LSNI » Members » Felix W. Wehrli

Felix Werlhi

Felix Werner Wehrli, Ph.D.

Professor of Radiologic Science

Director of the Laboratory for Structural NMR Imaging

Department of Radiology
University of Pennsylvania Health System
1 Founders Building
3400 Spruce Street
Philadelphia, PA 19104
Phone: (215) 662-7951
Fax: (215) 662-7263
wehrli@mail.med.upenn.edu

GRADUATE GROUP AFFILIATIONS

Biochemistry and Molecular Biophysics

LINKS

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Department of Radiology

EDUCATION

M.S. (Chemistry)
Swiss Federal Institute of Technology, 1967.
Ph.D. (Chemistry)
Swiss Federal Institute of Technology, 1970.

 

Dr. Wehrli’s research centers on the conception, implementation and translation to the clinic, of new quantitative imaging approaches using predominantly MRI principles. All research conducted in the laboratory is supported by grants from the National Institute of Health, the Department of Defense, or the Institute of Translational Medicine and Therapeutics.

Study of Brain Metabolism:

New methods being developed for the study of brain metabolism via MRI susceptometry providing venous oxygen saturation (SvO2) which together with total blood flow to the brain yield CMRO2, the total cerebral metabolic rate of oxygen consumption, in physiologic units. The techniques are being applied to the study of neurovascular reactivity in various cohorts of patients including subjects with obstructive sleep apnea, hemoglobinopathies (e.g. sickle cell disease) and newborns with congenital heart disease in response to stimuli. Advances in this technology now allow measurements of these functional parameters at a temporal resolution of 2-3 seconds.

 

effect of hypercapnia

Effect of hypercapnia (5% CO2 in room air) on brain blood flow (a) and SvO2 (b) measured in the internal carotid and vertebral arteries and superior sagittal sinus, showing increased flow commensurate with increased SvO2 as expected for a isometabolic stimulus (Jain, et al, JCBFM 2011)

Assessment of Endothelial Dysfunction and Muscle Perfusion:

In a project to evaluate of endothelial dysfunction in high-risk patients (including smokers) or patients with peripheral arterial disease (PAD) vascular reactivity is assessed by using hemoglobin oxygen saturation (HbO2) as an endogenous dynamic tracer following induced limb ischemia. In a protocol involving simultaneous measurement of limb perfusion and dynamic oximetry the technology is being applied to PAD patients undergoing exercise rehabilitation.

time course movie

Dynamic oximetry for the evaluation of vascular reactivity showing the temporal changes in oxygen saturation in the femoral vein following reperfusion after induced limb ischemia (top), plotted below.

Quantification of Arterial and Microvascular Compliance:

New MRI methods for measurement of pulse-wave velocity provide insight into age- and disease-related increases in arterial stiffness. Rapid projection-based approaches yield measurement of flow velocity at multiple sites along the arterial tree yielding, from the delays in arrival of systolic flow wave, the pulse-wave velocity. Measurements at multiple sites provide new insight into the location-specific changes during aging and atherogenesis. Another approach provides a measure of brain compliance based on the temporal mismatch between arterial inflow and venous drainage, a method that is currently being applied to evaluation of patients with neurodegenerative disorders.

projection-based measurement

Projection-based measurement of pulse-wave velocity from temporal shift in the arrival of the systolic velocity wave at the downstream location (Langham et al, JCVMR 2012)

Image-based Assessment Myelin Density:

Myelin is critical to efficient neuronal current transport and loss of myelin is at the core of many neural disorders. A new method conceived in the laboratory aims to directly detect and quantify the signal from the immobilized lipids of the myelin membrane. The approach is based on zero-TE radial acquisition strategies in conjunction with tissue water suppression. Initial results in reconstituted myelin and rodent spinal cord demonstrate feasibility of the approach.


Study of Bone Architecture and Mechanics:

A core activity of the lab is on development and translation of image-based assessment of trabecular and cortical bone structure, changes of which during aging and hormone depletion have been implicated as key determinants in osteoporotic fracture risk. Methods developed and being refined focus on high-resolution 3D image acquisition and processing as a means to establish accurate models of the bone’s architecture. These, in turn, then serve as input into a finite-element (FE) solver yielding mechanical constants such as stiffness and failure load. Recent algorithmic developments in the lab now allow large-scale simulations with tens of millions of finite elements in both linear and nonlinear regimes. The methodology is currently applied to two large studies aimed at evaluating bone strength in patients at risk of fracture and in a trial of early postmenopausal women undergoing experimental intervention with low-magnitude mechanical stimulation.

 

strain energy map

Strain energy map computed via FE analysis based on high-resolution CT images (80µm isotropic voxel) of cadaveric femur simulating stance loading. Model comprised 90 million elements and total computation time was 4 hours on a dual-quad core Xeon 3.16 GHz with 40 GB of RAM and custom-designed FE solver. (Zhang et al, ORS 2012)

Cortical Bone Nanostructure and Chemistry:

At the core of this project is the study of cortical bone, which plays a pivotal role as a transport and signaling medium as well as for load transfer. This project involves the development of radial imaging strategies with T2-selective soft-tissue suppression pulses as a means to separate the functionally and structurally different pore and collagen-associated water fractions. In recent work the two fractions have been uniquely identified on the basis of deuterium NMR. Other elements of the project focus on the development of solid-state scanning techniques for quantifying mineral phosphorus with goal of creating an integrated examination that would distinguish osteomalacia from osteoporosis.