2011 - ExMI – Experimental Molecular Imaging - RWTH

Chair of Experimental Molecular Imaging
Faculty of Medicine
Imaging
Pathophysiology
Down to the
Molecular Level
Director
Univ.-Prof. Dr. med. Fabian Kießling
RWTH Aachen University Hospital
Pauwelsstrasse 30, D-52074 Aachen
Helmholtz-Institute for Biomedical Engineering
Pauwelsstrasse 20, D-52074 Aachen
Phone: +49 (0)241 80 80116 (Secretary)
+49 (0)241 80 80117 (Office)
Fax: +49 (0)241 80 33 80116
Email: fkiessling@ukaachen.de
Web: http://www.molecular-imaging.ukaachen.de
Staff
Abou-Elkacem, Lotfi, Dipl.-Biol, PhD student
Al Rawashdeh, Wa’el, MSc, PhD student
Appold, Lia, BSc student
Arns, Susanne, Technical assistant
Bätke, Sarah, MSc, PhD student
Berker, Yannick, Dipl.-Ing. MSc, PhD student
Bölükbas, Ali, MSc student
Bzyl, Jessica, BSc, PhD student
Curaj, Adelina, MD, PhD student
Doleschel, Dennis, Dipl.-Biol, PhD student
Duarte Jorge, Samuel, MSc student
Dueppenbecker, Peter, Dipl.-Ing., PhD student
Ehling, Josef, Dr. med., Postdoc
Fokong, Stanley, MSc, PhD student
Franke, Jochen, MSc student
Fuge, Felix, Dipl.-Chem, PhD student
Gätjens, Jessica, Dr. rer. nat., Group leader
Gebhardt, Pierre, Dipl.-Ing., PhD student
Goldschmidt, Benjamin, Dipl.-Ing., PhD student
Gremse, Felix, Dipl.-Ing., PhD student
Grouls, Christoph, MD Student
Jayapaul, Jabadurai, MSc, PhD student
Koczera, Patrick, MD student
Kunjachan, Sijumon, MSc, PhD Student
Lammers, Twan, PhD, DSc, Group leader
Lederle, Wiltrud, Dr. rer. nat., Group leader
Liu, Zhe, PhD, Postdoc
Mertens, Marianne, MSc, PhD student
Mertens, Natascha, Technical assistant
2011
Helmholtz-Institute for Biomedical Engineering
RWTH Aachen University
Möckel, Diana, Technical assistant
Novak, Mara, Technical assistant
Palmowski, Karin, Dr. med., Postdoc
Palmowski, Moritz, PD Dr. med., Group leader
Rix, Anne, Technical Assistant
Salomon, Andre, Dr.-Ing., Postdoc
Schultz, Volkmar, Dr.-ing., Group leader
Theek, Benjamin, MSc, student
Tiemann, Birgit, Administrative assistant
Truhn, Daniel, Dipl.-Phys., MSc, PhD student
Weiler, Marek, Technical Assistant
Weissler, Bjoern, Dipl.-Ing., PhD Student
Wu, Zhuojun, MSc, PhD student
Yokota Rizzo, Larissa, MSc, PhD student
35

Experimental Molecular
Imaging
36
Helmholtz-Institute for Biomedical Engineering
RWTH Aachen University
Introduction
The Chair of Experimental Molecular Imaging (ExMI) at the
Helmholtz-Institute for Biomedical Engineering (HIA) at
RWTH Aachen University focuses on the development and
evaluation of novel imaging methods and contrast agents
to characterize and treat cancer and cardiovascular disorders.
This is mainly achieved by vascular targeting and
theranostic approaches, which are developed and tested in
preclinical animal models. In this context, novel biomaterials,
including nanoparticles, polymeric carriers, liposomes
and microbubbles can play a major role. Their delivery and
therapeutic efficacy can be assessed by functional and molecular
imaging, which has become an established tool in
preclinical research.
ExMI follows a multimodal approach, based on combinations
of MRI, CT, ultrasound, optical imaging and nuclear
medicine techniques. Image fusion, hybrid imaging as well
as multimodal contrast agents are in the research scope.
Usually, the choice of imaging strategies and contrast agents
follows the biological and medical problem to be investigated.
Furthermore, we intend to better connect preclinical
and clinical research, and to translate novel surrogate markers
and (molecular) diagnostics into clinical evaluation.
Currently, the department consists of five research groups,
working on the biological mechanisms of tumor development
and angiogenesis, on the synthesis of novel imaging
probes, on theranostic concepts to treat cancer and cardiovascular
diseases, on MR-PET hybrid imaging, and on translational
studies to bring functional and molecular ultrasound
to the clinic.
Mechanisms of Tumor
Progression and Metastasis
The group “Mechanisms of Tumor Progression and
Metastasis” aims at elucidating the mechanisms of tumor
growth and progression, with a special focus on the impact
of the tumor microenvironment and the longitudinal in
vivo characterization by non-invasive imaging. Besides tumor
staging and improved diagnosis, further attempts are
directed to monitor therapy effects, including the evaluation
of novel therapeutics. In vivo imaging is complemented
by histological and functional in vitro analyses in order
to validate the data and to identify new potential markers
and targets.
We recently compared different imaging modalities with
respect to the non-invasive assessment of tumor growth
and size in GFP/RFP-expressing colon carcinoma xenografts.
Magnetic resonance imaging (MRI) was proven to
be highly sensitive and accurate for tumor size and growth
assessment. Micro-computed tomography (µCT) provided
an almost similar accuracy. Optical reflectance imaging
(ORI) was as sensitive as MRI, but overestimated the tumor
size. Fluorescent intensity measurements provided more
accurate data of the tumor size than fluorescent area analyses
(Fig. 1) [1] .
[1] Abou-Elkacem et al, Anticancer Res 31: 2907 (2011)
2011
Fig.1. A: Monitoring of tumor growth in s.c. HCT 116-GFP-
RFP xenografts using ORI, MRI and μCT. Representative
images show tumors at day 1, 3 and 15 after inoculation.
B: Correlation of the tumor volumes determined in vivo by
MRI, μCT and ORI with ex vivo caliper data at day 12 and
15 (n=9). From [1] .
A second study aimed at non-invasive apoptosis assessment
in response to anti-angiogenic therapy, using both
optical imaging (Annexin-Vivo) and gamma counting
( 99m Tc-HYNIC-Annexin V). As opposed to immunohistochemistry,
which clearly showed apoptosis induction
after treatment with the multi-tyrosine kinase inhibitor
SU11248, both Annexin probes were found to be unable
to specifically detect apoptosis in vivo, most probably because
of the breakdown of the vasculature and reduced
probe delivery [2] .
Due to the discovery of the erythropoietin-receptor
(EpoR) on tumor cells, the use of erythropoietin (Epo) for
the treatment of cancer-induced anemia is currently under
intense debate. In order to elucidate the role of Epo
and EpoR in lung cancer, a near-infrared probe for fluorescence
mediated tomography (FMT) was developed and
tested for longitudinally assessing EpoR status in lung cancer
xenografts with different EpoR expression levels. As
shown in Fig. 2, the probe was found to be highly specific,
and could accurately determine the EpoR expression level
of the xenografts in vivo, as demonstrated by FMT/µCT
hybrid imaging. These data suggest a high potential of this
newly developed probe for analyzing the EpoR status in
tumors and the role of Epo in lung cancer [3] .
Fig. 2. Specific binding of Cy5.5-labeled Epo (red) to tumors
with different EpoR expression levels (lower in A549
(A); higher in H838 (B)), as demonstrated via in vivo competition
experiments with excess unlabeled Epo (blue).
FMT/μCT hybrid imaging clearly confirmed the stronger
accumulation of Epo-Cy5.5 in H838 (E) as compared to
A549 (D). White arrows indicate tumors, hatched arrows
bone. From [3] .
[2] Lederle et al, EJNMMI Research 1: 26 (2011)
[3] Doleschel et al, J Nucl Med (in press)

Probe Design for Molecular
Imaging
The chemical group within ExMI, which focuses on the development
of novel probes for molecular imaging, has in
the past year made significant progress towards the development
of FMN- and FAD-coated superparamagnetic iron
oxide (USPIO) nanoparticles, which were shown to be highly
suitable for in vivo imaging of tumors and tumor angiogenesis,
as well as for ex vivo labeling endothelial cells [4] .
In addition, USPIO have been incorporated into poly(butyl
cyanoacrylate)-based microbubbles (MB), thereby enabling
the non-invasive visualization of MB destruction using MRI [5] .
These USPIO-containing MB have furthermore been shown
to be useful for mediating and monitoring drug delivery
across the blood-brain-barrier (BBB). This is exemplified by
Fig. 3, showing the deposition of USPIO nanoparticles released
from MB into the brain upon ultrasound-mediated destruction,
as well as extravasation of the blood pool marker
FITC-dextran from systemic circulation across the BBB [6] .
Fig. 3. Mediating and monitoring blood-brain-barrier
(BBB) permeation using USPIO-containing MB. A-B: T2*relaxation
rates in the brains of mice before (A) and 45
min after (B) the application of USPIO-MB plus destructive
ultrasound (US)
pulses, showing
efficient deposition
of released
USPIO across
the BBB. C-D:
Upon combining
USPIO-MB
with US, significantextravasation
of FITCdextran
(green)
into the brain
was observed
(C), which was
not the case for
non-US-treated
controls (D).
Blood vessels
counterstained
in red.
As part of Patim.NRW, USPIO nanoparticles are also being
developed for visualizing the localization, the resorption and
the functionality of cardiovascular implants, such as stents,
shunts and patches. To this end, as part of an initial proof-ofprinciple
study, collagen-based scaffolds have been prepared
which contain different amounts of USPIO, they have been
characterized using TEM and SEM, cell growth onto and into
these scaffolds has been evaluated, and they have been
used to non-invasively monitor their localization in mice. As
shown in Fig. 4, depending on the amount of USPIO incorporated,
the labeled scaffolds could be visualized with high
sensitivity, both ex vivo and in vivo, and USPIO incorporation
did not affect their structural properties [7] . Experiments
evaluating the impact of USPIO labeling on cell growth and
[4] Jayapaul et al, Biomaterials 32: 5863 (2011)
[5] Liu et al, Biomaterials 32: 6155 (2011)
[6] Koczera et al (in prep)
[7] Mertens et al (in prep)
2011
Helmholtz-Institute for Biomedical Engineering
RWTH Aachen University
aiming to assess the suitability of these matrices for monitoring
scaffold resorption are currently ongoing.
Fig. 4. USPIO-labeled scaffolds. A-C: Collagen-based matrices
were labeled with different amounts of USPIO (A), and
their structural properties were evaluated using scanning
electron microscopy at 20x (B) and 80x (C) magnification.
D-E: Standard (D) and color-coded (E) T2*-imaging of a
USPIO-labeled scaffold (arrow) upon intraperitoneal implantation.
Nanomedicines and theranostics
Efforts in our group primarily focus on the development of image-guided
nanomedicines for treating cancer and inflammatory
disorders. In the past year, significant progress has been in
the development of passively and actively targeted polymers
and micelles for drug targeting to tumors, as well as in the design
and evaluation of various different nanomedicine formulations
for treating rheumatoid arthritis [8]; [9]; [10] .
In addition, we have evaluated how well nanocarrier materials
are able to overcome multidrug resistance (MDR). To
this end, three different doxorubicin-containing nanomedicines
(i.e. liposomes, polymers and micelles) and four different
cell lines were used (i.e. A431, SW620, B16 and CT26;
both in parental and in MDR-form; obtained upon continuously
exposing the cells to IC90 concentrations, and selecting
surviving cells; see Fig. 5A-B). In line with the literature,
nanomedicines suffered less from the expression of MDRconferring
drug efflux pumps than did free doxorubicin, as
confirmed by both cytotoxicity and cell uptake experiments
(Fig. 5C). As opposed to the literature, however, in which
often pharmacologically active carrier materials and/or artificially
resistant (e.g. Pgp-overexpressing) cells are used, the
differences in IC50 between parental and MDR-cells were
much smaller (2-4; vs. 10-100), indicating that the ability of
clinically relevant nanomedicines to overcome physiologically
relevant MDR should not be overestimated [11] .
Additional experiments in our group, performed as part of
the ForSaTum project, have aimed at imaging and analyzing
[8] Huis in ‘t Veld et al, Nanoscale 3: 4022 (2011)
[9] Talleli et al, J Control Release 153: 93 (2011)
[10] Crielaard et al (in prep)
[11] Kunjachan et al, Eur J Pharm Sci (in press)
Experimental Molecular
Imaging
37

Experimental Molecular
Imaging
38
Helmholtz-Institute for Biomedical Engineering
RWTH Aachen University
tumor angiogenesis using a combination of in vivo and ex vivo
micro-computed tomography (µCT) and immunohistochemistry
(IHC). To this end, as exemplified in part by Fig.
6, blood vessels in 4 different subcutaneous xenograft tumors
(A431, Calu-6, MLS and A549) were visualized using
both µCT and IHC, and morphological characteristics such
as vessel size, vessel distribution and vessel branching were
analyzed [12] Fig. 5. Overcoming multidrug-resistance (MDR) using nanomedicines.
A-B: Three different doxorubicin (Dox) -containing
nanomedicine formulations (polymers, liposomes and
micelles; B) were used to evaluate to the impact of drug
targeting on overcoming MDR, hypothesizing that nanomedicines
are more useful than free drugs for achieving target
site (nuclear) localization in vitro (A). C: Fluorescence microscopy
studies, confirming that the upregulation of MDRconferring
drug efflux pumps affects the cellular uptake of
free Dox more strongly than that of Dox-containing nanomedicines.
Dox: red. Nuclei: blue. Cell membranes: green.
. In addition, in vivo µCT imaging
was implemented to non-invasively assess
the relative blood volume (rBV) in these 4
tumors models. Upon comparing the results
obtained using µCT to those obtained
using IHC, which still is the golden standard
in (anti-)angiogenesis experiments, it was
found that the results obtained using both
Fig. 6: Visualization of tumor blood vessels in A549 (A,B,E)
and A431 (C,D,F) tumor xenografts using in vivo (A,C) and
ex vivo (B,D) micro-computed tomography and immunohistochemistry
(E-F). Arrows indicate degree of blood vessel
branching. Blood vessels are stained in green, α-SMA in
red and nuclei in blue.
2011
experimental procedures correlated very
well, with correlation coefficients far above
0.9 and p-values far below 0.05, indicating that
functional in vivo µCT imaging is a highly suitable
modality for non-invasively evaluating tumor
angiogenesis and the vascular response
to anti-angiogenic therapies.
Hybrid Imaging
Technologies
New system developments: The group Hybrid Imaging
Technology (HIT) has developed a new detector concept
for simultaneous Positron Emission Tomography (PET) and
Magnetic Resonance Imaging (MRI). The team succeeded in
applying this new detector technology in a preclinical PET/
MR scanner (see Fig. 7). The scanner is designed as an insert
for a human 3T MRI system [13] . The system was designed,
built, and tested within the timeframe of the EU FP7 project
HYPERImage and will be further optimized within the
NRW project ForSaTum. The new MR-compatible detector
stack uses analog and digital Silicon PhotoMultiplier (SiPM)
technology which further advances the performance (sub
nano-second coincidence resolution time) of future semiconductor
based PET system. The detector has been developed
in cooperation with the University of Heidelberg
(Prof. Peter Fischer) and the Fondazione Bruno Kessler
(Claudio Piemonte, PhD). The team has developed a new
data acquisition and control environment for this new generation
of digital PET scanners, which enables a purely SW
based data processing and thus the application of new iterative
algorithms, like self normalization and calibration [14] ,
or maximum likelihood crystal identification to improve the
image resolution and sensitivity [15] . A special gamma-transparent
Radio Frequency (RF) coil supporting simultaneous
PET/MR has been developed for imaging of animals with a
size up to rabbits [16] Fig. 7: Left: simultaneously acquired PET-, MR-, and fused
PET plus MR image. Right: preclinical PET/MR system
. The interference investigation using
the new MR-compatible PET modules finally shows no significant
performance degradation of PET and MRI during simultaneous
acquisition.
MR-based attenuation correction for hybrid PET/MRI systems:
Accurate gamma photon attenuation correction
(AC) is essential for quantitative PET/MRI as there is no
simple relation between MR image intensity and attenuation
coefficients. Attenuation maps (µ-maps) can be
[12] Ehling et al (in prep)
[13] Schulz et al, IEEE NSS, J2-05 (2011)
[14] Goldschmidt et al, IEEE NSS, MIC18.M-194 (2011)
[15] Lerche et al, IEEE NSS, MIC18.M-180 (2011)
[16] Truhn et al, Med Phys 38: 3995 (2011)

derived by segmenting MR images and assigning attenuation
values to the compartments. Ultra-short echo time
(UTE) sequences have been used to separate cortical bone
and air, and the Dixon technique has enabled distinguishing
soft and adipose tissues. Unfortunately, sequential application
of these sequences is time-consuming and complicates
image registration. Within the HIT we develop new
MR sequences and mathematical techniques to extract
the attenuation of the gamma photon out of the MR and
the PET data [17] . We recently proposed a UTE triple-echo
(UTILE) MR- sequence [18] Fig. 8: MRI pulse sequence diagram of our UTILE sequence
(left) with image processing flowchart (right)
combining UTE sampling for
bone detection and gradient echoes for Dixon water/fat
separation in a single-shot 3D acquisition (TE1/TE2/TE3/
TR = 0.09/1.09/2.09/4.1 ms at 3T), see Fig. 2. Thus the
UTILE MR- sequence enables the generation of MR-based
four-class µ-maps without anatomical priors, yielding results
more similar to CT-based ones than with three-class
segmentation only.
Translational Studies
The group translational studies focuses on the late preclinical
imaging and early translational research for monitoring
of tumor angiogenesis, predominantly in skin, breast,
kidney and liver cancer. In this regard, novel imaging techniques
are being developed and evaluated in preclinical animal
models. The group members are radiologists, biologists
and chemists. The main focus is on functional and molecular
ultrasound imaging using in-house prepared non-specific
as well as targeted ultrasound contrast agents. Additionally,
small animal imaging is being performed using MRI, optical
imaging and PET. To verify in vivo experiments, imaging data
is supplemented with immunohistochemical and other
biological methods.
Breast Cancer Imaging: Clinically translatable ultrasound
contrast agents are tested for their potential application on
humans. These contrast agents are well suited for characterizing
and distinguishing breast cancer models with different
angiogenesis and aggressiveness [19] . Further, the
molecular information alone is better suited to discriminate
differently aggressive tumor models compared to functional
information alone. We now focus on examining breast
cancer models during tumor growth and treatment using
molecular and functional ultrasound.
[17] Salomon et al, IEEE TMI 30: 804 (2011)
[18] Berker et al, J Nucl Med (in press)
[19] Bzyl et al, Eur Radiol 21: 1988 (2011)
[20] Rix et al, Eur J Radiol (in press)
2011
Helmholtz-Institute for Biomedical Engineering
RWTH Aachen University
Liver Imaging: In cooperation with
the group of Prof. Trautwein, transgenic
mice which spontaneously develop
liver fibrosis and hepatocellular
carcinoma are being examined using
ultrasound and MRI. The aim of these
studies is to investigate the potential
role of targeted ultrasound contrast
agents for assessment of liver dysplasia
compared to the gold standard
MRI.
Kidney Imaging: In cooperation with Prof. Dr. Koesters,
transgenic mice which spontaneously develop renal cell
cancer are being examined using ultrasound and CT. The
aim of these studies is to investigate the potential role of
novel ultrasound contrast agents for the characteritzation
of renal cell cancer.
Development of
Novel Imaging
Probes and Techniques:
For ultrasoundimaging,
2D and 3D
Doppler and
B-mode based imaging
approaches
have been established
[20] . Novel
tumor specific
contrast agents
which are being
synthesized,
characterized and
tested in vitro and
in vivo.
Acknowledgements
This work was supported by
• European Commission (FP7)
• German Research Foundation (DFG)
• German Federal Ministry of Education and Research
(BMBF)
• HighTech.NRW
• START
• Bracco
Awards
Fig. 9: 3D-Reconstruction of a tumor,
used to facilitate functional and molecular
ultrasound imaging.
• Dennis Doleschel, Jabaduraj Jayapaul, Dr. Zhe Liu:
WMIC Travel Grant
• Felix Gremse: Preis für Wissenstransfer der
Medizinischen Gesellschaft Aachen
• Dr. Twan Lammers: DGBMT-Klee prize for
Biomedical Engineering (2nd place)
• Dr. Twan Lammers: International Journal of
Nanomedicine Early Career Award
Experimental Molecular
Imaging
39

Experimental Molecular
Imaging
40
Helmholtz-Institute for Biomedical Engineering
RWTH Aachen University
Most relevant Publications:
[1.] Berker Y, Franke J, Salomon A, Palmowski M, Donker H, Temur Y,
Mottaghy F, Kuhl C, Izquierdo D, Fayad Z, Kiessling F, Schulz V. MRbased
attenuation correction for hybrid PET/MRI systems: A fourclass
tissue segmentation technique using a combined ultrashort echo
time (UTE)/Dixon MR sequence. J Nucl Med (in press)
[2.] Bzyl J, Lederle W, Rix A, Grouls C, Tardy I, Pochon S, Siepmann M,
Penzkofer T, Schneider M, Kiessling F, Palmowski M. Molecular and
functional ultrasound imaging in differently aggressive breast cancer
xenografts using two novel ultrasound contrast agents (BR55 and
BR38). Eur Radiol 2011;21:1988-1995
[3.] Crielaard B, Yousefi A, Schillemans J, Vermehren C, Buyens K, Braekmans
K, Lammers T, Storm G. An in vitro assay based on surface plasmon
resonance to predict the in vivo circulation kinetics of liposomes.
J Control Release 2011;156:307-314
[4.] Doleschel D, Mundigl O, Wessner A, Gremse F, Bachmann J, Rodriguez
A, Klingmüller U, Jarsch M, Kiessling F, Lederle W. Targeted
near-infrared imaging of the erythropoietin receptor in human lung
cancer xenografts. J Nucl Med 2011 (in press)
[5.] Fokong S., Siepmann M., Liu Z., Schmitz G., Kiessling F., Gätjens J. Advanced
characterization and refinement of poly n-butyl cyanoacrylate
(PBCA) microbubbles for ultrasound imaging. Ultrasound Med Biol
2011;37:1622-1634
[6.] Gremse F, Grouls C, Palmowski M, Vries A, Gruell H, Das M, Mühlenbruch
G, Akhtar S, Schober A, Kiessling F. Virtual Elastic Sphere
Processing Enables Reproducible Quantification of Vessel Stenosis in
CT and MR Angiographies. Radiology 2011;260:709-717
[7.] Huis In ‘t Veld R, Storm G, Hennink W, Kiessling F, Lammers T. Macromolecular
nanotheranostics for multimodal anticancer therapy. Nanoscale
2011;4:4022-4034
[8.] Jayapaul J, Hodenius M, Arns S, Lederle W, Lammers T, Comba P,
Kiessling F, Gaetjens J. FMN-coated fluorescent iron oxide nanoparticles
for RCP-mediated targeting and labeling of metabolically active
cancer and endothelial cells. Biomaterials 2011;32:5863-5871
[9.] Kiessling F, Gaetjens J, Palmowski M. Application of Molecular
Ultrasound for Imaging Integrin Expression. Theranostics
2011;1:127-134
Team
2011
[10.] Kiessling I, Bzyl J, Kiessling F. Molecular ultrasound imaging and its
potential for paediatric radiology. Pediatr Radiol 2011;41:176-84
[11.] Lammers T, Aime S, Hennink W, Storm G, Kiessling F. Theranostic
Nanomedicines. Acc Chem Res 2011;44:1029-1038
[12.] Lammers T, Kiessling F, Hennink W, Storm G. Drug targeting to
tumors: Principles, pitfalls and (pre-)clinical progress. J Control
Release (in press)
[13.] Lederle W, Depner S, Schnur S, Obermueller E, Catone N, Just
A, Fusenig NE, Mueller MM. IL-6 promotes malignant growth of
skin SCCs by regulating a network of autocrine and paracrine cytokines.
Int J Cancer 2011;128:2803-2814.
[14.] Liehn E, Tuchscheerer N, Kanzler I, Drechsler M, Fraehmos L,
Schuh A, Koenen R, Zandler S, Soehnlein O, Hristov M, Grigorescu
G, Urs A, Leabu M, Bucur I, Merx M, Zernecke A, Ehling J,
Gremse F, Lammers T, Kiessling F, Bernhagen J, Schober A, Weber
C. Double-edged role of the CXCL12-CXCR4 axis in experimental
myocardial infarction. J Am Coll Cardiol 2011;58:2415-2423
[15.] Liu Z, Lammers T, Ehling J, Fokong S, Bornemann J, Kiessling F,
Gätjens L Iron oxide nanoparticle-containing microbubble composites
as contrast agents for MR and ultrasound dual-modality
imaging. Biomaterials 2011;32:6155-6163
[16.] Rix A, Lederle W, Siepmann M, Fokong S, Behrendt FF, Bzyl J,
Grouls C, Kiessling F, Palmowski M. Evaluation of high frequency
ultrasound methods and contrast agents for characterising tumor
response to anti-angiogenic treatment. Eur J Radiol 2011 (in
press)
[17.] Salomon A, Goedicke A, Schweizer B, Aach T, Schulz V. Attenuation
maps for PET/MR uing using simultaneous reconstruction. IEEE
Transaction on Medical Imaging. 2011;30:804-813
[18.] Truhn D, Kiessling F, Schulz V. Optimised RF Shielding Techniques for
Simultaneous PET/MR. Med Phys 2011;38:3995-4000
[19.] Wiessler M, Hennrich U, Pipkorn R, Waldeck W, Cao L, Peter J,
Ehemann V, Semmler W, Lammers T, Braun K. Theranostic cRGD-
BioShuttle Constructs Containing Temozolomide- and Cy7 For NIR-
Imaging and Therapy. Theranostics 2011;1:381-394
[20.] Xiao L, Li J, Brougham D, Fox E, Feliu N, Bushmelev A, Schmidt A,
Mertens N, Kiessling F, Fadeel B, Mathur S. Water-Soluble Superparamagnetic
Magnetite Nanoparticles with Biocompatible Coating
for Enhanced Magnetic Resonance Imaging (MRI). ACS Nano
2011;5:6315-6324