In this work we demonstrate for the first time directly detected manganese-55 ((55)Mn) magnetic resonance imaging (MRI) using a clinical 3T MRI scanner designed for human hyperpolarized (13)C clinical studies with no additional hardware modifications. Due to the similar frequency of the (55)Mn and (13)C resonances, the use of aqueous permanganate for large, signal-dense, and cost-effective "(13)C" MRI phantoms was investigated, addressing the clear need for new phantoms for these studies. Due to 100% natural abundance, higher intrinsic sensitivity, and favorable relaxation properties, (55)Mn MRI of aqueous permanganate demonstrates dramatically increased sensitivity over typical (13)C phantom MRI, at greatly reduced cost as compared with large (13)C-enriched phantoms. A large sensitivity advantage (22-fold) was demonstrated. A cylindrical phantom (d=8 cm) containing concentrated aqueous sodium permanganate (2.7 M) was scanned rapidly by (55)Mn MRI in a human head coil tuned for (13)C, using a balanced steady state free precession acquisition. The requisite penetration of radiofrequency magnetic fields into concentrated permanganate was investigated by experiments and high frequency electromagnetic simulations, and found to be sufficient for (55)Mn MRI with reasonably sized phantoms. A sub-second slice-selective acquisition yielded mean image signal-to-noise ratio of ~60 at 0.5 cm(3) spatial resolution, distributed with minimum central signal ~40% of the maximum edge signal. We anticipate that permanganate phantoms will be very useful for testing HP (13)C coils and methods designed for human studies.
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http://dx.doi.org/10.1016/j.mri.2014.08.030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4254142PMC
December 2014

Simultaneous multiagent hyperpolarized (13)C perfusion imaging.

Magn Reson Med 2014 Dec 31;72(6):1599-609. Epub 2013 Dec 31.

Department of Radiology and Biomedical Imaging, University of California, San Francisco, California, USA.

Purpose: To demonstrate simultaneous hyperpolarization and imaging of three (13)C-labeled perfusion MRI contrast agents with dissimilar molecular structures ([(13)C]urea, [(13)C]hydroxymethyl cyclopropane, and [(13)C]t-butanol) and correspondingly variable chemical shifts and physiological characteristics, and to exploit their varying diffusibility for simultaneous measurement of vascular permeability and perfusion in initial preclinical studies.

Methods: Rapid and efficient dynamic multislice imaging was enabled by a novel pulse sequence incorporating balanced steady state free precession excitation and spectral-spatial readout by multiband frequency encoding, designed for the wide, regular spectral separation of these compounds. We exploited the varying bilayer permeability of these tracers to quantify vascular permeability and perfusion parameters simultaneously, using perfusion modeling methods that were investigated in simulations. "Tripolarized" perfusion MRI methods were applied to initial preclinical studies with differential conditions of vascular permeability, in normal mouse tissues and advanced transgenic mouse prostate tumors.

Results: Dynamic imaging revealed clear differences among the individual tracer distributions. Computed permeability maps demonstrated differential permeability of brain tissue among the tracers, and tumor perfusion and permeability were both elevated over values expected for normal tissues.

Conclusion: Tripolarized perfusion MRI provides new molecular imaging measures for specifically monitoring permeability, perfusion, and transport simultaneously in vivo.
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http://dx.doi.org/10.1002/mrm.25071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4077988PMC
December 2014

High resolution (13)C MRI with hyperpolarized urea: in vivo T(2) mapping and (15)N labeling effects.

IEEE Trans Med Imaging 2014 Feb 25;33(2):362-71. Epub 2013 Oct 25.

(13)C steady state free precession (SSFP) magnetic resonance imaging and effective spin-spin relaxation time (T2) mapping were performed using hyperpolarized [(13)C] urea and [(13) C,(15)N2] urea injected intravenously in rats. (15)N labeling gave large T2 increases both in solution and in vivo due to the elimination of a strong scalar relaxation pathway. The T2 increase was pronounced in the kidney, with [(13) C,(15) N2] urea giving T2 values of 6.3±1.3 s in the cortex and medulla, and 11±2 s in the renal pelvis. The measured T2 in the aorta was 1.3±0.3 s. [(13)C] urea showed shortened T2 values in the kidney of 0.23±0.03 s compared to 0.28±0.03 s measured in the aorta. The enhanced T2 of [(13)C,(15)N2] urea was utilized to generate large signal enhancement by SSFP acquisitions with flip angles approaching the fully refocused regime. Projection images at 0.94 mm in-plane resolution were acquired with both urea isotopes, with [(13)C,(15) N2] urea giving a greater than four-fold increase in signal-to-noise ratio over [(13)C] urea.
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http://dx.doi.org/10.1109/TMI.2013.2285120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4011557PMC
February 2014

Optimal variable flip angle schemes for dynamic acquisition of exchanging hyperpolarized substrates.

J Magn Reson 2013 Sep 14;234:75-81. Epub 2013 Jun 14.

Department of Radiology and Biomedical Imaging, University of California-San Francisco, San Francisco, CA, United States.

In metabolic MRI with hyperpolarized contrast agents, the signal levels vary over time due to T1 decay, T2 decay following RF excitations, and metabolic conversion. Efficient usage of the nonrenewable hyperpolarized magnetization requires specialized RF pulse schemes. In this work, we introduce two novel variable flip angle schemes for dynamic hyperpolarized MRI in which the flip angle is varied between excitations and between metabolites. These were optimized to distribute the magnetization relatively evenly throughout the acquisition by accounting for T1 decay, prior RF excitations, and metabolic conversion. Simulation results are presented to confirm the flip angle designs and evaluate the variability of signal dynamics across typical ranges of T1 and metabolic conversion. They were implemented using multiband spectral-spatial RF pulses to independently modulate the flip angle at various chemical shift frequencies. With these schemes we observed increased SNR of [1-(13)C]lactate generated from [1-(13)C]pyruvate, particularly at later time points. This will allow for improved characterization of tissue perfusion and metabolic profiles in dynamic hyperpolarized MRI.
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http://dx.doi.org/10.1016/j.jmr.2013.06.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3765634PMC
September 2013

Frequency-specific SSFP for hyperpolarized ¹³C metabolic imaging at 14.1 T.

Magn Reson Imaging 2013 Feb 13;31(2):163-70. Epub 2012 Aug 13.

Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA 94158, USA.

Metabolic imaging of hyperpolarized [1-(13)C] pyruvate co-polarized with [(13)C]urea by dynamic nuclear polarization with rapid dissolution is a promising new method for assessing tumor metabolism and perfusion simultaneously in vivo. Novel pulse sequences are required to enable dynamic imaging of multiple (13)C spectral lines with high spatiotemporal resolution. The goal of this study was to investigate a new frequency-specific approach for rapid metabolic imaging of multiple (13)C resonances using the spectral selectivity of steady-state free precession pulse (SSFP) trains. Methods developed in simulations were implemented in a dynamic frequency-cycled balanced SSFP pulse sequence on a 14.1-T animal magnetic resonance imaging scanner. This acquisition was tested in thermal and hyperpolarized phantom imaging studies and in a transgenic mouse with prostate cancer.
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http://dx.doi.org/10.1016/j.mri.2012.06.037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3651030PMC
February 2013

Multiparametric 3T endorectal mri after external beam radiation therapy for prostate cancer.

J Magn Reson Imaging 2012 Aug 25;36(2):430-7. Epub 2012 Apr 25.

Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA.

Purpose: To determine the best combination of magnetic resonance imaging (MRI) parameters for the detection of locally recurrent prostate cancer after external beam radiation therapy.

Materials And Methods: Our Institutional Review Board approved this study with a waiver of informed consent. Twenty-six patients with suspected recurrence due to biochemical failure were part of this research. The MR protocol included T2-weighted, MR spectroscopy, and diffusion-weighted MRI. Transrectal ultrasound-guided biopsy was the standard of reference. We used logistic regression to model the probability of a positive outcome and generalized estimating equations to account for clustering. The diagnostic performance of imaging was described using receiver operating characteristic (ROC) curves.

Results: The area under the ROC curve of MR spectroscopic imaging (MRSI) was 83.0% (95% confidence interval [CI] = 75.5-89.1). The combination of all MR techniques did not significantly improve the performance of imaging beyond the accuracy of MRSI alone, but a trend toward improved discrimination was noted (86.9%; 95% CI = 77.6-93.4; P = 0.09).

Conclusion: Incorporation of MRSI to T2-weighted and/or diffusion-weighted MRI significantly improves the assessment of patients with suspected recurrence after radiotherapy and a combined approach with all three modalities may have the best diagnostic performance.
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http://dx.doi.org/10.1002/jmri.23672DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3565567PMC
August 2012

A method for simultaneous echo planar imaging of hyperpolarized ¹³C pyruvate and ¹³C lactate.

J Magn Reson 2012 Apr 24;217:41-7. Epub 2012 Feb 24.

Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, USA.

A rapid echo planar imaging sequence for dynamic imaging of [1-(13)C] lactate and [1-(13)C] pyruvate simultaneously was developed. Frequency-based separation of these metabolites was achieved by spatial shifting in the phase-encoded direction with the appropriate choice of echo spacing. Suppression of the pyruvate-hydrate and alanine resonances is achieved through an optimized spectral-spatial RF waveform. Signal sampling efficiency as a function of pyruvate and lactate excitation angle was simulated using two site exchange models. Dynamic imaging is demonstrated in a transgenic mouse model, and phantom validations of the RF pulse frequency selectivity were performed.
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http://dx.doi.org/10.1016/j.jmr.2012.02.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3326401PMC
April 2012

Generating super stimulated-echoes in MRI and their application to hyperpolarized C-13 diffusion metabolic imaging.

IEEE Trans Med Imaging 2012 Feb 21;31(2):265-75. Epub 2011 Oct 21.

Department of Radiology and Biomedical Imaging, University of California—San Francisco, San Francisco, CA 94158, USA.

Stimulated-echoes in MR can be used to provide high sensitivity to motion and flow, creating diffusion and perfusion weighting as well as T(1) contrast, but conventional approaches inherently suffer from a 50% signal loss. The super stimulated-echo, which uses a specialized radio-frequency (RF) pulse train, has been proposed in order to improve the signal while preserving motion and T(1) sensitivity. This paper presents a novel and straightforward method for designing the super stimulated-echo pulse train using inversion pulse design techniques. This method can also create adiabatic designs with an improved response to RF transmit field variations. The scheme was validated in phantom experiments and shown in vivo to improve signal-to-noise ratio (SNR). We have applied a super stimulated-echo to metabolic MRI with hyperpolarized (13)C-labeled molecules. For spectroscopic imaging of hyperpolarized agents, several repetition times are required but only a single stimulated-echo encoding is feasible, which can lead to unwanted motion blurring. To address this, a super stimulated-echo preparation scheme was used in which the diffusion weighting is terminated prior to the acquisition, and we observed a SNR increases of 60% in phantoms and 49% in vivo over a conventional stimulated-echo. Experiments following injection of hyperpolarized [1-(13)C] -pyruvate in murine transgenic cancer models have shown improved delineation for tumors since signals from metabolites within tumor tissues are retained while those from the vasculature are suppressed by the diffusion preparation scheme.
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http://dx.doi.org/10.1109/TMI.2011.2168235DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3274664PMC
February 2012

Post-processing correction of the endorectal coil reception effects in MR spectroscopic imaging of the prostate.

J Magn Reson Imaging 2010 Sep;32(3):654-62

The Center for Molecular and Functional Imaging, Department of Radiology and Biomedical Imaging, The University of California, San Francisco, California 94107, USA.

Purpose: To develop and validate a post-processing correction algorithm to remove the effect of the inhomogeneous reception profile of the endorectal coil on MR spectroscopic imaging (MRSI) data.

Materials And Methods: A post-processing algorithm to correct for the endorectal coil reception effects on MRSI data was developed based upon theoretical modeling of the endorectal coil reception profile and of the spatial saturation pulse profiles. This algorithm was evaluated on three-dimensional (3D) MRSI data acquired at 3T from a uniform phantom and from 18 patients with known or suspected prostate cancer.

Results: For the phantom data, the coefficient of variation of metabolite peak areas decreased 16% to 46% and the peak area distributions became more Gaussian with correction, as demonstrated by higher Q-Q plot linear correlations (R(2) = 0.98 +/- 0.007 vs. R(2) = 0.89 +/- 0.066). Across the 18 patients, the mean coefficient of variation for suppressed water decreased significantly, from 0.95 +/- 0.18, to 0.66 +/- 0.11, (P < 10(-6), paired t-test) and the linear correlations of the Q-Q plots for the suppressed water increased from R(2) = 0.91 to R(2) = 0.95 (P = 0.0083, paired t-test) with correction.

Conclusion: An algorithm for reducing the effect of the inhomogeneous reception profile in endorectal coil acquired 3D MRSI prostate data was demonstrated, illustrating increased homogeneity and more Gaussian peak area distributions.
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http://dx.doi.org/10.1002/jmri.22258DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2957824PMC
September 2010
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