FMD - OMICS Publishing Group

FMD - OMICS Publishing Group

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The Hong Kong Polytechnic University My research profile 1. Imaging Atherosclerosis 2. Identification of new imaging pr obes 3. Radiation Protection 4. Upper limb functional imaging r elated to daily activities Coutesy: D.J. Maizels/Gyldendal Akademisk, 2011 Clinical detection of plaque and stenos Lindsay and Choudhury, Nature Rev Drug: Disc 7: 517 2008 Pre-clinical and sub-clinical detection of atheroscleros

is Impaired Endothelial cells encourage the secretion of various molecules A glycoprotein involved in haemostasis Markers of Inflammations Upregulated adhesion molecules and selectin Von willebrand factor (Mannucci PM et al, 1998) C-reactive protein Cytokines

Intracellular adhesion molecule-1 (ICAM-1) Vascular cell adhesion molecule-1 (VCAM-1) E- or P- Selectin Vascular endothelium In response to various insults (oxidative stress) promote endothelial dysfunction Vasomotor tone Thrombosis Haemostasi s

Initiate step in atherosclerosis coronary arteries peripheral conduit arteries ED found important advanced atherosclerosis subjects asymptomatic subjects Forearm blood flow (Strain-gauge plethysmography)

1990: Panza and co-workers Resistance vessel reactivity in resp onse to pharmacological or physiol ogical stimuli FBF is measured by temporarily oc cluding the venous return (by a cu ff inflated to 40 mmHg) and measu red the slight swelling of the distal portion of the limb due to pharmac ological or physiological stimuli Forearm blood flow (Strain-gauge plethysmography) Benefits good sensitivity and specificity

reproducible and less observer dependent Drawback relatively invasive cannot examine large vessel physiology which is more relevant to vascular disease Flow Mediated Dilation Brachial flowmediated dilation(FM D) Impaired FMD :

1989: Anderson and coworkers a validated non-invasive measure of endothelial function Surrogate Marker for CHD measurement of changes up to 0.1mm in arterial diameter subjects with overt vascular disease subjects with cardiovascular risk factors even in asymptomatic subjects diabetic patients The Setup

Fatty streaks Intimal thickening Reactive Hyperemia From Clifford et al. FASEB J. 24: 804.12, 2010. The Examination Placement of Cuff at forearm Locate the brachial artery by color flow and pulsed Doppler Inflate and then deflate the cuff Hyperemic flow generated

Monitor the lumen diameter continuously Offline measurement with computer Factors influence the resultant vessel dilatation Shear Stress Courtesy: Tousoulis Heart2005; 2005;91:353-358 Tousoulis,D,etet al.,al,Heart 91: 353-358. Factors induce vascular dilatation impairment Dysfunction in NO production in the endothelial cells (e.g. deficiency of NOS co-factor)

Over production of endogenous inhibitors of NOS Reduced NO bioavailability VSMC insensitivity to NO Dysfunction of VSMC FMD was proposed as a new tests for evaluating endothelial function Costeffective, reproducible and standardizati on

Ability to predict risk and relationship to established tests of risk. Can identify individual patients predict a reduction in the risk of clinical events. Useful as a

screen for drug development . Research / clinical Appli cation FMD was proposed as a new tests for evaluating endothelial function (surrogate marker) Costeffective, reproducible and standardizati on Ability to

predict risk and relationship to established tests of risk. Can identify individual patients predict a reduction in the risk of clinical events. Useful as a screen for drug

development . In Chinese subjects with type 2 diabetes, hyperglycaemia, hype rtriglyceridemia, smoking and albuminuria were independent p redictors for endothelial dysfunction Type 2 diabetic subjects with overt nephropathy had impaired e ndothelium-dependent and endothelium-independent dilatatio n, suggesting vascular dysfunction beyond the endothelium. In agreement with studies from Caucasians, smoking was the most important determinant for vascular dysfunction in Chines e type 2 diabetic patients with overt nephropathy. Furthermore, FMD was predictive of new onset of cardiovascul

ar events and related death in Chinese type 2 diabetic patients with overt nephropathy. My study Recruitment Invite those relatives of diabetes patients whom follow up at the diabetic mellitus and endocrine clinic at the Prince of Wales Hospital at least 40 years old (middle-aged Chinese) No previous diagnosis for diabetes No previous diagnosis for any cardiovascular disease Not taking any kind of long-term medications except hypertensive drugs Demographic N=52 Age (y)

Male Sex Height M) Weight (Kg) BMI 55y8 32(62%) 1.598.3 59.38.9 23.62. 5 Waist Hip WHR With

Smoke Circumfere Circumferen regular r nce ce exercis (cm) (cm) e 82.89.7 Systolic BP (mmHg) 126 21 97.413.3 0.860. 35

19 08 (67%) (37%) Diastolic BP Mean BP Hypertensi (mmHg) (mmHg) on 8310 9813 6 (12%) Total Cholesterol

(mmol/L) HDL-C (mmol/ L) LDL-C (mmol/ L) TG (mmol/ L) Glucose (mmol/ L)

5.50.9 1.490. 34 3.00.9 0 1.400. 5.11.2 68 Measurement Carotid Artery: Intimamedia Thickness (IMT)

Brachial artery: Timed-averaged velocity (TAV) % change in brahcial blood flow velocity % change in brachial blood flow volume (Q) Q=TAV(rr2) FMD % change in Lumen diameter Results Carotid IMT (mm)

0.740.23 554195 % change in Brachial blood flow Volume (%) Flow Mediated Dilation 4.542.26 (FMD%) (endothelium dependant) Glycerin Tri-nitrate Induced 14.33.77 Dilation (GTND%) (endothelium independent) FMD/GTND ratio 0.320.15 Main findings

*=p<0.05, **=p<0.01 Spearmans Correlation coefficients with FMD Age Waist circumference BMI Carotid IMT Systolic BP Diastolic BP Glucose TC HDL LDL TG - 0.343* -0.363*

-0.313* -0.349* -0.233 -0.143 -0.290 -0.290 0.206 -0.127 -0.529** Leptin plays an important role in the regulation of body weight and energy balance women have higher circulating leptin level than men. However, the present study demonstrate that: Serum leptin concentrations were higher in Type 2 di abetic patients with nephropathy than normoalbumin

uric diabetic patients and controls. Finding: Diabetic men with nephropathy had proportionally hi gher serum leptin such that the gender difference in l eptin observed in non-nephropathic individuals was a bolished. Further study using MR I 1 2 J.C. Carr and T.J. Carroll (eds.), Magnetic Resonance Angiography: Principles and Applications, 199 DOI 10.1007/978-1-4419-1686-0_15 1. MR imaging of lipid-rich plaques Gadofluorine : Macrocyclic Gd chelate (diameter 5 nm) T1W MR imaging in atherosclerotic NZW rabbits at 1.5 T

Successful targeting of lipid-rich plaques Successful differentiation between early and advanced plaques 2. MR imaging of fibrin EP-1873 : fibrin-binding peptide coupled to 4 Gd chelates T1W MR imaging of plaque rupture in atherosclerotic NZW rabbits Successful targeting of thrombus in ruptured atherosclerotic plaques Further study using Ultrasound 1 2 Ultrasound Radiology: Volume 260: Number 2August 2011

Conclusion: Use of a magnetic targeted microbubble system results in greater attachment to endothelial VCAM-1 in atherosclerotic aorta in conditions of high shear stress and improved detection of early inflammatory Plaque neo-vascularisation detected by contrastenhanced molecular ultrasound. Common ultrasound molecular imaging probes:

A and B : showing microbubles with the plaque C: immunohistological staining of the fibrous cap of the lesion imaged showing positive staining for CD31 corresponding to a large firstorder neovessel (asterisk) and a smaller second-order neovessel (arrowhead) Reproduced from Coli et al, Elsevier. microbubbles microparticles like echogenic liposomes acoustically active nanoparticles Characteristic: These particles are targeted to specific molecular structures present on the

cell surface in the tissue of interest. The concept of ultrasound molecular imaging is that, after intravenous injection, these probes bind to disease-specific epitopes and can then be imaged 1. Plaque composition 2. Arterial wall biomechanics 3. Plaque neo-vasuclarisation 4. Molecular imaging of vascular phenotype changes on a sub-cellular level OMICS Journal of Radiology related journals Journal of Nuclear Medicine &

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