Contrast Agents for CT-3 and Next Generation CT Techniques.
Contrast Agents for CT-3
Next Generation CT Techniques
Examples of plasmonic GNPs: 16-nm Au nanospheres; gold nanorodsand 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; plasmonicnanopowders of gold nanospheres, nanorods, nanostars, and Au-Ag nanocages.
Spectral tuning of gold nanorods with silver coatings and Au-Ag nanocages across vis-NIR spectral bands and of gold nanorods and SiO2/Au nanoshells across red-NIR spectral bands. nanoroddiameter (d) and length (L), nanocage edge length L and wall thickness (s), nanoshell outer diameter (d) and gold shell thickness (s).
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).
Kinetics of suspension laser heating for SiO2/Au nanoshells, Au nanorods, and Au-Ag nanocages.
Au-Ag nanocages and nanocomposites (nanocageswith 50-nm silica coatings). Suspensions were irradiated by a diode laser at a power density of 2 W/cm2 and a wavelength of 810 nm, which was close to the plasmon resonance wavelengths of all three particle types: SiO2/Au nanoshells (core diameter of 160 nm, shell thickness of 20 nm), Au nanorods (length of 40 nm, diameter of 12 nm), and Au-Ag nanocages (edge length of 54 nm).
(a) Xenografted tumor (implanted rat liver cancer cells PC-1) after the administration of AuNRs/SiO2-HP nanocomposites at a dose 400 μg of gold directly to the tumor before irradiation. (b) The tumor after simultaneous 20-min exposure of 633-nm CW He-Ne laser (160 mW/сm2) and 808-nm CW NIR laser (2.2 W/сm2). (c) 72 h after combined irradiation.
ActivatableTheranostic Gold Nanoparticle
Matrix metalloproteinase (MMP) activatable gold nanoparticles for dual CT/optical imaging probes.
CT image (middle) and NIR fluorescence image (right) of the tumor-bearing mouse 24 h after injection of the nanoparticles.
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
In vivo micro-CT volume reconstructions post–injection polyethyleneglycol
5000 coated Bi2S3 nanoparticles that do not contain a peptide label.
X-ray CT images of tumor-bearing mouse immediately (a), 2 h (b), 4.5 h (c), and 24 (d) after injection of Bi2S3nanoparticles labeled with LyP-1.
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 X-ray 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 outer-shell electrons, producing a characteristic X-ray (Photoelectron effect).
(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.
Mass attenuation coefficients of several materials as function of X-ray energy
Excitation of a 1s electron occurs at the K-edge, while excitation of a 2s or 2p electron occurs at an L-edge
Spectral CT with Energy-Resolving Detector
Energy-resolving detectors discriminate colors
Spectral CT with energy-resolving detector is like the human eye at day
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
Patient presented at ER with chest pain
Stress Test/ Hospitalization
Cardiac CT angiography (CCTA)
Surplant invasive diagnostic cardiac catheterization with a quicker, noninvasive, lower cost procedure
Detecting Atherosclerotic Plaque
Clinical Significance of Spectral CT
Nanobeacons target fibrin of thrombus on ruptured plaque
non-separated attenuation from nanoparticle and Ca
Selective imaging of nanoparticles
Quantitative Tissue Differentiation
Targeted bismuth nanocolloids distinguishes fibrin microdeposits from calcium
Human Coronary phantom
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).
Calciumred& Bismuth Gold)
Soft tissue invisible due to low X-ray attenuation
Pan et. al. AngewChemInt Ed. 9635-9639 (2010)
Pan, Schirra et al., ACS Nano. 2012 Apr 24;6(4):3364-70
Pan, Schirra et al., ACS Nano. 2012 Apr 24;6(4):3364-70
Micro-CT image of a mouse bearing tumor cells that are visualized using Qdot/Ba-nanoparticle-conjugated tumor-targeting 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.
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.
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.
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.
Color Coding of Contrast Material/Virtual Non-Contrast Images
The ability to map iodine content in soft tissue organs can be used to study the contrast enhancement of focal lesions, e.g. in the liver or kidney.
The CT scan is obtained in normal venous phase. The iodine-related enhancement is color-coded in the image and superimposed with the normal CT image.
Additionally, a virtual non-contrast image can be derived from the contrast picture.
Differentiation of Tendons and Ligaments
Tendons and ligaments have weak spectral properties, presumably due to the densely packed collagen.
It is possible to identify thick tendons and ligaments in Dual Energy CT datasets and to display them separately, for example, to visualize the tendons of the wrist and identify ruptures.
However, signal-to-noise ratio is not sufficient to depict thin ligaments; thus the clinical value of this application is limited.