Sorption of Nanomaterials to Sandstone Rock.

We investigated the interaction of silica nanostructured particles and sandstone rock using various experimental approaches, such as fluid compatibility, batch sorption and single-phase core-floods. Diol and polyethylenglycol (PEG) surface-modified nanostructured silica materials were tested using two brines differing in ionic strength and with the addition of sodium carbonate (Na2CO3). Berea and Keuper outcrop materials (core plug and crushed samples) were used. Core-flood effluents were analysed to define changes in concentration and a rock's retention compared to a tracer. Field Flow Fractionation (FFF) and Dynamic Light Scattering (DLS) were performed to investigate changes in the effluent's size distribution. Adsorption was evaluated using UV-visible spectroscopy and scanning electron microscopy (SEM). The highest adsorption was observed in brine with high ionic strength, whereas the use of alkali reduced the adsorption. The crushed material from Berea rock showed slightly higher adsorption compared to Keuper rock, whereas temperature had a minor effect on adsorption behaviour. In core-flood experiments, no effects on permeability have been observed. The used particles showed a delayed breakthrough compared to the tracer, and bigger particles passed the rock core faster. Nanoparticle recovery was significantly lower for PEG-modified nanomaterials in Berea compared to diol-modified nanomaterials, suggesting high adsorption. SEM images indicate that adsorption spots are defined via surface roughness rather than mineral type. Despite an excess of nanomaterials in the porous medium, monolayer adsorption was the prevailing type observed.

A Phase II Study to Evaluate the Safety and Efficacy of Prasinezumab in Early Parkinson's Disease (PASADENA): Rationale, Design, and Baseline Data.

Background: Currently available treatments for Parkinson's disease (PD) do not slow clinical progression nor target alpha-synuclein, a key protein associated with the disease. Objective: The study objective was to evaluate the efficacy and safety of prasinezumab, a humanized monoclonal antibody that binds aggregated alpha-synuclein, in individuals with early PD. Methods: The PASADENA study is a multicenter, randomized, double-blind, placebo-controlled treatment study. Individuals with early PD, recruited across the US and Europe, received monthly intravenous doses of prasinezumab (1,500 or 4,500 mg) or placebo for a 52-week period (Part 1), followed by a 52-week extension (Part 2) in which all participants received active treatment. Key inclusion criteria were: aged 40-80 years; Hoehn & Yahr (H&Y) Stage I or II; time from diagnosis ≤2 years; having bradykinesia plus one other cardinal sign of PD (e.g., resting tremor, rigidity); DAT-SPECT imaging consistent with PD; and either treatment naïve or on a stable monoamine oxidase B (MAO-B) inhibitor dose. Study design assumptions for sample size and study duration were built using a patient cohort from the Parkinson's Progression Marker Initiative (PPMI). In this report, baseline characteristics are compared between the treatment-naïve and MAO-B inhibitor-treated PASADENA cohorts and between the PASADENA and PPMI populations. Results: Of the 443 patients screened, 316 were enrolled into the PASADENA study between June 2017 and November 2018, with an average age of 59.9 years and 67.4% being male. Mean time from diagnosis at baseline was 10.11 months, with 75.3% in H&Y Stage II. Baseline motor and non-motor symptoms (assessed using Movement Disorder Society-Unified Parkinson's Disease Rating Scale [MDS-UPDRS]) were similar in severity between the MAO-B inhibitor-treated and treatment-naïve PASADENA cohorts (MDS-UPDRS sum of Parts I + II + III [standard deviation (SD)]; 30.21 [11.96], 32.10 [13.20], respectively). The overall PASADENA population (63.6% treatment naïve and 36.4% on MAO-B inhibitor) showed a similar severity in MDS-UPDRS scores (e.g., MDS-UPDRS sum of Parts I + II + III [SD]; 31.41 [12.78], 32.63 [13.04], respectively) to the PPMI cohort (all treatment naïve). Conclusions: The PASADENA study population is suitable to investigate the potential of prasinezumab to slow disease progression in individuals with early PD. Trial Registration: NCT03100149.

Wettability Changes Due to Nanomaterials and Alkali-A Proposed Formulation for EOR.

We investigated the usage of two silica nanomaterials (surface-modified) and alkali in enhanced oil recovery through Amott spontaneous imbibition tests, interfacial tension (IFT) measurements, and phase behavior. We evaluated the wettability alteration induced by the synergy between nanomaterials and alkali. Moreover, numerical analysis of the results was carried out using inverse Bond number and capillary diffusion coefficient. Evaluations included the use of Berea and Keuper outcrop material, crude oil with different total acid numbers (TAN), and Na2CO3 as alkaline agent. Data showed that nanomaterials can reduce the IFT, with surface charge playing an important role in this process. In synergy with alkali, the use of nanomaterials led to low-stable IFT values. This effect was also seen in the phase behavior tests, where brine/oil systems with lower IFT exhibited better emulsification. Nanomaterials' contribution to the phase behavior was mainly the stabilization of the emulsion middle phase. The influence of TAN number on the IFT and phase behavior was prominent especially when combined with alkali. Amott spontaneous imbibition resulted in additional oil recovery ranging from 4% to 50% above the baseline, which was confirmed by inverse Bond number analysis. High recoveries were achieved using alkali and nanomaterials; these values were attributed to wettability alteration that accelerated the imbibition kinetics as seen in capillary diffusion coefficient analysis.

Evidence-Based Clinical Practice Guideline: Reconstruction after Skin Cancer Resection.

SUMMARY: A multi-disciplinary work group involving stakeholders from various backgrounds and societies was convened to develop guidelines for the management of reconstruction after skin cancer resection. The goal was to identify areas of common ground and provide evidence-based recommendations to improve patient care. Given the heterogeneity of reconstructive techniques and clinical scenarios, investigation centered around common elements in the process. In some cases, a distinction was made between treatment options in the office-based setting as opposed to those in the facility setting. A systematic literature review was performed, and an established appraisal process was used to rate the quality of relevant scientific research (Grading of Recommendations Assessment, Development, and Evaluation methodology). Final recommendations are related to concepts concerning the timing of reconstruction, management of anticoagulation, use of antibiotics, methods of pain control, and follow-up assessment. At times, there was insufficient evidence to make high-level recommendations. The literature analysis highlights the need for additional methodologically robust studies in this area, to help guide clinical practice.

Evidence-based clinical practice guideline: Reconstruction after skin cancer resection.

A multi-disciplinary work group involving stakeholders from various backgrounds and societies was convened to develop guidelines for the management of reconstruction after skin cancer resection. The goal was to identify areas of common ground and provide evidence-based recommendations to improve patient care. Given the heterogeneity of reconstructive techniques and clinical scenarios, investigation centered around common elements in the process. In some cases, a distinction was made between treatment options in the office-based setting as opposed to those in the facility setting. A systematic literature review was performed, and an established appraisal process was used to rate the quality of relevant scientific research (Grading of Recommendations Assessment, Development, and Evaluation methodology). Final recommendations are related to concepts concerning the timing of reconstruction, management of anticoagulation, use of antibiotics, methods of pain control, and follow-up assessment. At times, there was insufficient evidence to make high-level recommendations. The literature analysis highlights the need for additional methodologically robust studies in this area, to help guide clinical practice.

Evidence-Based Clinical Practice Guideline: Reconstruction after Skin Cancer Resection.

SUMMARY: A multi-disciplinary work group involving stakeholders from various backgrounds and societies was convened to develop guidelines for the management of reconstruction after skin cancer resection. The goal was to identify areas of common ground and provide evidence-based recommendations to improve patient care. Given the heterogeneity of reconstructive techniques and clinical scenarios, investigation centered around common elements in the process. In some cases, a distinction was made between treatment options in the office-based setting as opposed to those in the facility setting. A systematic literature review was performed, and an established appraisal process was used to rate the quality of relevant scientific research (Grading of Recommendations Assessment, Development, and Evaluation methodology). Final recommendations are related to concepts concerning the timing of reconstruction, management of anticoagulation, use of antibiotics, methods of pain control, and follow-up assessment. At times, there was insufficient evidence to make high-level recommendations. The literature analysis highlights the need for additional methodologically robust studies in this area, to help guide clinical practice.

Evidence-based clinical practice guideline: Reconstruction after skin cancer resection

A multi-disciplinary work group involving stakeholders from various backgrounds and societies was convened to develop guidelines for the management of reconstruction after skin cancer resection. The goal was to identify areas of common ground and provide evidence-based recommendations to improve patient care. Given the heterogeneity of reconstructive techniques and clinical scenarios, investigation centered around common elements in the process. In some cases, a distinction was made between treatment options in the office-based setting as opposed to those in the facility setting. A systematic literature review was performed, and an established appraisal process was used to rate the quality of relevant scientific research (Grading of Recommendations Assessment, Development, and Evaluation methodology). Final recommendations are related to concepts concerning the timing of reconstruction, management of anticoagulation, use of antibiotics, methods of pain control, and follow-up assessment. At times, there was insufficient evidence to make high-level recommendations. The literature analysis highlights the need for additional methodologically robust studies in this area, to help guide clinical practice.

Spectral Photon-Counting Computed Tomography for Coronary Stent Imaging: Evaluation of the Potential Clinical Impact for the Delineation of In-Stent Restenosis.

OBJECTIVES: In-stent restenosis (ISR) is one of the main long-term complications after coronary stent placement, and the ability to evaluate ISR noninvasively using coronary computed tomography (CT) angiography remains challenging. For this application, spectral photon-counting CT (SPCCT) has the potential to increase image quality and reduce artifacts due to its advanced detector technology.Our study aimed to verify the technical and clinical potential of a novel SPCCT prototype using an ISR phantom setup. MATERIALS AND METHODS: Soft plaque-like restenosis (45 HU; approximately 50% of the stent lumen) were inserted into 10 different coronary stents (3 mm diameter), which were placed in a vessel phantom and filled with a contrast agent (400 HU). A research prototype SPCCT and a clinical dual-layer CT (DLCT; IQon; Philips) with comparable acquisition and reconstruction parameters were used to scan the phantoms. Conventional polyenergetic (PolyE) and monoenergetic (MonoE) images with 4 different energy levels (40, 60, 90, 120 keV) were reconstructed. Qualitative (delineation of the stenosis and adjacent residual lumen using a 5-point Likert scale) and quantitative (image noise, visible lumen diameter, lumen diameter adjacent to the stenosis, contrast-to-noise ratio of the restenosis) parameters were evaluated for both systems. RESULTS: The qualitative results averaged over all reconstructions were significantly superior for SPCCT compared with DLCT (eg, subjective rating of the best reconstruction of each scanner: DLCT PolyE: 2.80 ± 0.42 vs SPCCT MonoE 40 keV: 4.25 ± 1.03). Stenosis could be clearly detected in 9 and suspected in 10 of the 10 stents with both SPCCT and DLCT. The residual lumen next to the stenosis was clearly delineable in 7 of 10 stents (0.64 ± 0.11 mm or 34.97% of the measured stent lumen) with SPCCT, while it was not possible to delineate the residual lumen for all stents using DLCT. The measured diameter of the lumen within the stent was significantly higher for SPCCT compared with DLCT in all reconstructions with the best results for the MonoE 40 keV images (SPCCT: 1.80 ± 0.17 mm; DLCT: 1.50 ± 0.31 mm). The image noise and the contrast-to-noise ratio were better for DLCT than for SPCCT (contrast-to-noise ratio: DLCT MonoE 40: 31.58 ± 12.54; SPCCT MonoE 40: 4.64 ± 1.30). CONCLUSIONS: Spectral photon-counting CT allowed for the noninvasive evaluation of ISR with reliable results regarding the residual lumen for most tested stents and the clear identification or suspicion of stenosis for all stents. In contrast, the residual lumen could not be detected for a single stent using DLCT.

UTI in kidney transplant.

Urinary tract infection (UTI) remains the most common type of infection contracted by kidney transplant patients. UTI reduces both patient and graft survival. Understanding and managing UTI in transplant patients requires an appreciation of their unique anatomy and physiology. Both the transplant and native urinary systems can be affected by upper and/or lower urinary tract infections. Factors that contribute to UTI in kidney transplant patients are numerous and interact with each other. Factors can include excessive immunosuppression by medications and/or chronic disease, foreign material in the urinary system, transplant kidneys affected by ischaemia-reperfusion injury, non-functioning native kidneys, and abnormal lower urinary tracts. Research is ongoing to highlight the roles each of these contributing factors play and how they may be mitigated to reduce the incidence of UTI. Antimicrobials remain the mainstays of treatment and prophylaxis and this has promoted the development of multi-drug resistant organisms. This challenge necessitates awareness of UTI and methods to reduce rates by all healthcare professionals involved in kidney transplantation.

Feasibility of improving vascular imaging in the presence of metallic stents using spectral photon counting CT and K-edge imaging.

Correct visualization of the vascular lumen is impaired in standard computed tomography (CT) because of blooming artifacts, increase of apparent size, induced by metallic stents and vascular calcifications. Recently, due to the introduction of photon-counting detectors in the X-ray imaging field, a new prototype spectral photon-counting CT (SPCCT) based on a modified clinical CT system has been tested in a feasibility study for improving vascular lumen delineation and visualization of coronary stent architecture. Coronary stents of different metal composition were deployed inside plastic tubes containing hydroxyapatite spheres to simulate vascular calcifications and in the abdominal aorta of one New Zealand White (NZW) rabbit. Imaging was performed with an SPCCT prototype, a dual-energy CT system, and a conventional 64-channel CT system (B64). We found the apparent widths of the stents significantly smaller on SPCCT than on the other two systems in vitro (p < 0.01), thus closer to the true size. Consequently, the intra-stent lumen was significantly larger on SPCCT (p < 0.01). In conclusion, owing to the increased spatial resolution of SPCCT, improved lumen visualization and delineation of stent metallic mesh is possible compared to dual-energy and conventional CT.

Liquid Embolic Agents in Spectral X-Ray Photon-Counting Computed Tomography using Tantalum K-Edge Imaging.

The aim was to evaluate the potential of Spectral Photon-Counting Computed Tomography (SPCCT) to differentiate between liquid embolic agents and iodinated contrast medium by using tantalum-characteristic K-edge imaging. Tubes with a concentration series of tantalum and inserts with different concentrations of iodine were scanned with a preclinical SPCCT system. Tantalum density maps (TDM) and iodine density maps (IDM) were generated from a SPCCT acquisition. Furthermore, region-of-interest (ROI) analysis was performed within the tubes in the conventional CT, the TDM and IDM. TDM and IDM enable clear differentiation between both substances. Quantitative measurements of different tantalum concentrations match well with those of actually diluted mixtures. SPCCT allows for differentiation between tantalum and iodine and may enable for an improved follow-up diagnosis in patients after vascular occlusion therapy.

Differentiation between blood and iodine in a bovine brain-Initial experience with Spectral Photon-Counting Computed Tomography (SPCCT).

OBJECTIVES: To evaluate the accuracy of Spectral Photon-Counting Computed Tomography (SPCCT) in the quantification of iodine concentrations and its potential for the differentiation between blood and iodine. METHODS: Tubes with blood and a concentration series of iodine were scanned with a preclinical SPCCT system (both in vitro and in an ex vivo bovine brain tissue sample). Iodine density maps (IDM) and virtual non-contrast (VNC) images were generated using the multi-bin spectral information to perform material decomposition. Region-of-interest (ROI) analysis was performed within the tubes to quantitatively determine the absolute content of iodine (mg/ml). RESULTS: In conventional CT images, ROI analysis showed similar Hounsfield Unit (HU) values for the tubes with blood and iodine (59.9 ± 1.8 versus 59.2 ± 1.5). Iodine density maps enabled clear differentiation between blood and iodine in vitro, as well as in the bovine brain model. Quantitative measurements of the different iodine concentrations matched well with those of actual known concentrations even for very small iodine concentrations with values below 1mg/ml (RMSE = 0.19). CONCLUSIONS: SPCCT providing iodine maps and virtual non-contrast images allows material decomposition, differentiation between blood and iodine in vitro and ex vivo in a bovine brain model and reliably quantifies the iodine concentration.

The Role of Clinical Examination in Predicting Relevant MRI Findings in Acute Knee Injuries: A Retrospective Study.

The objective of this study was to delineate the usefulness of clinical examination and magnetic resonance imaging (MRI) in acute knee injuries. We aim to establish whether the time period post acute knee injury is related to the diagnostic accuracy of clinical examination and to investigate the strength of specific clinical examination findings in predicting a clinically relevant MRI abnormality. Seventy patients were referred to fracture clinic with an acute knee injury who subsequently went on to be investigated with MRI over 12 months. These patients were retrospectively analyzed looking at the time period they were reviewed, the components that were assessed at physical examination, and the results of their eventual MRI scan looking for any correlation. A greater proportion of patients who were examined at 2 weeks had relevant positive findings on MRI scan, p = 0.03. Range of movement and lateral joint line tenderness were not associated with a positive MRI scan at any period after injury. The presence of a moderate to large effusion was not associated with an MRI abnormality if the examination was within 2 weeks of injury but was if present 2 weeks after injury, p = 0.0001. Range of movement should not form part of the decision making on whether an injury should be investigated with MRI. Joint effusion in isolation within 2 weeks after injury should not be an indication for MRI but a repeat clinical examination in 2 weeks, where if still present, should be investigated with MRI.

Multicolour imaging with spectral photon-counting CT: a phantom study.

BACKGROUND: To evaluate the feasibility of multicolour quantitative imaging with spectral photon-counting computed tomography (SPCCT) of different mixed contrast agents. METHODS: Phantoms containing eleven tubes with mixtures of varying proportions of two contrast agents (i.e. two selected from gadolinium, iodine or gold nanoparticles) were prepared so that the attenuation of each tube was about 280 HU. Scans were acquired at 120 kVp and 100 mAs using a five-bin preclinical SPCCT prototype, generating conventional, water, iodine, gadolinium and gold images. The correlation between prepared and measured concentrations was assessed using linear regression. The cross-contamination was measured for each material as the root mean square error (RMSE) of its concentration in the other material images, where no signal was expected. The contrast-to-noise ratio (CNR) relative to a phosphate buffered saline tube was calculated for each contrast agent. RESULTS: The solutions had similar attenuations (279 ± 10 HU, mean ± standard deviation) and could not be differentiated on conventional images. However, a distinction was observed in the material images within the same samples, and the measured and prepared concentrations were strongly correlated (R2 ≥ 0.97, 0.81 ≤ slope ≤ 0.95, -0.68 ≤ offset ≤ 0.89 mg/mL). Cross-contamination in the iodine images for the mixture of gold and gadolinium contrast agents (RMSE = 0.34 mg/mL) was observed. CNR for 1 mg/mL of contrast agent was better for the mixture of iodine and gadolinium (CNRiodine = 3.20, CNRgadolinium = 2.80) than gold and gadolinium (CNRgadolinium = 1.67, CNRgold = 1.37). CONCLUSIONS: SPCCT enables multicolour quantitative imaging. As a result, it should be possible to perform imaging of multiple uptake phases of a given tissue/organ within a single scan by injecting different contrast agents sequentially.

Assessment of candidate elements for development of spectral photon-counting CT specific contrast agents.

Spectral photon-counting computed tomography (SPCCT) is a rapidly emerging imaging modality that provides energy-dependent information on individual x-ray photons, leading to accurate material decomposition and simultaneous quantification of multiple contrast generating materials. Development of SPCCT-specific contrast agents is needed to overcome the issues with currently used iodinated contrast agents, such as difficulty in differentiation from calcified structures, and yield SPCCT's full promise. In this study, the contrast generation of different elements is investigated using a prototype SPCCT scanner based on a modified clinical CT system and suitable elements for novel contrast agent development for SPCCT imaging are identified. Furthermore, nanoparticles were synthesized from tantalum as a proof of concept spectral photon-counting CT agent and tested for their in vitro cytotoxicity and contrast generation to provide insight into the feasibility of nanoparticle contrast agent development from these elements. We found that gadolinium, ytterbium and tantalum generate high contrast in spectral photon-counting CT imaging and may be suitable elements for contrast agent development for this modality. Our proof of concept results with tantalum-based nanoparticles underscore this conclusion due to their detectability with spectral photon-counting CT, as well as their biocompatibility.

Safety and Tolerability of Multiple Ascending Doses of PRX002/RG7935, an Anti-α-Synuclein Monoclonal Antibody, in Patients With Parkinson Disease: A Randomized Clinical Trial.

Importance: Aggregated α-synuclein is believed to be central to the pathogenesis of Parkinson disease (PD). PRX002/RG7935 (PRX002) is a humanized monoclonal antibody designed to target aggregated forms of α-synuclein, thereby inhibiting neuron-to-neuron transfer of presumed pathogenic forms of α-synuclein, potentially resulting in neuronal protection and slowing disease progression. Objective: To evaluate the safety and tolerability of multiple intravenous infusions of PRX002 in patients with idiopathic PD. Design, Setting, and Participants: Multicenter, randomized, double-blind, placebo-controlled, multiple ascending-dose trial at 8 US study centers from July 2014 to September 2016. Eligible participants were aged 40 to 80 years with mild to moderate idiopathic PD (Hoehn and Yahr stages 1-3). Interventions: Participants were enrolled into 6 ascending-dose cohorts and randomly assigned to receive PRX002 (0.3 mg/kg, 1.0 mg/kg, 3.0 mg/kg, 10 mg/kg, 30 mg/kg, or 60 mg/kg) or placebo. Participants received 3 intravenous infusions every 4 weeks of PRX002 or placebo and were monitored during a 24-week observational period. Main Outcomes and Measures: Safety and tolerability assessments included physical and neurological examinations, laboratory tests, vital signs, and adverse events. Pharmacokinetic parameters included maximum PRX002 concentration, area under the curve, and half-life. Results: Of the 80 participants, most were white (97.5%; n = 78) and male (80%; n = 64); median (SD) age was 58 (8.4) years. PRX002 was generally safe and well tolerated; no serious or severe PRX002-related treatment-emergent adverse events (TEAEs) were reported. The TEAEs experienced by at least 5% of patients receiving PRX002, irrespective of relatedness to study drug, were constipation (9.1%; n = 5), infusion reaction (7.3%; n = 4), diarrhea (5.5%; n = 3), headache (5.5%; n = 3), peripheral edema (5.5%; n = 3), post-lumbar puncture syndrome (5.5%; n = 3), and upper respiratory tract infection (5.5%; n = 3). No antidrug antibodies were detected. Serum PRX002 levels increased in an approximately dose-proportional manner; mean terminal elimination half-life was similar across all doses (10.2 days). Rapid dose- and time-dependent mean reductions from baseline vs placebo in free serum α-synuclein levels of up to 97% were seen after a single infusion at the highest dose (F78,284 = 1.66; P = .002), with similar reductions after 2 additional infusions. Mean cerebrospinal fluid PRX002 concentration increased with PRX002 dose and was approximately 0.3% relative to serum across all dose cohorts. Conclusions and Relevance: Single and multiple doses of PRX002 were generally safe and well tolerated and resulted in robust binding of peripheral α-synuclein and dose-dependent increases of PRX002 in cerebrospinal fluid, reaching cerebrospinal fluid concentrations that may be expected to engage extracellular aggregated α-synuclein in the brain. Findings support the design of an ongoing phase 2 clinical study (NCT03100149). Trial Registration: ClinicalTrials.gov Identifier: NCT02157714.

Improved Peritoneal Cavity and Abdominal Organ Imaging Using a Biphasic Contrast Agent Protocol and Spectral Photon Counting Computed Tomography K-Edge Imaging.

OBJECTIVES: To validate in vitro the capability of a high-spatial-resolution prototype spectral photon-counting computed tomography (SPCCT) scanner to differentiate between 2 contrast agents and to assess in vivo the image quality and the feasibility to image the peritoneal cavity in rats using the 2 contrast agents simultaneously within the vascular and peritoneal compartments. MATERIALS AND METHODS: The authors performed SPCCT imaging (100 mAs, 120 kVp) with energy bin thresholds set to 30, 51, 64, 72, and 85 keV in vitro on a custom-made polyoxymethylene cylindrical phantom consisting of tubes with dilutions of both contrast agents and in vivo on 2 groups of adult rats using 2 injection protocols. Approval from the institutional animal ethics committee was obtained. One group received macrocylic gadolinium chelate intraperitoneal (IP) and iodine intravenous (IV) injections (protocol A, n = 3), whereas the second group received iodine IP and gadolinium IV (protocol B, n = 3). Helical scans were performed 35 minutes after IP injection and 20 seconds after IV injection. The SPCCT and contrast material images, that is, iodine and gadolinium maps, were reconstructed with a field of view of 160 mm, an isotropic voxel size of 250 µm, and a matrix size of 640 × 640 pixels using a soft reconstruction kernel. The SPCCT images were reconstructed with 2 different spatial resolutions to compare the image quality (sharpness, diagnostic quality, and organ visualization) of SPCCT (250 µm) with single-energy computed tomography (CT) (600 µm). Two radiologists evaluated the peritoneal opacification index in 13 regions (score = 0-3 per region) on each type of image. Concentrations of contrast agents were measured in the organs of interest. RESULTS: In vitro, the concentration measurements correlated well with the expected concentrations. The linear regressions both had R values of 0.99, slopes of 0.84 and 0.87, and offsets at -0.52 and -0.38 mg/mL for iodine and gadolinium, respectively. In vivo, the SPCCT images were of better diagnostic quality, with increased sharpness compared with the CT-like images (P < 0.0001). Intraperitoneal diffusion was excellent, with similar peritoneal opacification index on SPCCT images and overlay of contrast material maps (P = 1) without a significant difference between protocol A (37.0 ± 1.7) and protocol B (35.3 ± 1.5) (P = 0.34). Only the contrast material maps demonstrated clear visual separation of the contrast agents, allowing specific quantification of the physiological enhancement in the liver, spleen, and kidney and the urinary clearance in the renal pelvis and bladder. Renal excretion of the contrast agents injected IP was observed and was consistent with blood diffusion. CONCLUSIONS: Spectral photon-counting CT can be used to perform a complete peritoneal dual-contrast protocol, enabling a good assessment of the peritoneal cavity and abdominal organs in rats.

Experimental feasibility of spectral photon-counting computed tomography with two contrast agents for the detection of endoleaks following endovascular aortic repair.

OBJECTIVES: After endovascular aortic repair (EVAR), discrimination of endoleaks and intra-aneurysmatic calcifications within the aneurysm often requires multiphase computed tomography (CT). Spectral photon-counting CT (SPCCT) in combination with a two-contrast agent injection protocol may provide reliable detection of endoleaks with a single CT acquisition. METHODS: To evaluate the feasibility of SPCCT, the stent-lined compartment of an abdominal aortic aneurysm phantom was filled with a mixture of iodine and gadolinium mimicking enhanced blood. To represent endoleaks of different flow rates, the adjacent compartments contained either one of the contrast agents or calcium chloride to mimic intra-aneurysmatic calcifications. After data acquisition with a SPCCT prototype scanner with multi-energy bins, material decomposition was performed to generate iodine, gadolinium and calcium maps. RESULTS: In a conventional CT slice, Hounsfield units (HU) of the compartments were similar ranging from 147 to 168 HU. Material-specific maps differentiate the distributions within the compartments filled with iodine, gadolinium or calcium. CONCLUSION: SPCCT may replace multiphase CT to detect endoleaks without sacrificing diagnostic accuracy. It is a unique feature of our method to capture endoleak dynamics and allow reliable distinction from intra-aneurysmatic calcifications in a single scan, thereby enabling a significant reduction of radiation exposure. KEY POINTS: • SPCCT might enable advanced endoleak detection. • Material maps derived from SPCCT can differentiate iodine, gadolinium and calcium. • SPCCT may potentially reduce radiation burden for EVAR patients under post-interventional surveillance.

Multicolor spectral photon-counting computed tomography: in vivo dual contrast imaging with a high count rate scanner.

A new prototype spectral photon-counting computed tomography (SPCCT) based on a modified clinical CT system has been developed. SPCCT analysis of the energy composition of the transmitted x-ray spectrum potentially allows simultaneous dual contrast agent imaging, however, this has not yet been demonstrated with such a system. We investigated the feasibility of using this system to distinguish gold nanoparticles (AuNP) and an iodinated contrast agent. The contrast agents and calcium phosphate were imaged in phantoms. Conventional CT, gold K-edge, iodine and water images were produced and demonstrated accurate discrimination and quantification of gold and iodine concentrations in a phantom containing mixtures of the contrast agents. In vivo experiments were performed using New Zealand White rabbits at several times points after injections of AuNP and iodinated contrast agents. We found that the contrast material maps clearly differentiated the distributions of gold and iodine in the tissues allowing quantification of the contrast agents' concentrations, which matched their expected pharmacokinetics. Furthermore, rapid, repetitive scanning was done, which allowed measurement of contrast agent kinetics with high temporal resolution. In conclusion, a clinical scale, high count rate SPCCT system is able to discriminate gold and iodine contrast media in different organs in vivo.

Evaluation of spectral photon counting computed tomography K-edge imaging for determination of gold nanoparticle biodistribution in vivo.

Spectral photon counting computed tomography (SPCCT) is an emerging medical imaging technology. SPCCT scanners record the energy of incident photons, which allows specific detection of contrast agents due to measurement of their characteristic X-ray attenuation profiles. This approach is known as K-edge imaging. Nanoparticles formed from elements such as gold, bismuth or ytterbium have been reported as potential contrast agents for SPCCT imaging. Furthermore, gold nanoparticles have many applications in medicine, such as adjuvants for radiotherapy and photothermal ablation. In particular, longitudinal imaging of the biodistribution of nanoparticles would be highly attractive for their clinical translation. We therefore studied the capabilities of a novel SPCCT scanner to quantify the biodistribution of gold nanoparticles in vivo. PEGylated gold nanoparticles were used. Phantom imaging showed that concentrations measured on gold images correlated well with known concentrations (slope = 0.94, intercept = 0.18, RMSE = 0.18, R2 = 0.99). The SPCCT system allowed repetitive and quick acquisitions in vivo, and follow-up of changes in the AuNP biodistribution over time. Measurements performed on gold images correlated with the inductively coupled plasma-optical emission spectrometry (ICP-OES) measurements in the organs of interest (slope = 0.77, intercept = 0.47, RMSE = 0.72, R2 = 0.93). TEM results were in agreement with the imaging and ICP-OES in that much higher concentrations of AuNPs were observed in the liver, spleen, bone marrow and lymph nodes (mainly in macrophages). In conclusion, we found that SPCCT can be used for repetitive and non-invasive determination of the biodistribution of gold nanoparticles in vivo.