Influence of parameter accuracy on pharmacokinetic analysis of hyperpolarized pyruvate

Sun, Changyu; Walker, Christopher M.; Michel, Keith A.; Venkatesan, Aradhana M.; Lai, Stephen Y.; Bankson, James A.

doi:10.1002/mrm.26992

Cited by 24 publications

(33 citation statements)

References 33 publications

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“…While Equation 1 can be used to model the longitudinal magnetization, signal detection requires that some of the longitudinal magnetization to be excited into the transverse plane. Previous analyses accounted for excitation losses by averaging over the TR interval . Excitation loss averaging can lead to errors in analysis .…”

Section: Methodsmentioning

confidence: 99%

“…Previous analyses accounted for excitation losses by averaging over the TR interval . Excitation loss averaging can lead to errors in analysis . An alternative and more accurate approach applies Equation 1 iteratively over TR intervals defined to span between signal excitations.…”

Section: Methodsmentioning

confidence: 99%

“…To explore total signal and the accuracy of pharmacokinetic analyses (

k_{italicpl}

) as a function of the number of excitations, all 3 sets of excitation angle schedules were generated with a 2‐s repetition time and 5–60 observations yielding a total acquisition time of 10–120 s. Equations 4 and 5 were used to generate noise‐free signal curves for CEA‐bb, VEA‐const, and VEA‐max excitation strategies. The amplitude of Gaussian noise required to achieve a peak HP pyruvate SNR of 25 was determined under reference CEA‐bb conditions (

T R = 2 s

θ = 20^{0}

n T R = 90

), and this noise level was added to all noise‐free signal curves. Equations 4 and 5 were then fit to the noisy synthetic data, assuming first that all system parameters were known a priori except

k_{italicpl}

, and again with perfusion terms

k_{italicve}

v_{e}

, and the AIF amplitude as additional unknowns.…”

Section: Methodsmentioning

confidence: 99%

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Effects of excitation angle strategy on quantitative analysis of hyperpolarized pyruvate

Walker

Fuentes

Larson

et al. 2019

Magnetic Resonance in Med

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Purpose Various excitation strategies have been proposed for dynamic imaging of hyperpolarized agents such as [1‐13C]‐pyruvate, but the impact of these strategies on quantitative evaluation of signal evolution remains unclear. To better understand their relative performance, we compared the accuracy and repeatability of measurements made using variable excitation angle strategies and conventional constant excitation angle strategies. Methods Signal evolution for constant and variable excitation angle schedules was simulated using a pharmacokinetic model of hyperpolarized pyruvate with 2 chemical pools and 2 physical compartments. Noisy synthetic data were then fit using the same pharmacokinetic model with the apparent chemical exchange term as an unknown, and fit results were compared with simulation parameters to determine accuracy and reproducibility. Results Constant excitations and a variable excitation strategy that maximizes the HP lactate signal yielded data that supported quantitative analyses with similar accuracy and repeatability. Variable excitation angle strategies that were designed to produce a constant signal level resulted in lower signal and worse quantitative accuracy and repeatability, particularly for longer acquisition times. Conclusions These results suggest that either constant excitation angle or variable excitation angles that attempt to maximize total signal, as opposed to maintaining a constant signal level, are preferred for metabolic quantification using hyperpolarized pyruvate.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…To explore total signal and the accuracy of pharmacokinetic analyses (

k_{italicpl}

T R = 2 s

θ = 20^{0}

n T R = 90

), and this noise level was added to all noise‐free signal curves. Equations 4 and 5 were then fit to the noisy synthetic data, assuming first that all system parameters were known a priori except

k_{italicpl}

, and again with perfusion terms

k_{italicve}

v_{e}

, and the AIF amplitude as additional unknowns.…”

Section: Methodsmentioning

confidence: 99%

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Effects of excitation angle strategy on quantitative analysis of hyperpolarized pyruvate

Walker

Fuentes

Larson

et al. 2019

Magnetic Resonance in Med

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“…Bahrami et al uses a two‐site exchange model that incorporates neither pyruvate nor lactate AIF for simplicity, and Hill et al and Daniels et al also adopted similar strategies . Recently, the works of Bankson et al and Sun et al summarized several modeling techniques, and found that a perfused‐voxel model works better than two compartments based on Akaike's information criterion in a preclinical setting …”

Section: Introductionmentioning

confidence: 99%

Pulse sequence considerations for quantification of pyruvate‐to‐lactate conversion k_PL in hyperpolarized ¹³C imaging

et al. 2019

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Hyperpolarized 13C 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.

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“…In the context of hyperpoliarized 13 C MRI, B 1 calibration is crucial for variable flip angle schemes 15,16,18 and quantification of metabolic activities. 22 Due to the virtually non-existent endogenous 13 C signal, 13 C B 1 calibration is typically performed on external phantoms, but this approach does not account for the variability of subject loading. Bloch-Siegert B 1 mapping has been applied to hyperpolarized 13 C imaging 23,24 and is advantageous due to its short acquisition time and efficient use of the hyperpolarization signal.…”

Section: Introductionmentioning

confidence: 99%

A regional bolus tracking and real‐time B₁ calibration method for hyperpolarized ¹³C MRI

Tang

Milshteyn

Reed

et al. 2018

Magnetic Resonance in Med

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Purpose Acquisition timing and B1 calibration are two key factors that affect the quality and accuracy of hyperpolarized 13C 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 13C 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 13C imaging was tested on healthy rats, tumor‐bearing mice and a healthy volunteer on a clinical 3T scanner following hyperpolarized [1‐13C]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 13C imaging.

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Influence of parameter accuracy on pharmacokinetic analysis of hyperpolarized pyruvate

Cited by 24 publications

References 33 publications

Effects of excitation angle strategy on quantitative analysis of hyperpolarized pyruvate

Effects of excitation angle strategy on quantitative analysis of hyperpolarized pyruvate

Pulse sequence considerations for quantification of pyruvate‐to‐lactate conversion k_PL in hyperpolarized ¹³C imaging

A regional bolus tracking and real‐time B₁ calibration method for hyperpolarized ¹³C MRI

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Influence of parameter accuracy on pharmacokinetic analysis of hyperpolarized pyruvate

Cited by 24 publications

References 33 publications

Effects of excitation angle strategy on quantitative analysis of hyperpolarized pyruvate

Effects of excitation angle strategy on quantitative analysis of hyperpolarized pyruvate

Pulse sequence considerations for quantification of pyruvate‐to‐lactate conversion kPL in hyperpolarized 13C imaging

A regional bolus tracking and real‐time B1 calibration method for hyperpolarized 13C MRI

Contact Info

Product

Resources

About

Pulse sequence considerations for quantification of pyruvate‐to‐lactate conversion k_PL in hyperpolarized ¹³C imaging

A regional bolus tracking and real‐time B₁ calibration method for hyperpolarized ¹³C MRI