Comparison of Tumor Non-specific and PD-L1 Specific Imaging by Near-Infrared Fluorescence/Cerenkov Luminescence Dual-Modality In-situ Imaging.

Background: Labeled antibodies are excellent imaging agents in oncology to non-invasively visualize cancer-related antigens expression levels. However, tumor tracer uptake (TTU) of specific antibodies in-vivo may be inferior to non-specific IgG in some cases. Objectives: To explore factors affecting labeled antibody visualization by PD-L1 specific and non-specific imaging of nude mouse tumors. Methods: TTU was observed in RKO model on Cerenkov luminescence (CL) and near-infrared fluorescence (NIRF) imaging of radionuclide 131I or NIRF dyes labeled Atezolizumab and IgG. A mixture of NIRF dyes labeled Atezolizumab and 131I-labeled IgG was injected, and TTU was observed in the RKO and HCT8 model by NIRF/CL dual-modality in-situ imaging. TTU were observed by 131I-labeled Atezolizumab and IgG in-vitro distribution. Results: Labeled IgG concentrated more in tumors than Atezolizumab. NIRF/CL imaging in 24 to 168 h showed that TTU gradually decreased over time, which decreased more slowly on CL imaging compared to NIRF imaging. The distribution data in-vitro showed that TTU of 131I-labeled IgG was higher than that of 131I-labeled Atezolizumab at any time point. Conclusion: Non-specific IgG may not be suitable as a control for Atezolizumab in comparing tumor PD-L1 expression in nude mice via labeled antibody optical imaging under certain circumstances.

A feasibility study of in vivo quantitative ultra-short echo time-MRI for detecting early cartilage degeneration.

OBJECTIVES: To explore the feasibility of Ultra-short echo time (UTE) - MRI quantitative imaging in detecting early cartilage degeneration in vivo and underlying pathological and biochemical basis. METHODS: Twenty volunteers with osteoarthritis (OA) planning for total knee arthroplasty (TKA) were prospectively recruited. UTE-MRI sequences and conventional sequences were performed preoperatively. Regions of interests (ROIs) were manually drawn on the tibial plateau and lateral femoral condyle images to calculate MRI values. Cartilage samples were collected during TKA according to the preset positions corresponding to MR images. Pathological and biochemical components of the corresponding ROI, including histological grading, glycosaminoglycan (GAG) content, collagen integrity, and water content were obtained. RESULTS: 91 ROIs from volunteers of 7 males (age range: 68 to 78 years; 74 ± 3 years) and 13 females (age range: 57 to 79 years; 67 ± 6 years) were evaluated. UTE-MTR (r = -0.619, p < 0.001), UTE-AdiabT1ρ (r = 0.568, p < 0.001), and UTE-T2* values (r = -0.495, p < 0.001) showed higher correlation with Mankin scores than T2 (r = 0.287, p = 0.006) and T1ρ (r = 0.435, p < 0.001) values. Of them, UTE-MTR had the highest diagnostic performance (AUC = 0.824, p < 0.001). UTE-MTR, UTE-AdiabT1ρ and UTE-T2* value was mainly related to collagen structural integrity, PG content and water content, respectively (r = 0.536, -0.652, -0.518, p < 0.001, respectively). CONCLUSION: UTE-MRI have shown greater in vivo diagnostic value for early cartilage degeneration compared to conventional T2 and T1ρ values. Of them, UTE-MTR has the highest diagnostic efficiency. UTE-MTR, UTE-AdiabT1ρ, and UTE-T2* value mainly reflect different aspects of cartilage degeneration--integrity of collagen structure, PG content, and water content, respectively. CRITICAL RELEVANCE STATEMENT: Ultra-short echo time (UTE)-MRI has the potential to be a novel image biomarkers for detecting early cartilage degeneration in vivo and was correlated with biochemical changes of early cartilage degeneration. KEY POINTS: Conventional MR may miss some early cartilage changes due to relatively long echo times. Ultra-short echo time (UTE)-MRI showed the ability in identifying early cartilage degeneration in vivo. UTE-MT, UTE-AdiabT1ρ, and UTE-T2* mapping mainly reflect different aspects of cartilage degeneration.

Cerebral pulsatility in relation with various imaging markers of cerebral small vessel disease: a longitudinal community-based study.

Background: Cerebral pulsatility is thought to reflect arterial stiffness and downstream microvascular resistance. Although previous studies indicated cerebral pulsatility might closely relate to development of cerebral small vessel disease (SVD), yet evidence remain controversial and longitudinal data are rare. Objective: We aimed to explore relationships of cerebral pulsatility with severity and progression of various SVD imaging markers among the community-dwelling elderly. Design: A longitudinal cohort study. Methods: As part of the prospective community-based Shanghai Aging Study cohort, dementia- and stroke-free elderly were recruited for baseline assessment of cerebral pulsatility and SVD severity during 2010-2011 and traced for SVD progression during 2016-2017. Cerebral pulsatility was quantified for both anterior and posterior circulation with transcranial Doppler ultrasound. SVD imaging markers were measured with brain magnetic resonance imaging (MRI) including white matter hyperintensities (WMHs), enlarged perivascular spaces (ePVS), lacunes, and microbleeds. The cross-sectional and longitudinal relationships between cerebral pulsatility and SVD were analyzed by univariable and multivariable regression models. Results: Totally, 188 eligible subjects were included at baseline and out of them, 100 (53.19%) returned for a 7-year follow-up. At baseline, increased pulsatility of posterior circulation was independently associated with more periventricular WMH (PWMH) and ePVS in basal ganglia (BG-ePVS) but not with other SVD markers. Longitudinally, higher posterior pulsatility predicted greater PWMH progression in participants with hypertension (ß = 2.694, standard error [SE] = 1.112, p = 0.020), whereas pulsatility of anterior circulation was shown to prevent BG-ePVS progression among followed-up elderly (ß = -6.737, SE = 2.685, p = 0.012). However, no significant relationship was found between cerebral pulsatility and burden of lacunes or cerebral microbleeds. Conclusion: Higher pulsatility of posterior circulation could worsen PWMH progression, especially for participants with hypertension. But for development of ePVS, increased cerebral pulsatility could play a compensatory role among several healthy elderly. The distinct relationships between cerebral pulsatility and various SVD markers emphasized the importance of individualized SVD management.

Machine learning-based radiomics to differentiate immune-mediated necrotizing myopathy from limb-girdle muscular dystrophy R2 using MRI.

Objectives: This study aimed to assess the feasibility of a machine learning-based radiomics tools to discriminate between Limb-girdle muscular dystrophy R2 (LGMDR2) and immune-mediated necrotizing myopathy (IMNM) using lower-limb muscle magnetic resonance imaging (MRI) examination. Methods: After institutional review board approval, 30 patients with genetically proven LGMDR2 (12 females; age, 34.0 ± 11.3) and 45 patients with IMNM (28 females; age, 49.2 ± 16.6) who underwent lower-limb MRI examination including T1-weighted and interactive decomposition water and fat with echos asymmetric and least-squares estimation (IDEAL) sequences between July 2014 and August 2022 were included. Radiomics features of muscles were obtained, and four machine learning algorithms were conducted to select the optimal radiomics classifier for differential diagnosis. This selected algorithm was performed to construct the T1-weighted (TM), water-only (WM), or the combined model (CM) for calf-only, thigh-only, or the calf and thigh MR images, respectively. And their diagnostic performance was studied using area under the curve (AUC) and compared to the semi-quantitative model constructed by the modified Mercuri scale of calf and thigh muscles scored by two radiologists specialized in musculoskeletal imaging. Results: The logistic regression (LR) model was the optimal radiomics model. The performance of the WM and CM for thigh-only images (AUC 0.893, 0.913) was better than those for calf-only images (AUC 0.846, 0.880) except the TM. For "calf + thigh" images, the TM, WM, and CM models always performed best (AUC 0.953, 0.907, 0.953) with excellent accuracy (92.0, 84.0, 88.0%). The AUCs of the Mercuri model of the calf, thigh, and "calf + thigh" images were 0.847, 0.900, and 0.953 with accuracy (84.0, 84.0, 88.0%). Conclusion: Machine learning-based radiomics models can differentiate LGMDR2 from IMNM, performing better than visual assessment. The model built by combining calf and thigh images presents excellent diagnostic efficiency.

Glioma grade discrimination with dynamic contrast-enhanced MRI: An accurate analysis based on MRI guided stereotactic biopsy.

PURPOSE: To evaluate the diagnostic performance of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) metrics for glioma grading on a point-to-point basis. METHODS: Forty patients with treatment-naïve glioma underwent DCE-MR examination and stereotactic biopsy. DCE-derived parameters including endothelial transfer constant (Ktrans), volume of extravascular-extracellular space (ve), fractional plasma volume (fpv), and reflux transfer rate (kep) were measured within ROIs on DCE maps accurately matched with biopsies used for histologic grades diagnosis. Differences in parameters between grades were evaluated by Kruskal-Wallis tests. Diagnostic accuracy of each parameter and their combination was assessed using receiver operating characteristic curve. RESULTS: Eighty-four independent biopsy samples from 40 patients were analyzed in our study. Significant statistical differences in Ktrans and ve were observed between grades except ve between grade 2 and 3. Ktrans showed good to excellent accuracy in discriminating grade 2 from 3, 3 from 4, and 2 from 4 (area under the curve = 0.802, 0.801 and 0.971, respectively). Ve indicated good accuracy in discriminating grade 3 from 4 and 2 from 4 (AUC = 0.874 and 0.899, respectively). The combined parameter demonstrated fair to excellent accuracy in discriminating grade 2 from 3, 3 from 4, and 2 from 4 (AUC = 0.794, 0.899 and 0.982, respectively). CONCLUSION: Our study had identified Ktrans, ve and the combination of parameters to be an accurate predictor for grading glioma.

Application of CUBE-STIR MRI and high-frequency ultrasound in contralateral cervical 7 nerve transfer surgery.

OBJECTIVE: The objective of the study was to investigate the feasibility of CUBE-SITR MRI and high-frequency ultrasound for the structural imaging of the brachial plexus to exclude neoplastic brachial plexopathy or structural variation and measure the lengths of anterior and posterior divisions of the C7 nerve, providing guidelines for surgeons before contralateral cervical 7 nerve transfer. METHODS: A total of 30 patients with CNS and 20 with brachial plexus injury were enrolled in this retrospective study. All patients underwent brachial plexus CUBE-STIR MRI and high-frequency ultrasound, and the lengths of the anterior and posterior divisions of C7 nerve were measured before surgery. Precise length of anterior and posterior divisions of contralateral C7 nerve was measured during surgery. RESULTS: MRI-measured lengths of anterior and posterior divisions of C7 nerves were positively correlated with that measured during surgery (anterior division, r = 0.94, p < .01; posterior division, r = 0.92, p < .01). High agreement was found between MRI-measured and intra-surgery measured length of anterior and posterior divisions of C7 nerve by BLAD-ALTMAN analysis. Ultrasonography could feasibly image supraclavicular C7 nerve and recognize small variant branches derived from middle trunk of C7 nerve root, which could be dissected intra-operatively and confirmed by electromyography during the procedure of contralateral C7 nerve transfer. CONCLUSION: CUBE-STIR MRI had advantages for the imaging of the brachial plexus and measurement of the length of root-trunk-anterior/posterior divisions of C7 nerve. The clinical role of ultrasonography may be a simple way of evaluating general condition of C7 nerve and provide guidelines for contralateral C7 nerve transfer surgery.

Preliminary study on the assessment of early cartilage degeneration by quantitative ultrashort echo time magnetic resonance imaging in vivo.

Background: To investigate the feasibility of quantitative ultrashort echo time magnetic resonance imaging (UTE-MRI) techniques for assessing early cartilage degeneration in vivo. Methods: A total of 46 patients with knee pain due to osteoarthritis (OA) as the main complaint were recruited into the study. We performed MRI examinations with different quantitative UTE-MRI techniques, including UTE-based magnetization transfer (MT), UTE-adiabaticT1ρ, and UTE-T2* mapping on a 3.0T clinical magnetic resonance (MR) scanner (MR750; GE Healthcare, Milwaukee, WI, USA). Three regions of interest (ROIs) were manually drawn on the medial and lateral femoral condyles and the corresponding medial and lateral tibial plateaus, respectively. A total of 561 ROIs (12 ROIs for each knee) were finally included and divided into 3 groups according to the MRI Osteoarthritis Knee Score (MOAKS): normal (MOAKS 0, n=175), mild degeneration (MOAKS 1, n=283), and moderate degeneration (MOAKS 2, n=103). One-way analysis of variance (ANOVA) and Tamhane's T2 test were used to compare the differences of quantitative UTE-biomarkers among different groups. The analysis of Spearman's correlation was used to assess the correlation between the UTE-biomarkers and MOAKS grading. The diagnostic efficacy of different quantitative UTE-MRI techniques for detecting mild cartilage degeneration was evaluated using the receiver operating characteristic (ROC) curve. Results: The UTE-MT ratio (UTE-MTR) and the UTE-adiabatic T1ρ values had a moderate correlation with the MOAKS grading (r=-0.523, P<0.001; r=0.531, P<0.001, respectively), while the UTE-T2* was weakly correlated with the MOAKS grading (r=-0.396, P<0.001). For the normal group (MOAKS 0) and the mild group (MOAKS 1), the UTE-MTR values were 21.09%±3.03% and 17.30%±3.22%, respectively. The UTE-adiabatic T1ρ values were 30.43±6.26 ms and 35.05±8.78 ms for the normal group (MOAKS 0) and the mild group (MOAKS 1), respectively. With respect to the UTE-T2* values, the normal group (MOAKS 0) values were 21.49±3.96 ms and the mild group (MOAKS 1) values were 19.86±3.08 ms. All the differences between the 2 groups of the 3 UTE-MRI values were significant. The AUCs of the UTE-MTR, UTE-adiabatic T1ρ, and UTE-T2* mapping were 0.794, 0.732, and 0.651, respectively. Conclusions: The quantitative UTE-MRI techniques (UTE-MT, UTE-adiabatic T1ρ, and UTE-T2* mapping) show great promise for assessing the early degeneration of articular cartilage in vivo, and the UTE-MT and UTE-adiabatic T1ρ values show better diagnostic efficacy than UTE-T2* mapping.

MRI-Based Optimization Design of the Pre-Spinal Route of Contralateral C7 Nerve Transfer for Spastic Arm Paralysis.

Purpose: The prespinal route of contralateral cervical 7 nerve transfer developed by Prof. Wendong Xu helps realize the direct anastomosis of the bilateral cervical 7 nerves. However, 20% of operations still require a nerve graft, which leads to an unfavorable prognosis. This study aims to explore the optimized prespinal route with MRI to further improve the prognosis. Methods: The current study enrolled 30 patients who suffered from central spastic paralysis of an upper limb and who underwent contralateral cervical 7 nerve transfer via Prof. Xu's prespinal route through the anterior edge of the contralateral longus colli. MRI images were used to analyze the route length, vertebral artery exposure, and contralateral cervical 7 nerve included angle. Three prespinal routes were virtually designed and analyzed. The selected optimal route was applied to another 50 patients with central spastic paralysis of an upper limb for contralateral cervical 7 nerve transfer. Results: By the interventions on the 30 patients, the middle and posterior routes were shorter than the anterior route in length, but with no statistical difference between the two routes. Of 30 contralateral vertebral arteries, 26 were located at the posterior medial edge of the longus colli. The average included angles of the anterior, middle, and posterior routes were 108.02 ± 7.89°, 95.51 ± 6.52°, and 72.48 ± 4.65°, respectively. According to these data, the middle route was optimally applied to 50 patients, in whom the rate of nerve transplantation was only 4%, and no serious complications such as vertebral artery or brachial plexus injury occurred. Conclusion: The low rate of nerve transplantation in 50 patients and the absence of any serious complications in these cases suggests that the middle route is the optimal one.

Computed tomography perfusion imaging evaluation of angiogenesis in patients with pancreatic adenocarcinoma.

BACKGROUND: Pancreatic adenocarcinoma is one of the most common malignant tumors of the digestive system. More than 80% of patients with pancreatic adenocarcinoma are not diagnosed until late stage and have distant or local metastases. AIM: To investigate the value of computed tomography (CT) perfusion imaging in the evaluation of angiogenesis in pancreatic adenocarcinoma patients. METHODS: This is a retrospective cohort study. Patients with pancreatic adenocarcinoma and volunteers without pancreatic diseases underwent CT perfusion imaging from December 2014 to August 2017 in Huashan Hospital, Fudan University Shanghai, China. RESULTS: A total number of 35 pancreatic adenocarcinoma patients and 33 volunteers were enrolled. The relative blood flow (rBF), and relative blood volume (rBV) were significantly lower in patients with pancreatic adenocarcinoma than in the control group (P < 0.05). Conversely, the relative permeability in patients with pancreatic adenocarcinoma was significantly higher than that in controls (P < 0.05). In addition, rBF, rBV, and the vascular maturity index (VMI) were significantly lower in grade III-IV pancreatic adenocarcinoma than in grade I-II pancreatic adenocarcinoma (P < 0.05). Vascular endothelial growth factor (VEGF), CD105-MVD, CD34-MVD, and angiogenesis rate (AR) were significantly higher in grade III-IV pancreatic adenocarcinoma than in grade I-II pancreatic adenocarcinoma (P < 0.05). Significant correlations between rBF and VEGF, CD105-MVD, AR, and VMI (P < 0.01) were observed. Moreover, the levels of rBV were statistically significantly correlated with those of VEGF, CD105-MVD, CD34-MVD, and VMI (P < 0.01). CONCLUSION: Perfusion CT imaging may be an appropriate approach for quantitative assessment of tumor angiogenesis in pancreatic adenocarcinoma.

Altered Intra- and Inter-Network Functional Connectivity in Patients With Crohn's Disease: An Independent Component Analysis-Based Resting-State Functional Magnetic Resonance Imaging Study.

Background: Many studies have reported changes in the structure and function of several brain areas in patients with Crohn's disease (CD). However, little is known about whether the possible functional connectivity of resting-state networks (RSNs) is altered in CD patients. Purpose: Aim to investigate the intra- and inter-network alterations between related RSNs in patients with CD and the potential relationships between altered neuroimaging and CD clinical indices. Materials and Methods: In this study, 20 CD patients and 22 age- and sex-matched healthy controls were included. All participants underwent functional magnetic resonance imaging examination. We used independent component analysis (ICA) to explore the changes in RSNs and evaluated functional connectivity between different RSNs using functional network connectivity (FNC) analysis, and Pearson correlation analysis was performed between altered intra- and inter-network functional connectivity and CD clinical index. Results: Six CD-related RSNs were identified via ICA, namely the high visual, prime visual, language, dorsal default mode, posterior insula, and precuneus networks. Compared to healthy controls, patients with CD showed significant changes in prime visual and language networks. Additionally, the functional connectivity (FC) values of the left calcarine within the prime visual network were negatively correlated with CD duration. The inter-alterations showed that a significantly increased FNC existed between the language and dorsal default mode networks. Conclusion: The results showed CD-related changes in brain functional networks. This evidence provides more insights into the pathophysiological mechanisms of brain plasticity in CD.

Brain functional changes in patients with Crohn's disease: A resting-state fMRI study.

BACKGROUND: Crohn's disease (CD) is a chronic recurrent intestinal inflammatory disease, often accompanied by poor adaptation and excessive stress response. However, the potential neurological mechanisms of these symptoms have not yet been studied in-depth. OBJECTIVE: To investigate alterations in brain activity in patients with Crohn's disease and study the relationship between altered regions and clinical indices. METHODS: A total of 15 CD patients and 26 matched healthy controls were recruited. All participants underwent fMRI scans. The amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo) assessed differences in spontaneous regional brain activity. Differences between the groups were selected as seeds for functional connectivity (FC) analyses. Correlations between disease duration and ALFF/ReHo/FC values in abnormal regions were analyzed. RESULTS: Patients with CD had significantly higher ALFF values in the left superior frontal gyrus, anterior cingulate cortex, and supplementary motor area, and lower values in the left hippocampus. They also had higher ReHo values in the left anterior cingulate cortex, supplementary motor area, putamen, and the bilateral superior frontal gyri. FC strength in the left precentral and middle temporal gyri was found to be increased when the left superior frontal gyrus was used as the seed point. FC strength was also observed to be increased in the left postcentral, middle frontal gyri, inferior frontal orbital cortex, and right rolandic operculum when the left anterior cingulate cortex was used as the seed point. CONCLUSION: CD demonstrated abnormal neural activity and FC in various regions primarily associated with emotional, pain and cognitive-related functions, which provides more information to further understand the neural mechanisms of the disease.

Incident cerebral microbleeds and hypertension defined by the 2017 ACC/AHA Guidelines.

BACKGROUND: The cut-off for hypertension was lowered to blood pressure (BP) over 130/80 mmHg in the 2017 American College of Cardiology/American Heart Association (ACC/AHA) guideline. Whether the new definition of hypertension remains a potent risk factor of cerebral microbleeds (CMBs) is uncertain. We aimed to analyze the relationship between the new definition of hypertension and incident CMBs in a 7-year longitudinal community study. METHODS: This study is a sub-study of the Shanghai Aging Study (SAS). A total of 317 participants without stroke or dementia were included at baseline (2009-2011), and were invited to repeated clinical examinations and cerebral magnetic resonance imaging (MRI) at follow-up (2016-2018). CMBs at baseline and follow-up were evaluated on T2*-weighted gradient recalled echo (GRE) and susceptibility-weighted angiography (SWAN) sequence of MRI. We classified baseline BP into four categories: normal BP, elevated systolic BP, stage 1 hypertension and stage 2 hypertension according to the ACC/AHA guideline. We assessed the associations between BP categories and incident CMBs by generalized linear models. RESULTS: A total of 159 participants (median age, 67 years) completed follow-up examinations with a mean interval of 6.9 years. Both stage 1 and stage 2 hypertension at baseline were significantly related with a higher risk of incident CMBs (IRR 2.77, 95% CI, 1.11-6.91, P=0.028; IRR 3.04, 95% CI, 1.29-7.16, P=0.011, respectively), indicating dose-response effects across BP categories. Participants with ≥5 incident CMBs or incident CMBs in the deep locations all had baseline stage 1 and 2 hypertension. CONCLUSIONS: Participants with baseline stage 1 and stage 2 hypertension had a significantly higher risk of incident CMBs in this 7-year longitudinal community cohort.

White matter hyperintensities induce distal deficits in the connected fibers.

White matter hyperintensities (WMH) are common in elderly individuals and cause brain network deficits. However, it is still unclear how the global brain network is affected by the focal WMH. We aimed to investigate the diffusion of WMH-related deficits along the connecting white matters (WM). Brain magnetic resonance imaging data and neuropsychological evaluations of 174 participants (aged 74 ± 5 years) were collected and analyzed. For each participant, WMH lesions were segmented using a deep learning method, and 18 major WM tracts were reconstructed using automated quantitative tractography. The diffusion characteristics of distal WM tracts (with the WMH penumbra excluded) were calculated. Multivariable linear regression analysis was performed. We found that a high burden of tract-specific WMH was related to worse diffusion characteristics of distal WM tracts in a wide range of WM tracts, including the forceps major (FMA), forceps minor (FMI), anterior thalamic radiation (ATR), cingulum cingulate gyrus (CCG), corticospinal tract (CST), inferior longitudinal fasciculus (ILF), superior longitudinal fasciculus-parietal (SLFP), superior longitudinal fasciculus-temporal (SLFT), and uncinate fasciculus (UNC). Furthermore, a higher mean diffusivity (MD) of distal tracts was linked to worse attention and executive function in the FMI, right CCG, left ILF, SLFP, SLFT, and UNC. The effect of WMH on the microstructural integrity of WM tracts may propagate along tracts to distal regions beyond the penumbra and might eventually affect attention and executive function.

5' UTR CGG repeat expansion in GIPC1 is associated with oculopharyngodistal myopathy.

Oculopharyngodistal myopathy is a late-onset degenerative muscle disorder characterized by ptosis and weakness of the facial, pharyngeal, and distal limb muscles. A recent report suggested a non-coding trinucleotide repeat expansion in LRP12 to be associated with the disease. Here we report a genetic study in a Chinese cohort of 41 patients with the clinical diagnosis of oculopharyngodistal myopathy (21 cases from seven families and 20 sporadic cases). In a large family with 12 affected individuals, combined haplotype and linkage analysis revealed a maximum two-point logarithm of the odds (LOD) score of 3.3 in chromosomal region chr19p13.11-p13.2 and narrowed the candidate region to an interval of 4.5 Mb. Using a comprehensive strategy combining whole-exome sequencing, long-read sequencing, repeat-primed polymerase chain reaction and GC-rich polymerase chain reaction, we identified an abnormal CGG repeat expansion in the 5' UTR of the GIPC1 gene that co-segregated with disease. Overall, the repeat expansion in GIPC1 was identified in 51.9% independent pedigrees (4/7 families and 10/20 sporadic cases), while the repeat expansion in LRP12 was only identified in one sporadic case (3.7%) in our cohort. The number of CGG repeats was <30 in controls but >60 in affected individuals. There was a slight correlation between repeat size and the age at onset. Both repeat expansion and retraction were observed during transmission but somatic instability was not evident. These results further support that non-coding CGG repeat expansion plays an essential role in the pathogenesis of oculopharyngodistal myopathy.

The correlation of clinical evaluation with life quality and mental status in a Chinese cohort with dysferlinopathy.

INTRODUCTION: Impaired mood and quality of life was common in muscular dystrophies and play an important role in long-term management. Previous studies in dysferlinopathies mainly focused on the genotype-phenotypes correlations. Currently there are very few reports regarding the mental status, life quality and the correlated factors. METHODS: A total of 22 patients with dysferlinopathy was recruited and evaluated by 6-minute walking test (6MWT) and adapted-North Star Ambulatory Assessment (a-NSAA). Chinese version of SF-36, PHQ-9, and GAD-7 scale were used to evaluate the Quality of Life (QoL), depression and anxiety. Statistical analysis was applied to investigate the correlation between clinical variables and life quality or mental status. RESULTS: SF-36 evaluation revealed multiple dimensional impairment in dysferlinopathy patients. Declined score in body pain (78.00 vs. 91.23, p = 0.0129) and mental health (56.00 vs.72.88, p = 0.0493) were of note in female patients. Some patients suffered from depression (23%) and anxiety (23%) with a high score in PHQ-9/GAD-7. The 6MWT was well-correlated with the severity of depression and most scores in QoL except Body Pain and Role emotion. CONCLUSION: The cross-sectional study revealed impaired mental status and life quality in dysferlinopathy, particularly in female patients. The life quality impairment is correlated with the clinical severity.

Cerenkov luminescence imaging is an effective preclinical tool for assessing colorectal cancer PD-L1 levels in vivo.

BACKGROUND: Preclinical and clinical studies have demonstrated that immunotherapy has effectively delayed tumor progression, and the clinical outcomes of anti-PD-1/PD-L1 therapy were related to PD-L1 expression level in the tumors. A 131I-labeled anti-PD-L1 monoclonal antibody tracer, 131I-PD-L1-Mab, was developed to study the target ability of noninvasive Cerenkov luminescence imaging in colorectal cancer xenograft mice. METHOD: Anti-PD-L1 monoclonal antibody labeled with 131I (131I-PD-L1-Mab), and in vitro binding assays were used to evaluate the affinity of 131I-PD-L1-Mab to PD-L1 and their binding level to different colorectal cancer cells, and compared with flow cytometry, Western blot analysis, and immunofluorescence staining. The clinical application value of 131I-PD-L1-Mab was evaluated through biodistribution and Cerenkov luminescence imaging, and different tumor-bearing models expressing PD-L1 were evaluated. RESULTS: 131I-PD-L1-Mab showed high affinity to PD-L1, and the equilibrium dissociation constant was 1.069 × 10-9 M. The competitive inhibition assay further confirmed the specific binding ability of 131I-PD-L1-Mab. In four different tumor-bearing models with different PD-L1 expression, the biodistribution and Cerenkov luminescence imaging showed that the RKO tumors demonstrated the highest uptake of the tracer 131I-PD-L1-Mab, with a maximum uptake of 1.613 ± 0.738% IA/g at 48 h. CONCLUSIONS: There is a great potential for 131I-PD-L1-Mab noninvasive Cerenkov luminescence imaging to assess the status of tumor PD-L1 expression and select patients for anti-PD-L1 targeted therapy.

White matter hyperintensities associated with progression of cerebral small vessel disease: a 7-year Chinese urban community study.

We aimed to explore the role of white matter hyperintensities (WMH) in progression of cerebral small vessel disease (CSVD) in an urban community in China over a period of 7 years, and to investigate associations between WMH volume (baseline and progression) and cognitive impairment. CSVD markers and neuropsychological tests at baseline and follow-up of 191 participants of the Shanghai Aging Study (SAS) were assessed. WMH volume were assessed by automatic segmentation based on U-net model. Lacunes, cerebral microbleeds (CMBs) and enlarged perivascular spaces (ePVS) were rated manually. Small vessel disease (SVD) score was rated as the total burden of CSVD markers. Global cognitive function and 5 main cognitive domains (memory, language, spatial construction, attention and executive function) were evaluated by neuropsychological tests. We performed multivariable linear regression and binominal logistic regression. Participants with higher baseline WMH volume developed more progression of WMH volume, increased risk of incident lacunes, incident CMBs, and ePVS progression. WMH (baseline and progression) were associated with decline of executive function. WMH were associated with progression of cerebral small vessel disease and decline of executive function in a Chinese urban community study over a period of 7 years.

Evaluation of Intravoxel Incoherent Motion Diffusion-Weighted Magnetic Resonance Imaging for Detection of Bowel Inflammation in Patients With Crohn Disease.

OBJECTIVES: This study aimed to evaluate the feasibility of intravoxel incoherent motion diffusion-weighted magnetic resonance imaging (DW-MRI) in detecting bowel inflammation in patients with Crohn disease (CD). METHODS: Sixteen patients who underwent intravoxel incoherent motion DW-MRI for CD and colonoscopy were recruited. Seventy-nine bowel segments were selected, and their mean D, D*, f, and apparent diffusion coefficient (ADC) values were measured. The receiver operating characteristic curve was performed to distinguish inflamed from normal bowel. RESULTS: The mean D, D*, f, and ADC values of inflamed bowel were significantly lower than those of normal bowel (P < 0.05). The area under the receiver operating characteristic curve for f (0.906) and ADC values (0.924) was greater than that for D (0.709) or D* values (0.686) for differentiating inflamed bowel from normal bowel (P < 0.05). CONCLUSIONS: Intravoxel incoherent motion DW-MRI is a feasible technique for detecting inflammation in CD patients. The ADC and f values have more potential than the D and D* values.

Clinical spectrum and gene mutations in a Chinese cohort with anoctaminopathy.

Recessive mutations in anoctamin-5 (ANO5) are causative for limb-girdle muscular dystrophy (LGMD) 2 L and non-dysferlin Miyoshi-like distal myopathy (MMD3). ANO5 mutations are highly prevalent in European countries; however it is not common in patients of Asian origin, and there is no data regarding the Chinese population. We retrospectively reviewed the clinical manifestations and gene mutations of Chinese patients with anoctaminopathy. A total of five ANO5 mutations including four novel mutations and one reported mutation were found in four patients from three families. No hotspot mutation was found. Three patients presented with presymptomatic hyperCKemia and one patient had limb muscle weakness. Muscle imaging of lower limbs showed preferential adductor magnus and medial gastrocnemius involvement. No hotspot mutation has been identified in Chinese patients to date.