DUKE UNIVERSITY
SCHOOL OF MEDICINE
DUKEHEALTH.ORG
| Projects & Publications |
| Projects | Publications |
Research Projects and Publications
New Grant -Acoustic Radiation Force Imaging of Carotid Plaque Morphology and Composition NHLBI-2RO1HL075485
In conjunction with the Duke Biomedical Engineers -Drs Gregg Trahey (PI) and Jeremy Dahl and vascular surgery Drs Lawson and Sileshi we are developing and testing Acoustic Radiation Force Impulse (ARFI) imaging for detection of vulnerable carotid artery plaques.
ARFI imaging is a new ultrasonic imaging method that uses short duration (.03-1 ms) acoustic radiation force to generate localized displacements in tissue. These displacements are tracked using conventional ultrasound and correlation-based speckle-tracking methods. Tissue displacement is inversely related to tissue stiffness, and the recovery of tissue to its original position is related to its viscoelastic properties. Because arterial walls, soft tissue, atheromas, and calcifications have a wide range in stiffness, they represent excellent candidates for ARFI imaging. Furthermore, because a single transducer on a diagnostic scanner is used to both generate the radiation force and track the resulting displacements, and there are thousands of installed ultrasonic scanners in vascular laboratories that could be programmed to include ARFI, this modality could quickly and inexpensively be added to current vascular diagnostic methods. The aim of this grant is to further develop the tecnology of ARFI and to evaluate the potential of ARFI imaging for the generation of high-resolution images of carotid plaque composition and detecting vulnerable plaques.
Above is a longitudinal view of a stiff, possibly fibrous, plaque in the common carotid artery of a 49 year-old male. The B-mode image indicates a plaque on the far wall of the common carotid artery. The plaque appears to wrap around a significant portion of the artery (for cross-section scans-not shown here), and is therefore visible on the near wall of the common carotid artery. The plaque to be homogeneously stiff throughout.
In contrast below is an example of an apparently heterogeneous plaque containing a soft region surrounded by a stiff cap in the carotid bifurcation of a 55 year old female volunteer. The plaque is located near the bifurcation of the carotid artery and is visible on both the proximal and distal walls. The soft region of the plaque is visible on the distal wall as the oval shaped region extending from 23 to 25mm depth and -2 to 4mm laterally in the ARFI image.
The soft region is surrounded by a significantly stiffer region. The displacement of the soft region ranges from 2.5-4 µm, compared to 0.5-1 µm in the surrounding stiffer tissue. The surrounding tissue is approximately 1.3mm thick between the soft region and the vessel lumen, except on the left side, where the thickness of the cap decreases to approximately 0.7mm. At 0.7mm, the stiff cap may be considered to be at the upper limit of the range indicating vulnerability (Ge et al., 1999). Geet al. (1999) also noted that a lipid core with area greater than 1mm2 or a core to plaque ratio greater than 20% also correlated well with rupture. The soft region in this plaque meets Ge’s definition of a vulnerable plaque, assuming that this region is a lipid core.
We are also working towards development of 3-D modeling of carotid arteries and plaques to enable us to match accurately with histology samples.
New Challenge Grant - Mechanisms and functional Outcomes of Exercise Progression Models in the Elderly-5RC1AG035822-02 (10/01/09-09/30/11)
By 2030, the number of Americans 65 years or older will account for roughly 20% of the
US
population, with a projected increase in the Nation’s health care spending of 25%. A major factor in the projected increase in health care costs is the consequences of a progressive decline in functional capacity with advancing age. The decline in functional capacity can be slowed with the help of exercise training as recommended by the
American
College
of Sports Medicine (ACSM) and American Heart Association (AHA). Unfortunately, improvements in functional capacity, in the elderly are rather small, in part, because many elderly cannot tolerate sufficiently high intensity exercise due to orthopedic and cardiovascular limitations. Thus, despite some success, existing training strategies, for the elderly, appear less than optimal.
Therefore, the challenge for our rapidly aging nation is to define interventions, for the elderly that can slow the decline in functional capacity and performance, prevent early onset of physical disability and loss of independence. The potential impact is a reduction in the probability of disease, disability, early mortality, and health care expenditures.
We hypothesize that regionally specific exercise stimuli, applied at the beginning of a training program, will serve as a physiological primer capable of removing peripheral barriers that limit functional capacity, in elderly at risk of losing independence. Removal of peripheral barriers early in a training program will unlock a greater potential for change in functional capacity.
Subsequently, the objectives of this proposal are twofold: (1) To determine differences between 4 weeks of a regionally specific exercise stimulus or standard aerobic exercise training on physical and functional performance; and (2) To determine the effects of subsequent 8 weeks of progressive whole-body training protocol on the magnitude of change in physical and functional performance. Of particular importance to these objectives is the combination of physiological information from biospecimens (vascular and muscular) with functional outcomes in the elderly, following two different types of exercise training progression models.
Other projects we are involved in...
1-08-CR-03 PI:- Brian Annex, MD. 01/01/08-12/31/09
American Diabetes Association Clinical Research Award.
Diabetes Mellitus and PAD: Mechanisms of Exercise Training. Specific Aim 1. Establish the changes in skeletal muscle measures (vascular density, oxidative metabolism/mitochondrial content and contractile protein composition) and vascular reactivity, with objective clinical outcomes (maximal and initial pain-free walking times on treadmill testing, and peak VO2) after 3-weeks and 12-weeks of supervised exercise training.
W81XWH-06 PI:- Lee Jones, Ph.D. 04/1/06–03/31/09
US Department of Defense
The Effects of Exercise Training on Tumor Vascularity and Response to Neoadjuvant Therapy in Operable Breast Cancer: A Phase I-II Study
The primary aim of phase I of this study is to establish whether combining endurance exercise training with chemotherapy leads to unacceptable exercise adherence rates or unusually high DLTs. In absence of these effects, the specific aims of phase II will be to explore the effects of combining endurance exercise training with chemotherapy versus chemotherapy alone in 23 patients with locally advanced breast cancer on (i) tumor physiology (blood flow, MVD), (ii) systemic response (circulating VEGF and EPCs, endothelial function and exercise capacity) and (iii) tumor response (pathologic and clinical response)
GlaxoSmithKline Inc. PI:- Lynda Szcech, MD. 11/01/06-10/31/08
Endothelial Cell Dysfunction as the Mediator of Increased Morbidity and Mortality among HIV infected Patients with Proteinuria
The aims of this proposal are to test the hypothesis that proteinuria is associated with abnormal markers of endothelial cell function among HIV-infected patients. These observations will provide information describing and supporting the potential for endothelial cell dysfunction as the link between proteinuria and poorer outcomes in this population. The conclusions from this proposal will be subsequently used as a foundation to design further interventions aimed at affecting these intermediate outcomes.
AHA Grant-in-Aid PI:- Pao-Hwa Lin, PhD. 06/01/07–05/31/10
Mechanism(s) of the blood pressure lowering effects of the Dietary Approaches to Stop Hypertension (DASH) dietary pattern: DASH mechanism study.
The BP-lowering effect of the DASH dietary pattern was maximal after two weeks of controlled feeding, and was comparable in magnitude to antihypertensive medication among participants with stage 1 hypertension. Thus efforts to determine the BP-lowering mechanisms of DASH should involve evaluation of hypertensive patients during the first two weeks of exposure to this dietary pattern.
PI:- Jula K Inrig, MD 09/01/07-02/01/09
Effect of Hectoral on Endothelial Cell Dysfunction in ESRD
This study is a prospective observational study describing the effect of hectoral on endothelial cell function in dialysis patients
American Heart Association PI:-Hardean E. Achneck MD. 07/08/08-06/31/10
Postdoctoral Fellowship
Cell seeding Endothelial Progenitor Cells onto Ventricular Assist Device Surface
DHTS WEB SERVICES