About

Dr. Matthew E Merritt leads a research program focused on applying advanced magnetic resonance techniques, including deuterium MRI and NMR spectroscopy, to investigate metabolic dysfunction in diseases such as MASLD and Type 1 Diabetes. His work emphasizes the use of stable isotope tracers to non-invasively monitor metabolic flux in vivo and to identify early biomarkers of disease progression. By integrating magnetic resonance methods with complementary tools like mass spectrometry, Dr. Merritt aims to develop a comprehensive understanding of metabolic alterations in various pathological states. His laboratory fosters translational research at the intersection of chemistry, biology, and medicine, enabling the application of metabolic imaging and tracer-based studies alongside computational data analysis.

Research topics

• Biology
• Biochemistry
• Chemistry
• Physics
• Physical chemistry
• Endocrinology
• Internal medicine
• Genetics
• Molecular biology
• Botany
• Cell biology
• Chromatography
• Medicine
• Nuclear magnetic resonance
• Biological system

Selected publications

• Physiological Interpretation of the Lactate to Pyruvate <scp>AUC</scp> Ratio for Hyperpolarized [ <scp> 1‐ ¹³ C </scp> ]‐Pyruvate Studies

  Magnetic Resonance in Medicine · 2026-02-27

  articleOpen access

  ABSTRACT Purpose To explore the relationship between potentially rate‐limiting steps in lactate production and the lactate area‐under‐the‐curve (AUC) to pyruvate AUC ratio for analysis of hyperpolarized (HP) [1‐ 13 C]‐pyruvate data. Theory and Methods Simplifying assumptions are introduced to a pharmacokinetic (PK) model with three physical compartments and two chemical pools to write the AUC ratio in terms of model parameters. Synthetic time curves are used to test sensitivity of the AUC ratio and model parameters to different physiological conditions and acquisition parameters. The simplified model is used to analyze data from patients with head and neck squamous cell carcinoma and determine the rate‐limiting step in lactate production. Results The simplified model leads to an expression that explicitly demonstrates the relationship between PK model parameters and the AUC ratio. The AUC ratio depends most strongly on intracellular metabolism when pyruvate signal predominantly arises from intracellular space. Simulations confirm that the parameterized AUC ratio can be used to correct for AUC ratio sensitivity to acquisition parameters such as TE. In patient data, the proposed analysis most commonly identified k ecP as the predominant rate limiting step in lactate production. Conclusion Changes observed in the AUC ratio may be driven by changes in pyruvate extravasation, transport into the cell, and/or intracellular metabolism. The proposed model permits parametric representation of the AUC ratio, identification of rate‐limiting steps in lactate production, and correction for differences induced by acquisition parameters.

  PublisherDOI

• Comparison of HDO production from [2,3,4,6,6- ² H ₅ ]Glucose and [ ² H ₇ ]Glucose as a marker of Glucose metabolism

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-04-07

  articleOpen accessSenior authorCorresponding

  ABSTRACT PURPOSE Glycolytic production of HDO from the metabolism of perdeuterated glucose provides a means for metabolic imaging with 2 H MRI. The present study compared HDO production from a cost-efficient [2,3,4,6,6- 2 H 5 ]glucose with [ 2 H 7 ]glucose in vitro and in vivo . METHODS 2 H NMR spectroscopy was performed to measure glucose consumption, lactate, and HDO production in the SFxL glioblastoma cell line. In vivo studies in healthy mice using 2 H magnetic resonance spectroscopy were performed at 11.1 T after administering a bolus of either metabolic contrast agent. In vivo metabolite levels were quantified using unlocalized and slice-selective localized spectra. RESULTS Our in vitro results demonstrated similar glucose consumption and HDO production kinetics, although significant differences in lactate labeling were observed. The in vivo study showed comparable glucose consumption and HDO production kinetics following tail-vein bolus administration of either metabolic contrast agent, while lactate was not detected in the brain. CONCLUSION [2,3,4,6,6- 2 H 5 ]glucose shows comparable HDO production to [ 2 H 7 ]glucose, while offering lower cost and reduced spectral complexity. These findings place [2,3,4,6,6- 2 H 5 ]glucose as an alternative to [ 2 H 7 ]glucose for HDO-based DMI studies.

  PublisherOA PDFDOI

• The state of imaging glycolytic metabolism in cancer with magnetic resonance

  npj Imaging · 2026-02-10

  articleOpen access

  Imaging is essential for probing cancer biology and tumor surveillance in humans. Combining isotopically labeled substrates with advanced imaging approaches yields a new platform, metabolic imaging. Although cancer metabolism research began ~100 years ago, breakthroughs in magnetic resonance imaging (MRI) like hyperpolarization, deuterium metabolic imaging, and novel probes have revolutionized our ability to appreciate deregulated glycolysis in cancer. Here, we discuss the state and future of glycolytic imaging with MRI.

  PublisherOA PDFDOI

• Best practices in NMR metabolomics: Current state

  UNC Libraries · 2026-04-23

  articleOpen access1st authorCorresponding
  PublisherDOI

• Adaptations in Central Carbon and Fatty Acid Metabolism in the Type 1 Diabetic Exocrine Pancreas by Magnetic Resonance

  Proceedings on CD-ROM - International Society for Magnetic Resonance in Medicine. Scientific Meeting and Exhibition/Proceedings of the International Society for Magnetic Resonance in Medicine, Scientific Meeting and Exhibition · 2025-09-16

  articleSenior author

  Motivation: The role of the exocrine pancreas in Type 1 Diabetes (T1D) pathophysiology is dramatically understudied. Goal(s): Our goal was to measure pyruvate metabolism and de novo lipogenesis (DNL) to determine if the exocrine pancreas displays metabolic adaptations in the context of T1D. Approach: : We utilized hyperpolarized [1-13C]pyruvate and JHSQC experiments as well as 2H spectroscopy after 2H2O administration in a mouse model of T1D to interrogate these metabolic pathways. Results: Pyruvate carboxylation was increased in the T1D exocrine pancreas with active pyruvate cycling. DNL was decreased in the liver with no significant changes in the pancreas. Impact: The consequences of pyruvate cycling and increased pyruvate carboxylation in the T1D exocrine pancreas can now be investigated, and may be a target for therapeutic intervention, whereas rates of DNL were unchanged in the T1D pancreas.

  PublisherDOI

• Spatial mapping of the brain metabolome lipidome and glycome

  Nature Communications · 2025-05-12 · 23 citations

  articleOpen access

  Metabolites, lipids, and glycans are fundamental but interconnected classes of biomolecules that form the basis of the metabolic network. These molecules are dynamically channeled through multiple pathways that govern cellular physiology and pathology. Here, we present a framework for the simultaneous spatial analysis of the metabolome, lipidome, and glycome from a single tissue section using mass spectrometry imaging. This workflow integrates a computational platform, the Spatial Augmented Multiomics Interface (Sami), which enables multiomics integration, high-dimensional clustering, spatial anatomical mapping of matched molecular features, and metabolic pathway enrichment. To demonstrate the utility of this approach, we applied Sami to evaluate metabolic diversity across distinct brain regions and to compare wild-type and Ps19 Alzheimer’s disease (AD) mouse models. Our findings reveal region-specific metabolic demands in the normal brain and highlight metabolic dysregulation in the Ps19 model, providing insights into the biochemical alterations associated with neurodegeneration. Clarke et al. presents a framework for spatial analysis of the metabolome, lipidome, and glycome from a single tissue section using mass spectrometry imaging. Applying this approach, they revealed region-specific metabolic diversity and dysregulation in both normal and diseased mouse brains.

  PublisherOA PDFDOI

• Abstract 2006 Assessing Alterations in Hepatic Oxidation In MASLD/MASH via Preclinical Deuterium Metabolic MRI

  Journal of Biological Chemistry · 2025-05-01

  articleOpen accessSenior author

  Metabolic dysfunction-associated steatotic liver disease (MASLD) and its advanced form, metabolic dysfunction-associated steatohepatitis (MASH) are a rising health risk in the US. MASLD/MASH patients are at an increased risk of liver fibrosis, cirrhosis, and ultimately liver failure. Due to the increased prevalence of obesity in the United States, MASH is anticipated to become the primary driver of liver transplantations by 2030. While previous studies have shown that hepatic oxidative metabolism in MASLD can be correlated to disease progression, the metabolic underpinnings of the disease remain elusive.

  PublisherOA PDFDOI

• Kinetic Modeling of HP [1-13C]-Pyruvate Determines Dominant Physiological Parameters Influencing Lactate to Pyruvate AUC Ratio

  Proceedings on CD-ROM - International Society for Magnetic Resonance in Medicine. Scientific Meeting and Exhibition/Proceedings of the International Society for Magnetic Resonance in Medicine, Scientific Meeting and Exhibition · 2025-09-16

  article

  Motivation: The translation of HP [1-13C]-pyruvate as a method for quantifying aerobic glycolysis in tumors depends on a careful analysis of the processes that drive lactate production. Goal(s): We seek to introduce a method to determine the rate-limiting steps in overall lactate production. Approach: The HP pyruvate study of a patient with oropharyngeal squamous cell carcinoma was reanalyzed with pharmacokinetic modeling to determine relative levels of HP pyruvate in the three physical compartments of a pharmacokinetic model. Results: Overall pyruvate signal was mostly dominated by extravascular/extracellular pyruvate, indicating that lactate production was not primarily influenced by intracellular metabolism. Impact: The proposed analysis has the potential to aid in the analysis of [1-13C]-pyruvate studies by distinguishing between the effects of pyruvate delivery to the cells and true Warburg metabolism in tumors.

  PublisherDOI

• Metabolic flux analysis of glioblastoma neural stem cells reveals distinctive metabolic phenotypes in ketogenic conditions

  Scientific Reports · 2025-05-28

  articleOpen accessSenior author

  Glioblastomas (GBM) are the most prevalent primary brain tumors, affecting 5 in every 100,000 people. GBMs optimize proliferation through adaptive cellular metabolism, frequently exploiting the Warburg effect by increasing aerobic glycolysis and glucose utilization to facilitate rapid cell growth. This disproportionate reliance on glucose has driven interest in using the ketogenic diet (KD) as a treatment for GBM. In this study, we explored metabolic flux in three primary human GBM cell samples using a media simulating a KD. Flux analysis using a detailed metabolic modeling approach revealed three unique metabolic phenotypes in the patient GBMs that correlated with cell viability. Notably, these phenotypes are apparent in the flux modeling, but were not evidenced by changes in the metabolite pool sizes. This variability in metabolic flux may underlie the inconsistent results observed in preclinical and clinical studies using the KD as a treatment paradigm.

  PublisherOA PDFDOI

• In vivo Imaging of Dysregulated β-Oxidation in a Diet-Induced Model of MASLD with [D15]octanoate

  Proceedings on CD-ROM - International Society for Magnetic Resonance in Medicine. Scientific Meeting and Exhibition/Proceedings of the International Society for Magnetic Resonance in Medicine, Scientific Meeting and Exhibition · 2025-09-16

  articleSenior author

  Motivation: Metabolic dysfunction-associated steatotic liver disease (MASLD) affects more than 30% of adults in the US. Disease can progress to more severe forms and eventually death. Current diagnosis by liver biopsy is limited by sampling error and morbidity risk. Development of improved diagnostics is required. Goal(s): Development of a minimally invasive method based on deuterium metabolic imaging (DMI) may improve MASLD diagnostics. Approach: Imaging deuterated water (HDO) production from [D15]octanoate metabolism to assess β-oxidative capacity in a MASLD mouse model. Results: [D15]octanoate DMI generated metabolic maps of β-oxidation and demonstrated reduced β-oxidative efficiency that correlated with clinically relevant assays for MASLD. Impact: Imaging HDO production from [D15]octanoate oxidation can detect organ specific metabolism and may lead to a novel clinical method for staging MASLD in a minimally invasive manner. [D15]octanoate DMI needs to be tested in humans to assess clinical capability.

  PublisherDOI

Recent grants

• Imaging Hepatic Gluconeogenesis with Hyperpolarized Dihydroxyacetone

  NIH · $354k · 2016–2021

• Hyperpolarized 13C imaging for studying beta-oxidative and anaplerotic pathways

  NIH · $437k · 2014–2017

• Imaging Hepatic Energy Metabolism in NAFLD/NASH

  NIH · $2.0M · 2022–2026

• Imaging Hepatic Gluconeogenesis with Hyperpolarized Dihydroxyacetone

  NIH · $1.4M · 2016–2022

• NIH Grant P41RR002584

  NIH · $5.3M · 2016

Frequent coauthors

• Craig R. Malloy

  The University of Texas Southwestern Medical Center

  236 shared

• A. Dean Sherry

  231 shared

• Shawn C. Burgess

  HumanN (United States)

  82 shared

• Zoltán Kovács

  Institute of Genetics

  77 shared

• Lloyd Lumata

  The University of Texas Southwestern Medical Center

  52 shared

• Ralph J. DeBerardinis

  The University of Texas Southwestern Medical Center

  51 shared

• Mukundan Ragavan

  St. Jude Children's Research Hospital

  49 shared

• Crystal Harrison

  Advanced Imaging Research (United States)

  43 shared

Labs

• The Merritt LaboratoryPI

Education

• Ph.D., Biochemistry and Molecular Biology

  University of Florida

  2000

• M.S., Biochemistry and Molecular Biology

  University of Florida

  1996

• B.S., Biochemistry and Molecular Biology

  University of Florida

  1994