Functional imaging of tumor vasculature using iodine and gadolinium-based nanoparticle contrast agents: a comparison of spectral micro-CT using energy integrating and photon counting detectors

Badea, Cristian T.; Clark, Darin P.; Holbrook, Matthew; Srivastava, Mayank; Mowery, Yvonne M.; Ghaghada, Ketan B.

doi:10.1088/1361-6560/ab03e2

Cited by 57 publications

(50 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The absorbed radiation dose associated with imaging was ∼190 mGy (vs. ∼170 mGy for our 4D EID-CT imaging protocols [19]). These doses are comparable to many commercial micro-CT scanners when reconstructing 10 cardiac phases [20], and are consistent with our previous results showing dose benefits associated with four-threshold, PCD-based spectral imaging over DE EID-CT [21]. Notably, additional PCD dose optimizations (e.g.…”

Section: Methodssupporting

confidence: 89%

“…Following previous work [6, 21], material decomposition was calibrated by scanning a 3D-printed, physical calibration phantom using data acquisition parameters identical to the in vivo data. The phantom has similar dimensions to a mouse and cradle (3.8 cm diameter) and is made from the same material as the mouse cradle used during CT scanning (polylactic acid, PLA).…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Photon-counting cine-cardiac CT in the mouse

Clark

Holbrook

Lee

et al. 2019

Preprint

Self Cite

View full text Add to dashboard Cite

12The maturation of photon-counting detector (PCD) technology promises to 13 enhance routine CT imaging applications with high-fidelity spectral information. In this 14 paper, we demonstrate the power of this synergy and our complementary reconstruction 15 techniques, performing 4D, cardiac PCD-CT data acquisition and reconstruction in a 16 mouse model of atherosclerosis, including calcified plaque. Specifically, in vivo cardiac 17 micro-CT scans were performed in four ApoE knockout mice, following their development 18 of calcified plaques. The scans were performed with a prototype PCD (DECTRIS, Ltd.) 19 with 4 energy thresholds. Projection sampling was performed with 10 ms temporal 20 resolution, allowing the reconstruction of 10 cardiac phases at each of 4 energies (40, 3D 21 volumes per mouse scan). Reconstruction was performed iteratively using the split 34 detected during slow moving phases of the cardiac cycle. Given these preliminary results, 35 we believe that PCD technology will enhance dynamic CT imaging applications with high-36 fidelity spectral and material information. 37 42 Philips (dual-layer). These DE scanners are associated with several routine imaging 43 applications, including plaque differentiation, myocardial perfusion, and kidney stone 44 characterization [5]. Preclinically, spectral CT has been utilized in several additional 3 45 applications, including differential imaging of vasculature and vascular permeability in 46 sarcoma [6] and lung [7] tumors, and with several preclinical contrast agents based on 100 gene [22], show a marked increase in total plasma cholesterol levels, and are prone to 101 develop atherosclerotic lesions [23]. At 8-12 weeks of age, the ApoE-/-mice were 102 exposed to 25 fractions of 2 Gy partial-heart irradiation, mimicking cardiac radiation 103 exposure of breast cancer patients treated with radiation therapy [24]. After irradiation, 104 the mice were kept on a regular diet for a year prior to imaging. Three days before 105 imaging, the mice were intravenously injected with gold nanoparticle contrast agent (15 106 nm AuroVist, www.nanoprobes.com) at a dose of 0.004 mL/g mouse, with gold 107 accumulation expected at the site of any myocardial injury [24]. Notably, with an 80 kVp 108 source spectrum, K-edge imaging of gold (edge at 80.7 keV) was not possible. Three 109 days later, immediately prior to imaging, the same mice were injected with a liposomal 110 iodinated contrast agent (described in [8]; 0.012 mL/g mouse) to measure cardiac 111 functional metrics. The free-breathing mice were scanned while under anesthesia 112 induced with 1-2% isoflurane delivered by nose cone. Both ECG and respiratory signals 6 113 were recorded during scanning (average heart rate: 448 ± 50 bpm; average respiratory 114 rate: 142 ± 19 breaths/min.). The ECG signal was used for retrospective projection 115 weighting during reconstruction. Respiratory gating was not performed. 116 Multi-channel image reconstruction 117Following from our past work on data-adaptive, iterative reconstruc...

show abstract

Section: Methodssupporting

confidence: 89%

Section: Methodsmentioning

confidence: 99%

Photon-counting cine-cardiac CT in the mouse

Clark

Holbrook

Lee

et al. 2019

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…These included tumor volume and tumor CT attenuation in delayed CT (CTD) and CTA scans. Tumor fractional blood volume was determined as [Tumor CT attenuation CTA − Tumor CT attenuation CTD ]/[Blood CT attenuation CTA − Blood CT attenuation CTD ], wherein CTA and CTD refers to CT angiogram and delayed CT scans (40). ROIs drawn in the inferior vena cava was used for CT attenuation in blood.…”

Section: Image and Radiomic Analysismentioning

confidence: 99%

Detection of response to tumor microenvironment–targeted cellular immunotherapy using nano-radiomics

et al. 2020

View full text Add to dashboard Cite

Immunotherapies, including cell-based therapies, targeting the tumor microenvironment (TME) result in variable and delayed responses. Thus, it has been difficult to gauge the efficacy of TME-directed therapies early after administration. We investigated a nano-radiomics approach (quantitative analysis of nanoparticle contrast–enhanced three-dimensional images) for detection of tumor response to cellular immunotherapy directed against myeloid-derived suppressor cells (MDSCs), a key component of TME. Animals bearing human MDSC-containing solid tumor xenografts received treatment with MDSC-targeting human natural killer (NK) cells and underwent nanoparticle contrast–enhanced computed tomography (CT) imaging. Whereas conventional CT-derived tumor metrics were unable to differentiate NK cell immunotherapy tumors from untreated tumors, nano-radiomics revealed texture-based features capable of differentiating treatment groups. Our study shows that TME-directed cellular immunotherapy causes subtle changes not effectively gauged by conventional imaging metrics but revealed by nano-radiomics. Our work provides a method for noninvasive assessment of TME-directed immunotherapy potentially applicable to numerous solid tumors.

show abstract

“…In order to be used as contrast agents with SPCCT, Gadolinium based systems must (i) be highly stable, (ii) contain a high amount of element for a better imaging, and (iii) show a blood half-life long enough to allow perfusion imaging. Recent development reports the use of molecularly based contrast media 22 . However as previously pointed out, the requirements on such technology, in particular the local concentration and the stability towards Gd 3+ release, led us to investigate the potential of hybrid nanoparticles with high gadolinium loading and stable inorganic core.…”

Section: Introductionmentioning

confidence: 99%

Hybrid Nano-GdF3 contrast media allows pre-clinical in vivo element-specific K-edge imaging and quantification

Halttunen

Lerouge

Chaput

et al. 2019

Sci Rep

View full text Add to dashboard Cite

Computed tomography (CT) is a widely used imaging modality. Among the recent technical improvements to increase the range of detection for optimized diagnostic, new devices such as dual energy CT allow elemental discrimination but still remain limited to two energies. Spectral photon-counting CT (SPCCT) is an emerging X-ray imaging technology with a completely new multiple energy detection and high spatial resolution (200 μm). This unique technique allows detection and quantification of a given element thanks to an element-specific increase in X-ray absorption for an energy (K-band) depending on its atomic number. The main contrast media used hitherto are iodine-based compounds but the K-edge of iodine (33.2 keV) is out of the range of detection. Therefore, it is crucial to develop contrast media suitable for this advanced technology. Gadolinium, well known and used element for MRI, possess a K-edge (50.2 keV) well suited for the SPCCT modality. The use of nano-objects instead of molecular entities is pushed by the necessity of high local concentration. In this work, nano-GdF 3 is validated on a clinical based prototype, to be used as efficient in vivo contrast media. Beside an extremely high stability, it presents long lasting time in the blood pool allowing perfusion imaging of small animals, without apparent toxicity.

show abstract

Functional imaging of tumor vasculature using iodine and gadolinium-based nanoparticle contrast agents: a comparison of spectral micro-CT using energy integrating and photon counting detectors

Cited by 57 publications

References 36 publications

Photon-counting cine-cardiac CT in the mouse

Photon-counting cine-cardiac CT in the mouse

Detection of response to tumor microenvironment–targeted cellular immunotherapy using nano-radiomics

Hybrid Nano-GdF3 contrast media allows pre-clinical in vivo element-specific K-edge imaging and quantification

Contact Info

Product

Resources

About