Mitochondrial DNA control region typing from highly degraded skeletal remains by single-multiplex next-generation sequencing.

Poor nuclear DNA preservation from highly degraded skeletal remains is the most limiting factor for the genetic identification of individuals. Mitochondrial DNA (mtDNA) typing, and especially of the control region (CR), using next-generation sequencing (NGS), enables retrieval of valuable genetic information in forensic contexts where highly degraded human skeletal remains are the only source of genetic material. Currently, NGS commercial kits can type all mtDNA-CR in fewer steps than the conventional Sanger technique. The PowerSeq CRM Nested System kit (Promega Corporation) employs a nested multiplex-polymerase chain reaction (PCR) strategy to amplify and index all mtDNA-CR in a single reaction. Our study analyzes the success of mtDNA-CR typing of highly degraded human skeletons using the PowerSeq CRM Nested System kit. We used samples from 41 individuals from different time periods to test three protocols (M1, M2, and M3) based on modifications of PCR conditions. To analyze the detected variants, two bioinformatic procedures were compared: an in-house pipeline and the GeneMarker HTS software. The results showed that many samples were not analyzed when the standard protocol (M1) was used. In contrast, the M3 protocol, which includes 35 PCR cycles and longer denaturation and extension steps, successfully recovered the mtDNA-CR from highly degraded skeletal samples. Mixed base profiles and the percentage of damaged reads were both indicators of possible contamination and can provide better results if used together. Furthermore, our freely available in-house pipeline can provide variants concordant with the forensic software.

Optimization of long-range PCR protocol to prepare filaggrin exon 3 libraries for PacBio long-read sequencing.

BACKGROUND: The filaggrin (FLG) protein, encoded by the FLG gene, is an intermediate filament-associated protein that plays a crucial role in the terminal stages of human epidermal differentiation. Loss-of-function mutations in the FLG exon 3 have been associated with skin diseases. The identification of causative mutations is challenging, due to the high sequence homology within its exon 3 (12,753 bp), which includes 10 to 12 filaggrin tandem repeats. With this study we aimed to obtain the whole FLG exon 3 sequence through PacBio technology, once 13-kb amplicons have been generated. METHODS AND RESULTS: For the preparation of SMRTbell libraries to be sequenced using PacBio technology, we focused on optimizing a 2-step long-range PCR protocol to generate 13-kb amplicons covering the whole FLG exon 3 sequence. The performance of three long-range DNA polymerases was assessed in an attempt to improve the PCR conditions required for the enzymes to function properly. We focused on optimization of the input template DNA concentration and thermocycling parameters to correctly amplify the entire FLG exon 3 sequence, minimizing non-specific amplification. CONCLUSIONS: Taken together, our findings suggested that the PrimeSTAR protocol is suitable for producing the amplicons of the 13-kb FLG whole exon 3 to prepare SMRTbell libraries. We suggest that sequencing the generated amplicons may be useful for identifying LoF variants that are causative of the patients' disorders.

Subject-specific optimization of background suppression for arterial spin labeling magnetic resonance imaging using a feedback loop on the scanner.

Background suppression (BGS) in arterial spin labeling (ASL) magnetic resonance imaging leads to a higher temporal signal-to-noise ratio (tSNR) of the perfusion images compared with ASL without BGS. The performance of the BGS, however, depends on the tissue relaxation times and on inhomogeneities of the scanner's magnetic fields, which differ between subjects and are unknown at the moment of scanning. Therefore, we developed a feedback loop (FBL) mechanism that optimizes the BGS for each subject in the scanner during acquisition. We implemented the FBL for 2D pseudo-continuous ASL scans with an echo-planar imaging readout. After each dynamic scan, the acquired ASL images were automatically sent to an external computer and processed with a Python processing tool. Inversion times were optimized on the fly using 80 iterations of the Nelder-Mead method, by minimizing the signal intensity in the label image while maximizing the signal intensity in the perfusion image. The performance of this method was first tested in a four-component phantom. The regularization parameter was then tuned in six healthy subjects (three males, three females, age 24-62 years) and set as λ = 4 for all other experiments. The resulting ASL images, perfusion images, and tSNR maps obtained from the last 20 iterations of the FBL scan were compared with those obtained without BGS and with standard BGS in 12 healthy volunteers (five males, seven females, age 24-62 years) (including the six volunteers used for tuning of λ). The FBL resulted in perfusion images with a statistically significantly higher tSNR (2.20) compared with standard BGS (1.96) ( p < 5 x 10 - 3 , two-sided paired t-test). Minimizing signal in the label image furthermore resulted in control images, from which approximate changes in perfusion signal can directly be appreciated. This could be relevant to ASL applications that require a high temporal resolution. Future work is needed to minimize the number of initial acquisitions during which the performance of BGS is reduced compared with standard BGS, and to extend the technique to 3D ASL.

Radiofrequency ablation for liver tumors abutting complex blood vessel structures: treatment protocol optimization using response surface method and computer modeling.

OBJECTIVE: To achieve a result of a large tumor ablation volume with minimal thermal damage to the surrounding blood vessels by designing a few clinically-adjustable operating parameters in radiofrequency ablation (RFA) for liver tumors abutting complex vascular structures. METHODS: Response surface method (RSM) was employed to correlate the ablated tumor volume (Ra) and thermal damage to blood vessels (Dt) based on RFA operating parameters: ablation time, electrode position, and insertion angle. A coupled electric-thermal-fluid RFA computer model was created as the testbed for RSM to simulate RFA process. Then, an optimal RFA protocol for the two conflicting goals, namely (1) large tumor ablation and (2) small thermal damage to the surrounding blood vessels, has been achieved under a specific ablation environment. RESULTS: Linear regression analysis confirmed that the RFA protocol significantly affected Ra and Dt (the adjusted coefficient of determination Radj2 = 93.61% and 95.03%, respectively). For a proposed liver tumor scenario (liver tumor with a dimension of 4×3×2.9 cm3 abutting a complex vascular structure), an optimized RFA protocol was found based on the regression results in RSM. Compared with a reference RFA protocol, in which the electrode was centered in the tumor with a 12-min ablation time, the optimized RFA protocol has increased Ra  from 98.1% to 99.6% and decreased Dt from 4.1% to 0.4%, achieving nearly the complete ablation of proposed liver tumor and ignorable thermal damages to vessels. CONCLUSION: This work showed that it is possible to design a few clinically-adjustable operating parameters of RFA for achieving a large tumor ablation volume while minimizing thermal damage to the surrounding blood vessels.

Total-body 18F-FDG PET/CT scan in oncology patients: how fast could it be?

PURPOSE: The aim of the study was to determine a faster PET acquisition protocol for a total-body PET/CT scanner by assessing the image quality that is equivalent to a conventional digital PET/CT scanner from both a phantom and a clinical perspective. METHODS: A phantom study using a NEMA/IEC NU-2 body phantom was first performed in both a total-body PET/CT (uEXPLORER) and a routine digital PET/CT (uMI 780), with a hot sphere to background activity concentration ratio of 4:1. The contrast recovery coefficient (CRC), background variability (BV), and recovery coefficient (RC: RCmax and RCmean) were assessed in the uEXPLORER with different scanning durations and reconstruction protocols, which were compared to those acquired from the uMI 780 with clinical acquisition settings. The coefficient of variation (COV) of the uMI 780 with clinical settings was calculated and used as a threshold reference to determine the optimized scanning duration and reconstruction protocol for the uEXPLORER. The obtained protocol from the phantom study was subsequently tested and validated in 30 oncology patients. Images acquired from the uMI 780 with 2-3 min per bed position were referred as G780 and served as the reference for comparison. All PET raw data from the uEXPLORER were reconstructed using the data-cutting technique to simulate a 30-s, 45-s, or 60-s acquisition duration, respectively. The iterations were 2 and 3 for the uEXPLORER, referred as G30s_3i, G45s_2i, G45s_3i, G60s_2i, and G60s_3i, respectively. A 5-point Likert scale was used in the qualitative analysis to assess the image quality. The image quality was also evaluated by the liver COV, the lesion target-to-background ratio (TBR), and the lesion signal-to-noise ratio (SNR). RESULTS: In the phantom study, CRC, BV, RCmax, and RCmean in the uEXPLORER with different scanning durations and reconstruction iterations were compared with those in the uMI 780 with clinical settings. A minor fluctuation was found among different scanning durations. COV of the uMI 780 with clinical settings was 11.6%, and a protocol with a 30-45-s scanning duration and 2 or 3 iterations for the uEXPLORER was found to provide an equivalent image quality as the uMI 780. An almost perfect agreement was shown with a kappa value of 0.875. The qualitative score of the G30s_3i in the uEXPLORER was inferior to the G780 reference (p = 0.001); however, the scores of other groups in the uEXPLORER with a 45-s and above acquisition time were higher than the G780 in the uMI 780. In quantitative analysis, the delay time between the two scans in the two orders was not significantly different. There was no significant difference of the liver COV between the G780 and G30s_3i (p = 0.162). A total of 33 lesions were analyzed in the clinical patient study. There was no significant difference in lesion TBR between the reference G780 and the G45s_2i obtained from the uEXPLORER (p = 0.072), while the latter showed a higher lesion SNR value compared to that in uMI 780 with clinical settings (p < 0.001). CONCLUSIONS: This study showed that a fast PET protocol with a 30-45-s acquisition time in the total-body uEXPLORER PET/CT can provide an equivalent image quality as the conventional digital uMI 780 PET/CT with longer clinical acquisition settings.

Protocol Optimization Considerations for Implementing Deep Learning CT Reconstruction.

OBJECTIVE. Previous advances over filtered back projection (FBP) have incorporated model-based iterative reconstruction. The purpose of this study was to characterize the latest advance in image reconstruction, that is, deep learning. The focus was on applying characterization results of a deep learning approach to decisions about clinical CT protocols. MATERIALS AND METHODS. A proprietary deep learning image reconstruction (DLIR) method was characterized against an existing advanced adaptive statistical iterative reconstruction method (ASIR-V) and FBP from the same vendor. The metrics used were contrast-to-noise ratio, spatial resolution as a function of contrast level, noise texture (i.e., noise power spectra [NPS]), noise scaling as a function of slice thickness, and CT number consistency. The American College of Radiology accreditation phantom and a uniform water phantom were used at a range of doses and slice thicknesses for both axial and helical acquisition modes. RESULTS. ASIR-V and DLIR were associated with improved contrast-to-noise ratio over FBP for all doses and slice thicknesses. No dose or contrast dependencies of spatial resolution were observed for ASIR-V or DLIR. NPS results showed DLIR maintained an FBP-like noise texture whereas ASIR-V shifted the NPS to lower frequencies. Noise changed with dose and slice thickness in the same manner for ASIR-V and FBP. DLIR slice thickness noise scaling differed from FBP, exhibiting less noise penalty with decreasing slice thickness. No clinically significant changes were observed in CT numbers for any measurement condition. CONCLUSION. In a phantom model, DLIR does not suffer from the concerns over reduction in spatial resolution and introduction of poor noise texture associated with previous methods.

Fractional CO2 laser therapy of hypertrophic scars - evaluation of efficacy and treatment protocol optimization.

INTRODUCTION: Hypertrophic scars are an unwanted and mutilating consequence of deep burns, and are further exacerbated by extensive burn injuries. Fractional CO2 laser therapy is one of the methods for complex treatment of hypertrophic scars, it has been used since 2007 [1]. Although its effectiveness has been objectively proven in clinical practice, the optimal settings parameters have not been determined. To evaluate the effect of laser therapy, previously designed evaluation tools are used, which evaluate the quality of scars well, but fail to capture specific changes for the performed laser therapy. MATERIAL AND METHODS: Fractional CO2 laser therapy of hypertrophic scars is performed at the Department of Plastic and Esthetic Surgery, University Hospital Olomouc, since 2017 and the systematic study took place in 2019-2020. In common, 25 hypertrophic scars were treated in 13 patients; each scar was treated by fractional CO2 laser therapy more than once. RESULTS: Statistical analysis detected statistically significant improvement of the texture of the scars and the improvement of overall functional and esthetic result. We found significant reduction of the height under 2 mm (62,5% of scars) in scars with the height > 2 mm before the initiation of laser therapy. Correlation analysis detected a statistically significant positive correlation between the energy of laser beam and the reduction volume of the scar protruding above the niveau of healthy surrounding tissue. Fractional CO2 laser therapy showed statistically significant efficacy in the reduction of the risks associated with full-format CO2 laser-therapy. Fractional treatment was very well tolerated by the patients. Topical 5% lidocaine gel was effective in 24 out of 25 patients. Further healing was without complications in all patients. CONCLUSION: Fractional CO2 laser therapy has achieved statistically significant improvement of the texture and reduction of hypertrophic scars and overall improvement of functional and esthetic result in our study.

Designing and comparing optimized pseudo-continuous Arterial Spin Labeling protocols for measurement of cerebral blood flow.

Arterial Spin Labeling (ASL) is a non-invasive, non-contrast, perfusion imaging technique which is inherently SNR limited. It is, therefore, important to carefully design scan protocols to ensure accurate measurements. Many pseudo-continuous ASL (PCASL) protocol designs have been proposed for measuring cerebral blood flow (CBF), but it has not yet been demonstrated which design offers the most accurate and repeatable CBF measurements. In this study, a wide range of literature PCASL protocols were first optimized for CBF accuracy and then compared using Monte Carlo simulations and in vivo experiments. The protocols included single-delay, sequential and time-encoded multi-timepoint protocols, and several novel protocol designs, which are hybrids of time-encoded and sequential multi-timepoint protocols. It was found that several multi-timepoint protocols produced more confident, accurate, and repeatable CBF estimates than the single-delay protocol, while also generating maps of arterial transit time. Of the literature protocols, the time-encoded protocol with T1-adjusted label durations gave the most confident and accurate CBF estimates in vivo (16% and 40% better than single-delay), while the sequential multi-timepoint protocol was the most repeatable (20% more repeatable than single-delay). One of the novel hybrid protocols, HybridT1-adj, was found to produce the most confident, accurate and repeatable CBF estimates out of all the protocols tested in both simulations and in vivo (24%, 47%, and 28% more confident, accurate, and repeatable than single-delay in vivo). The HybridT1-adj protocol makes use of the best aspects of both time-encoded and sequential multi-timepoint protocols and should be a useful tool for accurately and efficiently measuring CBF.

fMRI protocol optimization for simultaneously studying small subcortical and cortical areas at 7 ​T.

Most fundamental cognitive processes rely on brain networks that include both cortical and subcortical structures. Studying such networks using functional magnetic resonance imaging (fMRI) requires a data acquisition protocol that provides blood-oxygenation-level dependent (BOLD) sensitivity across the entire brain. However, when using standard single echo, echo planar imaging protocols, researchers face a tradeoff between BOLD-sensitivity in cortex and in subcortical areas. Multi echo protocols avoid this tradeoff and can be used to optimize BOLD-sensitivity across the entire brain, at the cost of an increased repetition time. Here, we empirically compare the BOLD-sensitivity of a single echo protocol to a multi echo protocol. Both protocols were designed to meet the specific requirements for studying small, iron rich subcortical structures (including a relatively high spatial resolution and short echo times), while retaining coverage and BOLD-sensitivity in cortical areas. The results indicate that both sequences lead to similar BOLD-sensitivity across the brain at 7 â€‹T.

Optimization of HU threshold for coronary artery calcium scans reconstructed at 0.5-mm slice thickness using iterative reconstruction.

PURPOSE: This work investigated the simultaneous influence of tube voltage, tube current, body size, and HU threshold on calcium scoring reconstructed at 0.5-mm slice thickness using iterative reconstruction (IR) through multivariate analysis. Regression results were used to optimize the HU threshold to calibrate the resulting Agatston scores to be consistent with those obtained from the conventional protocol. METHODS: A thorax phantom set simulating three different body sizes was used in this study. A total of 14 coronary artery calcium (CAC) protocols were studied, including 1 conventional protocol reconstructed at 3-mm slice thickness, 1 FBP protocol, and 12 statistical IR protocols (3 kVp values*4 SD values) reconstructed at 0.5-mm slice thickness. Three HU thresholds were applied for calcium identification, including 130, 150, and 170 HU. A multiple linear regression method was used to analyze the impact of kVp, SD, body size, and HU threshold on the Agatston scores of three calcification densities for IR-reconstructed CAC scans acquired with 0.5-mm slice thickness. RESULTS: Each regression relationship has R2 larger than 0.80, indicating a good fit to the data. Based on the regression models, the HU thresholds as a function of SD estimated to ensure the quantification accuracy of calcium scores for 120-, 100-, and 80-kVp CAC scans reconstructed at 0.5-mm slice thickness using IR for three different body sizes were proposed. Our results indicate that the HU threshold should be adjusted according to the imaging condition, whereas a 130-HU threshold is appropriate for 120-kVp CAC scans acquired with SD = 55 for body size of 24.5 cm. CONCLUSION: The optimized HU thresholds were proposed for CAC scans reconstructed at 0.5-mm slice thickness using IR. Our study results may provide a potential strategy to improve the reliability of calcium scoring by reducing partial volume effect while keeping radiation dose as low as reasonably achievable.

An optimized framework for quantitative magnetization transfer imaging of the cervical spinal cord in vivo.

PURPOSE: To develop a framework to fully characterize quantitative magnetization transfer indices in the human cervical cord in vivo within a clinically feasible time. METHODS: A dedicated spinal cord imaging protocol for quantitative magnetization transfer was developed using a reduced field-of-view approach with echo planar imaging (EPI) readout. Sequence parameters were optimized based in the Cramer-Rao-lower bound. Quantitative model parameters (i.e., bound pool fraction, free and bound pool transverse relaxation times [ T2F, T2B], and forward exchange rate [kFB ]) were estimated implementing a numerical model capable of dealing with the novelties of the sequence adopted. The framework was tested on five healthy subjects. RESULTS: Cramer-Rao-lower bound minimization produces optimal sampling schemes without requiring the establishment of a steady-state MT effect. The proposed framework allows quantitative voxel-wise estimation of model parameters at the resolution typically used for spinal cord imaging (i.e. 0.75 × 0.75 × 5 mm3 ), with a protocol duration of ∼35 min. Quantitative magnetization transfer parametric maps agree with literature values. Whole-cord mean values are: bound pool fraction = 0.11(±0.01), T2F = 46.5(±1.6) ms, T2B = 11.0(±0.2) µs, and kFB = 1.95(±0.06) Hz. Protocol optimization has a beneficial effect on reproducibility, especially for T2B and kFB . CONCLUSION: The framework developed enables robust characterization of spinal cord microstructure in vivo using qMT. Magn Reson Med 79:2576-2588, 2018. © 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

The Current State of CT Dose Management Across Radiology: Well Intentioned but Not Universally Well Executed.

OBJECTIVE: Recent well-publicized sentinel events have resulted in an appropriately heightened awareness of CT dose. Concern also exists regarding the potential of CT dose increasing the risk of cancer. Several professional societies, governmental and accreditation agencies, and CT vendors have responded to these concerns with campaigns, mandatory standards, and software enhancements. The objective of this article is to review such CT dose management efforts. CONCLUSION: Although CT dose awareness campaigns, mandatory standards, and software enhancements are well intentioned, their implementation is often suboptimal.

Transmission Optimization Metrics Setup Issues in the Field of Time Constrained Communications.

This article introduces a new approach in the field of network optimization based on Transmission Optimization Metric (TOM), which is aimed at improving traffic flow continuity and increasing the chances for traffic flow sustainability in a way that helps to minimize inter-packet gaps. The work is mainly focused on harsh transmission conditions in narrow-band networks. Finally, the presented approach has impact on better resource allocation as fewer attempts are necessary for successful completion of a transmission. A significant part of the article deals with parameterization of coefficients used by the TOM optimization method. Examples of analysis for several topologies of narrow-band wireless networks based on CSMA/CA and TDMA protocols are used to demonstrate various issues related to proper setting of parameters. The introduced TOM metric has the potential to become a standard for optimization, for example, in sensor networks that are characterized by the specific nature of data traffic.

An experimental guideline for the analysis of histologically heterogeneous tumors by MALDI-TOF mass spectrometry imaging.

Mass spectrometry imaging (MSI) has been widely used for the direct molecular assessment of tissue samples and has demonstrated great potential to complement current histopathological methods in cancer research. It is now well established that tissue preparation is key to a successful MSI experiment; for histologically heterogeneous tumor tissues, other parts of the workflow are equally important to the experiment's success. To demonstrate these facets here we describe a matrix-assisted laser desorption/ionization MSI biomarker discovery investigation of high-grade, complex karyotype sarcomas, which often have histological overlap and moderate response to chemo-/radio-therapy. Multiple aspects of the workflow had to be optimized, ranging from the tissue preparation and data acquisition protocols, to the post-MSI histological staining method, data quality control, histology-defined data selection, data processing and statistical analysis. Only as a result of developing every step of the biomarker discovery workflow was it possible to identify a panel of protein signatures that could distinguish between different subtypes of sarcomas or could predict patient survival outcome. This article is part of a Special Issue entitled: MALDI Imaging, edited by Dr. Corinna Henkel and Prof. Peter Hoffmann.

PET/CT for Head and Neck Squamous Cell Carcinoma: Should We Routinely Include the Head and Abdomen?

OBJECTIVE: The purpose of our study was to determine the diagnostic and therapeutic yield of the head and abdomen portions of PET/CT scans of patients with head and neck squamous cell cancer (HNSCC) to determine whether these areas should be routinely included with PET/CT of the neck and chest. MATERIALS AND METHODS: Patients with pathologically proven HNSCC who underwent full-body PET/CT were evaluated for metastases to the head, chest, and abdomen. Medical records were reviewed to determine whether the head and abdominal findings changed the clinical management, beyond the findings in the neck and chest. RESULTS: Five hundred ninety-eight patients who underwent 1625 PET/CT scans were included. All studies included the head, neck, and chest. For 542 of 598 patients (91%), the PET/CT scans included the abdomen. Two of 598 patients (0.3%) had distant calvarial metastases. Neither of the calvarial metastases changed patient management. Twelve of 542 patients (2.2%) had abdominal metastases. For 10 of 542 patients (1.8%), the abdominal findings changed patient management. Thoracic metastases were found in 82 of 598 patients (13.7%). The total rate of distant metastases to the head and abdomen in patients with thoracic metastatic disease was 12.2% (10/82), whereas in patients without thoracic metastases, it was 0.8% (4/460). CONCLUSION: Routine extension of PET/CT scans to include the head and abdomen in patients with HNSCC is not indicated. For patients without evidence of thoracic metastases, routine PET/CT examinations should include the neck and chest only.

Targeted CT Dose Reduction Using a Novel Dose Metric and the American College of Radiology Dose Index Registry: Application to Thoracic CT Angiography.

OBJECTIVE: The purpose of this article is to illustrate the use of the American College of Radiology Dose Index Registry data with a novel measurement of exposure to guide quality improvement efforts. MATERIALS AND METHODS: Using information from the Dose Index Registry report covering July through December 2012, we examined our relative ranking compared with the national median CT dose for the 20 most frequently performed examinations at our institution. The total exposure variance, defined as the difference between institutional and median national dose multiplied by the local examination frequency and expressed in units of mGy-persons, was calculated. Using this metric, two examinations were selected for investigation: pulmonary and thoracic CT angiography (CTA). Protocol modifications were implemented, and postintervention dose data were assessed from the report 1 year later. RESULTS: As indicated by size-specific dose estimates (SSDEs), the 2012 pulmonary CTA was within the national interquartile range; however, total exposure variance analysis showed that it presented the greatest opportunity for improvement on a population basis. Thoracic CTA was a top quartile examination and offered the second highest potential savings. After protocol modification, the average pulmonary CTA SSDEs decreased by 16%, for a population exposure savings of 1776 mGy-persons in the 2013 report. Average thoracic CTA SSDEs decreased by 44%, for a population exposure savings of 1050 mGy-persons. CONCLUSION: Total exposure variance analysis can increase the usefulness of Dose Index Registry data by relating per-examination dose differences to the local examination frequency. This study exhibited reduction of dose metrics for two commonly performed examinations.

Radiation Dose Reduction in Pediatric Body CT Using Iterative Reconstruction and a Novel Image-Based Denoising Method.

OBJECTIVE: The objective of this study was to evaluate the radiation dose reduction potential of a novel image-based denoising technique in pediatric abdominopelvic and chest CT examinations and compare it with a commercial iterative reconstruction method. MATERIALS AND METHODS: Data were retrospectively collected from 50 (25 abdominopelvic and 25 chest) clinically indicated pediatric CT examinations. For each examination, a validated noise-insertion tool was used to simulate half-dose data, which were reconstructed using filtered back-projection (FBP) and sinogram-affirmed iterative reconstruction (SAFIRE) methods. A newly developed denoising technique, adaptive nonlocal means (aNLM), was also applied. For each of the 50 patients, three pediatric radiologists evaluated four datasets: full dose plus FBP, half dose plus FBP, half dose plus SAFIRE, and half dose plus aNLM. For each examination, the order of preference for the four datasets was ranked. The organ-specific diagnosis and diagnostic confidence for five primary organs were recorded. RESULTS: The mean (± SD) volume CT dose index for the full-dose scan was 5.3 ± 2.1 mGy for abdominopelvic examinations and 2.4 ± 1.1 mGy for chest examinations. For abdominopelvic examinations, there was no statistically significant difference between the half dose plus aNLM dataset and the full dose plus FBP dataset (3.6 ± 1.0 vs 3.6 ± 0.9, respectively; p = 0.52), and aNLM performed better than SAFIRE. For chest examinations, there was no statistically significant difference between the half dose plus SAFIRE and the full dose plus FBP (4.1 ± 0.6 vs 4.2 ± 0.6, respectively; p = 0.67), and SAFIRE performed better than aNLM. For all organs, there was more than 85% agreement in organ-specific diagnosis among the three half-dose configurations and the full dose plus FBP configuration. CONCLUSION: Although a novel image-based denoising technique performed better than a commercial iterative reconstruction method in pediatric abdominopelvic CT examinations, it performed worse in pediatric chest CT examinations. A 50% dose reduction can be achieved while maintaining diagnostic quality.

Automated Technique to Measure Noise in Clinical CT Examinations.

OBJECTIVE: The purpose of this study was to develop and validate an automated method to measure noise in clinical CT examinations. MATERIALS AND METHODS: An automated algorithm was developed to measure noise in CT images. To assess its validity, the global noise level was compared with image noise measured using an image subtraction technique in an anthropomorphic phantom. The global noise level was further compared with image noise values from clinical patient CT images obtained by an observer study. Finally, the clinical utility of the global noise level was shown by assessing variability of image noise across scanner models for abdominopelvic CT examinations performed in 2358 patients. RESULTS: The global noise level agreed well with the phantom-based and clinical image-based noise measurements, with an average difference of 3.4% and 4.7% from each of these measures, respectively. No significant difference was detected between the global noise level and the validation dataset in either case. It further indicated differences across scanners, with the median global noise level varying significantly between different scanner models (15-35%). CONCLUSION: The global noise level provides an accurate, robust, and automated method to measure CT noise in clinical examinations for quality assurance programs. The significant difference in noise across scanner models indicates the unexploited potential to efficiently assess and subsequently improve protocol consistency. Combined with other automated characterization of imaging performance (e.g., dose monitoring), the global noise level may offer a promising platform for the standardization and optimization of CT protocols.

A Case Study Assessment on the Rationale for, and Relevance of, Non-Core Protocol Data.

To better understand the nature of Non-Core procedures and derive new insight into protocol simplification and optimization, Tufts CSDD collaborated with the FDA and sponsor companies to assess alignment on the rationale for collecting, and relevance of, Non-Core protocol data. Twelve sponsor companies classified and rated 700 distinct procedures from 19 pivotal trials supporting new drug and biologics approvals. FDA reviewers classified and rated 80 distinct procedures for three of the 19 pivotal trials. The results of this assessment indicate areas of alignment and misalignment. Sponsors and FDA reviewers agreed on the classification for more than half of endpoints. However, FDA reviewers classified a much higher percentage of procedures as Non-Core (26% vs. 18%) with the largest proportion (50%) of these procedures perceived as Core by sponsor companies. Sponsors indicated that one-out-of-six Non-Core procedures were administered due to perceived regulatory requirement and expectation. The results of this study characterize the challenge in aligning the different-and potentially conflicting-imperatives of sponsors and regulators and speak to the importance of more effective FDA-sponsor communication to help simplify protocol designs.

Protocol optimization for abdominal imaging using photon-counting CT: a consensus of two academic institutions.

PURPOSE: Photon-counting detector CT (PCD CT) is a promising technology for abdominal imaging due to its ability to provide high spatial and contrast resolution images with reduced patient radiation exposure. However, there is currently no consensus regarding the optimal imaging protocols for PCD CT. This article aims to present the PCD CT abdominal imaging protocols used by two tertiary care academic centers in the United States. METHODS: A review of PCD CT abdominal imaging protocols was conducted by two abdominal radiologists at different academic institutions. Protocols were compared in terms of acquisition parameters and reconstruction settings. Both imaging centers independently selected similar protocols for PCD CT abdominal imaging, using QuantumPlus mode. RESULTS: There were some differences in the use of reconstruction kernels and iterative reconstruction levels, however the individual combination at each site resulted in similar image impressions. Overall, the imaging protocols used by both centers provide high-quality images with low radiation exposure. CONCLUSION: These findings provide valuable insights into the development of standardized protocols for PCD CT abdominal imaging, which can help to ensure consistent as well as high-quality imaging across different institutions and allow for future multicenter research collaborations.