Arterial spin labeling MR image denoising and reconstruction using unsupervised deep learning

Arterial spin labeling (ASL) imaging is a powerful magnetic resonance imaging technique that allows to quantitatively measure blood perfusion non-invasively, which has great potential for assessing tissue viability in various clinical settings. However, the clinical applications of ASL are currently limited by its low signal-to-noise ratio (SNR), limited spatial resolution, and long imaging time. In this work, we propose an unsupervised deep learning-based image denoising and reconstruction framework to improve the SNR and accelerate the imaging speed of high resolution ASL imaging. The unique feature of the proposed framework is that it does not require any prior training pairs but only the subject's own anatomical prior, such as T1-weighted images, as network input. The neural network was trained from scratch in the denoising or reconstruction process, with noisy images or sparely sampled k-space data as training labels. Performance of the proposed method was evaluated using in vivo experiment data obtained from 3 healthy subjects on a 3T MR scanner, using ASL images acquired with 44-min acquisition time as the ground truth. Both qualitative and quantitative analyses demonstrate the superior performance of the proposed txtc framework over the reference methods. In summary, our proposed unsupervised deep learning-based denoising and reconstruction framework can improve the image quality and accelerate the imaging speed of ASL imaging.     

黄芩苷改善肿瘤缺氧微环境抑制乳腺癌移植瘤的生长＊

目的 通过观察黄芩苷对乳腺癌组织毛细血管通透性（Capillary Vessel Permeability，CVP）、赖氨酰氧化酶（Lysyl Oxidase，LOX）及血清丙二醛（Malondialdehyde，MDA）等相关指标的影响，探讨黄芩苷可能的抗乳腺癌作用机制。方法 通过在裸鼠皮下接种MDA-MB-231乳腺癌细胞株建立乳腺癌移植瘤模型；实验分为模型组、黄芩苷组、阿霉素组、黄芩苷+阿霉素组。于接种第7日开始：黄芩苷组每天灌胃黄芩苷水溶液（100 mg·kg^-1），连续14天；阿霉素组每3天腹腔注射一次阿霉素（5mg·kg^-1），共用药5次；模型组每天灌胃生理盐水（10 mL·kg^-1），连续14天；黄芩苷+阿霉素组每天灌胃黄芩苷水溶液（100 mg·kg^-1），连续14天，并每3天腹腔注射一次阿霉素5 mg·kg^-1，共5次。给药期间监测移植瘤体积；紫外可见分光光度计620 nm下测OD值来反映黄芩苷对肿瘤毛细血管通透性的影响；硫代巴比妥酸（Thiobarbituric acid，TBA）比色法检测黄芩苷对裸鼠血清中丙二醛（MDA）的影响；免疫组化染色法检测乳腺癌组织中赖氨酰氧化酶（LOX）的表达情况。结果 ①与模型组比较，黄芩苷组、阿霉素组、黄芩苷+阿霉素组瘤体重量均明显减轻（P<0.05）；黄芩苷+阿霉素组瘤体重量较阿霉素组明显减轻（P<0.05）。②与模型组比较，黄芩苷组降低乳腺癌组织毛细血管的通透性，而阿霉素组则增加肿瘤组织中毛细血管的通透性，差异均具有统计学意义（P<0.05）。③黄芩苷组能够明显抑制荷瘤裸鼠血清MDA的表达，与模型组比较差异有显著统计学意义（P<0.01）；阿霉素组促进MDA的表达，与模型组比较差异有统计学意义；黄芩苷+阿霉素组促进MDA的表达，与模型组比较差异无统计学意义。④与模型组比较，黄芩苷组裸鼠乳腺癌组织LOX的表达显著下调（P<0.01），阿霉素组肿瘤组织中LOX表达增加（P<0.05）；黄芩苷+阿霉素组能下调裸鼠乳腺癌组织LOX的表达，与模型组比较差异无统计学意义。结论 黄芩苷能够明显抑制乳腺癌移植瘤的生长，其机制可能与黄芩苷降低肿瘤组织毛细血管的通透性，抑制裸鼠血清中丙二醛、乳腺癌组织中赖氨酰氧化酶的表达，从而改变肿瘤缺氧微环境有关。     

Quality of life after hemifacial spasm surgery: French versions of the HFS-8 and HFS-30 questionnaires

ObjectivesThe aim of the present study was to assess quality of life before and after surgery for hemifacial spasm, in order to validate two specific quality of life scales translated in French. Surgical results and complications were reported.Material and methodsTwenty-three patients with hemifacial spasm treated by microvascular decompression were retrospectively included. The HFS-8 and HFS-30 quality of life scales were translated from English into French using a forward-backward method and implemented on patients at least one year after surgery.ResultsMedian HFS-8 and HFS-30 values were respectively 16 ± 12.5 (range: 8–20.5) and 38 ± 38.5 (range: 23–61.5) before surgery and 0.5 ± 4.5 (range: 0–4.5) and 5 ± 17.5 (range: 1–18.5) after surgery, showing significant improvement in quality of life (P < 0.001). The internal consistency of both scales was excellent (Cronbach's alpha > 0.9), and they were significantly correlated (Pearson coefficient = 0.95; 95% CI [0.91; 0.98]; P < 0.0001). Success rates were 83% and 91%, respectively, after primary and revision surgeries. Complications were transient with minor consequences in 80% of cases, but could impact quality of life when lasting.ConclusionsThese results support the validity of the French versions of HFS-8 and HFS-30. Microvascular decompression is a safe and effective treatment for hemifacial spasm, and these scales are reliable tools to assess postoperative quality of life.     

Deep learning radiomics based on contrast enhanced computed tomography predicts microvascular invasion and survival outcome in early stage hepatocellular carcinoma

ObjectiveTo evaluate the performance of a deep learning (DL)-based radiomics strategy on contrast-enhanced computed tomography (CT) to predict microvascular invasion (MVI) status and clinical outcomes, recurrence-free survival (RFS) and overall survival (OS) in patients with early stage hepatocellular carcinoma (HCC) receiving surgical resection.MethodsAll 283 eligible patients were included retrospectively between January 2008 and December 2015, and assigned into the training cohort (n = 198) and the testing cohort (n = 85). We extracted radiomics features via handcrafted radiomics analysis manually and DL analysis of pretrained convolutional neural networks via transfer learning automatically. Support vector machine was adopted as the classifier. A clinical-radiological model for MVI status integrated significant clinical features and the radiological signature generated from the radiological model with the optimal area under the receiver operating characteristics curve (AUC) in the testing cohort. Otherwise, DL-based prognostic models were constructed in prediction of recurrence and mortality via Cox proportional hazard analysis.ResultsThe clinical-radiological model for MVI represented an AUC of 0.909, accuracy of 96.47%, sensitivity of 90.91%, specificity of 97.30%, positive predictive value of 83.33%, and negative predictive value of 98.63% in the testing cohort. The clinical-radiological models for identification of RFS and OS outperformed prediction performance of the clinical model or the DL signature alone. The DL-based integrated model for prognostication showed great predictive value with significant classification and discrimination abilities after validation.ConclusionsThe integrated DL-based radiomics models achieved accurate preoperative prediction of MVI status, and might facilitate predicting tumor recurrence and mortality in order to optimize clinical decisions for patients with early stage HCC.     

Nonlinear elasticity of biological basement membrane revealed by rapid inflation and deflation

Basement membrane (BM) is a thin layer of extracellular matrix that surrounds most animal tissues, serving as a physical barrier while allowing nutrient exchange. Although they have important roles in tissue structural integrity, physical properties of BMs remain largely uncharacterized, which limits our understanding of their mechanical functions. Here, we perform pressure-controlled inflation and deflation to directly measure the nonlinear mechanics of BMs in situ. We show that the BMs behave as a permeable, hyperelastic material whose mechanical properties and permeability can be measured in a model-independent manner. Furthermore, we find that BMs exhibit a remarkable nonlinear stiffening behavior, in contrast to the reconstituted Matrigel. This nonlinear stiffening behavior helps the BMs to avoid the snap-through instability (or structural softening) widely observed during the inflation of most elastomeric balloons and thus maintain sufficient confining stress to the enclosed tissues during their growth.

Basement membrane (BM) is a thin layer of fibrous matrix separating cells from the connecting tissues, which functions as a physical barrier and widely exists across multicellular organisms (1). The BM is typically composed of laminins, collagen IV, nidogens, and proteoglycans; laminin and collagen IV are the major components that constitute networks forming the structure of the BM, and nidogen and proteoglycans are associated with the laminin and collagen IV networks. As a physical barrier, the structural and mechanical properties of BM are important in the organization and morphogenesis of tissues and organs as well as in the maintenance of adult functions (2); abnormal BM has been associated with a variety of diseases such as cancer (3). For example, in metastasis, cancer cells must invade through BMs to escape from the primary tumor—a process that causes 90% of cancer-related death (4). Indeed, breaks in BMs can be observed in malignant tumors (5). Thus, mechanical properties of the BM are considered to play important roles in regulating cancer cell invasion (6, 7). Furthermore, as a physical barrier differentiating different parts of tissues, BMs are required to be permeable to small molecules to allow exchange of water and nutrients; the permeability of BM is thus one of the essential kinetic parameters regulating biomolecule exchange and activities of internal cells (8, 9). Given the importance of BMs as a semipermeable barrier maintaining tissue structural integrity, however, their permeability and mechanical properties remain largely unknown, mainly due to the lack of direct measurement methods, especially in situ. This limits our understanding of the physical role of BMs in various physiological and pathological processes such as tumor development and angiogenesis.Determining the mechanical properties of intact BMs in situ is challenging because of their irregular shape, small thickness, and tight connection to the cells inside. Due to these limitations, conventional mechanical tests such as tensile, compression, and bending tests are difficult to be applied to characterize the mechanical behavior of the BM in situ. Instead, previous measurements had been carried out on fragmented BMs isolated from various tissues (e.g., via atomic force microscopy [AFM] indentation) and found that the BM stiffness ranges from ∼kPa to ∼MPa (10–17). In addition, a constitutive relationship is required to extract the material parameters such as elastic modulus and permeability from these experimental measurements. However, like most biological tissues, a reliable constitutive model for the BM is not yet available, causing additional difficulties in obtaining its mechanical parameters from most traditional experiments.In this work, we demonstrate an in situ method to simultaneously measure both the elastic properties and permeability of intact BM in breast cancer spheroid by recording the deflation process of an inflated BM filled with phosphate buffered saline (PBS) by microinjection without requiring complex sample preparation and post-data processing. During the deflation of the BM, its elastic retraction generates a pressure difference to drive the liquid flow through the membrane; the liquid flux can be calculated from the reduction of the intact BM diameter. With the BM thickness measured by transmission electron microscopy (TEM), we can determine the shear modulus, permeability, and diffusivity of the intact BM. Moreover, we find from our measurements that the elasticity of BM is highly nonlinear with a strong strain-stiffening effect. Furthermore, we discuss the possible impact of the strain-stiffening effects of BM on its functions.     

Hemifacial spasm caused by a tortuous recurrent perforating artery: A case report

IntroductionWhen the culprit vessel in hemifacial spasm (HFS) is hard to determine, this is a challenge in microvascular decompression (MVD) surgery. In such a situation, small arteries such as perforators to the brainstem might be suspected. But small arteries are omnipresent near the facial nerve root exit/entry zone (fREZ). How to decide whether a given small artery is responsible for HFS is unclear.MethodWe report a case with a previously unreported form of neurovascular impingement, in which the culprit was found to be the recurrent perforating artery (RPA) from the anterior inferior cerebellar artery (AICA). An aberrant anatomic configuration of the RPA was found intraoperatively, which we thought was responsible for generating focal pressure on the facial nerve.Case reportA 62-year-old woman presented with a 1-year history of paroxysmal but increasingly frequent twitching in her right face. MRI showed tortuosity of the vertebral artery and apparently marked neurovascular impingement on the asymptomatic left side, while only the right AICA could be implicated as the possible culprit. Hemifacial spasm was diagnosed based on the typical clinical manifestation, and MVD was performed. The pre-meatal segment of the AICA was found not to be impinging the facial nerve at any susceptible portion near the fREZ: root exit point, attached segment, or root detachment point. The real culprit was in fact the RPA. This occult culprit vessel was tortuous, forming a coil-shaped twist which was interposed between the facial nerve and the intermediate nerve near the root detachment point. Focal pressure atrophy of the nerve was clearly observed at the compressing site. The patient achieved total spasm relief immediately after surgery, and remained spasm-free at 1-year follow-up, without any postoperative complications.ConclusionMVD is the only curative treatment for hemifacial spasm, but with a failure rate of around 10%. Mistaking the real culprit has been reported to be the most likely reason for surgical failure. Therefore, intraoperative identification of atypical occult forms of vascular compression is of importance to improve surgical outcome. In the present case, the RPA formed a coil-shaped twist, which inflicted focal vascular compression causing hemifacial spasm. We recommend careful inspection of the recurrent perforating artery during MVD for HFS, and decompressing any such neurovascular impingement.     

A novel prognostic nomogram based on microvascular invasion and hematological biomarkers to predict survival outcome for hepatocellular carcinoma patients

PurposeThis study aimed to develop and validate a nomogram for overall survival (OS) prediction in which combine clinical characteristics and hematological biomarkers in patients with hepatocellular carcinoma (HCC).MethodsWe performed a retrospective analysis of 807 HCC patients. All the clinical data of these patients were collected through electronic medical record (EMR). The independent predictive variables were identified by cox regression analysis. We tested the accuracy of the nomograms by discrimination and calibration, and then plotted decision curves to assess the benefits of nomogram-assisted decisions in a clinical context, and compared with the TNM staging systems and microvascular invasion (MVI) on HCC prognosis.ResultsThe primary cohort consisted of 545 patients with clinicopathologically diagnosed with HCC from 2008 to 2013, while 262 patients from 2014 to 2016 in external validation cohort. Variables included in the nomograms were TNM Stage, microvascular invasion (MVI), alpha fetoprotein (AFP), platelet to lymphocyte ratio (PLR) and prothrombin time (PT). The C-index of nomogram was 0.768, which was superior than the C-index of TNM Stage (0.660, P < 0.001) and MVI(0.664, P < 0.001) alone in the primary cohort. In the validation cohort, the models had a C-index of 0.845, and were also statistically higher when compared to C-index values for TNM Stage (0.687, P < 0.001) and MVI(0.684, P < 0.001). Calibration curves showed adequate calibration of predicted and reported OS prediction throughout the range of HCC outcomes. Decision curve analysis demonstrated that the nomogram was clinically useful than the TNM Stage and MVI alone. Moreover, patients were divided into three distinct risk groups for OS by the nomogram: low risk group, middle risk group and a high risk group, respectively.ConclusionThe nomogram presents more accurate and useful prognostic power, which could be used to predict OS for patients with HCC.     

脑干听觉诱发电位在面肌痉挛显微血管减压术中的应用价值

目的探讨脑干听觉诱发电位（BAEPs）V波潜伏期和（或）波幅的变化与面肌痉挛（HFS）显微血管减压术（MVD）后听力损失的应用价值。 方法选取中日友好医院神经外科自2015年9月至2019年8月行MVD治疗的HFS患者的临床资料，分析MVD始末BAEPs的V波潜伏期和波幅的变化以及手术前后听力状况的改变，听力学评估采用平均纯音听力阈值及言语识别率改变。根据美国耳鼻咽喉头颈外科学会分级方法，将术后患者听力分为听力未明显下降组和听力明显下降组。收集术中全程的BAEPs改变，并将BAEPs的V波术中改变分为：无显著异常，单纯V波潜伏期（LwV）延长>1.5 ms，单纯V波波幅（AwV）下降>50%，LwV延长>1.5 ms且AwV下降>50%，LwV延长>1.5 ms或AwV下降>50%，对5组分类模式下术后听力损伤程度与分组的相关性进行统计分析，并分析4组BAEPs改变对术后听力损伤的预测价值。 结果本研究纳入的1009例行MVD治疗的HFS患者中，943例患者听力未明显下降，66例患者术后听力异常，术中BAEPs监测波形无显著改变，术后出现听力下降5例（0.6%）；术中仅LwV延长>1.5 ms，术后出现听力下降4例（18.2%）；术中仅AwV降低>50%，术后出现听力下降19例（25.0%）；术中"LwV延长>1.5 ms且AwV降低>50%"，术后出现听力下降38例（64.4%）；术中"LwV延长>1.5 ms或AwV降低>50%"，术后出现听力下降61例（38.8%）。各组的阳性预测值比较，结果显示"LwV延长>1.5 ms且AwV降低>50%"最高；"LwV延长>1.5 ms或AwV下降>50%"组的敏感度最高；"LwV延长>1.5 ms且AwV下降>50%"组的特异度最强。 结论术中BAEPs监测可为MVD术者提供听力参考。术末V波潜伏期延长1.5 ms且波幅降低50%以上阳性预测值最高。术中根据BAEPs监测结果及时调整手术策略，可有效改善术后听力障碍的发生率。     

Predictive value of intraoperative blink reflex monitoring for surgical outcome during microvascular decompression for hemifacial spasm

ObjectiveTo investigate the prognostic and predictive value of intraoperative blink reflex (BR) monitoring during microvascular decompression (MVD) for hemifacial spasm (HFS).MethodsWe retrospectively reviewed 41 patients with HFS undergoing MVD with intraoperative BR and lateral spread response (LSR) monitoring. Facial spasm was evaluated for six months postoperatively.ResultsThe BR resolved in 38 patients and persisted in three after MVD. For patients who exhibited BR resolution, 1-day, 1-month, and 6-month follow-ups revealed that 35 (92.1%), 35 (92.1%), and 38 (100%) patients had spasm resolution, respectively. However, of the three patients with persistent BR, one (33.3%), one (33.3%), and zero (0%) patients exhibited spasm resolution at the three corresponding follow-ups. We found a statistically significant difference in spasm resolution between the persistent and resolved BR groups at six months postoperatively. A comparison between intraoperative BR and LSR monitoring revealed that BR was a better predictor of clinical outcomes.ConclusionsIntraoperative BR monitoring is a potentially useful tool to help facilitate an adequate decompression and is a reliable prognostic predictor of surgical outcome.SignificanceThis study is the first to document the relationship between intraoperative BR monitoring and surgical outcome in patients with HFS.