The ISMRM Open Science Initiative for Perfusion Imaging (OSIPI): Results from the OSIPI-Dynamic Contrast-Enhanced challenge.

PURPOSE: K trans $$ {K}^{\mathrm{trans}} $$ has often been proposed as a quantitative imaging biomarker for diagnosis, prognosis, and treatment response assessment for various tumors. None of the many software tools for K trans $$ {K}^{\mathrm{trans}} $$ quantification are standardized. The ISMRM Open Science Initiative for Perfusion Imaging-Dynamic Contrast-Enhanced (OSIPI-DCE) challenge was designed to benchmark methods to better help the efforts to standardize K trans $$ {K}^{\mathrm{trans}} $$ measurement. METHODS: A framework was created to evaluate K trans $$ {K}^{\mathrm{trans}} $$ values produced by DCE-MRI analysis pipelines to enable benchmarking. The perfusion MRI community was invited to apply their pipelines for K trans $$ {K}^{\mathrm{trans}} $$ quantification in glioblastoma from clinical and synthetic patients. Submissions were required to include the entrants' K trans $$ {K}^{\mathrm{trans}} $$ values, the applied software, and a standard operating procedure. These were evaluated using the proposed OSIP I gold $$ \mathrm{OSIP}{\mathrm{I}}_{\mathrm{gold}} $$ score defined with accuracy, repeatability, and reproducibility components. RESULTS: Across the 10 received submissions, the OSIP I gold $$ \mathrm{OSIP}{\mathrm{I}}_{\mathrm{gold}} $$ score ranged from 28% to 78% with a 59% median. The accuracy, repeatability, and reproducibility scores ranged from 0.54 to 0.92, 0.64 to 0.86, and 0.65 to 1.00, respectively (0-1 = lowest-highest). Manual arterial input function selection markedly affected the reproducibility and showed greater variability in K trans $$ {K}^{\mathrm{trans}} $$ analysis than automated methods. Furthermore, provision of a detailed standard operating procedure was critical for higher reproducibility. CONCLUSIONS: This study reports results from the OSIPI-DCE challenge and highlights the high inter-software variability within K trans $$ {K}^{\mathrm{trans}} $$ estimation, providing a framework for ongoing benchmarking against the scores presented. Through this challenge, the participating teams were ranked based on the performance of their software tools in the particular setting of this challenge. In a real-world clinical setting, many of these tools may perform differently with different benchmarking methodology.

Activated brown adipose tissue releases exosomes containing mitochondrial methylene tetrahydrofolate dehydrogenase (NADP dependent) 1-like protein (MTHFD1L).

Brown adipose tissue (BAT) is a promising weapon to combat obesity and metabolic disease. BAT is thermogenic and consumes substantial amounts of glucose and fatty acids as fuel for thermogenesis and energy expenditure. To study BAT function in large human longitudinal cohorts, safe and precise detection methodologies are needed. Although regarded a gold standard, the foray of PET-CT into BAT research and clinical applications is limited by its high ionizing radiation doses. Here, we show that brown adipocytes release exosomes in blood plasma that can be utilized to assess BAT activity. In the present study, we investigated circulating protein biomarkers that can accurately and reliably reflect BAT activation triggered by cold exposure, capsinoids ingestion and thyroid hormone excess in humans. We discovered an exosomal protein, methylene tetrahydrofolate dehydrogenase (NADP+ dependent) 1-like (MTHFD1L), to be overexpressed and detectable in plasma for all three modes of BAT activation in human subjects. This mitochondrial protein is packaged as a cargo within multivesicular bodies of the endosomal compartment and secreted as exosomes via exocytosis from activated brown adipocytes into the circulation. To support MTHFD1L as a conserved BAT activation response in other vertebrates, we examined a rodent model and also proved its presence in blood of rats following BAT activation by cold exposure. Plasma concentration of exosomal MTHFD1L correlated with human BAT activity as confirmed by PET-MR in humans and supported by data from rats. Thus, we deduce that MTHFD1L appears to be overexpressed in activated BAT compared to BAT in the basal nonstimulated state.

Differential expression of proteins in Pseudomonas mendocina SMSKVR-3 under arsenate stress.

This study focuses on analyzing the protein expression pattern of intracellular proteins when Pseudomonas mendocina SMSKVR-3 exposed to 300 mM of arsenate to find out the proteins that are overexpressed or exclusively expressed in response to arsenate. The sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of protein expression at different time intervals showed the highest number of protein bands (14) that are overexpressed at 8 h of the time interval. It was also observed that treatment with at least 200 mM of As(V) is required to induce a difference in protein expression. Two-dimensional (2D)-PAGE analysis of 8-h sample exhibited 146 unique spots, 45 underexpressed, and 46 overexpressed spots in arsenate-treated sample. Based on the highest percent volume and fold change, three unique spots and one overexpressed spot were selected and analyzed by matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF/TOF) mass spectrometry (MS) analysis followed by the MASCOT search. These proteins were identified as ribosome-recycling factor (20.13 kDa), polyphosphate:ADP/GDP phosphotransferase (40.88 kDa), ribonuclease P protein component (14.96 kDa) and cobalt-precorrin-5B C(1)-methyltransferase (38.43 kDa) with MASCOT score of 54, 81, 94, and 100, respectively. All of these proteins help the bacteria to overcome arsenate stress.

Dy(III)-Based Metal-Organic Framework as a Fluorescent Probe for Highly Selective Detection of Picric Acid in Aqueous Medium.

A dysprosium metal-organic framework, {[Dy(µ2-FcDCA)1.5(MeOH)(H2O)]·0.5H2O}n (1), where FcDCA = 1,1'-ferrocene dicarboxylic acid, was prepared by slow-diffusion technique at room temperature. The crystal structure analysis of 1 by single-crystal X-ray diffraction reveals different binding modes of FcDCA linkers coordinated with Dy(III) metal ions, which forms continuous porous two-dimensional (2D) infinite framework. The resulting 2D layers are linked by π···π interactions to build three-dimensional (3D) supramolecular framework. Observably, this thermally stable 3D architecture was topologically simplified as a three-connected uninodal net with fes topology. Furthermore, the practical applicability of 1 was investigated as a fluorescence sensor for the sensitive detection of picric acid in aqueous medium with an impressive detection limit of 0.71 µM with quenching constant (KSV) quantified to be 8.55 × 104 M-1. The distinguished selectivity in the presence of other nitroaromatics suggests the possible incorporation of 1 in real-world futuristic diagnostic kits. Additionally, the electrochemical behavior of 1 exhibits reversible in nature attributed to the ferrocene/ferrocenium cation.

A facile two-photon fluorescent probe: an endoplasmic reticulum tracker monitoring ER stress and vesicular transport to lysosomes.

The morphological divergence of the Endoplasmic Reticulum (ER) during stress is a powerful indicator of several diseases. A new two-photon, non-cytotoxic, fluorescent probe (ERLp) was designed and synthesized in a facile manner for selective tracking of the Endoplasmic Reticulum (ER) with a high Pearson co-localization coefficient (0.91) in live cells and tumor spheroids. Further, ER stress during cell apoptosis and vesicular transport from the ER to the lysosomal compartment were also explored by employing ERLp. Therefore, ERLp can be used as a potent tool for examining vesicle transport or ER stress associated diseases in real time.

A novel mesoionic carbene based highly fluorescent Pd(ii) complex as an endoplasmic reticulum tracker in live cells.

A recent study advocates that endoplasmic reticulum (ER) dysfunction may be linked to critical neurotrauma and advanced tauopathy. In this regard, targeting the ER warrants urgent attention towards the therapeutic treatment of neurotrauma-related neurodegeneration. Herein, we report the synthesis of a new N-heterocyclic mesoionic carbene based highly fluorescent square-planar Pd(ii) complex 1, with a high quantum yield (0.737). Probe 1 is a non-toxic probe for selectively labeling the endoplasmic reticulum in live cells.

Rodent Abdominal Adipose Tissue Imaging by MR.

Rodents including rats and mice are important models to study obesity, diabetes, and metabolic syndrome in a preclinical setting. Translational and longitudinal imaging of these rodents permit investigation of metabolic diseases and identification of imaging biomarkers suitable for clinical translation. Here we describe the imaging protocols for achieving quantitative abdominal imaging in small animals followed by segmentation and quantification of fat volumes.

Capsinoids activate brown adipose tissue (BAT) with increased energy expenditure associated with subthreshold 18-fluorine fluorodeoxyglucose uptake in BAT-positive humans confirmed by positron emission tomography scan.

Background: Capsinoids are reported to increase energy expenditure (EE) via brown adipose tissue (BAT) stimulation. However, imaging of BAT activation by capsinoids remains limited. Because BAT activation is a potential therapeutic strategy for obesity and related metabolic disorders, we sought to prove that capsinoid-induced BAT activation can be visualized by 18-fluorine fluorodeoxyglucose (18F-FDG) positron emission tomography (PET). Objective: We compared capsinoids and cold exposure on BAT activation and whole-body EE. Design: Twenty healthy participants (8 men, 12 women) with a mean age of 26 y (range: 21-35 y) and a body mass index (kg/m2) of 21.7 (range: 18.5-26.0) underwent 18F-FDG PET and whole-body calorimetry after ingestion of 12 mg capsinoids or ≤2 h of cold exposure (∼14.5°C) in a crossover design. Mean standardized uptake values (SUVs) of the region of interest and BAT volumes were calculated. Blood metabolites were measured before and 2 h after each treatment. Results: All of the participants showed negligible 18F-FDG uptake post-capsinoid ingestion. Upon cold exposure, 12 participants showed avid 18F-FDG uptake into supraclavicular and lateral neck adipose tissues (BAT-positive group), whereas the remaining 8 participants (BAT-negative group) showed undetectable uptake. Capsinoids and cold exposure increased EE, although cold induced a 2-fold increase in whole-body EE and higher fat oxidation, insulin sensitivity, and HDL cholesterol compared with capsinoids. Conclusions: Capsinoids only increased EE in BAT-positive participants, which suggests that BAT mediates EE evoked by capsinoids. This implies that capsinoids stimulate BAT to a lesser degree than cold exposure as evidenced by 18F-FDG uptake below the presently accepted SUV thresholds defining BAT activation. This trial was registered at www.clinicaltrials.gov as NCT02964442.

Water soluble two-photon fluorescent organic probes for long-term imaging of lysosomes in live cells and tumor spheroids.

The morphological alteration of lysosomes is a powerful indicator of various pathological disorders. In this regard, we have designed and synthesized a new water soluble fluorescent Schiff-base ligand (L-lyso) containing two hydroxyl groups. L-lyso exhibits excellent two-photon properties with tracking of lysosomes in live cells as well as in 3D tumor spheroids. Furthermore, it can label lysosomes for more than 3 days. Thus, L-lyso has an edge over the commercially available expensive LysoTracker probes and also over other reported probes in terms of its long-term imaging, water solubility and facile synthesis.

Segmentation and characterization of interscapular brown adipose tissue in rats by multi-parametric magnetic resonance imaging.

OBJECTIVE: The aim was to auto-segment and characterize brown adipose, white adipose and muscle tissues in rats by multi-parametric magnetic resonance imaging with validation by histology and UCP1. MATERIALS AND METHODS: Male Wistar rats were randomized into two groups for thermoneutral (n = 8) and cold exposure (n = 8) interventions, and quantitative MRI was performed longitudinally at 7 and 11 weeks. Prior to imaging, rats were maintained at either thermoneutral body temperature (36 ± 0.5 °C), or short term cold exposure (26 ± 0.5 °C). Neural network based automatic segmentation was performed on multi-parametric images including fat fraction, T2 and T2* maps. Isolated tissues were subjected to histology and UCP1 analysis. RESULTS: Multi-parametric approach showed precise delineation of the interscapular brown adipose tissue (iBAT), white adipose tissue (WAT) and muscle regions. Neural network based segmentation results were compared with manually drawn regions of interest, and showed 96.6 and 97.1% accuracy for WAT and BAT respectively. Longitudinal assessment of the iBAT volumes showed a reduction at 11 weeks of age compared to 7 weeks. The cold exposed group showed increased iBAT volume compared to thermoneutral group at both 7 and 11 weeks. Histology and UCP1 expression analysis supported our imaging results. CONCLUSION: Multi-parametric MR based neural network auto-segmentation provides accurate separation of BAT, WAT and muscle tissues in the interscapular region. The cold exposure improves the classification and quantification of heterogeneous BAT.

Improved bolus arrival time and arterial input function estimation for tracer kinetic analysis in DCE-MRI.

PURPOSE: To develop a methodology for improved estimation of bolus arrival time (BAT) and arterial input function (AIF) which are prerequisites for tracer kinetic analysis of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) data and to verify the applicability of the same in the case of intracranial lesions (brain tumor and tuberculoma). MATERIALS AND METHODS: A continuous piecewise linear (PL) model (with BAT as one of the free parameters) is proposed for concentration time curve C(t) in T(1)-weighted DCE-MRI. The resulting improved procedure suggested for automatic extraction of AIF is compared with earlier methods. The accuracy of BAT and other estimated parameters is tested over simulated as well as experimental data. RESULTS: The proposed PL model provides a good approximation of C(t) trends of interest and fit parameters show their significance in a better understanding and classification of different tissues. BAT was correctly estimated. The automatic and robust estimation of AIF obtained using the proposed methodology also corrects for partial volume effects. The accuracy of tracer kinetic analysis is improved and the proposed methodology also reduces the time complexity of the computations. CONCLUSION: The PL model parameters along with AIF measured by the proposed procedure can be used for an improved tracer kinetic analysis of DCE-MRI data.