MR three-dimensional molecular imaging of intramural biomarkers with targeted nanoparticles.
ABSTRACT In this study, porcine carotid arteries were subjected to balloon overstretch injury followed by local delivery of paramagnetic nanoparticles targeted to alphavbeta3-integrin expressed by smooth muscle cells or collagen III within the extracellular matrix. Carotid T1-weighted angiography and vascular imaging was performed at 1.5T. While MR angiograms were indistinguishable between control and targeted vessel segments, alphavbeta3-integrin-and collagen Ill-targeted nanoparticles spatially delineated patterns and volumes of stretch injury. In conclusion, MR molecular imaging with alphavbeta3-integrin or collagen Ill-targeted nanoparticles enables the non-invasive, three-dimensional characterization of arterial pathology unanticipated from routine angiography.
- SourceAvailable from: Peter M Frederik[show abstract] [hide abstract]
ABSTRACT: One of the features of high-risk atherosclerotic plaques is a preponderance of macrophages. Experimental studies with hyperlipidemic rabbits have shown that ultrasmall superparamagnetic particles of iron oxide (USPIOs) accumulate in plaques with a high macrophage content and that this induces magnetic resonance (MR) signal changes. The purpose of our study was to investigate whether USPIO-enhanced MRI can also be used for in vivo detection of macrophages in human plaques. MRI was performed on 11 symptomatic patients scheduled for carotid endarterectomy before and 24 (n=11) and 72 (n=5) hours after administration of USPIOs (Sinerem) at a dose of 2.6 mg Fe/kg. Histological and electron microscopical analyses of the plaques showed USPIOs primarily in macrophages within the plaques in 10 of 11 patients. Histological analysis showed USPIOs in 27 of 36 (75%) of the ruptured and rupture-prone lesions and 1 of 14 (7%) of the stable lesions. Of the patients with USPIO uptake, signal changes in the post-USPIO MRI were observed by 2 observers in the vessel wall in 67 of 123 (54%) and 19 of 55 (35%) quadrants of the T2*-weighted MR images acquired after 24 and 72 hours, respectively. For those quadrants with changes, there was a significant signal decrease of 24% (95% CI, 33% to 15%) in regions of interest in the images acquired after 24 hours, whereas no significant signal change was found after 72 hours. Accumulation of USPIOs in macrophages in predominantly ruptured and rupture-prone human atherosclerotic lesions caused signal decreases in the in vivo MR images.Circulation 06/2003; 107(19):2453-8. · 15.20 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: Based on the observation that ultrasmall superparamagnetic particles of iron oxides (USPIOs) are phagocytosed by cells of the mononuclear phagocytic system, the purpose of this study was to evaluate their use as a marker of atherosclerosis-associated inflammatory changes in the vessel wall before luminal narrowing is present. Experiments were conducted on 6 heritable hyperlipidemic and 3 New Zealand White rabbits. 3D MR angiography (MRA) of the thoracic aorta was performed on all rabbits by use of a conventional paramagnetic contrast agent that failed to reveal any abnormalities. One week later, all rabbits except 1 of the hyperlipidemic animals were injected with a USPIO contrast agent (Sinerem, Guerbet) at a dose of 1 mmol Fe/kg. 3D MRA data sets collected over the subsequent 5 days showed increasing signal in the aortic lumen. Whereas the aortic wall of the control rabbits remained smooth and bright, marked susceptibility effects became evident on day 4 within the aortic walls of hyperlipidemic rabbits. Ex vivo imaging of aortic specimens confirmed the in vivo results. Histopathology documented marked Fe uptake in macrophages embedded in atherosclerotic plaque of the hyperlipidemic rabbits. Electron microscopy showed multiple cytoplasmic Fe particles in macrophages. No such changes were seen in control rabbits or in the hyperlipidemic rabbit that had not received Sinerem. USPIOs are phagocytosed by macrophages in atherosclerotic plaques of the aortic wall of hyperlipidemic rabbits in a quantity sufficient to cause susceptibility effects detectable by MRI.Circulation 02/2001; 103(3):415-22. · 15.20 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: We sought to investigate whether early and late outcome after percutaneous transluminal coronary angioplasty (PTCA) could be predicted by baseline levels of acute-phase reactants. Although some risk factors for acute complications and restenosis have been identified, an accurate preprocedural risk stratification of patients undergoing PTCA is still lacking. Levels of C-reactive protein (CRP), serum amyloid A protein (SAA) and fibrinogen were measured in 52 stable angina and 69 unstable angina patients undergoing single vessel PTCA. Tertiles of CRP levels (relative risk [RR] = 12.2, p < 0.001), systemic hypertension (RR = 4.3, p = 0.046) and female gender (RR = 4.1, p = 0.033) were the only independent predictors of early adverse events. Intraprocedural and in-hospital complications were observed in 22% of 69 patients with high serum levels (>0.3 mg/dl) of CRP and in none of 52 patients with normal CRP levels (p < 0.001). Tertiles of CRP levels (RR = 6.2, p = 0.001), SAA levels (RR = 6.0, p = 0.011), residual stenosis (RR = 3.2, p = 0.007) and acute gain (RR = 0.3, p = 0.01) were the only independent predictors of clinical restenosis. At one-year follow-up, clinical restenosis developed in 63% of patients with high CRP levels and in 27% of those with normal CRP levels (p < 0.001). Preprocedural CRP level, an easily measurable marker of acute phase response, is a powerful predictor of both early and late outcome in patients undergoing single vessel PTCA, suggesting that early complications and clinical restenosis are markedly influenced by the preprocedural degree of inflammatory cell activation.Journal of the American College of Cardiology 11/1999; 34(5):1512-21. · 14.09 Impact Factor
Journal of Cardiovascular Magnetic Resonance (2006) 8, 535–541
Copyrightc ?2006 Taylor & Francis Group, LLC
ISSN: 1097-6647 print / 1532-429X online
MOLECULAR IMAGING AND NANOTECHNOLOGY
MR Three-Dimensional Molecular Imaging of
Intramural Biomarkers with Targeted Nanoparticles
Tillmann Cyrus, MD, PhD,1Dana R. Abendschein, PhD,1Shelton D. Caruthers, PhD,2Thomas D. Harris, PhD,3
Veronica Glattauer, PhD,4Jerome A. Werkmeister, PhD,4John A. M. Ramshaw, PhD,4Samuel A. Wickline, MD,1
and Gregory M. Lanza, MD, PhD1
1Division of Cardiology, Washington University School of Medicine, Saint Louis, Missouri, USA
2Philips Medical Systems, Cleveland, Ohio, USA
3Bristol-Myers Squibb Medical Imaging, Billerica, Massachusetts, USA
4CSIRO, Victoria, Australia
In this study, porcine carotid arteries were subjected to balloon overstretch injury followed
by local delivery of paramagnetic nanoparticles targeted to αvβ3-integrin expressed by smooth
muscle cells or collagen III within the extracellular matrix. Carotid T1-weighted angiography and
vascular imaging was performed at 1.5T. While MR angiograms were indistinguishable between
control and targeted vessel segments, αvβ3-integrin-and collagen III-targeted nanoparticles
spatially delineated patterns and volumes of stretch injury. In conclusion, MR molecular imag-
ing with αvβ3-integrin or collagen III-targeted nanoparticles enables the non-invasive, three-
dimensional characterization of arterial pathology unanticipated from routine angiography.
Magnetic resonance (MR) molecular imaging is emerging as
an important technique for noninvasively assessing atheroscle-
rotic vascular disease (1–3). While fluoroscopic-guided angiog-
raphy and interventions are the dominant approaches used for
Keywords: Magnetic Resonance Imaging, Molecular Imaging,
Nanoparticles, Integrins, Collagen III, Angioplasty, Restenosis.
Received 4 September 2005; accepted 18 December 2005
The present research was conducted while Dr. T. Cyrus was a
SCAI/Bracco Diagnostics, Inc.-ACIST Fellowship Program
awardee. Additional funding and equipment were provided
through National Institutes of Health grant support (HL-42950,
HL-59865, HL-78631, NO1-CO-37007 and EB-01704), and the
American Heart Association.
Gregory M. Lanza MD PhD
Washington University School of Medicine
660 South Euclid Ave., Campus Box 8086
Saint Louis, MO 63110
revascularization, MRI–based techniques are in rapid devel-
opment and beginning to gain acceptance. Angiographic ap-
eate the extent of mural injury imparted by angioplasty. Despite
marked improvements in revascularization techniques and de-
vices, restenosis persists as a serious complication, which is
at least partially dependent upon the inflammatory character
of atherosclerotic plaque (4–14) and the impact of mechani-
cal stress imparted by balloon injury (15, 16). MR molecular
imaging probes infused locally into the balloon injured wall
offer the potential to concomitantly delineate interventional in-
jury patterns and characterize biochemical features exposed in
the plaque at the time of intervention.
specific targeting of biochemical epitopes (17). These nanopar-
ticles are inherently echogenic (18) when bound to surfaces and
can be modified for compatibility with MR (19), x-ray (20), or
nuclear imaging (21). Ligand-targeted nanoparticles have been
used for systemic vascular imaging of thrombosis (17) and an-
giogenesis (3, 22). Although nanoparticles are normally steri-
cally precluded from reaching extravascular biomarkers, they
can readily penetrate the vessel wall following stretch-injury.
In prior experiments, tissue factor (TF) expressed by smooth
muscle cells was targeted (23, 24), but unfortunately, the delay
incubation used in those studies are incompatible with real-time
phenotypic characterization and clinical application.
In this study, we evaluated the potential of ligand-targeted
paramagnetic nanoparticles to detect αvβ3-integrin, constitu-
tively expressed by smooth muscle cells or native collagen III
within the extracellular matrix of carotid arteries immediately
after balloon injury. Three-dimensional reconstruction was uti-
lized to compare balloon injury patterns determined by molecu-
the relative intramural MR contrast enhancement achieved with
the two molecular imaging targets was compared.
Preparation of targeted nanoparticles
Ligand-targeted paramagnetic nanoparticles were prepared
as previously described (17, 25). Briefly, the nanoparti-
cles comprised 20% (volume/volume) perfluorooctylbromide
(PFOB; Exfluor Research, Round Rock, TX, USA) and 1.5%
(weight/volume) of a surfactant co-mixture, 1.7% (w/v) glyc-
erin and water for the balance. The surfactant co-mixture in-
cluded 69.9 mole% lecithin (Avanti Polar Lipids, Inc., Al-
abaster, AL, USA), 0.1 mole% peptidomimetic vitronectin
antagonist (26–28) (Bristol-Myers Squibb Medical Imag-
ing, Billerica, MA, USA) or anti-collagen III f(ab) (28,
29) (CSIRO, Victoria, Australia) coupled to MPB-PEG2000-
phosphatidylethanolamine (Northern Lipids, Inc., Vancouver,
British Columbia, Canada), and 30 mole% of gadolin-
ium diethylene-triamine-pentaacetic acid-bis-oleate (Gateway
Chemical Technologies, St. Louis, MO, USA). Nontargeted,
lipid conjugate with lecithin. The nominal sizes for each
formulation were measured with a submicron particle ana-
lyzer (Malvern Zetasizer, Malvern Instruments, Malvern, PA,
USA) and were 245 nm ± 117 nm for the αvβ3-targeted,
262 nm ± 99 nm for the collagen III-targeted, and 323 nm ±
26 nm non-targeted control nanoparticles.
Preparation of targeted fluorescent
AlexaFluor 488-labeled nanoparticles were produced by in-
clusion of 0.5 mole% AlexaFluor 488 coupled to caproyl-
phosphatidylethanolamine. AlexaFluor 488-caproyl-phospha-
tidylethanolamine was synthesized by dissolving 7.8 µmole
AlexaFluor 488 carboxylic succinimidyl ester (Molecu-
lar Probes, Carlsbad, CA, USA) in 1.4 mL dimethylfor-
mamide and mixing it with 10 µmole caproylamine phos-
phatidylethanolamine (Avanti Polar Lipids, Alabaster, AL,
USA) in 200 µL chloroform at 37◦C for one hour. Follow-
ing addition of 200 µL of chloroform, reaction temperature
was increased to 50◦C and continued overnight. TLC us-
ing a reverse phase hydrocarbon (C18) impregnated silica gel
and a mobile phase consisting of 0.1M sodium acetate buffer
(pH5.6):methanol:water at a ratio of 20:100:200 was performed
to monitor and purify the conjugated product from the uncou-
pled AlexaFluor dye. The red fluorescent lipid was recovered at
the origin, extracted with chloroform:methanol (3:1) and evap-
orated to dryness until use.
imal Studies Committee and are based on National Institutes of
Health laboratory standards. Healthy domestic pigs weighing
20 kg were fed a normal diet (n = 12). Animals were fasted
overnight before sedation with telazol cocktail (1 mL/23 kg
IM) followed by intubation and 1–2% isoflurane anesthesia
in oxygen. The ECG, blood gases and arterial blood pressure
were monitored. A 12F (size necessary to fit the double-balloon
catheter during incubation) catheter sheath was aseptically in-
serted into the femoral artery via a cut-down and a bolus of hep-
arin (200 U/kg) was given to inhibit clot formation in catheters.
No antiplatelet agents were administered. A guide catheter was
placed under fluoroscopy into the left or right carotid artery at
the level of the 5th cervical vertebra. A baseline carotid an-
giogram was obtained and lidocaine and nitroglycerin were
used to treat vasospasm. An 8 mm × 2 cm balloon catheter
at the level of the 2nd and 3rd cervical vertebrae and inflated
three times to a pressure of 6 atmospheres for 30 seconds with
60 second pauses between inflations. A balloon-to-artery ratio
of approximately 1.5 was employed. This procedure produces a
consistent rupture of the internal elastic lamina and injury to the
media (31, 32).
Following carotid overstretch-injury, nanoparticles were ad-
ministered via a local delivery with a double-balloon catheter
balloon catheter was inserted via the sheath in the right femoral
artery and guided into the respective carotid artery. The inner
distance between the distal and the proximal balloons was 6 cm.
Under fluoroscopy, the catheter was placed in a fashion that the
two balloons. The site of injury had been marked both on x-ray
and on the overlying skin during the injury. Upon satisfactory
confirmation of the double-balloon catheter position, the prox-
imal and then distal balloons were each gently (1 atm) inflated
to occlude the artery. Blood was aspirated through the central
porthole, and the arterial segment flushed with normal saline.
Targeted nanoparticles (n = 9 for αvβ3-integrin and n = 6 for
collagen III) or non-targeted control nanoparticles (n = 3; into
the contralateral artery), or saline alone as control (n = 6) were
thoroughly with saline before carotid flow was reestablished. A
post-angioplasty carotid angiogram was obtained, and the ani-
mals were transferred for MR imaging of the neck vasculature.
Magnetic resonance imaging
and NMR analysis
Animals were imaged with MRI using a 1.5 Tesla clinical
scanner (NT Intera CV, Philips Medical Systems, Cleveland,
536T. Cyrus et al.
Figure 1. (A) Time-of-flight angiogram depicting blood flow in the carotid arteries of domestic pigs following balloon overstretch injury (femoral
approach) and exposure to αvβ3-integrin targeted nanoparticles (left) or non-targeted nanoparticles as control (right). T1-weighted black blood
MR images of carotid arteries exposed for 10 minutes locally to paramagnetic nanoparticles covalently coupled to either (B) peptidomimetics
targeted to αvβ3-integrin or (C) collagen III F(ab)fragments. T1-weighted MRI at 1.5 T.
OH, USA) and techniques optimized to assess persistence of
contrast enhancement and in vivo luminal dimensions through-
out the injured vessels. A 5-element phased array surface coil
gradient-echo, fat-suppressed, time-of-flight angiograms of the
ternal and internal carotid were performed with repetition times
(TR) of 40 ms and echo times (TE) of 4.6 ms. T1-weighted,
fat-suppressed, fast spin-echo (TSE) imaging was performed to
image the vascular wall (TR = 532 ms, TE = 11 ms, 250 ×
250 µm in-plane, 2 mm slice thickness, echo train = 4, num-
ber of signals averaged = 8). To ensure complete nulling of the
blood signal, “sliding” radiofrequency saturation bands were
placed proximal and distal to the region of image acquisition
and moved with the selected imaging plane. Contrast to noise
as the difference of the signal between the nanoparticle targeted
area and a region of interest within the surrounding tissue, re-
spectively, divided by the standard deviation of the background
signal (33). Contrast image analysis was performed with Easy
Vision v5.1 (Philips Medical Systems, Cleveland, OH, USA)
using regions of interest manually applied in each slice of the
Histology and immunohistology
morphology and immunohistology. Frozen (OCT) segments
from the injured vessels were sectioned every 7 microns and
Verhoeff-van Gieson for elastic tissue, and oil-red O for lipids.
Microscopic images were obtained with a Nikon E800 micro-
scope using a Nikon DXM 1200 digital camera connected to a
Dell Dimension 4100 computer (Round Rock, TX) using Nikon
ACT-1 image capture software (Nikon Inc., Melville, NY). His-
tal vessel area were obtained. Immunohistology included detec-
tion of αvβ3−integrin (LM-609, Chemicon Int., Temecula, CA,
USA) and collagen III (AB757P, Chemicon Int., Temecula, CA,
USA). Vectastain Elite avidin-biotin complex method kits were
used (Vector Laboratories, Burlingame, CA, USA).
in the adventitia and endothelium.
MR Molecular Imaging of Vascular Epitopes 537
All quantitative data were analyzed with SAS (Cary, NC,
USA) using general linear models and other descriptive statis-
tics. Differences between means were declared significant at
p < 0.05 and b = 0.80.
During MR scanning, T1-weighted black blood images were
obtained to evaluate vascular injury, and MR angiograms were
obtained to assess luminal patency. No evidence of luminal nar-
rowing was appreciated and time-of-flight carotid angiograms
were indistinguishable between the targeted and contralateral
control vessel segments (Fig. 1A). These results were consis-
tent with X-ray contrast angiograms obtained immediately post
procedure and before animal transfer to the MR suite.
Both biomarkers, collagen III and αvβ3-integrin, were ex-
posed by stretch fracture of the carotid wall and were avail-
able immediately after injury for MR molecular imaging. The
and αvβ3-integrin molecular imaging were similar (Fig. 1B, C)
and indicated that both biomarkers were generously distributed
throughout the vessel wall. The resultant contrast pattern re-
flected the asymmetric pattern of injury imparted to the me-
dia and adventia by balloon overstretch shear forces, since the
particles are otherwise sterically precluded from deep penetra-
tion into the extracellular matrix. Non-targeted nanoparticles
and saline treatment produced no MR contrast enhancement
and provided no information about the extent of mural injury.
Successful targeting of intravascular epitopes was corroborated
by histology using immunofluorescence in independent exper-
iments where carotid arteries were incubated with fluorescent
PFC nanoparticles targeted against the αvβ3-integrin (Fig. 2).
MR signal enhancement for the nanoparticle targeted vessel
segments was intense and easily allowed for the determination
of injury morphology. The contrast to noise ratio (CNR) be-
ing arterial tissue measured with T1-weighted, fat-suppressed,
fast spin-echo (TSE) imaging was 13.8 ± 5.2, whereas the col-
lagen III targeted nanoparticles provided a CNR of 3.3 ± 0.3
(p < 0.05; Fig. 3A). The difference in contrast presumably re-
flected the relative density of the biomarkers accessible to the
nanoparticles within the wall and or differential probe avidity.
The peptidomimetic ligand is small, with a molecular weight of
∼1050 d, whereas the collagen III f(ab)fragment has a mass of
approximately 50,000 d. As a result, the αvβ3-integrin nanopar-
ticles presented 250 to 300 homing ligands per particle while
the collagen III nanoparticles had 25 to 50 f(ab)fragments per
binding advantage that was minimized by locally infusing both
nanoprobes at receptor-saturating concentrations.
The length of injury determined in all vascular segments ex-
was similar (p > 0.05) for the collagen III targeted carotids
Figure 3. (A) Contrast to noise ratio for αvβ3-integrin and colla-
gen III targeted nanoparticle emulsions (∗p < 0.05). (B) Length of
vascular injury as determined by MRI. (C) Quantitation of injury
volume. T1-weighted MRI at 1.5 T. None of the controls (vessels
incubated with non-targeted nanoparticles or saline) displayed de-
tectable signal for MR imaging.
actual balloon length (20 mm) by 50% (Fig. 3B). The absolute
reconstructions of the contrast-segmented vessels did not differ
(p > 0.05) between the αvβ3-targeted (955 mm3± 234 mm3)
538T. Cyrus et al.
Figure 4. Volume-rendered image consisting of a 3-D MR angiogram co-registered with T1enhancement in the wall of carotid arteries of a do-
mestic pig following angioplasty and exposure to αvβ3-targeted paramagnetic nanoparticles. Depiction of αvβ3-targeted contrast (golden; arrows)
in the vascular wall. Frames at different angles detailing the asymetry and morphology of balloon overstretch injury pattern. MR angiography:
TR 16 ms, TE 3.5 ms, a 60. MR vascular wall image: T1-weighted MRI at 1.5 T, black-blood fast SE, TR 540 ms, TE 11 ms, a 90.
and collagen III targeted (903 mm3± 218 mm3) arteries
Histology of the carotid arteries showed irregular loss of
endothelium and disruptions in the media and internal elastic
lamina propria as well as fractures reaching into the adventi-
targeted, collagen-III targeted, non-targeted nanoparticles, or
saline were not significantly different. The presence and distri-
bution of αvβ3-integrin and collagen III expression in the media
were confirmed histologically (Fig. 5).
Figure 5. Representative cryosections from carotid arteries harvested immediately after MRI. Upper row: Hematoxylin eosin stains of uninjured
versus balloon overstretch injured vessel. Lower row: αvβ3-integrin (LM-609) and collagen III (AB757P). S/p = status post, L = vascular lumen,
M = media, A = adventitia, arrows point at molecular markers.
MR Molecular Imaging of Vascular Epitopes539
In the current experiments, we have established that param-
agnetic nanoparticles can be used to target important biosigna-
tures in the extracellular matrix or expressed on cell surfaces
following balloon overstretch injury. In contrast to conventional
angiography, which delineates vascular filling defects, these
nanoparticles are capable of infiltrating the vessel wall through
the fissures created by balloon overstretch injury and then
binding to epitopes within the vessel wall thereby delineat-
ing the wall morphology. This unique MR-based technol-
ogy could permit in situ physiological characterization of
atherosclerotic plaques immediately after injury, which may fa-
In the present study, we sought to establish the feasibility of
and to compare their efficacy. Both the extracellular matrix tar-
get collagen III and the smooth muscle cell membrane epitope
αvβ3-integrin were generously distributed and bioavailable for
binding. Interestingly, the αvβ3-integrin targeted nanoparticles
produced a four-fold greater contrast signal relative to the wall
than the collagen III targeted agent. This suggests a higher re-
tention of the integrin-targeted agent, which may be due in part
to differences in the number of binding sites exposed or avail-
able to the particulate probe. Although the surface presentation
of ligands varied considerably between the two formulations
due to molecular weight differences, it is likely that this effect
was minimized by administering saturating concentrations of
nanoparticles into the wall.
Importantly, despite the difference in contrast signal relative
to wall, both nanoparticle formulations provided adequate im-
age quality, and there was no difference in the ability to analyze
lesion length, three-dimensional geometry, and volume. Thus,
both collagen III targeted and αvβ3-integrin targeted nanopar-
ticles equivalently delineated vascular wall stretch-injury pat-
terns. These data illustrate the ability of MR molecular imaging
probes to supplement the characterization of vascular pathol-
ogy beyond luminal dimensions with biochemical and mechan-
ical injury data in a timely fashion. An incubation time of
10 minutes was chosen in the current study to achieve ad-
equate exposure of injured media to the nanoparticle emul-
sion. In the future, delivery devices such as porous balloons
may be chosen to minimize or eliminate vascular occlusion
a significant subset of patients and lesions remain in which
restenosis or thrombosis is still prevalent. The potential to de-
velop clinical restenosis after vascular injury is influenced by
the mechanical shear forces of angioplasty and the underlying
biochemicalcharacter of the atheroma. Many investigators have
demonstrated the influence of mechanical shear force created
by balloon injury on the stimulation of biochemical and in-
tracellular signaling processes, which contribute to restenosis
(8, 13, 15, 34). Recurrent unstable angina and restenosis may
also depend upon the overall inflammatory status of the plaque,
which can vary considerably among lesions and patients. His-
tological analysis of coronary plaque atherectomy specimens
have demonstrated that increased atheroma inflammation, sug-
gested by larger infiltrations of macrophages and T-cells, was
related to recurrent unstable angina and that the concentra-
tion of macrophages was an independent predictor of resteno-
sis (8). Ligand-directed paramagnetic nanoparticles may allow
real-time pathologic characterization of the injured atheroma,
which could be predictive of recurrent symptoms after angio-
plasty and may provide a convenient drug-delivery vehicle for
individualized therapy (35).
In contradistinction to conventional angiograms, which de-
lineate patency of vasculature, MR molecular imaging nanopar-
ticles provide an assessment of the spatial distribution of both
cell surface and extracellular matrix biomarkers. The quantita-
tive measurements of three-dimensional balloon injury pattern
and the prevalence of pathologic biomarkers may provide prog-
MR molecular imaging could reveal unique assessments and al-
low individualized revascularization strategies.
We are grateful for the expert technical assistance by John S.
Allen, BS, and Todd A. Williams, BS. We also appreciate the
support and helpful discussions with Thomas D. Harris, PhD,
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