Application of Fourier Analysis of Cerebral Glucose Metabolism in Color-Induced Long-Term Potentiation: A Novel Functional PET Spectroscopy (<em>f</em>PETS) Study in Mice

Fourier time-series analysis could be used to segregate changes in the ventral and dorsal streams of the visual system in male and female mice. Color memory processes of long-term potentiation and long-term depression could be identified through spectral analysis. We used small animal positron emission tomography and magnetic resonance imaging (PET/MRI) to measure the accumulation of [18F]fluorodeoxyglucose ([18F]FDG) in the mouse brain during light stimulation with blue and yellow filters compared to darkness condition. The mean standardized uptake values (SUV) of [18F]FDG for each stimulus condition was analyzed using standard Fourier analysis software to derive spectral density estimates for each condition. Spectral peaks were identified as originating from the subcortical region (S-peak) by subcortical long-term potentiation (SLTP) or depression (SLTD), and originating from the cortical region (C-peak) by cortical long-term potentiation (CLTP) or depression (CLTD). Luminance opponency occurred at S-peak by SLTP in the dorsal stream in the left visual cortex in male mice. On the other hand, chromatic opponency occurred by wavelength-differencing at C-peak by CLTP in the cortico-subcortical pathways in the ventral stream in the left visual cortex in male mice. In contrast in female mice, during luminance processing, there was resonance phenomenon at C-peak in the ventral stream in the right visual cortex. Chromatic opponency occurred at S-peak by SLTP in the dorsal stream in the right visual cortex in female mice. Application of Fourier analysis improved spatial and temporal resolutions of conventional fPET/MRI methods. Computation of color processing as a conscious experience has wide range applications in neuroscience and artificial intelligence

Weakly supervised semantic segmentation for MRI: exploring the advantages and disadvantages of class activation maps for biological image segmentation with soft boundaries

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Magnetic resonance imaging for non-invasive measurement of plastic ingestion in marine wildlife

Monitoring plastic ingestion by marine wildlife is important for both characterizing the extent of plastic pollution in the environment and understanding its effect on species and ecosystems. Current methods to detect plastic in the digestive system of animals are slow and invasive, such that the number of animals that can be screened is limited. In this article, magnetic resonance imaging (MRI) is investigated as a possible technology to perform rapid, non-invasive detection of plastic ingestion. Standard MRI methods were able to directly measure one type of plastic in a fulmar stomach and another type was able to be indirectly detected. In addition to MRI, other standard nuclear magnetic resonance (NMR) measurements were made. Different types of plastic were tested, and distinctive NMR signal characteristics were found in common for each type, allowing them to be distin- guished from one another. The NMR results indicate specialized MRI sequences could be used to directly image several types of plastic. Although current commercial MRI technology is not suitable for field use, existing single- sided MRI research systems could be adapted for use outside the laboratory and become an important tool for future monitoring of wild animals

Diffusion tensor imaging for spatially-resolved characterization of muscle fiber structure in seafood

The fiber structure of tissue in meat and seafood has a significant impact on their perceived quality. However, quantifiable description of muscle structure is challenging. We investigate diffusion tensor imaging (DTI) magnetic resonance imaging (MRI) as a method to quantitatively describe tissue structure. DTI measures the anisotropy of water molecule diffusion within muscle fibers. A pilot study evaluated three different cod loin samples: one of high-quality, one of medium-quality, and one of poor-quality. DTI parameters such as fractional anisotropy, axial diffusion and radial diffusion showed clear differences between the sample qualities. Changes in the DTI metrics consistent with freezing and thawing damage to the tissue were observed. The DTI maps were compared to T2-weighted images and DTI detected significant details that were not visible in T2-weighted images. Overall, these results indicate that DTI is a promising method for spatially-resolved characterization of tissue structure in seafood and meat

Characterization of vasskveite (water halibut) syndrome for automated detection

In recent years, cases of vasskveite (water halibut) syndrome in halibut have been increasing. At the moment, there exists no way to screen for the syndrome immediately after capture, which is problematic for both exporters and purchasers. In this article, we compared good quality halibut and halibut exhibiting the syndrome using a variety of techniques. Hyperspectral imaging was used to quantify the relative amounts of fat and water in the tissue. Diffusion tensor imaging was used to characterize tissue structure. Histology was performed to provide direct visual characterization of the tissue. Results indicate the muscle fibers in afflicted fish exhibit disordered growth and the tissue is lacking in fat. These results are in line with the current theory that the syndrome stems from a nutritional deficiency in the halibut diet. Hyperspectral imaging appears to be a promising technology to rapidly identify afflicted halibut immediately after capture

Thyroid hormone status defines brown adipose tissue activity and browning of white adipose tissues in mice

The present study aimed to determine the effect of thyroid hormone dysfunction on brown adipose tissue activity and white adipose tissue browning in mice. Twenty randomized female C57BL/6NTac mice per treatment group housed at room temperature were rendered hypothyroid or hyperthyroid. In-vivo small animal 18F-FDG PET/MRI was performed to determine the effects of hypo- and hyperthyroidism on BAT mass and BAT activity. Ex-vivo14C-acetate loading assay and assessment of thermogenic gene and protein expression permitted analysis of oxidative and thermogenic capacities of WAT and BAT of eu-, hyper and hypothyroid mice. 18F-FDG PET/MRI revealed a lack of brown adipose tissue activity in hypothyroid mice, whereas hyperthyroid mice displayed increased BAT mass alongside enhanced 18F-FDG uptake. In white adipose tissue of both, hyper- and hypothyroid mice, we found a significant induction of thermogenic genes together with multilocular adipocytes expressing UCP1. Taken together, these results suggest that both the hyperthyroid and hypothyroid state stimulate WAT thermogenesis most likely as a consequence of enhanced adrenergic signaling or compensation for impaired BAT function, respectively

The marine natural product mimic MPM-1 is cytolytic and induces DAMP release from human cancer cell lines

Bioprospecting contributes to the discovery of new molecules with anticancer properties. Compounds with cytolytic activity and the ability to induce immunogenic cell death can be administered as intratumoral injections with the aim to activate anti-tumor immune responses by causing the release of tumor antigens as well as damage-associated molecular patterns (DAMPs) from dying cancer cells. In the present study, we report the cytolytic and DAMP-releasing efects of a new natural product mimic termed MPM-1 that was inspired by the marine Eusynstyelamides. We found that MPM-1 rapidly killed cancer cells in vitro by inducing a necrosis-like death, which was accompanied by lysosomal swelling and perturbation of autophagy in HSC-3 (human oral squamous cell carcinoma) cells. MPM-1 also induced release of the DAMPs adenosine triphosphate (ATP) and high mobility group box 1 (HMGB1) from Ramos (B-cell lymphoma) and HSC-3 cells, as well as cell surface expression of calreticulin in HSC-3 cells. This indicates that MPM-1 has the ability to induce immunogenic cell death, further suggesting that it may have potential as a novel anticancer compound

Sigma-1 Receptor Positron Emission Tomography: A New Molecular Imaging Approach Using (S)-(−)-[18F]Fluspidine in Glioblastoma

Glioblastoma multiforme (GBM) is the most devastating primary brain tumour characterised by infiltrative growth and resistance to therapies. According to recent research, the sigma-1 receptor (sig1R), an endoplasmic reticulum chaperone protein, is involved in signaling pathways assumed to control the proliferation of cancer cells and thus could serve as candidate for molecular characterisation of GBM. To test this hypothesis, we used the clinically applied sig1R-ligand (S)-(−)-[18F]fluspidine in imaging studies in an orthotopic mouse model of GBM (U87-MG) as well as in human GBM tissue. A tumour-specific overexpression of sig1R in the U87-MG model was revealed in vitro by autoradiography. The binding parameters demonstrated target-selective binding according to identical KD values in the tumour area and the contralateral side, but a higher density of sig1R in the tumour. Different kinetic profiles were observed in both areas, with a slower washout in the tumour tissue compared to the contralateral side. The translational relevance of sig1R imaging in oncology is reflected by the autoradiographic detection of tumour-specific expression of sig1R in samples obtained from patients with glioblastoma. Thus, the herein presented data support further research on sig1R in neuro-oncology

Sigma-1 receptor positron emission tomography: A new molecular imaging approach using (S)-(-)-[18F]fluspidine in glioblastoma

Glioblastoma multiforme (GBM) is the most devastating primary brain tumour characterised by infiltrative growth and resistance to therapies. According to recent research, the sigma-1 receptor (sig1R), an endoplasmic reticulum chaperone protein, is involved in signaling pathways assumed to control the proliferation of cancer cells and thus could serve as candidate for molecular characterisation of GBM. To test this hypothesis, we used the clinically applied sig1R-ligand (S)-(−)-[18F]fluspidine in imaging studies in an orthotopic mouse model of GBM (U87-MG) as well as in human GBM tissue. A tumour-specific overexpression of sig1R in the U87-MG model was revealed in vitro by autoradiography. The binding parameters demonstrated target-selective binding according to identical KD values in the tumour area and the contralateral side, but a higher density of sig1R in the tumour. Different kinetic profiles were observed in both areas, with a slower washout in the tumour tissue compared to the contralateral side. The translational relevance of sig1R imaging in oncology is reflected by the autoradiographic detection of tumour-specific expression of sig1R in samples obtained from patients with glioblastoma. Thus, the herein presented data support further research on sig1R in neuro-oncology

Preclinical Incorporation Dosimetry of [18F]FACH—A Novel 18F-Labeled MCT1/MCT4 Lactate Transporter Inhibitor for Imaging Cancer Metabolism with PET

Overexpression of monocarboxylate transporters (MCTs) has been shown for a variety of human cancers (e.g., colon, brain, breast, and kidney) and inhibition resulted in intracellular lactate accumulation, acidosis, and cell death. Thus, MCTs are promising targets to investigate tumor cancer metabolism with positron emission tomography (PET). Here, the organ doses (ODs) and the effective dose (ED) of the first 18F-labeled MCT1/MCT4 inhibitor were estimated in juvenile pigs. Whole-body dosimetry was performed in three piglets (age: ~6 weeks, weight: ~13–15 kg). The animals were anesthetized and subjected to sequential hybrid Positron Emission Tomography and Computed Tomography (PET/CT) up to 5 h after an intravenous (iv) injection of 156 ± 54 MBq [18F]FACH. All relevant organs were defined by volumes of interest. Exponential curves were fitted to the time–activity data. Time and mass scales were adapted to the human order of magnitude and the ODs calculated using the ICRP 89 adult male phantom with OLINDA 2.1. The ED was calculated using tissue weighting factors as published in Publication 103 of the International Commission of Radiation Protection (ICRP103). The highest organ dose was received by the urinary bladder (62.6 ± 28.9 µSv/MBq), followed by the gall bladder (50.4 ± 37.5 µSv/MBq) and the pancreas (30.5 ± 27.3 µSv/MBq). The highest contribution to the ED was by the urinary bladder (2.5 ± 1.1 µSv/MBq), followed by the red marrow (1.7 ± 0.3 µSv/MBq) and the stomach (1.3 ± 0.4 µSv/MBq). According to this preclinical analysis, the ED to humans is 12.4 µSv/MBq when applying the ICRP103 tissue weighting factors. Taking into account that preclinical dosimetry underestimates the dose to humans by up to 40%, the conversion factor applied for estimation of the ED to humans would rise to 20.6 µSv/MBq. In this case, the ED to humans upon an iv application of ~300 MBq [18F]FACH would be about 6.2 mSv. This risk assessment encourages the translation of [18F]FACH into clinical study phases and the further investigation of its potential as a clinical tool for cancer imaging with PET