Self-supervised anatomical continuity enhancement network for 7T SWI synthesis from 3T SWI.

Synthesizing 7T Susceptibility Weighted Imaging (SWI) from 3T SWI could offer significant clinical benefits by combining the high sensitivity of 7T SWI for neurological disorders with the widespread availability of 3T SWI in diagnostic routines. Although methods exist for synthesizing 7T Magnetic Resonance Imaging (MRI), they primarily focus on traditional MRI modalities like T1-weighted imaging, rather than SWI. SWI poses unique challenges, including limited data availability and the invisibility of certain tissues in individual 3T SWI slices. To address these challenges, we propose a Self-supervised Anatomical Continuity Enhancement (SACE) network to synthesize 7T SWI from 3T SWI using plentiful 3T SWI data and limited 3T-7T paired data. The SACE employs two specifically designed pretext tasks to utilize low-level representations from abundant 3T SWI data for assisting 7T SWI synthesis in a downstream task with limited paired data. One pretext task emphasizes input-specific morphology by balancing the elimination of redundant patterns with the preservation of essential morphology, preventing the blurring of synthetic 7T SWI images. The other task improves the synthesis of tissues that are invisible in a single 3T SWI slice by aligning adjacent slices with the current slice and predicting their difference fields. The downstream task innovatively combines clinical knowledge with brain substructure diagrams to selectively enhance clinically relevant features. When evaluated on a dataset comprising 97 cases (5495 slices), the proposed method achieved a Peak Signal-to-Noise Ratio (PSNR) of 23.05 dB and a Structural Similarity Index (SSIM) of 0.688. Due to the absence of specific methods for 7T SWI, our method was compared with existing enhancement techniques for general 7T MRI synthesis, outperforming these techniques in the context of 7T SWI synthesis. Clinical evaluations have shown that our synthetic 7T SWI is clinically effective, demonstrating its potential as a clinical tool.

Profiling functional networks identify activation of corticostriatal connectivity in ET patients after MRgFUS thalamotomy.

BACKGROUND: MR-guided focused ultrasound (MRgFUS) thalamotomy is a novel and effective treatment for medication-refractory tremor in essential tremor (ET), but how the brain responds to this deliberate lesion is not clear. OBJECTIVE: The current study aimed to evaluate the immediate and longitudinal alterations of functional networks after MRgFUS thalamotomy. METHODS: We retrospectively obtained preoperative and postoperative 30-day, 90-day, and 180-day data of 31 ET patients subjected with MRgFUS thalamotomy from 2018 to 2020. Their archived resting-state functional MRI data were used for functional network comparison as well as graph-theory metrics analysis. Both partial least squares (PLS) regression and linear regression were conducted to associate functional features to tremor symptoms. RESULTS: MRgFUS thalamotomy dramatically abolished tremors, while global functional network only sustained immediate fluctuation within one week after the surgery. Network-based statistics have identified a long-term enhanced corticostriatal subnetwork by comparison between 180-day and preoperative data (P = 0.019). Within this subnetwork, network degree, global efficiency and transitivity were significantly recovered in ET patients right after MRgFUS thalamotomy compared to the pre-operative timepoint (P < 0.05), as well as hemisphere lateralization (P < 0.001). The PLS main component significantly accounted for 33.68 % and 34.16 % of the total variances of hand tremor score and clinical rating scale for tremor (CRST)-total score (P = 0.037 and 0.027). Network transitivity of this subnetwork could serve as a reliable biomarker for hand tremor score control prediction at 180-day after the surgery (ß = 2.94, P = 0.03). CONCLUSION: MRgFUS thalamotomy promoted corticostriatal connectivity activation correlated with tremor improvement in ET patient after MRgFUS thalamotomy.

Identification of QTLs responsible for culturability, and fine-mapping of QTL qCBT9 related to callus browning derived from Dongxiang common wild rice (Oryza rufipogon Griff.).

Compared to japonica, the lower genetic transformation efficiency of indica is a technical bottleneck for rice molecular breeding. Specifically, callus browning frequently occurs during the culture of the elite indica variety 93-11, leading to poor culturability and lower genetic transformation efficiency. Here, 67 QTLs related to culturability were detected using 97 introgression lines (designated as 9DILs) derived from Dongxiang common wild rice (DXCWR, Oryza rufipogon Griff.) with 93-11 genetic background, explaining 4% ~12% of the phenotypic variations. The QTL qCBT9 on chromosome 9 was a primary QTL for reducing callus browning derived from DXCWR. Five 9DILs with light callus browning and high differentiation were screened. We evaluated the callus browning index (CBI) of 100 F2 population crossed of 93-11 and 9DIL71 and the recombinant plants screened from 3270 individuals. The qCBT9 was delimited to a ~148kb region between the markers X16 and X23. RNA-seq analysis of DEGs between 9DIL71 and 93-11 showed three upregulated DEGs (Os09g0526500, Os09g0527900, Os09g0528200,) and three downregulated DEGs (Os09g0526700, Os09g0526800, Os09g0527700) were located in the candidate region of qCBT9. Furthermore, callus browning may be involved in cell senescence and death caused by oxidative stress. The differentiation of indica and japonica in this region suggested that qCBT9 was possibly a vital QTL contributed to better culturability of japonica. Our results laid a foundation for further cloning of the gene for reduced callus browning in O. rufipogon, and also provided a new genetic resource and material basis for improving the culturability and genetic transformation efficiency of cultivated rice. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-024-01470-z.

Cancer immunometabolism: advent, challenges, and perspective.

For decades, great strides have been made in the field of immunometabolism. A plethora of evidence ranging from basic mechanisms to clinical transformation has gradually embarked on immunometabolism to the center stage of innate and adaptive immunomodulation. Given this, we focus on changes in immunometabolism, a converging series of biochemical events that alters immune cell function, propose the immune roles played by diversified metabolic derivatives and enzymes, emphasize the key metabolism-related checkpoints in distinct immune cell types, and discuss the ongoing and upcoming realities of clinical treatment. It is expected that future research will reduce the current limitations of immunotherapy and provide a positive hand in immune responses to exert a broader therapeutic role.

Genome assembly of autotetraploid Actinidia arguta highlights adaptive evolution and enables dissection of important economic traits.

Actinidia arguta, the most widely distributed Actinidia species and the second cultivated species in the genus, can be distinguished from the currently cultivated Actinidia chinensis on the basis of its small and smooth fruit, rapid softening, and excellent cold tolerance. Adaptive evolution of tetraploid Actinidia species and the genetic basis of their important agronomic traits are still unclear. Here, we generated a chromosome-scale genome assembly of an autotetraploid male A. arguta accession. The genome assembly was 2.77 Gb in length with a contig N50 of 9.97 Mb and was anchored onto 116 pseudo-chromosomes. Resequencing and clustering of 101 geographically representative accessions showed that they could be divided into two geographic groups, Southern and Northern, which first diverged 12.9 million years ago. A. arguta underwent two prominent expansions and one demographic bottleneck from the mid-Pleistocene climate transition to the late Pleistocene. Population genomics studies using paleoclimate data enabled us to discern the evolution of the species' adaptation to different historical environments. Three genes (AaCEL1, AaPME1, and AaDOF1) related to flesh softening were identified by multi-omics analysis, and their ability to accelerate flesh softening was verified through transient expression assays. A set of genes that characteristically regulate sexual dimorphism located on the sex chromosome (Chr3) or autosomal chromosomes showed biased expression during stamen or carpel development. This chromosome-level assembly of the autotetraploid A. arguta genome and the genes related to important agronomic traits will facilitate future functional genomics research and improvement of A. arguta.

The stromal microenvironment endows pancreatic neuroendocrine tumors with spatially specific invasive and metastatic phenotypes.

Cancer-associated fibroblasts (CAFs) play an important role in a variety of cancers. However, the role of tumor stroma in nonfunctional pancreatic neuroendocrine tumors (NF-PanNETs) is often neglected. Profiling the heterogeneity of CAFs can reveal the causes of malignant phenotypes in NF-PanNETs. Here, we found that patients with high stromal proportion had poor prognosis, especially for that with infiltrating stroma (stroma and tumor cells that presented an infiltrative growth pattern and no regular boundary). In addition, myofibroblastic CAFs (myCAFs), characterized by FAP+ and α-SMAhigh, were spatially closer to tumor cells and promoted the EMT and tumor growth. Intriguingly, only tumor cells which were spatially closer to myCAFs underwent EMT. We further elucidated that myCAFs stimulate TGF-ß expression in nearby tumor cells. Then, TGF-ß promoted the EMT in adjacent tumor cells and promoted the expression of myCAFs marker genes in tumor cells, resulting in distant metastasis. Our results indicate that myCAFs cause spatial heterogeneity of EMT, which accounts for liver metastasis of NF-PanNETs. The findings of this study might provide possible targets for the prevention of liver metastasis.

Deep medullary vein damage correlates with small vessel disease in small vessel occlusion acute ischemic stroke.

OBJECTIVES: We aim to investigate whether cerebral small vessel disease (cSVD) imaging markers correlate with deep medullary vein (DMV) damage in small vessel occlusion acute ischemic stroke (SVO-AIS) patients. METHODS: The DMV was divided into six segments according to the regional anatomy. The total DMV score (0-18) was calculated based on segmental continuity and visibility. The damage of DMV was grouped according to the quartiles of the total DMV score. Neuroimaging biomarkers of cSVD including white matter hyperintensity (WMH), cerebral microbleed (CMB), perivascular space (PVS), and lacune were identified. The cSVD score were further analyzed. RESULTS: We included 229 SVO-AIS patients, the mean age was 63.7 ± 23.1 years, the median NIHSS score was 3 (IQR, 2-6). In the severe DMV burden group (the 4th quartile), the NIHSS score grade (6 (3-9)) was significantly higher than other groups (p < 0.01). The grade scores for basal ganglia PVS (BG-PVS) were positively correlated with the degree of DMV (R = 0.67, p < 0.01), rather than centrum semivole PVS (CS-PVS) (R = 0.17, p = 0.1). In multivariate analysis, high CMB burden (adjusted odds ratio [aOR], 25.38; 95% confidence interval [CI], 1.87-345.23) was associated with severe DMV scores. In addition, BG-PVS was related to severe DMV burden in a dose-dependent manner: when BG-PVS score was 3 and 4, the aORs of severe DMV burden were 18.5 and 12.19, respectively. CONCLUSION: The DMV impairment was associated with the severity of cSVD, which suggests that DMV burden may be used for risk stratification in SVO-AIS patients. CLINICAL RELEVANCE STATEMENT: The DMV damage score, based on the association between small vessel disease and the deep medullary veins impairment, is a potential new imaging biomarker for the prognosis of small vessel occlusion acute ischemic stroke, with clinical management implications. KEY POINTS: • The damage to the deep medullary vein may be one mechanism of cerebral small vessel disease. • Severe burden of the basal ganglia perivascular space and cerebral microbleed is closely associated with significant impairment to the deep medullary vein. • The deep medullary vein damage score may reflect a risk of added vascular damage in small vessel occlusion acute ischemic stroke patients.

Tumor characteristics, brain functional activity, and connectivity of tinnitus in patients with vestibular schwannoma: a pilot study.

Background: The mechanism underlying tinnitus remains unclear, and when it coexists with vestibular schwannoma (VS), it can significantly diminish the quality of life for affected patients. This study aimed to determine the correlation between preoperative clinical characteristics of VS, postoperative changes in brain function, and tinnitus in patients with VS through a cohort study. Methods: We collected data from 80 patients with VS preoperatively and 28 patients with VS preoperatively and postoperatively, and recruited 28 healthy controls. We used Chi-squared tests and unpaired t-tests to identify clinical characteristics with a significant preoperative effect. We used paired t-tests to identify brain regions where patients demonstrated significant changes in amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) postoperatively. Tinnitus severity was evaluated using the Tinnitus Handicap Inventory (THI) and Visual Analogue Scale (VAS). Pearson correlation coefficients were applied to assess the relationship between the changes in ALFF and ReHo and the changes in THI and VAS scores postoperatively. We also conducted seed- and region of interest (ROI)-based functional connectivity (FC) analyses. Results: Before surgery, patients with VS with tinnitus (n=49) had smaller tumors (t=3.293; P<0.001), more solid tumor (χ2=4.559; P=0.033), and less extrusion into the cerebellum brain stem (χ2=10.345; P=0.001) than those without tinnitus (n=31). After surgery, the 28 patients with VS showed a significant reduction in ALFF in the left Cerebellum_Crus2 (a lobule in the cerebellum anatomy) (ROI 1) and a significant reduction in ReHo in the left Cerebellum_Crus1 (a lobule in the cerebellum anatomy) (ROI 2) and the right precuneus (ROI 3). Conversely, ReHo was significantly increased in the right precentral gyrus (ROI 4) [cluster-level P value family-wise error (PFWE) <0.05]. The changes in ALFF values were negatively correlated with changes in the VAS score (r=-0.32; P<0.05). The FC strengths of patients between ROI 2 and the left and right posterior cingulate gyrus were significantly decreased postoperatively [false discovery rate (FDR) correction; P<0.05]. Conclusions: Preoperative tinnitus in patients with VS may be influenced by tumor characteristics. The functional activities of brain regions are possibly altered postoperatively, which may be involved in the maintenance of postoperative tinnitus. Notably, the changes in ALFF are correlated with tinnitus.

Magnetic resonance-guided focused ultrasound for essential tremor: a prospective, single center, single-arm study.

JOURNAL/nrgr/04.03/01300535-202409000-00041/figure1/v/2024-01-16T170235Z/r/image-tiff The safety and effectiveness of magnetic resonance-guided focused ultrasound thalamotomy has been broadly established and validated for the treatment of essential tremor. In 2018, the first magnetic resonance-guided focused ultrasound system in Chinese mainland was installed at the First Medical Center of the PLA General Hospital. This prospective, single center, open-label, single-arm study was part of a worldwide prospective multicenter clinical trial (ClinicalTrials.gov Identifier: NCT03253991) conducted to confirm the safety and efficacy of magnetic resonance-guided focused ultrasound for treating essential tremor in the local population. From 2019 to 2020, 10 patients with medication refractory essential tremor were recruited into this open-label, single arm study. The treatment efficacy was determined using the Clinical Rating Scale for Tremor. Safety was evaluated according to the incidence and severity of adverse events. All of the subjects underwent a unilateral thalamotomy targeting the ventral intermediate nucleus. At the baseline assessment, the estimated marginal mean of the Clinical Rating Scale for Tremor total score was 58.3 ± 3.6, and this improved after treatment to 23.1 ± 6.4 at a 12-month follow-up assessment. A total of 50 adverse events were recorded, and 2 were defined as serious. The most common intraoperative adverse events were nausea and headache. The most frequent postoperative adverse events were paresthesia and equilibrium disorder. Most of the adverse events were mild and usually disappeared within a few days. Our findings suggest that magnetic resonance-guided focused ultrasound for the treatment of essential tremor is effective, with a good safety profile, for patients in Chinese mainland.

Alteration of White Matter Connectivity for MR-Guided Focused Ultrasound in the Treatment of Essential Tremor.

BACKGROUND: Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy has been implemented as a therapeutic alternative for the treatment of drug-refractory essential tremor (ET). However, its impact on the brain structural network is still unclear. PURPOSE: To investigate both global and local alterations of the white matter (WM) connectivity network in ET after MRgFUS thalamotomy. STUDY TYPE: Retrospective. SUBJECTS: Twenty-seven ET patients (61 ± 11 years, 19 males) with MRgFUS thalamotomy and 28 healthy controls (HC) (61 ± 11 years, 20 males) were recruited for comparison. FIELD STRENGTH/SEQUENCE: A 3 T/single shell diffusion tensor imaging by using spin-echo-based echo-planar imaging, three-dimensional T1 weighted imaging by using gradient-echo-based sequence. ASSESSMENT: Patients were undergoing MRgFUS thalamotomy and their clinical data were collected from pre-operation to 6-month post-operation. Network topological metrics, including rich-club organization, small-world, and efficiency properties were calculated. Correlation between the topological metrics and tremor scores in ET groups was also calculated to assess the role of neural remodeling in the brain. STATISTICAL TESTS: Two-sample independent t-tests, chi-squared test, ANOVA, Bonferroni test, and Spearman's correlation. Statistical significance was set at P < 0.05. RESULTS: For ET patients, the strength of rich-club connection and clustering coefficient significantly increased vs. characteristic path length decreased at 6-month post-operation compared with pre-operation. The distribution pattern of rich-club regions was different in ET groups. Specifically, the order of the rich-club regions was changed according to the network degree value after MRgFUS thalamotomy. Moreover, the altered nodal efficiency in the right temporal pole of the superior temporal gyrus (R = 0.434-0.596) and right putamen (R = 0.413-0.436) was positively correlated with different tremor improvement. DATA CONCLUSION: These findings might improve understanding of treatment-induced modulation from a network perspective and may work as an objective marker in the assessment of ET tremor control with MRgFUS thalamotomy. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 4.

Synthesized 7T MPRAGE From 3T MPRAGE Using Generative Adversarial Network and Validation in Clinical Brain Imaging: A Feasibility Study.

BACKGROUND: Ultra-high field 7T MRI can provide excellent tissue contrast and anatomical details, but is often cost prohibitive, and is not widely accessible in clinical practice. PURPOSE: To generate synthetic 7T images from widely acquired 3T images with deep learning and to evaluate the feasibility of this approach for brain imaging. STUDY TYPE: Prospective. POPULATION: 33 healthy volunteers and 89 patients with brain diseases, divided into training, and evaluation datasets in the ratio 4:1. SEQUENCE AND FIELD STRENGTH: T1-weighted nonenhanced or contrast-enhanced magnetization-prepared rapid acquisition gradient-echo sequence at both 3T and 7T. ASSESSMENT: A generative adversarial network (SynGAN) was developed to produce synthetic 7T images from 3T images as input. SynGAN training and evaluation were performed separately for nonenhanced and contrast-enhanced paired acquisitions. Qualitative image quality of acquired 3T and 7T images and of synthesized 7T images was evaluated by three radiologists in terms of overall image quality, artifacts, sharpness, contrast, and visualization of vessel using 5-point Likert scales. STATISTICAL TESTS: Wilcoxon signed rank tests to compare synthetic 7T images with acquired 7T and 3T images and intraclass correlation coefficients to evaluate interobserver variability. P < 0.05 was considered significant. RESULTS: Of the 122 paired 3T and 7T MRI scans, 66 were acquired without contrast agent and 56 with contrast agent. The average time to generate synthetic images was ~11.4 msec per slice (2.95 sec per participant). The synthetic 7T images achieved significantly improved tissue contrast and sharpness in comparison to 3T images in both nonenhanced and contrast-enhanced subgroups. Meanwhile, there was no significant difference between acquired 7T and synthetic 7T images in terms of all the evaluation criteria for both nonenhanced and contrast-enhanced subgroups (P ≥ 0.180). DATA CONCLUSION: The deep learning model has potential to generate synthetic 7T images with similar image quality to acquired 7T images. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 1.

Multifunctional Optical Tomography System With High-Fidelity Surface Extraction Based on a Single Programmable Scanner and Unified Pinhole Modeling.

OBJECTIVE: Macroscopic optical tomography is a non-invasive method that can visualize the 3D distribution of intrinsic optical properties or exogenous fluorophores, making it highly attractive for small animal imaging. However, reconstructing the images requires prior knowledge of surface information. To address this, existing systems often use additional hardware components or integrate multimodal information, which is expensive and introduces new issues such as image registration. Our goal is to develop a multifunctional optical tomography system that can extract surface information using a concise hardware design. METHODS: Our proposed system uses a single programmable scanner to implement both surface extraction and optical tomography functions. A unified pinhole model is used to describe both the illumination and detection procedures for capturing 3D point cloud. Line-shaped scanning is adopted to improve both spatial resolution and speed of surface extraction. Finally, we integrate the extracted surface information into the optical tomographic reconstruction to more accurately map the fluorescence distribution. RESULT: Comprehensive phantom experiments with different levels of complexity were designed to evaluate the performance of surface extraction and fluorescence tomography. We also imaged the axillary lymph nodes in living mice after injection of fluorophore, demonstrating the proposed system facilitates more reliable fluorescence tomography. CONCLUSION: We have successfully developed a versatile optical tomography system by leveraging concise hardware design and unified pinhole modeling. Phantom validation demonstrates that our system provides high-precision surface information with a maximum error of 0.1 mm, while the surface-guided FMT reconstruction is more reliable than the blind reconstruction using simplified surface geometry, elevating several quantitative metrics including RMSE, CNR, and Dice. SIGNIFICANCE: Our work explores the feasibility of obtaining additional surface information using existing components of standalone optical tomography. This makes the optical tomographic technique more accurate and more accessible to biomedical researchers.

MRI Assessment of Brain Frailty and Clinical Outcome in Patients With Acute Posterior Perforating Artery Infarction.

BACKGROUND: Global brain health has gained increasing attention recently. Imaging markers of brain frailty have been related to functional outcomes in previous studies on anterior circulation; however, little data are available on imaging markers and posterior circulation. PURPOSE: To investigate the impact of brain frailty on functional outcomes in patients with acute perforating artery infarction (PAI) of the posterior circulation. STUDY TYPE: Prospective. POPULATION: One hundred patients (60.78 ± 9.51 years, 72% men) with acute posterior circulation PAI (determined by diffusion-weighted magnetic resonance imaging (MRI)/time-of-flight MR angiography). FIELD STRENGTH/SEQUENCE: T1- and T2-weighted fast spin echo, T2-weighted fluid-attenuated inversion recovery, diffusion-weighted echo planar, gradient echo (susceptibility-weight imaging), and 3D time-of-flight MR angiography sequences at 3.0 T. ASSESSMENT: Periventricular and deep white matter hyperintensities (WMH), enlarged perivascular spaces (EPVS) in the basal ganglia and centrum semiovale area, lacunes, cerebral microbleeds (CMB), and total brain frailty score by calculating the above imaging characters were rated visually by three radiologists with 9, 10, and 11 years of experience and one neuroradiologist with 12. Infarction volume was assessed using baseline diffusion-weighted imaging (DWI) data obtained within 24 hours of symptom onset. A modified Rankin Scale (mRS) score >1 on day 90 defined an adverse functional outcome. Associations between the imaging markers of brain frailty and functional outcomes were assessed. STATISTICAL TESTS: Fisher's exact test, Mann-Whitney U test, and multivariable binary logistic regression. A P value <0.05 was considered statistically significant. RESULTS: Adverse prognoses (mRS > 1) were observed in 34 (34%) patients. Infarction volume, periventricular WMH, deep WMH, basal ganglia EPVS, CMB, and the brain frailty score were significantly associated with adverse functional outcomes. An increased brain frailty score was significantly associated with unfavorable mRS score on day 90 (odds ratio 1.773, 95% confidence interval 1.237-2.541). DATA CONCLUSION: Advanced MRI imaging markers of brain frailty, individually or combined as a total brain frailty score, were associated with worse functional outcomes after acute posterior circulation PAI. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 3.

Relay learning: a physically secure framework for clinical multi-site deep learning.

Big data serves as the cornerstone for constructing real-world deep learning systems across various domains. In medicine and healthcare, a single clinical site lacks sufficient data, thus necessitating the involvement of multiple sites. Unfortunately, concerns regarding data security and privacy hinder the sharing and reuse of data across sites. Existing approaches to multi-site clinical learning heavily depend on the security of the network firewall and system implementation. To address this issue, we propose Relay Learning, a secure deep-learning framework that physically isolates clinical data from external intruders while still leveraging the benefits of multi-site big data. We demonstrate the efficacy of Relay Learning in three medical tasks of different diseases and anatomical structures, including structure segmentation of retina fundus, mediastinum tumors diagnosis, and brain midline localization. We evaluate Relay Learning by comparing its performance to alternative solutions through multi-site validation and external validation. Incorporating a total of 41,038 medical images from 21 medical hosts, including 7 external hosts, with non-uniform distributions, we observe significant performance improvements with Relay Learning across all three tasks. Specifically, it achieves an average performance increase of 44.4%, 24.2%, and 36.7% for retinal fundus segmentation, mediastinum tumor diagnosis, and brain midline localization, respectively. Remarkably, Relay Learning even outperforms central learning on external test sets. In the meanwhile, Relay Learning keeps data sovereignty locally without cross-site network connections. We anticipate that Relay Learning will revolutionize clinical multi-site collaboration and reshape the landscape of healthcare in the future.

Generative Adversarial Network-based Noncontrast CT Angiography for Aorta and Carotid Arteries.

Background Iodinated contrast agents (ICAs), which are widely used in CT angiography (CTA), may cause adverse effects in humans, and their use is time-consuming and costly. Purpose To develop an ICA-free deep learning imaging model for synthesizing CTA-like images and to assess quantitative and qualitative image quality as well as the diagnostic accuracy of synthetic CTA (Syn-CTA) images. Materials and Methods A generative adversarial network (GAN)-based CTA imaging model was trained, validated, and tested on retrospectively collected pairs of noncontrast CT and CTA images of the neck and abdomen from January 2017 to June 2022, and further validated on an external data set. Syn-CTA image quality was evaluated using quantitative metrics. In addition, two senior radiologists scored the visual quality on a three-point scale (3 = good) and determined the vascular diagnosis. The validity of Syn-CTA images was evaluated by comparing the visual quality scores and diagnostic accuracy of aortic and carotid artery disease between Syn-CTA and real CTA scans. Results CT scans from 1749 patients (median age, 60 years [IQR, 50-68 years]; 1057 male patients) were included in the internal data set: 1137 for training, 400 for validation, and 212 for testing. The external validation set comprised CT scans from 42 patients (median age, 67 years [IQR, 59-74 years]; 37 male patients). Syn-CTA images had high similarity to real CTA images (normalized mean absolute error, 0.011 and 0.013 for internal and external test set, respectively; peak signal-to-noise ratio, 32.07 dB and 31.58 dB; structural similarity, 0.919 and 0.906). The visual quality of Syn-CTA and real CTA images was comparable (internal test set, P = .35; external validation set, P > .99). Syn-CTA showed reasonable to good diagnostic accuracy for vascular diseases (internal test set: accuracy = 94%, macro F1 score = 91%; external validation set: accuracy = 86%, macro F1 score = 83%). Conclusion A GAN-based model that synthesizes neck and abdominal CTA-like images without the use of ICAs shows promise in vascular diagnosis compared with real CTA images. Clinical trial registration no. NCT05471869 © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Zhang and Turkbey in this issue.

Developing mitochondrial base editors with diverse context compatibility and high fidelity via saturated spacer library.

DddA-derived cytosine base editors (DdCBEs) greatly facilitated the basic and therapeutic research of mitochondrial DNA mutation diseases. Here we devise a saturated spacer library and successfully identify seven DddA homologs by performing high-throughput sequencing based screen. DddAs of Streptomyces sp. BK438 and Lachnospiraceae bacterium sunii NSJ-8 display high deaminase activity with a strong GC context preference, and DddA of Ruminococcus sp. AF17-6 is highly compatible to AC context. We also find that different split sites result in wide divergence on off-target activity and context preference of DdCBEs derived from these DddA homologs. Additionally, we demonstrate the orthogonality between DddA and DddIA, and successfully minimize the nuclear off-target editing by co-expressing corresponding nuclear-localized DddIA. The current study presents a comprehensive and unbiased strategy for screening and characterizing dsDNA cytidine deaminases, and expands the toolbox for mtDNA editing, providing additional insights for optimizing dsDNA base editors.

Hydrodynamics-Induced Long-Range Attraction between Plates in Bacterial Suspensions.

We perform optical-tweezers experiments and mesoscale fluid simulations to study the effective interactions between two parallel plates immersed in bacterial suspensions. The plates are found to experience a long-range attraction, which increases linearly with bacterial density and decreases with plate separation. The higher bacterial density and orientation order between plates observed in the experiments imply that the long-range effective attraction mainly arises from the bacterial flow field, instead of the direct bacterium-plate collisions, which is confirmed by the simulations. Furthermore, the hydrodynamic contribution is inversely proportional to the squared interplate separation in the far field. Our findings highlight the importance of hydrodynamics on the effective forces between passive objects in active baths, providing new possibilities to control activity-directed assembly.

Case report: Short-term efficacy and changes in 18F-FDG-PET with acute multi-target stimulation in spinocerebellar ataxia type 3 (SCA3/MJD).

Objective: Spinocerebellar ataxia type 3 (SCA3), also known as Machado-Joseph disease (MJD), is a rare neurodegenerative disease for which there is no specific treatment. Very few cases have been treated with single-target deep brain stimulation (DBS), and the results were not satisfactory. We applied multi-target DBS to an SCA3/MJD patient and performed positron emission computed tomography (PET) before and after DBS to explore the short-term clinical therapeutic effect. Materials and methods: A 26-year-old right-hand-dominant female with a family history of SCA3/MJD suffered from cerebellar ataxia and dystonia. Genetic testing indicated an expanded CAG trinucleotide repeat in the ATXN3 gene and a diagnosis of SCA3/MJD. Conservative treatment had no obvious effect; therefore, leads were implanted in the bilateral dentate nucleus (DN) and the globus pallidus internus (GPi) and connected to an external stimulation device. The treatment effect was evaluated in a double-blind, randomized protocol in five phases (over a total of 15 days): no stimulation, GPi, DN, or sham stimulation, and combined GPi and DN stimulation. 18F-fluoro-2-deoxy-d-glucose and dopamine transporter PET, Scale for the Assessment and Rating of Ataxia, Fahn-Tolosa-Marin Clinical Rating Scale for Tremor (FTM), Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS), and SF-36 quality of life scores were compared before and after DBS. Results: The Total Scale for the Assessment and Rating of Ataxia scores improved by ~42% (from 24 to 14). The BFMDRS movement scores improved by ~30% (from 40.5 to 28.5). The BFMDRS disability scores improved by ~12.5% (from 16 to 14). Daily living activities were not noticeably improved. Compared with the findings in pre-DBS imaging, 18F-fluoro-2-deoxy-d-glucose uptake increased in the cerebellum, while according to dopamine transporter imaging, there were no significant differences in the bilateral caudate nucleus and putamen. Conclusion: Multi-target acute stimulation (DN DBS and GPi DBS) in SCA3/MJD can mildly improve cerebellar ataxia and dystonia and increase cerebellar metabolism.

Magnetic Resonance-Guided Focused Ultrasound Thalamotomy Rebalances Atypical Functional Hierarchy in Patients with Essential Tremor.

Magnetic resonance-guided focused ultrasound (MRgFUS) has brought thalamotomy back to the frontline for essential tremor (ET). As functional organization of human brain strictly follows hierarchical principles which are frequently deficient in neurological diseases, whether additional damage from MRgFUS thalamotomy induces further disruptions of ET functional scaffolds are still controversial. This study was to examine the alteration features of brain functional frameworks following MRgFUS thalamotomy in patients with ET. We retrospectively obtained preoperative (ETpre) and postoperative 6-month (ET6m) data of 30 ET patients underwent MRgFUS thalamotomy from 2018 to 2020. Their archived functional MR images were used to functional gradient comparison. Both supervised pattern learning and stepwise linear regression were conducted to associate gradient features to tremor symptoms with additional neuropathophysiological analysis. MRgFUS thalamotomy relieved 78.19% of hand tremor symptoms and induced vast global framework alteration (ET6m vs. ETpre: Cohen d = - 0.80, P < 0.001). Multiple robust alterations were identified especially in posterior cingulate cortex ([Formula: see text] ET6m vs. [Formula: see text] ETpre: Cohen d = 0.87, P = 0.048). Compared with matched health controls (HCs), its gradient distances to primary communities were significantly increased in [Formula: see text] ETpre patients with anomalous stepwise connectivity (P < 0.05 in ETpre vs. HCs), which were restored after MRgFUS thalamotomy. Both global and regional gradient features could be used for tremor symptom prediction and were linked to neuropathophysiological features of Parkinson disease and oxidative phosphorylation. MRgFUS thalamotomy not only suppress tremor symptoms but also rebalances atypical functional hierarchical architecture of ET patients.