Early versus late response to PD-1-based immunotherapy in metastatic melanoma.

BACKGROUND: Immune checkpoint inhibition (ICI) currently is the most effective treatment to induce durable responses in metastatic melanoma. The aims of this study are the characterization of patients with early, late and non-response to ICI and analysis of survival outcomes in a real-world patient cohort. METHODS: Patients who received PD-1-based immunotherapy for non-resectable stage-IV melanoma in any therapy line were selected from the prospective multicenter real-world DeCOG study ADOREG-TRIM (NCT05750511). Patients showing complete (CR) or partial (PR) response already during the first 3 months of treatment (Early Responders, EarlyR) were compared to patients showing CR/PR at a later time (Late Responders, LateR), a stable disease (SD) and to patients showing progressive disease (Non-Responders, NonR). RESULTS: Of 522 patients, 8.2 % were EarlyR (n = 43), 19.0 % were LateR (n = 99), 37.0 % had a SD (n = 193) and 35.8 % were NonR (n = 187). EarlyR, LateR and SD patients had comparable baseline characteristics. Multivariate logbinomial regression analyses adjusted for age and sex revealed positive tumor PD-L1 (RR=1.99, 95 %-CI=1.14-3.46, p = 0.015), and normal serum CRP (RR=1.59, 95 %-CI=0.93-2.70, p = 0.036) as independently associated with the achievement of an early response compared to NonR. The median progression-free and overall survival was 46.0 months (95 % CI 19.1; NR) and 47.8 months (95 %-CI 36.9; NR) for EarlyR, NR (95 %-CI NR; NR) for LateR, 8.1 months (7.0; 10.4) and 35.4 months (29.2; NR) for SD, and 2.0 months (95 %-CI 1.9; 2.1) and 6.1 months (95 %-CI 4.6; 8.8) for NonR patients. CONCLUSION: Less than 10 % of metastatic melanoma patients achieved an early response during the first 3 months of PD-1-based immunotherapy. Early responders were not superior to late responders in terms of response durability and survival.

Shortened progression free and overall survival to immune-checkpoint inhibitors in BRAF-, RAS- and NF1- ("Triple") wild type melanomas.

BACKGROUND: Melanomas lacking mutations in BRAF, NRAS and NF1 are frequently referred to as "triple wild-type" (tWT) melanomas. They constitute 5-10 % of all melanomas and remain poorly characterized regarding clinical characteristics and response to therapy. This study investigates the largest multicenter collection of tWT-melanomas to date. METHODS: Targeted next-generation sequencing of the TERT promoter and 29 melanoma-associated genes were performed on 3109 melanoma tissue samples of the prospective multicenter study ADOREG/TRIM of the DeCOG revealing 292 patients suffering from tWT-melanomas. Clinical characteristics and mutational patterns were analyzed. As subgroup analysis, we analyzed 141 tWT-melanoma patients receiving either anti-CTLA4 plus anti-PD1 or anti PD1 monotherapy as first line therapy in AJCC stage IV. RESULTS: 184 patients with cutaneous melanomas, 56 patients with mucosal melanomas, 34 patients with acral melanomas and 18 patients with melanomas of unknown origin (MUP) were included. A TERT promoter mutation could be identified in 33.2 % of all melanomas and 70.5 % of all tWT-melanomas harbored less than three mutations per sample. For the 141 patients with stage IV disease, mPFS independent of melanoma type was 6.2 months (95 % CI: 4-9) and mOS was 24.8 months (95 % CI: 14.2-53.4) after first line anti-CTLA4 plus anti-PD1 therapy. After first-line anti-PD1 monotherapy, mPFS was 4 months (95 %CI: 2.9-8.5) and mOS was 29.18 months (95 % CI: 17.5-46.2). CONCLUSIONS: While known prognostic factors such as TERT promoter mutations and TMB were equally distributed among patients who received either anti-CTLA4 plus anti-PD1 combination therapy or anti-PD1 monotherapy as first line therapy, we did not find a prolonged mPFS or mOS in either of those. For both therapy concepts, mPFS and mOS were considerably shorter than reported for melanomas with known oncogene mutations.

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.

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.

Chondrosarcoma evaluation using hematein-based x-ray staining and high-resolution 3D micro-CT: a feasibility study.

BACKGROUND: Chondrosarcomas are rare malignant bone tumors diagnosed by analyzing radiological images and histology of tissue biopsies and evaluating features such as matrix calcification, cortical destruction, trabecular penetration, and tumor cell entrapment. METHODS: We retrospectively analyzed 16 cartilaginous tumor tissue samples from three patients (51-, 54-, and 70-year-old) diagnosed with a dedifferentiated chondrosarcoma at the femur, a moderately differentiated chondrosarcoma in the pelvis, and a predominantly moderately differentiated chondrosarcoma at the scapula, respectively. We combined a hematein-based x-ray staining with high-resolution three-dimensional (3D) microscopic x-ray computed tomography (micro-CT) for nondestructive 3D tumor assessment and tumor margin evaluation. RESULTS: We detected trabecular entrapment on 3D micro-CT images and followed bone destruction throughout the volume. In addition to staining cell nuclei, hematein-based staining also improved the visualization of the tumor matrix, allowing for the distinction between the tumor and the bone marrow cavity. The hematein-based staining did not interfere with further conventional histology. There was a 5.97 ± 7.17% difference between the relative tumor area measured using micro-CT and histopathology (p = 0.806) (Pearson correlation coefficient r = 0.92, p = 0.009). Signal intensity in the tumor matrix (4.85 ± 2.94) was significantly higher in the stained samples compared to the unstained counterparts (1.92 ± 0.11, p = 0.002). CONCLUSIONS: Using nondestructive 3D micro-CT, the simultaneous visualization of radiological and histopathological features is feasible. RELEVANCE STATEMENT: 3D micro-CT data supports modern radiological and histopathological investigations of human bone tumor specimens. It has the potential for being an integrative part of clinical preoperative diagnostics. KEY POINTS: • Matrix calcifications are a relevant diagnostic feature of bone tumors. • Micro-CT detects all clinically diagnostic relevant features of x-ray-stained chondrosarcoma. • Micro-CT has the potential to be an integrative part of clinical diagnostics.

Tumor-Like Distal Femoral Cortical Irregularities of the Knee in Adolescent Competitive Alpine Skiers: Longitudinal Assessment Over 48 Months.

BACKGROUND: Tumor-like distal femoral cortical irregularities (DFCIs) are a frequent incidental finding on knee magnetic resonance imaging (MRI) and are common in young competitive athletes. PURPOSE: To assess and compare the morphology and prevalence of DFCIs in competitive alpine skiers over 48 months during adolescence. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Adolescent competitive alpine skiers were prospectively recruited in 2018 and received bilateral 3-T MRI of the knee at baseline and after 48 months. All MRIs were evaluated for the presence and location of DFCIs, which were marked at 1 of 3 anatomic positions: (1) the femoral attachment of the medial head of the gastrocnemius muscle, (2) the lateral head of the gastrocnemius muscle, or (3) the attachment of the adductor magnus aponeurosis. The size of the DFCI was measured by 2 radiologists independently. The measurements were compared using the Wilcoxon signed-rank test, the interclass correlation coefficient (ICC), and Cohen Kappa. RESULTS: A total of 63 athletes (mean age at follow-up, 19.6 ± 1.2 years; n = 25 female) were included in the study. At baseline, DFCIs were detected in 84 out of 126 knees (67%). At the 48-month follow-up, DFCIs were found in 88 out of 126 knees (70%), with multiple DFCIs in 3 knees and no significant difference between male and female patients (n = 24 male, n = 19 female; P = .71). No significant increase was detected for the number (P = .21) and size of the DFCIs between the baseline and the 48-month follow-up (mean size: baseline, 3.7 ± 0.8 mm; 48-month follow-up: 3.6 ± 0.9 mm; P = .66). The interrater agreement for the mean size measurements of DFCIs was good to excellent (ICC 0.88). CONCLUSION: DFCIs remain a frequent finding on knee MRI in competitive alpine skiers after skeletal maturation and do not disappear during adolescence. The DFCI size was constant in athletes aged between 15 and 19 years. Moreover, DFCIs should not be mistaken for a pathologic finding.

Quantifying Tendon Degeneration Using Magic Angle Insensitive Ultra-Short Echo Time Magnetization Transfer: A Phantom Study in Bovine Tendons.

OBJECTIVES: The aim of this study was to qualitatively and quantitatively assess changes in bovine flexor tendons before and after collagen degradation and at different angles in relation to the static B0 field using 3-dimensional ultra-short echo time (UTE) magnetization transfer (MT) imaging within a clinically feasible acquisition time. MATERIALS AND METHODS: Eight bovine flexor tendons were examined at 3 T magnetic resonance imaging including 3-dimensional UTE MT and UTE T2* research application sequences (acquired within 4:04 and 6:38 minutes, respectively) before and after enzyme-induced degradation. The tendons were divided into 2 groups: group 1 (controls) treated with phosphate-buffered saline and group 2 treated with collagenase I to induce collagen degeneration. Magnetic resonance imaging was repeated at 0, 27, 55, and 90 degrees to the B0 field. To calculate quantitative tissue properties, all tendons were semiautomatically segmented, and changes in quantitative UTE T2* and UTE MT ratios (MTRs) were compared at different angles and between groups. In addition to descriptive statistics, the coefficient of variation was calculated to compare UTE MT and UTE T2* imaging. RESULTS: Ultra-short echo time MTR showed a significantly lower coefficient of variation compared with UTE T2* values, indicating a more robust imaging method (UTE MTR 9.64%-11.25%, UTE T2* 18.81%-24.06%, P < 0.001). Both methods showed good performance in detecting degenerated tendons using histopathology as reference standard, with UTE MT imaging having a better area under the curve than UTE T2* mapping (0.918 vs 0.865). Falsely high UTE T2* values were detected at the 55 degrees acquisition angle, whereas UTE MTR values were robust, that is, insensitive to the MAE. CONCLUSIONS: Ultra-short echo time MT imaging is a reliable method for quantifying tendon degeneration that is robust to the MAE and can be acquired in a clinically reasonable time.

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.

Inflammatory Knee Synovitis: Evaluation of an Accelerated FLAIR Sequence Compared With Standard Contrast-Enhanced Imaging.

OBJECTIVES: The aim of this study was to assess the diagnostic value and accuracy of a deep learning (DL)-accelerated fluid attenuated inversion recovery (FLAIR) sequence with fat saturation (FS) in patients with inflammatory synovitis of the knee. MATERIALS AND METHODS: Patients with suspected knee synovitis were retrospectively included between January and September 2023. All patients underwent a 3 T knee magnetic resonance imaging including a DL-accelerated noncontrast FLAIR FS sequence (acquisition time: 1 minute 38 seconds) and a contrast-enhanced (CE) T1-weighted FS sequence (acquisition time: 4 minutes 50 seconds), which served as reference standard. All knees were scored by 2 radiologists using the semiquantitative modified knee synovitis score, effusion synovitis score, and Hoffa inflammation score. Diagnostic confidence, image quality, and image artifacts were rated on separate Likert scales. Wilcoxon signed rank test was used to compare the semiquantitative scores. Interreader and intrareader reproducibility were calculated using Cohen κ. RESULTS: Fifty-five patients (mean age, 52 ± 17 years; 28 females) were included in the study. Twenty-seven patients (49%) had mild to moderate synovitis (synovitis score 6-13), and 17 patients (31%) had severe synovitis (synovitis score >14). No signs of synovitis were detected in 11 patients (20%) (synovitis score <5). Semiquantitative assessment of the whole knee synovitis score showed no significant difference between the DL-accelerated FLAIR sequence and the CE T1-weighted sequence (mean FLAIR score: 10.69 ± 8.83, T1 turbo spin-echo FS: 10.74 ± 10.32; P = 0.521). Both interreader and intrareader reproducibility were excellent (range Cohen κ [0.82-0.96]). CONCLUSIONS: Assessment of inflammatory knee synovitis using a DL-accelerated noncontrast FLAIR FS sequence was feasible and equivalent to CE T1-weighted FS imaging.

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.

Natural History of Quantitative Fatty Infiltration and 3D Muscle Volume After Nonoperative Treatment of Symptomatic Rotator Cuff Tears: A Prospective MRI Study of 79 Patients.

BACKGROUND: The severity of fatty infiltration (FI) predicts the treatment outcome of rotator cuff tears. The purpose of this investigation was to quantitatively analyze supraspinatus (SSP) muscle FI and volume at the initial presentation and after a 3-month minimum of conservative management. We hypothesized that progression of FI could be predicted with initial tear size, FI, and muscle volume. METHODS: Seventy-nine shoulders with rotator cuff tears were prospectively enrolled, and 2 magnetic resonance imaging (MRI) scans with 6-point Dixon sequences were acquired. The fat fraction within the SSP muscle was measured on 3 sagittal slices, and the arithmetic mean was calculated (FI SSP ). Advanced FI SSP was defined as ≥8%, pathological FI SSP was defined as ≥13.5%, and relevant progression was defined as a ≥4.5% increase in FI SSP . Furthermore, muscle volume, tear location, size, and Goutallier grade were evaluated. RESULTS: Fifty-seven shoulders (72.2%) had normal FI SSP , 13 (16.5%) had advanced FI SSP , and 9 (11.4%) had pathological FI SSP at the initial MRI scan. Eleven shoulders (13.9%) showed a ≥4.5% increase in FI SSP at 19.5 ± 14.7 months, and 17 shoulders (21.5%) showed a ≥5-mm 3 loss of volume at 17.8 ± 15.3 months. Five tears (7.1%) with initially normal or advanced FI SSP turned pathological. These tears, compared with tears that were not pathological, had significantly higher initial mediolateral tear size (24.8 compared with 14.3 mm; p = 0.05), less volume (23.5 compared with 34.2 mm 3 ; p = 0.024), more FI SSP (9.6% compared with 5.6%; p = 0.026), and increased progression of FI SSP (8.6% compared with 0.5%; p < 0.001). An initial mediolateral tear size of ≥20 mm yielded a relevant FI SSP progression rate of 81.8% (odds ratio [OR], 19.0; p < 0.001). Progression rates of 72.7% were found for both initial FI SSP of ≥9.9% (OR, 17.5; p < 0.001) and an initial anteroposterior tear size of ≥17 mm (OR, 8.0; p = 0.003). Combining these parameters in a logistic regression analysis led to an area under the receiver operating characteristic curve (AUC) of 0.913. The correlation between FI SSP progression and the time between MRI scans was weak positive (ρ = 0.31). CONCLUSIONS: Three risk factors for relevant FI progression, quantifiable on the initial MRI, were identified: ≥20-mm mediolateral tear size, ≥9.9% FI SSP , and ≥17-mm anteroposterior tear size. These thresholds were associated with a higher risk of tear progression: 19 times higher for ≥20-mm mediolateral tear size, 17.5 times higher for ≥9.9% FI SSP , and 8 times higher for ≥17-mm anteroposterior tear size. The presence of all 3 yielded a 91% chance of ≥4.5% progression of FI SSP within a mean of 19.5 months. LEVEL OF EVIDENCE: Diagnostic Level II . See Instructions for Authors for a complete description of levels of evidence.

Superolateral Hoffa fat pad edema in adolescent competitive alpine skiers: temporal evolution over 4 years and risk factors.

OBJECTIVES: To longitudinally assess and correlate the prevalence of superolateral Hoffa fat pad (SHFP) edema with changes in features of the knee extensor mechanism in adolescent competitive alpine skiers over 48 months. METHODS: Competitive alpine skiers were prospectively enrolled in 2018 and underwent bilateral knee MRI at baseline and after 48 months. MRI was assessed for the prevalence of SHFP edema. Features of the knee extensor mechanism were assessed by measuring the trochlear sulcus angle and depth, lateral and medial trochlear inclination, trochlear angle, patella tilt, Insall‒Salvati ratio (ISR), and patellar ligament to lateral trochlear facet (PL-T) distance. Separate logistic regression models were used to calculate the odds ratios between each measurement and the presence of SHFP edema at both time points. RESULTS: Sixty-three athletes were included in the study (mean age 15.3 ± 1.3 years, 25 women). At baseline, 23 knees had SHFP edema, increasing to 34 knees at the 48-month follow-up. At baseline, knees with measurements in the highest quartile for ISR and lowest quartile for trochlear depth and PL-T were 9.3, 5.1, and 7.7 times more likely to show SHFP edema, respectively. At follow-up, these correlations were confirmed and additionally, knees with measurements in the highest quartile for trochlear sulcus angle and the lowest quartile for lateral trochlear inclination were 4.1 and 3.4 times more likely to show SHFP edema. CONCLUSION: An increased prevalence of SHFP edema in competitive alpine skiers during adolescence was associated with persistent high-riding patella, reduced patellar ligament to trochlear distance, and flattened lateral trochlear facet. CRITICAL RELEVANCE STATEMENT: In clinical routine, assessment of the mechanical properties of the knee extensor mechanism, together with anatomical developments during adolescence, may improve the understanding and management of patellofemoral instability. KEY POINTS: • Superolateral Hoffa fat pad (SHFP) edema is a frequent cause of anterolateral knee pain but the role of predisposing factors is still debated. • A higher prevalence of SHFP edema was associated with high-riding patella, reduced patellar ligament to trochlear distance, and flattened lateral trochlear facet. • Understanding of the mechanical interaction and the anatomical development of the knee during adolescence provides further insight into the development of SHFP edema.

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).

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.

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.

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.

Potential Application of Organic Electronics in Electrical Sensing of Insects and Integrated Pest Management towards Developing Ecofriendly Replacements for Chemical Insecticides.

Synthetic insecticides are widely used against plant pest insects to protect the crops. However, many insecticides have poor selectivity and are toxic also to beneficial insects, animals, and humans. In addition, insecticide residues can remain on fruits for many days, jeopardizing food safety. For these reasons, a reusable, low-cost electronic trap that can attract, detect, and identify, but attack only the pest while leaving beneficial insects unharmed could provide a sustainable, nature-friendly replacement. Here, for the first time, research results are presented suggesting the great potential and compatibility of organic electronic devices and technologies with pest management. Electrical characterizations confirm that an insect's body has relatively high dielectric permittivity. Adaptive memcapacitor circuits can track the impedance change for insect detection. Other experiments show that printed polymer piezoelectric transducers on a plastic substrate can collect information about the weight and activity of insects for identification. The breakdown voltage of most insects´ integument is measured to be <200 V. Long channel organic transistors easily work at such high voltages while being safe to touch for humans thanks to their inherent low current. This feasibility study paves the way for the future development of organic electronics for physical pest control and biodiversity protection.

Fat Fractions of the Rotator Cuff Muscles Acquired With 2-Point Dixon MRI: Predicting Outcome After Arthroscopic Rotator Cuff Repair.

OBJECTIVES: The aim of this study was to quantify and compare fat fraction (FF) and muscle volume between patients with failed and intact rotator cuff (RC) repair as well as a control group with nonsurgical conservative treatment to define FF cutoff values for predicting the outcome of RC repair. MATERIALS AND METHODS: Patients with full-thickness RC tears who received magnetic resonance imaging (MRI) before and after RC repair including a 2-point Dixon sequence were retrospectively screened. Patients with retear of 1 or more tendons diagnosed on MRI (Sugaya IV-V) were enrolled and matched to patients with intact RC repair (Sugaya I-II) and to a third group with conservatively treated RC tears. Two radiologists evaluated morphological features (Cofield, Patte, and Goutallier), as well as the integrity of the RC after repair (Sugaya). Fat fractions were calculated from the 2-point Dixon sequence, and the RC muscles were segmented semiautomatically to calculate FFs and volume for each muscle. Receiver operator characteristics curves were used to determine FF cutoff values that best predict RC retears. RESULTS: In total, 136 patients were enrolled, consisting of 3 groups: 41 patients had a failed RC repair (58 ± 7 years, 16 women), 50 patients matched into the intact RC repair group, and 45 patients were matched into the conservative treatment group. Receiver operator characteristics curves showed reliable preoperative FF cutoff values for predicting retears at 6.0% for the supraspinatus muscle (0.83 area under the curve [AUC]), 7.4% for the infraspinatus muscle (AUC 0.82), and 8.3% for the subscapularis muscle (0.94 AUC). CONCLUSIONS: Preoperative quantitative FF calculated from 2-point Dixon MRI can be used to predict the risk of retear after arthroscopic RC repair with cutoff values between 6% and 8.3%.