Ex vivo 18F-fluoride uptake and hydroxyapatite deposition in human coronary atherosclerosis

With increase of social aging, Alzheimer's disease (AD) has been one of the serious diseases threatening human health. The occurrence of Aβ fibrils or plaques is recognized as the hallmark of AD. Currently, optical imaging has stood out to be a promising technique for the imaging of Aβ fibrils/plaques and the diagnosis of AD. However, restricted by their poor blood-brain barrier (BBB) penetrability, short-wavelength excitation and emission, and aggregation-caused quenching (ACQ) effect, the clinically used gold-standard optical probes such as <a>thioflavin</a> T (ThT) and thioflavin S (ThS), are not effective enough in the early diagnosis of AD in vivo. Herein, we put forward an “all-in-one” design principle and demonstrate its feasibility in developing high-performance fluorescent probes which are specific to Aβ fibrils/plaques and promising for super-early in-vivo diagnosis of AD. As a proof of concept, a simple rod-like amphiphilic NIR fluorescent AIEgen, i.e., AIE-CNPy-AD, is developed by taking the specificity, BBB penetration ability, deep-tissue penetration capacity, high signal-to-noise ratio (SNR) into consideration. AIE-CNPy-AD is constituted by connecting the electron-donating and accepting moieties through single bonds and tagging with a propanesulfonate tail, giving rise to the NIR fluorescence, aggregation-induced emission (AIE) effect, amphiphilicity, and rod-like structure, which in turn result in high binding-affinity and excellent specificity to Aβ fibrils/plaques, satisfactory ability to penetrate BBB and deep tissues, ultrahigh SNR and sensitivity, and high-fidelity imaging capability. In-vitro, ex-vivo, and in-vivo <a>identifying of Aβ fibrils/plaques</a> in different strains of mice indicate that AIE-CNPy-AD holds the universality to the detection of Aβ fibrils/plaques. It is noteworthy that AIE-CNPy-AD is even able to trace the small and sparsely distributed Aβ fibrils/plaques in very young AD model mice such as 4-month-old APP/PS1 mice which are reported to be the youngest mice to have Aβ deposits in brains, suggesting its great potential in diagnosis and intervention of AD at a super-early stage.

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MR Susceptibility Imaging for Detection of Tumor-Associated Macrophages in Glioblastoma

10.21203/rs.3.rs-1017881/v1 ◽

2021 ◽

Author(s):

Amir Nazem ◽

Samantha Guiry ◽

Mehrdad Pourfathi ◽

Jeffrey B. Ware ◽

Hannah Anderson ◽

...

Keyword(s):

Ex Vivo ◽

Imaging Biomarker ◽

Tumor Associated Macrophages ◽

Intracellular Iron ◽

Positive Correlation ◽

Non Invasive ◽

Cell Counts ◽

Susceptibility Maps ◽

Invasive Method ◽

M1 Phenotype

Abstract Purpose Tumor-associated macrophages (TAMs) are a key component of glioblastoma (GBM) microenvironment. Considering the differential role of different TAM phenotypes in iron metabolism with the M1 phenotype storing intracellular iron, and M2 phenotype releasing iron in the tumor microenvironment, we investigated MRI to quantify iron as an imaging biomarker for TAMs in GBM patients. Methods 21 adult patients with GBM underwent a 3D single echo gradient echo MRI sequence and quantitative susceptibility maps were generated. In 3 subjects, ex vivo imaging of surgical specimens was performed on a 9.4 Tesla MRI using 3D multi-echo GRE scans, and R2* (1/T2*) maps were generated. Each specimen was stained with hematoxylin and eosin, as well as CD68, CD86, CD206, and L-Ferritin. Results Significant positive correlation was observed between mean susceptibility for the tumor enhancing zone and the L-ferritin positivity percent (r =0.56, p=0.018) and the combination of tumor’s enhancing zone and necrotic core and the L-Ferritin positivity percent (r=0.72; p=0.001). The mean susceptibility significantly correlated with positivity percent for CD68 (ρ = 0.52, p=0.034) and CD86 (r=0.7 p=0.001), but not for CD206 (ρ = 0.09; p=0.7). There was a positive correlation between mean R2* values and CD68 positive cell counts (r =0.6, p=0.016). Similarly, mean R2* values significantly correlated with CD86 (r=0.54, p=0.03) but not with CD206 (r=0.15, p=0.5). Conclusion MR quantitative susceptibility mapping can quantify the iron content of GBM and provide a non-invasive method for TAM quantification and phenotyping.

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Rationally Designing Simple Rod-Like Amphiphilic NIR-Emissive AIE Probes for Precise In-Vivo Detection of Aβ Fibrils/Plaques at A Super-Early Stage

10.26434/chemrxiv.13699222 ◽

2021 ◽

Author(s):

Yipu Wang ◽

Dong Mei ◽

Xinyi Zhang ◽

Da-Hui Qu ◽

Ju Mei ◽

...

Keyword(s):

High Performance ◽

Ex Vivo ◽

Early Stage ◽

Signal To Noise Ratio ◽

High Signal ◽

In Vivo Detection ◽

Different Strains ◽

Aβ Fibrils

With increase of social aging, Alzheimer's disease (AD) has been one of the serious diseases threatening human health. The occurrence of Aβ fibrils or plaques is recognized as the hallmark of AD. Currently, optical imaging has stood out to be a promising technique for the imaging of Aβ fibrils/plaques and the diagnosis of AD. However, restricted by their poor blood-brain barrier (BBB) penetrability, short-wavelength excitation and emission, and aggregation-caused quenching (ACQ) effect, the clinically used gold-standard optical probes such as <a>thioflavin</a> T (ThT) and thioflavin S (ThS), are not effective enough in the early diagnosis of AD in vivo. Herein, we put forward an “all-in-one” design principle and demonstrate its feasibility in developing high-performance fluorescent probes which are specific to Aβ fibrils/plaques and promising for super-early in-vivo diagnosis of AD. As a proof of concept, a simple rod-like amphiphilic NIR fluorescent AIEgen, i.e., AIE-CNPy-AD, is developed by taking the specificity, BBB penetration ability, deep-tissue penetration capacity, high signal-to-noise ratio (SNR) into consideration. AIE-CNPy-AD is constituted by connecting the electron-donating and accepting moieties through single bonds and tagging with a propanesulfonate tail, giving rise to the NIR fluorescence, aggregation-induced emission (AIE) effect, amphiphilicity, and rod-like structure, which in turn result in high binding-affinity and excellent specificity to Aβ fibrils/plaques, satisfactory ability to penetrate BBB and deep tissues, ultrahigh SNR and sensitivity, and high-fidelity imaging capability. In-vitro, ex-vivo, and in-vivo <a>identifying of Aβ fibrils/plaques</a> in different strains of mice indicate that AIE-CNPy-AD holds the universality to the detection of Aβ fibrils/plaques. It is noteworthy that AIE-CNPy-AD is even able to trace the small and sparsely distributed Aβ fibrils/plaques in very young AD model mice such as 4-month-old APP/PS1 mice which are reported to be the youngest mice to have Aβ deposits in brains, suggesting its great potential in diagnosis and intervention of AD at a super-early stage.

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Sodium accumulation in breast cancer predicts malignancy and treatment response

10.1101/2021.04.14.439494 ◽

2021 ◽

Author(s):

Andrew D James ◽

Theresa K Leslie ◽

Joshua D Kaggie ◽

Laura Wiggins ◽

Lewis Patten ◽

...

Keyword(s):

Breast Cancer ◽

Ex Vivo ◽

Breast Tumour ◽

Cytotoxic Chemotherapy ◽

Tumour Tissue ◽

Imaging Biomarker ◽

Sodium Accumulation ◽

Non Invasive ◽

Significant Clinical Improvement ◽

Breast Tumour Tissue

AbstractBreast cancer is the leading cause of cancer-related death in women worldwide. Development of novel noninvasive diagnostic and predictive pathophysiological biomarkers would represent a significant clinical improvement. Here, we explored the utility of non-invasive 23Na MRI to profile tumour physiology using preclinical mouse models of breast cancer. We establish that tissue Na+ concentration ([Na+]) is elevated vs non-tumour regions across multiple different tumour models. Ex vivo SBFI fluorescence imaging corroborated that this elevation in tumour [Na+] is due to increased intracellular [Na+]. Effective treatment with cytotoxic chemotherapy reduced tumour tissue [Na+], but was not detected by 1H diffusion-weighted imaging (DWI). Moreover, combining 23Na MRI and DWI measurements enabled superior classification accuracy of tumour vs non-tumour regions compared to either parameter alone. Quantification of breast tumour tissue [Na+] using 23Na MRI thus represents a novel, accurate, non-invasive diagnostic and predictive imaging biomarker.

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A compact guided-wave EMAT with pulsed electromagnet for ferromagnetic tube inspection

International Journal of Applied Electromagnetics and Mechanics ◽

10.3233/jae-209409 ◽

2020 ◽

Vol 64 (1-4) ◽

pp. 951-958

Author(s):

Tianhao Liu ◽

Yu Jin ◽

Cuixiang Pei ◽

Jie Han ◽

Zhenmao Chen

Keyword(s):

Power Plants ◽

Signal To Noise Ratio ◽

Small Diameter ◽

Performance Testing ◽

Guided Wave ◽

High Signal ◽

Receiver Coil ◽

Signal To Noise ◽

Corrosion Defects

Small-diameter tubes that are widely used in petroleum industries and power plants experience corrosion during long-term services. In this paper, a compact inserted guided-wave EMAT with a pulsed electromagnet is proposed for small-diameter tube inspection. The proposed transducer is noncontact, compact with high signal-to-noise ratio and unattractive to ferromagnetic tubes. The proposed EMAT is designed with coils-only configuration, which consists of a pulsed electromagnet and a meander pulser/receiver coil. Both the numerical simulation and experimental results validate its feasibility on generating and receiving L(0,2) mode guided wave. The parameters for driving the proposed EMAT are optimized by performance testing. Finally, feasibility on quantification evaluation for corrosion defects was verified by experiments.

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Application of Novel Low Current OBIRCH Amplifier and Nanoprobing to Identify Subtle Leakages in Advanced Node Technologies

10.31399/asm.cp.istfa2018p0303 ◽

2018 ◽

Author(s):

Satish Kodali ◽

Liangshan Chen ◽

Yuting Wei ◽

Tanya Schaeffer ◽

Chong Khiam Oh

Keyword(s):

Signal To Noise Ratio ◽

Semiconductor Industry ◽

Fault Isolation ◽

Ring Oscillator ◽

High Signal ◽

The Novel ◽

Resistance Change ◽

Three Samples ◽

Relative Threshold ◽

First Time

Abstract Optical beam induced resistance change (OBIRCH) is a very well-adapted technique for static fault isolation in the semiconductor industry. Novel low current OBIRCH amplifier is used to facilitate safe test condition requirements for advanced nodes. This paper shows the differences between the earlier and novel generation OBIRCH amplifiers. Ring oscillator high standby leakage samples are analyzed using the novel generation amplifier. High signal to noise ratio at applied low bias and current levels on device under test are shown on various samples. Further, a metric to demonstrate the SNR to device performance is also discussed. OBIRCH analysis is performed on all the three samples for nanoprobing of, and physical characterization on, the leakage. The resulting spots were calibrated and classified. It is noted that the calibration metric can be successfully used for the first time to estimate the relative threshold voltage of individual transistors in advanced process nodes.

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Faculty Opinions recommendation of In vivo and ex vivo comparative transcriptional profiling of invasive and non-invasive Candida albicans isolates identifies genes associated with tissue invasion.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1085792.538709 ◽

2007 ◽

Author(s):

John Perfect

Keyword(s):

Candida Albicans ◽

Ex Vivo ◽

Transcriptional Profiling ◽

Non Invasive ◽

Tissue Invasion

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VS2 as saturable absorber for Q-switched pulse generation

Nanophotonics ◽

10.1515/nanoph-2020-0128 ◽

2020 ◽

Vol 9 (8) ◽

pp. 2569-2576 ◽

Cited By ~ 4

Author(s):

Lu Li ◽

Lihui Pang ◽

Qiyi Zhao ◽

Yao Wang ◽

Wenjun Liu

Keyword(s):

Saturable Absorber ◽

Nonlinear Optical ◽

Modulation Depth ◽

Signal To Noise Ratio ◽

Transition Metal Dichalcogenides ◽

Laser Cavity ◽

Pulse Generation ◽

High Signal ◽

Power Pulse ◽

Metal Dichalcogenides

AbstractTransition metal dichalcogenides have been widely utilized as nonlinear optical materials for laser pulse generation applications. Herein, we study the nonlinear optical properties of a VS2-based optical device and its application as a new saturable absorber (SA) for high-power pulse generation. Few-layer VS2 nanosheets are deposited on the tapered region of a microfiber to form an SA device, which shows a modulation depth of 40.52%. After incorporating the microfiber-VS2 SA into an Er-doped fiber laser cavity, passively Q-switched pulse trains could be obtained with repetition rates varying from 95 to 233 kHz. Under the pump power of 890 mW, the largest output power and shortest pulse duration are measured to be 43 mW and 854 ns, respectively. The high signal-to-noise ratio of 60 dB confirms the excellent stability of the Q-switching state. To the best of our knolowdge, this is the first illustration of using VS2 as an SA. Our experimental results demonstrate that VS2 nanomaterials have a large potential for nonlinear optics applications.

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TAMI-08. A TALE OF TWO TELOMERE MAINTENANCE MECHANISMS: TERT EXPRESSION AND THE ALT PATHWAY INDUCE UNIQUE MRS-DETECTABLE METABOLIC REPROGRAMMING IN LOW-GRADE GLIOMAS

Neuro-Oncology ◽

10.1093/neuonc/noaa215.897 ◽

2020 ◽

Vol 22 (Supplement_2) ◽

pp. ii214-ii214

Author(s):

Pavithra Viswanath ◽

Georgios Batsios ◽

Anne Marie Gillespie ◽

Hema Artee Luchman ◽

Joseph Costello ◽

...

Keyword(s):

Treatment Response ◽

Metabolic Reprogramming ◽

Telomere Maintenance ◽

Imaging Biomarker ◽

Low Grade ◽

Tumor Proliferation ◽

Nicotinamide Phosphoribosyltransferase ◽

Non Invasive ◽

Key Enzyme ◽

Tert Expression

Abstract Telomeres are nucleoprotein structures at chromosomal ends that shorten with cell division and constitute a natural barrier to proliferation. In order to proliferate indefinitely, all tumors require a telomere maintenance mechanism (TMM). Telomerase reverse transcriptase (TERT) expression is the TMM in most tumors, including low-grade oligodendrogliomas (LGOGs). In contrast, low-grade astrocytomas (LGAs) use the alternative lengthening of telomeres (ALT) pathway as their TMM. As molecular hallmarks of tumor proliferation, TMMs are attractive tumor biomarkers and therapeutic targets. Non-invasive imaging of TMM status will, therefore, allow assessment of tumor proliferation and treatment response. However, translational methods of imaging TMM status are lacking. Here, we show that TERT expression and the ALT pathway are associated with unique magnetic resonance spectroscopy (MRS)-detectable metabolic reprogramming in LGOGs and LGAs respectively. In genetically-engineered and patient-derived LGOG models, TERT expression is linked to elevated 1H-MRS-detectable NAD(P)/H, glutathione, aspartate and AXP. In contrast, the ALT pathway in LGAs is associated with higher α-ketoglutarate, glutamate, alanine and AXP. Importantly, elevated flux of hyperpolarized [1-13C]-alanine to pyruvate, which depends on α-ketoglutarate, is a non-invasive in vivo imaging biomarker of the ALT pathway in LGAs while elevated flux of hyperpolarized [1-13C]-alanine to lactate, which depends on NADH, is an imaging biomarker of TERT expression in LGOGs. Mechanistically, the ALT pathway in LGAs is linked to higher glutaminase (GLS), a key enzyme for α-ketoglutarate biosynthesis while TERT expression in LGOGs is associated with elevated nicotinamide phosphoribosyltransferase (NAMPT), a key enzyme for NADH biosynthesis. Notably, TERT expression and the ALT pathway are linked to MRS-detectable metabolic reprogramming in LGOG and LGA patient biopsies, emphasizing the clinical validity of our observations. Collectively, we have identified unique metabolic signatures of TMM status that integrate critical oncogenic information with noninvasive imaging modalities that can improve diagnosis and treatment response monitoring for LGOG and LGA patients.

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A NOVEL EXTENSIVE EX-VIVO OCT DATABASE FROM MURINE MODELS OF COLORECTAL CANCER

British Journal of Surgery ◽

10.1093/bjs/znab160.030 ◽

2021 ◽

Vol 108 (Supplement_3) ◽

Author(s):

J Bote ◽

J F Ortega-Morán ◽

C L Saratxaga ◽

B Pagador ◽

A Picón ◽

...

Keyword(s):

Colorectal Cancer ◽

Machine Learning ◽

Structural Information ◽

Ex Vivo ◽

Ground Truth ◽

Colon Polyps ◽

Learning Methods ◽

Non Invasive ◽

Machine Learning Methods ◽

In Situ Methods

Abstract INTRODUCTION New non-invasive technologies for improving early diagnosis of colorectal cancer (CRC) are demanded by clinicians. Optical Coherence Tomography (OCT) provides sub-surface structural information and offers diagnosis capabilities of colon polyps, further improved by machine learning methods. Databases of OCT images are necessary to facilitate algorithms development and testing. MATERIALS AND METHODS A database has been acquired from rat colonic samples with a Thorlabs OCT system with 930nm centre wavelength that provides 1.2KHz A-scan rate, 7μm axial resolution in air, 4μm lateral resolution, 1.7mm imaging depth in air, 6mm x 6mm FOV, and 107dB sensitivity. The colon from anaesthetised animals has been excised and samples have been extracted and preserved for ex-vivo analysis with the OCT equipment. RESULTS This database consists of OCT 3D volumes (C-scans) and 2D images (B-scans) of murine samples from: 1) healthy tissue, for ground-truth comparison (18 samples; 66 C-scans; 17,478 B-scans); 2) hyperplastic polyps, obtained from an induced colorectal hyperplastic murine model (47 samples; 153 C-scans; 42,450 B-scans); 3) neoplastic polyps (adenomatous and adenocarcinomatous), obtained from clinically validated Pirc F344/NTac-Apcam1137 rat model (232 samples; 564 C-scans; 158,557 B-scans); and 4) unknown tissue (polyp adjacent, presumably healthy) (98 samples; 157 C-scans; 42,070 B-scans). CONCLUSIONS A novel extensive ex-vivo OCT database of murine CRC model has been obtained and will be openly published for the research community. It can be used for classification/segmentation machine learning methods, for correlation between OCT features and histopathological structures, and for developing new non-invasive in-situ methods of diagnosis of colorectal cancer.

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