Particle-based MR modeling with diffusion, microstructure, and enzymatic reactions.

Purpose: To develop a novel particle-based in silico MR model and demonstrate applications of this model to signal mechanisms which are affected by the spatial organization of particles, including metabolic reaction kinetics, microstructural effects on diffusion, and radiofrequency (RF) refocusing effects in gradient-echo sequences.

Methods: The model was developed by integrating a forward solution of the Bloch equations with a Brownian dynamics simulator. Simulation configurations were then designed to model MR signal dynamics of interest, with a primary focus on hyperpolarized C MRI methods.

Task Activation Results in Regional C-Lactate Signal Increase in the Human Brain.

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.

Evidence of C-lactate oxidation in the human brain from hyperpolarized C-MRI.

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.

First in-human evaluation of [1-C]pyruvate in DO for hyperpolarized MRI of the brain: A safety and feasibility study.

Purpose: To investigate the safety and value of hyperpolarized (HP) MRI of [1-C]pyruvate in healthy volunteers using deuterium oxide (DO) as a solvent.

Methods: Healthy volunteers (n = 5), were injected with HP [1-C]pyruvate dissolved in DO and imaged with a metabolite-specific 3D dual-echo dynamic EPI sequence at 3T at one site (Site 1). Volunteers were monitored following the procedure to assess safety.

Current Methods for Hyperpolarized [1-C]pyruvate MRI Human Studies.

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.

Age-associated change in pyruvate metabolism investigated with hyperpolarized C-MRI of the human brain.

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.

Imaging and treatment of brain tumors through molecular targeting: Recent clinical advances.

Molecular imaging techniques have rapidly progressed over recent decades providing unprecedented in vivo characterization of metabolic pathways and molecular biomarkers. Many of these new techniques have been successfully applied in the field of neuro-oncological imaging to probe tumor biology. Targeting specific signaling or metabolic pathways could help to address several unmet clinical needs that hamper the management of patients with brain tumors.

Cardiac metabolic imaging using hyperpolarized [1- C]lactate as a substrate.

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.

Predicting response to radiotherapy of intracranial metastases with hyperpolarized [Formula: see text]C MRI.

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).

Correlation of hyperpolarized C-MRI data with tissue extract measurements.

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.

Partial Fourier reconstruction for improved resolution in 3D hyperpolarized C EPI.

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.

Lactate topography of the human brain using hyperpolarized C-MRI.

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.

Hyperpolarized C MRI: Path to Clinical Translation in Oncology.

This white paper discusses prospects for advancing hyperpolarization technology to better understand cancer metabolism, identify current obstacles to HP (hyperpolarized) C magnetic resonance imaging's (MRI's) widespread clinical use, and provide recommendations for overcoming them. Since the publication of the first NIH white paper on hyperpolarized C MRI in 2011, preclinical studies involving [1-C]pyruvate as well a number of other C labeled metabolic substrates have demonstrated this technology's capacity to provide unique metabolic information. A dose-ranging study of HP [1-C]pyruvate in patients with prostate cancer established safety and feasibility of this technique.

Noninvasive Immunometabolic Cardiac Inflammation Imaging Using Hyperpolarized Magnetic Resonance.

Rationale: Current cardiovascular clinical imaging techniques offer only limited assessment of innate immune cell-driven inflammation, which is a potential therapeutic target in myocardial infarction (MI) and other diseases. Hyperpolarized magnetic resonance (MR) is an emerging imaging technology that generates contrast agents with 10- to 20 000-fold improvements in MR signal, enabling cardiac metabolite mapping.

Objective: To determine whether hyperpolarized MR using [1-C]pyruvate can assess the local cardiac inflammatory response after MI.

Simultaneous multislice acquisition without trajectory modification for hyperpolarized C experiments.

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.

Probing the cardiac malate-aspartate shuttle non-invasively using hyperpolarized [1,2- C ]pyruvate.

Previous studies have demonstrated that using hyperpolarized [2- C]pyruvate as a contrast agent can reveal C signals from metabolites associated with the tricarboxylic acid (TCA) cycle. However, the metabolites detectable from TCA cycle-mediated oxidation of [2- C]pyruvate are the result of several metabolic steps. In the instance of the [5- C]glutamate signal, the amplitude can be modulated by changes to the rates of pyruvate dehydrogenase (PDH) flux, TCA cycle flux and metabolite pool size.

Noninvasive Interrogation of Cancer Metabolism with Hyperpolarized C MRI.

This review will highlight recent advances in hyperpolarized C MR spectroscopic imaging, which can be used to noninvasively interrogate tumor metabolism. After providing an overview of MR and hyperpolarization, we will discuss the latest advances in data acquisition techniques. Next, we will shift our focus to hyperpolarized probe design and provide an overview of the latest hyperpolarized C MR spectroscopic imaging probes developed in the last several years.

Dual-Echo EPI sequence for integrated distortion correction in 3D time-resolved hyperpolarized C MRI.

Purpose: To provide built-in off-resonance correction in time-resolved, volumetric hyperpolarized C metabolic imaging by implementing a novel dual-echo 3D echo-planar imaging (EPI) sequence and reconstruction.

Methods: A spectral-spatial pulse for single-resonance excitation followed by a dual-echo 3D EPI readout was implemented to provide 64 × 8 × 6 cm coverage at 5 × 5 × 5 mm nominal resolution. Multiple sources of EPI distortions were encoded using a multi-echo H EPI reference scan.

Diffusion-weighted J-resolved spectroscopy.

Purpose: To develop a novel diffusion-weighted magnetic resonance spectroscopy (DW-MRS) technique in conjunction with J-resolved spatially localized spectroscopy (JPRESS) to measure the apparent diffusion coefficients (ADCs) of brain metabolites beyond N-acetylaspartic acid (NAA), creatine (Cr), and choline (Cho) at 3T. This technique will be useful to probe tissue microstructures in vivo, as the various metabolites have different physiological characteristics.

Methods: Two JPRESS spectra were collected (high b-value and low b-value), and the ADCs of 16 different metabolites were estimated.

Hyperpolarized 13C Metabolic MRI of the Human Heart: Initial Experience.

Rationale: Altered cardiac energetics is known to play an important role in the progression toward heart failure. A noninvasive method for imaging metabolic markers that could be used in longitudinal studies would be useful for understanding therapeutic approaches that target metabolism.

Objective: To demonstrate the first hyperpolarized C metabolic magnetic resonance imaging of the human heart.

A rapid inversion technique for the measurement of longitudinal relaxation times of brain metabolites: application to lactate in high-grade gliomas at 3 T.

The aim of this study was to develop a time-efficient inversion technique to measure the T1 relaxation time of the methyl group of lactate (Lac) in the presence of contaminating lipids and to measure T1 at 3 T in a cohort of primary high-grade gliomas. Three numerically optimized inversion times (TIs) were chosen to minimize the expected error in T1 estimates for a given input total scan duration (set to be 30 min). A two-cycle spectral editing scheme was used to suppress contaminating lipids.

Voxel-by-voxel correlations of perfusion, substrate, and metabolite signals in dynamic hyperpolarized (13) C imaging.

In this study, a mixture of pyruvic acid and the perfusion agent HP001 was co-polarized for simultaneous assessment of perfusion and metabolism in vivo. The pre-polarized mixture was administered to rats with subcutaneous MDA-MB-231 breast cancer xenografts and imaged using an interleaved sequence with designed spectral-spatial pulses and flyback echo-planar readouts. Voxel-by-voxel signal correlations from 10 animals (15 data sets) were analyzed for tumour, kidney, and muscle regions of interest.