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Contrast Agents for CT-3 and Next Generation CT Techniques

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Presentation on theme: "Contrast Agents for CT-3 and Next Generation CT Techniques"— Presentation transcript:

1 Contrast Agents for CT-3 and Next Generation CT Techniques

2 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.

3 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. nanorod diameter (d) and length (L), nanocage edge length L and wall thickness (s), nanoshell outer diameter (d) and gold shell thickness (s).


5 Dendrimer-entrapped Gold Nanoparticle
Schematic illustration of the preparation of dendrimer-entrapped gold nanoparticles.


7 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).

8 Shuming Nie

9 Kinetics of suspension laser heating for SiO2/Au nanoshells, Au nanorods, and Au-Ag nanocages.
Au-Ag nanocages and nanocomposites (nanocages with 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).

10 (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.

11 Activatable Theranostic Gold Nanoparticle
NIR 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.

12 Theranostic Gold Nanoparticle

13 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

14 X-ray CT images of tumor-bearing mouse immediately (a), 2 h (b), 4
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.

15 Serial CT Imaging

16 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).

17 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.

18 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.

19 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

20 Spectral CT with Energy-Resolving Detector
Energy-resolving detectors discriminate colors Total attenuation energy Compton Scatter Photo-electric Spectral CT with energy-resolving detector is like the human eye at day

21 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. Traditional anatomical CT is evolving toward multicolored or spectral CT, which has the potential to detect and quantify intraluminal fibrin presented by ruptured plaque Philips Research, Hamburg, DE Relevant Patents: US ; (Philips)

22 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 Plaque Coronary CT Angio Detecting Atherosclerotic Plaque

23 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. Negative predictive value of CT angiography established early (non- reimbursable) Poor anatomic correlation with cath Cost Inability to separate coronary Ca

24 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 Methods and Results: Bismuth (NanoKB) and gold (NanoKA) (~185±20 nm) polysorbate nanocolloids containing 50 and 4 v/v% metal content were prepared. NanoKB targeted to fibrin acellular phantoms and human carotid specimens revealed high contrast signal and intravascular constraint. Anti-human fibrin NanoKB was targeted to rabbit thrombus and imaged. Spectral CT readily detected the NanoKB bound at physiologic fibrin presentation density. In a second study, the total bioelimination of bismuth from mice (n=6) injected IV was studied. Weekly analysis by ICP revealed that 95% of the metal was cleared in 7 days and more 96% at 14 days (p<0.05). Further image reconstruction research comparing iterative versus classic filtered back projection techniques improved signal to noise (SNR) by greater than 5 fold (p<0.05) in a series of in vitro phantom studies. Utilizing this reconstruction improvement, NanoKA, containing only 4% gold (v/v) was developed and detected with high contrast when bound to fibrin. NanoKA utilized only 1/10th of the metal in NanoKB. Conclusions: The expansion of new agents, the rapid bioelimination of injected heavy metals in parallel with improved Spectral CT imaging technique, and the related X-ray dose reduction opportunity continue to encourage the advancement of this technology to the ED where quick differentiation of patients with chest pain due to coronary plaque rupture from others with noncoronary sources of symptoms will markedly change our medical evaluation paradigm. Mice (n=2/time point) were injected via tail vein; The whole animal (ground in toto), microwave digested, and analyzed by ICP-OES.

25 Human Coronary phantom
Quantitative Tissue Differentiation Targeted bismuth nanocolloids distinguishes fibrin microdeposits from calcium Specimen removal Carotid Enderectamy Calcium red & Bismuth Gold) Soft tissue invisible due to low X-ray attenuation Local Bi-conc ~0.1 g/cm3 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). Ca-separated Pan et. al. Angew Chem Int Ed (2010)

26 Ytterbium Nanocolloids for Multicolor CT
Simultaneous Data Acquisition for Perfect Image Registration Pan, Schirra et al., ACS Nano Apr 24;6(4):

27 PET-Like “Hot Spot” Imaging with Spectral CT
Simultaneous Data Acquisition for Perfect Image Registration Pan, Schirra et al., ACS Nano Apr 24;6(4):

28 Micro-CT image of a mouse bearing tumor cells that are visualized using Qdot/Ba-nanoparticle-conjugated tumor-targeting antibodies

29 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. Xenon Broncheography

30 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.


32 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)

33 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.

34 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. 

35 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.

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