Quantitative 1H Magnetic Resonance Imaging on Normal and Pathologic Rat Bones by Solid-State 1H ZTE Sequence with Water and Fat Suppression.

BACKGROUND: Osteoporosis (OP) and osteomalacia (OM) are metabolic bone diseases characterized by mineral and matrix density changes. Quantitative bone matrix density differentiates OM from OP. MRI is a noninvasive and nonionizing imaging technique that can measure bone matrix density quantitatively in ex vivo and in vivo. PURPOSE: To demonstrate water + fat suppressed 1H MRI to compute bone matrix density in ex vivo rat femurs in the preclinical model. STUDY TYPE: Prospective. ANIMAL MODEL: Fifteen skeletally mature female Sprague-Dawley rats, five per group (normal, ovariectomized (OVX), partially nephrectomized/vitamin D (Vit-D) deficient), 250-275 g, ∼15 weeks old. FIELD STRENGTH/SEQUENCE: 7T, zero echo time sequence with water + fat (VAPOR) suppression capability, µCT imaging, and gravimetric measurements. ASSESSMENT: Cortical and trabecular bone segments from normal and disease models were scanned in the same coil along with a dual calibration phantom for quantitative assessment of bone matrix density. STATISTICAL TESTS: ANOVA and linear regression were used for data analysis, with P-values <0.05 statistically significant. RESULTS: The MRI-derived three-density PEG pellet densities have a strong linear relationship with physical density measures (r2 = 0.99). The Vit-D group had the lowest bone matrix density for cortical bone (0.47 ± 0.16 g cm-3), whereas the OVX had the lowest bone matrix density for trabecular bone (0.26 ± 0.04 g cm-3). Gravimetry results confirmed these MRI-based observations for Vit-D cortical (0.51 ± 0.07 g cm-3) and OVX trabecular (0.26 ± 0.03 g cm-3) bone groups. DATA CONCLUSION: Rat femur images were obtained using a modified pulse sequence and a custom-designed double-tuned (1H/31P) transmit-receive solenoid-coil on a 7T preclinical MRI scanner. Phantom experiments confirmed a strong linear relation between MRI-derived and physical density measures and quantitative bone matrix densities in rat femurs from normal, OVX, and Vit-D deficient/partially nephrectomized animals were computed. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

Quantitative 31P magnetic resonance imaging on pathologic rat bones by ZTE at 7T.

BACKGROUND: Osteoporosis is characterized by low bone mineral density (BMD), which predisposes individuals to frequent fragility fractures. Quantitative BMD measurements can potentially help distinguish bone pathologies and allow clinicians to provide disease-relieving therapies. Our group has developed non-invasive and non-ionizing magnetic resonance imaging (MRI) techniques to measure bone mineral density quantitatively. Dual-energy X-ray Absorptiometry (DXA) is a clinically approved non-invasive modality to diagnose osteoporosis but has associated disadvantages and limitations. PURPOSE: Evaluate the clinical feasibility of phosphorus (31P) MRI as a non-invasive and non-ionizing medical diagnostic tool to compute bone mineral density to help differentiate between different metabolic bone diseases. MATERIALS AND METHODS: Fifteen ex-vivo rat bones in three groups [control, ovariectomized (osteoporosis), and vitamin-D deficient (osteomalacia - hypo-mineralized) were scanned to compute BMD. A double-tuned (1H/31P) transmit-receive single RF coil was custom-designed and in-house-built with a better filling factor and strong radiofrequency (B1) field to acquire solid-state 31P MR images from rat femurs with an optimum signal-to-noise ratio (SNR). Micro-computed tomography (µCT) and gold-standard gravimetric analyses were performed to compare and validate MRI-derived bone mineral densities. RESULTS: Three-dimensional 31P MR images of rat bones were obtained with a zero-echo-time (ZTE) sequence with 468 µm spatial resolution and 12-17 SNR on a Bruker 7 T Biospec having multinuclear capability. BMD was measured quantitatively on cortical and trabecular bones with a known standard reference. A strong positive correlation (R = 0.99) and a slope close to 1 in phantom measurements indicate that the densities measured by 31P ZTE MRI are close to the physical densities in computing quantitative BMD. The 31P NMR properties (resonance linewidth of 4 kHz and T1 of 67 s) of ex-vivo rat bones were measured, and 31P ZTE imaging parameters were optimized. The BMD results obtained from MRI are in good agreement with µCT and gravimetry results. CONCLUSION: Quantitative measurements of BMD on ex-vivo rat femurs were successfully conducted on a 7 T preclinical scanner. This study suggests that quantitative measurements of BMD are feasible on humans in clinical MRI with suitable hardware, RF coils, and pulse sequences with optimized parameters within an acceptable scan time since human femurs are approximately ten times larger than rat femurs. As MRI provides quantitative in-vivo data, various systemic musculoskeletal conditions can be diagnosed potentially in humans.

Detecting upper extremity native joint dislocations using deep learning: A multicenter study.

OBJECTIVE: Joint dislocations are orthopedic emergencies that require prompt intervention. Automatic identification of these injuries could help improve timely patient care because diagnostic delays increase the difficulty of reduction. In this study, we developed convolutional neural networks (CNNs) to detect elbow and shoulder dislocations, and tested their generalizability on external datasets. METHODS: We collected 106 elbow radiographs (53 with dislocation [50 %]) and 140 shoulder radiographs (70 with dislocation [50 %]) from a level-1 trauma center. After performing 24× data augmentation on training/validation data, we trained multiple CNNs to detect elbow and shoulder dislocations, and also evaluated the best-performing models using external datasets from an external hospital and online radiology repositories. To examine CNN decision-making, we generated class activation maps (CAMs) to visualize areas of images that contributed the most to model decisions. RESULTS: On all internal test sets, CNNs achieved AUCs >0.99, and on all external test sets, CNNs achieved AUCs >0.97. CAMs demonstrated that the CNNs were focused on relevant joints in decision-making regardless of whether or not dislocations were present. CONCLUSION: Joint dislocations in both shoulders and elbows were readily identified with high accuracy by CNNs with excellent generalizability to external test sets. These findings suggest that CNNs could expedite access to intervention by assisting in diagnosing dislocations.

Management of arthrofibrosis in neuromuscular disorders: a review.

Arthrofibrosis, or rigid contracture of major articular joints, is a significant morbidity of many neurodegenerative disorders. The pathogenesis depends on the mechanism and severity of the precipitating neuromuscular disorder. Most neuromuscular disorders, whether spastic or hypotonic, culminate in decreased joint range of motion. Limited range of motion precipitates a cascade of pathophysiological changes in the muscle-tendon unit, the joint capsule, and the articular cartilage. Resulting joint contractures limit functional mobility, posing both physical and psychosocial burdens to patients, economic burdens on the healthcare system, and lost productivity to society. This article reviews the pathophysiology of arthrofibrosis in the setting of neuromuscular disorders. We describe current non-surgical and surgical interventions for treating arthrofibrosis of commonly affected joints. In addition, we preview several promising modalities under development to ameliorate arthrofibrosis non-surgically and discuss limitations in the field of arthrofibrosis secondary to neuromuscular disorders.

Can images crowdsourced from the internet be used to train generalizable joint dislocation deep learning algorithms?

OBJECTIVE: Deep learning has the potential to automatically triage orthopedic emergencies, such as joint dislocations. However, due to the rarity of these injuries, collecting large numbers of images to train algorithms may be infeasible for many centers. We evaluated if the Internet could be used as a source of images to train convolutional neural networks (CNNs) for joint dislocations that would generalize well to real-world clinical cases. METHODS: We collected datasets from online radiology repositories of 100 radiographs each (50 dislocated, 50 located) for four joints: native shoulder, elbow, hip, and total hip arthroplasty (THA). We trained a variety of CNN binary classifiers using both on-the-fly and static data augmentation to identify the various joint dislocations. The best-performing classifier for each joint was evaluated on an external test set of 100 corresponding radiographs (50 dislocations) from three hospitals. CNN performance was evaluated using area under the ROC curve (AUROC). To determine areas emphasized by the CNN for decision-making, class activation map (CAM) heatmaps were generated for test images. RESULTS: The best-performing CNNs for elbow, hip, shoulder, and THA dislocation achieved high AUROCs on both internal and external test sets (internal/external AUC): elbow (1.0/0.998), hip (0.993/0.880), shoulder (1.0/0.993), THA (1.0/0.950). Heatmaps demonstrated appropriate emphasis of joints for both located and dislocated joints. CONCLUSION: With modest numbers of images, radiographs from the Internet can be used to train clinically-generalizable CNNs for joint dislocations. Given the rarity of joint dislocations at many centers, online repositories may be a viable source for CNN-training data.

Detecting total hip arthroplasty dislocations using deep learning: clinical and Internet validation.

OBJECTIVE: Periprosthetic dislocations of total hip arthroplasty (THA) are time-sensitive injuries, as the longer diagnosis and treatment are delayed, the more difficult they are to reduce. Automated triage of radiographs with dislocations could help reduce these delays. We trained convolutional neural networks (CNNs) for the detection of THA dislocations, and evaluated their generalizability by evaluating them on external datasets. METHODS: We used 357 THA radiographs from a single hospital (185 with dislocation [51.8%]) to develop and internally test a variety of CNNs to identify THA dislocation. We performed external testing of these CNNs on two datasets to evaluate generalizability. CNN performance was evaluated using area under the receiving operating characteristic curve (AUROC). Class activation mapping (CAM) was used to create heatmaps of test images for visualization of regions emphasized by the CNNs. RESULTS: Multiple CNNs achieved AUCs of 1 for both internal and external test sets, indicating good generalizability. Heatmaps showed that CNNs consistently emphasized the THA for both dislocated and located THAs. CONCLUSION: CNNs can be trained to recognize THA dislocation with high diagnostic performance, which supports their potential use for triage in the emergency department. Importantly, our CNNs generalized well to external data from two sources, further supporting their potential clinical utility.

The Role of Minimally Invasive Percutaneous Pedicle Screw Fixation for the Management of Spinal Metastatic Disease.

OBJECTIVE: Optimal surgical management of spinal metastatic disease remains controversial. Skip and diffuse spinal lesions, patient frailty, and the need for timely adjuvant chemoradiation complicate surgical decision-making. Minimally invasive percutaneous pedicle screw fixation (MIPSF) is an attractive concept that can confer stability and allow early postoperative mobilization. To date, outcomes of the MIPSF technique remain under-investigated. METHODS: A single-center retrospective review of patients undergoing percutaneous instrumentation for multilevel spinal metastatic disease between January 2012 and October 2020 was performed. Twenty-four patients were identified, and their primary tumor diagnoses, modified Tokuhashi scores, Spine Instability Neoplastic Scores, neurologic functions, pain scores, and procedure types were noted. Of these patients, 17 underwent fixation of 6 or more levels (L-MIPSF), whereas 7 underwent fixation of <6 levels (S-MIPSF). All patients had screw-and-rod constructs placed percutaneously using bi-planar fluoroscopy guidance. Patients undergoing corpectomy, multilevel laminectomies, or open posterior instrumentation were excluded. RESULTS: Improvement in pain and neurological function was noted in nearly all patients who underwent MIPSF. Average skin incision-to-closing time was 130 minutes, and standard deviation of 55 minutes. Likewise, the average estimated operative blood loss was 402 mL, and standard deviation of 388 mL. Only one patient required hardware revision due to proximal loss of fixation. Two patients required mini-open decompression procedures due to tumor recurrence at different levels than the index pathology. CONCLUSIONS: Multilevel minimally invasive spinal fixation is feasible in patients with diffuse spinal metastasis. The percutaneous nature of the technique minimizes dissection, blood loss, and operative times. Early outcomes of MIPSF are promising and demonstrate utility in avoiding multiple subsequent procedures in a cohort of deconditioned patients.

Genetic reduction of mTOR extends lifespan in a mouse model of Hutchinson-Gilford Progeria syndrome.

Hutchinson-Gilford progeria syndrome (HGPS) is a rare accelerated aging disorder most notably characterized by cardiovascular disease and premature death from myocardial infarction or stroke. The majority of cases are caused by a de novo single nucleotide mutation in the LMNA gene that activates a cryptic splice donor site, resulting in production of a toxic form of lamin A with a 50 amino acid internal deletion, termed progerin. We previously reported the generation of a transgenic murine model of progeria carrying a human BAC harboring the common mutation, G608G, which in the single-copy state develops features of HGPS that are limited to the vascular system. Here, we report the phenotype of mice bred to carry two copies of the BAC, which more completely recapitulate the phenotypic features of HGPS in skin, adipose, skeletal, and vascular tissues. We further show that genetic reduction of the mechanistic target of rapamycin (mTOR) significantly extends lifespan in these mice, providing a rationale for pharmacologic inhibition of the mTOR pathway in the treatment of HGPS.

The Imperative for Diversity and Inclusion in Interventional Radiology.

OBJECTIVE. The purpose of our study was to review key social justice and competitive advantage arguments for diversity in interventional radiology (IR) to substantiate the need for a more inclusive workforce. CONCLUSION. As a specialty based on innovation and flexibility of thought, IR is well positioned to be a driver of diversity and inclusion in medicine. The status quo is far from ideal. Social justice and business advantage arguments provide us with the imperative for change.

Tendinopathy and tendon material response to load: What we can learn from small animal studies.

Tendinopathy is a debilitating disease that causes as much as 30% of all musculoskeletal consultations. Existing treatments for tendinopathy have variable efficacy, possibly due to incomplete characterization of the underlying pathophysiology. Mechanical load can have both beneficial and detrimental effects on tendon, as the overall tendon response depends on the degree, frequency, timing, and magnitude of the load. The clinical continuum model of tendinopathy offers insight into the late stages of tendinopathy, but it does not capture the subclinical tendinopathic changes that begin before pain or loss of function. Small animal models that use high tendon loading to mimic human tendinopathy may be able to fill this knowledge gap. The goal of this review is to summarize the insights from in-vivo animal studies of mechanically-induced tendinopathy and higher loading regimens into the mechanical, microstructural, and biological features that help characterize the continuum between normal tendon and tendinopathy. STATEMENT OF SIGNIFICANCE: This review summarizes the insights gained from in-vivo animal studies of mechanically-induced tendinopathy by evaluating the effect high loading regimens have on the mechanical, structural, and biological features of tendinopathy. A better understanding of the interplay between these realms could lead to improved patient management, especially in the presence of painful tendon.

Modifiable lifestyle factors associated with fragility hip fracture: a systematic review and meta-analysis.

INTRODUCTION: Among the various hip fracture predictors explored to date, modifiable risk factors warrant special consideration, since they present promising targets for preventative measures. This systematic review and meta-analysis aims to assess various modifiable risk factors. MATERIAL AND METHODS: We searched four online databases in September 2017. We included studies that reported on modifiable lifestyle risk factors for sustaining fragility hip fractures. The quality of the included studies was assessed using the Newcastle-Ottawa Scale (NOS). The inclusion criteria consisted of (1) adult patients with osteoporotic hip fracture, (2) original study, (3) availability of full text articles in English, and (4) report of a modifiable lifestyle risk factor. RESULTS: Thirty-five studies, containing 1,508,366 subjects in total, were included in this study. The modifiable risk factors that were significantly associated with an increased risk of hip fracture were the following: weight < 58 kg (128 lbs) (pooled OR 4.01, 95% CI 1.62-9.90), underweight body mass index (BMI) (< 18.5) (pooled OR 2.83, 95% CI 1.82-4.39), consumption of ≥ 3 cups of coffee daily (pooled OR 2.27, 95% CI 1.04-4.97), inactivity (pooled OR 2.14, 95% CI 1.21-3.77), weight loss (pooled OR 1.88, 95% CI 1.32-2.68), consumption of ≥ 27 g (approx. > 2 standard drinks) alcohol per day (pooled OR 1.54, 95% CI 1.12-2.13), and being a current smoker (pooled OR 1.50, 95% CI 1.22-1.85). Conversely, two factors were significantly associated with a decreased risk of hip fracture: obese BMI (> 30) (pooled OR 0.58, 95% CI 0.34-0.99) and habitual tea drinking (pooled OR 0.72, 95% CI 0.66-0.80). CONCLUSION: Modifiable factors may be utilized clinically to provide more effective lifestyle interventions for at risk populations. We found that low weight and underweight BMI carried the highest risk, followed by high coffee consumption, inactivity, weight loss, and high daily alcohol consumption.

Multivitamins and risk of fragility hip fracture: a systematic review and meta-analysis.

PURPOSE: Hip fracture is a severe complication of osteoporosis and is associated with a significant healthcare burden worldwide. This meta-analysis explores the association between combined multivitamin use and hip fracture risk. Our results provide more patient-centered insight into the impact of supplement use on osteoporosis outcomes. METHODS: We searched three online databases in August 2019 and included studies that reported on multivitamin use in patients with osteoporotic hip fractures. The inclusion criteria were (1) adult patients with osteoporotic hip fractures, (2) availability of full-text articles in English, and (3) at least 1 year of follow-up. No suitable randomized controlled trials could be identified for inclusion in the analysis. The quality of the included studies was assessed using the Newcastle-Ottawa Scale (NOS). RESULTS: Eight studies containing 80,148 subjects in total were included in this study. Among these, 4237 cases of fragility hip fracture were reported. The average age was 69±5.3 years, and 21% of subjects were male. Multivitamin use was found to be significantly associated with a lower risk of sustaining a fragility hip fracture (OR 0.49, 95%CI: 0.32-0.77). The Begg and Mazumdar test and funnel plot indicated that no significant publication bias was present. CONCLUSION: Combined multivitamins are amongst the most widely used supplements and are often preferred over single vitamins. Our meta-analysis indicates that multivitamin use is significantly protective against osteoporotic hip fracture. In the future, randomized controlled trials should be performed to establish multivitamins as effective preventative measures for this injury.

Clinical outcomes and inflammatory marker levels in patients with Covid-19 and obesity at an inner-city safety net hospital.

OBJECTIVES: Patients with Covid-19 and obesity have worse clinical outcomes which may be driven by increased inflammation. This study aimed to characterize the association between clinical outcomes in patients with obesity and inflammatory markers. METHODS: We analyzed data for patients aged ≥18 years admitted with a positive SARS-CoV-2 PCR test. We used multivariate logistic regression to determine the association between BMI and intensive care unit (ICU) transfer and all-cause mortality. Inflammatory markers (C-reactive protein [CRP], lactate dehydrogenase [LDH], ferritin, and D-dimer) were compared between patients with and without obesity (body mass index [BMI] ≥30 kg/m2). RESULTS: Of 791 patients with Covid-19, 361 (45.6%) had obesity. In multivariate analyses, BMI ≥35 was associated with a higher odds of ICU transfer (adjusted odds ratio [aOR] 2.388 (95% confidence interval [CI]: 1.074-5.310) and hospital mortality (aOR = 4.3, 95% CI: 1.69-10.82). Compared to those with BMI<30, patients with obesity had lower ferritin (444 vs 637 ng/mL; p<0.001) and lower D-dimer (293 vs 350 mcg/mL; p = 0.009), non-significant differences in CRP (72.8 vs 84.1 mg/L, p = 0.099), and higher LDH (375 vs 340, p = 0.009) on the first hospital day. CONCLUSIONS: Patients with obesity were more likely to have poor outcomes even without increased inflammation.