Labeling Imaging Research Articles

Non-invasive imaging modalities for diagnosing pulsatile tinnitus: a comprehensive review and recommended imaging algorithm.

Pulsatile tinnitus (PT) is a challenging diagnostic condition arising from various vascular, neoplastic, and systemic disorders. Non-invasive imaging is essential for identifying underlying causes while minimizing risks of invasive diagnostic angiography. Although no consensus exists on the primary imaging modality for PT and currently CT, ultrasound, and MRI are used in the diagnostic pathway, MRI is increasingly preferred as the first-line screening test for its diagnostic efficacy and safety. MRI protocols such as time-of-flight, magnetic resonance angiography, diffusion-weighted imaging, and arterial spin labeling can identify serious causes, including vascular shunting lesions, venous sinus stenosis, and tumors. In this narrative review of the current literature we discuss the benefits and limitations of various non-invasive imaging modalities in identifying the characteristic imaging findings of the most common causes of PT and also provide an algorithm that clinicians can use to guide the imaging evaluation.

Deep adversarial learning models for distribution patterns of piezoelectric plate energy harvesting

This paper presents a novel approach utilizing piezoelectric plate structures with random electrode distribution patterns for energy harvesting applications across various vibration modes. For the first time, leveraging electromechanical Finite Element Analysis (eFEA) and data extraction techniques, we investigate the integration of conditional Generative Adversarial Networks (cGAN)-based dynamic models for this purpose. The cGAN offers an effective technique for generating realistic synthetic data conditioned on input parameters, thereby enabling the creation of diverse and representative datasets for training energy harvesting systems. The integration of eFEA with cGAN opens up new possibilities for optimizing the design and performance of piezoelectric energy harvesters across various applications. Specifically, we explore four distinct cGAN models-based mechanics of energy harvesters by deploying distribution patterns. These models include training data generated by stacking simultaneously mode images, utilizing separate cGAN models for each mode, labeling images by mode, and concatenating all mode images into one. Our study focuses on assessing the effectiveness of these models in minimizing loss in cGAN-based power generation and predicting Structural Similarity Index Measure (SSIM) values, and more importantly, identifying the predicted data point outputs from the generated pixel image extractions. By analyzing the generated data from numerical model and its application in deep learning, we aim to enhance the understanding of the effects of distribution patterns and image processing techniques for optimal power generation and the effectiveness of piezoelectric energy harvesting systems across different vibration modes. The studies explore how different distribution patterns affect the power harvesting efficiency and frequency bandwidth, utilizing the generated datasets.

The influence of alterations in the composition of intestinal microbiota on neurovascular coupling and cognitive dysfunction in individuals afflicted with CSVD

IntroductionAn expanding body of research has explored the crucial role of gut microbiota in cerebral small vessel disease (CSVD). The objective of this study is to investigate alterations in the gut microbiota structure among CSVD patients, to explore the correlation between differential taxonomic levels and the neurovascular coupling index as well as cognitive function and to elucidate the imaging and biomarkers of mild cognitive impairment (MCI) in CSVD. MethodsWe enrolled 104 patients with CSVD and 40 healthy controls (HC). Based on cognitive test scores, CSVD patients were categorized into a cognitively normal group (CSVD-NCI, n=61) and a mild cognitive impairment group (CSVD-MCI, n=43). Performing magnetic resonance imaging (MRI) scans, gut microbiota analysis, as well as clinical and neuropsychological assessments for all participants. Based on arterial spin labeling (ASL) and blood oxygen level-dependent (BOLD) imaging data, cerebral blood flow (CBF) and neural activity indices are computed. The coupling indices of CBF/mReHo, CBF/mfALFF, CBF/mALFF, and CBF/mDC are calculated to assess the whole-brain neurovascular coupling changes in patients with CSVD. ResultsSpecies annotation revealed differences in the composition at the phylum and genus levels among the HC, CSVD-NCI, and CSVD-MCI groups. Additionally, differential analysis using the Kruskal-Wallis test demonstrated specific dominant microbial communities in all three groups. The relative abundance of certain dominant microbial communities in CSVD patients exhibited correlations with neurovascular coupling and cognitive function. The combined assessment of Bacteroides genus and CBF/mDC proved effective in distinguishing between CSVD-NCI and CSVD-MCI, providing a novel non-invasive approach for the diagnosis of MCI in CSVD.

The value of nomogram based on MRI functional imaging in differentiating cerebral alveolar echinococcosis from brain metastases

ObjectiveThis study aims to evaluate the effectiveness of a nomogram model constructed using Diffusion Kurtosis Imaging (DKI) and 3D Arterial Spin Labeling (3D-ASL) functional imaging techniques in distinguishing between cerebral alveolar echinococcosis (CAE) and brain metastases (BM).MethodsProspectively collected were 24 cases (86 lesions) of patients diagnosed with CAE and 16 cases (69 lesions) of patients diagnosed with BM at the affiliated hospital of Qinghai University from 2018 to 2023, confirmed either pathologically or through comprehensive diagnosis. Both patient groups underwent DKI and 3D-ASL scanning. DKI parameters (Kmean, Dmean, FA, ADC) and cerebral blood flow (CBF) were analyzed for the parenchymal area, edema area, and symmetrical normal brain tissue area in both groups. There were 155 lesions in total in the two groups of patients. We used SPSS to randomly select 70% as the training set (108 lesions) and the remaining 30% as the test set (47 lesions) and performed a difference analysis between the two groups. The independent factors distinguishing CAE from BM were identified using univariate and multivariate logistic regression analyses. Based on these factors, a diagnostic model was constructed and expressed as a nomogram.ResultUnivariate and multivariate logistic regression analyses identified nDmean1 and nCBF1 in the lesion parenchyma area, as well as nKmean2 and nDmean2 in the edema area, as independent factors for distinguishing CAE from BM. The model's performance, measured by the area under the ROC curve (AUC), had values of 0.942 and 0.989 for the training and test sets, respectively. Calibration curves demonstrated that the predicted probabilities were highly consistent with the actual values, and DCA confirmed the model's high clinical utility.ConclusionThe nomogram model, which incorporates DKI and 3D-ASL functional imaging, effectively distinguishes CAE from BM. It offers an intuitive, accurate, and non-invasive method for differentiation, thus providing valuable guidance for subsequent clinical decisions.

Evaluation of segmentation and semi‐supervised learning for spotted spurge recognition in bermudagrass turf

AbstractDiverse datasets are crucial for training machine learning‐based weed recognition models. However, annotating (i.e., labeling) images can be laborious and time‐consuming. Choice of annotation method and training approach not only affects the overall model effectiveness but also its minimum training data requirements and development pace. Segmentation and semi‐supervised learning (SSL) may offer performance or training enhancements. This study evaluated (1) segmentation against object detection in spotted spurge [Chamaesyce maculata (L.) Small] recognition in Latitude 36 hybrid bermudagrass [Cynodon dactylon (L.) Pers. × C. transvaalensis Burtt‐Davy] maintained as a golf course fairway and (2) the potential of two‐step SSL‐based training procedure using data labeled both manually and automatically with a pre‐trained model to expedite the model development. The architecture used across this research was You Only Look Once version 8 (YOLOv8) employing nano, small, and medium variants. All models were trained with a dataset restricted to 1200 training and 300 validation images. Both annotation methods resulted in adequate spotted spurge identification, as evidenced with >0.60 (>0.50 acceptability threshold) medium average precision at intersection over union threshold of 0.50 (mAP@50). Although the difference was minimal, object detection performed superior to segmentation. The two‐step training effectively accelerated image annotation while preserving or improving (with 8:4 and 6:6 splits between manually and auto‐labeled data) object detection performance. Segmentation tolerated only 10:2 split and exhibited increased sensitivity to declining dataset quality proportionally to the increase in auto‐labeled images in the final training dataset. Findings show a two‐step SSL‐based training procedure expedites annotation, enhancing model development efficiency.

Isotope Encoded chemical Imaging Identifies Amyloid Plaque Age Dependent Structural Maturation, Synaptic Loss, and Increased Toxicity.

It is of critical importance to our understanding of Alzheimer's disease (AD) pathology to determine how key pathological factors are interconnected and implicated in nerve cell death, clinical symptoms, and disease progression. The formation of extracellular beta-amyloid (Aβ) plaques is the major pathological hallmark of AD and Aβ has been suggested to be a critical inducer of AD, driving disease pathogenesis. Exactly how Aβ plaque formation begins and how ongoing plaque deposition proceeds and initiates subsequent neurotoxic mechanisms is not well understood. The primary aim of our research is to elucidate the biochemical processes underlying early Aβ plaque formation in brain tissue. We recently introduced a chemical imaging paradigm based on mass spectrometry imaging (MSI) and metabolic isotope labelling to follow stable isotope labelling kinetics (iSILK) in vivo to track the in vivo build-up and deposition of Aβ. Herein, knock-in Aβ mouse models ( App NL-F ) that develop Aβ pathology gradually are metabolically labeled with stable isotopes. This chemical imaging approach timestamps amyloid plaques during the period of initial deposition allowing the fate of aggregating Aβ species from before and during the earliest events of plaque pathology through plaque maturation to be tracked. To identify the molecular and cellular response to plaque maturation, we integrated iSILK with single plaque transcriptomics performed on adjacent tissue sections. This enabled changes in gene expression to be tracked as a function of plaque age (as encoded in the Aβ peptide isotopologue pattern) distinct from changes due to the chronological age or pathological severity. This approach identified that plaque age correlates negatively with gene expression patterns associated with synaptic function as early as in 10-month-old animals but persists into 18 months. Finally, we integrated hyperspectral confocal microscopy into our multiomic approach to image amyloid structural isomers, revealing a positive correlation between plaque age and amyloid structural maturity. This analysis identified three categories of plaques, each with a distinct impact on the surrounding microenvironment. Here, we identified that older, more compact plaques were associated with the most significant synapse loss and toxicity. These data show how isotope-encoded MS imaging can be used to delineate Aβ toxicity dynamics in vivo. Moreover, we show for the first time a functional integration of dynamic MSI, structural plaque imaging and whole genome-wide spatial transcriptomics at the single plaque level. This multiomic approach offers an unprecedented combination of temporal and spatial resolution enabling a description of the earliest events of precipitating amyloid pathology and how Aβ modulates synaptotoxic mechanisms.

Whole-Tumor Clearing and Imaging of Intratumor Microbiota in Three Dimensions with miCDaL Strategy.

Acquiring detailed spatial information about intratumor microbiota in situ is challenging, which leaves 3D distributions of microbiota within entire tumors largely unexplored. Here, a modified iDISCO-CUBIC tissue clearing and D-amino acid microbiome labeling-based (miCDaL) strategy are proposed, that integrates microbiota in situ labeling, tissue clearing, and whole-mount tissue imaging to enable 3D visualization of indigenous intratumor microbiota. Leveraging whole-mount spatial resolution and centimeter-scale imaging depth, the 3D biogeography of microbiota is successfully charted across various tumors at different developmental stages, providing quantitative spatial insights in relation to host tumors. By incorporating an immunostaining protocol, 3D imaging of the immunologic microenvironment is achieved in both murine and human mammary tumors that is previously assumed to be bacteria-free. Notably, immune infiltrates, including T cells and NK cells, and tertiary lymphoid structures are conspicuously absent in bacteria-colonized regions. This 3D imaging strategy for mapping Indigenous intratumor microbiota offers valuable insights into host-microbiota interactions.

7703 Adrenal Cortical Carcinoma With Vascular Involvement - Complex Case Requiring Life-Saving Surgery With Bovine Pericardium- IVC Reconstruction

Abstract Disclosure: V. mehta: None. M. Renzu: None. K.N. Pereira: None. S. Sampath: None. S. Sruthi: None. E.B. Ruby: None. Adrenocortical carcinomas (ACCs) are rare endocrine tumors that exhibit unusual biological characteristics. Roughly 66% of cases are functional and have excessive hormone release causing classic symptoms of hypercortisolism, including plethora, diabetes, muscle weakness/atrophy, virilization, and osteoporosis. Few present with vague signs due to mass effects, including but not limited to abdominal/flank pain, fullness, or early satiety; the rest are incidental findings. We present a case of a 55-year-old female with no medical history presented following weeks of progressive abdominal pain with abdominal wall erythema, leg swelling, and dyspnea along with hirsutism, leukocytosis, elevated BNP, hematuria concerning for abdominal wall cellulitis and new-onset CHF. Initial CT chest revealed incompletely visualized incidental adrenal mass. Further investigations with CT abdomen and lab work revealed a left adrenal mass suspicious for ACC, extending into the left renal vein and IVC, elevated urine metanephrines and normetanephrine, and elevated cortisol levels with low ACTH. The dexamethasone suppression test confirmed inadequate cortisol suppression. Patient underwent aggressive surgery with exploratory laparotomy revealing tumor thrombus in left renal vein extending into Inferior vena cava (IVC). A left adrenalectomy, nephrectomy, and IVC reconstruction using a Bovine Pericardial Patch (BPP), which is majorly used for arterial reconstruction, was performed. Pathology results indicated ACC, measuring 13.5 cm, with extension into renal vein and vascular invasion, staged as pT4pN0 cM0 without evidence of deficient mismatch repair protein expression. ACCs are rare and profoundly aggressive malignancies with an incidence rate of 0.7–2.0 per million per year with bimodal age distribution. Disease peaks before the age of five and in the fourth to fifth decade of life, with increased incidence in females. Diagnosis cannot be conclusively established by a single histological technique, imaging, hormonal work-up, or immunohistochemical labeling, but surgical excision is the gold standard. Complete surgical resection is the only possible approach for curing or improving survival chances in patients with adrenal mass/metastasis. A retrospective case study of 36 venous reconstructions using BPP showed few complications like thrombosis in 14% (versus 11% in autologous venous repair), 11% reoperated, 3-4% developed partial thrombus and hematoma. Our case exemplifies the successful management of challenging ACC with vascular involvement using BPP, which is mostly used for arterial repairs and is now expanding to venous repairs. Outcomes stress the ongoing need for research and collaborative efforts to refine and standardize the ideal approach to ACC patients with IVC thrombosis and the use of BPP in venous repair. Presentation: 6/1/2024

Cationic fluorinated micelles for cell labeling and 19F-MR imaging

Magnetic resonance imaging (MRI) relies on appropriate contrast agents, especially for visualizing transplanted cells within host tissue. In recent years, compounds containing fluorine-19 have gained significant attention as MRI probe, particularly in dual 1H/19F-MR imaging. However, various factors affecting probe sensitivity, such as fluorine content and the equivalency of fluorine atoms, must be considered. In this study, we synthesized fluorinated micelles with adjustable surface positive charge density and investigated their physicochemical properties and MRI efficacy in phantoms and labeled cells. While the micelles exhibited clear signals in 19F-MR spectra and imaging, the concentrations required for MRI visualization of labeled cells were relatively high, adversely affecting cell viability. Despite their favourable physicochemical properties, achieving higher labeling rates without compromising cell viability during labeling remains a challenge for potential in vivo applications.

Cerebral perfusion in patients with unilateral internal carotid artery occlusion by dual post-labeling delays arterial spin labeling imaging.

Global and regional cerebral blood flow (CBF) changes in patients with unilateral internal carotid artery occlusion (ICAO) are unclear when the dual post-labeling delays (PLD) arterial spin labeling (ASL) magnetic resonance imaging (MRI) technique is used. Manual delineation of regions of interest for CBF measurement is time-consuming and laborious. To assess global and regional CBF changes in patients with unilateral ICAO with the ASL-MRI perfusion technique. Twenty hospitalized patients with ICAO and sex- and age-matched controls were included in the study. Regional CBF was measured by Dr. Brain's ASL software. The present study evaluated differences in global, middle cerebral artery (MCA) territory, anterior cerebral artery territory, and Alberta Stroke Program Early Computed Tomography Score (ASPECTS) regions (including the caudate nucleus, lentiform nucleus, insula ribbon, internal capsule, and M1-M6) and brain lobes (including frontal, parietal, temporal, and insular lobes) between ICAO patients and controls at PLD 1.5 s and PLD 2.5 s. When comparing CBF between ICAO patients and controls, the global CBF in ICAO patients was lower at both PLD 1.5 s and PLD 2.5 s; the CBF on the occluded side was lower in 15 brain regions at PLD 1.5 s, and it was lower in 9 brain regions at PLD 2.5 s; the CBF in the contralateral hemisphere was lower in the caudate nucleus and internal capsule at PLD 1.5 s and in M6 at PLD 2.5 s. The global CBF in ICAO patients was lower at PLD 1.5 s than at PLD 2.5 s. The ipsilateral CBF at PLD 1.5 s was lower than that at PLD 2.5 s in 15 regions, whereas the contralateral CBF was lower at PLD 1.5 s than at PLD 2.5 s in 12 regions. The ipsilateral CBF was lower than the contralateral CBF in 15 regions at PLD 1.5 s, and in M6 at PLD 2.5 s. Unilateral ICAO results in hypoperfusion in the global and MCA territories, especially in the ASPECTS area. Dual PLD settings prove more suitable for accurate CBF quantification in ICAO.

Arterial spin labeling detects trapped labeled spins in flow-diverted aneurysms and it reflects intra-aneurysmal flow stasis.

This study evaluated arterial spin labeling (ASL) imaging findings in flow-diverted aneurysms (FD-ANs). Twenty-one patients with internal carotid artery aneurysms treated with flow-diverter stent (FDS) were included. Time-of-flight magnetic resonance angiography (TOF-MRA) and ASL were performed before and after follow-up digital subtraction angiography (DSA) on the day, 6 months, and/or 1 year after treatment. Two radiologists rated the clarity of the depiction of FD-ANs for MRA on a 3-point scale and the ASL signal intensity of the aneurysm as negative or positive. A neurosurgeon assessed DSA findings using the O'Kelly-Marotta (OKM) grading scale, categorizing them into filling and stasis grades. The 23 examinations were classified according to the OKM grading scale, and the proportion of ASL-positive cases and the proportion of cases with MRA scores of 1-2 (detectable) were calculated for each grade. The relationship between the OKM grading scale and ASL positivity or MRA detectable was examined using Fisher's exact test. Of seven examinations where the statis grade was 1 or 2, no examinations showed ASL positivity. However, among the 16 examinations in which the stasis grade was 3, 9 examinations showed ASL positivity. A significant association was observed between stasis grade and ASL positivity (p = 0.035). In contrast, no significant relationship was observed between the OKM grading scale and the MRA 3-point scale. High-signal ASL in FD-ANs could reflect stasis within the aneurysm; therefore, noninvasive ASL can indicate reduction in intra-aneurysmal blood flow after treatment and reperfusion during posttreatment observation.

A Novel Framework for Multimodal Brain Tumor Detection with Scarce Labels.

Brain tumor detection has advanced significantly with the development of deep learning technology. Although multimodal data, such as Magnetic Resonance Imaging (MRI) and Computed Tomography (CT), has potential advantages in diagnostics, most existing studies rely solely on a single modality. This is because common fusion methods may lead to the loss of critical information when attempting multimodal fusion. Therefore, effectively integrating multimodal data has become a significant challenge. Additionally, medical image analysis requires large amounts of annotated data, and labeling images is a resourceintensive task that demands experienced professionals to spend a considerable amount of time. To address these challenges, this paper introduces a new unsupervised learning framework named Double-SimCLR. This framework builds on the foundation of contrastive learning and features a dual-branch structure, enabling direct and simultaneous processing of MRI and CT images for multimodal feature fusion. Given the "weak feature" characteristics of CT images (e.g., low soft tissue contrast and low resolution), we incorporated adaptive weight masking technology to enhance CT feature extraction. Moreover, we introduced a multimodal attention mechanism, which ensures that the model focuses on salient information, thereby elevating the precision and robustness of brain tumor detection. Even without substantial labeled data, experimental results demonstrate that Double-SimCLR achieves 93.458% accuracy, 92.463% precision, and a 93.058% F1-score, outperforming state-of-the-art (SOTA) models by 2.871%, 2.643%, and 3.098%, respectively.

Ethynylbenzaldehydes as novel reaction-based “turn-on” fluorescent probes for primary amine detection in solution, vapor, food, proteins, and live cells

Amine detection is of great importance as excess volatile amine exposure and increased concentration of biogenic amines in human body can cause adverse effects to human health. Thus, the development of easy-accessible and efficient fluorescent probes for amine detection is of great importance. In this study, we are the first to establish a cascade reaction sequence featuring imine formation followed by 6-endo-dig cyclization reaction for the development of sensitive and selective “turn-on” fluorescent probes toward primary amines by using the ortho-ethynylbenzaldehydes (EBAs) as the reaction site. The corresponding isoquinolinium products generated give a significant red-shifted absorbance change and highly intense “turn-on” fluorescence. Nine EBAs (EBA-1a-1e, EBA-2–5) were designed and synthesized to study the structure-photophysical property relationship (SPPR) for selective primary amine sensing. Our EBAs possessed a highly sensitive response toward primary amines in aqueous conditions within 30 min (LOD as low as 0.45 µM) with tunable absorption (338–430 nm) and emission (410–535 nm), large Stokes shift (up to 115 nm), and high fluorescence quantum yield (up to 0.86). EBA-loaded paper strips were prepared as a portable low cost tool for amine detection in solution, vapor, and food. Fluorogenic protein labelling and in-gel fluorescent imaging were efficiently achieved by using EBAs in which the fluorescence signal was obviously observed by naked eyes under 365 nm UV lamp. Moreover, the favorable membrane permeabilization, low to moderate cytotoxicity, and “turn-on” fluorescent response of EBA-1a-1e and EBA-4–5 allow wash-free live cell imaging. Interestingly, EBA-1a-1e and EBA-4 showed high selectivity to fluorescent imaging of mitochondria.

Fluorogenic in-situ Labelling of Gelatin Polymer in Aqueous Solution and Hydrogel.

Gelatin polymers made from partially degraded collagen are important biomaterials, but their in-situ analysis suffers from uncontrollable covalent labelling and poor spatial-temporal imaging resolution. Herein, three tetrazolate-tagged tetraphenylethylene fluorophores (TPE-TAs) are introduced for practical fluorogenic labelling of gelatin in aqueous phase and hydrogels. These probes with aggregation-induced emission characteristics offer negligible background and elicit turn-on fluorescence by simply mixing with the gelatin in aqueous phase, giving a detection limit of 0.15 mg/L over a linear dynamic range up to 100 mg/L. This method does not work for collagens and causes minimal interference with gelatin properties. Mechanistic studies reveal a key role for multivalent electrostatic interactions between the abundant basic residues in gelatin (e. g., lysine, hydroxylysine, arginine) and anionic tetrazolate moieties of the lipophilic fluorophore synergistically in spatially rigid macromolecular encapsulation to achieve fluorogenic labelling. The AIE strategy by forming non-covalent fluorophore-gelatin complexes was developed for novel hydrogels that exhibited reversible fluorescence in response to dynamic microstructural changes in the hydrogel scaffold upon salting-in/out treatments, and enabled high spatial-temporal imaging of the fiber network in lyophilized samples. This work may open up avenues for in-situ imaging analysis and evaluation of gelatin-based biomaterials during processes such as in vivo degradation and mineralization.

Impact of the Peripheral Ligand Layer on the Excited-State Deactivation Mechanism of Au38S2(S-Adm)20 and Au30(S-Adm)18 (S-Adm = Adamantanethiolate) Clusters.

Gold nanoclusters are ideal fluorescent labels for biological imaging, disease diagnosis, and treatment. Understanding the origin of the photoluminescence phenomenon in ligand-protected gold nanoclusters is crucial for both basic science and practical applications. In this study, density functional theory (DFT) and time-dependent DFT (TD-DFT) calculations were performed to study the mechanism of excited state deactivation of Au38S2(S-Adm)20 and Au30(S-Adm)18 (S-Adm = adamantanethiolate) clusters, which have similar sizes and compositions. The computational results indicate that the differences in structural symmetry and peripheral ligand layer lead to quite different excited state deactivation mechanisms and excited state lifetimes in Au38S2(S-Adm)20 and Au30(S-Adm)18. Specifically, the μ3-S atoms and bridging thiolate (SR) in the ligand layer of Au38S2(S-Adm)20 significantly suppress the structural relaxation of ligand motifs, resulting in a prolonged excited state lifetime and higher quantum yield. For the Au30(S-Adm)18, due to the symmetry forbidden and large structural relaxation of the ligand shell, a rapid nonradiative transition process resulted. This study provides new insights into how the photoluminescence of ligand-protected gold nanoclusters is influenced by their structure and symmetry.

Is initial unilateral revascularization acceptable in pediatric patients with bilateral moyamoya disease with mild contralateral hemodynamic disturbance?

Although asymmetrical vascular involvement between hemispheres is common in pediatric patients with bilateral moyamoya disease, whether hemispheres with mild vascular changes and hemodynamic impairment require immediate surgical revascularization or whether they can be observed until disease progression remains unclear. The authors evaluated the long-term outcomes of their strategy to initially perform unilateral surgery and withhold surgery to the contralateral hemispheres with mild vascular changes and hemodynamic impairment. The authors retrospectively evaluated Japanese pediatric patients (onset age ≤ 15 years) diagnosed with bilateral sporadic moyamoya disease who underwent unilateral revascularization. The authors investigated whether the patient underwent additional collateral surgery and the incidence of ischemic events during follow-up. They also compared visual assessments of arterial spin labeling (ASL) images obtained before initial surgery, before additional contralateral surgery, and at last follow-up. Overall, 30/47 patients (63.8%) experienced progression of hemodynamic impairment in the contralateral hemisphere and underwent additional surgery. The age at initial surgery of the patients who needed additional contralateral surgery was significantly younger than that of the patients who did not require contralateral surgery (mean [SD] 7.0 [3.0] years vs 9.8 [2.6] years, p = 0.002). One patient (age 4 years) developed ischemic stroke before admission for preoperative evaluation 2 months after novel symptom onset, and another patient (age 6 years) experienced ischemic stroke in the contralateral hemisphere while discontinuing antiplatelet agents before surgery; both patients fully recovered from the neurological deficits. In contralateral hemispheres that required additional surgery, the ASL visual assessment scores significantly decreased before the additional contralateral surgery compared to those obtained before the initial surgery (p = 0.008). In pediatric patients with bilateral moyamoya disease, withholding surgery for hemispheres with mild vascular changes and hemodynamic impairment is generally safe. Younger patients were more likely to experience contralateral progression and require additional surgery, so close follow-up is needed. ASL imaging is useful for detecting and following the progression of hemodynamic impairment in conservatively treated hemispheres.

Effect of active loop extrusion on the two-contact correlations in the interphase chromosome.

The population-averaged contact maps generated by the chromosome conformation capture technique provide important information about the average frequency of contact between pairs of chromatin loci as a function of the genetic distance between them. However, these datasets do not tell us anything about the joint statistics of simultaneous contacts between genomic loci in individual cells. This kind of statistical information can be extracted using the single-cell Hi-C method, which is capable of detecting a large fraction of simultaneous contacts within a single cell, as well as through modern methods of fluorescent labeling and super-resolution imaging. Motivated by the prospect of the imminent availability of relevant experimental data, in this work, we theoretically model the joint statistics of pairs of contacts located along a line perpendicular to the main diagonal of the single-cell contact map. The analysis is performed within the framework of an ideal polymer model with quenched disorder of random loops, which, as previous studies have shown, allows us to take into account the influence of the loop extrusion process on the conformational properties of interphase chromatin.

Higher Validity, Lower Radiation: A New Ictal Single-Photon Emission Computed Tomography Framework.

To assess whether arterial spin labeling perfusion images of healthy controls can enhance ictal single-photon emission computed tomography analysis and whether the acquisition of the interictal image can be omitted. We developed 2 pipelines: The first uses ictal and interictal images and compares these to single-photon emission computed tomography and arterial spin labeling of healthy controls. The second pipeline uses only the ictal image and the analogous healthy controls. Both pipelines were compared to the gold standard analysis and evaluated on data of individuals with epilepsy who underwent ictal single-photon emission computed tomography imaging during presurgical evaluation between 2010 and 2022. Fifty healthy controls prospectively underwent arterial spin labeling imaging. The correspondence between the detected hyperperfusion and the postoperative resection cavity or the presumably affected lobe was assessed using Dice score and mean Euclidean distance. Additionally, the outcomes of the pipelines were automatically assigned to 1 of 5 concordance categories. Inclusion criteria were met by 43 individuals who underwent epilepsy surgery and by 73 non-surgical individuals with epilepsy. Compared to the gold standard analysis, both pipelines resulted in significantly higher Dice scores and lower mean distances (p < 0.05). The combination of both provided localizing results in 85/116 cases, compared to 54/116 generated by the current gold standard analysis and the ictal image alone produced localizing results in 60/116 (52%) cases. We propose a new ictal single-photon emission computed tomography protocol; it finds relevantly more ictal hyperperfusion, and halves the radiation dose in about half of the individuals. ANN NEUROL 2024.

Cell Proliferation and Cytotoxicity Assays, The Fundamentals for Drug Discovery

Review Cell Proliferation and Cytotoxicity Assays, The Fundamentals for Drug Discovery Jingyi Niu†, Minai Li† and Ying Wang* State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Avenida da Universidade, Taipa, Macao 999078, China * Correspondence: emilyywang@um.edu.mo † These authors contributed equally to this work Received: 6 May 2024; Revised: 19 June 2024; Accepted: 21 June 2024; Published: 20 August 2024 Abstract: Cell proliferation and cytotoxicity assays are fundamental to drug discovery. This review summarizes prevalent methodologies for assessing cell proliferation and cytotoxicity, including direct cell count, metabolic activity, luminescent labeling, and tri-color viability imaging. The critical determinants that can significantly impact these assay outcomes, such as cellular doubling time, transitional states like quiescence and autophagy, cell cycle stages, metabolic enzyme functions, and genetic variability, are also explored. It is necessary to integrate the commonly used assays with additional analytical techniques to achieve precision in drug discovery. A multi-tiered approach that combines cellular assays with molecular analyses can improve screening processes, reduce false negatives, and increase confidence in the therapeutic potential of lead compounds.

Comparisons of magnetic resonance imaging, histopathological and Ki-67 labeling index findings in a single myxofibrosarcoma: a case report

BackgroundMyxofibrosarcoma is a myxoid soft tissue sarcoma showing T2 high intensity on magnetic resonance imaging. However, myxofibrosarcoma is a heterogeneous sarcoma with both myxoid and cellular portions. Magnetic resonance imaging findings were obtained MRI findings for comparison with histological and Ki-67 immunohistochemical features, in different portions of one myxofibrosarcoma.Case presentationMagnetic resonance imaging observations were compared with gross pathological and microscopic findings of a myxofibrosarcoma from a 50-year-old Japanese female. The Ki-67 labeling indices of different portions of the tumor, that is, the myxoid, cellular, and histologically confirmed infiltrative margin portions (pathological tail sign), were compared. The T2 low intensity area was more cellular than the T2 high intensity area, while the cellular portion had a significantly higher Ki-67 index than the myxoid portion (p = 0.0313). The portions with the pathological tail sign had a significantly higher Ki-67 labeling index than those without this sign (p = 0.0313).ConclusionsMore cellular portions of a myxofibrosarcoma correspond to more areas of the tumor showing aggressive features. Furthermore, our data also support the hypothesis of high aggressiveness being associated with the pathological tail sign in myxofibrosarcoma. To our knowledge, this is the first case report to describe comparisons among the imaging findings, histological features, and Ki-67 immunohistochemistry results for different portions of one myxofibrosarcoma.