Detecting altered hepatic lipid oxidation by MRI in an animal model of MASLD.

Metabolic dysfunction-associated steatotic liver disease (MASLD) prevalence is increasing annually and affects over a third of US adults. MASLD can progress to metabolic dysfunction-associated steatohepatitis (MASH), characterized by severe hepatocyte injury, inflammation, and eventual advanced fibrosis or cirrhosis. MASH is predicted to become the primary cause of liver transplant by 2030.

New Horizons in Hyperpolarized C MRI.

Hyperpolarization techniques significantly enhance the sensitivity of magnetic resonance (MR) and thus present fascinating new directions for research and applications with in vivo MR imaging and spectroscopy (MRI/S). Hyperpolarized C MRI/S, in particular, enables real-time non-invasive assessment of metabolic processes and holds great promise for a diverse range of clinical applications spanning fields like oncology, neurology, and cardiology, with a potential for improving early diagnosis of disease, patient stratification, and therapy response assessment. Despite its potential, technical challenges remain for achieving clinical translation.

Mutual-information based optimal experimental design for hyperpolarized [Formula: see text]C-pyruvate MRI.

A key parameter of interest recovered from hyperpolarized (HP) MRI measurements is the apparent pyruvate-to-lactate exchange rate, [Formula: see text], for measuring tumor metabolism. This manuscript presents an information-theory-based optimal experimental design approach that minimizes the uncertainty in the rate parameter, [Formula: see text], recovered from HP-MRI measurements. Mutual information is employed to measure the information content of the HP measurements with respect to the first-order exchange kinetics of the pyruvate conversion to lactate.

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.

A Simulation of the Effects of Diffusion on Hyperpolarized [1-C]-Pyruvate Signal Evolution.

Objective: Hyperpolarized [1-C]-pyruvate magnetic resonance imaging is an emerging metabolic imaging method that offers unprecedented spatiotemporal resolution for monitoring tumor metabolism in vivo. To establish robust imaging biomarkers of metabolism, we must characterize phenomena that may modulate the apparent pyruvate-to-lactate conversion rate (k). Here, we investigate the potential effect of diffusion on pyruvate-to-lactate conversion, as failure to account for diffusion in pharmacokinetic analysis may obscure true intracellular chemical conversion rates.

Model-constrained reconstruction accelerated with Fourier-based undersampling for hyperpolarized [1- C] pyruvate imaging.

Purpose: Model-constrained reconstruction with Fourier-based undersampling (MoReFUn) is introduced to accelerate the acquisition of dynamic MRI using hyperpolarized [1- C]-pyruvate.

Methods: The MoReFUn method resolves spatial aliasing using constraints introduced by a pharmacokinetic model that describes the signal evolution of both pyruvate and lactate. Acceleration was evaluated on three single-channel data sets: a numerical digital phantom that is used to validate the accuracy of reconstruction and model parameter restoration under various SNR and undersampling ratios, prospectively and retrospectively sampled data of an in vitro dynamic multispectral phantom, and retrospectively undersampled imaging data from a prostate cancer patient to test the fidelity of reconstructed metabolite time series.

GdO-mesoporous silica/gold nanoshells: A potential dual / contrast agent for MRI-guided localized near-IR photothermal therapy.

A promising clinical trial utilizing gold-silica core-shell nanostructures coated with polyethylene glycol (PEG) has been reported for near-infrared (NIR) photothermal therapy (PTT) of prostate cancer. The next critical step for PTT is the visualization of therapeutically relevant nanoshell (NS) concentrations at the tumor site. Here we report the synthesis of PEGylated GdO-mesoporous silica/gold core/shell NSs (GdO-MS NSs) with NIR photothermal properties that also supply sufficient MRI contrast to be visualized at therapeutic doses (≥10 NSs per milliliter).

Development of a rational strategy for integration of lactate dehydrogenase A suppression into therapeutic algorithms for head and neck cancer.

Background: Lactate dehydrogenase (LDH) is a critical metabolic enzyme. LDH A (LDHA) overexpression is a hallmark of aggressive malignancies and has been linked to tumour initiation, reprogramming and progression in multiple tumour types. However, successful LDHA inhibition strategies have not materialised in the translational and clinical space.

Impact of diabetes on promoting the growth of breast cancer.

Background: Type II diabetes mellitus (DM2) is a significant risk factor for cancers, including breast cancer. However, a proper diabetic breast cancer mouse model is not well-established for treatment strategy design. Additionally, the precise diabetic signaling pathways that regulate cancer growth remain unresolved.

Comparison of selective excitation and multi-echo chemical shift encoding for imaging of hyperpolarized [1-C]pyruvate.

Imaging methods for hyperpolarized (HP) C agents must sample the evolution of signal from multiple agents with distinct chemical shifts within a very brief timeframe (typically < 1 min), which is challenging using conventional imaging methods. In this work, we compare two of the most commonly used HP spectroscopic imaging methods, spectral-spatial selective excitation and multi-echo chemical shift encoding (CSE, also referred to as IDEAL), for a typical preclinical HP [1-C]pyruvate imaging scan at 7 T. Both spectroscopic encoding techniques were implemented and validated in HP experiments imaging enzyme phantoms and the murine kidney.

Correction and optimization of symmetric echo-planar spectroscopic imaging for hyperpolarized [1-C]-pyruvate.

Symmetric echo-planar spectroscopic imaging (EPSI) supports higher spectral bandwidth and improves signal-to-noise efficiency compared to flyback EPSI with the same readout bandwidth, but suffers from artifacts that are associated with non-uniform temporal sampling in k-t space. Our goal is to eliminate these artifacts and enhance observation of hyperpolarized [1-C] pyruvate and its metabolites using symmetric EPSI. We used symmetric EPSI to efficiently acquire radially encoded spectroscopic imaging projections with a spectral under-sampling scheme that was optimized for HP pyruvate and its metabolites.

An information theory model for optimizing quantitative magnetic resonance imaging acquisitions.

Acquisition parameter selection is currently performed empirically for many quantitative MRI (qMRI) acquisitions. Tuning parameters for different scan times, tissues, and resolutions requires some amount of trial and error. There is an opportunity to quantitatively optimize these acquisition parameters in order to minimize variability of quantitative maps and post-processing techniques such as synthetic image generation.

Slice profile effects on quantitative analysis of hyperpolarized pyruvate.

Magnetic resonance imaging of hyperpolarized pyruvate provides a new imaging biomarker for cancer metabolism, based on the dynamic in vivo conversion of hyperpolarized pyruvate to lactate. Methods for quantification of signal evolution need to be robust and reproducible across a range of experimental conditions. Pharmacokinetic analysis of dynamic spectroscopic imaging data from hyperpolarized pyruvate and its metabolites generally assumes that signal arises from ideal rectangular slice excitation profiles.

Quantitative Dynamic Contrast-Enhanced MRI Identifies Radiation-Induced Vascular Damage in Patients With Advanced Osteoradionecrosis: Results of a Prospective Study.

Purpose: We aim to characterize the quantitative dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) parameters associated with advanced mandibular osteoradionecrosis (ORN) compared with the contralateral normal mandible.

Methods And Materials: Patients with a diagnosis of advanced ORN after curative-intent radiation treatment of head and neck cancer were prospectively enrolled after institutional review board approval and study-specific informed consent were obtained. Quantitative maps generated with the Tofts and extended Tofts pharmacokinetic models were used for analysis.

Development and application of an elastic net logistic regression model to investigate the impact of cardiac substructure dose on radiation-induced pericardial effusion in patients with NSCLC.

Background: Typically, cardiac substructures are neither delineated nor analyzed during radiation treatment planning. Therefore, we developed a novel machine learning model to evaluate the impact of cardiac substructure dose for predicting radiation-induced pericardial effusion (PCE).

Materials And Methods: One-hundred and forty-one stage III NSCLC patients, who received radiation therapy in a prospective clinical trial, were included in this analysis.

magnetic resonance imaging of orthotopic prostate cancer.

Methods for imaging orthotopic prostate tumors within the prostate or small tumors with extension outside the prostate are needed to more closely model human prostate tumors, which are most commonly located within the gland or may extend just through the gland. By comparing MR sequences, we found that the T2-based Dixon 'water only' sequence best visualized tumors within the prostate of mouse models in both young and old mice and that tumor weight derived from this sequence correlated highly with tumor weight (r = 0.98, p < 0.

Technical Note: A deuterated C-urea reference for clinical multiparametric MRI prostate cancer studies including hyperpolarized pyruvate.

Purpose: Metabolic magnetic resonance imaging (MRI) using hyperpolarized [1- C]-pyruvate offers unprecedented new insight into disease and response to therapy. C-enriched reference standards are required to enable fast and accurate calibration for C studies, but care must be taken to ensure that the reference is compatible with both C and H acquisitions. The goal of this study was to optimize the composition of a C-urea reference for a dual-tuned C/ H endorectal coil and minimize imaging artifacts in metabolic and multiparametric MRI studies involving hyperpolarized [1- C]-pyruvate.

Effect of Radiation on DCE-MRI Pharmacokinetic Parameters in a Rabbit Model of Compromised Maxillofacial Wound Healing: A Pilot Study.

Purpose: Osteoradionecrosis (ORN), a potentially debilitating complication of maxillofacial radiation, continues to present a challenging clinical scenario, with limited treatment options that often fail. Translational animal models that can accurately mimic the human characteristics of the condition are lacking. In the present pilot study, we aimed to characterize the effects of radiation on the dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) pharmacokinetic parameters in a rabbit model of compromised maxillofacial wound healing to determine its potential as a translational model of ORN.

Application of Trifluoroacetic Acid as a Theranostic Agent for Chemical Ablation of Solid Tissue.

Purpose: To evaluate trifluoroacetic acid (TFA) as a theranostic chemical ablation agent and determine the efficacy of TFA for both noninvasive imaging and tissue destruction.

Materials And Methods: Fluorine-19 magnetic resonance imaging (F-MRI) was optimized at 7 T using a custom-built volume coil. Fluorine images were acquired with both rapid acquisition with relaxation enhancement and balanced steady-state free precession (bSSFP) sequences with varying parameters to determine the optimal sequence for TFA.