Possibility of two-dimensional ordering of cryptochrome 4a from European robin.

Cryptochrome (Cry) in some species could act as a quantum senser to detect the inclination angle of geomagnetic field, the function of which attributes the magnetic sensitivity of spins of unpaired electrons in radical pair (RP) in CRY generated by blue light irradiation. However, the effect of blue light on the structure and molecular behavior of Cry has not been well investigated. We conducted the size exclusion chromatography (SEC) and small-angle X-ray scattering (SAXS) analyses to inspect the molecular structure and behavior of cryptochrome 4a (ErCry4a) from European robin, a representative magnetosensory animal. The results indicated that ErCry4a could form flat-shape oligomers. Moreover, blue light irradiation induced the contraction of the ErCry4a molecule at the monomer scale and simultaneously accelerated the two-dimensional oligomerization of ErCry4a. This oligomerization may enhance the regularity of the two-dimensional arrangement of ErCry4a molecules, providing a positive effect for detecting the inclination angle.

Imaging Features of Uncommon Entities That Manifest with Torsion.

Torsion is the twisting of an object along the axis, and various structures (organs and tumors) in the body can twist. Torsion causes initial lymphatic and venous outflow obstruction, leading to congestive edema, enlargement, venous hemorrhagic infarction, and surrounding edema. It can also cause subsequent arterial obstruction depending on the degree of torsion, leading to ischemia, infarction, necrosis, gangrene, and surrounding inflammation. Therefore, in several cases of torsion, immediate surgical intervention is required to improve blood flow and prevent serious complications. Clinical manifestations of torsion are often nonspecific and can affect individuals of varying ages and sex. Imaging plays an important role in the early diagnosis and management of torsion. Multiple imaging modalities, including US, radiography, CT, and MRI, are used to evaluate torsion, and each modality has its specific characteristics. The imaging findings reflect the pathophysiologic mechanism: a twisted pedicle (whirlpool sign), enlargement of the torsed structures, reduced blood flow, internal heterogeneity, and surrounding reactive changes. The whirlpool sign is a definitive characteristic of torsion. In some cases, despite poor internal enhancement, capsular enhancement is observed on contrast-enhanced CT and MR images and is considered to be associated with preserved capsular arterial flow or capsular neovascularization due to inflammation. Radiologists should be familiar with the pathophysiologic mechanisms, clinical characteristics, and imaging characteristics of torsion in various structures in the body. Since other articles about common organ torsions already exist, the authors of this article focus on the uncommon entities that manifest with torsion. ©RSNA, 2024.

Magnetic resonance imaging features of complete androgen insensitivity syndrome in comparison to Mayer-Rokitansky-Küster-Hauser syndrome.

PURPOSE: Complete androgen insensitivity syndrome (CAIS) and Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) share common clinical features such as female phenotype, vaginal hypoplasia, and primary amenorrhea. Magnetic resonance imaging (MRI) is performed to investigate the cause of primary amenorrhea. However, the MRI features are also similar in both disorders. They are ultimately diagnosed by chromosome testing, but there is a possibility of misdiagnosis if chromosome testing is not performed. This study aimed to identify MRI features that are useful for differentiating CAIS from MRKHS. METHOD: This multicenter retrospective study included 12 patients with CAIS and 19 patients with MRKHS. Three radiologists blindly evaluated the following features: (1) detection of vagina, (2) detection of nodular and cystic structures in the lateral pelvis; undescended testicles and paratesticular cysts in CAIS and rudimentary uteri and ovaries in MRKHS, (3) their location, (4) number of cysts in the cystic structures, and (5) signal intensity on diffusion-weighted images (DWI) and apparent diffusion coefficient (ADC) values of the nodular structures. Statistical comparisons were performed using Mann-Whitney U and Fisher's exact tests. RESULTS: Compared with MRKHS, the CAIS group showed significantly detectable vagina, more ventrally located nodular and cystic structures, fewer cysts within the cystic structures, and nodular structures with higher signal intensity on DWI and lower ADC values. CONCLUSIONS: MRI features of detectable vagina, location of nodular and cystic structures, number of cysts within the cystic structures, signal intensity on DWI and ADC values of the nodular structures were useful in differentiating CAIS from MRKHS.

EPR and Related Magnetic Resonance Imaging Techniques in Cancer Research.

Imaging tumor microenvironments such as hypoxia, oxygenation, redox status, and/or glycolytic metabolism in tissues/cells is useful for diagnostic and prognostic purposes. New imaging modalities are under development for imaging various aspects of tumor microenvironments. Electron Paramagnetic Resonance Imaging (EPRI) though similar to NMR/MRI is unique in its ability to provide quantitative images of pO2 in vivo. The short electron spin relaxation times have been posing formidable challenge to the technology development for clinical application. With the availability of the narrow line width trityl compounds, pulsed EPR imaging techniques were developed for pO2 imaging. EPRI visualizes the exogenously administered spin probes/contrast agents and hence lacks the complementary morphological information. Dynamic nuclear polarization (DNP), a phenomenon that transfers the high electron spin polarization to the surrounding nuclear spins (1H and 13C) opened new capabilities in molecular imaging. DNP of 13C nuclei is utilized in metabolic imaging of 13C-labeled compounds by imaging specific enzyme kinetics. In this article, imaging strategies mapping physiologic and metabolic aspects in vivo are reviewed within the framework of their application in cancer research, highlighting the potential and challenges of each of them.

Development and Preclinical Study of Free Radical Imaging Using Field-Cycling Dynamic Nuclear Polarization MRI.

Free radicals, such as metabolic intermediates, reactive oxygen species, and metal enzymes, are key substances in organisms, although they can also cause various oxidative diseases. Thus, in vivo free radical imaging should be considered as the ultimate form of metabolic imaging. Unfortunately, electron spin resonance (ESR) imaging has inherent disadvantages, such as free radicals with large linewidths generating blurred images and the presence of two or more free radicals resulting in a complicated imaging procedure. Dynamic nuclear polarization-magnetic resonance imaging (DNP-MRI) is a noninvasive imaging method to visualize in vivo free radicals, theoretically, with the same resolution as the MRI anatomical resolution, and fixed low-field DNP-MRI provides unique information on oxidative diseases and cancer. However, the large gyromagnetic ratio of the electron spin, which is 660-fold greater than that of a proton, requires field cycling, wherein the external magnetic field should be varied during DNP-MRI observations. This causes difficulties in developing a DNP-MRI system for clinical purposes. We developed a novel field-cycling DNP-MRI system for a preclinical study. In the said system, the magnetic field is switched by rotationally moving two magnets, with a magnetic flux density of 0.3 T for MRI and 5 mT for ESR. The image quality was examined using various pulse sequences and ESR irradiation using nitroxyl radical as the phantom, and the optimum conditions were established. Using the system, we performed a preclinical study involving free radical imaging by placing the free radicals under the palm of a human hand.

Development of Redox Metabolic Imaging Using Endogenous Molecules.

Redox metabolism plays a central role in maintaining homeostasis in living organisms. The electron transfer system in mitochondria produces ATP via endogenous redox molecules such as flavin mononucleotide (FMN), flavin adenine dinucleotide (FAD), and coenzyme Q10 (CoQ10), which have flavin or quinone moieties. One-electron transfer reactions convert FMN, FAD, and CoQ10 to the free radical intermediates FMNH and FADH, and CoQ10H, respectively. Dynamic nuclear polarization-magnetic resonance imaging (DNP-MRI) allows us to visualize free radicals in vitro and in vivo. We present a spectroscopic imaging technology with DNP-MRI, which enables the imaging of multiple free radical intermediates such as FADH and CoQH. DNP-MRI can also identify various endogenous free radical intermediates derived from redox transformations.

Redox imaging of skeletal muscle using in vivo DNP-MRI and its application to an animal model of local inflammation.

Disorders of skeletal muscle are often associated with inflammation and alterations in redox status. A non-invasive technique that could localize and evaluate the severity of skeletal muscle inflammation based on its redox environment would be useful for disease identification and monitoring, and for the development of treatments; however, no such technique currently exists. We describe a method for redox imaging of skeletal muscle using dynamic nuclear polarization magnetic resonance imaging (DNP-MRI), and apply this method to an animal model of local inflammation. Female C57/BL6 mice received injections of 0.5% bupivacaine into their gastrocnemius muscles. Plasma biomarkers, myeloperoxidase activity, and histological sections were assessed at 4 and 24h after bupivacaine injection to measure the inflammatory response. In vivo DNP-MRI was performed with the nitroxyl radicals carbamoyl-PROXYL (cell permeable) and carboxy-PROXYL (cell impermeable) as molecular imaging probes at 4 and 24h after bupivacaine administration. The images obtained after carbamoyl-PROXYL administration were confirmed with the results of L-band EPR spectroscopy. The plasma biomarkers, myeloperoxidase activity, and histological findings indicated that bupivacaine injection caused acute muscle damage and inflammation. DNP-MRI images of mice treated with carbamoyl-PROXYL or carboxy-PROXYL at 4 and 24h after bupivacaine injection showed similar increases in image intensity and decay rate was significantly increased at 24h. In addition, reduction rates in individual mice at 4h and 24h showed faster trends with bupivacaine injection than in their contralateral sides by image-based analysis. These findings indicate that in vivo DNP-MRI with nitroxyl radicals can non-invasively detect changes in the focal redox status of muscle resulting from locally-induced inflammation.

Simultaneous and spectroscopic redox molecular imaging of multiple free radical intermediates using dynamic nuclear polarization-magnetic resonance imaging.

Redox reactions that generate free radical intermediates are essential to metabolic processes. However, their intermediates can produce reactive oxygen species, which may promote diseases related to oxidative stress. We report here the use of dynamic nuclear polarization-magnetic resonance imaging (DNP-MRI) to conduct redox molecular imaging. Using DNP-MRI, we obtained simultaneous images of free radical intermediates generated from the coenzyme Q10 (CoQ10), flavin mononucleotide (FMN), and flavin adenine dinucleotide (FAD) involved in the mitochondrial electron transport chain as well as the radicals derived from vitamins E and K1. Each of these free radicals was imaged in real time in a phantom comprising a mixture of free radicals localized in either lipophilic or aqueous environments. Changing the frequency of electron spin resonance (ESR) irradiation also allowed each of the radical species to be distinguished in the spectroscopic images. This study is the first to report the spectroscopic DNP-MRI imaging of free radical intermediates that are derived from endogenous species involved in metabolic processes.