Abdominopelvic CT Image Quality: Evaluation of Thin (0.5-mm) Slices Using Deep Learning Reconstruction.

BACKGROUND. Because thick-section images (typically 3-5 mm) have low image noise, radiologists typically use them to perform clinical interpretation, although they may additionally refer to thin-section images (typically 0.5-0.625 mm) for problem solving. Deep learning reconstruction (DLR) can yield thin-section images with low noise. OBJECTIVE. The purpose of this study is to compare abdominopelvic CT image quality between thin-section DLR images and thin- and thick-section hybrid iterative reconstruction (HIR) images. METHODS. This retrospective study included 50 patients (31 men and 19 women; median age, 64 years) who underwent abdominopelvic CT between June 15, 2020, and July 29, 2020. Images were reconstructed at 0.5-mm section using DLR and at 0.5-mm and 3.0-mm sections using HIR. Five radiologists independently performed pairwise comparisons (0.5-mm DLR and either 0.5-mm or 3.0-mm HIR) and recorded the preferred image for subjective image quality measures (scale, -2 to 2). The pooled scores of readers were compared with a score of 0 (denoting no preference). Image noise was quantified using the SD of ROIs on regions of homogeneous liver. RESULTS. For comparison of 0.5-mm DLR images and 0.5-mm HIR images, the median pooled score was 2 (indicating a definite preference for DLR) for noise and overall image quality and 1 (denoting a slight preference for DLR) for sharpness and natural appearance. For comparison of 0.5-mm DLR and 3.0-mm HIR, the median pooled score was 1 for the four previously mentioned measures. These assessments were all significantly different (p < .001) from 0. For artifacts, the median pooled score for both comparisons was 0, which was not significant for comparison with 3.0-mm HIR (p = .03) but was significant for comparison with 0.5-mm HIR (p < .001) due to imbalance in scores of 1 (n = 28) and -1 (slight preference for HIR, n = 1). Noise for 0.5-mm DLR was lower by mean differences of 12.8 HU compared with 0.5-mm HIR and 4.4 HU compared with 3.0-mm HIR (both p < .001). CONCLUSION. Thin-section DLR improves subjective image quality and reduces image noise compared with currently used thin- and thick-section HIR, without causing additional artifacts. CLINICAL IMPACT. Although further diagnostic performance studies are warranted, the findings suggest the possibility of replacing current use of both thin- and thick-section HIR with the use of thin-section DLR only during clinical interpretations.

Intra-therapeutic dosimetry of [177Lu]Lu-PSMA-617 in low-volume hormone-sensitive metastatic prostate cancer patients and correlation with treatment outcome.

INTRODUCTION: While [177Lu]Lu-PSMA radioligand therapy is currently only applied in end-stage metastatic castrate-resistant prostate cancer (mCRPC) patients, also low-volume hormone-sensitive metastatic prostate cancer (mHSPC) patients can benefit from it. However, there are toxicity concerns related to the sink effect in low-volume disease. This prospective study aims to determine the kinetics of [177Lu]Lu-PSMA in mHSPC patients, analyzing the doses to organs at risk (salivary glands, kidneys, liver, and bone marrow) and tumor lesions < 1 cm diameter. METHODS: Ten mHSPC patients underwent two cycles of [177Lu]Lu-PSMA therapy. Three-bed position SPECT/CT was performed at 5 time points after each therapy. Organ dosimetry and lesion dosimetry were performed using commercial software and a manual approach, respectively. Correlation between absorbed index lesion dose and treatment response (PSA drop of > 50% at the end of the study) was calculated and given as Spearman's r and p-values. RESULTS: Kinetics of [177Lu]Lu-PSMA in mHSPC patients are comparable to those in mCRPC patients. Lesion absorbed dose was high (3.25 ± 3.19 Gy/GBq) compared to organ absorbed dose (salivary glands: 0.39 ± 0.17 Gy/GBq, kidneys: 0.49 ± 0.11 Gy/GBq, liver: 0.09 ± 0.01 Gy/GBq, bone marrow: 0.017 ± 0.008 Gy/GBq). A statistically significant correlation was found between treatment response and absorbed index lesion dose (p = 0.047). CONCLUSIONS: We successfully performed small lesion dosimetry and showed that the tumor sink effect in mHSPC patients is of less concern than was expected. Tumor-to-organ ratio of absorbed dose was high and tumor uptake correlates with PSA response. Additional treatment cycles are legitimate in terms of organ toxicity and could lead to better tumor response.

[68Ga]Ga-PSMA-11 PET imaging as a predictor for absorbed doses in organs at risk and small lesions in [177Lu]Lu-PSMA-617 treatment.

INTRODUCTION: Patient eligibility for [177Lu]Lu-PSMA therapy remains a challenge, with only 40-60% response rate when patient selection is done based on the lesion uptake (SUV) on [68Ga]Ga-PSMA-PET/CT. Prediction of absorbed dose based on this pre-treatment scan could improve patient selection and help to individualize treatment by maximizing the absorbed dose to target lesions while adhering to the threshold doses for the organs at risk (kidneys, salivary glands, and liver). METHODS: Ten patients with low-volume hormone-sensitive prostate cancer received a pre-therapeutic [68Ga]Ga-PSMA-11 PET/CT, followed by 3 GBq [177Lu]Lu-PSMA-617 therapy. Intra-therapeutically, SPECT/CT was acquired at 1, 24, 48, 72, and 168 h. Absorbed dose in organs and lesions (n = 22) was determined according to the MIRD scheme. Absorbed dose prediction based on [68Ga]Ga-PSMA-PET/CT was performed using tracer uptake at 1 h post-injection and the mean tissue effective half-life on SPECT. Predicted PET/actual SPECT absorbed dose ratios were determined for each target volume. RESULTS: PET/SPECT absorbed dose ratio was 1.01 ± 0.21, 1.10 ± 0.15, 1.20 ± 0.34, and 1.11 ± 0.29 for kidneys (using a 2.2 scaling factor), liver, submandibular, and parotid glands, respectively. While a large inter-patient variation in lesion kinetics was observed, PET/SPECT absorbed dose ratio was 1.3 ± 0.7 (range: 0.4-2.7, correlation coefficient r = 0.69, p < 0.01). CONCLUSION: A single time point [68Ga]Ga-PSMA-PET scan can be used to predict the absorbed dose of [177Lu]Lu-PSMA therapy to organs, and (to a limited extent) to lesions. This strategy facilitates in treatment management and could increase the personalization of [177Lu]Lu-PSMA therapy.

Deep learning-based reconstruction may improve non-contrast cerebral CT imaging compared to other current reconstruction algorithms.

OBJECTIVES: To evaluate image quality and reconstruction times of a commercial deep learning reconstruction algorithm (DLR) compared to hybrid-iterative reconstruction (Hybrid-IR) and model-based iterative reconstruction (MBIR) algorithms for cerebral non-contrast CT (NCCT). METHODS: Cerebral NCCT acquisitions of 50 consecutive patients were reconstructed using DLR, Hybrid-IR and MBIR with a clinical CT system. Image quality, in terms of six subjective characteristics (noise, sharpness, grey-white matter differentiation, artefacts, natural appearance and overall image quality), was scored by five observers. As objective metrics of image quality, the noise magnitude and signal-difference-to-noise ratio (SDNR) of the grey and white matter were calculated. Mean values for the image quality characteristics scored by the observers were estimated using a general linear model to account for multiple readers. The estimated means for the reconstruction methods were pairwise compared. Calculated measures were compared using paired t tests. RESULTS: For all image quality characteristics, DLR images were scored significantly higher than MBIR images. Compared to Hybrid-IR, perceived noise and grey-white matter differentiation were better with DLR, while no difference was detected for other image quality characteristics. Noise magnitude was lower for DLR compared to Hybrid-IR and MBIR (5.6, 6.4 and 6.2, respectively) and SDNR higher (2.4, 1.9 and 2.0, respectively). Reconstruction times were 27 s, 44 s and 176 s for Hybrid-IR, DLR and MBIR respectively. CONCLUSIONS: With a slight increase in reconstruction time, DLR results in lower noise and improved tissue differentiation compared to Hybrid-IR. Image quality of MBIR is significantly lower compared to DLR with much longer reconstruction times. KEY POINTS: • Deep learning reconstruction of cerebral non-contrast CT results in lower noise and improved tissue differentiation compared to hybrid-iterative reconstruction. • Deep learning reconstruction of cerebral non-contrast CT results in better image quality in all aspects evaluated compared to model-based iterative reconstruction. • Deep learning reconstruction only needs a slight increase in reconstruction time compared to hybrid-iterative reconstruction, while model-based iterative reconstruction requires considerably longer processing time.

Correction to: Physical evaluation of an ultra-high-resolution CT scanner.

The original version of this article, published on 10 February 2019, unfortunately contained a mistake. The axes of the graphs in Fig. 3 are incorrect. The correct figure is given below. Therefore, the last two sentences in "Results," section "Noise," should read: "The peak frequency of the HR and SHR was 0.21 lp/mm. For the NR mode and the MDCT, the peak frequencies were 0.17 lp/mm and 0.21 lp/mm, respectively."

Physical evaluation of an ultra-high-resolution CT scanner.

OBJECTIVES: To evaluate the technical performance of an ultra-high-resolution CT (UHRCT) system. METHODS: The physico-technical capabilities of a novel commercial UHRCT system were assessed and compared with those of a current-generation multi-detector (MDCT) system. The super-high-resolution (SHR) mode of the system uses 0.25 mm (at isocentre) detector elements (dels) in the in-plane and longitudinal directions, while the high-resolution (HR) mode bins two dels in the longitudinal direction. The normal-resolution (NR) mode bins dels 2 × 2, resulting in a del-size equivalent to that of the MDCT system. In general, standard procedures and phantoms were used to perform these assessments. RESULTS: The UHRCT MTF (10% MTF 4.1 lp/mm) is twice as high as that of the MDCT (10% MTF 1.9 lp/mm), which is comparable to the MTF in the NR mode (10% MTF 1.7 lp/mm). The width of the slice sensitivity profile in the SHR mode (FWHM 0.45 mm) is about 60% of that of the MDCT (FWHM 0.77 mm). Uniformity and CT numbers are within the expected range. Noise in the high-resolution modes has a higher magnitude and higher frequency components compared with MDCT. Low-contrast visibility is lower for the NR, HR and SHR modes compared with MDCT, but about a 14%, for NR, and 23%, for HR and SHR, dose increase gives the same results. CONCLUSIONS: HR and SHR mode scanning results in double the spatial resolution, with about a 23% increase in dose required to achieve the same low-contrast detectability. KEY POINTS: • Resolution on UHRCT is up to twice as high as for the tested MDCT. • With abdominal settings, UHRCT needs higher dose for the same low-contrast detectability as MDCT, but dose is still below achievable levels as defined by current diagnostic reference levels. • The UHRCT system used in normal-resolution mode yields comparable resolution and noise characteristics as the MDCT system.

Fast 3-T MR-guided transrectal prostate biopsy using an in-room tablet device for needle guide alignment: a feasibility study.

OBJECTIVES: To assess the feasibility of adding a tablet device inside the scanner room to assist needle-guide alignment during magnetic resonance (MR)-guided transrectal prostate biopsy. METHODS: Twenty patients with one cancer-suspicious region (CSR) with PI-RADS score ≥ 4 on diagnostic multiparametric MRI were prospectively enrolled. Two orthogonal scan planes of an MR fluoroscopy sequence (~3 images/s) were aligned to the CSR and needle-guide pivoting point. Targeting was achieved by manipulating the needle-guide under MR fluoroscopy feedback on the in-room tablet device. Technical feasibility and targeting success were assessed. Complications and biopsy procedure times were also recorded. RESULTS: Needle-guide alignment with the in-room tablet device was technically successful in all patients and allowed sampling after a single alignment step in 19/20 (95%) CSRs (median size 14 mm, range: 4-45). Biopsy cores contained cancer in 18/20 patients. There were no per-procedural or post-biopsy complications. Using the tablet device, the mean time to first biopsy was 5.8 ± 1.0 min and the mean total procedure time was 23.7 ± 4.1 min. CONCLUSIONS: Use of an in-room tablet device to assist needle-guide alignment was feasible and safe during MR-guided transrectal prostate biopsy. Initial experience indicates potential for procedure time reduction. KEY POINTS: • Performing MR-guided prostate biopsy using an in-room tablet device is feasible. • CSRs could be sampled after a single alignment step in 19/20 patients. • The mean procedure time for biopsy with the tablet device was 23.7 min.

Comparing dual energy CT and subtraction CT on a phantom: which one provides the best contrast in iodine maps for sub-centimetre details?

OBJECTIVES: To compare contrast-to-noise ratios (CNRs) and iodine discrimination thresholds on iodine maps derived from dual energy CT (DECT) and subtraction CT (SCT). METHODS: A contrast-detail phantom experiment was performed with 2 to 15 mm diameter tubes containing water or iodinated contrast concentrations ranging from 0.5 mg/mL to 20 mg/mL. DECT scans were acquired at 100 kVp and at 140 kVp+Sn filtration. SCT scans were acquired at 100 kVp. Iodine maps were created by material decomposition (DECT) or by subtraction of water scans from iodine scans (SCT). Matched exposure levels varied from 8 to 15 mGy. Iodine discrimination thresholds (Cr) and response times were determined by eight observers. RESULTS: The adjusted mean CNR was 1.9 times higher for SCT than for DECT. Exposure level had no effect on CNR. All observers discriminated all details ≥10 mm at 12 and 15 mGy. For sub-centimetre details, the lowest calculated Cr was ≤ 0.50 mg/mL for SCT and 0.64 mg/mL for DECT. The smallest detail was discriminated at ≥4.4 mg/mL with SCT and at ≥7.4 mg/mL with DECT. Response times were lower for SCT than DECT. CONCLUSIONS: SCT results in higher CNR and reduced iodine discrimination thresholds compared to DECT for sub-centimetre details. KEY POINTS: • Subtraction CT iodine maps exhibit higher CNR than dual-energy iodine maps • Lower iodine concentrations can be discriminated for sub-cm details with SCT • Response times are lower using SCT compared to dual-energy CT.

MR imaging-guided focal cryoablation in patients with recurrent prostate cancer.

PURPOSE: To assess the feasibility of magnetic resonance (MR) imaging-guided focal cryoablation in patients with locally recurrent prostate cancer after radiation therapy. MATERIALS AND METHODS: This was a prospective study, and informed consent was obtained from all patients. Ten consecutive patients with histopathologically proved recurrent prostate cancer after radiation therapy, without evidence of distant metastases, were treated while under general anesthesia in a 1.5-T MR unit. A urethral warmer was inserted. Cryoneedles were transperineally inserted under real-time MR imaging. Then, a rectal warmer was inserted. Ice ball growth was continuously monitored under MR imaging guidance. Two freeze-thaw cycles were performed. Follow-up consisted of a visit to the urologist, measurement of prostate-specific antigen level, and multiparametric MR imaging at 3, 6, and 12 months. Potential complications were recorded. RESULTS: All patients were successfully treated. In one patient, the urethral warmer could not be inserted and the procedure was cancelled. Two months later, the procedure was successfully repeated. Another patient had urinary retention. Follow-up data were available for all patients. A local recurrence or remnant tumor was found in two patients after 6 months and in another patient after 12 months. These three patients underwent successful retreatment with MR imaging-guided focal cryoablation. CONCLUSION: MR imaging-guided focal cryoablation of recurrent prostate cancer after radiation therapy is feasible and safe. Initial results are promising; however, longer follow-up is needed and more patients must be studied.

Assessment of needle guidance devices for their potential to reduce fluoroscopy time and operator hand dose during C-arm cone-beam computed tomography-guided needle interventions.

PURPOSE: To assess whether the use of needle guidance devices can reduce fluoroscopy time and operator hand dose during cone-beam computed tomography-guided needle interventions. MATERIALS AND METHODS: The freehand technique was compared with techniques employing two distinct needle holders and a ceiling-mounted laser guidance technique. Laser guidance was used either alone or in combination with needle holders. Four interventional radiologists were instructed to reach predetermined targets in an abdominal phantom using these techniques. Each operator used all six techniques three times. Fluoroscopy time, procedure time, operator hand dose, and needle tip deviation were obtained for all simulated needle interventions. All data are presented as median (ranges). RESULTS: All procedures were successfully completed within 2-4 minutes, resulting in a deviation from target of 0.8 mm (0-4.7). In freehand procedures, the fluoroscopy time to reach the target was 50 seconds (31-98 s). Laser guidance, used alone or in combination with needle holders, reduced fluoroscopy time to 31 seconds (14-68 s) (P<.02). The operator hand dose in freehand procedures was 275 µSv (20-603 µSv). Laser guidance alone or in combination with needle holders resulted in a reduction of the hand dose to<36 µSv (5-82 µSv) per procedure (P<.001). There were no statistically significant effects on hand dose levels or fluoroscopy time when the needle holders were employed alone. CONCLUSIONS: Compared with the freehand technique, all three tested needle guidance devices performed with equivalent efficiency in terms of accuracy and procedure time. Only the addition of laser guidance was found to reduce both fluoroscopy time and operator hand dose.

Technical performance of a dual-energy CT system with a novel deep-learning based reconstruction process: Evaluation using an abdomen protocol.

BACKGROUND: A new tube voltage-switching dual-energy (DE) CT system using a novel deep-learning based reconstruction process has been introduced. Characterizing the performance of this DE approach can help demonstrate its benefits and potential drawbacks. PURPOSE: To evaluate the technical performance of a novel DECT system and compare it to that of standard single-kV CT and a rotate/rotate DECT, for abdominal imaging. METHODS: DE and single-kV images of four different phantoms were acquired on a kV-switching DECT system, and on a rotate/rotate DECT. The dose for the acquisitions of each phantom was set to that selected for the kV-switching DE mode by the automatic tube current modulation (ATCM) at manufacturer-recommended settings. The dose that the ATCM would have selected in single-kV mode was also recorded. Virtual monochromatic images (VMIs) from 40 to 130 keV, as well as iodine maps, were reconstructed from the DE data. Single-kV images, acquired at 120 kV, were reconstructed using body hybrid iterative reconstruction. All reconstructions were made at 0.5 mm section thickness. Task transfer functions (TTFs) were determined for a Teflon and LDPE rod. Noise magnitude (SD), and noise power spectrum (NPS) were calculated using 240 and 320 mm diameter water phantoms. Iodine quantification accuracy and contrast-to-noise ratios (CNRs) relative to water for 2, 5, 10, and 15 mg I/ml were determined using a multi-energy CT (MECT) phantom. Low-contrast visibility was determined and the presence of beam-hardening artifacts and inhomogeneities were evaluated. RESULTS: The TTFs of the kV-switching DE VMIs were higher than that of the single-kV images for Teflon (20% TTF: 6.8 lp/cm at 40 keV, 6.2 lp/cm for single-kV), while for LDPE the DE TTFs at 70 keV and above were equivalent or higher than the single-kV TTF. All TTFs of the kV-switching DECT were higher than for the rotate/rotate DECT. The SD was lowest in the 70 keV VMI (12.0 HU), which was lower than that of single-kV (18.3 HU). The average NPS frequency varied between 2.3 lp/cm and 4.2 lp/cm for the kV-switching VMIs and was 2.2 lp/cm for single-kV. The error in iodine quantification was at maximum 1 mg I/ml (at 5 mg I/ml). The highest CNR for all iodine concentrations was at 60 keV, 2.5 times higher than the CNR for single-kV. At 70-90 keV, the number of visible low contrast objects was comparable to that in single-kV, while other VMIs showed fewer objects. At manufacturer-recommended ATCM settings, the CTDIvol for the DE acquisitions of the water and MECT phantoms were 12.6 and 15.4 mGy, respectively, and higher than that for single-kV. The 70 keV VMI had less severe beam hardening artifacts than single-kV images. Hyper- and hypo-dense blotches may appear in VMIs when object attenuation exceeds manufacturer recommended limits. CONCLUSIONS: At manufacturer-recommended ATCM settings for abdominal imaging, this DE implementation results in higher CTDIvol compared to single-kV acquisitions. However, it can create sharper, lower noise VMIs with up to 2.5 times higher iodine CNR compared to single-kV images acquired at the same dose.

Optimization of the radiation dosimetry protocol in Lutetium-177-PSMA therapy: toward clinical implementation.

BACKGROUND: Dosimetry in [177Lu]Lu-PSMA therapy is a valuable tool to assess treatment efficacy and toxicity. This study aims to develop a clinically implementable protocol to determine the absorbed dose in organs and tumor lesions after [177Lu]Lu-PSMA-617 therapy, by reducing the imaging time points and utilizing population-based kinetics with a single scan, with evaluation of its influence on the uncertainty in absorbed dose. METHODS: Ten patients with metastatic hormone-sensitive prostate cancer received two cycles of [177Lu]Lu-PSMA-617. Post-treatment imaging was performed at 1 h, 24 h, 48 h, 72 h and 168 h, consisting of three-bed positions SPECT/CT and a whole-body planar scan. Five-time point SPECT dosimetry was performed for lesions and organs with physiological uptake (kidneys, liver and salivary glands) and used as the reference standard. Absorbed dose values for various simplified protocols were compared to the reference standard. RESULTS: Accurate lesion dosimetry is possible using one-time point SPECT imaging at 168 h, with an increase in uncertainty (20% vs. 14% for the reference standard). By including a second time point, uncertainty was comparable to the reference standard (13%). Organ dosimetry can be performed using a single SPECT at 24 h or 48 h. Dosimetry based on planar scans did not provide accurate dose estimations. CONCLUSION: Accurate lesion dosimetry in [177Lu]Lu-PSMA therapy can be performed using a one- or two-time point protocol, making dosimetry assessments more suitable for routine clinical implementation, although dosimetry based om multiple time points is more accurate. Clinical trial registration This study was approved by the Medical Review Ethics Committee Region Arnhem-Nijmegen on January 23, 2018 and was registered on clinicaltrials.gov (NCT03828838).

Coronary Artery Calcium Scoring: Toward a New Standard.

OBJECTIVES: Although the Agatston score is a commonly used quantification method, rescan reproducibility is suboptimal, and different CT scanners result in different scores. In 2007, McCollough et al (Radiology 2007;243:527-538) proposed a standard for coronary artery calcium quantification. Advancements in CT technology over the last decade, however, allow for improved acquisition and reconstruction methods. This study aims to investigate the feasibility of a reproducible reduced dose alternative of the standardized approach for coronary artery calcium quantification on state-of-the-art CT systems from 4 major vendors. MATERIALS AND METHODS: An anthropomorphic phantom containing 9 calcifications and 2 extension rings were used. Images were acquired with 4 state-of-the-art CT systems using routine protocols and a variety of tube voltages (80-120 kV), tube currents (100% to 25% dose levels), slice thicknesses (3/2.5 and 1/1.25 mm), and reconstruction techniques (filtered back projection and iterative reconstruction). Every protocol was scanned 5 times after repositioning the phantom to assess reproducibility. Calcifications were quantified as Agatston scores. RESULTS: Reducing tube voltage to 100 kV, dose to 75%, and slice thickness to 1 or 1.25 mm combined with higher iterative reconstruction levels resulted in an on average 36% lower intrascanner variability (interquartile range) compared with the standard 120 kV protocol. Interscanner variability per phantom size decreased by 34% on average. With the standard protocol, on average, 6.2 ± 0.4 calcifications were detected, whereas 7.0 ± 0.4 were detected with the proposed protocol. Pairwise comparisons of Agatston scores between scanners within the same phantom size demonstrated 3 significantly different comparisons at the standard protocol (P < 0.05), whereas no significantly different comparisons arose at the proposed protocol (P > 0.05). CONCLUSIONS: On state-of-the-art CT systems of 4 different vendors, a 25% reduced dose, thin-slice calcium scoring protocol led to improved intrascanner and interscanner reproducibility and increased detectability of small and low-density calcifications in this phantom. The protocol should be extensively validated before clinical use, but it could potentially improve clinical interscanner/interinstitutional reproducibility and enable more consistent risk assessment and treatment strategies.

A viral protein that blocks Arf1-mediated COP-I assembly by inhibiting the guanine nucleotide exchange factor GBF1.

Many viruses modify cellular processes for their own benefit. The enterovirus 3A protein inhibits endoplasmic reticulum (ER)-to-Golgi transport, a function previously suggested to be important for viral suppression of immune responses. Here, we show that a virus carrying a 3A protein defective in inhibiting ER-to-Golgi transport is indeed less virulent in mice, and we unravel the mechanism by which 3A inhibits this trafficking step. Evidence is provided that 3A inhibits the activation of the GTPase ADP-ribosylation factor 1 (Arf1), which regulates the recruitment of the COP-I coat complex to membranes. 3A specifically inhibits the function of GBF1, a guanine nucleotide exchange factor for Arf1, by interacting with its N terminus. By specifically interfering with GBF1-mediated Arf1 activation, 3A may prove a valuable tool in dissecting the early steps of the secretory pathway.

Creatine kinase-mediated ATP supply fuels actin-based events in phagocytosis.

Phagocytosis requires locally coordinated cytoskeletal rearrangements driven by actin polymerization and myosin motor activity. How this actomyosin dynamics is dependent upon systems that provide access to ATP at phagosome microdomains has not been determined. We analyzed the role of brain-type creatine kinase (CK-B), an enzyme involved in high-energy phosphoryl transfer. We demonstrate that endogenous CK-B in macrophages is mobilized from the cytosolic pool and coaccumulates with F-actin at nascent phagosomes. Live cell imaging with XFP-tagged CK-B and beta-actin revealed the transient and specific nature of this partitioning process. Overexpression of a catalytic dead CK-B or CK-specific cyclocreatine inhibition caused a significant reduction of actin accumulation in the phagocytic cup area, and reduced complement receptor-mediated, but not Fc-gammaR-mediated, ingestion capacity of macrophages. Finally, we found that inhibition of CK-B affected phagocytosis already at the stage of particle adhesion, most likely via effects on actin polymerization behavior. We propose that CK-B activity in macrophages contributes to complement-induced F-actin assembly events in early phagocytosis by providing local ATP supply.

Microdomains of the C-type lectin DC-SIGN are portals for virus entry into dendritic cells.

The C-type lectin dendritic cell (DC)-specific intercellular adhesion molecule grabbing non-integrin (DC-SIGN; CD209) facilitates binding and internalization of several viruses, including HIV-1, on DCs, but the underlying mechanism for being such an efficient phagocytic pathogen-recognition receptor is poorly understood. By high resolution electron microscopy, we demonstrate a direct relation between DC-SIGN function as viral receptor and its microlocalization on the plasma membrane. During development of human monocyte-derived DCs, DC-SIGN becomes organized in well-defined microdomains, with an average diameter of 200 nm. Biochemical experiments and confocal microscopy indicate that DC-SIGN microdomains reside within lipid rafts. Finally, we show that the organization of DC-SIGN in microdomains on the plasma membrane is important for binding and internalization of virus particles, suggesting that these multimolecular assemblies of DC-SIGN act as a docking site for pathogens like HIV-1 to invade the host.

Organization of the integrin LFA-1 in nanoclusters regulates its activity.

The beta2-integrin LFA-1 facilitates extravasation of monocytes (MOs) into the underlying tissues, where MOs can differentiate into dendritic cells (DCs). Although DCs express LFA-1, unlike MOs, they cannot bind to ICAM-1. We hypothesized that an altered integrin organization on the DC plasma membrane might cause this effect and investigated the relationship between membrane organization and function of LFA-1 on MOs and DCs. High-resolution mapping of LFA-1 surface distribution revealed that on MOs LFA-1 function is associated with a distribution in well-defined nanoclusters (100-150-nm diameter). Interestingly, a fraction of these nanoclusters contains primed LFA-1 molecules expressing the specific activation-dependent L16-epitope. Live imaging of MO-T-cell conjugates showed that only these primed nanoclusters are dynamically recruited to the cellular interface forming micrometer-sized assemblies engaged in ligand binding and linked to talin. We conclude that besides affinity regulation, LFA-1 function is controlled by at least three different avidity patterns: random distributed inactive molecules, well-defined ligand-independent proactive nanoclusters, and ligand-triggered micrometer-sized macroclusters.

Arm raising at exposure-controlled multidetector trauma CT of thoracoabdominal region: higher image quality, lower radiation dose.

PURPOSE: To evaluate the effect of arm position on image quality and effective radiation dose in an automatic exposure-controlled (AEC) multidetector thoracoabdominal computed tomography (CT) protocol in trauma patients. MATERIALS AND METHODS: This retrospective study of the data of 177 trauma patients (117 male; median age, 39 years) was approved by the institutional ethics board, with informed patient consent waived. Patients underwent scanning by using an AEC 16-detector thoracoabdominal CT protocol in which both arms were raised above the shoulder region (standard-position group, 132 patients), one arm was raised and the other was down (one-arm group, 27 patients), or both arms were down (two-arm group, 18 patients). Objective and subjective image quality was assessed. Individual effective radiation dose was calculated from the effective tube current-time product per exposed section. For this purpose, section location-dependent conversion factors were derived by using a CT dosimetry calculator. The effect of arm position on effective dose was quantified by using linear regression analysis with correction for patient volume and attenuation. RESULTS: Compared with the image quality in the standard-position group, the image quality in the one- and two-arm groups was decreased but within acceptable diagnostic limits. The median corrected effective dose in the standard-position group was 18.6 mSv; the dose in the one-arm group was 18% (95% confidence interval: 11%, 25%) higher than this, and that in the two-arm group was 45% (95% confidence interval: 34%, 57%) higher. CONCLUSION: Omitting arm raising results in lower but acceptable image quality and a substantially higher effective radiation dose. Hence, effort should be made to position the arms above the shoulder when scanning trauma patients. Clinical trial registration no. NCT00228111.

Laser Guidance in C-Arm Cone-Beam CT-Guided Radiofrequency Ablation of Osteoid Osteoma Reduces Fluoroscopy Time.

PURPOSE: To assess whether laser guidance can reduce fluoroscopy and procedure time of cone-beam computed tomography (CBCT)-guided radiofrequency (RF) ablations of osteoid osteoma compared to freehand CBCT guidance. MATERIALS AND METHODS: 32 RF ablations were retrospectively analyzed, 17 laser-guided and 15 procedures using the freehand technique. Subgroup selection of 18 ablations in the hip-pelvic region with a similar degree of difficulty was used for a direct comparison. Data are presented as median (ranges). RESULTS: Comparison of all 32 ablations resulted in fluoroscopy times of 365 s (193-878 s) for freehand and 186 s (75-587 s) for laser-guided procedures (p = 0.004). Corresponding procedure times were 56 min (35-97 min) and 52 min (30-85 min) (p = 0.355). The subgroup showed comparable target sizes, needle path lengths, and number of scans between groups. Fluoroscopy times were lower for laser-guided procedures, 215 s (75-413 s), compared to 384 s (193-878 s) for freehand (p = 0.012). Procedure times were comparable between groups, 51 min (30-72 min) for laser guidance and 58 min (35-79 min) for freehand (p = 0.172). CONCLUSION: Adding laser guidance to CBCT-guided osteoid osteoma RF ablations significantly reduced fluoroscopy time without increasing procedure time. LEVEL OF EVIDENCE: Level 4, case series.