Diagnostic accuracy of quantitative dual-energy CT-based volumetric bone mineral density assessment for the prediction of osteoporosis-associated fractures.

OBJECTIVES: To evaluate the predictive value of volumetric bone mineral density (BMD) assessment of the lumbar spine derived from phantomless dual-energy CT (DECT)-based volumetric material decomposition as an indicator for the 2-year occurrence risk of osteoporosis-associated fractures. METHODS: L1 of 92 patients (46 men, 46 women; mean age, 64 years, range, 19-103 years) who had undergone third-generation dual-source DECT between 01/2016 and 12/2018 was retrospectively analyzed. For phantomless BMD assessment, dedicated DECT postprocessing software using material decomposition was applied. Digital files of all patients were sighted for 2 years following DECT to obtain the incidence of osteoporotic fractures. Receiver operating characteristic (ROC) analysis was used to calculate cut-off values and logistic regression models were used to determine associations of BMD, sex, and age with the occurrence of osteoporotic fractures. RESULTS: A DECT-derived BMD cut-off of 93.70 mg/cm3 yielded 85.45% sensitivity and 89.19% specificity for the prediction to sustain one or more osteoporosis-associated fractures within 2 years after BMD measurement. DECT-derived BMD was significantly associated with the occurrence of new fractures (odds ratio of 0.8710, 95% CI, 0.091-0.9375, p < .001), indicating a protective effect of increased DECT-derived BMD values. Overall AUC was 0.9373 (CI, 0.867-0.977, p < .001) for the differentiation of patients who sustained osteoporosis-associated fractures within 2 years of BMD assessment. CONCLUSIONS: Retrospective DECT-based volumetric BMD assessment can accurately predict the 2-year risk to sustain an osteoporosis-associated fracture in at-risk patients without requiring a calibration phantom. Lower DECT-based BMD values are strongly associated with an increased risk to sustain fragility fractures. KEY POINTS: •Dual-energy CT-derived assessment of bone mineral density can identify patients at risk to sustain osteoporosis-associated fractures with a sensitivity of 85.45% and a specificity of 89.19%. •The DECT-derived BMD threshold for identification of at-risk patients lies above the American College of Radiology (ACR) QCT guidelines for the identification of osteoporosis (93.70 mg/cm3 vs 80 mg/cm3).

The constitutive differential transcriptome of a brain circuit for vocal learning.

BACKGROUND: The ability to imitate the vocalizations of other organisms, a trait known as vocal learning, is shared by only a few organisms, including humans, where it subserves the acquisition of speech and language, and 3 groups of birds. In songbirds, vocal learning requires the coordinated activity of a set of specialized brain nuclei referred to as the song control system. Recent efforts have revealed some of the genes that are expressed in these vocal nuclei, however a thorough characterization of the transcriptional specializations of this system is still missing. We conducted a rigorous and comprehensive analysis of microarrays, and conducted a separate analysis of 380 genes by in situ hybridizations in order to identify molecular specializations of the major nuclei of the song system of zebra finches (Taeniopygia guttata), a songbird species. RESULTS: Our efforts identified more than 3300 genes that are differentially regulated in one or more vocal nuclei of adult male birds compared to the adjacent brain regions. Bioinformatics analyses provided insights into the possible involvement of these genes in molecular pathways such as cellular morphogenesis, intrinsic cellular excitability, neurotransmission and neuromodulation, axonal guidance and cela-to-cell interactions, and cell survival, which are known to strongly influence the functional properties of the song system. Moreover, an in-depth analysis of specific gene families with known involvement in regulating the development and physiological properties of neuronal circuits provides further insights into possible modulators of the song system. CONCLUSION: Our study represents one of the most comprehensive molecular characterizations of a brain circuit that evolved to facilitate a learned behavior in a vertebrate. The data provide novel insights into possible molecular determinants of the functional properties of the song control circuitry. It also provides lists of compelling targets for pharmacological and genetic manipulations to elucidate the molecular regulation of song behavior and vocal learning.

Effects of hearing acuity on psychophysiological responses to effortful speech perception.

In recent studies, psychophysiological measures have been used as markers of listening effort, but there is limited research on the effect of hearing loss on such measures. The aim of the current study was to investigate the effect of hearing acuity on physiological responses and subjective measures acquired during different levels of listening demand, and to investigate the relationship between these measures. A total of 125 participants (37 males and 88 females, age range 37-72 years, pure-tone average hearing thresholds at the best ear between -5.0 to 68.8 dB HL and asymmetry between ears between 0.0 and 87.5 dB) completed a listening task. A speech reception threshold (SRT) test was used with target sentences spoken by a female voice masked by male speech. Listening demand was manipulated using three levels of intelligibility: 20 % correct speech recognition, 50 %, and 80 % (IL20 %/IL50 %/IL80 %, respectively). During the task, peak pupil dilation (PPD), heart rate (HR), pre-ejection period (PEP), respiratory sinus arrhythmia (RSA), and skin conductance level (SCL) were measured. For each condition, subjective ratings of effort, performance, difficulty, and tendency to give up were also collected. Linear mixed effects models tested the effect of intelligibility level, hearing acuity, hearing asymmetry, and tinnitus complaints on the physiological reactivity (compared to baseline) and subjective measures. PPD and PEP reactivity showed a non-monotonic relationship with intelligibility level, but no such effects were found for HR, RSA, or SCL reactivity. Participants with worse hearing acuity had lower PPD at all intelligibility levels and showed lower PEP baseline levels. Additionally, PPD and SCL reactivity were lower for participants who reported suffering from tinnitus complaints. For IL80 %, but not IL50 % or IL20 %, participants with worse hearing acuity rated their listening effort to be relatively high compared to participants with better hearing. The reactivity of the different physiological measures were not or only weakly correlated with each other. Together, the results suggest that hearing acuity may be associated with altered sympathetic nervous system (re)activity. Research using psychophysiological measures as markers of listening effort to study the effect of hearing acuity on such measures are best served by the use of the PPD and PEP.

Accuracy and precision of volumetric bone mineral density assessment using dual-source dual-energy versus quantitative CT: a phantom study.

BACKGROUND: Dual-source dual-energy computed tomography (DECT) offers the potential for opportunistic osteoporosis screening by enabling phantomless bone mineral density (BMD) quantification. This study sought to assess the accuracy and precision of volumetric BMD measurement using dual-source DECT in comparison to quantitative CT (QCT). METHODS: A validated spine phantom consisting of three lumbar vertebra equivalents with 50 (L1), 100 (L2), and 200 mg/cm3 (L3) calcium hydroxyapatite (HA) concentrations was scanned employing third-generation dual-source DECT and QCT. While BMD assessment based on QCT required an additional standardised bone density calibration phantom, the DECT technique operated by using a dedicated postprocessing software based on material decomposition without requiring calibration phantoms. Accuracy and precision of both modalities were compared by calculating measurement errors. In addition, correlation and agreement analyses were performed using Pearson correlation, linear regression, and Bland-Altman plots. RESULTS: DECT-derived BMD values differed significantly from those obtained by QCT (p < 0.001) and were found to be closer to true HA concentrations. Relative measurement errors were significantly smaller for DECT in comparison to QCT (L1, 0.94% versus 9.68%; L2, 0.28% versus 5.74%; L3, 0.24% versus 3.67%, respectively). DECT demonstrated better BMD measurement repeatability compared to QCT (coefficient of variance < 4.29% for DECT, < 6.74% for QCT). Both methods correlated well to each other (r = 0.9993; 95% confidence interval 0.9984-0.9997; p < 0.001) and revealed substantial agreement in Bland-Altman plots. CONCLUSIONS: Phantomless dual-source DECT-based BMD assessment of lumbar vertebra equivalents using material decomposition showed higher diagnostic accuracy compared to QCT.

Diagnostic accuracy of quantitative dual-energy CT-based bone mineral density assessment in comparison to Hounsfield unit measurements using dual x-ray absorptiometry as standard of reference.

PURPOSE: To assess the diagnostic accuracy of phantomless dual-energy computed tomography (DECT)-based volumetric material decomposition to assess bone mineral density (BMD) of the lumbar spine for the detection of osteoporosis compared to Hounsfield unit (HU) measurements with dual x-ray absorptiometry (DXA) as reference standard. METHOD: A total of two hundred lumbar vertebrae in 53 patients (28 men, 25 women; mean age, 52 years, range, 23-87 years) who had undergone clinically-indicated third-generation dual-source DECT and DXA within 30 days were retrospectively analyzed. For volumetric BMD assessment, dedicated DECT postprocessing software using material decomposition was applied, which enables color-coded three-dimensional mapping of the trabecular BMD distribution. Manual HU measurements were performed by defining five trabecular regions of interest (ROI) per vertebra as suggested by literature. The DXA T-score served as standard of reference (osteoporosis: T < -2.5). Sensitivity, specificity and the area under the curve (AUC) were primary metrics of diagnostic accuracy. RESULTS: An optimal patient-based DECT-derived BMD cut-off of 84 mg/cm³ yielded 96 % sensitivity (22/23) and 93 % specificity (28/30) for detecting osteoporosis, while an optimal CT attenuation cut-off of 139 HU showed 65 % sensitivity (15/23) and 93 % specificity (28/30) for the detection of osteoporosis. Overall patient-based AUC were 0.930 (volumetric DECT) and 0.790 (HU analysis) (p < .001). Pearson's product-moment correlation showed higher correlation between DECT BMD and DXA values (r=0.780) compared to HU and DXA values (r=0.528) (p < .001). CONCLUSIONS: Phantomless volumetric DECT yielded significantly more accurate BMD assessment of the lumbar spine and superior diagnostic accuracy of osteoporosis compared to HU measurements.

Diagnostic accuracy of color-coded virtual noncalcium dual-energy CT for the assessment of bone marrow edema in sacral insufficiency fracture in comparison to MRI.

PURPOSE: To evaluate the diagnostic accuracy of color-coded dual-energy CT virtual noncalcium (VNCa) reconstructions for the assessment of traumatic bone marrow edema in sacral insufficiency fracture (SIF). METHOD: Data from 52 consecutive patients (28 women, 24 men; mean age, 61 ±â€¯13 years; range, 49-94 years) who had undergone third-generation dual-source CT and 3-Tesla (T) MRI due to low back pain without adequate trauma were retrospectively evaluated. Five radiologists, blinded to MRI and clinical information, independently analyzed conventional grayscale dual-energy CT series for sacral fractures according to the Denis classification. Eight weeks later, readers re-assessed all scans using color-coded VNCa reconstructions for sacral bone marrow edema. CT numbers on VNCa reconstructions were measured by a sixth radiologist. One experienced radiologist (33 years of experience in musculoskeletal [MSK] imaging), blinded to CT and clinical information, defined the reference standard by analyzing the MRI scans. The primary indices for diagnostic accuracy were sensitivity, specificity, and the area under the curve (AUC). RESULTS: MRI revealed a total of 39 zones with SIF-associated bone marrow edema in 27 patients. In the qualitative analysis, VNCa showed high overall sensitivity (93 %) and specificity (95 %) for assessing SIF-associated bone marrow edema. The quantitative analysis of color-coded VNCa reconstructions revealed an overall AUC of 0.976. A cut-off value of -43 Hounsfield units provided a sensitivity of 85 % and a specificity of 95 % for differentiating bone marrow edema. CONCLUSIONS: Color-coded dual-energy CT VNCa reconstructions yield excellent diagnostic accuracy in the analysis of SIF-associated bone marrow edema compared to MRI.

Artificial intelligence in bone age assessment: accuracy and efficiency of a novel fully automated algorithm compared to the Greulich-Pyle method.

BACKGROUND: Bone age (BA) assessment performed by artificial intelligence (AI) is of growing interest due to improved accuracy, precision and time efficiency in daily routine. The aim of this study was to investigate the accuracy and efficiency of a novel AI software version for automated BA assessment in comparison to the Greulich-Pyle method. METHODS: Radiographs of 514 patients were analysed in this retrospective study. Total BA was assessed independently by three blinded radiologists applying the GP method and by the AI software. Overall and gender-specific BA assessment results, as well as reading times of both approaches, were compared, while the reference BA was defined by two blinded experienced paediatric radiologists in consensus by application of the Greulich-Pyle method. RESULTS: Mean absolute deviation (MAD) and root mean square deviation (RSMD) were significantly lower between AI-derived BA and reference BA (MAD 0.34 years, RSMD 0.38 years) than between reader-calculated BA and reference BA (MAD 0.79 years, RSMD 0.89 years; p < 0.001). The correlation between AI-derived BA and reference BA (r = 0.99) was significantly higher than between reader-calculated BA and reference BA (r = 0.90; p < 0.001). No statistical difference was found in reader agreement and correlation analyses regarding gender (p = 0.241). Mean reading times were reduced by 87% using the AI system. CONCLUSIONS: A novel AI software enabled highly accurate automated BA assessment. It may improve efficiency in clinical routine by reducing reading times without compromising the accuracy compared with the Greulich-Pyle method.

Measurement Reliability and Diagnostic Accuracy of Virtual Monoenergetic Dual-Energy CT in Patients with Colorectal Liver Metastases.

RATIONALE AND OBJECTIVES: To compare dual-energy CT virtual monoenergetic images (VMI) and standard reconstructions for reliability of quantitative size measurements and diagnostic accuracy for the detection of colorectal liver metastases (CRLM). MATERIALS AND METHODS: We retrospectively included 98 patients (mean age, 61.1±11.5 years) with colorectal cancer, of whom 49 subjects had CRLM. All patients underwent a portal-venous phase dual-energy CT examination. Standard linearly-blended reformats and 40-keV VMI were reconstructed. For both reconstruction techniques, two blinded readers performed measurements of CRLM twice in a preset sequence. Three additional radiologists independently assessed all liver lesions in terms of dignity (benign vs. malignant). Sensitivity, specificity and diagnostic accuracy were calculated on a per-patient basis using MRI as reference standard. Readers scored the suitability for metric measurements and their diagnostic confidence using 5-point Likert scales. Inter-rater agreement was evaluated using intraclass correlation coefficient (ICC). RESULTS: Inter-rater agreement for lesion size measurements was higher for 40-keV VMI (ICC, 0.88) compared to standard linearly-blended series (ICC, 0.80). Sensitivity and diagnostic accuracy for the detection of CRLM were significantly higher for VMI at 40-keV compared to standard reconstructions (90.6% vs. 80.6%, and 89.1% vs. 81.3%; p < 0.001). Reader scores indicated that 40-keV VMI were more suitable for metric lesion measurements and provided greater diagnostic confidence compared to standard reformats (median, 5 vs. 3, and 5 vs. 4; both p < 0.001). CONCLUSION: Low-keV VMI reconstructions improve reliability of quantitative size measurements and diagnostic accuracy for the assessment of CRLM compared to standard linearly-blended images.

Traumatic bone marrow edema of the calcaneus: Evaluation of color-coded virtual non-calcium dual-energy CT in a multi-reader diagnostic accuracy study.

PURPOSE: To investigate the diagnostic accuracy of dual-energy computed tomography (CT) virtual non-calcium (VNCa) reconstructions for the depiction of traumatic bone marrow edema of the calcaneus. METHOD: Data from 62 patients (33 women, 29 men; mean age: 41 years, range: 19-84 years) with acute tarsal trauma who had undergone third-generation dual-source dual-energy CT and 3-T magnetic resonance imaging (MRI) within seven days between January 2017 and July 2018 were retrospectively analyzed. Five radiologists, blinded to clinical and MRI information, independently assessed conventional grayscale dual-energy CT series for the presence of fractures; after at least eight weeks, readers re-evaluated all cases using color-coded VNCa reconstructions for the presence of bone marrow edema. Quantitative analysis of CT numbers on VNCa reconstructions was performed by a sixth radiologist. Two additional experienced radiologists, blinded to clinical and CT information, assessed MRI series in consensus to define the reference standard. Sensitivity, specificity and the area under the curve (AUC) were the primary indices for diagnostic accuracy. RESULTS: MRI revealed 62 areas with bone marrow edema in 39 patients. In the qualitative analysis, VNCa showed high overall sensitivity (286/310 [92%]) and specificity (899/930 [97%]) for the depiction of bone marrow edema. A cut-off value of -53 Hounsfield units (HU) provided a sensitivity of 82% (51/62) and specificity of 95% (176/186]) for differentiating bone marrow edema. The overall AUC was 0.98. CONCLUSIONS: In both quantitative and qualitative analyses, dual-energy CT VNCa reconstructions show excellent diagnostic accuracy for the visualization of traumatic calcaneal bone marrow edema compared to MRI.

Curation of microarray oligonucleotides and corresponding ESTs/cDNAs used for gene expression analysis in zebra finches.

OBJECTIVES: Zebra finches are a major model organism for investigating mechanisms of vocal learning, a trait that enables spoken language in humans. The development of cDNA collections with expressed sequence tags (ESTs) and microarrays has allowed for extensive molecular characterizations of circuitry underlying vocal learning and production. However, poor database curation can lead to errors in transcriptome and bioinformatics analyses, limiting the impact of these resources. Here we used genomic alignments and synteny analysis for orthology verification to curate and reannotate ~ 35% of the oligonucleotides and corresponding ESTs/cDNAs that make-up Agilent microarrays for gene expression analysis in finches. DATA DESCRIPTION: We found that: (1) 5475 out of 43,084 oligos (a) failed to align to the zebra finch genome, (b) aligned to multiple loci, or (c) aligned to Chr_un only, and thus need to be flagged until a better genome assembly is available, or (d) reflect cloning artifacts; (2) Out of 9635 valid oligos examined further, 3120 were incorrectly named, including 1533 with no known orthologs; and (3) 2635 oligos required name update. The resulting curated dataset provides a reference for correcting gene identification errors in previous finch microarrays studies, and avoiding such errors in future studies.