Elevated plasma neurofilament light was associated with multi-modal neuroimaging features in Alzheimer's disease signature regions and predicted future tau deposition.

BACKGROUND: Neurofilament Light (NfL) is a biomarker for early neurodegeneration in Alzheimer's disease (AD). This study aims to examine the association between plasma NfL and multi-modal neuroimaging features across the AD spectrum and whether NfL predicts future tau deposition. METHODS: The present study recruited 517 participants comprising Aß negative cognitively normal (CN-) participants (n = 135), Aß positive cognitively normal (CN +) participants (n = 64), individuals with amnestic mild cognitive impairment (aMCI) (n = 212), and those diagnosed with AD dementia (n = 106). All the participants underwent multi-modal neuroimaging examinations. Cross-sectional and longitudinal associations between plasma NfL and multi-modal neuro-imaging features were evaluated using partial correlation analysis and linear mixed effects models. We also used linear regression analysis to investigate the association of baseline plasma NfL with future PET tau load. Mediation analysis was used to explore whether the effect of NfL on cognition was mediated by these imaging biomarkers. RESULTS: The results showed that baseline NfL levels and the rate of change were associated with Aß deposition, brain atrophy, brain connectome, glucose metabolism, and brain perfusion in AD signature regions (P<0.05). In both Aß positive CN and MCI participants, baseline NfL showed a significant predictive value of elevating tau burden in the left medial orbitofrontal cortex and para-hippocampus (ß = 0.336, P = 0.032; ß = 0.313, P = 0.047). Lastly, the multi-modal neuroimaging features mediated the association between plasma NfL and cognitive performance. CONCLUSIONS: The study supports the association between plasma NfL and multi-modal neuroimaging features in AD-vulnerable regions and its predictive value for future tau deposition.

Multi-planar dual adversarial network based on dynamic 3D features for MRI-CT head and neck image synthesis.

Objective.Head and neck radiotherapy planning requires electron densities from different tissues for dose calculation. Dose calculation from imaging modalities such as MRI remains an unsolved problem since this imaging modality does not provide information about the density of electrons.Approach.We propose a generative adversarial network (GAN) approach that synthesizes CT (sCT) images from T1-weighted MRI acquisitions in head and neck cancer patients. Our contribution is to exploit new features that are relevant for improving multimodal image synthesis, and thus improving the quality of the generated CT images. More precisely, we propose a Dual branch generator based on the U-Net architecture and on an augmented multi-planar branch. The augmented branch learns specific 3D dynamic features, which describe the dynamic image shape variations and are extracted from different view-points of the volumetric input MRI. The architecture of the proposed model relies on an end-to-end convolutional U-Net embedding network.Results.The proposed model achieves a mean absolute error (MAE) of18.76±5.167in the target Hounsfield unit (HU) space on sagittal head and neck patients, with a mean structural similarity (MSSIM) of0.95±0.09and a Frechet inception distance (FID) of145.60±8.38. The model yields a MAE of26.83±8.27to generate specific primary tumor regions on axial patient acquisitions, with a Dice score of0.73±0.06and a FID distance equal to122.58±7.55. The improvement of our model over other state-of-the-art GAN approaches is of 3.8%, on a tumor test set. On both sagittal and axial acquisitions, the model yields the best peak signal-to-noise ratio of27.89±2.22and26.08±2.95to synthesize MRI from CT input.Significance.The proposed model synthesizes both sagittal and axial CT tumor images, used for radiotherapy treatment planning in head and neck cancer cases. The performance analysis across different imaging metrics and under different evaluation strategies demonstrates the effectiveness of our dual CT synthesis model to produce high quality sCT images compared to other state-of-the-art approaches. Our model could improve clinical tumor analysis, in which a further clinical validation remains to be explored.

Intrinsic Infant Hippocampal Function Supports Inhibitory Processing.

Impaired cerebral inhibition is commonly observed in neurodevelopmental disorders and may represent a vulnerability factor for their development. The hippocampus plays a key role in inhibition among adults and undergoes significant and rapid changes during early brain development. Therefore, the structure represents an important candidate region for early identification of pathology that is relevant to inhibitory dysfunction. To determine whether hippocampal function corresponds to inhibition in the early postnatal period, the present study evaluated relationships between hippocampal activity and sensory gating in infants 4-20 weeks of age (N = 18). Resting-state functional magnetic resonance imaging was used to measure hippocampal activity, including the amplitude of low-frequency fluctuations (ALFFs) and fractional ALFF. Electroencephalography during a paired-stimulus paradigm was used to measure sensory gating (P50). Higher activity of the right hippocampus was associated with better sensory gating (P50 ratio), driven by a reduction in response to the second stimulus. These findings suggest that meaningful effects of hippocampal function can be detected early in infancy. Specifically, higher intrinsic hippocampal activity in the early postnatal period may support effective inhibitory processing. Future work will benefit from longitudinal analysis to clarify the trajectory of hippocampal function, alterations of which may contribute to the risk of neurodevelopmental disorders and represent an intervention target.

The blushing brain: neural substrates of cheek temperature increase in response to self-observation.

Darwin proposed that blushing-the reddening of the face owing to heightened self-awareness-is 'the most human of all expressions'. Yet, relatively little is known about the underlying mechanisms of blushing. Theories diverge on whether it is a rapid, spontaneous emotional response that does not involve reflection upon the self or whether it results from higher-order socio-cognitive processes. Investigating the neural substrates of blushing can shed light on the mental processes underlying blushing and the mechanisms involved in self-awareness. To reveal neural activity associated with blushing, 16-20 year-old participants (n = 40) watched pre-recorded videos of themselves (versus other people as a control condition) singing karaoke in a magnetic resonance imaging scanner. We measured participants' cheek temperature increase-an indicator of blushing-and their brain activity. The results showed that blushing is higher when watching oneself versus others sing. Those who blushed more while watching themselves sing had, on average, higher activation in the cerebellum (lobule V) and the left paracentral lobe and exhibited more time-locked processing of the videos in early visual cortices. These findings show that blushing is associated with the activation of brain areas involved in emotional arousal, suggesting that it may occur independently of higher-order socio-cognitive processes. Our results provide new avenues for future research on self-awareness in infants and non-human animals.

[Radiographic parameters and influencing factors of paraspinal muscle degeneration in healthy people].

Objective: To measure the paraspinal muscle parameters, explore the characteristics of paraspinal muscles, and investigate the influence factors of paraspinal muscle degeneration in healthy people. Methods: Eighty-two healthy Chinese people were prospectively recruited between February 2020 and November 2020, including 36 males and 46 females. The age ranged from 21 to 75 years, with a mean of 48.0 years. The height ranged from 150 to 183 cm, with a mean of 165.6 cm. The body mass ranged from 43 to 100 kg, with a mean of 65.4 kg. The body mass index (BMI) ranged from 16.7 to 32.4 kg/m 2, with a mean of 23.7 kg/m 2. Parameters of the paraspinal muscles (multifidus muscle, erector spinae muscle, and psoas major muscle) at L 3, L 4, and L 5 levels were measured by MRI, including the relative total cross-sectional area (rtCSA), relative fatty cross-sectional area (rfCSA), relative signal intensity (rSI), and fatty infiltration (FI). The differences of paraspinal muscle parameters at different genders and different measurement levels were compared; Pearson or Spearman correlation analysis was used to explore the relationship between paraspinal muscle parameters and age, height, body mass, BMI. Results: From L 3 to L 5 level, the rtCSA and rfCSA of multifidus muscle and psoas major muscle as well as the rfCSA of erector spinae muscle increased, while rtCSA of erector spinae muscle decreased. The FI and rSI of paraspinal muscles increased gradually. The parameters of paraspinal muscles at L 4 and L 5 levels were significantly different from those at L 3 levels ( P<0.05). There were significant differences in rtCSA and rfCSA of multifidus muscle, rtCSA, FI, and rSI of erector spinae muscle as well as rtCSA, rfCSA, and FI of psoas major muscle between L 4 and L 5 levels ( P<0.05). Compared with males, the rfCSA and FI of multifidus muscle, FI of erector spinae muscle, and FI of psoas major muscle were significantly higher in females, while the rtCSA of psoas major muscle was significantly lower ( P<0.05). Age was significantly negatively correlated with rtCSA of paraspinal muscles ( P<0.05), but significantly positively correlated with FI of paraspinal muscles, rfCSA and rSI of multifidus and erector spinae muscles ( P<0.05). Height was significantly negatively correlated with rfCSA and FI of paraspinal muscles ( P<0.05). Conclusion: The degree of paraspinal muscle degeneration increases gradually along the spine axis from head to tail. Paraspinal muscle degeneration is related to age, height, and gender. The relationship between the body mass, BMI and paraspinal muscle degeneration needs further study.

Neurostructural subgroup in 4291 individuals with schizophrenia identified using the subtype and stage inference algorithm.

Machine learning can be used to define subtypes of psychiatric conditions based on shared biological foundations of mental disorders. Here we analyzed cross-sectional brain images from 4,222 individuals with schizophrenia and 7038 healthy subjects pooled across 41 international cohorts from the ENIGMA, non-ENIGMA cohorts and public datasets. Using the Subtype and Stage Inference (SuStaIn) algorithm, we identify two distinct neurostructural subgroups by mapping the spatial and temporal 'trajectory' of gray matter change in schizophrenia. Subgroup 1 was characterized by an early cortical-predominant loss with enlarged striatum, whereas subgroup 2 displayed an early subcortical-predominant loss in the hippocampus, striatum and other subcortical regions. We confirmed the reproducibility of the two neurostructural subtypes across various sample sites, including Europe, North America and East Asia. This imaging-based taxonomy holds the potential to identify individuals with shared neurobiological attributes, thereby suggesting the viability of redefining existing disorder constructs based on biological factors.

Hippocampal connectivity patterns echo macroscale cortical evolution in the primate brain.

While the hippocampus is key for human cognitive abilities, it is also a phylogenetically old cortex and paradoxically considered evolutionarily preserved. Here, we introduce a comparative framework to quantify preservation and reconfiguration of hippocampal organisation in primate evolution, by analysing the hippocampus as an unfolded cortical surface that is geometrically matched across species. Our findings revealed an overall conservation of hippocampal macro- and micro-structure, which shows anterior-posterior and, perpendicularly, subfield-related organisational axes in both humans and macaques. However, while functional organisation in both species followed an anterior-posterior axis, we observed a marked reconfiguration in the latter across species, which mirrors a rudimentary integration of the default-mode-network in non-human primates. Here we show that microstructurally preserved regions like the hippocampus may still undergo functional reconfiguration in primate evolution, due to their embedding within heteromodal association networks.

Gut proinflammatory bacteria is associated with abnormal functional connectivity of hippocampus in unmedicated patients with major depressive disorder.

Accumulating evidence has revealed the gut bacteria dysbiosis and brain hippocampal functional and structural alterations in major depressive disorder (MDD). However, the potential relationship between the gut microbiota and hippocampal function alterations in patients with MDD is still very limited. Data of resting-state functional magnetic resonance imaging were acquired from 44 unmedicated MDD patients and 42 demographically matched healthy controls (HCs). Severn pairs of hippocampus subregions (the bilateral cornu ammonis [CA1-CA3], dentate gyrus (DG), entorhinal cortex, hippocampal-amygdaloid transition area, and subiculum) were selected as the seeds in the functional connectivity (FC) analysis. Additionally, fecal samples of participants were collected and 16S rDNA amplicon sequencing was used to identify the altered relative abundance of gut microbiota. Then, association analysis was conducted to investigate the potential relationships between the abnormal hippocampal subregions FC and microbiome features. Also, the altered hippocampal subregion FC values and gut microbiota levels were used as features separately or together in the support vector machine models distinguishing the MDD patients and HCs. Compared with HCs, patients with MDD exhibited increased FC between the left hippocampus (CA2, CA3 and DG) and right hippocampus (CA2 and CA3), and decreased FC between the right hippocampal CA3 and bilateral posterior cingulate cortex. In addition, we found that the level of proinflammatory bacteria (i.e., Enterobacteriaceae) was significantly increased, whereas the level of short-chain fatty acids producing-bacteria (i.e., Prevotellaceae, Agathobacter and Clostridium) were significantly decreased in MDD patients. Furthermore, FC values of the left hippocampal CA3- right hippocampus (CA2 and CA3) was positively correlated with the relative abundance of Enterobacteriaceae in patients with MDD. Moreover, altered hippocampal FC patterns and gut microbiota level were considered in combination, the best discrimination was obtained (AUC = 0.92). These findings may provide insights into the potential role of gut microbiota in the underlying neuropathology of MDD patients.

Image classification and reconstruction from low-density EEG.

Recent advances in visual decoding have enabled the classification and reconstruction of perceived images from the brain. However, previous approaches have predominantly relied on stationary, costly equipment like fMRI or high-density EEG, limiting the real-world availability and applicability of such projects. Additionally, several EEG-based paradigms have utilized artifactual, rather than stimulus-related information yielding flawed classification and reconstruction results. Our goal was to reduce the cost of the decoding paradigm, while increasing its flexibility. Therefore, we investigated whether the classification of an image category and the reconstruction of the image itself is possible from the visually evoked brain activity measured by a portable, 8-channel EEG. To compensate for the low electrode count and to avoid flawed predictions, we designed a theory-guided EEG setup and created a new experiment to obtain a dataset from 9 subjects. We compared five contemporary classification models with our setup reaching an average accuracy of 34.4% for 20 image classes on hold-out test recordings. For the reconstruction, the top-performing model was used as an EEG-encoder which was combined with a pretrained latent diffusion model via double-conditioning. After fine-tuning, we reconstructed images from the test set with a 1000 trial 50-class top-1 accuracy of 35.3%. While not reaching the same performance as MRI-based paradigms on unseen stimuli, our approach greatly improved the affordability and mobility of the visual decoding technology.

Metabolic imaging across scales reveals distinct prostate cancer phenotypes.

Hyperpolarised magnetic resonance imaging (HP-13C-MRI) has shown promise as a clinical tool for detecting and characterising prostate cancer. Here we use a range of spatially resolved histological techniques to identify the biological mechanisms underpinning differential [1-13C]lactate labelling between benign and malignant prostate, as well as in tumours containing cribriform and non-cribriform Gleason pattern 4 disease. Here we show that elevated hyperpolarised [1-13C]lactate signal in prostate cancer compared to the benign prostate is primarily driven by increased tumour epithelial cell density and vascularity, rather than differences in epithelial lactate concentration between tumour and normal. We also demonstrate that some tumours of the cribriform subtype may lack [1-13C]lactate labelling, which is explained by lower epithelial lactate dehydrogenase expression, higher mitochondrial pyruvate carrier density, and increased lipid abundance compared to lactate-rich non-cribriform lesions. These findings highlight the potential of combining spatial metabolic imaging tools across scales to identify clinically significant metabolic phenotypes in prostate cancer.

Value of Optic Nerve MRI in Multiple Sclerosis Clinical Management: A MAGNIMS Position Paper and Future Perspectives.

The optic nerve is frequently involved in multiple sclerosis (MS). However, MRI of the optic nerve is considered optional in the differential diagnosis of optic neuropathy symptoms either at presentation or in established MS. In addition, unlike spinal cord imaging in comparable scenarios, no role is currently recommended for optic nerve MRI in patients presenting with optic neuritis for its confirmation, to plan therapeutic strategy, within the MS diagnostic framework, nor for the detection of subclinical activity in established MS. In this article, evidence related to these 3 aspects will be summarized and gaps in knowledge will be highlighted, including (1) the acquisition challenges and novel sequences that assess pathologic changes within the anterior visual pathways; (2) the clinical implications of quantitative magnetic resonance studies of the optic nerve, focusing on atrophy measures, magnetization transfer, and diffusion tensor imaging; and (3) the relevant clinical studies performed to date. Finally, an algorithm for the application of optic nerve MRI will be proposed to guide future studies aimed at addressing our knowledge gaps.

Pearls & Oy-sters: Case Report of a Ruptured Suprasellar Dermoid Cyst Presenting With Junctional Scotoma of Traquair.

A 27-year-old woman with a known suprasellar dermoid cyst and stable idiopathic intracranial hypertension (IIH) presented with new monocular vision change and new-onset headaches. Formal visual field testing accurately identified progressive chiasmal compression due to her suprasellar dermoid cyst before radiographic change was appreciable on magnetic resonance imaging. Accurate interpretation of her visual field findings avoided the common pitfall of attributing new visual symptoms to her IIH diagnosis. This case highlights the value of recognizing visual field changes that localize to the chiasm even in patients with history of other ophthalmologic conditions.

[A quantitative MRI comparative study of imaging markers for cerebral small vessel disease in the middle-aged and elderly patients with and without hypertension].

Objective: To explore the difference of MRI markers of small cerebral vascular disease in middle-aged and elderly patients with hypertension and non-hypertension. Methods: A cross-sectional study. The clinical data of 316 patients who underwent head MRI with susceptibility weighted imaging scans at the Affiliated Zhongda Hospital of Southeast University from November 2013 to August 2022 were retrospectively analyzed, including 190 males and 126 females, with the age of (71.6±8.9)years. According to the history of hypertension, the patients were divided into hypertension group(n=259) and the non-hypertension group(n=57). The patients in the non-hypertension group were further divided into abnormal blood pressure group on admission (n=19) and normal blood pressure group on admission (n=38). The imaging features of different CSVD dimensions in the patient's images were quantified or graded and compared between hypertensive and non-hypertensive patient groups. Deep learning methods were employed to segment white matter lesions, and voxel-wise analysis was conducted to investigate the differences in whole-brain white matter lesion probability between patients in both groups. Spearman correlation analysis was used to analyze the correlation between hypertension and small cerebral vascular disease. Results: Compared with the non-hypertensive group, the cerebral microhemorrhage count, deep microhemorrhage count, basal ganglia level lacunae count, perivascular space (EPVS) grade of hemioval center level and EPVS grade of basal ganglia level were higher in the hypertensive group (all P<0.05). The cerebral microhemorrhage count [3.0(1.0, 15.0) vs 1.0 (0, 4.2)], deep microhemorrhage count [1.0 (0, 7.0) vs 1.0 (0, 4.2)] and EPVS classification at basal ganglium level [2.0(1.0, 3.0) vs 1.0(1.0, 2.0)] in the group with history of hypertension were higher than those in the group with normal blood pressure at admission (all P<0.05). The EPVS grade at the central level of the semiovale in the hypertension group was higher than that of the group with normal blood pressure at admission [2.0(1.0, 2.0) vs 1.0 (1.0, 2.0)], and also higher than that of the group with abnormal blood pressure at admission [2.0(1.0, 2.0) vs 1.0(1.0, 2.0)](both P<0.05). Voxel-by-voxel analysis showed no significant difference in the probability of white matter lesions in the whole brain between patients with and without a history of hypertension, but patients with a history of hypertension showed more extensive para-ventricular white matter hypersignaling than those without a history of hypertension. Spearman correlation analysis showed that hypertension grade was correlated with the number of microbleeding lesions in depth (r=0.149), the number of lacunae lesions in the center of the hemioval (r=0.209), and the number of lacunae lesions in the basal ganglia (r=0.204) (all P<0.05). Conclusions: Chronic hypertension can affect different dimensions of small vessel disease imaging, primarily manifested in the increases of deep microbleed counts and the EPVS grade.

Formation of Zwitterionic and Self-Healable Hydrogels via Amino-yne Click Chemistry for Development of Cellular Scaffold and Tumor Spheroid Phantom for MRI.

In situ-forming biocompatible hydrogels have great potential in various medical applications. Here, we introduce a pH-responsive, self-healable, and biocompatible hydrogel for cell scaffolds and the development of a tumor spheroid phantom for magnetic resonance imaging. The hydrogel (pMAD) was synthesized via amino-yne click chemistry between poly(2-methacryloyloxyethyl phosphorylcholine-co-2-aminoethylmethacrylamide) and dialkyne polyethylene glycol. Rheology analysis, compressive mechanical testing, and gravimetric analysis were employed to investigate the gelation time, mechanical properties, equilibrium swelling, and degradability of pMAD hydrogels. The reversible enamine and imine bond mechanisms leading to the sol-to-gel transition in acidic conditions (pH ≤ 5) were observed. The pMAD hydrogel demonstrated potential as a cellular scaffold, exhibiting high viability and NIH-3T3 fibroblast cell encapsulation under mild conditions (37 °C, pH 7.4). Additionally, the pMAD hydrogel also demonstrated the capability for in vitro magnetic resonance imaging of glioblastoma tumor spheroids based on the chemical exchange saturation transfer effect. Given its advantages, the pMAD hydrogel emerges as a promising material for diverse biomedical applications, including cell carriers, bioimaging, and therapeutic agent delivery.

High-resolution and highly accelerated MRI T2 mapping as a tool to characterise renal tumour subtypes and grades.

BACKGROUND: Clinical imaging tools to probe aggressiveness of renal masses are lacking, and T2-weighted imaging as an integral part of magnetic resonance imaging protocol only provides qualitative information. We developed high-resolution and accelerated T2 mapping methods based on echo merging and using k-t undersampling and reduced flip angles (TEMPURA) and tested their potential to quantify differences between renal tumour subtypes and grades. METHODS: Twenty-four patients with treatment-naïve renal tumours were imaged: seven renal oncocytomas (RO); one eosinophilic/oncocytic renal cell carcinoma; two chromophobe RCCs (chRCC); three papillary RCCs (pRCC); and twelve clear cell RCCs (ccRCC). Median, kurtosis, and skewness of T2 were quantified in tumours and in the normal-adjacent kidney cortex and were compared across renal tumour subtypes and between ccRCC grades. RESULTS: High-resolution TEMPURA depicted the tumour structure at improved resolution compared to conventional T2-weighted imaging. The lowest median T2 values were present in pRCC (high-resolution, 51 ms; accelerated, 45 ms), which was significantly lower than RO (high-resolution; accelerated, p = 0.012) and ccRCC (high-resolution, p = 0.019; accelerated, p = 0.008). ROs showed the lowest kurtosis (high-resolution, 3.4; accelerated, 4.0), suggestive of low intratumoural heterogeneity. Lower T2 values were observed in higher compared to lower grade ccRCCs (grades 2, 3 and 4 on high-resolution, 209 ms, 151 ms, and 106 ms; on accelerated, 172 ms, 160 ms, and 102 ms, respectively), with accelerated TEMPURA showing statistical significance in comparison (p = 0.037). CONCLUSIONS: Both high-resolution and accelerated TEMPURA showed marked potential to quantify differences across renal tumour subtypes and between ccRCC grades. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03741426 . Registered on 13 November 2018. RELEVANCE STATEMENT: The newly developed T2 mapping methods have improved resolution, shorter acquisition times, and promising quantifiable readouts to characterise incidental renal masses.

Targeted opening of the blood-brain barrier using VCAM-1 functionalised microbubbles and "whole brain" ultrasound.

Metastatic tumours in the brain now represent one of the leading causes of death from cancer. Current treatments are largely ineffective owing to the combination of late diagnosis and poor delivery of therapies across the blood-brain barrier (BBB). Conjugating magnetic resonance imaging (MRI) contrast agents with a monoclonal antibody for VCAM-1 (anti-VCAM1) has been shown to enable detection of micrometastases, two to three orders of magnitude smaller in volume than those currently detectable clinically. The aim of this study was to exploit this targeting approach to enable localised and temporary BBB opening at the site of early-stage metastases using functionalised microbubbles and ultrasound. Methods: Microbubbles functionalised with anti-VCAM1 were synthesised and shown to bind to VCAM-1-expressing cells in vitro. Experiments were then conducted in vivo in a unilateral breast cancer brain metastasis mouse model using Gadolinium-DTPA (Gd-DTPA) enhanced MRI to detect BBB opening. Following injection of Gd-DTPA and targeted microbubbles, the whole brain volume was simultaneously exposed to ultrasound (0.5 MHz, 10% duty cycle, 0.7 MPa peak negative pressure, 2 min treatment time). T1-weighted MRI was then performed to identify BBB opening, followed by histological confirmation via immunoglobulin G (IgG) immunohistochemistry. Results: In mice treated with targeted microbubbles and ultrasound, statistically significantly greater extravasation of Gd-DTPA and IgG was observed in the left tumour-bearing hemisphere compared to the right hemisphere 5 min after treatment. No acute adverse effects were observed. There was no investigation of longer term bioeffects owing to the nature of the study. Conclusion: The results demonstrate the feasibility of using targeted microbubbles in combination with low intensity ultrasound to localise opening of the BBB to metastatic sites in the brain. This approach has potential application in the treatment of metastatic tumours whose location cannot be established a priori with conventional imaging methods.