Comparison of volumetric and areal bone mineral density in CT and scout scans using spectral detector technology.

BACKGROUND: To determine whether denoised areal bone mineral density (BMD) measurements from scout scans in spectral detector computed tomography (CT) correlate with volumetric trabecular BMD for opportunistic osteoporosis screening. METHODS: A 64-slice single-source dual-layer spectral CT scanner was used to acquire scout scan data of 228 lumbar vertebral bodies within 57 patients. Scout scans in anterior-posterior (AP) view were performed with a dose of < 0.06 mSv and spectrally decomposed into areal BMD (aBMD) values. A spectral dictionary denoising algorithm was applied to increase the signal-to-noise ratio (SNR). Volumetric trabecular bone mineral density (vBMD) was determined via material decomposition. A 3D convolutional network for image segmentation and labeling was applied for automated vBMD quantification. Projected maps were used to compare the classification accuracy of AP and lateral scout scans. RESULTS: The denoising algorithm led to the minimization of anticorrelated noise in spectral maps and an SNR increase from 5.23 to 13.4 (p < 0.002). Correlation analysis between vBMD and measured AP aBMD, projected AP, and lateral aBMD showed a Pearson correlation coefficient of 0.68, 0.81, and 0.90, respectively. The sensitivity and specificity for the osteoporosis classification task were higher in lateral projection images than in AP crystallizing in an increased area under the curve value of 0.99 versus 0.90. CONCLUSION: Denoised material-specific aBMD maps show a positive correlation to vBMD, enabling spectral scout scans as an opportunistic predictor for osteoporotic patients. This could be applied routinely as a screening tool in patients undergoing a CT examination. RELEVANCE STATEMENT: Scout-based DEXA could be applied routinely as a screening tool in patients undergoing a CT examination. KEY POINTS: • Spectral scout scans can be used as a dual-energy x-ray absorptiometry-like screening tool. • Spectral dictionary denoising on projection images increases the signal-to-noise ratio. • Positive correlation between volumetric and areal bone mineral density is observed. • Lateral projections increase osteoporosis classification accuracy compared to anterior-posterior projections.

Gadolinium K-edge angiography with a spectral photon counting CT in atherosclerotic rabbits.

PURPOSE: The purpose of this study was to investigate the feasibility of gadolinium-K-edge-angiography (angio-Gd-K-edge) with gadolinium-based contrast agents (GBCAs) as obtained with spectral photon counting CT (SPCCT) in atherosclerotic rabbits. MATERIALS AND METHODS: Seven atherosclerotic rabbits underwent angio-SPCCT acquisitions with two GBCAs, with similar intravenous injection protocol. Conventional and angio-Gd-K-edge images were reconstructed with the same parameters. Regions of interest were traced in different locations of the aorta and its branches. Hounsfield unit values, Gd concentrations, signal-to-noise (SNR) and contrast-to-noise (CNR) were calculated and compared. The maximum diameter and the diameter of the aorta in regard to atherosclerotic plaques were measured by two observers. Images were subjectively evaluated regarding vessels' enhancement, artefacts, border sharpness and overall image quality. RESULTS: In the analyzable six rabbits, Gd-K-edge allowed visualization of target vessels and no other structures. HU values and Gd concentrations were greatest in the largest artery (descending aorta, 5.6 ± 0.8 [SD] mm), and lowest in the smallest (renal arteries, 2.1 ± 0.3 mm). While greater for conventional images, CNR and SNR were satisfactory for both images (all P < 0.001). For one observer there were no statistically significant differences in either maximum or plaque-diameters (P = 0.45 and all P > 0.05 in post-hoc analysis, respectively). For the second observer, there were no significant differences for images reconstructed with the same parameters (all P < 0.05). All subjective criteria scored higher for conventional images compared to K-edge (all P < 0.01), with the highest scores for enhancement (4.3-4.4 vs. 3.1-3.4). CONCLUSION: With SPCCT, angio-Gd-K-edge after injection of GBCAs in atherosclerotic rabbits is feasible and allows for angiography-like visualization of small arteries and for the reliable measurement of their diameters.

Coronary CT Angiography with Photon-counting CT: First-In-Human Results.

Background Spatial resolution, soft-tissue contrast, and dose-efficient capabilities of photon-counting CT (PCCT) potentially allow a better quality and diagnostic confidence of coronary CT angiography (CCTA) in comparison to conventional CT. Purpose To compare the quality of CCTA scans obtained with a clinical prototype PCCT system and an energy-integrating detector (EID) dual-layer CT (DLCT) system. Materials and Methods In this prospective board-approved study with informed consent, participants with coronary artery disease underwent retrospective electrocardiographically gated CCTA with both systems after injection of 65-75 mL of 400 mg/mL iodinated contrast agent at 5 mL/sec. A prior phantom task-based quality assessment of the detectability index of coronary lesions was performed. Ultra-high-resolution parameters were used for PCCT (1024 matrix, 0.25-mm section thickness) and EID DLCT (512 matrix, 0.67-mm section thickness). Three cardiac radiologists independently performed a blinded analysis using a five-point quality score (1 = insufficient, 5 = excellent) for overall image quality, diagnostic confidence, and diagnostic quality of calcifications, stents, and noncalcified plaques. A logistic regression model, adjusted for radiologists, was used to evaluate the proportion of improvement in scores with the best method. Results Fourteen consecutive participants (12 men; mean age, 61 years ± 17) were enrolled. Scores of overall quality and diagnostic confidence were higher with PCCT images with a median of 5 (interquartile range [IQR], 2) and 5 (IQR, 1) versus 4 (IQR, 1) and 4 (IQR, 3) with EID DLCT images, using a mean tube current of 255 mAs ± 0 versus 349 mAs ± 111 for EID DLCT images (P < .01). Proportions of improvement with PCCT images for quality of calcification, stent, and noncalcified plaque were 100%, 92% (95% CI: 71, 98), and 45% (95% CI: 28, 63), respectively. In the phantom study, detectability indexes were 2.3-fold higher for lumen and 2.9-fold higher for noncalcified plaques with PCCT images. Conclusion Coronary CT angiography with a photon-counting CT system demonstrated in humans an improved image quality and diagnostic confidence compared with an energy-integrating dual-layer CT. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Sandfort and Bluemke in this issue.

First In-Human Results of Computed Tomography Angiography for Coronary Stent Assessment With a Spectral Photon Counting Computed Tomography.

OBJECTIVES: The aim of this study is to compare the image quality of in vivo coronary stents between an energy integrating detectors dual-layer computed tomography (EID-DLCT) and a clinical prototype of spectral photon counting computed tomography (SPCCT). MATERIALS AND METHODS: In January to June 2021, consecutive patients with coronary stents were prospectively enrolled to undergo a coronary computed tomography (CT) with an EID-DLCT (IQon, Philips) and an SPCCT (Philips). The study was approved by the local ethical committee and patients signed an informed consent. A retrospectively electrocardiogram-gated acquisition was performed with optimized matching parameters on the 2 scanners (EID-DLCT: collimation, 64 × 0.625 mm; kVp, 120, automatic exposure control with target current at 255 mAs; rotation time, 0.27 seconds; SPCCT: collimation, 64 × 0.275 mm; kVp, 120; mAs, 255; rotation time, 0.33 seconds). The injection protocol was the same on both scanners: 65 to 75 mL of Iomeron (Bracco) at 5 mL/s. Images were reconstructed with slice thickness of 0.67 mm, 512 matrix, XCB (Xres cardiac standard) and XCD (Xres cardiac detailed) kernel, iDose 3 for EID-DLCT and 0.25-mm slice thickness, 1024 matrix, Detailed 2 and Sharp kernel, and iDose 6 for SPCCT. Two experienced observers measured the proximal and distal external and internal diameters of the stents to quantify blooming artifacts. Regions of interest were drawn in the lumen of the stent and of the upstream coronary artery. The difference (Δ S-C) between the respective attenuation values was calculated as a quantification of stent-induced artifacts on intrastent image quality. For subjective image quality, 3 experienced observers graded with a 4-point scale the image quality of different parameters: coronary wall before the stent, stent lumen, stent structure, calcifications surrounding the stent, and beam-hardening artifacts. RESULTS: Eight patients (age, 68 years [interquartile range, 8]; all men; body mass index, 26.2 kg/m2 [interquartile range, 4.2]) with 16 stents were scanned. Five stents were not evaluable owing to motion artifacts on the SPCCT. Of the remaining, all were drug eluting stents, of which 6 were platinum-chromium, 3 were cobalt-platinum-iridium, and 1 was stainless steel. For 1 stent, no information could be retrieved. Radiation dose was lower with the SPCCT (fixed CT dose index of 25.7 mGy for SPCCT vs median CT dose index of 35.7 [IQ = 13.6] mGy; P = 0.02). For 1 stent, the internal diameter was not assessable on EID-DLCT. External diameters were smaller and internal diameters were larger with SPCCT (all P < 0.05). Consequently, blooming artifacts were reduced on SPCCT (P < 0.05). Whereas Hounsfield unit values within the coronary arteries on the 2 scanners were similar, the Δ S-C was lower for SPCCT-Sharp as compared with EID-DLCT-XCD and SPCCT-Detailed 2 (P < 0.05). The SPCCT received higher subjective scores than EID-DLCT for stent lumen, stent structure, surrounding calcifications and beam-hardening for both Detailed 2 and Sharp (all P ≤ 0.05). The SPCCT-Sharp was judged better for stent structure and beam-hardening assessment as compared with SPCCT-Detailed 2. CONCLUSION: Spectral photon counting CT demonstrated improved objective and subjective image quality as compared with EID-DLCT for the evaluation of coronary stents even with a reduced radiation dose.

Comparison of image quality between spectral photon-counting CT and dual-layer CT for the evaluation of lung nodules: a phantom study.

OBJECTIVES: To evaluate the image quality (IQ) of a spectral photon-counting CT (SPCCT) using filtered back projection (FBP) and hybrid iterative reconstruction (IR) algorithms (iDose4), in comparison with a dual-layer CT (DLCT) system, and to choose the best image quality according to the IR level for SPCCT. METHODS: Two phantoms were scanned using a standard lung protocol (120 kVp, 40 mAs) with SPCCT and DLCT systems. Raw data were reconstructed using FBP and 9 iDose4 levels (i1/i2/i3/i4/i5/i6/i7/i9/i11) for SPCCT and 7 for DLCT (i1/i2/i3/i4/i5/i6/i7). Noise power spectrum and task-based transfer function (TTF) were computed. Detectability index (d') was computed for detection of 4 mm ground-glass nodule (GGN) and solid nodule. Two chest radiologists performed an IQ evaluation (noise/nodule sharpness/nodule conspicuity/overall IQ) in consensus, and chose the best image for SPCCT. RESULTS: Noise magnitude was -47% ± 2% lower on average with SPCCT than with DLCT for iDose4 range from i1 to i6. Average NPS spatial frequencies increased for SPCCT in comparison with DLCT. TTF also increased, except for the air insert with FBP, and i1/i2/i3. Higher detectability was found for SPCCT for both GGN and solid nodules. IQ for both types of nodule was rated consistently higher with SPCCT than with DLCT for the same iDose4 level. For SPCCT and both nodules, the scores for noise and conspicuity improved with increasing iDose4 level. iDose4 level 6 provided the best subjective IQ for both types of nodule. CONCLUSIONS: Higher IQ for GGN and solid nodules was demonstrated with SPCCT compared with DLCT with better detectability using iDose4. KEY POINTS: Using spectral photon-counting CT compared with dual-layer CT, noise magnitude was reduced with improvements in spatial resolution and detectability of ground-glass nodules and solid lung nodules. As the iDose4 level increased, noise magnitude was reduced and detectability of ground-glass and solid lung nodules was better for both CT systems. For spectral photon-counting CT imaging, two chest radiologists determined iDose4 level 6 as the best image quality for detecting ground-glass nodules and solid lung nodules.

Feasibility of lung imaging with a large field-of-view spectral photon-counting CT system.

PURPOSE: The purpose of this study was to characterize the technical capabilities and feasibility of a large field-of-view clinical spectral photon-counting computed tomography (SPCCT) prototype for high-resolution (HR) lung imaging. MATERIALS AND METHODS: Measurement of modulation transfer function (MTF) and acquisition of a line pairs phantom were performed. An anthropomorphic lung nodule phantom was scanned with standard (120kVp, 62mAs), low (120kVp, 11mAs), and ultra-low (80kVp, 3mAs) radiation doses. A human volunteer underwent standard (120kVp, 63mAs) and low (120kVp, 11mAs) dose scans after approval by the ethics committee. HR images were reconstructed with 1024 matrix, 300mm field of view and 0.25mm slice thickness using a filtered-back projection (FBP) and two levels of iterative reconstruction (iDose 5 and 9). The conspicuity and sharpness of various lung structures (distal airways, vessels, fissures and proximal bronchial wall), image noise, and overall image quality were independently analyzed by three radiologists and compared to a previous HR lung CT examination of the same volunteer performed with a conventional CT equipped with energy integrating detectors (120kVp, 10mAs, FBP). RESULTS: Ten percent MTF was measured at 22.3lp/cm with a cut-off at 31lp/cm. Up to 28lp/cm were depicted. While mixed and solid nodules were easily depicted on standard and low-dose phantom images, higher iDose levels and slice thicknesses (1mm) were needed to visualize ground-glass components on ultra-low-dose images. Standard dose SPCCT images of in vivo lung structures were of greater conspicuity and sharpness, with greater overall image quality, and similar image noise (despite a flux reduction of 23%) to conventional CT images. Low-dose SPCCT images were of greater or similar conspicuity and sharpness, similar overall image quality, and lower but acceptable image noise (despite a flux reduction of 89%). CONCLUSIONS: A large field-of-view SPCCT prototype demonstrates HR technical capabilities and high image quality for high resolution lung CT in human.

Functional interrogation of neural circuits with virally transmitted optogenetic tools.

The vertebrate brain comprises a plethora of cell types connected by intertwined pathways. Optogenetics enriches the neuroscientific tool set for disentangling these neuronal circuits in a manner which exceeds the spatio-temporal precision of previously existing techniques. Technically, optogenetics can be divided in three types of optical and genetic combinations: (1) it is primarily understood as the manipulation of the activity of genetically modified cells (typically neurons) with light, i.e. optical actuators. (2) A second combination refers to visualizing the activity of genetically modified cells (again typically neurons), i.e. optical sensors. (3) A completely different interpretation of optogenetics refers to the light activated expression of a genetically induced construct. Here, we focus on the first two types of optogenetics, i.e. the optical actuators and sensors in an attempt to give an overview into the topic. We first cover methods to express opsins into neurons and introduce strategies of targeting specific neuronal populations in different animal species. We then summarize combinations of optogenetics with behavioral read out and neuronal imaging. Finally, we give an overview of the current state-of-the-art and an outlook on future perspectives.

A starting kit for training and establishing in vivo electrophysiology, intracranial pharmacology, and optogenetics.

BACKGROUND: In accordance with the three R principles of research, animal usage should be limited as much as possible. Especially for the training of entry-level scientists in surgical techniques underlying opto- and electrophysiology, alternative training tools are required before moving on to live animals. We have developed a cost-effective rat brain model for training a wide range of surgical techniques, including, but not limited to optogenetics, electrophysiology, and intracranial pharmacological treatments. RESULTS: Our brain model creates a realistic training experience in animal surgery. The success of the surgeries (e.g. implantation accuracy) is readily assessable in cross sections of the model brain. Moreover, the model allows practicing electrophysiological recordings as well as testing for movement or light related artefacts. COMPARISON WITH EXISTING METHOD(S): The surgery and recording experience in our model closely resembles that in an actual rat in terms of the necessary techniques, considerations and time span. A few differences to an actual rat brain slightly reduce the difficulty in our model compared to a live animal. Thus, entry level scientists can first learn basic techniques in our model before moving on to the slightly more complex procedures in live animals. CONCLUSIONS: Our brain model is a useful training tool to equip scientist who are new in the field of electrophysiology and optogenetic manipulations with a basic skill set before applying it in live animals. It can be adapted to fit the desired training content or even to serve in testing and optimizing new lab equipment for more senior scientists.

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.

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.

Virtual versus true non-contrast dual-energy CT imaging for the diagnosis of aortic intramural hematoma.

PURPOSE: To assess whether virtual non-contrast (VNC) images derived from contrast dual-layer dual-energy computed tomography (DL-DECT) images could replace true non-contrast (TNC) images for aortic intramural hematoma (IMH) diagnosis in acute aortic syndrome (AAS) imaging protocols by performing quantitative as well as qualitative phantom and clinical studies. MATERIALS AND METHODS: Patients with confirmed IMH were included retrospectively in two centers. For in vitro imaging, a custom-made phantom of IMH was placed in a semi-anthropomorphic thorax phantom (QRM GmbH) and imaged on a DL-DECT at 120 kVp under various conditions of patient size, radiation exposure, and reconstruction modes. For in vivo imaging, 21 patients (70 ± 13 years) who underwent AAS imaging protocols at 120 kVp were included. In both studies, contrast-to-noise ratio (CNR) between hematoma and lumen was compared using a paired t test. Diagnostic confidence (1 = non-diagnostic, 4 = exemplary) for VNC and TNC images was rated by two radiologists and compared. Effective radiation doses for each acquisition were calculated. RESULTS: In both the phantom and clinical studies, we observed that the CNRs were similar between the VNC and TNC images. Moreover, both methods allowed differentiating the hyper-attenuation within the hematoma from the blood. Finally, we obtained equivalent high diagnostic confidence with both VNC and TNC images (VNC = 3.2 ± 0.7, TNC = 3.1 ± 0.7; p = 0.3). Finally, by suppressing TNC acquisition and using VNC, the mean effective dose reduction would be 40%. CONCLUSION: DL-DECT offers similar performances with VNC and TNC images for IMH diagnosis without compromise in diagnostic image quality. KEY POINTS: • Dual-layer dual-energy CT enables virtual non-contrast imaging from a contrast-enhanced acquisition. • Virtual non-contrast imaging with dual-layer dual-energy CT reduces the number of acquisitions and radiation exposure in acute aortic syndrome imaging protocol. • Dual-layer dual-energy CT has the potential to become a suitable imaging tool for acute aortic syndrome.

Spectral Photon-Counting Computed Tomography (SPCCT): in-vivo single-acquisition multi-phase liver imaging with a dual contrast agent protocol.

Diagnostic imaging of hepatocellular carcinoma (HCC) requires a liver CT or MRI multiphase acquisition protocol. Patients would benefit from a high-resolution imaging method capable of performing multi-phase imaging in a single acquisition without an increase in radiation dose. Spectral Photon-Counting Computed Tomography (SPCCT) has recently emerged as a novel and promising imaging modality in the field of diagnostic radiology. SPCCT is able to distinguish between two contrast agents referred to as multicolor imaging because, when measuring in three or more energy regimes, it can detect and quantify elements with a K-edge in the diagnostic energy range. Based on this capability, we tested the feasibility of a dual-contrast multi-phase liver imaging protocol via the use of iodinated and gadolinated contrast agents on four healthy New Zealand White (NZW) rabbits. To perform a dual-contrast protocol, we injected the agents at different times so that the first contrast agent visualized the portal phase and the second the arterial phase, both of which are mandatory for liver lesion characterization. We demonstrated a sensitive discrimination and quantification of gadolinium within the arteries and iodine within the liver parenchyma. In the hepatic artery, the concentration of gadolinium was much higher than iodine (8.5 ± 3.9 mg/mL versus 0.7 ± 0.1 mg/mL) contrary to the concentrations found in the liver parenchyma (0.5 ± 0.3 mg/mL versus 4.2 ± 0.3 mg/mL). In conclusion, our results confirm that SPCCT allows in-vivo dual contrast qualitative and quantitative multi-phase liver imaging in a single acquisition.

Optogenetic approaches to study the mammalian brain.

Optogenetics has revolutionized neurobiological research by allowing to disentangle intricate neuronal circuits at a spatio-temporal precision unmatched by other techniques. Here, we review current advances of optogenetic applications in mammals, especially focusing on freely moving animals. State-of-the-art strategies allow the targeted expression of opsins in neuronal subpopulations, defined either by genetic cell type or neuronal projection pattern. Optogenetic manipulations of these subpopulations become particularly powerful when combined with behavioral paradigms and neurophysiological readout techniques. Thereby, specific roles can be assigned to identified cells. All-optical approaches with the opportunity to write complex three dimensional patterns into neuronal networks have recently emerged. While clinical implications of the new tool set seem tempting, we emphasize here the role of optogenetics for basic research.

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.

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.

The Potential Role of Gap Junctional Plasticity in the Regulation of State.

Electrical synapses are the functional correlate of gap junctions and allow transmission of small molecules and electrical current between coupled neurons. Instead of static pores, electrical synapses are actually plastic, similar to chemical synapses. In the thalamocortical system, gap junctions couple inhibitory neurons that are similar in their biochemical profile, morphology, and electrophysiological properties. We postulate that electrical synaptic plasticity among inhibitory neurons directly interacts with the switching between different firing patterns in a state-dependent and type-dependent manner. In neuronal networks, electrical synapses may function as a modifiable resonance feedback system that enables stable oscillations. Furthermore, the plasticity of electrical synapses may play an important role in regulation of state, synchrony, and rhythmogenesis in the mammalian thalamocortical system, similar to chemical synaptic plasticity. Based on their plasticity, rich diversity, and specificity, electrical synapses are thus likely to participate in the control of consciousness and attention.

Spectral Photon-counting CT: Initial Experience with Dual-Contrast Agent K-Edge Colonography.

Purpose To investigate the feasibility of using spectral photon-counting computed tomography (CT) to differentiate between gadolinium-based and nonionic iodine-based contrast material in a colon phantom by using the characteristic k edge of gadolinium. Materials and Methods A custom-made colon phantom was filled with nonionic iodine-based contrast material, and a gadolinium-filled capsule representing a contrast material-enhanced polyp was positioned on the colon wall. The colon phantom was scanned with a preclinical spectral photon-counting CT system to obtain spectral and conventional data. By fully using the multibin spectral information, material decomposition was performed to generate iodine and gadolinium maps. Quantitative measurements were performed within the lumen and polyp to quantitatively determine the absolute content of iodine and gadolinium. Results In a conventional CT section, absorption values of both contrast agents were similar at approximately 110 HU. Contrast material maps clearly differentiated the distributions, with gadolinium solely in the polyp and iodine in the lumen of the colon. Quantitative measurements of contrast material concentrations in the colon and polyp matched well with those of actual prepared mixtures. Conclusion Dual-contrast spectral photon-counting CT colonography with iodine-filled lumen and gadolinium-tagged polyps may enable ready differentiation between polyps and tagged fecal material. © RSNA, 2016.

Reducing Radiation Dose at Chest CT: Comparison Among Model-based Type Iterative Reconstruction, Hybrid Iterative Reconstruction, and Filtered Back Projection.

RATIONALE AND OBJECTIVES: The study aimed to evaluate the performances of two iterative reconstruction (IR) algorithms and of filtered back projection (FBP) when using reduced-dose chest computed tomography (RDCT) compared to standard-of-care CT. MATERIALS AND METHODS: An institutional review board approval was obtained. Thirty-six patients with hematologic malignancies referred for a control chest CT of a known lung disease were prospectively enrolled. Patients underwent standard-of-care scan reconstructed with hybrid IR, followed by an RDCT reconstructed with FBP, hybrid IR, and iterative model reconstruction. Objective and subjective quality measurements, lesion detectability, and evolution assessment on RDCT were recorded. RESULTS: For RDCT, the CTDIvol (volumetric computed tomography dose index) was 0.43 mGy⋅cm for all patients, and the median [interquartile range] effective dose was 0.22 mSv [0.22-0.24]; corresponding measurements for standard-of-care scan were 3.4 mGy [3.1-3.9] and 1.8 mSv [1.6-2.0]. Noise significantly decreased from FBP to hybrid IR and from hybrid IR to iterative model reconstruction on RDCT, whereas lesion conspicuity and diagnostic confidence increased. Accurate evolution assessment was obtained in all cases with IR. Emphysema identification was higher with iterative model reconstruction. CONCLUSION: Although iterative model reconstruction offered better diagnostic confidence and emphysema detection, both IR algorithms allowed an accurate evolution assessment with an effective dose of 0.22 mSv.