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Felix Werner Wehrli

Felix Werner Wehrli

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University of Pennsylvania · Rehabilitation Medicine

Active 1953–2026

h-index76
Citations16.9k
Papers48670 last 5y
Funding$77.8M4 active
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About

Felix Werner Wehrli, PhD, is a Professor of Radiologic Science in Radiology at the University of Pennsylvania Perelman School of Medicine. He serves as the Director of the Laboratory for Structural, Physiologic and Functional Imaging at the University of Pennsylvania Medical Center and is a member of the Research Executive Committee in the Department of Radiology. His educational background includes an MS in Chemistry and a PhD in Chemistry from the Swiss Federal Institute of Technology, obtained in 1967 and 1970 respectively. His research focuses on quantitatively characterizing tissue properties and their relationship to physiology and function through spatially resolved magnetic resonance in humans. Current projects involve developing novel image-based quantitative methods for studying tissue oxygen metabolism with enhanced temporal and spatial resolution, and applying these methods to investigate degenerative and acquired vascular diseases of the brain and other organs. Wehrli's work also includes developing technology for evaluating preclinical vascular disease, quantifying markers of endothelial dysfunction, and studying the effects of lifestyle factors such as e-cigarette aerosol inhalation. Additionally, his research encompasses the development of techniques for studying bone matrix and mineral properties, constructing cranial models for surgical applications, and assessing metabolic and degenerative skeletal disorders through image-based computational biomechanics, with the goal of creating orthopedic applications like patient-specific hip fracture prediction.

Research topics

  • Environmental health
  • Medicine
  • Psychology
  • Anesthesia

Selected publications

  • Age dependence of brain oxygen metabolism in adults assessed by 3D constrained quantitative BOLD MRI

    NeuroImage · 2026-04-30

    articleOpen accessSenior author

    differed between older vs younger subjects only in the amygdala (126.6 ± 35.9 vs 97.5 ± 31.6 μmol/min/100 g, P = 0.01). Exploring regional heterogeneity, MTL and its substructures exhibited reduced OEF relative to whole-brain averages in both groups. Overall findings indicate that cerebral oxygen metabolism remains largely preserved throughout adulthood. The combined qBOLD-ASL technique offers a robust framework for detecting regional variations in brain oxygen metabolism, characterizing both normative cerebrovascular aging and possibly early stages of neurodegeneration.

  • 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.

  • Simultaneous solid and multiple-contrast soft tissue musculoskeletal magnetic resonance imaging

    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: MRI and CT are widely used for clinical assessment of musculoskeletal pathology. These modalities provide complementary information, but the scheduling of separate scans creates a logistically cumbersome scenario. Goal(s): To demonstrate the capabilities of a specialized pulse sequence that yields bone-selective and soft-tissue contrasts (T1-weighted and T2-weighted) in a single scan. Approach: DREAMER is a dual-echo UTE sequence combined with a phase-based encoding strategy to simultaneously obtain bone-selective, T1-weighted, and T2-weighted images. Imaging was performed at the knee, calf, and foot in healthy volunteers. Results: DREAMER enables a rapid and radiation-free method to assess bony anatomy and surrounding soft tissue for musculoskeletal applications. Impact: DREAMER performs simultaneous imaging of musculoskeletal solid and soft tissues, potentially obviating the need for additional CT. It can reduce the use of ionizing radiation in clinical imaging and remove logistical complexities related to scheduling examinations.

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

    NMR in Biomedicine · 2025-11-14

    articleOpen accessSenior authorCorresponding

    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 < 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 > 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.

  • <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 accessSenior authorCorresponding

    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.

  • <scp>DREAMER</scp> : Rapid and Simultaneous Multiple Contrast Magnetic Resonance Imaging of Solid and Soft Tissue

    Magnetic Resonance in Medicine · 2025-10-29 · 1 citations

    articleOpen access

    ABSTRACT Purpose Pediatric craniofacial imaging may involve examination of both the skull and brain tissues via CT and MRI, respectively. DREAMER (Dual Repetition and Echo Acquisition with Multi‐contrast Encoding and Reconstruction) simultaneously acquires solid‐ and soft‐tissue images, potentially providing a rapid, high‐resolution, and radiation‐free protocol whenever bone‐selective, T 1 w, and T 2 w images are required. Methods The DREAMER sequence combines a solid‐state MRI method with phase‐based T 2 encoding to produce a multi‐contrast signal model that enables retrospective customization of image contrast weighting. DREAMER is paired with an iterative image reconstruction algorithm for accelerated and high‐resolution structural imaging of solid‐ and soft‐tissue compartments. Two healthy adult volunteers and two pediatric patients were scanned at 3 T to qualitatively compare soft‐tissue DREAMER image contrasts with their corresponding clinical standards, T 1 w MPRAGE and T 2 w fast spin‐echo (FSE). Two patients also underwent clinical CT to compare the bone‐selective images and skull renderings. Results DREAMER images are self‐registered, high‐resolution, and spatially isotropic. The bone‐selective, T 1 w, and T 2 w images approximate the image contrasts and structural imaging capabilities of their corresponding clinical standards (CT, T 1 w MPRAGE, and T 2 w FSE). Unlike the standard techniques, DREAMER imaging occurs at a single scanner using a single pulse sequence. Conclusion DREAMER combines mechanisms for solid‐ and multiple‐contrast soft‐tissue imaging into a single scan. For craniofacial imaging, DREAMER may consolidate CT and MRI demand, reduce exposure to ionizing radiation, decrease patient examination and wait times, and simplify the radiological workflow.

  • DREAMER: Rapid, high-resolution, and simultaneous multiple-contrast magnetic resonance imaging of solid and soft tissues

    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: Certain clinical cases may warrant both CT and MRI. The two modalities may provide complementary information, but separate scans create a multifaceted and economic burden for the patient and imaging center. Goal(s): To develop a single scan with desirable properties from CT (bone-selective, rapid, and high-resolution) and MRI (multiple soft-tissue contrasts, no ionizing radiation). Approach: DREAMER, a dual-echo UTE sequence combined with a phase-based T2 encoding method, simultaneously encodes bone-selective, T1w, and T2w images in a single acquisition. Results: The sequence is a rapid, high-resolution, and radiation-free method to perform concurrent solid and soft tissue 3D imaging. Impact: DREAMER jointly images solid and soft tissues. The sequence may enable consolidation of CT and MRI demand at imaging centers, thereby decreasing patient examination and wait times, reducing exposure to ionizing radiation, and simplifying the clinical workflow.

  • Rapid whole-brain venous cerebral blood volume mapping using velocity-selective venous-spin-labeling with 3D GRASE

    NeuroImage · 2025-11-27

    articleOpen access

    across the whole brain.

  • Self-Correction of B0 Field Drift and k-space Trajectory Errors in Alternating Unbalanced SSFP for Robust R2 and R2’ Mapping

    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: Accurate estimation of R2 and R2' provides insights into physiologic and functional states of tissues. Goal(s): To investigate the feasibility of self-correction of B0 field drift and radial trajectory errors in the nonbalanced SSFP-based R2 and R2' mapping technique. Approach: The inherent phase characteristics of the alternating nonbalanced SSFP are utilized, enabling self-correction of B0 field drift and k-space trajectory errors. Results: In both phantom and brain scans, accuracy of parametric maps were enhanced with the self-correction of the two types of image artifacts. Impact: The proposed method, which mitigates artifacts from B0 drift and trajectory mismatch in a self-correction manner, may prove to be a useful means in a wide range of neuroimaging studies seeking rapid and accurate quantifications of R2 and R2'.

  • 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

    articleSenior author

    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.

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  • Laboratory for Structural, Physiologic and Functional ImagingPI

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