Imaging living mice using a 1‐T compact MRI system

Inoue, Yusuke; Nomura, Yukihiro; Haishi, Tomoyuki; Yoshikawa, Kohki; Seki, Takaomi; Tsukiyama-Kohara, Kyoko; Cui, Kai; Okubo, Toshiyuki; Ohtomo, Kuni

doi:10.1002/jmri.20713

Cited by 20 publications

(23 citation statements)

References 20 publications

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“…A single operator working alone was able to achieve the mouse restraint, but the mice were restrained more easily through the cooperation of two operators. Although insufficient restraint may increase motion artifacts (12), excessive restraint may cause health problems. We visually confirmed shallow but evident breathing after restraint.…”

Section: Discussionmentioning

confidence: 99%

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Effect of isoflurane anesthesia and hypothermia on the hepatic kinetics of Gd‐EOB‐DTPA: Evaluation using MRI of conscious mice

Kiryu

Inoue

Watanabe

et al. 2011

Magnetic Resonance Imaging

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Purpose: To develop a method for body magnetic resonance imaging (MRI) of conscious mice and investigate the effect of isoflurane anesthesia and hypothermia on the hepatic kinetics of gadoxetate disodium (Gd-EOB-DTPA). Materials and Methods:Conscious or anesthetized mice were restrained on a holder and the rectal temperature was measured serially. Serial MRI of the liver was performed after intravenous injection of Gd-EOB-DTPA with or without temperature control. Three mice were studied for each condition. Results:The temperature dropped rapidly in anesthetized mice beside the MR unit. The decline was less prominent in conscious mice. The temperature decreased less in anesthetized mice and remained constant in conscious mice in the radiofrequency (RF) coil. The washout of Gd-EOB-DTPA was slower in anesthetized hypothermic mice than in conscious normothermic mice. Warmed anesthetized mice showed faster washout, and cooled conscious mice showed delayed washout. Severer hypothermia in anesthetized mice resulted in weaker initial enhancement and slower washout.Conclusion: By separately manipulating the presence or absence of anesthesia and hypothermia, we demonstrated that washout of Gd-EOB-DTPA was delayed under hypothermia, regardless of anesthesia. Serial body MRI of conscious mice was feasible and allowed the evaluation of kinetics of a contrast agent, while excluding the possible effects of anesthesia. MAGNETIC RESONANCE IMAGING (MRI) is a noninvasive technique that provides 3D information about both anatomy and function and is accepted as a powerful modality for small animal experiments as well as for clinical practice (1-4). Small animal MRI is usually performed under anesthesia, which may change physiological conditions and affect the experimental results including the pharmacokinetics of a contrast agent. The kinetics of a hepatobiliary contrast agent reflects liver function in humans and small animals (5,6) and is important to determine the optimal timing of imaging. It has been suggested that the kinetics of two hepatobiliary contrast agents, gadobenate dimeglumine (Gd-BOPTA) (7) and gadoxetate disodium (Gd-EOB-DTPA) (8), differ between anesthetized and conscious mice, and that anesthesia using isoflurane or pentobarbital prolongs contrast enhancement in the liver. Although the body temperature in mice decreases under anesthesia (9,10), the kinetics of contrast agents was evaluated without warming or measurement of body temperature in the previous studies. Therefore, hypothermia, other than the direct action of anesthetic, might have affected the kinetics.We developed a method for acquiring body MR images in conscious mice and evaluated the kinetics of Gd-EOB-DTPA in mouse liver under conditions of isoflurane anesthesia and consciousness. Furthermore, we manipulated the body temperature to separately assess the direct action of the anesthetic and the effect of hypothermia. The aim of this study was to determine the feasibility and potential usefulness of serial body MRI in conscious mice and to investigat...

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Section: Discussionmentioning

confidence: 99%

“…MRI was performed using a compact MRI system (MRmini; MRTechnology, Tsukuba, Japan), consisting of a 1-T permanent magnet, made of Nd-Fe-B material (Hitachi Metals, Tokyo, Japan) and a compact console (11,12). A solenoid coil with a 30-mm inner diameter was used as a radiofrequency (RF) detection coil.…”

Section: Imaging Proceduresmentioning

confidence: 99%

Effect of isoflurane anesthesia and hypothermia on the hepatic kinetics of Gd‐EOB‐DTPA: Evaluation using MRI of conscious mice

Kiryu

Inoue

Watanabe

et al. 2011

Magnetic Resonance Imaging

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“…24,25 The maximum amplitude and slew rate of the gradient system were 140 mT/m and 350 T/m/s, respectively. The mice were fed only autoclaved potatoes for 24 hours before imaging to reduce high signal intensity in the gastrointestinal system and achieve fewer artifacts and better image quality.…”

Section: Imaging Proceduresmentioning

confidence: 99%

Interstitial MR Lymphography in Mice: Comparative Study with Gadofluorine 8, Gadofluorine M, and Gadofluorine P

et al. 2012

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Purpose: We investigated the characteristics and capability of interstitial MR lymphography in mice using gado‰uorine 8, gado‰uorine M, and gado‰uorine P.Methods: We injected healthy mice with 0.5 mmol of Gd gado‰uorine 8, gado‰uorine M, or gado‰uorine P subcutaneously into the right rear footpad and assessed the time courses of contrast enhancement in the lymph nodes. Six mice were studied for each contrast agent. We also used gado‰uorine M to assess the lymphatic pathway from the right and left rear feet or tail.Results: Contrast enhancement was demonstrated for the right popliteal, sacral, and iliac lymph nodes in all mice 5 minutes after injection of each of the 3 agents and decreased gradually. Enhancement in the lymph nodes was still detectable 30 minutes after injection of gado‰uorine 8 or gado‰uorine M. Enhancement became obscure sooner after gado‰uo-rine P injection and was mildly stronger with the other 2 contrast agents. Clear diŠerences were found in the hepatobiliary and urinary kinetics of the 3 agents. Gado‰uorine M injected into various sites delineated the lymphatic pathway from the site of injection.Conclusion: Interstitial MR lymphography using gado‰uorine 8, gado‰uorine M, and gado‰uorine P oŠered clear visualization of the lymphatic pathway in healthy mice during a su‹cient imaging time window, and allowed repeated assessment of the pathway and clariˆcation of the lymphatic system.

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“…In contrast, the dry form of Gd-chelates provides no signal on MR images without contact with water. 2,3) The release of substances from tablets and capsules has been visualized in rats 3,4) and humans 2) using this technique. Despite its usefulness, few studies have employed MRI in pharmaceutical analyses because of the size and expense of superconducting MRI systems.…”

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“…Compact MRI systems were recently developed with 0.5-1.0 T permanent magnets and used in pathological studies on mice and human hands 5,6) as well as in analyses of the biodistribution of paramagnetic substances in rats and mice. 7,8) We previously investigated the pharmacokinetics of nitroxyl radicals, paramagnetic probes sensitive to biological redox, in mice using compact MRI with 1.5 T permanent magnets.…”

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confidence: 99%

Application of a Compact Magnetic Resonance Imaging System with 1.5 T Permanent Magnets to Visualize Release from and the Disintegration of Capsule Formulations <i>in Vitro</i> and <i>in Vivo</i>

Takeshita

Okazaki

Shinada

et al. 2017

Biological & Pharmaceutical Bulletin

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Although magnetic resonance imaging (MRI) has potential in assessments of formulations, few studies have been conducted because of the size and expense of the instrument. In the present study, the processes of in vitro and in vivo release in a gelatin capsule formulation model were visualized using a compact MRI system with 1.5 T permanent magnets, which is more convenient than the superconducting MRI systems typically used for clinical and experimental purposes. A Gd-chelate of diethylenetriamine-N,N,N′,N″,N″-pentaacetic acid, a contrast agent that markedly enhances proton signals via close contact with water, was incorporated into capsule formulations as a marker compound. In vitro experiments could clearly demonstrate the preparation-dependent differences in the release/disintegration of the formulations. In some preparations, the penetration of water into the formulation and generation of bubbles in the capsule were also observed prior to the disintegration of the formulation. When capsule formulations were orally administered to rats, the release of the marker into the stomach and its transit to the duodenum were visualized. These results strongly indicate that the compact MRI system is a powerful tool for pharmaceutical studies.Key words magnetic resonance imaging (MRI); capsule formulation; release; disintegration; gadoliniumchelate of diethylenetriamine-N,N,N′,N″,N″-pentaacetic acid (Gd-DTPA) Capsule formulations are convenient drug delivery systems that control the stability and release of drugs in the gastrointestinal tract; therefore, they are used in a wide range of drugs that are administered orally. The performance of formulations is influenced by the swelling and/or disintegration of capsules, the penetration of water in formulations, and the release of drug contents in the gastrointestinal tract. Since these processes influence the bioavailability of drugs, visualizing these processes may provide direct information for assessing capsule formulations.Magnetic resonance imaging (MRI) is a non-invasive imaging technique that provides unique information that is useful for diagnostic purposes. MRI is sensitive to the local concentrations and physical state of protons, mainly those in water in biological specimens. The advantages of MRI over other non-invasive imaging techniques such as γ-scintigraphy are its high spatial and temporal resolutions and representation of anatomical structures. Paramagnetic compounds such as chelate compounds of Gd(III) are typically used as contrast agents.1) Gd-chelates shorten the longitudinal relaxation time (T 1 ) of protons in water by making close contact with water, which markedly enhances proton signals on T 1 -weighted magnetic resonance (MR) images. In contrast, the dry form of Gd-chelates provides no signal on MR images without contact with water.2,3) The release of substances from tablets and capsules has been visualized in rats 3,4) and humans 2) using this technique. Despite its usefulness, few studies have employed MRI in pharmaceutical analyses because of ...

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Imaging living mice using a 1‐T compact MRI system

Cited by 20 publications

References 20 publications

Effect of isoflurane anesthesia and hypothermia on the hepatic kinetics of Gd‐EOB‐DTPA: Evaluation using MRI of conscious mice

Effect of isoflurane anesthesia and hypothermia on the hepatic kinetics of Gd‐EOB‐DTPA: Evaluation using MRI of conscious mice

Interstitial MR Lymphography in Mice: Comparative Study with Gadofluorine 8, Gadofluorine M, and Gadofluorine P

Application of a Compact Magnetic Resonance Imaging System with 1.5 T Permanent Magnets to Visualize Release from and the Disintegration of Capsule Formulations <i>in Vitro</i> and <i>in Vivo</i>

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