The Impact of Closed-Loop Imaging on Actionable CT-Detected Breast Findings.

PURPOSE: Closed-loop imaging programs (CLIPs) are designed to ensure that patients receive appropriate follow-up, but a review of incidental CT-detected breast findings in the setting of CLIPs has not been performed. METHODS: A retrospective review was conducted of CT reports at a single academic institution from July 1, 2020, to January 31, 2022, to identify reports with recommendations for breast imaging follow-up. Medical records were reviewed to evaluate patient adherence to follow-up, CLIP intervention, subsequent BI-RADS assessment, and diagnosis. Adherence was defined as diagnostic breast imaging performed within 6 months of the CT recommendation. RESULTS: Follow-up recommendations for breast imaging were included in CT report impressions for 311 patients. Almost half of patients (47.3% [147 of 311]) underwent follow-up breast imaging within 6 months, yielding breast cancer diagnoses in 12.9% (19 of 147) and a biopsy-proven positive predictive value of 65.5% (19 of 29). Most patients who returned for follow-up within 6 months did so without CLIP intervention. The majority of CT report impressions in the follow-up group (85.0% [125 of 147]) contained specific recommendations for "diagnostic breast imaging." For patients who did not receive follow-up, the CLIP team tracked all cases and intervened in 19.1% (28 of 147). The most common intervention was a phone call and/or fax to the primary care provider. Outpatient CT examination setting and specific recommendation for diagnostic breast imaging were significantly associated with higher follow-up adherence (P < .0001). CONCLUSIONS: Actionable CT-detected breast findings require follow-up diagnostic breast imaging because of a relevant cancer detection rate of 12.9%. Although many patients return for breast imaging without intervention, almost half of patients did not receive follow-up and may account for a significant number of missed cancer diagnoses. Specific CT recommendation verbiage is associated with higher follow-up adherence, which can be addressed across settings even without CLIPs.

Stability of steady-state visual evoked potential contrast response functions.

Repetitive sensory stimulation has been shown to induce neuroplasticity in sensory cortical circuits, at least under certain conditions. We measured the plasticity-inducing effect of repetitive contrast-reversal-sweep steady-state visual-evoked potential (ssVEP) stimuli, hoping to employ the ssVEP's high signal-to-noise electrophysiological readout in the study of human visual cortical neuroplasticity. Steady-state VEP contrast-sweep responses were measured daily for 4 days (four 20-trial blocks per day, 20 participants). No significant neuroplastic changes in response amplitude were observed either across blocks or across days. Furthermore, response amplitudes were stable within-participant, with measured across-block and across-day coefficients of variation (CV = SD/mean) of 15-20 ± 2% and 22-25 ± 2%, respectively. Steady-state VEP response phase was also highly stable, suggesting that temporal processing delays in the visual system vary by at most 2-3 ms across blocks and days. While we fail to replicate visual stimulation-dependent cortical plasticity, we show that contrast-sweep steady-state VEPs provide a stable human neurophysiological measure well suited for repeated-measures longitudinal studies.

X-FAST: A versatile, high-throughput, and user-friendly XUV femtosecond absorption spectroscopy tabletop instrument.

We present the X-FAST (XUV Femtosecond Absorption Spectroscopy Tabletop) instrument at the University of Wisconsin-Madison. The instrument produces femtosecond extreme ultraviolet photon pulses via high-harmonic generation in the range of 40-72 eV, as well as optical pump pulses for transient-absorption experiments. The system implements a gas-cooled sample cell that enables studying the dynamics of thermally sensitive thin-film samples. This paper provides potential users with specifications of the optical, vacuum, data acquisition, and sample cooling systems of the X-FAST instrument, along with performance metrics and data of an ultrafast laser-induced phase transition in a Ni2MnGa Heusler thin film.

A Multicenter Assessment of Interreader Reliability of LI-RADS Version 2018 for MRI and CT.

Background Various limitations have impacted research evaluating reader agreement for Liver Imaging Reporting and Data System (LI-RADS). Purpose To assess reader agreement of LI-RADS in an international multicenter multireader setting using scrollable images. Materials and Methods This retrospective study used deidentified clinical multiphase CT and MRI and reports with at least one untreated observation from six institutions and three countries; only qualifying examinations were submitted. Examination dates were October 2017 to August 2018 at the coordinating center. One untreated observation per examination was randomly selected using observation identifiers, and its clinically assigned features were extracted from the report. The corresponding LI-RADS version 2018 category was computed as a rescored clinical read. Each examination was randomly assigned to two of 43 research readers who independently scored the observation. Agreement for an ordinal modified four-category LI-RADS scale (LR-1, definitely benign; LR-2, probably benign; LR-3, intermediate probability of malignancy; LR-4, probably hepatocellular carcinoma [HCC]; LR-5, definitely HCC; LR-M, probably malignant but not HCC specific; and LR-TIV, tumor in vein) was computed using intraclass correlation coefficients (ICCs). Agreement was also computed for dichotomized malignancy (LR-4, LR-5, LR-M, and LR-TIV), LR-5, and LR-M. Agreement was compared between research-versus-research reads and research-versus-clinical reads. Results The study population consisted of 484 patients (mean age, 62 years ± 10 [SD]; 156 women; 93 CT examinations, 391 MRI examinations). ICCs for ordinal LI-RADS, dichotomized malignancy, LR-5, and LR-M were 0.68 (95% CI: 0.61, 0.73), 0.63 (95% CI: 0.55, 0.70), 0.58 (95% CI: 0.50, 0.66), and 0.46 (95% CI: 0.31, 0.61) respectively. Research-versus-research reader agreement was higher than research-versus-clinical agreement for modified four-category LI-RADS (ICC, 0.68 vs 0.62, respectively; P = .03) and for dichotomized malignancy (ICC, 0.63 vs 0.53, respectively; P = .005), but not for LR-5 (P = .14) or LR-M (P = .94). Conclusion There was moderate agreement for LI-RADS version 2018 overall. For some comparisons, research-versus-research reader agreement was higher than research-versus-clinical reader agreement, indicating differences between the clinical and research environments that warrant further study. © RSNA, 2023 Supplemental material is available for this article. See also the editorials by Johnson and Galgano and Smith in this issue.

Transition From Peer Review to Peer Learning: Lessons Learned.

Landmark publications, such as To Err is Human, confronted the healthcare community with the egregious toll medical errors played in both patient safety and overall healthcare costs. This heralded a paradigm shift and a call for action by professional organizations to enact methods to ensure physician competency and quality assurance. The American College of Radiology similarly convened a task force to discuss these concerns and how best to address quality assurance in radiology practice, leading to the development of RADPEER, a score-based peer review system. However, critics were quick to point out the deficiencies of this model, highlighting it as punitive and a poor evaluator of physician performance. The recognized deficiencies in score-based peer review prompted the pursuit of an alternate model that would instead emphasize learning and improvement. Peer learning was proposed and highlighted the necessity of an inclusive and collaborative environment where colleagues could discuss case errors as learning opportunities without fear of punitive consequence. This paper explores peer learning, its benefits and challenges, as well as how to identify specific learning opportunities by utilizing case examples.

Utilizing 3D printing to assist pre-procedure planning of transjugular intrahepatic portosystemic shunt (TIPS) procedures: a pilot study.

BACKGROUND: 3D (three-dimensional) printing has been adopted by the medical community in several ways, procedure planning being one example. This application of technology has been adopted by several subspecialties including interventional radiology, however the planning of transjugular intrahepatic portosystemic shunt (TIPS) placement has not yet been described. The impact of a 3D printed model on procedural measures such as procedure time, radiation exposure, intravascular contrast dosage, fluoroscopy time, and provider confidence has also not been reported. METHODS: This pilot study utilized a quasi-experimental design including patients who underwent TIPS. For the control group, retrospective data was collected on patients who received a TIPS prior to Oct 1, 2020. For the experimental group, patient-specific 3D printed models were integrated in the care of patients that received TIPS between Oct 1, 2020 and April 15, 2021. Data was collected on patient demographics and procedural measures. The interventionalists were surveyed on their confidence level and model usage following each procedure in the experimental group. RESULTS: 3D printed models were created for six TIPS. Procedure time (p = 0.93), fluoroscopy time (p = 0.26), and intravascular contrast dosage (p = 0.75) did not have significant difference between groups. Mean radiation exposure was 808.8 mGy in the group with a model compared to 1731.7 mGy without, however this was also not statistically significant (p = 0.09). Out of 11 survey responses from interventionists, 10 reported "increased" or "significantly increased" confidence after reviewing the 3D printed model and all responded that the models were a valuable tool for trainees. CONCLUSIONS: 3D printed models of patient anatomy can consistently be made using consumer-level, desktop 3D printing technology. This study was not adequately powered to measure the impact that including 3D printed models in the planning of TIPS procedures may have on procedural measures. The majority of interventionists reported that patient-specific models were valuable tools for teaching trainees and that confidence levels increased as a result of model inclusion in procedure planning.

Nanosecond Metal-to-Ligand Charge-Transfer State in an Fe(II) Chromophore: Lifetime Enhancement via Nested Potentials.

Examples of Fe complexes with long-lived (≥1 ns) charge-transfer states are limited to pseudo-octahedral geometries with strong σ-donor chelates. Alternative strategies based on varying both coordination motifs and ligand donicity are highly desirable. Reported herein is an air-stable, tetragonal FeII complex, Fe(HMTI)(CN)2 (HMTI = 5,5,7,12,12,14-hexamethyl-1,4,8,11-tetraazacyclotetradeca-1,3,8,10-tetraene), with a 1.25 ns metal-to-ligand charge-transfer (MLCT) lifetime. The structure has been determined, and the photophysical properties have been examined in a variety of solvents. The HMTI ligand is highly π-acidic due to low-lying π*(C═N), which enhances ΔFe via stabilizing t2g orbitals. The inflexible geometry of the macrocycle results in short Fe-N bonds, and density functional theory calculations show that this rigidity results in an unusual set of nested potential energy surfaces. Moreover, the lifetime and energy of the MLCT state depends strongly on the solvent environment. This dependence is caused by modulation of the axial ligand-field strength by Lewis acid-base interactions between the solvent and the cyano ligands. This work represents the first example of a long-lived charge transfer state in an FeII macrocyclic species.

Transcranial ultrasound neuromodulation of the thalamic visual pathway in a large animal model and the dose-response relationship with MR-ARFI.

Neuromodulation of deep brain structures via transcranial ultrasound stimulation (TUS) is a promising, but still elusive approach to non-invasive treatment of brain disorders. The purpose of this study was to confirm that MR-guided TUS of the lateral geniculate nucleus (LGN) can modulate visual evoked potentials (VEPs) in the intact large animal; and to study the impact on cortical brain oscillations. The LGN on one side was identified with T2-weighted MRI in sheep (all male, n = 9). MR acoustic radiation force imaging (MR-ARFI) was used to confirm localization of the targeted area in the brain. Electroencephalographic (EEG) signals were recorded, and the visual evoked potential (VEP) peak-to-peak amplitude (N70 and P100) was calculated for each trial. Time-frequency spectral analysis was performed to elucidate the effect of TUS on cortical brain dynamics. The VEP peak-to-peak amplitude was reversibly suppressed relative to baseline during TUS. Dynamic spectral analysis demonstrated a change in cortical oscillations when TUS is paired with visual sensory input. Sonication-associated microscopic displacements, as measured by MR-ARFI, correlated with the TUS-mediated suppression of visual evoked activity. TUS non-invasively delivered to LGN can neuromodulate visual activity and oscillatory dynamics in large mammalian brains.

MeCP2 deficiency impairs motor cortical circuit flexibility associated with motor learning.

Loss of function mutations in the X-linked gene encoding methyl-CpG binding protein 2 (MECP2) cause Rett syndrome (RTT), a postnatal neurological disorder. The loss of motor function is an important clinical feature of RTT that manifests early during the course of the disease. RTT mouse models with mutations in the murine orthologous Mecp2 gene replicate many human phenotypes, including progressive motor impairments. However, relatively little is known about the changes in circuit function during the progression of motor deficit in this model. As the motor cortex is the key node in the motor system for the control of voluntary movement, we measured firing activity in populations of motor cortical neurons during locomotion on a motorized wheel-treadmill. Different populations of neurons intermingled in the motor cortex signal different aspects of the locomotor state of the animal. The proportion of running selective neurons whose activity positively correlates with locomotion speed gradually decreases with weekly training in wild-type mice, but not in Mecp2-null mice. The fraction of rest-selective neurons whose activity negatively correlates with locomotion speed does not change with training in wild-type mice, but is higher and increases with the progression of locomotion deficit in mutant mice. The synchronization of population activity that occurs in WT mice with training did not occur in Mecp2-null mice, a phenotype most clear during locomotion and observable across all functional cell types. Our results could represent circuit-level biomarkers for motor regression in Rett syndrome.

Increased Reliability of Visually-Evoked Activity in Area V1 of the MECP2-Duplication Mouse Model of Autism.

Atypical sensory processing is now thought to be a core feature of the autism spectrum. Influential theories have proposed that both increased and decreased neural response reliability within sensory systems could underlie altered sensory processing in autism. Here, we report evidence for abnormally increased reliability of visual-evoked responses in layer 2/3 neurons of adult male and female primary visual cortex in the MECP2-duplication syndrome animal model of autism. Increased response reliability was due in part to decreased response amplitude, decreased fluctuations in endogenous activity, and an abnormal decoupling of visual-evoked activity from endogenous activity. Similar to what was observed neuronally, the optokinetic reflex occurred more reliably at low contrasts in mutant mice compared with controls. Retinal responses did not explain our observations. These data suggest that the circuit mechanisms for combining sensory-evoked and endogenous signal and noise processes may be altered in this form of syndromic autism.SIGNIFICANCE STATEMENT Atypical sensory processing is now thought to be a core feature of the autism spectrum. Influential theories have proposed that both increased and decreased neural response reliability within sensory systems could underlie altered sensory processing in autism. Here, we report evidence for abnormally increased reliability of visual-evoked responses in primary visual cortex of the animal model for MECP2-duplication syndrome, a high-penetrance single-gene cause of autism. Visual-evoked activity was abnormally decoupled from endogenous activity in mutant mice, suggesting in line with the influential "hypo-priors" theory of autism that sensory priors embedded in endogenous activity may have less influence on perception in autism.

Triple therapy with adalimumab, ustekinumab and methotrexate for induction of remission in moderate to severe ileocolonic Crohn's disease with upper gastrointestinal involvement in a biologic-experienced individual.

Induction of remission in biologic-experienced individuals with moderate to severe Crohn's disease (CD) can be a challenge. We hereby present a case of CD with secondary non-response to infliximab. Adding methotrexate and switching to ustekinumab plus methotrexate did not stop the inflammatory process. Therefore, combination therapy with two classes of biologics consisting of ustekinumab and adalimumab plus methotrexate was initiated. He achieved clinical remission in 4 weeks and remained on triple therapy for 6 months which was subsequently tailored to adalimumab/methotrexate combination therapy due to insurance restriction on ustekinumab. He remained in remission for the duration of follow-up, 14 months after initiation of triple therapy and 8 months after switching to methotrexate/adalimumab biologic monotherapy. Triple therapy with anti-TNF, IL-12/23 inhibitor and methotrexate could potentially be an option for induction of remission in biologic-experienced individuals with good initial clinical response to anti-TNF agents.

Motor training improves coordination and anxiety in symptomatic Mecp2-null mice despite impaired functional connectivity within the motor circuit.

Rett syndrome (RTT) is a severe neurodevelopmental disorder caused by loss of function of the X-linked methyl-CpG­binding protein 2 (MECP2). Several case studies report that gross motor function can be improved in children with RTT through treadmill walking, but whether the MeCP2-deficient motor circuit can support actual motor learning remains unclear. We used two-photon calcium imaging to simultaneously observe layer (L) 2/3 and L5a excitatory neuronal activity in the motor cortex (M1) while mice adapted to changing speeds on a computerized running wheel. Despite circuit hypoactivity and weakened functional connectivity across L2/3 and L5a, the Mecp2-null circuit's firing pattern evolved with improved performance over 2 weeks. Moreover, trained mice became less anxious and lived 20% longer than untrained mice. Because motor deficits and anxiety are core symptoms of RTT, which is not diagnosed until well after symptom onset, these results underscore the benefit of motor learning.

Inhibition of Elevated Ras-MAPK Signaling Normalizes Enhanced Motor Learning and Excessive Clustered Dendritic Spine Stabilization in the MECP2-Duplication Syndrome Mouse Model of Autism.

The inflexible repetitive behaviors and "insistence on sameness" seen in autism imply a defect in neural processes controlling the balance between stability and plasticity of synaptic connections in the brain. It has been proposed that abnormalities in the Ras-ERK/MAPK pathway, a key plasticity-related cell signaling pathway known to drive consolidation of clustered synaptic connections, underlie altered learning phenotypes in autism. However, a link between altered Ras-ERK signaling and clustered dendritic spine plasticity has yet to be explored in an autism animal model in vivo The formation and stabilization of dendritic spine clusters is abnormally increased in the MECP2-duplication syndrome mouse model of syndromic autism, suggesting that ERK signaling may be increased. Here, we show that the Ras-ERK pathway is indeed hyperactive following motor training in MECP2-duplication mouse motor cortex. Pharmacological inhibition of ERK signaling normalizes the excessive clustered spine stabilization and enhanced motor learning behavior in MECP2-duplication mice. We conclude that hyperactive ERK signaling may contribute to abnormal clustered dendritic spine consolidation and motor learning in this model of syndromic autism.

Excessive Formation and Stabilization of Dendritic Spine Clusters in the MECP2-Duplication Syndrome Mouse Model of Autism.

Autism-associated genetic mutations may perturb the balance between stability and plasticity of synaptic connections in the brain. Here, we report an increase in the formation and stabilization of dendritic spines in the cerebral cortex of the mouse model of MECP2-duplication syndrome, a high-penetrance form of syndromic autism. Increased stabilization is mediated entirely by spines that form cooperatively in 10-µm clusters and is observable across multiple cortical areas both spontaneously and following motor training. Excessive stability of dendritic spine clusters could contribute to behavioral rigidity and other phenotypes in syndromic autism.

Controversies in Rectal Cancer Treatment and Management.

Incorporation of new treatment modalities has significantly increased the complexity of the treatment and management of rectal cancer, including perioperative therapy for local advanced disease and organ preservation for those with response to the preoperative treatment. This review may help practitioners better understand the rationale and selection.

Clinicians and surgeon survey regarding current and future versions of CT/MRI LI-RADS.

PURPOSE: To determine preferences of clinicians and surgeons regarding radiology reporting of liver observations in patients at risk for hepatocellular carcinoma (HCC). METHODS: Members of the American College of Radiology Liver Imaging and Data Reporting System (LI-RADS) Outreach & Education Group (30 members) as well as Society of Abdominal Radiology Disease-Focused Panel on HCC diagnosis (27 members) created and distributed an 18-question survey to clinicians and surgeons, with focus on preferences regarding radiology reporting of liver observations in patients. The survey questions were directed to physician demographics, current use of LI-RADS by their local radiologists, their opinions about current LI-RADS and potential improvements. RESULTS: A total of 152 physicians responded, 66.4% (101/152) from North America, including 42 surgeons, 81 physicians and 29 interventional radiologists. Participants were predominantly from academic centers 83% (126/152), while 13.8% (21/152) worked in private/community centers and 3.2% (5/152) worked in a hybrid practice. Almost 90% (136/152) of participants preferred the use of LI-RADS (compared to nothing or other standardized reporting systems; OPTN and AASLD) to communicate liver-related observations. However, only 28.5% (43/152) of participants input was sought at the time of implementing LI-RADS in their institutions. Fifty-eight percent (88/152) of all participants found standardized LI-RADS management recommendations in radiology reports to be clinically helpful. However, a subgroup analysis of surgeons in academic centers showed that 61.8% (21/34) prefer not to receive standardized LI-RADS recommendations. CONCLUSIONS: Most participants preferred the use LI-RADS in reporting CT and MRI examination. When considering inclusion of management recommendations, radiologists should consult with their referring physicians, as preference may differ.

LI-RADS v2018: utilizing ancillary features on gadoxetate-enhanced MRI to modify final LI-RADS category.

PURPOSE: To quantify how often the LI-RADS v2018 category changed when utilizing major features only, when utilizing major and ancillary features, and when utilizing major and ancillary features excluding gadoxetate-specific ancillary features. METHODS: Retrospective analysis of 100 patients age 18 and older at high risk for hepatocellular carcinoma who had an MRI abdomen performed with intravenous contrast gadoxetate between 1/1/2017 and 3/23/2018. Each examination was reviewed by a body fellowship-trained radiologist. LI-RADS category was assigned to the liver observation after review of major features only. Ancillary features were then reviewed and LI-RADS category assigned both including and excluding ancillary features specific to gadoxetate. RESULTS: Utilizing all MRI ancillary features, including those specific to gadoxetate, changed the final LI-RADS category in 56.4% of liver observations, the majority an increase or decrease from LR-3. When not including the ancillary features specific to gadoxetate, the final LI-RADS category changed in 30.9% of observations, the majority increasing from LR-3 to LR-4. CONCLUSION: Utilizing LI-RADS v2018 ancillary features can significantly alter the final LI-RADS category, especially when using gadoxetate-specific ancillary features. Understanding the correct application of ancillary features for the final LI-RADS category helps implement a more consistent category assessment amongst users.

Contribution of apical and basal dendrites to orientation encoding in mouse V1 L2/3 pyramidal neurons.

Pyramidal neurons integrate synaptic inputs from basal and apical dendrites to generate stimulus-specific responses. It has been proposed that feed-forward inputs to basal dendrites drive a neuron's stimulus preference, while feedback inputs to apical dendrites sharpen selectivity. However, how a neuron's dendritic domains relate to its functional selectivity has not been demonstrated experimentally. We performed 2-photon dendritic micro-dissection on layer-2/3 pyramidal neurons in mouse primary visual cortex. We found that removing the apical dendritic tuft did not alter orientation-tuning. Furthermore, orientation-tuning curves were remarkably robust to the removal of basal dendrites: ablation of 2 basal dendrites was needed to cause a small shift in orientation preference, without significantly altering tuning width. Computational modeling corroborated our results and put limits on how orientation preferences among basal dendrites differ in order to reproduce the post-ablation data. In conclusion, neuronal orientation-tuning appears remarkably robust to loss of dendritic input.