Thorsten R. Fleiter

Syntheses and Characterization of Lisinopril-Coated Gold Nanoparticles as Highly Stable Targeted CT Contrast Agents in Cardiovascular Diseases

Lisinopril was used as the targeting moiety to prepare gold nanoparticle-based functional CT contrast agents. Pure lisinopril, thioctic acid-lisinopril conjugate, and reduced thioctic acid-lisinopril conjugate were used to obtain GNP-Lis, GNP-TA-Lis, and GNP-RTA-Lis, respectively, via ligand exchange reaction on citrate-coated gold nanoparticles (GNPs). These lisinopril-decorated GNPs were fully characterized, and their chemical stabilities in biological relevant media and in high salt concentration were compared. Their relative stabilities toward lyophilization and against cyanide-induced decomposition were also investigated. Because of their higher stability, GNP-TA-Lis were used to assess the targeting of angiotensin converting enzyme (ACE) using X-ray computed tomography (CT). The images obtained displayed high contrast in the region of the lungs and heart, clearly indicating the targeting of ACE, whose overexpression is associated with development of cardiac and pulmonary fibrosis. Thus, the new nanoprobes prepared here will serve as very useful tools for the monitoring of cardiovascular pathophysiologies using CT imaging.

Spectral coronary multidetector computed tomography angiography: dual benefit by facilitating plaque characterization and enhancing lumen depiction.

Objective: To assess ex vivo specimens of atherosclerotic coronary arteries by dual energy (DE) multidetector computed tomography (MDCT) imaging, and to correlate depicted vessel lumen morphology and detected tissue characteristics with histopathologic analysis. Methods: Coronary arteries were imaged on a 16-slice MDCT using a DE protocol consisting of a 90- and 140-kV scan. Coronary arteries were perfused with iodine- and gadolinium-based contrast agents. The DE K-edge subtractions were performed. Regions-of-interest were placed on histopathologically/radiographically-matched vascular lumen and wall, fibromuscular and calcified plaque, and fat tissues. Vascular/tissue contrast-to-noise ratios (CNR) were calculated, and their dependence on tissue type and contrast agent type was statistically evaluated. Results: Tissue CNR analysis confirmed that all tissue types were successfully distinguished. Vascular wall and fibromuscular plaque achieved a significant increase in CNR ratios when DE techniques were used compared with 140 kV protocols. Conclusions: Spectral DE MDCT imaging of ex vivo atherosclerotic coronary arteries allows successful tissue characterization and enhances depiction of coronary lumen.

Magnetic resonance imaging versus multislice computed tomography of thoracic aortic endografts.

Purpose: To compare the potential of magnetic resonance imaging (MRI) to multislice computed tomography (CT) for evaluating stent-graft placement in the thoracic aorta. Methods: Susceptibility artifacts in 2 different stent-graft systems (Talent and Excluder) were evaluated in vitro in 2 angulations (straight and 33° curved) using 3 different MRI gradient echo sequences (True FISP, 2-dimensional FLASH, and 3-dimensional Turbo FLASH). The size of the stent-related artifact was measured, and the relative stent lumen was calculated. In vivo stent demarcation, stent patency, and additional findings were determined in 13 patients (3 Talent, 9 Excluder, and 1 combined) and compared to CT findings. Results: In vitro, both endograft systems proved to be MR compatible, with the relative stent lumen value ranging from 82% to 100% in the straight configuration; in a curved model, the relative stent lumen value ranged from 56% to 92% with the 3D Turbo FLASH sequence, which provided the smallest susceptibility artifacts. The Excluder endoprosthesis caused significant signal inhomogeneity within the stent in a curved configuration. In vivo, MRI and multislice CT showed similar results, with CT imaging slightly superior in stent demarcation and MRI better in demonstrating thrombus. CT beam hardening artifacts were pronounced in the Talent system, while the Excluder device caused significant signal inhomogeneity within the stent on magnetic resonance angiography. Conclusions: Multislice CT and contrast-enhanced MRI are fast, reliable means of providing all relevant information for surveillance of fully MR-compatible stent-grafts in the thoracic aorta.

Targeted in-vivo computed tomography (CT) imaging of tissue ACE using concentrated lisinopril-capped gold nanoparticle solutions

The development of cardiac and pulmonary fibrosis have been associated with overexpression of angiotensin-converting enzyme (ACE). Moreover, ACE inhibitors, such as lisinopril, have shown a benificial effect for patients diagnosed with heart failure or systemic hypertension. Thus targeted imaging of the ACE is of crucial importance for monitoring of the tissue ACE activity as well as the treatment efficacy in heart failure. In this respect, lisinopril-capped gold nanoparticles were prepared to provide a new type of probe for targeted molecular imaging of ACE by tuned K-edge computed tomography (CT) imaging. Concentrated solutions of these modified gold nanoparticles, with a diameter around 16 nm, showed high contrast in CT imaging. These new targeted imaging agents were thus used for in vivo imaging on rat models.

Dual-Energy CT in Enhancing Subdural Effusions that Masquerade as Subdural Hematomas: Diagnosis with Virtual High-Monochromatic (190-keV) Images

BACKGROUND AND PURPOSE: Extravasation of iodinated contrast into subdural space following contrast-enhanced radiographic studies results in hyperdense subdural effusions, which can be mistaken as acute subdural hematomas on follow-up noncontrast head CTs. Our aim was to identify the factors associated with contrast-enhancing subdural effusion, characterize diffusion and washout kinetics of iodine in enhancing subdural effusion, and assess the utility of dual-energy CT in differentiating enhancing subdural effusion from subdural hematoma. MATERIALS AND METHODS: We retrospectively analyzed follow-up head dual-energy CT studies in 423 patients with polytrauma who had undergone contrast-enhanced whole-body CT. Twenty-four patients with enhancing subdural effusion composed the study group, and 24 randomly selected patients with subdural hematoma were enrolled in the comparison group. Postprocessing with syngo.via was performed to determine the diffusion and washout kinetics of iodine. The sensitivity and specificity of dual-energy CT for the diagnosis of enhancing subdural effusion were determined with 120-kV, virtual monochromatic energy (190-keV) and virtual noncontrast images. RESULTS: Patients with enhancing subdural effusion were significantly older (mean, 69 years; 95% CI, 60–78 years; P < .001) and had a higher incidence of intracranial hemorrhage (P = .001). Peak iodine concentration in enhancing subdural effusions was reached within the first 8 hours of contrast administration with a mean of 0.98 mg/mL (95% CI, 0.81–1.13 mg/mL), and complete washout was achieved at 38 hours. For the presence of a hyperdense subdural collection on 120-kV images with a loss of hyperattenuation on 190-keV and virtual noncontrast images, when considered as a true-positive for enhancing subdural effusion, the sensitivity was 100% (95% CI, 85.75%–100%) and the specificity was 91.67% (95% CI, 73%–99%). CONCLUSIONS: Dual-energy CT has a high sensitivity and specificity in differentiating enhancing subdural effusion from subdural hematoma. Hence, dual-energy CT has a potential to obviate follow-up studies.

Dual-Energy CT in Hemorrhagic Progression of Cerebral Contusion: Overestimation of Hematoma Volumes on Standard 120-kV Images and Rectification with Virtual High-Energy Monochromatic Images after Contrast-Enhanced Whole-Body Imaging

BACKGROUND AND PURPOSE: In patients with hemorrhagic contusions, hematoma volumes are overestimated on follow-up standard 120-kV images obtained after contrast-enhanced whole-body CT. We aimed to retrospectively determine hemorrhagic progression of contusion rates on 120-kV and 190-keV images derived from dual-energy CT and the magnitude of hematoma volume overestimation. MATERIALS AND METHODS: We retrospectively analyzed admission and follow-up CT studies in 40 patients with hemorrhagic contusions. After annotating the contusions, we measured volumes from admission and follow-up 120-kV and 190-keV images using semiautomated 3D segmentation. Bland-Altman analysis was used for hematoma volume comparison. RESULTS: On 120-kV images, hemorrhagic progression of contusions was detected in 24 of the 40 patients, while only 17 patients had hemorrhagic progression of contusions on 190-keV images (P = .008). Hematoma volumes were systematically overestimated on follow-up 120-kV images (9.68 versus 8 mm3; mean difference, 1.68 mm3; standard error, 0.37; P < .001) compared with 190-keV images. There was no significant difference in volumes between admission 120-kV and 190-keV images. Mean and median percentages of overestimation were 29% (95% CI, 18–39) and 22% (quartile 3 − quartile 1 = 36.8), respectively. CONCLUSIONS: The 120-kV images, which are comparable with single-energy CT images, significantly overestimated the hematoma volumes, hence the rate of hemorrhagic progression of contusions, after contrast-enhanced whole-body CT. Hence, follow-up of hemorrhagic contusions should be performed on dual-energy CT, and 190-keV images should be used for the assessment of hematoma volumes.