Assistant: - Project coordination- Project coordination - Budget management- Budget management - Regulatory compliance- Regulatory compliance - Manuscript/abstract preparation- Manuscript/abstract preparation - Seminar/meeting organization- Seminar/meeting organization - Interaction with NIH Program Officer- Interaction with NIH Program Officer

1. NIH Program Project GrantNIH Program Project Grant
Proposal forProposal for
Detection of Vulnerable PlaqueDetection of Vulnerable Plaque
Center for Vulnerable Plaque Research (CVPR)
University of Texas at Houston and Texas Heart Institute
Submission Date: June 2003

2. Scientific Research ProjectsScientific Research Projects
1)1) Magnetic Resonance Imaging of InflammationMagnetic Resonance Imaging of Inflammation
and Vulnerable Plaqueand Vulnerable Plaque
2)2) Intravascular Thermographic Detection ofIntravascular Thermographic Detection of
Inflammation and Vulnerable PlaqueInflammation and Vulnerable Plaque
3)3) Nanocontrast Agents DevelopmentNanocontrast Agents Development
4)4) Enhanced Intravascular and SuperconductiveEnhanced Intravascular and Superconductive
Surface MR CoilSurface MR Coil
5)5) Nanoparticle Development and Its InteractionNanoparticle Development and Its Interaction
With Macrophage and RESWith Macrophage and RES
6)6) Core Project: Pathology, Imaging Analysis andCore Project: Pathology, Imaging Analysis and
BiostaticsBiostatics

3. Core ProjectsCore Projects
1)1) PathologyPathology
2)2) Image ProcessingImage Processing
3)3) Data AnalysisData Analysis
4)4) AdministrationAdministration

4. Project 1: MRI-SPIOProject 1: MRI-SPIO
 Title:Title:
Contrast Enhanced Magnetic Resonance ImagingContrast Enhanced Magnetic Resonance Imaging
of Vulnerable Plaqueof Vulnerable Plaque
PI:PI: Chun Yuan, Ph.D.Chun Yuan, Ph.D.
Co-IsCo-Is: James T. Willerson, Morteza Naghavi, Ponnada: James T. Willerson, Morteza Naghavi, Ponnada
Narayana, John Hazel, Larry A. Kramer, Kooi, SchmitzNarayana, John Hazel, Larry A. Kramer, Kooi, Schmitz
Institutes:Institutes:
-University of Washington, Seattle-University of Washington, Seattle
-MD Anderson Cancer Center, Houston, Texas-MD Anderson Cancer Center, Houston, Texas
-CVPR, University of Texas-Houston Health Science-CVPR, University of Texas-Houston Health Science
Center and Texas Heart InstituteCenter and Texas Heart Institute

5. Project 1: MRI-SPIOProject 1: MRI-SPIO
Major Specific Aims:Major Specific Aims:
Development of MR imaging protocols for 1- Gd enhanced 2-SPIO-Development of MR imaging protocols for 1- Gd enhanced 2-SPIO-
enhanced plaque characterization and validation with reference toenhanced plaque characterization and validation with reference to
plaque pathology.plaque pathology.
 Kooi (Netherlands) Combidex USPIO and Taupitz VSIOP (Germany)Kooi (Netherlands) Combidex USPIO and Taupitz VSIOP (Germany)
– Schmitz (Combidex) – Yuan and Kramer Feridexs– Schmitz (Combidex) – Yuan and Kramer Feridexs
 Comparison of the SPIO-enhanced protocols with gadolinium-Comparison of the SPIO-enhanced protocols with gadolinium-
enhanced plaque imaging protocols.enhanced plaque imaging protocols.
 Creating a novel MRI scoring method for imaging plaqueCreating a novel MRI scoring method for imaging plaque
inflammation (SPIO score like calcium score)inflammation (SPIO score like calcium score)
 Correlating SPIO score withCorrelating SPIO score with calcium scorecalcium score and other emerging riskand other emerging risk
markers (e.g. CRP, IL-6, CD 40L)markers (e.g. CRP, IL-6, CD 40L)
 Correlating SPIO score with temperature heterogeneity of plaqueCorrelating SPIO score with temperature heterogeneity of plaque

6. Project 1: MRI-SPIOProject 1: MRI-SPIO
Study SettingsStudy Settings
Subjects:Subjects:
-Human carotid clinical study-Human carotid clinical study
-Atherosclerotic Watanabe rabbit study-Atherosclerotic Watanabe rabbit study
-Atherosclerotic apoE deficient mice study-Atherosclerotic apoE deficient mice study
Scanners:Scanners:
-Clinical magnet; 1.5 tesla-Clinical magnet; 1.5 tesla
-Research magnet 4.7 and 7.1 tesla-Research magnet 4.7 and 7.1 tesla

7. Project-2 -ThermographyProject-2 -Thermography
 Title:Title:
Intravascular Thermographic Detection of VulnerableIntravascular Thermographic Detection of Vulnerable
PlaquePlaque
 PI:PI: Ward CasscellsWard Casscells
 Co-PIs:Co-PIs: James T. Willerson, Morteza Naghavi, Mohammad MadjidJames T. Willerson, Morteza Naghavi, Mohammad Madjid
 Institute:Institute:
- CVPR, University of Texas-Houston Health Science Center and- CVPR, University of Texas-Houston Health Science Center and
Texas Heart InstituteTexas Heart Institute
 Industry Support:Industry Support:
Volcano therapeutics, Inc.Volcano therapeutics, Inc.

8. Project 2-ThermographyProject 2-Thermography
Major Specific Aims:Major Specific Aims:
- Thermal mapping of human carotid and SFA atherosclerotic plaque using Thermosensor- Thermal mapping of human carotid and SFA atherosclerotic plaque using Thermosensor
Basket Catheter (with distal protection) and its correlation withBasket Catheter (with distal protection) and its correlation with
- CLINICAL SYMPTOMS- CLINICAL SYMPTOMS
- plaque pathology- plaque pathology (debris from dital protection can be used as surrogate tissue)(debris from dital protection can be used as surrogate tissue)
- SPIO / Gd enhanced MRI- SPIO / Gd enhanced MRI
- Thermal mapping of human coronary artery comparing patients with:- Thermal mapping of human coronary artery comparing patients with:
- control- control
- SA- SA
- UA- UA
- MI- MI
- compare culprit lesion vs no-culprit lesion in the same segment – culprit segment vs non-- compare culprit lesion vs no-culprit lesion in the same segment – culprit segment vs non-
culpritculprit
- Study the effect of Apo –A Milano and Statin on temperature heterogeneity- Study the effect of Apo –A Milano and Statin on temperature heterogeneity
- Correlation between thermal characteristics of human coronary arteries and coronary- Correlation between thermal characteristics of human coronary arteries and coronary
calcium score, serum CRP, IL-6, CD40/L, PAPP-A and Framingham risk score across 4calcium score, serum CRP, IL-6, CD40/L, PAPP-A and Framingham risk score across 4
groups of MI, unstable angina, stable angina, and asymptomatic patientsgroups of MI, unstable angina, stable angina, and asymptomatic patients
Settings:Settings:
Animal studies in NZW and WHHL rabbitsAnimal studies in NZW and WHHL rabbits
Human studies in patients subjects to carotid or superficial femoral arteriesHuman studies in patients subjects to carotid or superficial femoral arteries
endartherctomy /endartherctomy / stent, and coronary procedures.stent, and coronary procedures.

9. Project-3 Nanoparticle Contrast AgentProject-3 Nanoparticle Contrast Agent
DevelopmentDevelopment
 :Title:Title
Nanocontrast Agents Development for DetectionNanocontrast Agents Development for Detection
of Vulnerable Plaqueof Vulnerable Plaque
 PI:PI: Richard E. SmalleyRichard E. Smalley
 Co-PIs:Co-PIs: Vicki Colvin, Bob Hauge, Morteza Naghavi, Bob Hauge, Morteza Naghavi
Institute:Institute:
-- Rice UniversityRice University
- CVPR, University of Texas-Houston Health- CVPR, University of Texas-Houston Health
Science Center and Texas Heart InstituteScience Center and Texas Heart Institute

10. Project 3: Nanoparticle DevelopemtProject 3: Nanoparticle Developemt
Major Specific Aims:Major Specific Aims:
Development of plaque targeted
contrast media:
Magnetic X-Ray
-Ferro - Heavy Atoms
-Para - Calcium
-SPIO

11. Project 4- MRI CoilProject 4- MRI Coil
 Title:Title: Development of New Intravascular andDevelopment of New Intravascular and
Superconductive Phase Array Surface MRI CoilsSuperconductive Phase Array Surface MRI Coils
PI:PI: Jarek WosikJarek Wosik
Co-I:Co-I: Morteza Naghavi, MD, Lei-Ming (Patrick ) Xie,Morteza Naghavi, MD, Lei-Ming (Patrick ) Xie,
Krzysztof Nesteruk, John Hazel, Pondana NarayanaKrzysztof Nesteruk, John Hazel, Pondana Narayana
Institute:Institute:
-- CVPR, UT-Houston and Texas Heart Institute,CVPR, UT-Houston and Texas Heart Institute,
Houston, TexasHouston, Texas
- Texas Center for Superconductivity Research,- Texas Center for Superconductivity Research,
University of HoustonUniversity of Houston

12. Project 4- MRI CoilProject 4- MRI Coil
Major Specific Aims:Major Specific Aims:
Surface MRI coil:Surface MRI coil:
– To build a superconductive phase array multi-channel surface coilTo build a superconductive phase array multi-channel surface coil
with enhanced signal to noise ratio.with enhanced signal to noise ratio.
– To test the above coil in human carotid studies.To test the above coil in human carotid studies.
Intravascular MRI coil:Intravascular MRI coil:
– To build an intravascular expandable MRI probe with a novelTo build an intravascular expandable MRI probe with a novel
sandwich design resonator providing enhanced signal to noisesandwich design resonator providing enhanced signal to noise
ratio.ratio.
– To test the above coil in atherosclerotic rabbits and correlate itTo test the above coil in atherosclerotic rabbits and correlate it
with noninvasive MRI and pathology.with noninvasive MRI and pathology.
Surface SQUID CoilSurface SQUID Coil
Intravascular SQUIDIntravascular SQUID

13. Project-5: Plaque-Targeted SPIOProject-5: Plaque-Targeted SPIO
Nanoparticle DevelopmentNanoparticle Development
 Title:Title:
Plaque Targeted Super Paramagnetic Iron OxidePlaque Targeted Super Paramagnetic Iron Oxide
Nanoparticle Development and Study of its BiologicalNanoparticle Development and Study of its Biological
Interactions with Macrophages, Reticulo-EndothelialInteractions with Macrophages, Reticulo-Endothelial
System, and PlaqueSystem, and Plaque
PI:PI: Chinnaswamy Jagannath, PhDChinnaswamy Jagannath, PhD
Co-I:Co-I: Zhongyun Dong, MD, PhD, Morteza Naghavi, MD,Zhongyun Dong, MD, PhD, Morteza Naghavi, MD,
Roxana Mehran, M.D., Narya, Hazel, XiaohongRoxana Mehran, M.D., Narya, Hazel, Xiaohong
Institute:Institute:
-- Department of Pathology, UT- Medical School, HoustonDepartment of Pathology, UT- Medical School, Houston
- MD Anderson Cancer Center, Houston, TX- MD Anderson Cancer Center, Houston, TX
- CVPR, UT-Houston and Texas Heart Institute- CVPR, UT-Houston and Texas Heart Institute

14. Project-5: Plaque-Targeted SPIOProject-5: Plaque-Targeted SPIO
Nanoparticle & MacrophageNanoparticle & Macrophage
Major Specific Aims:Major Specific Aims:
 Development of new plaque-targeted SPIO withDevelopment of new plaque-targeted SPIO with
enhanced T2 valueenhanced T2 value
 Study the uptake of SPIO by macrophage and itsStudy the uptake of SPIO by macrophage and its
receptor pathwayreceptor pathway
 in vitro and ex-vivoin vitro and ex-vivo study the effect of SPIO onstudy the effect of SPIO on
macrophage biologymacrophage biology
 in vivoin vivo study the effect of SPIO on plaque pathology instudy the effect of SPIO on plaque pathology in
atherosclerotic rabbits and mice.atherosclerotic rabbits and mice.
 Development of liposomal calcium containing contrastDevelopment of liposomal calcium containing contrast
agent for CT imaging of inflammation and macrophagesagent for CT imaging of inflammation and macrophages
NMR Scanner: Bruker MiniSpec

15. Pathology CorePathology Core
Title:Title: Pathological Examination and Interpretation ofPathological Examination and Interpretation of
Atherosclerotic PlaqueAtherosclerotic Plaque
PI:PI: Renu Virmani, MDRenu Virmani, MD
Co-I:Co-I: Silvio Litovsky, MDSilvio Litovsky, MD
Institute:Institute:
-- Department of Cardiovascular Pathology, ArmedDepartment of Cardiovascular Pathology, Armed
Forces Institute of Pathology, Washington DCForces Institute of Pathology, Washington DC
- University of Texas-Houston Health Science Center- University of Texas-Houston Health Science Center
and Texas Heart Instituteand Texas Heart Institute

16. Pathology CorePathology Core
Service:Service:
-- Pathology studies of atheroscleroticPathology studies of atherosclerotic
plaque including planimetry,plaque including planimetry,
immunohistochemistry, specific stainingimmunohistochemistry, specific staining
for different plaque components includingfor different plaque components including
SPIO (iron staining and measurement) toSPIO (iron staining and measurement) to
correlate with imaging findings.correlate with imaging findings.

17. Statistics and Software CoreStatistics and Software Core
Title:Title:
PI:PI: Morteza Naghavi, MDMorteza Naghavi, MD
Co-I: Ionnis Kakadiaris, Ph.D.Co-I: Ionnis Kakadiaris, Ph.D.
Institute:Institute:
– University of Texas-Houston Health Science CenterUniversity of Texas-Houston Health Science Center
and Texas Heart Instituteand Texas Heart Institute

18. Statistics and Software CoreStatistics and Software Core
Service:Service:
- Develop customized MRI image processing- Develop customized MRI image processing
and analysis software (SPIO scoring system).and analysis software (SPIO scoring system).
- Biostatistical data processing and analysis- Biostatistical data processing and analysis

19. Administrative CoreAdministrative Core
Title: Administrative CoreTitle: Administrative Core
PI:PI: Ward CasscellsWard Casscells
Co-Is:Co-Is: James T. Willerson, Morteza NaghaviJames T. Willerson, Morteza Naghavi
Institute:Institute:
– University of Texas-Houston Health Science CenterUniversity of Texas-Houston Health Science Center
and Texas Heart Instituteand Texas Heart Institute