Zero-DeepSub: Zero-shot deep subspace reconstruction for rapid multiparametric quantitative MRI using 3D-QALAS.

PURPOSE: To develop and evaluate methods for (1) reconstructing 3D-quantification using an interleaved Look-Locker acquisition sequence with T2 preparation pulse (3D-QALAS) time-series images using a low-rank subspace method, which enables accurate and rapid T1 and T2 mapping, and (2) improving the fidelity of subspace QALAS by combining scan-specific deep-learning-based reconstruction and subspace modeling. THEORY AND METHODS: A low-rank subspace method for 3D-QALAS (i.e., subspace QALAS) and zero-shot deep-learning subspace method (i.e., Zero-DeepSub) were proposed for rapid and high fidelity T1 and T2 mapping and time-resolved imaging using 3D-QALAS. Using an ISMRM/NIST system phantom, the accuracy and reproducibility of the T1 and T2 maps estimated using the proposed methods were evaluated by comparing them with reference techniques. The reconstruction performance of the proposed subspace QALAS using Zero-DeepSub was evaluated in vivo and compared with conventional QALAS at high reduction factors of up to nine-fold. RESULTS: Phantom experiments showed that subspace QALAS had good linearity with respect to the reference methods while reducing biases and improving precision compared to conventional QALAS, especially for T2 maps. Moreover, in vivo results demonstrated that subspace QALAS had better g-factor maps and could reduce voxel blurring, noise, and artifacts compared to conventional QALAS and showed robust performance at up to nine-fold acceleration with Zero-DeepSub, which enabled whole-brain T1, T2, and PD mapping at 1 mm isotropic resolution within 2 min of scan time. CONCLUSION: The proposed subspace QALAS along with Zero-DeepSub enabled high fidelity and rapid whole-brain multiparametric quantification and time-resolved imaging.

Compartment-specific regulation of NaV1.7 in sensory neurons after acute exposure to TNF-α.

Tumor necrosis factor α (TNF-α) is a major pro-inflammatory cytokine, important in many diseases, that sensitizes nociceptors through its action on a variety of ion channels, including voltage-gated sodium (NaV) channels. We show here that TNF-α acutely upregulates sensory neuron excitability and current density of threshold channel NaV1.7. Using electrophysiological recordings and live imaging, we demonstrate that this effect on NaV1.7 is mediated by p38 MAPK and identify serine 110 in the channel's N terminus as the phospho-acceptor site, which triggers NaV1.7 channel insertion into the somatic membrane. We also show that the N terminus of NaV1.7 is sufficient to mediate this effect. Although acute TNF-α treatment increases NaV1.7-carrying vesicle accumulation at axonal endings, we did not observe increased channel insertion into the axonal membrane. These results identify molecular determinants of TNF-α-mediated regulation of NaV1.7 in sensory neurons and demonstrate compartment-specific effects of TNF-α on channel insertion in the neuronal plasma membrane.

A Prospective Multi-Institutional Study Comparing the Brain Development in the Third Trimester between Opioid-Exposed and Nonexposed Fetuses Using Advanced Fetal MR Imaging Techniques.

BACKGROUND AND PURPOSE: While the adverse neurodevelopmental effects of prenatal opioid exposure on infants and children in the United States are well described, the underlying causative mechanisms have yet to be fully understood. This study aims to compare quantitative volumetric and surface-based features of the fetal brain between opioid-exposed fetuses and unexposed controls by using advanced MR imaging processing techniques. MATERIALS AND METHODS: This is a multi-institutional IRB-approved study in which pregnant women with and without opioid use during the current pregnancy were prospectively recruited to undergo fetal MR imaging. A total of 14 opioid-exposed (31.4 ± 2.3 weeks of gestation) and 15 unexposed (31.4 ± 2.4 weeks) fetuses were included. Whole brain volume, cortical plate volume, surface area, sulcal depth, mean curvature, and gyrification index were computed as quantitative features by using our fetal brain MR imaging processing pipeline. RESULTS: After correcting for gestational age, fetal sex, maternal education, polysubstance use, high blood pressure, and MR imaging acquisition site, all of the global morphologic features were significantly lower in the opioid-exposed fetuses compared with the unexposed fetuses, including brain volume, cortical volume, cortical surface area, sulcal depth, cortical mean curvature, and gyrification index. In regional analysis, the opioid-exposed fetuses showed significantly decreased surface area and sulcal depth in the bilateral Sylvian fissures, central sulci, parieto-occipital fissures, temporal cortices, and frontal cortices. CONCLUSIONS: In this small cohort, prenatal opioid exposure was associated with altered fetal brain development in the third trimester. This adds to the growing body of literature demonstrating that prenatal opioid exposure affects the developing brain.

Sleep Spindle Generation Before and After Epilepsy Surgery: A Source Imaging Study in Children with Drug-Resistant Epilepsy.

INTRODUCTION: Literature lacks studies investigating the cortical generation of sleep spindles in drug-resistant epilepsy (DRE) and how they evolve after resection of the epileptogenic zone (EZ). Here, we examined sleep EEGs of children with focal DRE who became seizure-free after focal epilepsy surgery, and aimed to investigate the changes in the spindle generation before and after the surgery using low-density scalp EEG and electrical source imaging (ESI). METHODS: We analyzed N2-sleep EEGs from 19 children with DRE before and after surgery. We identified slow (8-12 Hz) and fast spindles (13-16 Hz), computed their spectral features and cortical generators through ESI and computed their distance from the EZ and irritative zone (IZ). We performed two-way ANOVA testing the effect of spindle type (slow vs. fast) and surgical phase (pre-surgery vs. post-surgery) on each feature. RESULTS: Power, frequency and cortical activation of slow spindles increased after surgery (p < 0.005), while this was not seen for fast spindles. Before surgery, the cortical generators of slow spindles were closer to the EZ (57.3 vs. 66.2 mm, p = 0.007) and IZ (41.3 vs. 55.5 mm, p = 0.02) than fast spindle generators. CONCLUSIONS: Our data indicate alterations in the EEG slow spindles after resective epilepsy surgery. Fast spindle generation on the contrary did not change after surgery. Although the study is limited by its retrospective nature, lack of healthy controls, and reduced cortical spatial sampling, our findings suggest a spatial relationship between the slow spindles and the epileptogenic generators.

Association of genetic and sulcal traits with executive function in congenital heart disease.

OBJECTIVE: Persons with congenital heart disease (CHD) are at increased risk of neurodevelopmental disabilities, including impairments to executive function. Sulcal pattern features correlate with executive function in adolescents with single-ventricle heart disease and tetralogy of Fallot. However, the interaction of sulcal pattern features with genetic and participant factors in predicting executive dysfunction is unknown. METHODS: We studied sulcal pattern features, participant factors, and genetic risk for executive function impairment in a cohort with multiple CHD types using stepwise linear regression and machine learning. RESULTS: Genetic factors, including predicted damaging de novo or rare inherited variants in neurodevelopmental disabilities risk genes, apolipoprotein E genotype, and principal components of sulcal pattern features were associated with executive function measures after adjusting for age at testing, sex, mother's education, and biventricular versus single-ventricle CHD in a linear regression model. Using regression trees and bootstrap validation, younger participant age and larger alterations in sulcal pattern features were consistently identified as important predictors of decreased cognitive flexibility with left hemisphere graph topology often selected as the most important predictor. Inclusion of both sulcal pattern and genetic factors improved model fit compared to either alone. INTERPRETATION: We conclude that sulcal measures remain important predictors of cognitive flexibility, and the model predicting executive outcomes is improved by inclusion of potential genetic sources of neurodevelopmental risk. If confirmed, measures of sulcal patterning may serve as early imaging biomarkers to identify those at heightened risk for future neurodevelopmental disabilities.

Outcomes of Consolidative Nephrectomy following Primary Immunotherapy in Advanced Renal Cell Carcinoma: A Multicenter Analysis.

BACKGROUND: To evaluate effect and outcomes of combination primary immunotherapy (IO) and nephrectomy for advanced renal cell carcinoma (RCC). METHODS: We conducted a multicenter, retrospective analysis of patients with advanced/metastatic RCC who received IO followed by nephrectomy. Primary outcome was Bifecta (negative surgical margins and no 30-day surgical complications). Secondary outcomes included progression-free survival (PFS) following surgery, reduction in tumor/thrombus size, RENAL score, and clinical/pathologic downstaging. Cox regression multivariable analysis was conducted for predictors of Bifecta and PFS. Kaplan-Meier analysis assessed PFS, comparing Bifecta and non-Bifecta groups. RESULTS: A total of 56 patients were analyzed (median age 63 years; median follow-up 22.5 months). A total of 40 (71.4%) patients were intermediate IMDC risk. Patients were treated with immunotherapy for median duration of 8.1 months. Immunotherapy resulted in reductions in tumor size (P < .001), thrombus size (P = .02), and RENAL score (P < .001); 38 (67.9%) patients were clinically downstaged on imaging (P < .001) and 25 (44.6%) patients were pathologically downstaged following surgery (P < .001). Bifecta was achieved in 38 (67.9%) patients. Predictors for bifecta achievement included decreasing tumor size (HR 1.08, P = .043) and pathological downstaging (HR 2.13, P = .047). Bifecta (HR 5.65, P = .009), pathologic downstaging (HR 5.15, P = .02), and increasing reduction in tumor size (HR 1.2, P = .007) were associated with improved PFS. Bifecta patients demonstrated improved 2-year PFS (84% vs. 71%, P = .019). CONCLUSIONS: Primary immunotherapy reduced tumor/thrombus size and complexity. Pathologically downstaged patients were more likely to achieve bifecta, and these patients displayed improved 2-year PFS. Our study supports further inquiry in the use of CRN following primary immunotherapy for advanced renal cancer.

Acute Diffusion-Weighted Imaging Signaling Severe Periventricular Leukomalacia in Preterm Infants: Case Report and Review of Literature.

Introduction: Periventricular leukomalacia occurs in up to 25% of very preterm infants resulting in adverse neurodevelopmental outcomes. In its acute phase, periventricular leukomalacia is clinically silent. Although ultrasonography is widely available, its sensitivity in the early detection of periventricular leukomalacia is low. Case Report and Published Literature: We identified a preterm infant with early diffusion-weighted imaging changes that later evolved to periventricular leukomalacia. Thirty-two cases of abnormal diffusion-weighted imaging reliably heralding severe periventricular leukomalacia in the preterm infant have been published in the literature. Notable features include the following: (1) infants were more mature preterm infants (29-36 weeks' gestation); (2) findings were often serendipitous with benign clinical courses; (3) diffusion-weighted imaging changes only were evident in the first weeks of life with later evolution to more classical abnormalities on conventional magnetic resonance imaging (MRI) or ultrasonography. Conclusion: Diffusion-weighted imaging in the first week of life may be a reliable early marker of severe periventricular leukomalacia injury in more mature preterm infants.

p53 restoration in small cell lung cancer identifies a latent cyclophilin-dependent necrosis mechanism.

The p53 tumor suppressor regulates multiple context-dependent tumor suppressive programs. Although p53 is mutated in ~90% of small cell lung cancer (SCLC) tumors, how p53 mediates tumor suppression in this context is unknown. Here, using a mouse model of SCLC in which endogenous p53 expression can be conditionally and temporally regulated, we show that SCLC tumors maintain a requirement for p53 inactivation. However, we identify tumor subtype heterogeneity between SCLC tumors such that p53 reactivation induces senescence in a subset of tumors, while in others, p53 induces necrosis. We pinpoint cyclophilins as critical determinants of a p53-induced transcriptional program that is specific to SCLC tumors and cell lines poised to undergo p53-mediated necrosis. Importantly, inhibition of cyclophilin isomerase activity, or genetic ablation of specific cyclophilin genes, suppresses p53-mediated necrosis by limiting p53 transcriptional output without impacting p53 chromatin binding. Our study demonstrates that intertumoral heterogeneity in SCLC influences the biological response to p53 restoration, describes a cyclophilin-dependent mechanism of p53-regulated cell death, and uncovers putative mechanisms for the treatment of this most-recalcitrant tumor type.

SSL-QALAS: Self-Supervised Learning for rapid multiparameter estimation in quantitative MRI using 3D-QALAS.

PURPOSE: To develop and evaluate a method for rapid estimation of multiparametric T1 , T2 , proton density, and inversion efficiency maps from 3D-quantification using an interleaved Look-Locker acquisition sequence with T2 preparation pulse (3D-QALAS) measurements using self-supervised learning (SSL) without the need for an external dictionary. METHODS: An SSL-based QALAS mapping method (SSL-QALAS) was developed for rapid and dictionary-free estimation of multiparametric maps from 3D-QALAS measurements. The accuracy of the reconstructed quantitative maps using dictionary matching and SSL-QALAS was evaluated by comparing the estimated T1 and T2 values with those obtained from the reference methods on an International Society for Magnetic Resonance in Medicine/National Institute of Standards and Technology phantom. The SSL-QALAS and the dictionary-matching methods were also compared in vivo, and generalizability was evaluated by comparing the scan-specific, pre-trained, and transfer learning models. RESULTS: Phantom experiments showed that both the dictionary-matching and SSL-QALAS methods produced T1 and T2 estimates that had a strong linear agreement with the reference values in the International Society for Magnetic Resonance in Medicine/National Institute of Standards and Technology phantom. Further, SSL-QALAS showed similar performance with dictionary matching in reconstructing the T1 , T2 , proton density, and inversion efficiency maps on in vivo data. Rapid reconstruction of multiparametric maps was enabled by inferring the data using a pre-trained SSL-QALAS model within 10 s. Fast scan-specific tuning was also demonstrated by fine-tuning the pre-trained model with the target subject's data within 15 min. CONCLUSION: The proposed SSL-QALAS method enabled rapid reconstruction of multiparametric maps from 3D-QALAS measurements without an external dictionary or labeled ground-truth training data.

Negative versus withdrawn maternal behavior: Differential associations with infant gray and white matter during the first 2 years of life.

Distinct neural effects of threat versus deprivation emerge by childhood, but little data are available in infancy. Withdrawn versus negative parenting may represent dimensionalized indices of early deprivation versus early threat, but no studies have assessed neural correlates of withdrawn versus negative parenting in infancy. The objective of this study was to separately assess the links of maternal withdrawal and maternal negative/inappropriate interaction with infant gray matter volume (GMV), white matter volume (WMV), amygdala, and hippocampal volume. Participants included 57 mother-infant dyads. Withdrawn and negative/inappropriate aspects of maternal behavior were coded from the Still-Face Paradigm at four months infant age. Between 4 and 24 months (M age = 12.28 months, SD = 5.99), during natural sleep, infants completed an MRI using a 3.0 T Siemens scanner. GMV, WMV, amygdala, and hippocampal volumes were extracted via automated segmentation. Diffusion weighted imaging volumetric data were also generated for major white matter tracts. Maternal withdrawal was associated with lower infant GMV. Negative/inappropriate interaction was associated with lower overall WMV. Age did not moderate these effects. Maternal withdrawal was further associated with reduced right hippocampal volume at older ages. Exploratory analyses of white matter tracts found that negative/inappropriate maternal behavior was specifically associated with reduced volume in the ventral language network. Results suggest that quality of day-to-day parenting is related to infant brain volumes during the first two years of life, with distinct aspects of interaction associated with distinct neural effects.

BOston Neonatal Brain Injury Dataset for Hypoxic Ischemic Encephalopathy (BONBID-HIE): Part I. MRI and Manual Lesion Annotation.

Hypoxic ischemic encephalopathy (HIE) is a brain injury that occurs in 1 ~ 5/1000 term neonates. Accurate identification and segmentation of HIE-related lesions in neonatal brain magnetic resonance images (MRIs) is the first step toward predicting prognosis, identifying high-risk patients, and evaluating treatment effects. It will lead to a more accurate estimation of prognosis, a better understanding of neurological symptoms, and a timely prediction of response to therapy. We release the first public dataset containing neonatal brain diffusion MRI and expert annotation of lesions from 133 patients diagnosed with HIE. HIE-related lesions in brain MRI are often diffuse (i.e., multi-focal), and small (over half the patients in our data having lesions occupying <1% of brain volume). Segmentation for HIE MRI data is remarkably different from, and arguably more challenging than, other segmentation tasks such as brain tumors with focal and relatively large lesions. We hope that this dataset can help fuel the development of MRI lesion segmentation methods for HIE and small diffuse lesions in general.

The interaction between Epstein-Barr virus and multiple sclerosis genetic risk loci: insights into disease pathogenesis and therapeutic opportunities.

Multiple sclerosis (MS) is a chronic neurodegenerative autoimmune disease, characterised by the demyelination of neurons in the central nervous system. Whilst it is unclear what precisely leads to MS, it is believed that genetic predisposition combined with environmental factors plays a pivotal role. It is estimated that close to half the disease risk is determined by genetic factors. However, the risk of developing MS cannot be attributed to genetic factors alone, and environmental factors are likely to play a significant role by themselves or in concert with host genetics. Epstein-Barr virus (EBV) infection is the strongest known environmental risk factor for MS. There has been increasing evidence that leaves little doubt that EBV is necessary, but not sufficient, for developing MS. One plausible explanation is EBV may alter the host immune response in the presence of MS risk alleles and this contributes to the pathogenesis of MS. In this review, we discuss recent findings regarding how EBV infection may contribute to MS pathogenesis via interactions with genetic risk loci and discuss possible therapeutic interventions.

Pathological Outcomes of Patients With Advanced Renal Cell Carcinoma Who Receive Nephrectomy Following Immunotherapy.

BACKGROUND: Even though cytoreductive nephrectomy (CN) was once the standard of care for patients with advanced renal cell carcinoma (RCC), its role in treatment has not been well analyzed or defined in the era of immunotherapy (IO). MATERIALS AND METHODS: This study analyzed pathological outcomes in patients with advanced or metastatic RCC who received IO prior to CN. This was a multi-institutional, retrospective study of patients with advanced or metastatic RCC. Patients were required to receive IO monotherapy or combination therapy prior to radical or partial CN. The primary endpoint assessed surgical pathologic outcomes, including American Joint Committee on Cancer (AJCC) staging and frequency of downstaging, at the time of surgery. Pathologic outcomes were correlated to clinical variables using a Wald-chi squared test from Cox regression in a multi-variable analysis. Secondary outcomes included objective response rate (ORR) defined by response evaluation criteria in solid tumors (RECIST) version 1.1 and progression-free survival (PFS), which were estimated using the Kaplan-Meier method with reported 95% CIs. RESULTS: Fifty-two patients from 9 sites were included. Most patients were male (65%), 81% had clear cell histology, 11% had sarcomatoid differentiation. Overall, 44% of patients experienced pathologic downstaging, and 13% had a complete pathologic response. The ORR immediately prior to nephrectomy was stable disease in 29% of patients, partial response in 63%, progressive disease in 4%, and 4% unknown. Median follow-up for the entire cohort was 25.3 months and median PFS was 3.5 years (95% CI, 2.1-4.9). CONCLUSIONS: IO-based interventions prior to CN in patients with advanced or metastatic RCC demonstrates efficacy, with a small fraction of patients showing a complete response. Additional prospective studies are warranted to investigate the role of CN in the modern IO-era.

Experimental Approaches for the Synthesis of Low-Valent Metal-Organic Frameworks from Multitopic Phosphine Linkers.

Metal-organic frameworks (MOFs) are the subject of intense research focus due to their potential applications in gas storage and separation, biomedicine, energy, and catalysis. Recently, low-valent MOFs (LVMOFs) have been explored for their potential use as heterogeneous catalysts, and multitopic phosphine linkers have been shown to be a useful building block for the formation of LVMOFs. However, the synthesis of LVMOFs using phosphine linkers requires conditions that are distinct from those in the majority of the MOF synthetic literature, including the exclusion of air and water and the use of unconventional modulators and solvents, making it somewhat more challenging to access these materials. This work serves as a general tutorial for the synthesis of LVMOFs with phosphine linkers, including information on the following: 1) the judicious choice of the metal precursor, modulator, and solvent; 2) the experimental procedures, air-free techniques, and required equipment; 3) the proper storage and handling of the resultant LVMOFs; and 4) useful characterization methods for these materials. The intention of this report is to lower the barrier to this new subfield of MOF research and facilitate advancements toward novel catalytic materials.

Morphological Features of Language Regions in Individuals with Tuberous Sclerosis Complex.

A significant number of individuals with tuberous sclerosis complex (TSC) exhibit language difficulties. Here, we examined the language-related brain morphometry in 59 participants (7 participants with TSC and comorbid autism spectrum disorder (ASD) (TSC + ASD), 13 with TSC but no ASD (TSC-ASD), 10 with ASD-only (ASD), and 29 typically developing (TD) controls). A hemispheric asymmetry was noted in surface area and gray matter volume of several cortical language areas in TD, ASD, and TSC-ASD groups, but not in TSC + ASD group. TSC + ASD group demonstrated increased cortical thickness and curvature values in multiple language regions for both hemispheres, compared to other groups. After controlling for tuber load in the TSC groups, within-group differences stayed the same but the differences between TSC-ASD and TSC + ASD were no longer statistically significant. These preliminary findings suggest that comorbid ASD in TSC as well as tuber load in TSC is associated with changes in the morphometry of language regions. Future studies with larger sample sizes will be needed to confirm these findings.

Diffusion-Weighted Magnetic Resonance Imaging Demonstrates White Matter Alterations in Watershed Regions in Children With Moyamoya Without Stroke or Silent Infarct.

BACKGROUND: Moyamoya is a disease with progressive cerebral arterial stenosis leading to stroke and silent infarct. Diffusion-weighted magnetic resonance imaging (dMRI) studies show that adults with moyamoya have significantly lower fractional anisotropy (FA) and higher mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) compared with controls, which raises concern for unrecognized white matter injury. Children with moyamoya have significantly lower FA and higher MD in their white matter compared with controls. However, it is unknown which white matter tracts are affected in children with moyamoya. METHODS: We present a cohort of 15 children with moyamoya with 24 affected hemispheres without stroke or silent infarct compared with 25 controls. We analyzed dMRI data using unscented Kalman filter tractography and extracted major white matter pathways with a fiber clustering method. We compared the FA, MD, AD, and RD in each segmented white matter tract and combined white matter tracts found within the watershed region using analysis of variance. RESULTS: Age and sex were not significantly different between children with moyamoya and controls. Specific white matter tracts affected included inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, superior longitudinal fasciculus, thalamofrontal, uncinate fasciculus, and arcuate fasciculus. Combined watershed region white matter tracts in children with moyamoya had significantly lower FA (-7.7% ± 3.2%, P = 0.02) and higher MD (4.8% ± 1.9%, P = 0.01) and RD (8.7% ± 2.8%, P = 0.002). CONCLUSIONS: Lower FA with higher MD and RD is concerning for unrecognized white matter injury. Affected tracts were located in watershed regions suggesting that the findings may be due to chronic hypoperfusion. These findings support the concern that children with moyamoya without overt stroke or silent infarction are sustaining ongoing injury to their white matter microstructure and provide practitioners with a noninvasive method of more accurately assessing disease burden in children with moyamoya.

Conserved but not critical: Trafficking and function of NaV1.7 are independent of highly conserved polybasic motifs.

Non-addictive treatment of chronic pain represents a major unmet clinical need. Peripheral voltage-gated sodium (NaV) channels are an attractive target for pain therapy because they initiate and propagate action potentials in primary afferents that detect and transduce noxious stimuli. NaV1.7 sets the gain on peripheral pain-signaling neurons and is the best validated peripheral ion channel involved in human pain, and previous work has shown that it is transported in vesicles in sensory axons which also carry Rab6a, a small GTPase known to be involved in vesicular packaging and axonal transport. Understanding the mechanism of the association between Rab6a and NaV1.7 could inform therapeutic modalities to decrease trafficking of NaV1.7 to the distal axonal membrane. Polybasic motifs (PBM) have been shown to regulate Rab-protein interactions in a variety of contexts. In this study, we explored whether two PBMs in the cytoplasmic loop that joins domains I and II of human NaV1.7 were responsible for association with Rab6a and regulate axonal trafficking of the channel. Using site-directed mutagenesis we generated NaV1.7 constructs with alanine substitutions in the two PBMs. Voltage-clamp recordings showed that the constructs retain wild-type like gating properties. Optical Pulse-chase Axonal Long-distance (OPAL) imaging in live sensory axons shows that mutations of these PBMs do not affect co-trafficking of Rab6a and NaV1.7, or the accumulation of the channel at the distal axonal surface. Thus, these polybasic motifs are not required for interaction of NaV1.7 with the Rab6a GTPase, or for trafficking of the channel to the plasma membrane.

NeSVoR: Implicit Neural Representation for Slice-to-Volume Reconstruction in MRI.

Reconstructing 3D MR volumes from multiple motion-corrupted stacks of 2D slices has shown promise in imaging of moving subjects, e. g., fetal MRI. However, existing slice-to-volume reconstruction methods are time-consuming, especially when a high-resolution volume is desired. Moreover, they are still vulnerable to severe subject motion and when image artifacts are present in acquired slices. In this work, we present NeSVoR, a resolution-agnostic slice-to-volume reconstruction method, which models the underlying volume as a continuous function of spatial coordinates with implicit neural representation. To improve robustness to subject motion and other image artifacts, we adopt a continuous and comprehensive slice acquisition model that takes into account rigid inter-slice motion, point spread function, and bias fields. NeSVoR also estimates pixel-wise and slice-wise variances of image noise and enables removal of outliers during reconstruction and visualization of uncertainty. Extensive experiments are performed on both simulated and in vivo data to evaluate the proposed method. Results show that NeSVoR achieves state-of-the-art reconstruction quality while providing two to ten-fold acceleration in reconstruction times over the state-of-the-art algorithms.