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Whole animal imaging

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Abstract Translational research plays a vital role in understanding the underlying pathophysiology of human diseases, and hence development of new diagnostic and therapeutic options for their management. After creating an animal disease model, pathophysiologic changes and effects of a therapeutic intervention on them are often evaluated on the animals using immunohistologic or imaging techniques. In contrast to the immunohistologic techniques, the imaging techniques are noninvasive and hence can be used to investigate the whole animal, oftentimes in a single exam which provides opportunities to perform longitudinal studies and dynamic imaging of the same subject, and hence minimizes the experimental variability, requirement for the number of animals, and the time to perform a given experiment. Whole animal imaging can be performed by a number of techniques including x‐ray computed tomography, magnetic resonance imaging, ultrasound imaging, positron emission tomography, single photon emission computed tomography, fluorescence imaging, and bioluminescence imaging, among others. Individual imaging techniques provide different kinds of information regarding the structure, metabolism, and physiology of the animal. Each technique has its own strengths and weaknesses, and none serves every purpose of image acquisition from all regions of an animal. In this review, a broad overview of basic principles, available contrast mechanisms, applications, challenges, and future prospects of many imaging techniques employed for whole animal imaging is provided. Our main goal is to briefly describe the current state of art to researchers and advanced students with a strong background in the field of animal research. Copyright © 2009 John Wiley & Sons, Inc. This article is categorized under: Laboratory Methods and Technologies > Imaging

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Virtual in vivo µCT images of growing lung tumors. Axial microcomputed tomogram (µCT) images of the thorax of a mouse at the indicated time points are shown. µCT images of two lung adenocarcinomas (a–c) and (d–f) and a lung adenoma (g–i) acquired at different ages. Tumors observed in the lung are circled. (Image reproduced with permission from Ref 33. Copyright 2008 Wiley‐Blackwell).

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Simultaneous in vivo 18F‐FDG‐positron emission tomography (PET) and computed tomography (CT) scans of a mouse 50 min after injection of 8.5 MBq of [18F]FDG. Note the strong signal in the kidneys and bladder in the PET images (transverse slice in (b), coronal slice in (e)) and the corresponding position of the kidneys and bladder in the CT images (transverse slice in (a), coronal slice in (d)). The fused transverse slice is shown in (c) and the coronal slice in (f). The scan was acquired using 200 views within a total scan time of 18 min. (Reprinted with permission from Ref 259. Copyright 2002 IOP Publishing Ltd.).

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Spectral analysis can be performed to quantify tumor‐specific probe activation using a Maestro™ small animal in vivo imaging system. Here, a quenched activity‐based imaging probe was injected intravenously and labeled a tumor in vivo. Total fluorescent signal from the tumor and the normal skin is quantified. (a) Spectral curves for each fluorophore as well as for autofluorescence can be generated and saved into a spectral library. Individual curves: white, mouse body; black, imaging stage; red, probe in vivo; magenta, pure probe. (b) By using spectral decomposition and artificial coloration for each spectral curve, a composite image is obtained. A ‘hotmap’ of the probe in vivo shows total fluorescent intensity of the imaging probe within the tumor. (c) Regions of interest can be delineated manually for quantitative analysis of images. (Image courtesy of Jennifer Cutter, NFCR Center for Molecular Imaging, Case Western Reserve University, Cleveland, OH, USA).

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Contrast‐enhanced US images of a rat tumor obtained 7 days after performing the ablation therapy. Inflammatory region can readily be identified because of US contrast agent (UCA) targeting by phosphatidyl serine. The images were taken 12 min after injection of phosphatidyl serine UCAs. (Images courtesy of Dr. Agata Exner, Case Western Reserve University, Cleveland, OH, USA).

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Contrast‐enhanced US images of microvasculature of a rat tumor at different delay times after the US contrast agent (UCA) injection. The microvasculature can not be seen in the image acquired at the beginning of the UCA injection (left), whereas, it can be properly delineated in the images acquired after delay times of 3 (center) and 15 s (left) (Images courtesy of Dr. Agata Exner, Case Western Reserve University, Cleveland, OH, USA).

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Axial magnetic resonance images of a normal adult male rat brain acquired before (left) and 24 h after (right) intraperitoneal injection of 45 mg/kg MnCl2. MnCl2 results in regions enhancement (arrows). Images were acquired with a conventional T1‐weighted spin echo acquisition (TR/TE = 600/10 ms) at 7T.

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Positron emission tomography (PET) images of a rat injected with 6‐deoxy‐6‐[18F]fluoro‐d‐glucose ([18F]6FDG) and scanned during glucose clamp under fasting (left) and hyperinsulimic (right) conditions. The tissue concentration of [18F]6FDG was elevated in response to insulin stimulation (Images courtesy of Dr. Raymond Muzic, Case Western Reserve University, Cleveland, OH, USA).

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Estimation of affect of photodynamic therapy (PDT) on U87 glioma implant in a rat model using dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI). DCE‐MRI images of a U87 glioma implant in a rat model acquired before (left upper) and immediately after (left lower) intravenous injection of Gd‐DTPA contrast agent. Analysis of the dynamic uptake (right) revealed that contrast uptake was increased as evidenced by higher peak signal level in MRI images acquired following PDT. The images were acquired using a fast low angle shot (FLASH) sequence (TR/TE = 200/3 ms).

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High‐resolution (500 × 100 × 100 µm) axial magnetic resonance imaging (MRI) image of dorsolateral prostate of transgenic mouse prone to prostate hyperplasia. Prostate region is outlined in green. The image was acquired by using rapid acquisition with refocused echoes (RARE) sequence (TR/TE = 5000/15 ms).

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Sixteen successive images (starting at second heartbeat post‐injection) from a digital subtraction angiography (DSA) sequence with a 100 ms contrast injection (A). The reproducibility for (n = 5) 100 ms injections (volume injected 83.22 µL) is shown by mean and standard error at each heartbeat (B) in a region of the aortic arch. Note that mean peak value of contrast‐to‐noise ratio (CNR) is 10. (Image reproduced with permission from Ref 7. Copyright 2007).

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