Deep Learning to Differentiate Benign and Malignant Vertebral Fractures at Multidetector CT.

Background Differentiating between benign and malignant vertebral fractures poses diagnostic challenges. Purpose To investigate the reliability of CT-based deep learning models to differentiate between benign and malignant vertebral fractures. Materials and Methods CT scans acquired in patients with benign or malignant vertebral fractures from June 2005 to December 2022 at two university hospitals were retrospectively identified based on a composite reference standard that included histopathologic and radiologic information. An internal test set was randomly selected, and an external test set was obtained from an additional hospital. Models used a three-dimensional U-Net encoder-classifier architecture and applied data augmentation during training. Performance was evaluated using the area under the receiver operating characteristic curve (AUC) and compared with that of two residents and one fellowship-trained radiologist using the DeLong test. Results The training set included 381 patients (mean age, 69.9 years ± 11.4 [SD]; 193 male) with 1307 vertebrae (378 benign fractures, 447 malignant fractures, 482 malignant lesions). Internal and external test sets included 86 (mean age, 66.9 years ± 12; 45 male) and 65 (mean age, 68.8 years ± 12.5; 39 female) patients, respectively. The better-performing model of two training approaches achieved AUCs of 0.85 (95% CI: 0.77, 0.92) in the internal and 0.75 (95% CI: 0.64, 0.85) in the external test sets. Including an uncertainty category further improved performance to AUCs of 0.91 (95% CI: 0.83, 0.97) in the internal test set and 0.76 (95% CI: 0.64, 0.88) in the external test set. The AUC values of residents were lower than that of the best-performing model in the internal test set (AUC, 0.69 [95% CI: 0.59, 0.78] and 0.71 [95% CI: 0.61, 0.80]) and external test set (AUC, 0.70 [95% CI: 0.58, 0.80] and 0.71 [95% CI: 0.60, 0.82]), with significant differences only for the internal test set (P < .001). The AUCs of the fellowship-trained radiologist were similar to those of the best-performing model (internal test set, 0.86 [95% CI: 0.78, 0.93; P = .39]; external test set, 0.71 [95% CI: 0.60, 0.82; P = .46]). Conclusion Developed models showed a high discriminatory power to differentiate between benign and malignant vertebral fractures, surpassing or matching the performance of radiology residents and matching that of a fellowship-trained radiologist. © RSNA, 2024 See also the editorial by Booz and D'Angelo in this issue.

Comparing CT-Like Images Based on Ultra-Short Echo Time and Gradient Echo T1-Weighted MRI Sequences for the Assessment of Vertebral Disorders Using Histology and True CT as the Reference Standard.

BACKGROUND: Several magnetic resonance (MR) techniques have been suggested for radiation-free imaging of osseous structures. PURPOSE: To compare the diagnostic value of ultra-short echo time and gradient echo T1-weighted MRI for the assessment of vertebral pathologies using histology and computed tomography (CT) as the reference standard. STUDY TYPE: Prospective. SUBJECTS: Fifty-nine lumbar vertebral bodies harvested from 20 human cadavers (donor age 73 ± 13 years; 9 male). FIELD STRENGTH/SEQUENCE: Ultra-short echo time sequence optimized for both bone (UTEb) and cartilage (UTEc) imaging and 3D T1-weighted gradient-echo sequence (T1GRE) at 3 T; susceptibility-weighted imaging (SWI) gradient echo sequence at 1.5 T. CT was performed on a dual-layer dual-energy CT scanner using a routine clinical protocol. ASSESSMENT: Histopathology and conventional CT were acquired as standard of reference. Semi-quantitative and quantitative morphological features of degenerative changes of the spines were evaluated by four radiologists independently on CT and MR images independently and blinded to all other information. Features assessed were osteophytes, endplate sclerosis, visualization of cartilaginous endplate, facet joint degeneration, presence of Schmorl's nodes, and vertebral dimensions. Vertebral disorders were assessed by a pathologist on histology. STATISTICAL TESTS: Agreement between T1GRE, SWI, UTEc, and UTEb sequences and CT imaging and histology as standard of reference were assessed using Fleiss' κ and intra-class correlation coefficients, respectively. RESULTS: For the morphological assessment of osteophytes and endplate sclerosis, the overall agreement between SWI, T1GRE, UTEb, and UTEc with the reference standard (histology combined with CT) was moderate to almost perfect for all readers (osteophytes: SWI, κ range: 0.68-0.76; T1GRE: 0.92-1.00; UTEb: 0.92-1.00; UTEc: 0.77-0.85; sclerosis: SWI, κ range: 0.60-0.70; T1GRE: 0.77-0.82; UTEb: 0.81-0.92; UTEc: 0.61-0.71). For the visualization of the cartilaginous endplate, UTEc showed the overall best agreement with the reference standard (histology) for all readers (κ range: 0.85-0.93). DATA CONCLUSIONS: Morphological assessment of vertebral pathologies was feasible and accurate using the MR-based bone imaging sequences compared to CT and histopathology. T1GRE showed the overall best performance for osseous changes and UTEc for the visualization of the cartilaginous endplate. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 2.

MAOA methylation is associated with impulsive and antisocial behaviour: dependence on allelic variation, family environment and diet.

Congenital absence of monoamine oxidase A (MAO-A) activity predisposes to antisocial impulsive behaviour, and the MAOA uVNTR low-expressing genotype (MAOA-L) together with childhood maltreatment is associated with similar phenotypes in males. A possible explanation of how family environment may lead to such behaviour involves DNA methylation. We have assessed MAOA methylation and impulsive/antisocial behaviour in 121 males from the Estonian Children Personality Behaviour and Health Study. Of the 12 CpG sites measured, methylation levels at the locus designated CpG3 were significantly lower in subjects with antisocial behaviour involving police contact. CpG3 methylation was lower in subjects with alcohol use disorder by age 25, but only in MAOA-H genotype. No correlation between MAOA CpG3 methylation levels and adaptive impulsivity was found at age 15, but in MAOA-L genotype a positive correlation appeared by age 18. By age 25, this positive correlation was no longer observed in subjects with better family relationships but had increased further with experience of adversity within the family. MAOA CpG3 methylation had different developmental dynamics in relation to maladaptive impulsivity. At age 18, a positive correlation was observed in MAOA-L genotype with inferior family relationships and a negative correlation was found in MAOA-H with superior home environment; both of these associations had disappeared by age 25. CpG3 methylation was associated with dietary intake of several micronutrients, most notable was a negative correlation with the intake of zinc, but also with calcium, potassium and vitamin E; a positive correlation was found with intake of phosphorus. In conclusion, MAOA CpG3 methylation is related to both maladaptive and adaptive impulsivity in adolescence in MAOA-L males from adverse home environment. By young adulthood, this relationship with maladaptive impulsivity had disappeared but with adaptive impulsivity strengthened. Thus, MAOA CpG3 methylation may serve as a marker for adaptive developmental neuroplasticity in MAOA-L genotype. The mechanisms involved may include dietary factors.

Radiopalmar ganglion cysts: prevalence, morphology, and clinical significance in wrist MRI.

OBJECTIVES: To assess radiopalmar ganglion cysts' (RPG) prevalence, morphology, and clinical significance in consecutive patients. MATERIALS AND METHODS: In this retrospective single-center study, two radiologists assessed the presence of RPG and morphologic features on wrist MRI. Radiopalmar complaints and scapholunate ligament (SLL) tears were evaluated. RESULTS: A total of 1053 wrists in 909 patients (mean age 43.4 ± 15.5 years, 602 females) were evaluated. All 308 RPG (Group 1; 308 patients, 29.2%) originated from the palmar capsule; 49 were unilocular, 95 oligolocular, and 164 multilocular; 745 wrists had no RPG (Group 2; 601 patients). One hundred and twenty-six RPG showed internal debris. The mean diameter was 8.5 ± 5.6 mm (cranio-caudal) (1.0-32.9 mm), 8.0 ± 4.1 mm (medio-lateral) (1.0-31.9 mm), and 3.7 ± 2.3 mm (dorso-palmar) (0.4-16.0 mm). 168 RPG showed direct contact with the radial vascular bundle, 24 with the flexor carpi radialis tendon, and 123 with the flexor pollicis longus tendon. In Group 1, significantly more patients showed partial (82/308) [group 2: 45/745, p < 0.001] or complete SLL tears (22/308) [group 2: 20/745, p < 0.001]. Of the patients with RPG, 15.3% presented with radiopalmar complaints. Only the dorso-palmar RPG diameter was positively correlated with radiopalmar complaints (for readers 1 and 2: rs = 0.66/0.61, p < 0.001, respectively), and the best dorso-palmar diameter cut-off value for the probability of having radiopalmar complaints was defined at 3 mm (area under the curve (AUC) 0.74). Other morphologic features were not eligible to discriminate symptomatic patients (AUC range 0.53-0.61). CONCLUSION: This study found RPG in 29% of patients, most of them asymptomatic. However, a dorso-palmar cyst diameter > 3 mm may be clinically significant. CLINICAL RELEVANCE STATEMENT: Radiopalmar ganglion cysts, observed in 29% of wrist MR examinations, are mostly asymptomatic, but those with a larger dorso-palmar diameter may be associated with radiopalmar complaints. KEY POINTS: Radiopalmar ganglion cysts are found in 29% of patients undergoing wrist MRI. Most patients with evidence of radiopalmar ganglion cysts do not show radiopalmar symptoms (85%). A dorso-palmar cyst diameter > 3 mm may be associated with radiopalmar complaints.

A visual marker for early atrophy of the supraspinatus muscle on conventional MRI: introduction of the blackbird sign.

OBJECTIVES: The aim of this study was to introduce the blackbird sign as a fast, qualitative measure of early supraspinatus (SSP) muscle atrophy and to correlate the sign with quantitatively assessed muscle volume and intramuscular fat fraction (FF) in patients with full-thickness SSP tears. MATERIALS AND METHODS: The blackbird sign describes the asymmetric pattern of early SSP atrophy: on sagittal MR images, the supero-posterior contour of the muscle becomes concave, resembling the shape of a blackbird. MRIs of patients with full-thickness SSP tears were retrospectively reviewed for the presence of the blackbird and tangent signs. Patients were then divided into group 1: negative tangent sign and negative blackbird sign (n = 67), group 2: negative tangent sign and positive blackbird sign (n = 31), and group 3: positive tangent sign (n = 32). A 2-point Dixon sequence was acquired in all patients from which quantitative FF and muscle volumes were calculated. RESULTS: In total 130 patients (mean age 67 ± 11 years) were included. Mean SSP volume was significantly smaller in group 3 (15.8 ± 8.1 cm3) compared to group 2 (23.9 ± 7.0 cm3, p = 0.01) and group 1 (29.7 ± 9.1 cm3, p < 0.01). Significantly lower muscle volumes were also found in group 2 compared to group 1 (p = 0.02), confirming that the blackbird sign is able to identify early SSP atrophy. Mean FF in the SSP was significantly higher in group 3 (18.5 ± 4.4%) compared to group 2 (10.9 ± 4.7%, p < 0.01) and group 1 (6.1 ± 2.6%, p < 0.01). CONCLUSION: Visual assessment of early muscle atrophy of the SSP is feasible and reproducible using the blackbird sign, allowing the diagnosis of early SSP atrophy. CLINICAL RELEVANCE STATEMENT: In routine clinical practice, the blackbird sign may be a useful tool for assessing early muscle degeneration before the risk of postoperative rotator cuff re-tears increases with progressive muscle atrophy and fatty infiltration. KEY POINTS: Quantitative measurements of rotator cuff injuries require time, limiting clinical practicality. The proposed blackbird sign is able to identify early SSP atrophy. Reader agreement for the blackbird sign was substantial, demonstrating reproducibility and ease of implementation in the clinical routine.

Photon-Counting Detector CT Versus Energy-Integrating Detector CT of the Lumbar Spine: Comparison of Radiation Dose and Image Quality.

BACKGROUND. Photon-counting detector (PCD) CT could be useful to help address the typically high radiation doses of conventional energy-integrating detector (EID) CT of the lumbar spine. OBJECTIVE. The purpose of our study was to compare PCD CT and EID CT of the lumbar spine, both performed using tin filtration, in terms of radiation dose and image quality. METHODS. This study included a prospective sample of 39 patients (22 men, 17 women; mean age, 27.2 years) who underwent investigational PCD CT of the lumbar spine as part of a separate study and a retrospective sample of 39 patients (22 men, 17 women; mean age, 34.9 years) who underwent clinically indicated EID CT of the lumbar spine. In both groups, all examinations were performed using unenhanced technique with tin prefiltration between June 2022 and January 2023. Patients were matched between groups using age, sex, and BMI. A custom gaussian curve-fitting algorithm was used to automatically calculate image noise, SNR, and CNR for each examination, on the basis of all voxels within the image set. Three radiologists independently reviewed examinations to perform a subjective visual assessment of visualization of trabecular architecture, cortical bone, neuroforaminal content, paraspinal muscles, and intervertebral disk, as well as overall image quality, using a 4-point Likert scale (1 = poor, 4 = excellent). PCD CT and EID CT examinations were compared. RESULTS. Mean CTDIvol was 4.4 ± 1.0 (SD) mGy for PCD CT versus 11.1 ± 1.9 mGy for EID CT (p < .001). Mean size-specific dose estimate (SSDE) was 6.2 ± 1.0 (SD) mGy for PCD CT versus 14.2 ± 1.8 mGy for EID CT (p < .001). PCD CT and EID CT examinations were not significantly different in terms of image noise or SNR (both p > .05). PCD CT, in comparison with EID CT, showed significantly higher CNR (mean ± SD, 33.6 ± 3.3 vs 29.3 ± 4.1; p < .001). For all three readers, the median score for overall image quality was 4 (range, 3-4) for both PCD CT and EID CT. PCD CT and EID CT examinations showed no significant difference in terms of any qualitative measure for any reader (all p > .05). CONCLUSION. PCD CT, in comparison with EID CT, yielded significantly lower radiation dose with preserved image quality. CLINICAL IMPACT. The findings support expanded use of PCD CT for lumbar spine evaluation.

Photon-Counting Detector CT With Denoising for Imaging of the Osseous Pelvis at Low Radiation Doses: A Phantom Study.

BACKGROUND. Photon-counting detector (PCD) CT may allow lower radiation doses than used for conventional energy-integrating detector (EID) CT, with preserved image quality. OBJECTIVE. The purpose of this study was to compare PCD CT and EID CT, reconstructed with and without a denoising tool, in terms of image quality of the osseous pelvis in a phantom, with attention to low radiation doses. METHODS. A pelvic phantom comprising human bones in acrylic material mimicking soft tissue underwent PCD CT and EID CT at various tube potentials and radiation doses ranging from 0.05 to 5.00 mGy. Additional denoised reconstructions were generated using a commercial tool. Noise was measured in the acrylic material. Two readers performed independent qualitative assessments that entailed determining the denoised EID CT reconstruction with the lowest acceptable dose and then comparing this reference reconstruction with PCD CT reconstructions without and with denoising, using subjective Likert scales. RESULTS. Noise was lower for PCD CT than for EID CT. For instance, at 0.05 mGy and 100 kV with tin filter, noise was 38.4 HU for PCD CT versus 48.8 HU for EID CT. Denoising further reduced noise; for example, for PCD CT at 100 kV with tin filter at 0.25 mGy, noise was 19.9 HU without denoising versus 9.7 HU with denoising. For both readers, lowest acceptable dose for EID CT was 0.10 mGy (total score, 11 of 15 for both readers). Both readers somewhat agreed that PCD CT without denoising at 0.10 mGy (reflecting reference reconstruction dose) was relatively better than the reference reconstruction in terms of osseous structures, artifacts, and image quality. Both readers also somewhat agreed that denoised PCD CT reconstructions at 0.10 mGy and 0.05 mGy (reflecting matched and lower doses, respectively, with respect to reference reconstruction dose) were relatively better than the reference reconstruction for the image quality measures. CONCLUSION. PCD CT showed better-quality images than EID CT when performed at the lowest acceptable radiation dose for EID CT. PCD CT with denoising yielded better-quality images at a dose lower than lowest acceptable dose for EID CT. CLINICAL IMPACT. PCD CT with denoising could facilitate lower radiation doses for pelvic imaging.

Treatment of adult attention-deficit hyperactivity disorder (ADHD) with transcranial direct current stimulation (tDCS): study protocol for a parallel, randomized, double-blinded, sham-controlled, multicenter trial (Stim-ADHD).

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation treatment used as an alternative or complementary treatment for various neuropsychiatric disorders, and could be an alternative or add-on therapy to psychostimulants in attention-deficit hyperactivity disorder (ADHD). Previous studies provided some evidence for improvements in cognition and clinical symptoms in pediatric and adult ADHD patients. However, data from multi-center randomized controlled trials (RCTs) for this condition are lacking. Thus, our aim is to evaluate short- and mid-term effects of tDCS in this multi-center, randomized, double blind, and sham-controlled, parallel group clinical trial with a 1:1 randomization ratio. Primary endpoint is the total score of DSM-IV scale of the internationally established Conners' Adult ADHD Rating Scales (German self-report screening version, CAARS-S-SR), at day 14 post-intervention (p.i.) to detect short-term lasting effects analyzed via analyses of covariance (ANCOVAs). In case of significant between-groups differences at day 14 p.i., hierarchically ordered hypotheses on mid-term lasting effects will be investigated by linear mixed models with visit (5 time points), treatment, treatment by visit interaction, and covariates as fixed categorical effects plus a patient-specific visit random effect, using an unstructured covariance structure to model the residual within-patient errors. Positive results of this clinical trial will expand the treatment options for adult ADHD patients with tDCS and provide an alternative or add-on therapy to psychostimulants with a low risk for side effects.Trial Registration The trial was registered on July 29, 2022 in the German Clinical Trials Register (DRKS00028148).

Managing hardware-related metal artifacts in MRI: current and evolving techniques.

Magnetic resonance imaging (MRI) around metal implants has been challenging due to magnetic susceptibility differences between metal implants and adjacent tissues, resulting in image signal loss, geometric distortion, and loss of fat suppression. These artifacts can compromise the diagnostic accuracy and the evaluation of surrounding anatomical structures. As the prevalence of total joint replacements continues to increase in our aging society, there is a need for proper radiological assessment of tissues around metal implants to aid clinical decision-making in the management of post-operative complaints and complications. Various techniques for reducing metal artifacts in musculoskeletal imaging have been explored in recent years. One approach focuses on improving hardware components. High-density multi-channel radiofrequency (RF) coils, parallel imaging techniques, and gradient warping correction enable signal enhancement, image acquisition acceleration, and geometric distortion minimization. In addition, the use of susceptibility-matched implants and low-field MRI helps to reduce magnetic susceptibility differences. The second approach focuses on metal artifact reduction sequences such as view-angle tilting (VAT) and slice-encoding for metal artifact correction (SEMAC). Iterative reconstruction algorithms, deep learning approaches, and post-processing techniques are used to estimate and correct artifact-related errors in reconstructed images. This article reviews recent developments in clinically applicable metal artifact reduction techniques as well as advances in MR hardware. The review provides a better understanding of the basic principles and techniques, as well as an awareness of their limitations, allowing for a more reasoned application of these methods in clinical settings.

Continuous Interscalene Brachial Plexus Blocks: An Anatomical Challenge between Scylla and Charybdis?

Brachial plexus blocks at the interscalene level are frequently chosen by physicians and recommended by textbooks for providing regional anesthesia and analgesia to patients scheduled for shoulder surgery. Published data concerning interscalene single-injection or continuous brachial plexus blocks report good analgesic effects. The principle of interscalene catheters is to extend analgesia beyond the duration of the local anesthetic's effect through continuous infusion, as opposed to a single injection. However, in addition to the recognized beneficial effects of interscalene blocks, whether administered as a single injection or through a catheter, there have been reports of consequences ranging from minor side effects to severe, life-threatening complications. Both can be simply explained by direct mispuncture, as well as undesired local anesthetic spread or misplaced catheters. In particular, catheters pose a high risk when advanced or placed uncontrollably, a fact confirmed by reports of fatal outcomes. Secondary catheter dislocations explain side effects or loss of effectiveness that may occur hours or days after the initial correct function has been observed. From an anatomical and physiological perspective, this appears logical: the catheter tip must be placed near the plexus in an anatomically tight and confined space. Thus, the catheter's position may be altered with the movement of the neck or shoulder, e.g., during physiotherapy. The safe use of interscalene catheters is therefore a balance between high analgesia quality and the control of side effects and complications, much like the passage between Scylla and Charybdis. We are convinced that the anatomical basis crucial for the brachial plexus block procedure at the interscalene level is not sufficiently depicted in the common regional anesthesia literature or textbooks. We would like to provide a comprehensive anatomical survey of the lateral neck, with special attention paid to the safe placement of interscalene catheters.

Preoperative fibrinogen/CRP score predicts survival in upper urothelial tract carcinoma patients undergoing radical curative surgery.

PURPOSE: Upper tract urothelial carcinoma (UTUC) represents an often aggressive malignancy associated with poor prognosis. Therefore, finding reliable prognostic biomarkers in patients undergoing curative surgery for improved risk stratification is crucial. We evaluated the prognostic value of the Fibrinogen/C-reactive protein (FC)-score in a cohort of surgically treated UTUC patients. METHODS: 170 patients with radiologically and histologically verified UTUC who underwent radical curative surgery between 1990 and 2020, were included. The FC-score was calculated for each patient, with patients receiving 1 point each if Fibrinogen and/or CRP levels were elevated above the 25th or 75th percentile, respectively. Patients were divided into three subgroups according to their FC-score of 0, 1 or 2 point(s). Kaplan-Meier analysis, uni- and multivariable Cox proportional hazard models were implemented. We determined cancer-specific survival (CSS) as primary endpoint, whereas overall survival (OS) and recurrence-free survival (RFS) were considered secondary endpoints. RESULTS: High FC-score (2 points) was significantly associated with adverse histological features such as vascular invasion (OR = 4.08, 95%CI 1.18-14.15, p = .0027) and tumour necrosis (OR = 6.67, 95%CI 1.35-32.96, p = 0.020). Both, uni- and multivariable Cox proportional hazard models showed the FC-score as a significant predictor for CSS (univariable analysis: FC-score = 1: HR = 1.90, 95%CI 0.92-3.93, p = 0.085 | FC-score = 2: HR = 2.86, 95%CI 1.22-6.72, p = 0.016). Furthermore, in univariable analysis, patients with higher FC-score had significantly shorter OS (FC-score = 1: HR = 1.32, 95%CI 0.70-2.49, p = 0.387 | FC-score = 2: HR = 2.19, 95%CI 1.02-4.67, p = 0.043). However, this did not prevail in multivariable analysis. CONCLUSION: The FC-score represents a novel potential biomarker in patients with UTUC undergoing radical curative surgery.

How accurate is MRI for diagnosing tarsal coalitions? A retrospective diagnostic accuracy study.

OBJECTIVES: This study aimed to evaluate the diagnostic accuracy, inter-reader agreement, and associated pathologies on MR images of patients with confirmed TC. METHODS AND MATERIALS: In this retrospective study, 168 ankle MRI exams were included, consisting of 56 patients with clinically or surgically confirmed TC and 112 controls without TC, matched for age and sex. Images were analyzed independently by three radiologists blinded to clinical information. The evaluation criteria included the presence, type, and location of TC, as well as associated pathologies. After calculating diagnostic accuracy and the odds ratio of demographic data and anatomic coalition type for associated pathologies, inter-reader agreement was assessed using kappa statistics. RESULTS: The majority of TCs were non-osseous (91.1%) and located at the calcaneonavicular (33.9%) or talocalcaneal joint (66.1%). Associated pathologies included adjacent and distant bone marrow edema (57.1% and 25.0%), osteochondral defect of the talar dome (OCD, 19.6%), and joint effusion (10.7%) and accessory anterolateral talar facet (17.9%). Talar OCD was associated with increased patient age (p = 0.03). MRI exhibited a cumulative sensitivity and specificity of 95.8% and 94.3% with almost perfect inter-reader agreement (κ = 0.895). CONCLUSION: MRI is a reliable method for detecting tarsal coalition and identifying commonly associated pathologies. Therefore, we recommend the routine use of MRI in the diagnostic workup of patients with foot pain and suspected tarsal coalition. CLINICAL RELEVANCE STATEMENT: MRI is an accurate and reliable modality for diagnosing tarsal coalitions and detecting associated pathologies, while improving patient safety compared to computed tomography by avoiding radiation exposure. KEY POINTS: • Despite the technological progress in magnetic resonance imaging (MRI), computed tomography (CT) is still regarded as the gold standard for diagnosing tarsal coalition (TC). • MRI had a cumulative sensitivity of 95.8% and specificity of 94.3% for detecting tarsal coalition with an almost perfect inter-reader agreement. • MRI demonstrates high accuracy and reliability in diagnosing tarsal coalitions and is useful for identifying associated pathologies, while also improving patient safety by avoiding radiation exposure.

Evaluation of a deep learning-based reconstruction method for denoising and image enhancement of shoulder MRI in patients with shoulder pain.

OBJECTIVES: To evaluate the diagnostic performance of an automated reconstruction algorithm combining MR imaging acquired using compressed SENSE (CS) with deep learning (DL) in order to reconstruct denoised high-quality images from undersampled MR images in patients with shoulder pain. METHODS: Prospectively, thirty-eight patients (14 women, mean age 40.0 ± 15.2 years) with shoulder pain underwent morphological MRI using a pseudo-random, density-weighted k-space scheme with an acceleration factor of 2.5 using CS only. An automated DL-based algorithm (CS DL) was used to create reconstructions of the same k-space data as used for CS reconstructions. Images were analyzed by two radiologists and assessed for pathologies, image quality, and visibility of anatomical landmarks using a 4-point Likert scale. RESULTS: Overall agreement for the detection of pathologies between the CS DL reconstructions and CS images was substantial to almost perfect (κ 0.95 (95% confidence interval 0.82-1.00)). Image quality and the visibility of the rotator cuff, articular cartilage, and axillary recess were overall rated significantly higher for CS DL images compared to CS (p < 0.03). Contrast-to-noise ratios were significantly higher for cartilage/fluid (CS DL 198 ± 24.3, CS 130 ± 32.2, p = 0.02) and ligament/fluid (CS DL 184 ± 17.3, CS 141 ± 23.5, p = 0.03) and SNR values were significantly higher for ligaments and muscle of the CS DL reconstructions (p < 0.04). CONCLUSION: Evaluation of shoulder pathologies was feasible using a DL-based algorithm for MRI reconstruction and denoising. In clinical routine, CS DL may be beneficial in particular for reducing image noise and may be useful for the detection and better discrimination of discrete pathologies. Assessment of shoulder pathologies was feasible with improved image quality as well as higher SNR using a compressed sensing deep learning-based framework for image reconstructions and denoising. KEY POINTS: • Automated deep learning-based reconstructions showed a significant increase in signal-to-noise ratio and contrast-to-noise ratio (p < 0.04) with only a slight increase of reconstruction time of 40 s compared to CS. • All pathologies were accurately detected with no loss of diagnostic information or prolongation of the scan time. • Significant improvements of the image quality as well as the visibility of the rotator cuff, articular cartilage, and axillary recess were detected.

Assessment of glenoid bone loss and other osseous shoulder pathologies comparing MR-based CT-like images with conventional CT.

OBJECTIVES: To evaluate and compare the diagnostic performance of CT-like images based on a 3D T1-weighted spoiled gradient-echo sequence (T1 GRE), an ultra-short echo time sequence (UTE), and a 3D T1-weighted spoiled multi-echo gradient-echo sequence (FRACTURE) with conventional CT in patients with suspected osseous shoulder pathologies. MATERIALS AND METHODS: Patients with suspected traumatic dislocation of the shoulder (n = 46, mean age 40 ± 14.5 years, 19 women) were prospectively recruited and received 3-T MR imaging including 3D T1 GRE, UTE, and 3D FRACTURE sequences. CT was performed in patients with acute fractures and served as standard of reference (n = 25). Agreement of morphological features between the modalities was analyzed including the glenoid bone loss, Hill-Sachs interval, glenoid track, and the anterior straight-line length. Agreement between the modalities was assessed using Bland-Altman plots, Student's t-test, and Pearson's correlation coefficient. Inter- and intrareader assessment was evaluated with weighted Cohen's κ and intraclass correlation coefficient. RESULTS: All osseous pathologies were detected accurately on all three CT-like sequences (n = 25, κ = 1.00). No significant difference in the percentage of glenoid bone loss was found between CT (mean ± standard deviation, 20.3% ± 8.0) and CT-like MR images (FRACTURE 20.6% ± 7.9, T1 GRE 20.4% ± 7.6, UTE 20.3% ± 7.7, p > 0.05). When comparing the different measurements on CT-like images, measurements performed using the UTE images correlated best with CT. CONCLUSION: Assessment of bony Bankart lesions and other osseous pathologies was feasible and accurate using CT-like images based on 3-T MRI compared with conventional CT. Compared to the T1 GRE and FRACTURE sequence, the UTE measurements correlated best with CT. CLINICAL RELEVANCE STATEMENT: In an acute trauma setting, CT-like images based on a T1 GRE, UTE, or FRACTURE sequence might be a useful alternative to conventional CT scan sparing associated costs as well as radiation exposure. KEY POINTS: • No significant differences were found for the assessment of the glenoid bone loss when comparing measurements of CT-like MR images with measurements of conventional CT images. • Compared to the T1 GRE and FRACTURE sequence, the UTE measurements correlated best with CT whereas the FRACTURE sequence appeared to be the most robust regarding motion artifacts. • The T1 GRE sequence had the highest resolution with high bone contrast and detailed delineation of even small fractures but was more susceptible to motion artifacts.

Diagnostic value of water-fat-separated images and CT-like susceptibility-weighted images extracted from a single ultrashort echo time sequence for the evaluation of vertebral fractures and degenerative changes of the spine.

OBJECTIVES: To evaluate the performance of single-echo Dixon water-fat imaging and computed tomography (CT)-like imaging based on a single ultrashort echo time (sUTE) MR sequence for imaging of vertebral fractures as well as degenerative bone changes of the spine in comparison to conventional CT and MR sequences. METHODS: Thirty patients with suspected acute vertebral fractures were examined using a 3-T MRI, including an sUTE sequence as well as short-tau inversion recovery (STIR) and T1-weighted sequences. During postprocessing, water-fat separation was performed by solving the smoothness-constrained inverse water-fat problem based on a single-complex UTE image. By removing the unwanted low-frequency phase terms, additional MR-based susceptibility-weighted-like (SW-like) images with CT-like contrast were created. Two radiologists evaluated semi-quantitative and quantitative features of fractures and degenerative changes independently and separately on CT and MR images. RESULTS: In total, all 58 fractures were accurately detected of whom 24 were correctly classified as acute fractures with an edema detected on the water-fat-separated UTE images, using STIR and T1w sequences as standard of reference. For the morphological assessment of fractures and degenerative changes, the overall agreement between SW-like images and CT was substantial to excellent (e.g., Genant: κ 0.90 (95% confidence interval 0.54-1.00); AO/Magerl: κ 0.75 (95% confidence interval 0.43-1.00)). Overall inter-reader agreement for water-fat-separated UTE images and SW-like images was substantial to almost perfect. CONCLUSION: Detection and assessment of vertebral fractures and degenerative bone changes of the spine were feasible and accurate using water-fat-separated images as well as SW-like images, both derived from the same sUTE-Dixon sequence. KEY POINTS: • The detection of acute vertebral fractures was feasible using water-fat-separated images and CT-like images reconstructed from one sUTE sequence. • Assessment of the vertebral fractures using SW-like images with CT-like contrast was found to be comparable to conventional CT. • sUTE imaging of the spine can help reduce examination times and radiation exposure.

Derotational distal femoral osteotomy for patients with recurrent patellar instability and increased femoral antetorsion improves knee function and adequately treats both torsional and valgus malalignment.

PURPOSE: The aim of the study was to evaluate the functional and radiological outcome following derotational distal femoral osteotomy (D-DFO) in patients with high-grade patellofemoral instability (PFI) and an associated increased femoral antetorsion (FA). It was hypothesized that D-DFO would lead to a good functional and radiological outcome, and that both torsional and coronal malalignment could be normalized. METHODS: Patients that underwent D-DFO between 06/2011 and 12/2018 for high-grade PFI with an increased FA (> 20°) were included. Patient-reported outcome measures (Visual Analog Scale [VAS] for pain, Kujala score, Lysholm score, International Knee Documentation Committee subjective knee form [IKDC], and Tegner Activity Scale [TAS]) were evaluated pre- and minimum 24 months postoperatively. Magnetic resonance imaging of the lower extremity and weight-bearing whole-leg anteroposterior radiographs were conducted pre- and postoperatively. The change in FA, coronal limb alignment, and PROMs were tested for statistical significance. RESULTS: In total, 27 patients (30 knees) were included. The D-DFO aimed to only correct FA (Group 1) or to additionally perform a varization (Group 2) in 14 cases each. In the remaining two cases, double-level osteotomies were performed to correct additional tibial deformities. In 25 cases (83.3%), concomitant procedures also addressing patellofemoral instability were performed. At follow-up (38.0 months [25-75% interquartile range 31.8-52.5 months]), a significant reduction in pain (VAS for pain: 2.0 [1.0-5.0] vs. 0 [0-1.0], p < 0.05), significant improvement in knee function (Kujala Score: 55.6 ± SD 13.6 vs. 80.3 ± 16.7, p < 0.05; Lysholm Score: 58.6 ± 17.4 vs. 79.5 ± 16.6, p < 0.05; IKDC: 54.6 ± 18.7 vs. 74.1 ± 15.0, p < 0.05), and an increase in sporting activity (TAS: 3.0 [3.0-4.0] vs. 4.0 [3.0-5.0], p = n.s.) were reported. Femoral antetorsion was significantly reduced (28.2 ± 6.4° vs. 13.6 ± 5.2°, p < 0.05). A significant varization was observed in Group 2 (2.4 ± 1.2° valgus vs. 0.3 ± 2.4° valgus; p < 0.05). In one case, patellar redislocation occurred 70 months postoperatively. CONCLUSION: In patients with PFI and an associated increased FA, D-DFO achieved a significant reduction in pain, an improvement of subjective knee function, as well as an adequate correction of torsional and coronal alignment. LEVEL OF EVIDENCE: Retrospective case series, Level IV.

Evaluation of 3D MRI for early detection of bone edema associated with apical periodontitis.

OBJECTIVES: To detect and evaluate early signs of apical periodontitis using MRI based on a 3D short-tau-inversion-recovery (STIR) sequence compared to conventional panoramic radiography (OPT) and periapical radiographs in patients with apical periodontitis. MATERIALS AND METHODS: Patients with clinical evidence of periodontal disease were enrolled prospectively and received OPT as well as MRI of the viscerocranium including a 3D-STIR sequence. The MRI sequences were assessed for the occurrence and extent of bone changes associated with apical periodontitis including bone edema, periradicular cysts, and dental granulomas. OPTs and intraoral periapical radiographs, if available, were assessed for corresponding periapical radiolucencies using the periapical index (PAI). RESULTS: In total, 232 teeth of 37 patients (mean age 62±13.9 years, 18 women) were assessed. In 69 cases reactive bone edema was detected on MRI with corresponding radiolucency according to OPT. In 105 cases edema was detected without corresponding radiolucency on OPT. The overall extent of edema measured on MRI was significantly larger compared to the radiolucency on OPT (mean: STIR 2.4±1.4 mm, dental radiograph 1.3±1.2 mm, OPT 0.8±1.1 mm, P=0.01). The overall PAI score was significantly higher on MRI compared to OPT (mean PAI: STIR 1.9±0.7, dental radiograph 1.3±0.5, OPT 1.2±0.7, P=0.02). CONCLUSION: Early detection and assessment of bone changes of apical periodontitis using MRI was feasible while the extent of bone edema measured on MRI exceeded the radiolucencies measured on OPT. CLINICAL RELEVANCE: In clinical routine, dental MRI might be useful for early detection and assessment of apical periodontitis before irreversible bone loss is detected on conventional panoramic and intraoral periapical radiographs.

Imaging of traumatic mandibular fractures in young adults using CT-like MRI: a feasibility study.

OBJECTIVES: To assess and compare the diagnostic performance of CT-like images based on a three- dimensional (3D) T1-weighted spoiled gradient-echo sequence (3D T1 GRE) with CT in patients with acute traumatic fractures of the mandible. MATERIALS AND METHODS: Subjects with acute mandibular fractures diagnosed on conventional CT were prospectively recruited and received an additional 3 T MRI with a CT-like 3D T1 GRE sequence. The images were assessed by two radiologists with regard to fracture localization, degree of dislocation, and number of fragments. Bone to soft tissue contrast, diagnostic confidence, artifacts, and overall image quality were rated using a five-point Likert-scale. Agreement of measurements was assessed using an independent t-test. RESULTS: Fourteen subjects and 22 fracture sites were included (26 ± 3.9 years; 4 females, 10 males). All traumatic fractures were accurately detected on CT-like MRI (n = 22, κ 1.00 (95% CI 1.00-1.00)). There was no statistically significant difference in the assessment of the fracture dislocation (axial mean difference (MD) 0.06 mm, p = 0.93, coronal MD, 0.08 mm, p = 0.89 and sagittal MD, 0.04 mm, p = 0.96). The agreement for the fracture classification as well as the inter- and intra-rater agreement was excellent (range κ 0.92-0.98 (95% CI 0.96-0.99)). CONCLUSION: Assessment of mandibular fractures was feasible and accurate using CT-like MRI based on a 3D T1 GRE sequence and is comparable to conventional CT. CLINICAL RELEVANCE: For the assessment of acute mandibular fractures, CT-like MRI might become a useful alternative to CT in order to reduce radiation exposure particularly in young patients.

Comprehensive cancer predisposition testing within the prospective MASTER trial identifies hereditary cancer patients and supports treatment decisions for rare cancers.

BACKGROUND: Germline variant evaluation in precision oncology opens new paths toward the identification of patients with genetic tumor risk syndromes and the exploration of therapeutic relevance. Here, we present the results of germline variant analysis and their clinical implications in a precision oncology study for patients with predominantly rare cancers. PATIENTS AND METHODS: Matched tumor and control genome/exome and RNA sequencing was carried out for 1485 patients with rare cancers (79%) and/or young adults (77% younger than 51 years) in the National Center for Tumor Diseases/German Cancer Consortium (NCT/DKTK) Molecularly Aided Stratification for Tumor Eradication Research (MASTER) trial, a German multicenter, prospective, observational precision oncology study. Clinical and therapeutic relevance of prospective pathogenic germline variant (PGV) evaluation was analyzed and compared to other precision oncology studies. RESULTS: Ten percent of patients (n = 157) harbored PGVs in 35 genes associated with autosomal dominant cancer predisposition, whereof up to 75% were unknown before study participation. Another 5% of patients (n = 75) were heterozygous carriers for recessive genetic tumor risk syndromes. Particularly, high PGV yields were found in patients with gastrointestinal stromal tumors (GISTs) (28%, n = 11/40), and more specifically in wild-type GISTs (50%, n = 10/20), leiomyosarcomas (21%, n = 19/89), and hepatopancreaticobiliary cancers (16%, n = 16/97). Forty-five percent of PGVs (n = 100/221) supported treatment recommendations, and its implementation led to a clinical benefit in 40% of patients (n = 10/25). A comparison of different precision oncology studies revealed variable PGV yields and considerable differences in germline variant analysis workflows. We therefore propose a detailed workflow for germline variant evaluation. CONCLUSIONS: Genetic germline testing in patients with rare cancers can identify the very first patient in a hereditary cancer family and can lead to clinical benefit in a broad range of entities. Its routine implementation in precision oncology accompanied by the harmonization of germline variant evaluation workflows will increase clinical benefit and boost research.

Unbound Brain-to-Plasma Partition Coefficient, Kp,uu,brain-a Game Changing Parameter for CNS Drug Discovery and Development.

PURPOSE: More than 15 years have passed since the first description of the unbound brain-to-plasma partition coefficient (Kp,uu,brain) by Prof. Margareta Hammarlund-Udenaes, which was enabled by advancements in experimental methodologies including cerebral microdialysis. Since then, growing knowledge and data continue to support the notion that the unbound (free) concentration of a drug at the site of action, such as the brain, is the driving force for pharmacological responses. Towards this end, Kp,uu,brain is the key parameter to obtain unbound brain concentrations from unbound plasma concentrations. METHODS: To understand the importance and impact of the Kp,uu,brain concept in contemporary drug discovery and development, a survey has been conducted amongst major pharmaceutical companies based in Europe and the USA. Here, we present the results from this survey which consisted of 47 questions addressing: 1) Background information of the companies, 2) Implementation, 3) Application areas, 4) Methodology, 5) Impact and 6) Future perspectives. RESULTS AND CONCLUSIONS: From the responses, it is clear that the majority of the companies (93%) has established a common understanding across disciplines of the concept and utility of Kp,uu,brain as compared to other parameters related to brain exposure. Adoption of the Kp,uu,brain concept has been mainly driven by individual scientists advocating its application in the various companies rather than by a top-down approach. Remarkably, 79% of all responders describe the portfolio impact of Kp,uu,brain implementation in their companies as 'game-changing'. Although most companies (74%) consider the current toolbox for Kp,uu,brain assessment and its validation satisfactory for drug discovery and early development, areas of improvement and future research to better understand human brain pharmacokinetics/pharmacodynamics translation have been identified.