About

Michael C. Langham, Ph.D., is a Research Associate Professor of Radiology at the University of Pennsylvania's Perelman School of Medicine. His research expertise includes physics, MRI physics, pulse sequence designing, and MRI techniques such as susceptometry, velocimetry, regional pulse-wave velocity quantification, vessel-wall imaging, non-contrast enhanced MR angiography, relaxometry, and arterial spin labeling (ASL). He has contributed to the development and application of advanced MRI methods to evaluate vascular and cerebral metabolic functions. Dr. Langham's work involves quantifying cerebral metabolic rate of oxygen, assessing vascular health impacts of inhaled substances like e-cigarette aerosols, and evaluating maternal vascular adaptations during pregnancy. His research also includes in vivo measurements of peripheral vascular function and the effects of sleep on cerebral oxygen metabolism. He has authored multiple publications in the field, advancing the understanding of MRI-based assessment of vascular and metabolic health.

Research topics

• Medicine
• Psychology
• Environmental health
• Anesthesia

Selected publications

• A reference-based PET/MRI method for quantifying activation-induced changes in cerebral oxygen metabolism

  Journal of Cerebral Blood Flow & Metabolism · 2026-03-15

  articleOpen access

  Hybrid PET/MRI can overcome the complexity of PET imaging of the cerebral metabolic rate of oxygen (CMRO 2 ), while retaining the ability to directly measure oxygen uptake in the brain. One technique, PMROx, incorporates complementary MRI methods acquired simultaneously with [ 15 O]O 2 -PET. Specifically, the MRI-based method arterial spin labelling (ASL) to image cerebral blood flow (CBF) and MR-susceptometry to measure whole-brain CMRO 2 . PMROx is non-invasive with imaging times around 5 min, making it feasible to image CMRO 2 under different conditions in one session. This study presents the first application of PMROx to humans with the aims of evaluating its reliability and sensitivity to increased CMRO 2 during functional activation (right-handed sequential finger tapping). In addition, blood-oxygen level dependent (BOLD) images were acquired to compare BOLD contrast to underlying changes in CBF and CMRO 2 . Across 14 participants, mean CMRO 2 was 3.2 ± 0.5 mLO 2 /100 g/min with excellent within-session repeatability. Significant increases in CBF, CMRO 2 and BOLD contrast were detected in the primary sensorimotor cortex, supplementary motor area and secondary somatosensory cortex. This study demonstrated the ability of PMROx to image CMRO 2 non-invasively, its sensitivity to increased regional CMRO 2 and how PET/MRI provides the opportunity to compare BOLD contrast to underlying changes in perfusion and oxygen metabolism.

  PublisherOA PDFDOI

• FUEL UTILIZATION DURING EXERCISE WITH EXOGENOUS KETONES VERSUS PLACEBO IN HEART FAILURE WITH PRESERVED EJECTION FRACTION: KETO-HFPEF

  Journal of the American College of Cardiology · 2025-03-29

  articleOpen access
  PublisherDOI

• Novel MRI Pulse Sequence to Image Upper Airway Anatomy and Measure Changes in Neurometabolism During Volitional Model Apneas

  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: While the neurometabolic consequences of obstructive sleep apnea (OSA) are thought to play a role in downstream risk for various disorders, quantifying these changes during natural sleep remains a scientific challenge. Goal(s): We aim to validate a custom MRI sequence for detecting neurometabolism and upper airway architecture during volitional apneas. Approach: During scanning, awake healthy volunteers were asked to perform breath holds and swallowing apneas. Results: Both breath-hold and swallowing model apneas increased CBF and SVO2 resulting in increased CMRO2, but only swallowing apneas were associated with an effective closure of the upper airway. Impact: Identifying specific changes in neurometabolism and upper-airway architecture with an experimental paradigm validates the proposed approach before applications in a more challenging naturalistic observation. Experiments in healthy subjects also helps contextualize the magnitude of changes noted in natural observations.

  PublisherDOI

• Quantification of bilateral renal metabolism in one minute with dual-band K-MOTIVE during free-breathing: a preliminary study

  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: Renal oxygen utilization is a potentially valuable biomarker of kidney function. However, quantification of individual kidney oxygen consumption can be challenging. Bilateral renal metabolic rate of oxygen (rblMRO2) has been previously reported by our group, though, under breath-held conditions. Goal(s): Evaluate feasibility of rblMRO2 quantification during free-breathing. Approach: A one-minute MRI pulse sequence was implemented during free-breathing to simultaneously measure two parameters (venous oxygen saturation and blood flow rate) at two locations (inferior vena cava, above and below the renal vasculature), yielding four total parameters. Measurements were also made under breath-held conditions. Results: Free-breathing, dual-band, and breath-held measurements of rblMRO2 were plausible. Impact: MRI-methods to evaluate renal metabolism may be limited by difficulty with identifying individual kidney's vasculature and breath-holds. Here, a free-breathing approach is implemented to quantify metabolism of both kidneys by imaging the (larger) inferior-vena-cava. These aspects may facilitate clinical translation.

  PublisherDOI

• Quantitative MRI Mapping of Upper Airway Anatomy and Cerebral Oxygen Metabolism with Concurrent EEG in OSA Patients During Sleep in Scanner

  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: Patients with obstructive sleep apnea (OSA) are at increased risk for various disorders, thought to be caused by apnea related disturbances in cerebral oxygen metabolism (CMRO2). Goal(s): To evaluate changes in CMRO2 and upper airway architecture during sleep and in response to apneas in a sample of OSA patients and healthy subjects. Approach: CMRO2 and upper airway architecture are evaluated during sleep using a custom MRI sequence, while sleep stage was evaluated by means of concurrently recorded EEG. Results: OSA-patients experienced disturbances in CMRO2 during sleep including a larger sleep-stage dependent decrease in CMRO2 over healthy controls. Impact: Seeing how the upper airway becomes obstructed during sleep may be valuable for surgical treatment planning. Further, identification of the neurometabolic consequences of OSA can enhance our basic understanding of neuro-and cardiovascular risk.

  PublisherDOI

• <scp>MRI</scp> ‐based quantification of whole‐organ renal metabolic rate of oxygen during free‐breathing

  Magnetic Resonance in Medicine · 2025-05-25 · 1 citations

  articleOpen access

  Abstract Purpose Renal metabolic rate of oxygen (rMRO 2 ) reflects the kidney's metabolic efficiency, making it a potential biomarker for early‐stage kidney disease. This study introduces an ungated, free‐breathing MRI sequence in comparison to its breath‐hold counterpart to noninvasively measure whole‐organ rMRO 2 . Methods Free‐breathing (FB) K‐MOTIVE sequence (kidney metabolism of oxygen via T 2 and interleaved velocity encoding) was developed to simultaneously measure renal blood flow rate (BFR) and T 2 of blood water using the conservation of mass. T 2 is converted to venous oxygen saturation (SvO 2 ) using a calibration curve. Compared to previous versions, FB K‐MOTIVE minimizes respiratory motion artifacts by acquiring fully sampled velocity maps with spiral readout instead of partially collecting radial views at each T 2 weighting. Healthy participants ( n = 15, 32 ± 9 years) were imaged at 3 T at the renal veins to quantify individual rMRO 2 , and at the suprarenal and infrarenal inferior vena cava to indirectly quantify bilateral rMRO 2 (the total metabolism from both kidneys). Results Renal venous blood was highly oxygenated (SvO 2 91% ± 3%) and exhibited high BFR of 460 ± 90 mL/min per kidney. Further, total rMRO 2 of the two kidneys (160 ± 80 (μmol O 2 /min)/100 g) was statistically comparable to the indirect bilateral rMRO 2 (250 ± 120 (μmol O 2 /min)/100 g, p = 0.066). Using Lin's concordance correlation coefficient, there was good agreement between breath‐hold and free‐breathing acquisitions at the individual kidneys for SvO 2 (&gt;0.75), BFR (&gt;0.96), and rMRO 2 (&gt;0.75). Conclusion FB K‐MOTIVE is a feasible approach to estimate rMRO 2 , yielding reproducible and physiologically plausible metabolic parameters. Free‐breathing acquisition can enhance patient comfort by eliminating the need for breath‐holding.

  PublisherOA PDFDOI

• Comparison of Brain Oxygen Metabolic Parameters Between Constrained qBOLD and Whole‐Brain Oximetric Methods at Baseline and in Response to a Physiologic Stimulus

  NMR in Biomedicine · 2025-08-11 · 3 citations

  articleOpen access

  ABSTRACT The measurement of cerebral oxygen metabolism is important to understand and treat many disorders. Constrained quantitative BOLD (qBOLD) MRI is a calibration‐free method for 3D voxel‐wise whole‐brain mapping of brain oxygen metabolism. This study aimed to evaluate the agreement between constrained qBOLD and global oximetry methods both at baseline and in response to a caffeine stimulus. Healthy volunteers ( N = 10, age 30 ± 8 years) were imaged with constrained qBOLD, MOTIVE (metabolism of oxygen via T 2 and interleaved velocity encoding), dual‐slice (DS), and single‐slice (SS) OxFlow. Subjects were then given a 200 mg caffeine pill and imaged at 2‐s temporal resolution immediately thereafter for 30 min by SS‐OxFlow. After 30 min, the baseline protocol was repeated. Constrained qBOLD uses prior constraints to the QSM + qBOLD model to solve for voxel‐wise oxygen extraction fraction (OEF). Quantification of cerebral blood flow (CBF) was accomplished for qBOLD from a separate measurement via pseudo‐continuous arterial spin labeling (pCASL) to yield CMRO 2 . Constrained qBOLD measured OEF (31 ± 5% gray matter [GM], 31 ± 6% white matter [WM] at baseline; 36 ± 7 GM, 35 ± 8 WM post‐caffeine) was in good agreement with global oximetry methods DS‐OxFlow (30 ± 4, 37 ± 5), SS‐OxFlow (31 ± 4, 37 ± 4), and MOTIVE (32 ± 5, 39 ± 5). Temporal data showed a gradual increase in OEF with a commensurate reduction in CBF while the caffeine was taking effect. No significant change in CMRO 2 was noted with any of the techniques. Regional analysis of the basal ganglia, hippocampus, and thalamus found there was a significant increase in OEF post caffeine. The results indicate constrained qBOLD to yield OEF with negligible bias to global oximetry methods, both at baseline and post caffeine. The results also suggest that constrained qBOLD has the sensitivity to detect changes in oxygen metabolism due to a vasoconstrictive stimulus.

  PublisherOA PDFDOI

• Comparing Activation-Induced Changes in Cerebral Oxygen Metabolism Measured by Calibrated fMRI and [15O]O2-PET

  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: Evaluate the accuracy of calibrated functional MRI (c-fMRI) for measuring relative changes in CMRO2. Goal(s): Compare activation-induced increases in CMRO2 measured by c-fMRI to measurements from [15O]O2-PET. Approach: Data acquired on a PET/MRI scanner while participants performed finger tapping. Calibrated fMRI protocol involved hypercapnia. [15O]O2-PET images acquired at rest and during tapping. Results: Good agreement in the average CMRO2 increase in the sensorimotor cortex between the two methods, although the variability for c-fMRI was considerably greater. Impact: This study is the first direct comparison of c-fMRI to [15O]O2-PET and demonstrated the accuracy of the MRI method.

  PublisherDOI

• Renal Metabolic Rate of Oxygen in Response to Hypoxia Challenges by Means of Quantitative MRI in Humans

  NMR in Biomedicine · 2025-11-14

  articleOpen access

  ABSTRACT In early kidney disease, tissue hypoxia occurs due to an imbalance between ATP supply and demand. Whole‐organ renal metabolic rate of oxygen (rMRO 2 ) is therefore a potential biomarker for assessing renal function. This study evaluated the sensitivity of a quantitative MRI method to detect within‐subject changes in metabolic parameters during hypoxic gas challenges. Ten healthy adults were imaged at 3 T (5 female, ages 23–53 years) while undergoing mild and moderate hypoxia (P ET O 2 62 and 52 mmHg, respectively). The utilized MRI sequence simultaneously quantified blood flow rate (BFR) and venous oxygen saturation (SvO 2 ) at the left renal vein, yielding, together with arterial oxygen saturation (SaO 2 ) obtained by pulse oximetry, whole‐organ rMRO 2 by invoking Fick's Principle. Repeated‐measures ANOVA was used to test differences in metabolic parameters between baseline and hypoxic conditions. SaO 2 at baseline was 99% ± 1%, while renal SvO 2 was 92% ± 3%. During progressive hypoxemia, the drop in SvO 2 (mild 83% ± 4%, moderate 76% ± 5%, p &lt; 0.01) paralleled the drop in SaO 2 (mild 90% ± 1%, moderate 84% ± 2%), such that the arteriovenous difference in oxygenation (AVDO 2 ) was constant when compared to baseline ( p = 1). Renal BFR did not vary significantly between baseline (410 ± 65 mL/min) and hypoxemic conditions (mild, moderate of 430 ± 56 and 440 ± 48 mL/min, p &gt; 0.34). Thus, rMRO 2 did not significantly change during hypoxemia (baseline, mild, and moderate of 140 ± 50, 180 ± 80, and 170 ± 90 (μmol O 2 /min)/100 g, respectively, p = 1). In conclusion, the results demonstrate the method's sensitivity in detecting within‐subject changes in metabolic parameters in response to graded hypoxia. Quantitative MRI oximetry may be a feasible tool to assess and longitudinally monitor early metabolic changes in kidney disease.

  PublisherOA PDFDOI

• Crossover Trial of Exogenous Ketones on Cardiometabolic Endpoints in Heart Failure With Preserved Ejection Fraction

  JACC Heart Failure · 2025-03-31 · 6 citations

  articleOpen access

  BACKGROUND: The etiology of exercise intolerance in heart failure with preserved ejection fraction (HFpEF) is multifactorial. Several contributing pathways may be improved by ketone ester (KE). OBJECTIVES: This study aims to determine whether KE improves exercise tolerance in HFpEF. METHODS: ) during incremental cardiopulmonary exercise testing and time to exhaustion during an additional constant-intensity exercise (75% peak workload) bout. RESULTS: -glucose infusions during constant-intensity exercise, plasma glucose appearance rate before and during exercise was lower with KE (-0.24 mg/kg/min; P < 0.001). During both exercise protocols, KE lowered: 1) respiratory exchange ratios, demonstrating decreased systemic carbohydrate use; 2) nonesterified fatty acids and glucose; and 3) estimated left ventricular filling pressures (E/e'). CONCLUSIONS: or constant-intensity exercise in HFpEF. (Ketogenic Exogenous Therapies in HFpEF [KETO-HFpEF]; NCT04633460).

  PublisherDOI

Recent grants

• NIH Grant K25HL111422

  NIH · $702k · 2018

Frequent coauthors

• Félix W. Wehrli

  70 shared

• Erin K. Englund

  27 shared

• Thomas F. Floyd

  The University of Texas Southwestern Medical Center

  18 shared

• Zachary B. Rodgers

  University of Pennsylvania

  16 shared

• Emile R. Mohler

  15 shared

• Jeremy F. Magland

  Flatiron Institute

  14 shared

• Alessandra Caporale

  14 shared

• Hyunyeol Lee

  11 shared