Publications by authors named "Cornelius Von Morze"
Non-alcoholic steatohepatitis (NASH) is characterized from its early stages by a profound remodeling of the liver microenvironment, encompassing changes in the composition and activities of multiple cell types and associated gene expression patterns. Hyperpolarized (HP) C MRI provides a unique view of the metabolic microenvironment, with potential relevance for early diagnosis of liver disease. Previous studies have detected changes in HP C pyruvate to lactate conversion, catalyzed by lactate dehydrogenase (LDH), with experimental liver injury.
View Article and Find Full Text PDFUnlabelled: The PI3K pathway regulates essential cellular functions and promotes chemotherapy resistance. Activation of PI3K pathway signaling is commonly observed in triple-negative breast cancer (TNBC). However previous studies that combined PI3K pathway inhibitors with taxane regimens have yielded inconsistent results.
View Article and Find Full Text PDFPurpose: To develop a flexible, vendor-neutral EPI sequence for hyperpolarized C metabolic imaging.
Methods: An open-source EPI sequence consisting of a metabolite-specific spectral-spatial RF excitation pulse and a customizable EPI readout was created using the Pulseq framework. To explore the flexibility of our sequence, we tested several versions of the sequence including a symmetric 3D readout with different spatial resolutions for each metabolite (1.
Purpose: To demonstrate hyperpolarization of N-caffeine and report exploratory findings as a potential probe of liver function and perfusion.
Methods: An amorphous formulation of [1,3-N]caffeine was developed for hyperpolarization via dissolution dynamic nuclear polarization. Polarizer hardware was augmented to support monitoring of solid-state N MR signals during the buildup of hyperpolarization.
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.
Purpose: To use the hepatocyte-specific gadolinium-based contrast agent gadoxetate combined with hyperpolarized (HP) [1- C]pyruvate MRI to selectively suppress metabolic signals from normal hepatocytes while preserving the signals arising from tumors.
Methods: Simulations were performed to determine the expected changes in HP C MR signal in liver and tumor under the influence of gadoxetate. CC531 colon cancer cells were implanted into the livers of five Wag/Rij rats.
Purpose: Nonalcoholic fatty liver disease is an important cause of chronic liver disease. There are limited methods for monitoring metabolic changes during progression to steatohepatitis. Hyperpolarized C MRSI (HP C MRSI) was used to measure metabolic changes in a rodent model of fatty liver disease.
View Article and Find Full Text PDFMRI 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.
View Article and Find Full Text PDFBackground: Hyperpolarized C MRI quantitatively measures enzyme-catalyzed metabolism in cancer and metabolic diseases. Whole-abdomen imaging will permit dynamic metabolic imaging of several abdominal organs simultaneously in healthy and diseased subjects.
Purpose: Image hyperpolarized [1- C]pyruvate and products in the abdomens of healthy volunteers, overcoming challenges of motion, magnetic field variations, and spatial coverage.
Article Synopsis
- The study focuses on creating a new rapid imaging technique using hyperpolarized carbon MRI to capture real-time metabolic reactions in small areas of the body during medical imaging.
- A specialized pulse sequence was developed, tested in laboratory settings, and later applied to live rats to track metabolic changes related to two carbon compounds, achieving impressive spatial and temporal resolution.
- Results showed that this new imaging strategy effectively differentiated metabolic activity across organs, with certain metabolic processes, like the conversion of pyruvate to lactate, prominent in the liver and others in the kidneys and heart, enabling better understanding of metabolic pathways.
Article Synopsis
- Hyperpolarization (HP) enhances C MRI sensitivity but has limitations due to the short lifespan of HP agents; the study focuses on improving this through a new imaging sequence.
- An echo-planar imaging (EPI) sequence with spectral-spatial radiofrequency (SSRF) pulses allows for faster, more efficient metabolite-specific imaging of HP [1-C]pyruvate and [1-C]lactate in rats.
- The findings show that metabolite-specific EPI offers better spatial and temporal resolution than traditional methods and effectively extends the HP signal lifetime, marking a significant advancement in imaging technology at 4.7 T.
Article Synopsis
- Hyperpolarized C MR is a new imaging technique that offers different signal characteristics than traditional H MR, necessitating new data processing methods to analyze metabolic and functional information.
- The chapter outlines detailed protocols for analyzing functional renal hyperpolarized C imaging, which can assess kidney blood flow, function, and metabolism in live rodents under different experimental conditions.
- This work is part of the COST Action PARENCHIMA initiative, which aims to enhance the consistency and reliability of kidney MRI biomarkers in research.
Article Synopsis
- Alterations in how the kidneys metabolize substances are linked to both normal bodily functions and disease processes, but current imaging techniques fall short in effectively studying these changes and diagnosing kidney issues.
- Hyperpolarized C MRI is a promising new imaging method that allows for real-time observation of metabolic changes in kidney substrates and overall kidney function.
- This chapter outlines detailed experimental protocols for using [1-C]pyruvate and C-urea imaging to study kidney function and metabolism in rodents, as part of a broader effort to improve kidney MRI biomarker standardization through the European COST Action PARENCHIMA initiative.
Article Synopsis
- - Current clinical markers for kidney disease have limitations, but hyperpolarized carbon MRI (HP C MRI) offers new imaging techniques to evaluate kidney structure, function, and metabolism.
- - The technique utilizes [C]urea to assess kidney structure and [1-C]pyruvate along with other small molecules to analyze metabolic changes, showing promise from preclinical studies for monitoring renal diseases.
- - This research is part of the PARENCHIMA COST Action, which focuses on enhancing the reproducibility of renal MRI biomarkers, and the chapter includes additional details on experimental procedures and data analysis.
Article Synopsis
- The study aimed to compare two metabolic imaging techniques, hyperpolarized (HP) C MRI and deuterium metabolic imaging (DMI), to analyze cerebral glucose metabolism in rats at 4.7 T.
- Experiments were conducted using localized conversions of specific isotopes, utilizing advanced imaging techniques and specially designed RF coils for accurate analysis.
- Results indicated that while HP-C MRI offered better signal-to-noise ratio and spatial resolution, DMI provided broader metabolic insights over time, revealing complex relationships in lactate and glutamate production in the brain.
Article Synopsis
- 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.
Purpose: To use fiducial markers containing manganese 55 to rapidly localize carbon 13 ( C) RF coils for correcting images for B variation.
Methods: Hollow high-density polyethylene spheres were filled with 3M sodium permanganate and affixed to a rectangular C-tuned RF coil. The relative positions of the markers and coil conductors were mapped using CT.
Article Synopsis
- The study introduces two novel methods for simultaneously mapping T1 and T2 relaxation times of hyperpolarized carbon (HP C) nuclei using balanced steady state free precession (bSSFP) imaging techniques.
- These methods were validated through simulations, experiments with HP C phantoms, and in vivo testing on normal Sprague-Dawley rats, showing consistency with previously established data.
- For the first time, multiple HP C compounds were effectively mapped across various organs, including the heart, liver, kidneys, and vasculature, within a single acquisition.
Hyperpolarized C 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, k , a metabolic biomarker of cancer aggressiveness and progression. Therefore, it is crucial to evaluate k reliably.
View Article and Find Full Text PDFMagnetic resonance (MR)-based hyperpolarized (HP) C metabolic imaging is under active pursuit as a new clinical diagnostic method for cancer detection, grading, and monitoring of therapeutic response. Following the tremendous success of metabolic imaging by positron emission tomography, which already plays major roles in clinical oncology, the added value of HP C MRI is emerging. Aberrant glycolysis and central carbon metabolism is a hallmark of many forms of cancer.
View Article and Find Full Text PDFOxidative stress is a critical feature of several common neurologic disorders. The brain is well adapted to neutralize oxidative injury by maintaining a high steady-state concentration of small-molecule intracellular antioxidants including glutathione in astrocytes and ascorbic acid in neurons. Ascorbate-derived imaging probes for hyperpolarized C magnetic resonance spectroscopy and positron emission tomography have been used to study redox changes (antioxidant depletion and reactive oxygen species accumulation) in vivo.
View Article and Find Full Text PDFA robust and selective late-stage deuteration methodology was applied to 13C-enriched amino and alpha hydroxy acids to increase spin-lattice relaxation constant T1 for hyperpolarized 13C magnetic resonance imaging. For the five substrates with 13C-labeling on the C1-position ([1-13C]alanine, [1-13C]serine, [1-13C]lactate, [1-13C]glycine, and [1-13C]valine), significant increase of their T1 was observed at 3 T with deuterium labeling (+26%, 22%, +16%, +25% and +29%, respectively). Remarkably, in the case of [2-13C]alanine, [2-13C]serine and [2-13C]lactate, deuterium labeling led to a greater than four fold increase in T1.
View Article and Find Full Text PDFArticle Synopsis
- A specialized reconstruction method combining low rank and sparse techniques was developed to accelerate dynamic 2D and 3D hyperpolarized C MRI using balanced steady-state free precession sequence.
- The methods were validated with in vivo data from normal rats and tumor-bearing mice, allowing for up to four-fold acceleration in isotropic 3D dynamic acquisitions and two-fold acceleration in 2D dynamic acquisitions.
- This acceleration enabled detailed visualization of the biodistribution of various compounds, like [2-C]pyruvate and [1-C]lactate, in critical organs and tumors, along with the calculation of high-resolution T maps.
Article Synopsis
- 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.