Molecular Contrast Agents for CT
and
Next Generation CT Techniques
MEng in Bioinstrumentation
Examples of plasmonic GNPs: 16-nm Au nanospheres; gold nanorods and gold
nanorods with silver coatings (inset); SiO2/Au nanoshells; gold nanostars; silver
nanocubes and Au-Ag nanocages obtained from them (insets); nanocomposites
containing a gold nanorod or nanocage core and a mesoporous silica shell doped
with hematoporphyrin; hollow mesoporous silica spheres and nanorattles
containing gold nanocages; plasmonic nanopowders of gold nanospheres,
nanorods, nanostars, and Au-Ag nanocages.
Dendrimer-entrapped Gold Nanoparticle
Schematic illustration of the preparation of
dendrimer-entrapped gold nanoparticles.
Anti-CD-4-Targeted Gold Nanoparticles
CT images of mice before (a, b) and after (c, d) injection of gold nanoparticles. While little
contrast enhancement is observed for the mouse administered with nonspecific
immunoglobulin G (IgG)-conjugated nanoparticles (a, c), anti-CD-4-targeted nanoparticles
show clear contrast enhancement of inguinal lymph nodes (c, d).
Targeted Bismuth Nanoparticles
Bismuth sulfide (Bi2S3) nanoparticles labeled with the cyclic nine amino acid peptide,
CGNKRTRGC (LyP-1)-targeted to 4T1 breast cancer in mice
X-ray CT images of tumor-bearing mouse
immediately (a), 2 h (b), 4.5 h (c), and 24 (d)
after injection of Bi2S3 nanoparticles labeled
with LyP-1.
In vivo micro-CT volume reconstructions
post–injection polyethylene glycol
5000 coated Bi2S3 nanoparticles that do
not contain a peptide label.
Serial CT Imaging
Interactions of X-ray with matters
(i) A portion of X-rays is transmitted without interaction.
(ii) The energy of the incident X-ray is absorbed by an atom, and then X-ray with
the same energy is emitted with a random direction (Coherent scattering).
(iii) When the incident X-ray collides with outer-shell electrons, a portion of the Xray energy is transferred to the electron, and the X-ray photon is deflected with
a reduced energy (Compton scattering).
(iv) When the incident X-ray transfers its energy to inner-shell electron, the electron
is subsequently ejected, and the vacancy of the electron shell is filled by outershell electrons, producing a characteristic X-ray (Photoelectron effect).
Spectra CT
(a) Schematic drawing of third-generation CT. CT images are acquired during the rotation of
an X-ray tube and an array of detectors. (b) Schematic attenuation profiles of voxels.
Measured X-ray intensity can be expressed as sum of the attenuation along the path of X-ray.
Advanced Detector Technology
Energy discriminating photon counting detectors
Spectral/multi energy
CT has the potential to
distinguish different
materials by K-edge
characteristics.
K-edge imaging involves
the two energy bins on
both sides of a K-edge.
11
Mass attenuation coefficients of several
materials as function of X-ray energy
Excitation of a 1s electron occurs at the Kedge, while excitation of a 2s or 2p electron
occurs at an L-edge
12
Spectral CT with Energy-Resolving Detector
Energy-resolving detectors discriminate colors
Spectral CT with energy-resolving detector is like
the human eye at day
Total attenuation
Compton Scatter
Photo-electric
energy
Emerging Opportunities with Spectral CT
Multicolored or
spectral CT has the
potential to detect and
quantify intraluminal
fibrin presented by
ruptured plaque in the
context of CT
angiograms all without
calcium interference.
Philips Research, Hamburg, DE
Relevant Patents: US20110096892;
20110096905 (Philips)
Diagnosis of Chest Pain of Cardiac Origin
Diagnostic Imaging – Treatment Planning –
Intervention Guidance
Symptoms
Patient presented at ER
with chest pain
Early Diagnosis
Stress Test/ Hospitalization
Diagnosis
Cardiac CT angiography
(CCTA)
Surplant invasive
diagnostic cardiac
catheterization with a
quicker, noninvasive,
lower cost procedure
Coronary
CT Angio
Plaque
Detecting
Atherosclerotic
Plaque
Clinical Significance of Spectral CT
• CORE-64 at the AHA
scientific sessions (2007),
noninvasive 64-slice MDCT
angiography was reported to
have a 91% positive and 83%
negative predictive value in a
large multicenter trial: 89/405
patients were excluded due to
high calcium scores
• Poor anatomic correlation
between CCTA and Cath.
wiki.medpedia.com/Coronary_Calcium_Scan
Negative predictive value of CT angiography
established early (non- reimbursable)
• Poor anatomic correlation with cath
• Cost
• Inability to separate coronary Ca
Coronary Thrombus Imaging by Spectral CT
Nanobeacons target fibrin of thrombus on ruptured
plaque
Fibrin
• Nanobeacons (Au, Bi,…) bind to fibrin
• Conventional CT is unable to selectively
image materials
• Spectral CT enables material specific
imaging of suitable metals
• New Nanobeacons and advances in
statistical image reconstruction methods
improve coronary fibrin imaging
Ca deposit
Plaque formation
non-separated
attenuation from
nanoparticle and Ca
Selective imaging of
nanoparticles
Quantitative Tissue Differentiation
Targeted bismuth nanocolloids distinguishes fibrin
microdeposits from calcium
Hospitaltour.com
Spectral CT
image of a
fibrin clot
phantom
with
embedded
calcium
chloride
(white
arrow)
targeted
(green
arrow) in a
glass tube
(blue arrows
denote wall).
Calcium
red &
Bismuth
Gold)
Soft tissue
invisible
due to low
X-ray
attenuation
Ca-separated
Pan et. al. Angew Chem Int Ed. 9635-9639 (2010)
Ytterbium Nanocolloids for Multicolor CT
Simultaneous Data Acquisition for Perfect Image
Registration
Pan, Schirra et al., ACS Nano. 2012 Apr 24;6(4):3364-70
PET-Like “Hot Spot” Imaging with Spectral CT
Simultaneous Data Acquisition for Perfect Image Registration
Pan, Schirra et al., ACS Nano. 2012 Apr 24;6(4):3364-70
Spectral CT identifies area of high
macrophage activity with Au-HDL contrast
Visualize the Au-HDL along with the iodinated contrast agents and calcified structures in the same scan.
Offers the potential to simultaneously acquire information on stenosis, calcification, and inflammation,
three valuable parameters of plaque characterization.
CT techniques require both a pre-injection image and a post-injection image that must be compared—
Spectral CT is sufficiently sensitive that it requires only one post-injection image and therefore has
potential to use lower doses of contrast.
Contrast agents are visible and there is no need for a contrast pre- and post- because there is no
[background] iodine or gold in the body
Micro-CT image of a mouse bearing tumor cells that are
visualized using Qdot/Ba-nanoparticle-conjugated tumortargeting antibodies
K-edge subtraction imaging (KES)
In
K-edge
subtraction
imaging
(KES),
two
simultaneous CT images are
acquired using two x-ray
beams at two different
energies above and below
the K-edge of Xe.
Xenon Broncheography
Absolute quantity of the CA
is determined directly on
any given point of a lung CT
image after subtracting
these two images on a
logarithmic scale.
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Dual Energy CT
The Selective Photon Shield ensures dose neutrality by eliminating spectral overlap.
This makes Dual Energy as dose-efficient as any single 120 kV scan.
• During a Dual Source Dual Energy scan,
two CT datasets are acquired
simultaneously with different kV and
mA levels, allowing to visualize
differences in the energy-dependence
of the attenuation coefficients of
different materials.
• These images are combined and
analyzed to visualize information about
anatomical and pathological
structures.
http://www.healthcare.siemens.com/computed-tomography/technologies-innovations/ct-dual-energy/technical-specifications
One Basic Reason for Use of Dual Energy CT: Material Differentiation
• By scanning a patient at two different energy spectra (e.g. at 56 kV
and 76 kV), the attenuation difference of the same material is
different.
• Iodine has higher attenuation difference, compared to bone.
• Scanning allows the computer to process bone and iodine content on
images differently.
Routine Use of Dual-energy CT for Material Differentiation
• Creation of 3D vascular images ("Direct Angio") by easy removal of
bony structures
• Plaque analysis (calcified vs. soft plaques)
• Lung perfusion
• Virtual unenhanced scan (creation of unenhanced scan from
enhanced images by deleting iodine content from the images)
• Calculi characterization (uric acid vs. others)
Dual Energy in Angiography
Use the spectral properties of iodine to
differentiate it from other dense materials in the
dataset (similar to magnetic resonance
angiography (MRA)).
With Dual Energy CT, it is possible to identify
bone by its spectral behavior and to erase it from
an angiogram. Then, the iodine in the vessels
remains the only dense material in the dataset
and a MIP can be calculated from a CT angiogram
to closely resemble an MRA.
Additionally, it is possible to detect those voxels
that contain both calcium and iodine and add
them back to the dataset.
Calcified plaques of atherosclerotic vessels can
thereby be switched on and off in the dataset to
visualize both the residual lumen and the plaque
distribution.
http://www.dsct.com/index.php/clinical-applications-dual-energy-ct/