Evaluating the added value of concurrent contrast-enhanced diagnostic CT for PSMA-PET/CT Interpretation.

RATIONALE AND OBJECTIVES: To determine whether concurrent contrast-enhanced diagnostic CT (DxCT) confers added diagnostic certainty compared to PSMA-PET/CT alone. MATERIALS AND METHODS: This retrospective multi-reader study analyzed imaging comprising combined F-18-piflufolastat PSMA-PET/CT with diagnostic chest/abdominopelvic CT from prostate cancer patients within the first 6 months of FDA-approval of the PET agent. Six nuclear radiology readers were randomly presented with PSMA-PET/CT studies with or without DxCT and asked to report their diagnostic certainty for PSMA-avid lesions found on PET. Subsequently, readers re-reviewed the same study after an interlude (with the CT if not previously presented and vice-versa) to determine if DxCT altered their diagnostic assessment. Inter-rater concordance was assessed on a subset of images read by all readers. Diagnostic certainties for PSMA-PET/CT with and without DxCT were compared, and the variables for which DxCT may add value were examined. RESULTS: Good inter-rater concordance across readers was noted for both PET/CT (Finn's coefficient of reliability for overall scan certainty: 0.85,p < 0.01) and combined DxCT-PET/CT (0.59,p < 0.01). Overall certainty and concordance between PET/CT and combined DxCT-PET/CT datasets were similar (overall scan certainty: 92% ± 16 vs. 92% ± 17,p = 0.43), with no significant advantage for adding DxCT across different anatomic locations or clinical parameters. A slight predilection for combined DxCT-PET/CT was noted when interpreting images acquired for the initial staging of prostate cancer (89% ± 16 vs. 93% ± 17,p = 0.08). CONCLUSION: Good inter-reader concordance can be achieved across different training levels with PSMA-PET/CT. Furthermore, using DxCT concurrent with PSMA-PET/CT does not significantly improve diagnostic certainty for most indications but may be useful for initial staging.

Synthetic Mammography: Benefits, Drawbacks, and Pitfalls.

Digital breast tomosynthesis (DBT) allows three-dimensional assessment of breast tissue; however, DBT requires a two-dimensional (2D) image for comparison with prior mammograms and accurate interpretation of calcifications. Traditionally, full-field digital mammography (FFDM) has been performed after the DBT image acquisition. Synthetic mammography (SM), the 2D reconstruction of the tomosynthesis slice dataset, has been designed to replace FFDM. Advantages of SM include decreased image acquisition time and decreased radiation exposure, with maintained or improved screening performance metrics. Because SM algorithms give extra weight to lesion-like characteristics (eg, calcifications and architectural distortions), they may enable increased visibility of these characteristics relative to that at FFDM. Although SM algorithms were designed to improve lesion identification, they have led to varied outcomes in studies reported in the literature. Compared with FFDM, SM has been reported to be associated with a higher false-positive rate for calcifications, decreased conspicuity of asymmetries, lower breast density assessments, and imaging artifacts (eg, metallic artifact, bright-band artifact, blurring of the axilla, and truncation artifact). The authors review the literature on SM, including its implementation, benefits, and artifacts. ©RSNA, 2023 Quiz questions for this article are available through the Online Learning Center.

Frequency and Outcomes of BI-RADS Category 3 Assessments in Patients With a Personal History of Breast Cancer: Full-Field Digital Mammography Versus Digital Breast Tomosynthesis.

BACKGROUND. Studies establishing the validity of BI-RADS category 3 excluded patients with personal history of breast cancer (PHBC). Use of category 3 in patients with PHBC may be impacted not only by this population's increased breast cancer risk, but also by adoption of digital breast tomosynthesis (DBT) over full-field digital mammography (FFDM). OBJECTIVE. The purpose of this article was to compare the frequency, outcomes, and additional characteristics of BI-RADS category 3 assessments between FFDM and DBT in patients with PHBC. METHODS. This retrospective study included 14,845 mammograms in 10,118 patients (mean age, 63 years) with PHBC who had undergone mastectomy and/or lumpectomy. Of these, 8422 examinations were performed by FFDM from October 2014 to September 2016, and 6423 examinations by FFDM with DBT from February 2017 to December 2018, after interval conversion of the center's mammography units. Information was extracted from the EHR and radiology reports. FFDM and DBT groups were compared in the entire sample and among index category 3 lesions (i.e., earliest category 3 assessment per lesion). RESULTS. The frequency of category 3 assessment was lower for DBT than FFDM (5.6% vs 6.4%; p = .05). DBT, compared with FFDM, showed a lower malignancy rate for category 3 lesions (1.8% vs 5.0%; p = .04), higher malignancy rate for category 4 lesions (32.0% vs 23.2%; p = .03), and no difference in malignancy rate for category 5 lesions (100.0% vs 75.0%; p = .24). Analysis of index category 3 lesions included 438 and 274 lesions for FFDM and DBT, respectively. For category 3 lesions, DBT, compared with FFDM, showed lower PPV3 (13.9% vs 36.1%; p = .02) and a more frequent mammographic finding of mass (33.2% vs 23.1%; p = .003). CONCLUSION. The malignancy rate for category 3 lesions in patients with PHBC was less than the accepted limit (2%) for DBT (1.8%), but not FFDM (5.0%). A lower malignancy rate for category 3 lesions but higher malignancy rate for category 4 lesions for DBT supports more appropriate application of category 3 assessment in patients with PHBC through use of DBT. CLINICAL IMPACT. These insights may help establish whether category 3 assessments in patients with PHBC are within benchmarks for early detection of second cancers and reduction of benign biopsies.

Lasting Adaptations in Social Behavior Produced by Social Disruption and Inhibition of Adult Neurogenesis.

UNLABELLED: Research on social instability has focused on its detrimental consequences, but most people are resilient and respond by invoking various coping strategies. To investigate cellular processes underlying such strategies, a dominance hierarchy of rats was formed and then destabilized. Regardless of social position, rats from disrupted hierarchies had fewer new neurons in the hippocampus compared with rats from control cages and those from stable hierarchies. Social disruption produced a preference for familiar over novel conspecifics, a change that did not involve global memory impairments or increased anxiety. Using the neuropeptide oxytocin as a tool to increase neurogenesis in the hippocampus of disrupted rats restored preference for novel conspecifics to predisruption levels. Conversely, reducing the number of new neurons by limited inhibition of adult neurogenesis in naive transgenic GFAP-thymidine kinase rats resulted in social behavior similar to disrupted rats. Together, these results provide novel mechanistic evidence that social disruption shapes behavior in a potentially adaptive way, possibly by reducing adult neurogenesis in the hippocampus. SIGNIFICANCE STATEMENT: To investigate cellular processes underlying adaptation to social instability, a dominance hierarchy of rats was formed and then destabilized. Regardless of social position, rats from disrupted hierarchies had fewer new neurons in the hippocampus compared with rats from control cages and those from stable hierarchies. Unexpectedly, these changes were accompanied by changes in social strategies without evidence of impairments in cognition or anxiety regulation. Restoring adult neurogenesis in disrupted rats using oxytocin and conditionally suppressing the production of new neurons in socially naive GFAP-thymidine kinase rats showed that loss of 6-week-old neurons may be responsible for adaptive changes in social behavior.

A recurrent germline PAX5 mutation confers susceptibility to pre-B cell acute lymphoblastic leukemia.

Somatic alterations of the lymphoid transcription factor gene PAX5 (also known as BSAP) are a hallmark of B cell precursor acute lymphoblastic leukemia (B-ALL), but inherited mutations of PAX5 have not previously been described. Here we report a new heterozygous germline variant, c.547G>A (p.Gly183Ser), affecting the octapeptide domain of PAX5 that was found to segregate with disease in two unrelated kindreds with autosomal dominant B-ALL. Leukemic cells from all affected individuals in both families exhibited 9p deletion, with loss of heterozygosity and retention of the mutant PAX5 allele at 9p13. Two additional sporadic ALL cases with 9p loss harbored somatic PAX5 substitutions affecting Gly183. Functional and gene expression analysis of the PAX5 mutation demonstrated that it had significantly reduced transcriptional activity. These data extend the role of PAX5 alterations in the pathogenesis of pre-B cell ALL and implicate PAX5 in a new syndrome of susceptibility to pre-B cell neoplasia.