Quantitative assessment of extraocular muscles in Graves' ophthalmopathy using T1 mapping.

OBJECTIVE: To evaluate the performance of T1 mapping in the characterization of extraocular muscles (EOMs) of Graves' ophthalmopathy (GO) patients and investigate its feasibility in assessing the response to glucocorticoid therapy in active GO patients. METHODS: A total of 133 participants (78 active GO, 23 inactive GO, 18 Graves' disease (GD) patients, and 14 healthy volunteers) were consecutively enrolled from July 2018 to December 2020. Native T1 (nT1) and postcontrast T1 (cT1) values of EOMs were measured and compared. The variations in T1 mapping metrics of EOMs were compared pre/post glucocorticoid treatment in 23 follow-up active GO patients. Logistic regression analysis and receiver operating characteristic (ROC) curve analysis were performed. RESULTS: The nT1 of EOMs in GO patients was higher than that in GD patients and healthy volunteers. The nT1 of superior rectus (SR) in active GO was higher than that in inactive GO patients, and it could be used as a potential marker of GO activity (OR: 1.003; 95% CI: 1.001, 1.004), with a diagnostic sensitivity of 86.3% and specificity of 43.7%. Meanwhile, the cT1 of SR, inferior rectus (IR), and medial rectus (MR) in inactive GO patients were higher than those in active GO patients. The nT1 of EOMs achieved sufficient diagnostic performance in evaluating the response to glucocorticoid therapy for follow-up active GO patients (AUC, 0.797; sensitivity, 71.9%; specificity, 85.7%). CONCLUSIONS: T1 mapping could quantitatively assess the activity of GO and the response to glucocorticoid therapy in active GO patients and may even potentially reflect the fibrosis of EOMs. CLINICAL RELEVANCE STATEMENT: T1 values can reflect the pathological status of the extraocular muscle. T1 mapping could help to quantitatively assess the clinical activity of GO and the response to glucocorticoid therapy in active GO patients. KEY POINTS: • Graves' ophthalmopathy patients had greater nT1 of extraocular muscles than Graves' disease patients and healthy volunteers, and nT1 of the superior rectus could be a potential marker of Graves' ophthalmopathy activity. • The cT1 of extraocular muscles in inactive Graves' ophthalmopathy patients was higher than that in active Graves' ophthalmopathy patients, and it might be associated with muscle fibrosis. • nT1 of extraocular muscles could offer sufficient diagnostic performance in evaluating the response to glucocorticoid therapy for follow-up active Graves' ophthalmopathy patients.

Generalizable Pancreas Segmentation via a Dual Self-Supervised Learning Framework.

Recently, numerous pancreas segmentation methods have achieved promising performance on local single-source datasets. However, these methods don't adequately account for generalizability issues, and hence typically show limited performance and low stability on test data from other sources. Considering the limited availability of distinct data sources, we seek to improve the generalization performance of a pancreas segmentation model trained with a single-source dataset, i.e., the single-source generalization task. In particular, we propose a dual self-supervised learning model that incorporates both global and local anatomical contexts. Our model aims to fully exploit the anatomical features of the intra-pancreatic and extra-pancreatic regions, and hence enhance the characterization of the high-uncertainty regions for more robust generalization. Specifically, we first construct a global-feature contrastive self-supervised learning module that is guided by the pancreatic spatial structure. This module obtains complete and consistent pancreatic features through promoting intra-class cohesion, and also extracts more discriminative features for differentiating between pancreatic and non-pancreatic tissues through maximizing inter-class separation. It mitigates the influence of surrounding tissue on the segmentation outcomes in high-uncertainty regions. Subsequently, a local-image-restoration self-supervised learning module is introduced to further enhance the characterization of the high-uncertainty regions. In this module, informative anatomical contexts are actually learned to recover randomly-corrupted appearance patterns in those regions. The effectiveness of our method is demonstrated with state-of-the-art performance and comprehensive ablation analysis on three pancreas datasets (467 cases). The results demonstrate a great potential in providing a stable support for the diagnosis and treatment of pancreatic diseases.

Subtraction coronary CT angiography in patients with high heart rate.

All the previous subtraction coronary CT angiography (CCTA) had strict heart rate (HR) inclusion criteria. In this study, a new subtraction method was applied to patients with various HR. The post-contrast scan time was respectively 3.5 s after ascending aorta peak enhancement while HR >80 bpm, 4 s while 65≤ HR ≤80 bpm and 4.5 s while HR <65 bpm. Forty-six patients who underwent the new subtraction protocol were enrolled and patients were stratified into the high HR group (≥70 bpm) and low HR group (<70 bpm). Eighteen patients with 15 severe calcification segments and 25 stent segments further received invasive coronary angiography (ICA). In all included patients, the coronary artery enhancement was compared between the high and low HR groups. In patients with ICA performed, the image quality improvement and diagnostic effectiveness for detection of significant coronary segments stenosis (>50%) were compared between the conventional CCTA and subtraction CCTA and between the high HR group and low HR group, respectively. All enrolled patients got sufficient coronary artery enhancement. In patients with ICA performed, receiver operating characteristic (ROC) curve analysis showed that the area under the curve (AUC) for the diagnosis of significant stenosis was 0.93 in subtraction CCTA and 0.73 in conventional CCTA (p < 0.05). Furthermore, there were no significant differences in image quality improvement, specificity, positive predictive value and accuracy between the high HR group and low HR group. The new subtraction CCTA method broadened the clinical availability for patients with high HR.

Ferritin Nanocaged Doxorubicin Potentiates Chemo-Immunotherapy against Hepatocellular Carcinoma via Immunogenic Cell Death.

Although immunotherapy of hepatocellular carcinoma using immune checkpoint inhibitors has achieved certain success, only a subset of patients benefits from this therapeutic strategy. The combination of immunostimulatory chemotherapeutics represents a promising strategy to enhance the effectiveness of immunotherapy. However, it is hampered by the poor delivery of conventional chemotherapeutics. Here, it is shown that H-ferritin nanocages loaded with doxorubicin (DOX@HFn) show potent chemo-immunotherapy in hepatocellular carcinoma tumor models. DOX@HFn is constructed with uniform size, high stability, favorable drug loading, and intracellular acidity-driven drug release. The receptor-mediated targeting of DOX@HFn to liver cancer cells promote cellular uptake and tumor penetration in vitro and in vivo. DOX@HFn triggers immunogenic cell death to tumor cells and promotes the subsequent activation and maturation of dendritic cells. In vivo studies in H22 subcutaneous hepatoma demonstrate that DOX@HFn significantly inhibits the tumor growth with >30% tumors completely eliminated, while alleviating the systemic toxicity of free DOX. DOX@HFn also exhibits robust antitumor immune response and tumoricidal effect in a more aggressive Hepa1-6 orthotopic liver tumor model, which is confirmed by the in situ magnetic resonance imaging and transcriptome sequencing. This study provides a facile and robust strategy to improve therapeutic efficacy of liver cancer.

Transplanting neurofibromatosis-1 gene knockout neural stem cells improve functional recovery in rats with spinal cord injury by enhancing the mTORC2 pathway.

The poor survival and low efficiency of neuronal differentiation limits the therapeutic effects of transplanted neural stem cells in the treatment of spinal cord injury. Neurofibromatosis-1 (NF-1) is a tumor suppressor gene that restricts the rapid and abnormal growth and differentiation of neural cells. In the present study, lentiviral vectors were used to knock out NF-1, Ricotr (the core member of mTORC2) or NF-1+Ricotr in neural stem cells in vitro, and the NF-1, Ricotr or NF-1+Ricotr knockout neural stem cells were transplanted at the lesion site in a rat model of spinal cord injury (SCI). We first demonstrated that targeted knockout of NF-1 had an antiapoptotic effect and improved neuronal differentiation by enhancing the mTORC2/Rictor pathway of neural stem cells in vitro. Subsequently, transplanting NF-1 knockout neural stem cells into the injured site sufficiently promoted the tissue repair and functional recovery of rats with spinal cord injury by enhancing the survival and neuronal differentiation of grafted neural stem cells. Collectively, these findings reveal a prominent role of NF-1 in neural stem cell biology, which is an invaluable step forward in enhancing the benefit of neural stem cell-mediated regenerative cell therapy for spinal cord injury and identifies the transplantation of NF-1 knockout neural stem cells as a promising strategy for spinal cord injury.

Multiparametric quantitative MRI for the evaluation of dysthyroid optic neuropathy.

OBJECTIVE: To evaluate the ability of quantitative MRI parameters for predicting dysthyroid optic neuropathy (DON). METHODS: We retrospectively collected and analyzed the clinical features and 3.0 T MRI data of 59 patients with Graves orbitopathy (GO), with (n = 26) and without DON (n = 33). We compared MRI quantitative parameters, including the modified muscle index (mMI), proptosis, volume of intra-orbital fat, mean apparent diffusion coefficient value, and T2 value of the optic nerve among patients with and without DON. A logistic regression analysis was performed to identify the risk factors associated with DON. Moreover, we performed a receiver operating characteristic curve analysis and decision curve analysis to evaluate the diagnostic performance of the identified parameters for DON. RESULTS: We studied 118 orbits (43 and 75 with and without DON, respectively). The mMI and mean T2 value of the optic nerve were significantly greater in orbits with DON (p < 0.001). A greater mMI at 21 mm (odds ratio (OR), 1.039; 95% confidence interval (CI): 1.019, 1.058) and higher mean T2 value of the optic nerve (OR, 1.035; 95% CI: 1.017, 1.054) were associated with a higher risk of DON. A model combining the mMI at 21 mm and mean T2 values for the optic nerve effectively predicted DON in patients with GO, with a sensitivity and specificity of 95.3% and 76%, respectively. CONCLUSION: A quantitative MRI parameter combining the mMI at 21 mm and mean T2 value of the optic nerve can be an effective imaging marker for identifying DON. KEY POINTS: • Patients with GO and DON had greater mMI than those without DON. • Optic nerves in patients with DON demonstrated an increased T2 value. • The quantitative MRI parameter combining the mMI at 21 mm and mean T2 value of the optic nerve is the most effective method for diagnosing DON.

Utility of multi-parametric quantitative magnetic resonance imaging of the lacrimal gland for diagnosing and staging Graves' ophthalmopathy.

PURPOSE: To explore radiological changes of the lacrimal gland (LG) in Graves' ophthalmopathy (GO) based on multi-parametric quantitative MRI and its clinical utility in LG diagnosis and activity in GO. METHODS: We enrolled 99 consecutive patients with GO (198 eyes) and 12 Graves' Disease (GD) patients (24 eyes) from July 2018 to June 2020. Clinical, laboratory, and MRI data were collected at the first visit. Based on clinical activity scores, eyes with GO were subdivided into active and inactive groups. T2-relaxation time (T2) and the absolute reduction in T1-relaxation time (ΔT1) were determined. After MRI and processing, we performed descriptive data analysis and group comparisons. Novel logistic regression predictive models were developed for diagnosing and staging GO. Diagnostic performance of MRI parameters and models was assessed by receiver operating characteristic curve analysis. RESULTS: LG in GO group had significantly higher T2 and ΔT1 values than the GD group [106.25(95.30,120.21) vs. 83.35(78.15,91.45), P<0.001, and 662.62(539.33,810.95) vs. 547.35(458.62,585.57), P = 0.002, respectively]. The GO group had higher T2 of LG indicating higher disease activity [110.93(102.54,127.67) vs. 93.29(87.06,101.96), P < 0.001]. Combining T2 and ΔT1 values of LG, Model I had higher diagnostic value for distinguishing GO from GD (AUC=0.94, 95 %CI: 0.89,0.99, P<0.001). Meanwhile, T2 of LG had higher diagnostic value for grading GO activity (AUC = 0.84, 95 %CI: 0.76,0.92, P<0.001). CONCLUSIONS: Multi-parametric quantitative MRI parameters of the LG in GO were significantly altered. Novel models combining LG T2 and ΔT1 values showed excellent predictive performances in diagnosing GO. Furthermore, T2 of LG showed practical utility for staging GO.

Saphenous Artery Perforator Flaps in Minipigs: Anatomical Study and a New Experimental Model.

This study describes the anatomy of the saphenous artery (SA) perforators in minipigs and the development of a new animal model. First, the anatomic characteristics of the SA and perforators in minipigs were examined after latex-lead oxide perfusion. Subsequently, the right hind limbs of 10 minipigs were used to generate capillary perforator flaps (group A; utilizing the SA and 5.5 cm of deep fascia above the knee), while all perforators of the left hind limbs were reserved (group B). Four additional minipigs were used to evaluate SA perforator flaps with capillary perforators plus sarcolemma and a small amount of muscle (group C). Preoperative and postoperative CTA of both hind limbs confirmed that all perforators were ligated in groups A and C. The average length of the SA was 14.86 ± 0.76 mm. The diameters of the SA at initiation, the medial tibial condyle, and the medial malleolus were 1.73 ± 0.15 mm, 1.50 ± 0.12 mm, and 1.30 ± 0.13 mm, respectively. There were 7.09 ± 1.16 perforators per hind limb, with an average diameter of 0.40 ± 0.13 mm (range, 0.10-0.78 mm), and the majority (96.2%) had a diameter >0.2 mm. The survival rates of the flaps in groups A, B, and C were 32 ± 39%, 100%, and 60.2 ± 17%, respectively. The position of the SA in minipigs is constant, its diameter is relatively large, and it has many perforators, allowing it to be used as a reliable model of perforator flaps, including capillary perforator flaps.

A versatile UCST-type composite microsphere for image-guided chemoembolization and photothermal therapy against liver cancer.

The development of novel chemoembolization agents to improve the treatment efficacy of transarterial chemoembolization (TACE) against liver cancer remains an urgent need in clinical practice. Herein, a versatile composite microsphere with upper critical solution temperature (UCST) properties was prepared to encapsulate polydopamine coated superparamagnetic iron oxide nanoparticles (SPION@PDA) and doxorubicin for simultaneous chemoembolization and photothermal therapy. The microspheres were spherical with an average diameter of 100-300 µm and exhibited favorable drug loading capability as well as strong photothermal effect. Strikingly, synergistic enhancement of photothermal therapy and chemotherapy against chemoresistant liver cancer cells was achieved. The in vivo therapeutic efficacy and safety evaluations were performed using rabbit VX2 liver tumor models. It was revealed that a single treatment of the combination of TACE and photothermal procedure resulted in 87.5% complete response and 12.5% partial response for the microsphere group, whereas all tumors in the control group progressed rapidly. Contrast-enhanced computed tomography (CT) evaluation indicated that the tumor diameter decreased by 91.5% after treatment, while that in the control group increased by 86.5%. The pathology-proven tumor necrotic rate was 87.2%, which significantly surpassed that of 65.2% in the control group. Furthermore, serum liver enzyme and biochemical studies indicated a temporary liver injury which can be fully recovered. Our findings demonstrated that this microsphere may be advantageous for enhancing therapeutic efficacy of TACE against liver cancer.

Revisiting the Blood Supply of the Rectus Femoris: A Case Report and Computed Tomography Angiography Study.

BACKGROUND: Rectus femoris necrosis is a rare but severe complication after anterolateral thigh flap (ALTF) harvesting. It has been previously reported that the blood supply of the rectus femoris (RF) often arises from the same source artery as the ALTF; however, precise descriptions of the relationship remain limited. This article revisits the blood supply of the RF based on computed tomography angiography (CTA) and analyzes the possible influence of the blood supply on the RF during ALTF harvesting. METHODS: Between December 2017 and June 2018, CTA images of the bilateral lower extremities of 25 patients were studied. The RF length, number, and diameter of branches at the entry point into muscle, location, and overall branch vessel origins were recorded. RESULTS: The average ± SD RF length was 384.73 ± 19.28 mm. There were 170 branches (mean ± SD, 3.4 ± 0.96 branches per thigh), mainly arising from the lateral circumflex femoral artery. The average ± SD diameter was 1.90 ± 0.51 mm. The first branch was located at 1/5 of the proximal site of the RF, and 91% of all branches were located above the midpoint. The RF vascularity can be classified into 2 types: type 1 (36% of sides) has branches that arise from a single artery (descending lateral circumflex femoral artery or femoral artery), whereas type 2 (64% of sides) has branches at the 1/5 proximal and 4/5 distal parts, which arise from different arteries. CONCLUSIONS: Preoperative CTA can provide anatomic information about the RF's nutrient vessel(s) and helps to optimize ALTF design.

Computed Tomography and Magnetic Resonance Imaging-aided Diagnosis of Primary Essential Cutis Verticis Gyrata: A Case Report with 5-year Follow-up and Review of the Literature.

BACKGROUND: Cutis Verticis Gyrata (CVG) is a rare skin disease caused by overgrowth of the scalp, presenting as cerebriform folds and wrinkles. CVG can be classified into two forms: primary (essential and non-essential) and secondary. The primary non-essential form is often associated with neurological and ophthalmological abnormalities, while the primary essential form occurs without associated comorbidities. DISCUSSION: We report on a rare case of primary essential CVG with a 4-year history of normal-colored scalp skin mass in the parietal-occipital region without symptom in a 34-year-old male patient, retrospectively summarizing his pathological and Computer Tomography (CT) and magnetic resonance imaging (MRI) findings. The major clinical observations on the CT and MR sectional images include a thickened dermis and excessive growth of the scalp, forming the characteristic scalp folds. With the help of CT and MRI Three-dimensional (3D) reconstruction techniques, the characteristic skin changes could be displayed intuitively, providing more evidence for a diagnosis of CVG. At the 5-year followup, there were no obvious changes in the lesion. CONCLUSION: Based on our observations, we propose that not all patients with primary essential CVG need surgical intervention, and continuous clinical observation should be an appropriate therapy for those in stable condition.

Pitavastatin attenuates atherosclerosis by suppressing NF-κB signaling in a high-cholesterol diet plus balloon catheter injury rabbit model.

Atherosclerosis (AS) induced by endothelial cell (EC) dysfunction significantly contributes to the onset and development of cardiovascular disease. Pitavastatin is a member of the lipid-lowering drugs, statins that are widely used in clinics. In the current study, we evaluated the effect of pitavastatin on AS and nuclear factor-kappa-light-chain-enhancer of activated B cells (NF-κB) signaling in abdominal aortic ECs. We induced AS in rabbits by high-cholesterol diet plus balloon catheter injury. The anti-AS effect of pitavastatin was assessed by measuring the intima-media thickness of the abdominal aorta, minimal lumen area (MLA), minimal lumen diameter (MLD), and other hemodynamic parameters. In addition, we measured the production of total cholesterol (CHOL, high density lipoproteins (HDL), low-density lipoprotein cholesterol (LDL-c), and triglycerides (TG) in the rabbits. To explore the underlying mechanism of pitavastatin on atherosclerosis, we isolated abdominal aortic ECs and determined the activity of NF-κB signaling. In our model, we found that the affected animals had structural impairments of the heart and arteries: reduced left atrium diameter, right ventricular internal diameter, MLA, and MLD and increased interventricular septal thickness, left ventricular internal diameter, left ventricular posterior wall thickness, right atrium diameter, and intima-media thickness of abdominal aorta. Most of these changes were restored by administration of pitavastatin. Moreover, concentrations of plasma lipids were also attenuated by pitavastatin. At the molecular level, pitavastatin inhibited the expression of NF-κB and Bax and induced the production of IL-1ß and Bcl-2. In addition, we demonstrated that the anti-AS effect of pitavastatin depends on restoring normal function of ECs and eliminating dysfunctional ECs by inducing apoptosis.

An Individually Optimized Protocol of Contrast Medium Injection in Enhanced CT Scan for Liver Imaging.

Objective: To investigate the effectiveness of a new individualized contrast medium injection protocol for enhanced liver CT scan. Methods: 324 patients who underwent plain and dual phase enhanced liver CT were randomly assigned to 2 groups: G1 (n = 224, individualized contrast medium injection protocol); G2 (n = 100, standard contrast medium injection with a dose of 1.5 ml/kg). CT values and ΔHU (CT values difference between plain and enhanced CT) of liver parenchyma and tumor-liver contrast (TLC) during hepatic arterial phase (HAP) and portal venous phase (PVP) and contrast medium dose were measured. The tumor conspicuity of hepatocellular carcinoma (HCC) between two groups was independently evaluated by two radiologists. Results: The mean contrast medium dose of G1 was statistically lower than that of G2. There were no significantly statistical differences in CT values and ΔHU of liver parenchyma during HAP, TLC values during HAP, and PVP between two groups. The CT values and ΔHU of liver parenchyma during PVP of G2 were significantly higher than those of G1. Two independent radiologists were both in substantial conformity in grading tumor conspicuity. Conclusion: Using the individually optimized injection protocol might reduce contrast medium dose without impacting on the imaging quality in enhanced liver CT.

The performance of transrectal ultrasound in the diagnosis of seminal vesicle defects: a comparison with magnetic resonance imaging.

Obstructive azoospermia (OA) is one of the most common causes of male infertility. Transrectal ultrasound (TRUS) has been used to diagnose OA for many years. From 2009 to 2013, we evaluated a prospective cohort of 1249 patients with suspected OA using TRUS. It was found that dilation of the ejaculatory duct (ED) (29.9%, 374/1249) was the most common cause of OA, followed by seminal vesicle (SV) abnormalities (28.5%, 356/1249). A total of 237 patients were diagnosed with congenital defects (agenesis and/or hypoplasia) of the SV, constituting more than half of the cases of SV disease in OA (19.0%, 237/1249). In contrast to ED, congenital defects of the SV could not be corrected with surgical treatment. Therefore, it is meaningful to compare TRUS and magnetic resonance imaging (MRI) for accurate diagnosis of SV defects. Among our patients, 30 with agenesis or/and hypoplasia of the SV on TRUS were further evaluated using pelvic MRI within 2 years, with the objective of verifying the TRUS results. The concordance rate for diagnosing congenital defects of the SV was 73.3% (22/30). We concluded that TRUS is a reliable and convenient method for diagnosing agenesis or hypoplasia of the SV in OA patients with a high concordance with MRI while MRI is useful in patients with inconclusive TRUS findings.