Lack of evidence for ribosomal frameshifting in ATP7B mRNA decoding.

The research article describing the discovery of ribosomal frameshifting in the bacterial CopA gene also reported the occurrence of frameshifting in the expression of the human ortholog ATP7B based on assays using dual luciferase reporters. An examination of the publicly available ribosome profiling data and the phylogenetic analysis of the proposed frameshifting site cast doubt on the validity of this claim and prompted us to reexamine the evidence. We observed similar apparent frameshifting efficiencies as the original authors using the same type of vector that synthesizes both luciferases as a single polyprotein. However, we noticed anomalously low absolute luciferase activities from the N-terminal reporter that suggests interference of reporter activity or levels by the ATP7B test cassette. When we tested the same proposed ATP7B frameshifting cassette in a more recently developed reporter system in which the reporters are released without being included in a polyprotein, no frameshifting was detected above background levels.

The wooden artifacts from Schöningen's Spear Horizon and their place in human evolution.

Ethnographic records show that wooden tools played a pivotal role in the daily lives of hunter-gatherers including food procurement tools used in hunting (e.g., spears, throwing sticks) and gathering (e.g. digging sticks, bark peelers), as well as, domestic tools (e.g., handles, vessels). However, wood rarely survives in the archeological record, especially in Pleistocene contexts and knowledge of prehistoric hunter-gatherer lifeways is strongly biased by the survivorship of more resilient materials such as lithics and bones. Consequently, very few Paleolithic sites have produced wooden artifacts and among them, the site of Schöningen stands out due to its number and variety of wooden tools. The recovery of complete wooden spears and throwing sticks at this 300,000-y-old site (MIS 9) led to a paradigm shift in the hunter vs. scavenger debate. For the first time and almost 30 y after their discovery, this study introduces the complete wooden assemblage from Schöningen 13 II-4 known as the Spear Horizon. In total, 187 wooden artifacts could be identified from the Spear Horizon demonstrating a broad spectrum of wood-working techniques, including the splitting technique. A minimum of 20 hunting weapons is now recognized and two newly identified artifact types comprise 35 tools made on split woods, which were likely used in domestic activities. Schöningen 13 II-4 represents the largest Pleistocene wooden artifact assemblage worldwide and demonstrates the key role woodworking had in human evolution. Finally, our results considerably change the interpretation of the Pleistocene lakeshore site of Schöningen.

Artifactual Orthologs and the Need for Diligent Data Exploration in Complex Phylogenomic Datasets: A Museomic Case Study from the Andean Flora.

The Andes mountains of western South America are a globally important biodiversity hotspot, yet there is a paucity of resolved phylogenies for plant clades from this region. Filling an important gap in our understanding of the World's richest flora, we present the first phylogeny of Freziera (Pentaphylacaceae), an Andean-centered, cloud forest radiation. Our dataset was obtained via hybrid-enriched target sequence capture of Angiosperms353 universal loci for 50 of the ca. 75 spp., obtained almost entirely from herbarium specimens. We identify high phylogenomic complexity in Freziera, including the presence of data artifacts. Via by-eye observation of gene trees, detailed examination of warnings from recently improved assembly pipelines, and gene tree filtering, we identified that artifactual orthologs (i.e., the presence of only one copy of a multicopy gene due to differential assembly) were an important source of gene tree heterogeneity that had a negative impact on phylogenetic inference and support. These artifactual orthologs may be common in plant phylogenomic datasets, where multiple instances of genome duplication are common. After accounting for artifactual orthologs as source of gene tree error, we identified a significant, but nonspecific signal of introgression using Patterson's D and f4 statistics. Despite phylogenomic complexity, we were able to resolve Freziera into 9 well-supported subclades whose evolution has been shaped by multiple evolutionary processes, including incomplete lineage sorting, historical gene flow, and gene duplication. Our results highlight the complexities of plant phylogenomics, which are heightened in Andean radiations, and show the impact of filtering data processing artifacts and standard filtering approaches on phylogenetic inference.

Identifying the origins of obsidian artifacts in the Deh Luran Plain (Southwestern Iran) highlights community connections in the Neolithic Zagros.

Exchange networks created by Neolithic pastoral transhumance have been central to explaining the distant transport of obsidian since chemical analysis was first used to attribute Near Eastern artifacts to their volcanic origins in the 1960s. Since then, critical reassessments of floral, faunal, and chronological data have upended long-held interpretations regarding the emergence of food production and have demonstrated that far-traveled, nomadic pastoralists were more myth than reality, at least during the Neolithic. Despite debates regarding their proposed conveyance mechanisms, obsidian artifacts' transport has received relatively little attention compared with zooarchaeological and archaeobotanical lines of investigation. The rise of nondestructive and portable instruments permits entire obsidian assemblages to be traced to their sources, renewing their significance in elucidating connections among early pastoral and agricultural communities. Here we share our findings about the obsidian artifacts excavated from the sites of Ali Kosh and Chagha Sefid in the southern Zagros. In the 1960s and 1970s, 28 obsidian artifacts from the sites were destructively tested, and the remainder were sorted by color. Our results emphasize a dynamic, accelerating connectivity among the Early and Late Neolithic communities. Here we propose and support an alternative model for obsidian distribution among more settled communities. In brief, diversity in the obsidian assemblage accelerated diachronically, an invisible trend in the earlier studies. Our model of increasing population densities is supported by archaeological data and computational simulations, offering insights regarding the Neolithic Demographic Transition in the Zagros, an equivalent of which is commonly thought to have occurred around the world.

Revisiting reactive oxygen species production in hypoxia.

Cellular responses to hypoxia are crucial in various physiological and pathophysiological contexts and have thus been extensively studied. This has led to a comprehensive understanding of the transcriptional response to hypoxia, which is regulated by hypoxia-inducible factors (HIFs). However, the detailed molecular mechanisms of HIF regulation in hypoxia remain incompletely understood. In particular, there is controversy surrounding the production of mitochondrial reactive oxygen species (ROS) in hypoxia and how this affects the stabilization and activity of HIFs. This review examines this controversy and attempts to shed light on its origin. We discuss the role of physioxia versus normoxia as baseline conditions that can affect the subsequent cellular response to hypoxia and highlight the paucity of data on pericellular oxygen levels in most experiments, leading to variable levels of hypoxia that might progress to anoxia over time. We analyze the different outcomes reported in isolated mitochondria, versus intact cells or whole organisms, and evaluate the reliability of various ROS-detecting tools. Finally, we examine the cell-type and context specificity of oxygen's various effects. We conclude that while recent evidence suggests that the effect of hypoxia on ROS production is highly dependent on the cell type and the duration of exposure, efforts should be made to conduct experiments under carefully controlled, physiological microenvironmental conditions in order to rule out potential artifacts and improve reproducibility in research.

Expanding the clinical application of OPM-MEG using an effective automatic suppression method for the dental brace metal artifact.

Optically pumped magnetometer magnetoencephalography (OPM-MEG) holds significant promise for clinical functional brain imaging due to its superior spatiotemporal resolution. However, effectively suppressing metallic artifacts, particularly from devices such as orthodontic braces and vagal nerve stimulators remains a major challenge, hindering the wider clinical application of wearable OPM-MEG devices. A comprehensive analysis of metal artifact characteristics from time, frequency, and time-frequency perspectives was conducted for the first time using an OPM-MEG device in clinical medicine. This study focused on patients with metal orthodontics, examining the modulation of metal artifacts by breath and head movement, the incomplete regular sub-Gaussian distribution, and the high absolute power ratio in the 0.5-8 Hz band. The existing metal artifact suppression algorithms applied to SQUID-MEG, such as fast independent component analysis (FastICA), information maximization (Infomax), and algorithms for multiple unknown signal extraction (AMUSE), exhibit limited efficacy. Consequently, this study introduced the second-order blind identification (SOBI) algorithm, which utilized multiple time delays for the component separation of OPM-MEG measurement signals. We modified the time delays of the SOBI method to improve its efficacy in separating artifact components, particularly those in the ultralow frequency range. This approach employs the frequency-domain absolute power ratio, root mean square (RMS) value, and mutual information methods to automate the artifact component screening process. The effectiveness of this method was validated through simulation experiments involving four subjects in both resting and evoked experiments. In addition, the proposed method was also validated by the actual OPM-MEG evoked experiments of three subjects. Comparative analyses were conducted against the FastICA, Infomax, and AMUSE algorithms. Evaluation metrics included normalized mean square error, normalized delta band power error, RMS error, and signal-to-noise ratio, demonstrating that the proposed method provides optimal suppression of metal artifacts. This advancement holds promise for enhancing data quality and expanding the clinical applications of OPM-MEG.

When light meets biology - how the specimen affects quantitative microscopy.

Fluorescence microscopy images should not be treated as perfect representations of biology. Many factors within the biospecimen itself can drastically affect quantitative microscopy data. Whereas some sample-specific considerations, such as photobleaching and autofluorescence, are more commonly discussed, a holistic discussion of sample-related issues (which includes less-routine topics such as quenching, scattering and biological anisotropy) is required to appropriately guide life scientists through the subtleties inherent to bioimaging. Here, we consider how the interplay between light and a sample can cause common experimental pitfalls and unanticipated errors when drawing biological conclusions. Although some of these discrepancies can be minimized or controlled for, others require more pragmatic considerations when interpreting image data. Ultimately, the power lies in the hands of the experimenter. The goal of this Review is therefore to survey how biological samples can skew quantification and interpretation of microscopy data. Furthermore, we offer a perspective on how to manage many of these potential pitfalls.

Reducing blood flow pulsation artifacts in 3D time-of-flight angiography by locally scrambling the order of the acquisition at 3 T and 7 T.

PURPOSE: Non-contrast-enhanced time of flight (TOF) is a standard method for magnetic resonance angiography used to depict vessel morphology. TOF is commonly performed with a 3D steady-state acquisition, employing a short repetition time to support high resolution imaging. At 7 T, TOF exhibits substantial increase in SNR and contrast, improving its clinical value. However, one of the remaining challenges, exacerbated at 7 T, is the presence of artifacts due to pulsatile blood flow, especially near major blood vessels. In this study we examine a method to significantly reduce these artifacts. METHODS: We recently introduced a new "local-scrambling" approach that semi-randomizes the acquisition order of the phase encodes, to achieve a controllable cutoff frequency above which the artifacts are drastically reduced. With this approach, artifacts resulting from fast local fluctuations such as cardiac pulsation are significantly reduced. In this study, we explore the ability of this local-scrambling approach to reduce pulsatile blood flow artifacts in a 3D TOF acquisition. Cartesian line-by-line and center-out ordering, with and without local-scrambling, were compared in simulations and in human brain imaging at 3 and 7 T scanners. RESULTS: In the simulations the artifact intensity showed a 10-fold reduction using local-scrambling compared to line-by-line and 4-fold compared to center-out ordering. In vivo results show that artifacts are much more pronounced at 7 T compared to 3 T, and in both cases they are effectively reduced by local-scrambling. CONCLUSION: Local-scrambling improves image quality for both line-by-line and center-out ordering. This approach can easily be implemented in the scanner without any changes to the reconstruction.

Referenceless Nyquist ghost correction outperforms standard navigator-based method and improves efficiency of in vivo diffusion tensor cardiovascular magnetic resonance.

PURPOSE: The study aims to assess the potential of referenceless methods of EPI ghost correction to accelerate the acquisition of in vivo diffusion tensor cardiovascular magnetic resonance (DT-CMR) data using both computational simulations and data from in vivo experiments. METHODS: Three referenceless EPI ghost correction methods were evaluated on mid-ventricular short axis DT-CMR spin echo and STEAM datasets from 20 healthy subjects at 3T. The reduced field of view excitation technique was used to automatically quantify the Nyquist ghosts, and DT-CMR images were fit to a linear ghost model for correction. RESULTS: Numerical simulation showed the singular value decomposition (SVD) method is the least sensitive to noise, followed by Ghost/Object method and entropy-based method. In vivo experiments showed significant ghost reduction for all correction methods, with referenceless methods outperforming navigator methods for both spin echo and STEAM sequences at b = 32, 150, 450, and 600 smm - 2 $$ {\mathrm{smm}}^{-2} $$ . It is worth noting that as the strength of the diffusion encoding increases, the performance gap between the referenceless method and the navigator-based method diminishes. CONCLUSION: Referenceless ghost correction effectively reduces Nyquist ghost in DT-CMR data, showing promise for enhancing the accuracy and efficiency of measurements in clinical practice without the need for any additional reference scans.

Minimization of eddy current artifacts in sequences with periodic dynamics.

PURPOSE: To minimize eddy current artifacts in periodic pulse sequences with balanced gradient moments as, for example, used for quantitative MRI. THEORY AND METHODS: Eddy current artifacts in balanced sequences result from large jumps in k-space. In quantitative MRI, one often samples some spin dynamics repeatedly while acquiring different parts of k-space. We swap individual k-space lines between different repetitions in order to minimize jumps in temporal succession without changing the overall trajectory. This reordering can be formulated as a traveling salesman problem and we tackle the discrete optimization with a simulated annealing algorithm. RESULTS: Compared to the default ordering, we observe a substantial reduction of artifacts in the reconstructed images and the derived quantitative parameter maps. Comparing two variants of our algorithm, one that resembles the pairing approach originally proposed by Bieri et al., and one that minimizes all k-space jumps equally, we observe slightly lower artifact levels in the latter. CONCLUSION: The proposed reordering scheme effectively reduces eddy current artifacts in sequences with balanced gradient moments. In contrast to previous approaches, we capitalize on the periodicity of the sampled signal dynamics, enabling both efficient k-space sampling and minimizing artifacts caused by eddy currents.

Efficient pulse sequence design framework for high-dimensional MR fingerprinting scans using systematic error index.

PURPOSE: For effective optimization of MR fingerprinting (MRF) pulse sequences, estimating and minimizing errors from actual scan conditions are crucial. Although virtual-scan simulations offer an approximation to these errors, their computational demands become expensive for high-dimensional MRF frameworks, where interactions between more than two tissue properties are considered. This complexity makes sequence optimization impractical. We introduce a new mathematical model, the systematic error index (SEI), to address the scalability challenges for high-dimensional MRF sequence design. METHODS: By eliminating the need to perform dictionary matching, the SEI model approximates quantification errors with low computational costs. The SEI model was validated in comparison with virtual-scan simulations. The SEI model was further applied to optimize three high-dimensional MRF sequences that quantify two to four tissue properties. The optimized scans were examined in simulations and healthy subjects. RESULTS: The proposed SEI model closely approximated the virtual-scan simulation outcomes while achieving hundred- to thousand-times acceleration in the computational speed. In both simulation and in vivo experiments, the optimized MRF sequences yield higher measurement accuracy with fewer undersampling artifacts at shorter scan times than the heuristically designed sequences. CONCLUSION: We developed an efficient method for estimating real-world errors in MRF scans with high computational efficiency. Our results illustrate that the SEI model could approximate errors both qualitatively and quantitatively. We also proved the practicality of the SEI model of optimizing sequences for high-dimensional MRF frameworks with manageable computational power. The optimized high-dimensional MRF scans exhibited enhanced robustness against undersampling and system imperfections with faster scan times.

Reduction of ringing artifacts induced by diaphragm drifting in free-breathing dynamic pulmonary MRI using 3D koosh-ball acquisition.

PURPOSE: To reduce the ringing artifacts of the motion-resolved images in free-breathing dynamic pulmonary MRI. METHODS: A golden-step based interleaving (GSI) technique was proposed to reduce ringing artifacts induced by diaphragm drifting. The pulmonary MRI data were acquired using a superior-inferior navigated 3D radial UTE sequence in an interleaved manner during free breathing. Successive interleaves were acquired in an incoherent fashion along the polar direction. Four-dimensional images were reconstructed from the motion-resolved k-space data obtained by retrospectively binning. The reconstruction algorithms included standard nonuniform fast Fourier transform (NUFFT), Voronoi-density-compensated NUFFT, extra-dimensional UTE, and motion-state weighted motion-compensation reconstruction. The proposed interleaving technique was compared with a conventional sequential interleaving (SeqI) technique on a phantom and eight subjects. RESULTS: The quantified ringing artifacts level in the motion-resolved image is positively correlated with the quantified nonuniformity level of the corresponding k-space. The nonuniformity levels of the end-expiratory and end-inspiratory k-space binned from GSI data (0.34 ± 0.07, 0.33 ± 0.05) are significantly lower with statistical significance (p < 0.05) than that binned from SeqI data (0.44 ± 0.11, 0.42 ± 0.12). Ringing artifacts are substantially reduced in the dynamic images of eight subjects acquired using the proposed technique in comparison with that acquired using the conventional SeqI technique. CONCLUSION: Ringing artifacts in the motion-resolved images induced by diaphragm drifting can be reduced using the proposed GSI technique for free-breathing dynamic pulmonary MRI. This technique has the potential to reduce ringing artifacts in free-breathing liver and kidney MRI based on full-echo interleaved 3D radial acquisition.

Maximum spherical mean value filtering for whole-brain QSM.

PURPOSE: To develop a tissue field-filtering algorithm, called maximum spherical mean value (mSMV), for reducing shadow artifacts in QSM of the brain without requiring brain-tissue erosion. THEORY AND METHODS: Residual background field is a major source of shadow artifacts in QSM. The mSMV algorithm filters large field-magnitude values near the border, where the maximum value of the harmonic background field is located. The effectiveness of mSMV for artifact removal was evaluated by comparing existing QSM algorithms in numerical brain simulation as well as using in vivo human data acquired from 11 healthy volunteers and 93 patients. RESULTS: Numerical simulation showed that mSMV reduces shadow artifacts and improves QSM accuracy. Better shadow reduction, as demonstrated by lower QSM variation in the gray matter and higher QSM image quality score, was also observed in healthy subjects and in patients with hemorrhages, stroke, and multiple sclerosis. CONCLUSION: The mSMV algorithm allows QSM maps that are substantially equivalent to those obtained using SMV-filtered dipole inversion without eroding the volume of interest.

Sidebands in CEST MR-How to recognize and avoid them.

PURPOSE: Clinical scanners require pulsed CEST sequences to maintain amplifier and specific absorption rate limits. During off-resonant RF irradiation and interpulse delay, the magnetization can accumulate specific relative phases within the pulse train. In this work, we show that these phases are important to consider, as they can lead to unexpected artifacts when no interpulse gradient spoiling is performed during the saturation train. METHODS: We investigated sideband artifacts using a CEST-3D snapshot gradient-echo sequence at 3 T. Initially, Bloch-McConnell simulations were carried out with Pulseq-CEST, while measurements were performed in vitro and in vivo. RESULTS: Sidebands can be hidden in Z-spectra, and their structure becomes clearly visible only at high sampling. Sidebands are further influenced by B0 inhomogeneities and the RF phase cycling within the pulse train. In vivo, sidebands are mostly visible in liquid compartments such as CSF. Multi-pulse sidebands can be suppressed by interpulse gradient spoiling. CONCLUSION: We provide new insights into sidebands occurring in pulsed CEST experiments and show that, similar as in imaging sequences, gradient and RF spoiling play an important role. Gradient spoiling avoids misinterpretations of sidebands as CEST effects especially in liquid environments including pathological tissue or for CEST resonances close to water. It is recommended to simulate pulsed CEST sequences in advance to avoid artifacts.

Wideband black-blood late gadolinium enhancement imaging for improved myocardial scar assessment in patients with cardiac implantable electronic devices.

PURPOSE: Wideband phase-sensitive inversion recovery (PSIR) late gadolinium enhancement (LGE) enables myocardial scar imaging in implantable cardioverter defibrillators (ICD) patients, mitigating hyperintensity artifacts. To address subendocardial scar visibility challenges, a 2D breath-hold single-shot electrocardiography-triggered black-blood (BB) LGE sequence was integrated with wideband imaging, enhancing scar-blood contrast. METHODS: Wideband BB, with increased bandwidth in the inversion pulse (0.8-3.8 kHz) and T2 preparation refocusing pulses (1.6-5.0 kHz), was compared with conventional and wideband PSIR, and conventional BB, in a phantom and sheep with and without ICD, and in six patients with cardiac devices and known myocardial injury. ICD artifact extent was quantified in the phantom and specific absorption rate (SAR) was reported for each sequence. Image contrast ratios were analyzed in both phantom and animal experiments. Expert radiologists assessed image quality, artifact severity, and scar segments in patients and sheep. Additionally, histology was performed on the sheep's heart. RESULTS: In the phantom, wideband BB reduced ICD artifacts by 62% compared to conventional BB while substantially improving scar-blood contrast, but with a SAR more than 24 times that of wideband PSIR. Similarly, the animal study demonstrated a considerable increase in scar-blood contrast with wideband BB, with superior scar detection compared with wideband PSIR, the latter confirmed by histology. In alignment with the animal study, wideband BB successfully eliminated severe ICD hyperintensity artifacts in all patients, surpassing wideband PSIR in image quality and scar detection. CONCLUSION: Wideband BB may play a crucial role in imaging ICD patients, offering images with reduced ICD artifacts and enhanced scar detection.

Unfolding coil localized errors from an imperfect slice profile using a structured autocalibration matrix: An application to reduce outflow effects in cine bSSFP imaging.

PURPOSE: Balanced steady-state free precession (bSSFP) imaging is susceptible to outflow effects where excited spins leaving the slice as part of the blood stream are misprojected back onto the imaging plane. Previous work proposed using slice-encoding steps to localize these outflow effects from corrupting the target slice, at the expense of prolonged scan time. This present study extends this idea by proposing a means of significantly reducing most of the outflowing signal from the imaged slice using a coil localization method that acquires a slice-encoded calibration scan in addition to the 2D data, without being nearly as time-demanding as our previous method. This coil localization method is titled UNfolding Coil Localized Errors from an imperfect slice profile using a Structured Autocalibration Matrix (UNCLE SAM). METHODS: Retrospective and prospective evaluations were carried out. Both featured a 2D acquisition and a separate slice-encoded calibration of the center in-plane k $$ k $$ -space lines across all desired slice-encoding steps. RESULTS: Retrospective results featured a slice-by-slice comparison of the slice-encoded images with UNCLE SAM. UNCLE SAM's subtraction from the slice-encoded image was compared with a subtraction from the flow-corrupted 2D image, to demonstrate UNCLE SAM's capability to unfold outflowing spins. UNCLE SAM's comparison with slice encoding showed that UNCLE SAM was able to unfold up to 74% of what slice encoding achieved. Prospective results showed significant reduction in outflow effects with only a marginal increase in scan time from the 2D acquisition. CONCLUSIONS: We developed a method that effectively unfolds most outflowing spins from corrupting the target slice and does not require the explicit use of slice-encoding gradients. This development offers a method to reduce most outflow effects from the target slice within a clinically feasible scan duration compared with the fully sampled slice-encoding technique.

The Psychological, Physiological, and Behavioral Responses of Patients to Magnetic Resonance Imaging (MRI): A Systematic Review and Meta-Analysis.

BACKGROUND: MRI is generally well-tolerated although it may induce physiological stress responses and anxiety in patients. PURPOSE: Investigate the psychological, physiological, and behavioral responses of patients to MRI, their evolution over time, and influencing factors. STUDY TYPE: Systematic review with meta-analysis. POPULATION: 181,371 adult patients from 44 studies undergoing clinical MRI. ASSESSMENT: Pubmed, PsycInfo, Web of Science, and Scopus were systematically searched according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Quality appraisal was conducted with the Joanna Briggs Institute critical appraisal tools. Meta-analysis was conducted via Meta-Essentials workbooks when five studies were available for an outcome. Psychological and behavioral outcomes could be analyzed. Psychological outcomes were anxiety (State-Trait-Anxiety Inventory, STAI-S; 37) and willingness to undergo MRI again. Behavioral outcomes included unexpected behaviors: No shows, sedation, failed scans, and motion artifacts. Year of publication, sex, age, and positioning were examined as moderators. STATISTICAL TESTS: Meta-analysis, Hedge's g. A P value <0.05 was considered to indicate statistical significance. RESULTS: Of 12,755 initial studies, 104 studies were included in methodological review and 44 (181,371 patients) in meta-analysis. Anxiety did not significantly reduce from pre- to post-MRI (Hedge's g = -0.20, P = 0.051). Pooled values of STAI-S (37) were 44.93 (pre-MRI) and 40.36 (post-MRI). Of all patients, 3.9% reported unwillingness to undergo MRI again. Pooled prevalence of unexpected patient behavior was 11.4%; rates for singular behaviors were: Failed scans, 2.1%; no-shows, 11.5%; sedation, 3.3%; motion artifacts, 12.2%. Year of publication was not a significant moderator (all P > 0.169); that is, the patients' response was not improved in recent vs. older studies. Meta-analysis of physiological responses was not feasible since preconditions were not met for any outcome. DATA CONCLUSION: Advancements of MRI technology alone may not be sufficient to eliminate anxiety in patients undergoing MRI and related unexpected behaviors. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 5.

15-color highly sensitive flow cytometry assay for post anti-CD19 targeted therapy (anti-CD19-CAR-T and blinatumomab) measurable residual disease assessment in B-lymphoblastic leukemia/lymphoma: Real-world applicability and challenges.

OBJECTIVES: Measurable residual disease (MRD) is the most relevant predictor of disease-free survival in B-cell acute lymphoblastic leukemia (B-ALL). We aimed to establish a highly sensitive flow cytometry (MFC)-based B-ALL-MRD (BMRD) assay for patients receiving anti-CD19 immunotherapy with an alternate gating approach and to document the prevalence and immunophenotype of recurrently occurring low-level mimics and confounding populations. METHODS: We standardized a 15-color highly-sensitive BMRD assay with an alternate CD19-free gating approach. The study included 137 MRD samples from 43 relapsed/refractory B-ALL patients considered for anti-CD19 immunotherapy. RESULTS: The 15-color BMRD assay with CD22/CD24/CD81/CD33-based gating approach was routinely applicable in 137 BM samples and could achieve a sensitivity of 0.0005%. MRD was detected in 29.9% (41/137) samples with 31.7% (13/41) of them showing <.01% MRD. Recurrently occurring low-level cells that showed immunophenotypic overlap with leukemic B-blasts included: (a) CD19+CD10+CD34+CD22+CD24+CD81+CD123+CD304+ plasmacytoid dendritic cells, (b) CD73bright/CD304bright/CD81bright mesenchymal stromal/stem cells (CD10+) and endothelial cells (CD34+CD24+), (c) CD22dim/CD34+/CD38dim/CD81dim/CD19-/CD10-/CD24- early lymphoid progenitor/precursor type-1 cells (ELP-1) and (d) CD22+/CD34+/CD10heterogeneous/CD38moderate/CD81moderate/CD19-/CD24- stage-0 B-cell precursors or ELP-2 cells. CONCLUSIONS: We standardized a highly sensitive 15-color BMRD assay with a non-CD19-based gating strategy for patients receiving anti-CD19 immunotherapy. We also described the immunophenotypes of recurrently occurring low-level populations that can be misinterpreted as MRD in real-world practice.

Breast MRI in patients with implantable loop recorder: initial experience.

OBJECTIVES: To investigate the feasibility of breast MRI exams and guided biopsies in patients with an implantable loop recorder (ILR) as well as the impact ILRs may have on image interpretation. MATERIALS AND METHODS: This retrospective study examined breast MRIs of patients with ILR, from April 2008 to September 2022. Radiological reports and electronic medical records were reviewed for demographic characteristics, safety concerns, and imaging findings. MR images were analyzed and compared statistically for artifact quantification on the various pulse sequences. RESULTS: Overall, 40/82,778 (0.049%) MRIs during the study period included ILR. All MRIs were completed without early termination. No patient-related or device-related adverse events occurred. ILRs were most commonly located in the left lower-inner quadrant (64.6%). The main artifact was a signal intensity (SI) void in a dipole formation in the ILR bed with or without areas of peripheral high SI. Artifacts appeared greatest in the cranio-caudal axis (p < 0.001), followed by the anterior-posterior axis (p < 0.001), and then the right-left axis. High peripheral rim-like SI artifacts appeared on the post-contrast and subtracted T1-weighted images, mimicking suspicious enhancement. Artifacts were most prominent on diffusion-weighted (p < 0.001), followed by T2-weighted and T1-weighted images. In eight patients, suspicious findings were found on MRI, resulting in four additional malignant lesions. Of six patients with left breast cancer, the tumor was completely visible in five cases and partially obscured in one. CONCLUSION: Breast MRI is feasible and safe among patients with ILR and may provide a significant diagnostic value, albeit with localized, characteristic artifacts. CLINICAL RELEVANCE STATEMENT: Indicated breast MRI exams and guided biopsies can be safely performed in patients with implantable loop recorder. Nevertheless, radiologists should be aware of associated limitations including limited assessment of the inner left breast and pseudo-enhancement artifacts. KEY POINTS: • Breast MRI in patients with an implantable loop recorder is an infrequent, feasible, and safe procedure. • Despite limited breast visualization of the implantable loop recorder bed and characteristic artifacts, MRI depicted additional lesions in 8/40 (20%) of cases, half of which were malignant. • Breast MRI in patients with an implantable loop recorder should be performed when indicated, taking into consideration typical associated artifacts.

Are dilution, slow injection and care bolus technique the causal solution to mitigating arterial-phase artifacts on gadoxetic acid-enhanced MRI? A large-cohort study.

OBJECTIVE: Arterial-phase artifacts are gadoxetic acid (GA)-enhanced MRI's major drawback, ranging from 5 to 39%. We evaluate the effect of dilution and slow injection of GA using automated fluoroscopic triggering on liver MRI arterial-phase (AP) acquisition timing, artifact frequency, and lesion visibility. METHODS AND MATERIALS: Saline-diluted 1:1 GA was injected at 1 ml/s into 1413 patients for 3 T liver MRI. Initially, one senior abdominal radiologist, i.e., principal investigator (PI), assessed all MR exams and compared them to previous and follow-up images, as well as the radiology report on record, determining the standard of reference for lesion detection and characterization. Then, three other readers independently evaluated the AP images for artifact type (truncation (TA), transient severe motion (TSM) or mixed), artifact severity (on a 5-point scale), acquisition timing (on a 4-point scale) and visibility (on a 5-point scale) of hypervascular lesions ≥ 5 mm, selected by the PI. Artifact score ≥ 4 and artifact score ≤ 3 were considered significant and non-significant artifacts, respectively. RESULTS: Of the 1413 exams, diagnostic-quality arterial-phase images included 1100 (77.8%) without artifacts, 220 (15.6%) with minimal, and 77 (5.4%) with moderate artifacts. Only 16 exams (1.1%) had significant artifacts, 13 (0.9%) with severe artifacts (score 4), and three (0.2%) non-diagnostic artifacts (score 5). AP acquisition timing was optimal in 1369 (96.8%) exams. Of the 449 AP hypervascular lesions, 432 (96.2%) were detected. CONCLUSION: Combined dilution and slow injection of GA with MR results in well-timed arterial-phase images in 96.8% and a reduction of exams with significant artifacts to 1.1%. CLINICAL RELEVANCE STATEMENT: Hypervascular lesions, in particular HCC detection, hinge on arterial-phase hyperenhancement, making well-timed, artifact-free arterial-phase images a prerequisite for accurate diagnosis. Saline dilution 1:1, slow injection (1 ml/s), and automated bolus triggering reduce artifacts and optimize acquisition timing. KEY POINTS: • There was substantial agreement among the three readers regarding the presence and type of arterial-phase (AP) artifacts, acquisition timing, and lesion visibility. • Impaired AP hypervascular lesion visibility occurred in 17 (3.8%) cases; in eight lesions due to mistiming and in nine lesions due to significant artifacts. • When AP timing was suboptimal, it was too late in 40 exams (3%) and too early in 4 exams (0.2%) of exams.