Penn Cardiovascular Institute

Mohler Lab

Contact the Lab

Emile R. Mohler III, MD

Emile R. Mohler III, MD
Principal Investigator

Emile R. Mohler III, MD
11-103 Smillow Center for Translational Research
3400 Civic Center Boulevard, Bldg. 421
Philadelphia, PA 19104-5159
215-573-6606
Fax: 215-746-7415
mohlere@uphs.upenn.edu

Overview

A component of the Vascular Medicine Research Program within the Cardiovascular Division and the Department of Medicine, the Mohler Lab investigates new diagnostic and therapeutic modalities for patients with vascular disease. The primary concentrations of the Mohler Lab include:

  • Peripheral artery disease (PAD) — Improving diagnostic imaging and treatment of PAD, particularly the development of a novel therapy for claudication;
  • Vascular Health Profile (VHP) — A powerful novel technique that provides a comprehensive assessment of vascular health;
  • Vascular Imaging — Near infrared optical technology for imaging of skeletal muscle oxygenation and blood flow in the legs of patients with PAD;
  • The genetic origins of varicose veins.

Research Projects at the Mohler Lab

Peripheral Artery Disease (PAD)

Previous clinical studies for treatment of claudication have included small molecule drugs, gene therapy to deliver proangiogenic compounds and cell therapy. The Mohler Lab is currently performing an IRB-approved study to evaluate how exercise improves the symptoms of claudication.

The Microcirculation in Claudication and Exercise Rehabilitation

Objectives:

  1. To determine in a group of patients with moderate PAD, the relationship between claudication limited exercise tolerance (Peak Walking Time-PWT) and microvascular blood flow.
  2. To determine if changes in PWT with exercise rehabilitation correlate with changes in microvascular blood flow.
  3. To determine if the vascular health profile, as measured with circulating Endothelial Progenitor Cells (EPCs) and endothelially-derived microparticles (MPs), biomarkers of endothelial health, improves following exercise rehabilitation and correlate with microvascular blood flow.

Design & Methods:

Subjects with moderate PAD will undergo measurement of treadmill PWT. Continuous Arterial Spin Labeling-Perfusion MRI will be used to measure skeletal muscle calf microvascular blood flow and flow cytometry will be used to characterize the endothelial vascular health profile described above. We anticipate that a supervised exercise rehabilitation program will improve PWT, microvascular blood flow, and the endothelial vascular health profile.

Public Health Relevance:

Peripheral arterial disease is a highly prevalent condition in the United States, affecting approximately 8-12 million Americans. Early disability derives from claudication or ischemic muscle pain, inhibiting ambulation. The pathophysiology of this disorder is thought to be of macrovascular origin, however the contribution of the microvasculature to this disorder is not well understood and may be important. Improved knowledge of the contribution of the microvasculature to this disorder, and improvement in our ability to monitor, via relatively noninvasive imaging and circulating cellular biomarker assays, the impact of rehabilitation or other therapeutic interventions, may assist in the treatment of this disorder.

Vascular Health Profile

Patients who appear to be similar in their vascular disease risk often demonstrate substantially different morbidity, mortality, and responses to therapy because of their differing clinical characteristics.

The Vascular Health Profile (VHP) is a powerful novel technique that provides a comprehensive assessment of vascular health. The VHP is a multicomponent clinical assay that integrates a number of cellular biomarkers of genetic and environmental risk factors, including vascular microparticles (MPs) and endothelial progenitor cells (EPCs) into a cost-effective clinically significant profile using unique computational methods. The VHP uses the power of cytomics (the study of cell systems in the body) to capture the biocomplexity of vascular disease and to deliver a simple, yet comprehensive measure of cardiovascular health. There are ongoing clinical studies evaluating the VHP is certain diseases that predispose to heart attack and stroke such as diabetes mellitus and psoriasis.

Vascular Imaging

Patients with PAD have abnormal skeletal muscle oxygenation and blood flow and the legs. The information obtained from this optical device could potentially assist with diagnosis, prognosis and optimize treatment for patients with PAD.

The Mohler laboratory is investigating diffuse optical imaging (DOI) using near infrared optical technology to noninvasively measure skeletal muscle oxygenation and blood flow in the legs of patients with PAD. DOI employs photons in the near-infrared range that diffuse through tissue and can be detected millimeters to centimeters away from the source. Diffuse optical techniques provide direct assessment of oxygenation and perfusion processes at the microvasculature level and have the advantage of portability and high temporal resolution, as well as the capacity to probe deep tissues.

Diffuse optical spectroscopy (DOS)

DOS involves the interaction of light with the main chromophores in the tissue — oxy-hemoglobin (HbO2) and deoxy-hemoglobin (Hb) — to provide dynamic information about HbO2 and Hb concentrations, total hemoglobin concentration (THC), and tissue blood oxygen saturation (StO2) in deep tissues.

Diffuse Correlation Spectroscopy (DCS)

DCS is an emerging diffuse optical technique for continuous noninvasive measurement of blood flow in deep tissues. DCS quantifies the temporal fluctuations of detected light with high temporal (~100 ms) and limited spatial (mm to cm) resolutions in tissue. These fluctuations are sensitive to the motions of scatterers in tissue, such as red blood cells. Therefore, the DCS signal provides a direct measure of blood flow, and can be used to derive a parameter typically known as blood flow index.

Varicose Veins

A clinical study is ongoing evaluating the genetic cause of varicose veins. The DNA of families with varicose veins is being study to determine the genes that influence the development of varicose veins.

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Members

  • Emile R. Mohler III, MD, Director
  • Emil deGoma, MD
  • Victor Ferrari, MD
  • Jay Giri, MD
  • Michael Parmacek, MD
  • Muredach Reilly, MB
  • Robert L. Wilensky, MD

Selected Publications

Selected publications from the Mohler Lab at Penn Cardiovascular Institute in Philadelphia, Pennsylvania.

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