Michael Lell

Aggregated neutrophil extracellular traps limit inflammation by degrading cytokines and chemokines

Gout is characterized by an acute inflammatory reaction and the accumulation of neutrophils in response to monosodium urate (MSU) crystals. Inflammation resolves spontaneously within a few days, although MSU crystals can still be detected in the synovial fluid and affected tissues. Here we report that neutrophils recruited to sites of inflammation undergo oxidative burst and form neutrophil extracellular traps (NETs). Under high neutrophil densities, these NETs aggregate and degrade cytokines and chemokines via serine proteases. Tophi, the pathognomonic structures of chronic gout, share characteristics with aggregated NETs, and MSU crystals can induce NETosis and aggregation of NETs. In individuals with impaired NETosis, MSU crystals induce uncontrolled production of inflammatory mediators from neutrophils and persistent inflammation. Furthermore, in models of neutrophilic inflammation, NETosis-deficient mice develop exacerbated and chronic disease that can be reduced by adoptive transfer of aggregated NETs. These findings suggest that aggregated NETs promote the resolution of neutrophilic inflammation by degrading cytokines and chemokines and disrupting neutrophil recruitment and activation.

Normalized metal artifact reduction (NMAR) in computed tomography

PURPOSE While modern clinical CT scanners under normal circumstances produce high quality images, severe artifacts degrade the image quality and the diagnostic value if metal prostheses or other metal objects are present in the field of measurement. Standard methods for metal artifact reduction (MAR) replace those parts of the projection data that are affected by metal (the so-called metal trace or metal shadow) by interpolation. However, while sinogram interpolation methods efficiently remove metal artifacts, new artifacts are often introduced, as interpolation cannot completely recover the information from the metal trace. The purpose of this work is to introduce a generalized normalization technique for MAR, allowing for efficient reduction of metal artifacts while adding almost no new ones. The method presented is compared to a standard MAR method, as well as MAR using simple length normalization. METHODS In the first step, metal is segmented in the image domain by thresholding. A 3D forward projection identifies the metal trace in the original projections. Before interpolation, the projections are normalized based on a 3D forward projection of a prior image. This prior image is obtained, for example, by a multithreshold segmentation of the initial image. The original rawdata are divided by the projection data of the prior image and, after interpolation, denormalized again. Simulations and measurements are performed to compare normalized metal artifact reduction (NMAR) to standard MAR with linear interpolation and MAR based on simple length normalization. RESULTS Promising results for clinical spiral cone-beam data are presented in this work. Included are patients with hip prostheses, dental fillings, and spine fixation, which were scanned at pitch values ranging from 0.9 to 3.2. Image quality is improved considerably, particularly for metal implants within bone structures or in their proximity. The improvements are evaluated by comparing profiles through images and sinograms for the different methods and by inspecting ROIs. NMAR outperforms both other methods in all cases. It reduces metal artifacts to a minimum, even close to metal regions. Even for patients with dental fillings, which cause most severe artifacts, satisfactory results are obtained with NMAR. In contrast to other methods, NMAR prevents the usual blurring of structures close to metal implants if the metal artifacts are moderate. CONCLUSIONS NMAR clearly outperforms the other methods for both moderate and severe artifacts. The proposed method reliably reduces metal artifacts from simulated as well as from clinical CT data. Computationally efficient and inexpensive compared to iterative methods, NMAR can be used as an additional step in any conventional sinogram inpainting-based MAR method.

Dose reduction in computed tomography by attenuation-based on-line modulation of tube current: evaluation of six anatomical regions.

Abstract. This study investigated the potential of attenuation-based on-line modulation of tube current to reduce the dose of computed tomography (in milliamperes) without loss in image quality. The dose can be reduced for non-circular patient cross-sections by reducing the tube current at the angular positions at which the diameter through the patient diameter is smallest. We investigated a new technical approach with attenuation-based on-line modulation of tube current. Computed tomographic projection data were analyzed to determine the optimal milliampere values for each projection angle in real time, instead of performing prior measurements with localizer radiographs. We compared image quality, noise pattern, and dose for standard scans and for scans with attenuation-based on-line modulation of tube current in a group of 30 radiation therapy patients. Six different anatomical regions were examined: head, shoulder, thorax, abdomen, pelvis, and extremities (knee). Image quality was evaluated by four radiologists in a blinded fashion. We found the dose to be reduced typically by 15–50 %. In general, no deterioration in image quality was observed. Thus the dose in computed tomography be reduced substantially by technical measures without sacrificing image quality. Attenuation-based on-line modulation of tube current is an efficient and practical means for this.

Dose reduction in CT examination of children by an attenuation-based on-line modulation of tube current (CARE Dose)

Abstract. In a controlled patient study we investigated the potential of attenuation-based on-line modulation of the tube current to reduce milliampere values (mAs) in CT examinations of children without loss of image quality. mAs can be reduced for non-circular patient cross sections without an increase in noise if tube current is reduced at those angular positions where the patient diameter and, consequently, attenuation are small. We investigated a technical approach with an attenuation-based on-line control for the tube current realised as a work-in-progress implementation. The CT projection data are analysed in real time to determine optimal mAs values for each projection angle. We evaluated mAs reduction for 100 spiral CT examinations with attenuation-based on-line modulation of the tube current in a group of children. Two radiologists evaluated image quality by visual interpretation in consensus. We compared the mAs values read from the CT scanner with preset mAs of a standard protocol. Four different scan regions were examined in spiral technique (neck, thorax, abdomen, thorax and abdomen). We found the mAs product to be reduced typically by 10–60% depending on patient geometry and anatomical regions. The mean reduction was 22.3% (neck 20%, thorax 23%, abdomen 23%, thorax and abdomen 22%). In general, no deterioration of image quality was observed. There was no correlation between the age and the mean mAs reduction in the different anatomical regions. By classifying the children respectively to their weight, there is a positive trend between increasing weight and mAs reduction. We conclude that mAs in spiral CT examinations of children can be reduced substantially by attenuation-based on-line modulation of the tube current without deterioration of image quality. Attenuation-based on-line modulation of tube current is efficient and practical for reducing dose exposure to children.

Detection of Coronary Artery Stenoses by Low-Dose, Prospectively ECG-Triggered, High-Pitch Spiral Coronary CT Angiography

OBJECTIVES We sought to evaluate the diagnostic accuracy of a new prospectively electrocardiogram (ECG)-triggered high-pitch scan mode for coronary computed tomography angiography (CTA), which allows an effective dose of less than 1 mSv. BACKGROUND Coronary CTA provides increasingly reliable image quality, but the associated radiation exposure can be high. METHODS Seventy-five patients with suspected coronary artery disease and in sinus rhythm were screened for participation. After exclusion of 25 patients for body weight >100 kg or failure to lower heart rate to ≤ 60 beats/min, 50 patients were studied by prospectively ECG-triggered high-pitch spiral computed tomography (CT). Coronary CTA was performed using a dual-source CT system with 2 × 128 × 0.6-mm collimation, 0.28-s rotation time, a pitch of 3.4, 100-kVp tube voltage, and current of 320 mA. Data acquisition was prospectively triggered at 60% of the R-R interval and completed within 1 cardiac cycle. Diagnostic accuracy for detection of coronary artery stenoses ≥ 50% diameter stenosis was determined by comparison to invasive coronary angiography. Per-patient diagnostic performance was the primary form of analysis. RESULTS In all 50 patients (34 males, 59 ± 12 years of age), imaging was successful. For the detection of 16 patients with at least 1 coronary artery stenosis, CT demonstrated a sensitivity of 100% (95% confidence interval [CI]: 79% to 100%) and specificity of 82% (95% CI: 65% to 93%). The positive predictive value was 72% (95% CI: 49% to 89%) and the negative predictive value was 100% (95% CI: 87% to 100%). Sensitivity was 100% (95% CI: 88% to 100%) and specificity was 94% (95% CI: 89% to 97%) on a per-vessel basis. Per-segment sensitivity was 92% (95% CI: 80% to 97%), and specificity was 98% (95% CI: 96% to 98%). Mean dose-length product for coronary CTA was 54 ± 6 mGy · cm, the effective dose was 0.76 ± 0.08 mSv (0.64 to 0.95 mSv). CONCLUSIONS In nonobese patients with a low and stable heart rate, prospectively ECG-triggered high-pitch spiral coronary CTA provides high diagnostic accuracy for the detection of coronary artery stenoses.

High-pitch spiral computed tomography: effect on image quality and radiation dose in pediatric chest computed tomography.

Objectives:Computed tomography (CT) is considered the method of choice in thoracic imaging for a variety of indications. Sedation is usually necessary to enable CT and to avoid deterioration of image quality because of patient movement in small children. We evaluated a new, subsecond high-pitch scan mode (HPM), which obviates the need of sedation and to hold the breath. Material and Methods:A total of 60 patients were included in this study. 30 patients (mean age, 14 ± 17 month; range, 0–55 month) were examined with a dual source CT system in an HPM. Scan parameters were as follows: pitch = 3.0, 128 × 0.6 mm slice acquisition, 0.28 seconds gantry rotation time, ref. mAs adapted to the body weight (50–100 mAs) at 80 kV. Images were reconstructed with a slice thickness of 0.75 mm. None of the children was sedated for the CT examination and no breathing instructions were given. Image quality was assessed focusing on motion artifacts and delineation of the vascular structures and lung parenchyma. Thirty patients (mean age, 15 ± 17 month; range, 0–55 month) were examined under sedation on 2 different CT systems (10-slice CT, n = 18; 64-slice CT, n = 13 patients) in conventional pitch mode (CPM). Dose values were calculated from the dose length product provided in the patient protocol/dose reports, Monte Carlo simulations were performed to assess dose distribution for CPM and HPM. Results:All scans were performed without complications. Image quality was superior with HPM, because of a significant reduction in motion artifacts, as compared to CPM with 10- and 64-slice CT. In the control group, artifacts were encountered at the level of the diaphragm (n = 30; 100%), the borders of the heart (n = 30; 100%), and the ribs (n = 20; 67%) and spine (n = 6; 20%), whereas motion artifacts were detected in the HPM-group only in 6 patients in the lung parenchyma next to the diaphragm or the heart (P < 0,001). Dose values were within the same range in the patient examinations (CPM, 1.9 ± 0.6 mSv; HPM, 1.9 ± 0.5 mSv; P = 0.95), although z-overscanning increased with the increase of detector width and pitch-value. Conclusion:High-pitch chest CT is a robust method to provide highest image quality making sedation or controlled ventilation for the examination of infants, small or uncooperative children unnecessary, whereas maintaining low radiation dose values.

Dose reduction in abdominal computed tomography: intraindividual comparison of image quality of full-dose standard and half-dose iterative reconstructions with dual-source computed tomography.

Objectives:We sought to evaluate the image quality of iterative reconstruction in image space (IRIS) in half-dose (HD) datasets compared with full-dose (FD) and HD filtered back projection (FBP) reconstruction in abdominal computed tomography (CT). Materials and Methods:To acquire data with FD and HD simultaneously, contrast-enhanced abdominal CT was performed with a dual-source CT system, both tubes operating at 120 kV, 100 ref.mAs, and pitch 0.8. Three different image datasets were reconstructed from the raw data: Standard FD images applying FBP which served as reference, HD images applying FBP and HD images applying IRIS. For the HD data sets, only data from 1 tube detector-system was used. Quantitative image quality analysis was performed by measuring image noise in tissue and air. Qualitative image quality was evaluated according to the European Guidelines on Quality criteria for CT. Additional assessment of artifacts, lesion conspicuity, and edge sharpness was performed. Results:Image noise in soft tissue was substantially decreased in HD-IRIS (−3.4 HU, −22%) and increased in HD-FBP (+6.2 HU, +39%) images when compared with the reference (mean noise, 15.9 HU). No significant differences between the FD-FBP and HD-IRIS images were found for the visually sharp anatomic reproduction, overall diagnostic acceptability (P = 0.923), lesion conspicuity (P = 0.592), and edge sharpness (P = 0.589), while HD-FBP was rated inferior. Streak artifacts and beam hardening was significantly more prominent in HD-FBP while HD-IRIS images exhibited a slightly different noise pattern. Conclusions:Direct intrapatient comparison of standard FD body protocols and HD-IRIS reconstruction suggest that the latest iterative reconstruction algorithms allow for approximately 50% dose reduction without deterioration of the high image quality necessary for confident diagnosis.

Frequency split metal artifact reduction (FSMAR) in computed tomography.

PURPOSE The problem of metal artifact reduction (MAR) is almost as old as the clinical use of computed tomography itself. When metal implants are present in the field of measurement, severe artifacts degrade the image quality and the diagnostic value of CT images. Up to now, no generally accepted solution to this issue has been found. In this work, a method based on a new MAR concept is presented: frequency split metal artifact reduction (FSMAR). It ensures efficient reduction of metal artifacts at high image quality with enhanced preservation of details close to metal implants. METHODS FSMAR combines a raw data inpainting-based MAR method with an image-based frequency split approach. Many typical methods for metal artifact reduction are inpainting-based MAR methods and simply replace unreliable parts of the projection data, for example, by linear interpolation. Frequency split approaches were used in CT, for example, by combining two reconstruction methods in order to reduce cone-beam artifacts. FSMAR combines the high frequencies of an uncorrected image, where all available data were used for the reconstruction with the more reliable low frequencies of an image which was corrected with an inpainting-based MAR method. The algorithm is tested in combination with normalized metal artifact reduction (NMAR) and with a standard inpainting-based MAR approach. NMAR is a more sophisticated inpainting-based MAR method, which introduces less new artifacts which may result from interpolation errors. A quantitative evaluation was performed using the examples of a simulation of the XCAT phantom and a scan of a spine phantom. Further evaluation includes patients with different types of metal implants: hip prostheses, dental fillings, neurocoil, and spine fixation, which were scanned with a modern clinical dual source CT scanner. RESULTS FSMAR ensures sharp edges and a preservation of anatomical details which is in many cases better than after applying an inpainting-based MAR method only. In contrast to other MAR methods, FSMAR yields images without the usual blurring close to implants. CONCLUSIONS FSMAR should be used together with NMAR, a combination which ensures an accurate correction of both high and low frequencies. The algorithm is computationally inexpensive compared to iterative methods and methods with complex inpainting schemes. No parameters were chosen manually; it is ready for an application in clinical routine.

Effects of Adaptive Section Collimation on Patient Radiation Dose in Multisection Spiral CT

PURPOSE To evaluate the potential effectiveness of adaptive collimation in reducing computed tomographic (CT) radiation dose owing to z-overscanning by using dose measurements and Monte Carlo (MC) dose simulations. MATERIALS AND METHODS Institutional review board approval was not necessary. Dose profiles were measured with thermoluminescent dosimeters in CT dose index phantoms and in an Alderson-Rando phantom without and with adaptive section collimation for spiral cardiac and chest CT protocols and were compared with the MC simulated dose profiles. Additional dose measurements were performed with an ionization chamber for scan ranges of 5-50 cm and pitch factors of 0.5-1.5. RESULTS The measured and simulated dose profiles agreed to within 3%. By using adaptive section collimation, a substantial dose reduction of up to 10% was achieved for cardiac and chest CT when measurements were performed free in air and of 7% on average when measurements were performed in phantoms. For scan ranges smaller than 12 cm, ionization chamber measurements and simulations indicated a dose reduction of up to 38%. CONCLUSION Adaptive section collimation allows substantial reduction of unnecessary exposure owing to z-overscanning in spiral CT. It can be combined in synergy with other means of dose reduction, such as spectral optimization and automatic exposure control.

Head and neck tumors: imaging recurrent tumor and post-therapeutic changes with CT and MRI.

OBJECTIVE To evaluate criteria for detection of tumor recurrence and post-treatment changes in patients with head and neck malignancies in computed tomography (CT) and magnetic resonance imaging (MRI). METHODS AND MATERIALS Thirty-nine patients with head and neck carcinoma receiving radiochemotherapy were examined before, during and after therapy with MRI. Changes in signal intensity were correlated to histology or clinical course. Three hundred and thirty-one patients with head and neck malignancies were examined with CT after therapy. CT diagnoses were correlated with histology or clinical course. RESULTS Main criteria for recurrent/residual tumor in MRI was infiltrative mass with high signal intensity in T2-weighted images and enhancement after Gd-DTPA in T1-weighted images. Radiation-induced changes led to false positive diagnosis in 46% in the interval up to 3 months after therapy and in 58% in the interval 3-6 months after therapy. The combination of a circumscribed, infiltrative mass with contrast enhancement in CT had a sensitivity of 86% and a specificity of 80%. CONCLUSION CT could accurately demonstrate postoperative changes and tumor recurrence. MRI had advantages in differentiation of tumor and scar, but edema after radiation therapy can spoil diagnosis.