Visual scoring of osteoporosis on low-dose CT in lung cancer screening population.

OBJECTIVES: The risk factors for lung cancer screening eligibility, age as well as smoking history, are also present for osteoporosis. This study aims to develop a visual scoring system to identify osteoporosis that can be applied to low-dose CT scans obtained for lung cancer screening. MATERIALS AND METHODS: We retrospectively reviewed 1000 prospectively enrolled participants in the lung cancer screening program at the Mount Sinai Hospital. Optimal window width and level settings for the visual assessment were chosen based on a previously described approach. Visual scoring of osteoporosis and automated measurement using dedicated software were compared. Inter-reader agreement was conducted using six readers with different levels of experience who independently visually assessed 30 CT scans. RESULTS: Based on previously validated formulas for choosing window and level settings, we chose osteoporosis settings of Width = 230 and Level = 80. Of the 1000 participants, automated measurement was successfully performed on 774 (77.4 %). Among these, 138 (17.8 %) had osteoporosis. There was a significant correlation between the automated measurement and the visual score categories for osteoporosis (Kendall's Tau = -0.64, p < 0.0001; Spearman's rho = -0.77, p < 0.0001). We also found substantial to excellent inter-reader agreement on the osteoporosis classification among the 6 radiologists (Fleiss κ = 0.91). CONCLUSIONS: Our study shows that a simple approach of applying specific window width and level settings to already reconstructed sagittal images obtained in the context of low-dose CT screening for lung cancer is highly feasible and useful in identifying osteoporosis.

Deep Learning for Automated Measurement of Patellofemoral Anatomic Landmarks.

BACKGROUND: Patellofemoral anatomy has not been well characterized. Applying deep learning to automatically measure knee anatomy can provide a better understanding of anatomy, which can be a key factor in improving outcomes. METHODS: 483 total patients with knee CT imaging (April 2017-May 2022) from 6 centers were selected from a cohort scheduled for knee arthroplasty and a cohort with healthy knee anatomy. A total of 7 patellofemoral landmarks were annotated on 14,652 images and approved by a senior musculoskeletal radiologist. A two-stage deep learning model was trained to predict landmark coordinates using a modified ResNet50 architecture initialized with self-supervised learning pretrained weights on RadImageNet. Landmark predictions were evaluated with mean absolute error, and derived patellofemoral measurements were analyzed with Bland-Altman plots. Statistical significance of measurements was assessed by paired t-tests. RESULTS: Mean absolute error between predicted and ground truth landmark coordinates was 0.20/0.26 cm in the healthy/arthroplasty cohort. Four knee parameters were calculated, including transepicondylar axis length, transepicondylar-posterior femur axis angle, trochlear medial asymmetry, and sulcus angle. There were no statistically significant parameter differences (p > 0.05) between predicted and ground truth measurements in both cohorts, except for the healthy cohort sulcus angle. CONCLUSION: Our model accurately identifies key trochlear landmarks with ~0.20-0.26 cm accuracy and produces human-comparable measurements on both healthy and pathological knees. This work represents the first deep learning regression model for automated patellofemoral annotation trained on both physiologic and pathologic CT imaging at this scale. This novel model can enhance our ability to analyze the anatomy of the patellofemoral compartment at scale.

Rescue of auditory function by a single administration of AAV-TMPRSS3 gene therapy in aged mice of human recessive deafness DFNB8.

Patients with mutations in the TMPRSS3 gene suffer from recessive deafness DFNB8/DFNB10. For these patients, cochlear implantation is the only treatment option. Poor cochlear implantation outcomes are seen in some patients. To develop biological treatment for TMPRSS3 patients, we generated a knockin mouse model with a frequent human DFNB8 TMPRSS3 mutation. The Tmprss3A306T/A306T homozygous mice display delayed onset progressive hearing loss similar to human DFNB8 patients. Using AAV2 as a vector to carry a human TMPRSS3 gene, AAV2-hTMPRSS3 injection in the adult knockin mouse inner ear results in TMPRSS3 expression in the hair cells and the spiral ganglion neurons. A single AAV2-hTMPRSS3 injection in Tmprss3A306T/A306T mice of an average age of 18.5 months leads to sustained rescue of the auditory function to a level similar to wild-type mice. AAV2-hTMPRSS3 delivery rescues the hair cells and the spiral ganglions neurons. This study demonstrates successful gene therapy in an aged mouse model of human genetic deafness. It lays the foundation to develop AAV2-hTMPRSS3 gene therapy to treat DFNB8 patients, as a standalone therapy or in combination with cochlear implantation.

Reprogramming by drug-like molecules leads to regeneration of cochlear hair cell-like cells in adult mice.

Strategies to overcome irreversible cochlear hair cell (HC) damage and loss in mammals are of vital importance to hearing recovery in patients with permanent hearing loss. In mature mammalian cochlea, co-activation of Myc and Notch1 reprograms supporting cells (SC) and promotes HC regeneration. Understanding of the underlying mechanisms may aid the development of a clinically relevant approach to achieve HC regeneration in the nontransgenic mature cochlea. By single-cell RNAseq, we show that MYC/NICD "rejuvenates" the adult mouse cochlea by activating multiple pathways including Wnt and cyclase activator of cyclic AMP (cAMP), whose blockade suppresses HC-like cell regeneration despite Myc/Notch activation. We screened and identified a combination (the cocktail) of drug-like molecules composing of small molecules and small interfering RNAs to activate the pathways of Myc, Notch1, Wnt and cAMP. We show that the cocktail effectively replaces Myc and Notch1 transgenes and reprograms fully mature wild-type (WT) SCs for HC-like cells regeneration in vitro. Finally, we demonstrate the cocktail is capable of reprogramming adult cochlea for HC-like cells regeneration in WT mice with HC loss in vivo. Our study identifies a strategy by a clinically relevant approach to reprogram mature inner ear for HC-like cells regeneration, laying the foundation for hearing restoration by HC regeneration.

Interstitial lung disease diagnosis and prognosis using an AI system integrating longitudinal data.

For accurate diagnosis of interstitial lung disease (ILD), a consensus of radiologic, pathological, and clinical findings is vital. Management of ILD also requires thorough follow-up with computed tomography (CT) studies and lung function tests to assess disease progression, severity, and response to treatment. However, accurate classification of ILD subtypes can be challenging, especially for those not accustomed to reading chest CTs regularly. Dynamic models to predict patient survival rates based on longitudinal data are challenging to create due to disease complexity, variation, and irregular visit intervals. Here, we utilize RadImageNet pretrained models to diagnose five types of ILD with multimodal data and a transformer model to determine a patient's 3-year survival rate. When clinical history and associated CT scans are available, the proposed deep learning system can help clinicians diagnose and classify ILD patients and, importantly, dynamically predict disease progression and prognosis.

Rescue of Auditory Function by a Single Administration of AAV- TMPRSS3 Gene Therapy in Aged Mice of Human Recessive Deafness DFNB8.

Patients with mutations in the TMPRSS3 gene suffer from recessive deafness DFNB8/DFNB10 for whom cochlear implantation is the only treatment option. Poor cochlear implantation outcomes are seen in some patients. To develop biological treatment for TMPRSS3 patients, we generated a knock-in mouse model with a frequent human DFNB8 TMPRSS3 mutation. The Tmprss3 A306T/A306T homozygous mice display delayed onset progressive hearing loss similar to human DFNB8 patients. Using AAV2 as a vector to carry a human TMPRSS3 gene, AAV2-h TMPRSS3 injection in the adult knock-in mouse inner ears results in TMPRSS3 expression in the hair cells and the spiral ganglion neurons. A single AAV2-h TMPRSS3 injection in aged Tmprss3 A306T/A306T mice leads to sustained rescue of the auditory function, to a level similar to the wildtype mice. AAV2-h TMPRSS3 delivery rescues the hair cells and the spiral ganglions. This is the first study to demonstrate successful gene therapy in an aged mouse model of human genetic deafness. This study lays the foundation to develop AAV2-h TMPRSS3 gene therapy to treat DFNB8 patients, as a standalone therapy or in combination with cochlear implantation.

Influence of thoracic radiology training on classification of interstitial lung diseases.

INTRODUCTION: Interpretation of high-resolution CT images plays an important role in the diagnosis and management of interstitial lung diseases. However, interreader variation may exist due to varying levels of training and expertise. This study aims to evaluate interreader variation and the role of thoracic radiology training in classifying interstitial lung disease (ILD). METHODS: This is a retrospective study where seven physicians (radiologists, thoracic radiologists, and a pulmonologist) classified the subtypes of ILD of 128 patients from a tertiary referral center, all selected from the Interstitial Lung Disease Registry which consists of patients from November 2014 to January 2021. Each patient was diagnosed with a subtype of interstitial lung disease by a consensus diagnosis from pathology, radiology, and pulmonology. Each reader was provided with only clinical history, only CT images, or both. Reader sensitivity and specificity and interreader agreements using Cohen's κ were calculated. RESULTS: Interreader agreement based only on clinical history, only on radiologic information, or combination of both was most consistent amongst readers with thoracic radiology training, ranging from fair (Cohen's κ: 0.2-0.46), moderate to almost perfect (Cohen's κ: 0.55-0.92), and moderate to almost perfect (Cohen's κ: 0.53-0.91) respectively. Radiologists with any thoracic training showed both increased sensitivity and specificity for NSIP as compared to other radiologists and the pulmonologist when using only clinical history, only CT information, or combination of both (p < 0.05). CONCLUSIONS: Readers with thoracic radiology training showed the least interreader variation and were more sensitive and specific at classifying certain subtypes of ILD. SUMMARY SENTENCE: Thoracic radiology training may improve sensitivity and specificity in classifying ILD based on HRCT images and clinical history.

Age and gender differences in vertebral bone marrow adipose tissue and bone mineral density, based on MRI and quantitative CT.

PURPOSE: To investigate the age and gender differences in vertebral bone marrow adipose tissue (BMAT) and volumetric bone mineral density (vBMD). METHOD: A total of 427 healthy adults, including 175 males (41 %) and 252 females (59 %) with an age range of 21-82 years, underwent MRI and quantitative CT examinations of the lumbar spine (L2-L4), and the corresponding BMAT and vBMD values were measured. The age-related progressions of BMAT and vBMD in men and women were evaluated and compared. RESULTS: In males, vertebral BMAT rose gradually throughout life, while in females, BMAT increased sharply between 41 and 60 years of age. In participants aged < 40 years, BMAT was greater in males compared to females (p ≤ 0.01), while after the age of 60, BMAT was higher in females (p < 0.05). In males, vBMD decreased gradually with age, while in females, there was a sharp decrease in vBMD after the age of 40 years. At age of 31-40 years, vBMD was higher in females (P < 0.002), while at age > 60 years, vBMD was higher in males (61-70 years, P < 0.01; > 70 years, P = 0.02). CONCLUSIONS: We found significant age and gender differences in lumbar BMAT and vBMD. These findings will help to improve our understanding of the interaction between bone marrow fat content and bone mineral density in the ageing process.

Primary bone tumor detection and classification in full-field bone radiographs via YOLO deep learning model.

OBJECTIVES: Automatic bone lesions detection and classifications present a critical challenge and are essential to support radiologists in making an accurate diagnosis of bone lesions. In this paper, we aimed to develop a novel deep learning model called You Only Look Once (YOLO) to handle detecting and classifying bone lesions on full-field radiographs with limited manual intervention. METHODS: In this retrospective study, we used 1085 bone tumor radiographs and 345 normal bone radiographs from two centers between January 2009 and December 2020 to train and test our YOLO deep learning (DL) model. The trained model detected bone lesions and then classified these radiographs into normal, benign, intermediate, or malignant types. The intersection over union (IoU) was used to assess the model's performance in the detection task. Confusion matrices and Cohen's kappa scores were used for evaluating classification performance. Two radiologists compared diagnostic performance with the trained model using the external validation set. RESULTS: In the detection task, the model achieved accuracies of 86.36% and 85.37% in the internal and external validation sets, respectively. In the DL model, radiologist 1 and radiologist 2 achieved Cohen's kappa scores of 0.8187, 0.7927, and 0.9077 for four-way classification in the external validation set, respectively. The YOLO DL model illustrated a significantly higher accuracy for intermediate bone tumor classification than radiologist 1 (95.73% vs 88.08%, p = 0.004). CONCLUSIONS: The developed YOLO DL model could be used to assist radiologists at all stages of bone lesion detection and classification in full-field bone radiographs. KEY POINTS: • YOLO DL model can automatically detect bone neoplasms from full-field radiographs in one shot and then simultaneously classify radiographs into normal, benign, intermediate, or malignant. • The dataset used in this retrospective study includes normal bone radiographs. • YOLO can detect even some challenging cases with small volumes.

RadImageNet: An Open Radiologic Deep Learning Research Dataset for Effective Transfer Learning.

Purpose: To demonstrate the value of pretraining with millions of radiologic images compared with ImageNet photographic images on downstream medical applications when using transfer learning. Materials and Methods: This retrospective study included patients who underwent a radiologic study between 2005 and 2020 at an outpatient imaging facility. Key images and associated labels from the studies were retrospectively extracted from the original study interpretation. These images were used for RadImageNet model training with random weight initiation. The RadImageNet models were compared with ImageNet models using the area under the receiver operating characteristic curve (AUC) for eight classification tasks and using Dice scores for two segmentation problems. Results: The RadImageNet database consists of 1.35 million annotated medical images in 131 872 patients who underwent CT, MRI, and US for musculoskeletal, neurologic, oncologic, gastrointestinal, endocrine, abdominal, and pulmonary pathologic conditions. For transfer learning tasks on small datasets-thyroid nodules (US), breast masses (US), anterior cruciate ligament injuries (MRI), and meniscal tears (MRI)-the RadImageNet models demonstrated a significant advantage (P < .001) to ImageNet models (9.4%, 4.0%, 4.8%, and 4.5% AUC improvements, respectively). For larger datasets-pneumonia (chest radiography), COVID-19 (CT), SARS-CoV-2 (CT), and intracranial hemorrhage (CT)-the RadImageNet models also illustrated improved AUC (P < .001) by 1.9%, 6.1%, 1.7%, and 0.9%, respectively. Additionally, lesion localizations of the RadImageNet models were improved by 64.6% and 16.4% on thyroid and breast US datasets, respectively. Conclusion: RadImageNet pretrained models demonstrated better interpretability compared with ImageNet models, especially for smaller radiologic datasets.Keywords: CT, MR Imaging, US, Head/Neck, Thorax, Brain/Brain Stem, Evidence-based Medicine, Computer Applications-General (Informatics) Supplemental material is available for this article. Published under a CC BY 4.0 license.See also the commentary by Cadrin-Chênevert in this issue.

Mebendazole-Induced Blood-Testis Barrier Injury in Mice Testes by Disrupting Microtubules in Addition to Triggering Programmed Cell Death.

Mebendazole (MBZ) is a synthetic benzimidazole known for its antiparasitic properties. In recent years, growing evidence showed that MBZ was also used as an anti-tumor agent. However, whether (and to what extent) this drug treatment affected the male reproductive system was not well-understood. In this study, male C57BL/6 mice were injected with 40 mg/kg/day of MBZ. The treatment was for 3 and 7 days. Our results showed that the injected mice exhibited an abnormal spermatogenic phase with a significant decrease in sperm. We further detected microtubule disruption and transient functional destruction of the blood-testes barrier (BTB) in the MBZ-injected mice testes (BTB). Our data confirmed that MBZ suppressed the expression of the BTB junction-associated proteins and disrupted the Sertoli cells' function in vivo. Moreover, MBZ-treated mice demonstrated an aberrant caspase-3 signalling pathway, which resulted in the apoptosis of the germ cells. Here, we present our data, indicating that MBZ impairs BTB by reducing the expression of the microtubules' and BTB junction-associated proteins. The last leads to activating the caspase-3 pathway, which triggers extensive germ cell apoptosis.

Preventing autosomal-dominant hearing loss in Bth mice with CRISPR/CasRx-based RNA editing.

CRISPR/RfxCas13d (CasRx) editing system can specifically and precisely cleave single-strand RNAs, which is a promising treatment for various disorders by downregulation of related gene expression. Here, we tested this RNA-editing approach on Beethoven (Bth) mice, an animal model for human DFNA36 due to a point mutation in Tmc1. We first screened 30 sgRNAs in cell cultures and found that CasRx with sgRNA3 reduced the Tmc1Bth transcript by 90.8%, and the Tmc1 wild type transcript (Tmc1+) by 44.3%. We then injected a newly developed AAV vector (AAV-PHP.eB) based CasRx into the inner ears of neonatal Bth mice, and we found that Tmc1Bth was reduced by 70.2% in 2 weeks with few off-target effects in the whole transcriptome. Consistently, we found improved hair cell survival, rescued hair bundle degeneration, and reduced mechanoelectrical transduction current. Importantly, the hearing performance, measured in both ABR and DPOAE thresholds, was improved significantly in all ages over 8 weeks. We, therefore, have validated the CRISPR/CasRx-based RNA editing strategy in treating autosomal-dominant hearing loss, paving way for its further application in many other hereditary diseases in hearing and beyond.

Fully automated radiomic screening pipeline for osteoporosis and abnormal bone density with a deep learning-based segmentation using a short lumbar mDixon sequence.

BACKGROUND: Although lumbar bone marrow fat fraction (BMFF) has been demonstrated to be predictive of osteoporosis, its utility is limited by the requirement of manual segmentation. Additionally, quantitative features beyond simple BMFF average remain to be explored. In this study, we developed a fully automated radiomic pipeline using deep learning-based segmentation to detect osteoporosis and abnormal bone density (ABD) using a <20 s modified Dixon (mDixon) sequence. METHODS: In total, 222 subjects underwent quantitative computed tomography (QCT) and lower back magnetic resonance imaging (MRI). Bone mineral density (BMD) were extracted from L1-L3 using QCT as the reference standard; 206 subjects (48.8±14.9 years old, 140 females) were included in the final analysis, and were divided temporally into the training/validation set (142/64 subjects). A deep-learning network was developed to perform automated segmentation. Radiomic models were built using the same training set to predict ABD and osteoporosis using the mDixon maps. The performance was evaluated using the temporal validation set comprised of 64 subjects, along with the automated segmentation. Additional 25 subjects (56.1±8.8 years, 14 females) from another site and a different scanner vendor was included as independent validation to evaluate the performance of the pipeline. RESULTS: The automated segmentation achieved an outstanding mean dice coefficient of 0.912±0.062 compared to manual in the temporal validation. Task-based evaluation was performed in the temporal validation set, for predicting ABD and osteoporosis, the area under the curve, sensitivity, specificity, and accuracy were 0.925/0.899, 0.923/0.667, 0.789/0.873, 0.844/0.844, respectively. These values were comparable to that of manual segmentation. External validation (cross-vendor) was also performed; the area under the curve, sensitivity, specificity, and accuracy were 0.688/0.913, 0.786/0.857, 0.545/0.944, 0.680/0.920 for ABD and osteoporosis prediction, respectively. CONCLUSIONS: Our work is the first attempt using radiomics to predict osteoporosis with BMFF map, and the deep-learning based segmentation will further facilitate the clinical utility of the pipeline as a screening tool for early detection of ABD.

Gene editing in a Myo6 semi-dominant mouse model rescues auditory function.

Myosin VI（MYO6） is an unconventional myosin that is vital for auditory and vestibular function. Pathogenic variants in the human MYO6 gene cause autosomal-dominant or -recessive forms of hearing loss. Effective treatments for Myo6 mutation causing hearing loss are limited. We studied whether adeno-associated virus (AAV)-PHP.eB vector-mediated in vivo delivery of Staphylococcus aureus Cas9 (SaCas9-KKH)-single-guide RNA (sgRNA) complexes could ameliorate hearing loss in a Myo6WT/C442Y mouse model that recapitulated the phenotypes of human patients. The in vivo editing efficiency of the AAV-SaCas9-KKH-Myo6-g2 system on Myo6C442Y is 4.05% on average in Myo6WT/C442Y mice, which was ∼17-fold greater than editing efficiency of Myo6WT alleles. Rescue of auditory function was observed up to 5 months post AAV-SaCas9-KKH-Myo6-g2 injection in Myo6WT/C442Y mice. Meanwhile, shorter latencies of auditory brainstem response (ABR) wave I, lower distortion product otoacoustic emission (DPOAE) thresholds, increased cell survival rates, more regular hair bundle morphology, and recovery of inward calcium levels were also observed in the AAV-SaCas9-KKH-Myo6-g2-treated ears compared to untreated ears. These findings provide further reference for in vivo genome editing as a therapeutic treatment for various semi-dominant forms of hearing loss and other semi-dominant diseases.

Shoulder adhesive capsulitis in cancer patients undergoing positron emission tomography - computed tomography and the association with shoulder pain.

BACKGROUND: Adhesive capsulitis is a relatively common condition that can develop in cancer patients during treatment. Positron emission tomography - computed tomography (PET-CT) is routinely performed as a follow-up study in cancer patients after therapy. Being aware of PET-CT findings to suggest shoulder adhesive capsulitis may help to alert clinicians for the diagnosis of unsuspected shoulder capsulitis. AIM: To assess the association of shoulder adhesive capsulitis with cancer/therapy type and symptoms in cancer patients undergoing PET-CT. METHODS: Our prospective study received Institutional Review Board approval. Written informed consent was obtained from all patients, who answered a questionnaire regarding shoulder pain/stiffness at the time of PET-CT study, between March 2015 and April 2019. Patients with advanced glenohumeral arthrosis, metastatic disease or other mass in the shoulder, or shoulder arthroplasty were excluded. Patterns of shoulder capsule 18F-fluorodeoxyglucose (FDG) uptake were noted. Standard Uptake Value (SUV)max and SUVmean values were measured at rotator interval (RI) and deltoid muscle in bilateral shoulders. Normalized SUV (SUV of RI/SUV of deltoid muscle) was also calculated. We assessed if SUV values are different between symptomatic and asymptomatic patients in both shoulders. Covariates were age, gender, and therapy type (surgery, chemotherapy, radiation). Wilcoxon rank sum tests were used to compare unadjusted marginal differences for age, SUV measurements between symptomatic and asymptomatic patients. Multiple linear regression models were used to examine the relationship between right or left shoulder SUV measurements and symptom status, after adjusting for covariates. Statistical significance level was set at P < 0.05. RESULTS: Of 252 patients initially enrolled for the study (mean age 66 years, 67 symptomatic), shoulder PET-CT data were obtained in 200 patients (52 were excluded due to exclusion criteria above). The most common cancer types were lymphoma (n = 61), lung (n = 54) and breast (n = 53). No significant difference was noted between symptomatic and asymptomatic patients in terms of age, gender, proportion of patients who had surgical therapy and radiation therapy. A proportion of patients who received chemotherapy was higher in patients who were asymptomatic in the right shoulder compared to those symptomatic in the right shoulder (65% vs 48%, P = 0.012). No such difference was seen for the left shoulder. In both shoulders, SUVmax and SUVmean were higher in symptomatic shoulders than asymptomatic shoulders (Left SUVmax 2.0 vs 1.6, SUVmean 1.6 vs 1.3, both P < 0.002; Right SUVmax 2.2 vs 1.8, SUVmean 1.8 vs 1.5, both P < 0.01). For lung cancer patients, bilateral RI SUVmax and SUVmean values were higher in symptomatic shoulders than asymptomatic shoulders. For other cancer patients, symptomatic patients had higher left RI SUVmax/mean than asymptomatic patients after adjustment. CONCLUSION: In symptomatic patients metabolic activities in RI were higher than asymptomatic patients. Adhesive capsulitis should be considered in cancer patients with shoulder symptoms and positive FDG uptake in RI.

MRI Evaluation of Various Elbow, Forearm, and Wrist Neuropathies: A Pictorial Review.

Upper extremity entrapment neuropathies are common and can cause pain, sensory loss, and muscle weakness leading to functional disability. We conducted a retrospective review from January 2007 until March 2020 of the magnetic resonance imaging (MRI) features of intrinsic and extrinsic causes of wrist, forearm, and elbow neuropathies of 637 patients who received a diagnosis of neuropathy by means of clinical and electrodiagnostic testing. We discuss cases with varying intrinsic and extrinsic nerve pathologies, including postoperative examples, affecting the median, radial, and ulnar nerve.Our collection of cases demonstrates a diversity of intrinsic and extrinsic causative factors. Intrinsic pathologies include neuritis as well as tumors arising from the nerve. Extrinsic causes resulting in nerve entrapment include masses, acute and chronic posttraumatic cases, anatomical variants, inflammatory and crystal deposition, calcium pyrophosphate deposition disease, and dialysis-related amyloidosis. Finally, we review postsurgical cases, such as carpal tunnel release and ulnar nerve transposition.Although upper extremity neuropathies tend to have a typical clinical presentation, imaging, particularly MRI, plays a vital role in evaluating the etiology and severity of each neuropathy and ultimately helps guide clinical management.

Epiphyseal Ewing Sarcoma in a skeletally mature patient: A case report and review of the literature.

While Ewing sarcoma of bone is the second most common primary osseous malignancy in childhood where it typically involves the diaphysis or metadiaphyses of long bones of skeletally immature patients, primary epiphyseal involvement of the long bone in skeletally mature patients is rare with no cases reported in the literature to our knowledge, rendering this case the first of its kind. We present the first case of primary Ewing Sarcoma of the epiphyses of the long bones in a skeletally mature 20-year-old male patient. The patient initially presented with left knee stiffness and pain that was empirically treated with non-steroidal anti-inflammatory medications. His pain progressed despite treatment. An x-ray of the left knee was obtained 5 months later demonstrating an irregular lucent lesion in the medial femoral condyle. A subsequent MRI revealed an enhancing lesion in the medial femoral condyle, and when biopsied it was consistent with Ewing sarcoma (positive for EWSR1gene rearrangement by fluorescence in situ hybridization). The lesion was resected surgically, and the patient underwent neoadjuvant chemotherapy with a good clinical outcome.

A Novel in vitro Model Delineating Hair Cell Regeneration and Neural Reinnervation in Adult Mouse Cochlea.

The study of an adult mammalian auditory system, such as regeneration, has been hampered by the lack of an in vitro system in which hypotheses can be tested efficiently. This is primarily due to the fact that the adult inner ear is encased in the toughest bone of the body, whereas its removal leads to the death of the sensory epithelium in culture. We hypothesized that we could take advantage of the integral cochlear structure to maintain the overall inner ear architecture and improve sensory epithelium survival in culture. We showed that by culturing adult mouse cochlea with the (surrounding) bone intact, the supporting cells (SCs) survived and almost all hair cells (HCs) degenerated. To evaluate the utility of the explant culture system, we demonstrated that the overexpression of Atoh1, an HC fate-determining factor, is sufficient to induce transdifferentiation of adult SCs to HC-like cells (HCLCs). Transdifferentiation-derived HCLCs resemble developmentally young HCs and are able to attract adult ganglion neurites. Furthermore, using a damage model, we showed that degenerated adult ganglions respond to regenerated HCLCs by directional neurite outgrowth that leads to HCLC-neuron contacts, strongly supporting the intrinsic properties of the HCLCs in establishing HCLC-neuron connections. The adult whole cochlear explant culture is suitable for diverse studies of the adult inner ear including regeneration, HC-neuron pathways, and inner ear drug screening.

Spontaneous osteonecrosis of the knee (SONK): The role of MR imaging in predicting clinical outcome.

BACKGROUND/AIM: We try to investigate the association between patterns of imaging findings in patients who had a diagnosis of subchondral fracture around the knee, formerly known as SONK and their clinical outcome. MATERIALS AND METHODS: We retrospectively identified 43 knees of 37 patients (28 males, 15 females) who had diagnosis of subchondral fractures around the knee. The mean age is 56-year-old (range 17-83). Musculoskeletal fellowship trained radiologist evaluated all 43 knee MRI in: 1)location of marrow edema 2)peri-osseous edema; 3) subchondral fracture line; 4) subchondral articular surface contour; 5)meniscal tear and extrusion; 6)adjacent soft tissue edema; 7) joint effusion. Independent clinical chart review was performed for clinical outcome with follow up time average of 13.3 months (range 0-88 months). Bad outcome was defined as worsening on imaging, continued complaint with surgical management and knee replacement or another episode of SONK. Chi-square analysis and Student's T tests were conducted to test the statistical significance of association between MR findings and outcomes. Statistical significance was set at p = 0.05 level. RESULTS: Of 43 knees, 6 patients had another episodes of SONK (14%), 11 patients were not improving or needed injection vs arthroscopy (26%), 4 patients required arthroplasty (9%), 22 patients had no negative outcome (51%). Gender, age, diabetic status, and location of the subchondral fracture show no influence on outcome. Worse outcome group had a significantly higher average BMI (31.7 vs. 28.0, P = 0.02). Positive change of subchondral articular surface contour is the only imaging finding with positive association with worse outcome (80% vs. 39.9%, P = 0.02). Presence of positive findings of above 3), 4), 5) and 6) had higher percentage of bad outcome (77.8%) compared to those with less positive findings (47.2%). CONCLUSION: MR imaging findings may help at identifying SONK patient with potential risk of developing bad outcome.

Chinese expert consensus on the diagnosis of osteoporosis by imaging and bone mineral density.

With an aging society, osteoporosis is one of the most common diseases threatening the health of China's elderly population and is an issue that is raising increasing concern. Osteoporosis is characterized by bone loss and increased susceptibility to fragility fractures. Various imaging modalities such as X-ray, CT, MRI and nuclear medicine along with assessment of bone mineral density (BMD) play an important role in its diagnosis and management, and the treatment requires multidisciplinary teamwork. A lack of consensus in the approach to imaging and BMD measurement is hampering the quality of service and patient care in China. Therefore a panel of Chinese experts from the fields of radiology, orthopedics, endocrinology and nuclear medicine reviewed the international guidelines, consensus and literature with the most recent data from China and, taking account of current clinical practice in China, the panel reached this consensus to help guide the diagnosis of osteoporosis using imaging and BMD. This consensus report provides guidelines and standards for the imaging and BMD assessment of osteoporosis and criteria for the diagnosis of osteoporosis in China.