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821:(with the PET inserted inside the MRI magnet). This provides a much more accurate picture far more quickly. By operating the PET and MRI systems simultaneously workflow within a laboratory can be increased. The MR-PET system from MR Solutions incorporates the latest technology in Silicon Photomultipliers (SiPM), which significantly reduces the size of the system and avoids the problems of using photomultipliers or other legacy detector types within the magnetic field of the MRI. The performance characteristics of SiPM are similar to a conventional PMT, but with the practical advantages of solid-state technology.
969:
458:
Furthermore, the image acquisition time is extremely long, spanning into minutes and even hours. This may negatively affect animals that are anesthetized for long periods of time. In addition, micro-MRI typically captures a snapshot of the subject in time, and thus it is unable to study blood flow and other real-time processes well. Even with recent advances in high strength functional micro-MRI, there is still around a 10–15 second lag time to reach peak signal intensity, making important information such as blood flow velocity quantification difficult to access.
345:(PAT) works on the natural phenomenon of tissues to thermalelastically expand when stimulated with externally applied electromagnetic waves, such as short laser pulses. This causes ultrasound waves to be emitted from these tissues, which can then be captured by an ultrasound transducer. The thermoelastic expansion and the resulting ultrasound wave is dependent on the wavelength of light used. PAT allows for complete non-invasiveness when imaging the animal. This is especially important when working with brain tumor models, which are notoriously hard to study.
844:
298:
sufficient for small animals such as mice. The performance of ultrasound imaging is often perceived as to be linked with the experience and skills of the operator. However, this is changing rapidly as systems are being designed into user-friendly devices that produce highly reproducible results. One other potential disadvantage of micro-ultrasound is that the targeted microbubble contrast agents cannot diffuse out of vasculature, even in tumors. However, this may actually be advantageous for applications such as tumor perfusion and angiogenesis imaging.
501:(CT) imaging works through X-rays that are emitted from a focused radiation source that is rotated around the test subject placed in the middle of the CT scanner. The X-ray is attenuated at different rates depending on the density of tissue it is passing through, and is then picked up by sensors on the opposite end of the CT scanner from the emission source. In contrast to traditional 2D X-ray, since the emission source in a CT scanner is rotated around the animal, a series of 2D images can then be combined into 3D structures by the computer.
862:
The animal translates automatically from one modality to the other along the same axis. By inserting a SPECT module inside the MRI magnet simultaneous acquisition of SPECT and MRI data is possible. The workflow of the laboratory can be increased by acquiring multiple modalities of the same subject in one session or by operating the SPECT and MRI systems separately, imaging different subjects at the same time. SPECT-MR is available in different configurations with different trans-axial field of views, allowing imaging from mice to rats.
570:
radiotherapy, and thus extra control groups might be needed to account for this potential confounding variable. Micro-PET also has poor spatial resolution of around 1 mm. In order to conduct a well rounded research that involves not only molecular imaging but also anatomical imaging, micro-PET needs to be used in conjunction with micro-MRI or micro-CT, which further decreases accessibility to many researchers because of high cost and specialized facilities.
267:, it can even be used to study high speed events such as blood flow and cardiac function in mice. Micro-ultrasound systems are portable, do not require any dedicated facilities, and is extremely cost-effective compared to other systems. It also does not run the risk of confounding results through side-effects of radiation. Currently, imaging of up to 30 μm is possible, allowing the visualization of tiny vasculature in cancer
556:(fludeoxyglucose), which is injected into the test subject. As the radioisotopes decay, they emit positrons which annihilates with electrons found naturally in the body. This produces 2 γ-rays at ~180° apart, which are picked up by sensors on opposite ends of the PET machine. This allows individual emission events to be localized within the body, and the data set is reconstructed to produce images.
123:
66:
488:
25:
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time, unlike micro-PET, micro-SPECT can reach very high spatial resolution by exploring pinhole collimation principle (Beekman et al.) In this approach, by placing the object (e.g. rodent) close to the aperture of the pinhole, one can reach high magnification of its projection on detector surface and effectively compensate for intrinsic resolution of the crystal.
480:
367:
micro-PAT is that it relies on optical absorbance of tissue to receive feedback, and thus poorly vascularized tissue such as the prostate is difficult to visualize. To date, 3 commercially available systems are on the market, namely by VisualSonics, iThera and Endra, the last one being the only machine doing real 3D image acquisition.
820:
Researchers can use standalone PET or MRI operation, or use multi-modality imaging. PET and MRI techniques can be carried out either independently (using either the PET or MRI systems as standalone devices), or in sequence (with a clip-on PET) in front of the bore of the MRI system, or simultaneously
562:
The strength of micro-PET is that because the radiation source is within the animal, it has practically unlimited depth of imaging. The acquisition time is also reasonably fast, usually around minutes. Since different tissues have different rates of uptake radiolabelled molecular probes, micro-PET is
405:
neuro-imaging devices. It is fast, non-invasive, and provides a plethora of data output. Micro-PAT can image the brain with high spatial resolution, detect molecular targeted contrast agents, simultaneously quantify functional parameters such as SO2 and HbT, and provide complementary information from
366:
Because micro-PAT is still limited by the penetrating strength of light and sound, it does not have unlimited depth of penetration. However, it is sufficient to pass through rat skull and image up to a few centimeters down, which is more than sufficient for most animal research. One other drawback of
351:
Micro-PAT can be described as an imaging modality that is applicable in a wide variety of functions. It combines the high sensitivity of optical imaging with the high spatial resolution of ultrasound imaging. For this reason, it can not only image structure, but also separate between different tissue
868:
As this is a combination of imaging systems the weaknesses associated with one or other imaging modality are no longer applicable. In sequential SPECT-MR, the operator needs to allow a little time to transfer the subject between the SPECT and MR acquisition positions. This is negated in simultaneous
576:
PET is usually widely used in clinical oncology, and thus results from small animal research are easily translated. Because of the way 18F-FDG is metabolized by tissues, it results in intense radiolabelling in most cancers, such as brain and liver tumors. Almost any biological compound can be traced
533:
Micro-CT is most often used as an anatomical imaging system in animal research because of the benefits that were mentioned earlier. Contrast agents can also be injected to study blood flow. However, contrast agents for micro-CT, such as iodine, are difficult to conjugate molecular targets1 with, and
432:
frequency of the target nuclei, perturbing the nuclei's alignment with the magnetic field. After the RF pulse the nuclei relax and emit a characteristic RF signal, which is captured by the machine. With this data a computer will generate an image of the subject based on the resonance characteristics
322:
Unlike conventional micro-ultrasound device with limited blood-flow sensitivity, dedicated real-time ultra fast ultrasound scanners with appropriate sequence and processing have been shown to be able to capture very subtle hemodynamic changes in the brain of small animals in real-time. This data can
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Because of poor depth of penetration, optical imaging is typically only used for molecular purposes, and not anatomical imaging. Due to poor depth of penetration in visible wavelengths, it is used for subcutaneous models of cancer, however near-infrared fluorescence has enabled orthotopic models to
304:
The advances in micro-ultrasound has been able to aid cancer research in a plethora of ways. For example, researchers can easily quantify tumor size in two and three dimensions. Not only so, blood flow speed and direction can also be observed through ultrasound. Furthermore, micro-ultrasound can be
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Research facilities no longer need to purchase multiple systems and may choose between different system imaging configurations. The SPECT or MRI equipment can each be used as a standalone device on a bench, or sequential imaging can be carried out by clipping the SPECT module on to the MRI system.
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also has very good sensitivity and only nanograms of molecular probes are needed. Furthermore, by using different energy radioisotopes conjugated to different molecular targets, micro-SPECT has the advantage over micro-PET in being able to image several molecular events simultaneously. At the same
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Micro-CT can have excellent spatial resolution, which can be up to 6 μm when combined with contrast agents. However, the radiation dose needed to achieve this resolution is lethal to small animals, and a 50 μm spatial resolution is a better representation of the limits of micro-CT. It is
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The new SPECT-MR for small animal imaging is based on multi-pinhole technology, allowing high resolution and high sensitivity. When coupled with cryogen-free MRI the combined SPECT-MR technology dramatically increases the workflow in research laboratories whilst reducing laboratory infrastructure
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The PET-MR technology for small animal imaging offers a major breakthrough in high performance functional imaging technology, particularly when combined with a cryogen-free MRI system. A PET-MR system provides superior soft tissue contrast and molecular imaging capability for great visualisation,
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Radioactive isotopes used in micro-PET have very short half-lives (110 min for 18F-FDG). In order to generate these isotopes, cyclotrons in radiochemistry laboratories are needed in close proximity of the micro-PET machines. Also, radiation may affect tumor size in cancer models as it mimics
464:
Micro-MRI is often used to image the brain because of its ability to non-invasively penetrate the skull. Because of its high resolution, micro-MRI can also detect early small-sized tumors. Antibody-bound paramagnetic nanoparticles can also be used to increase resolution and to visualize molecular
450:
The advantage of micro-MRI is that it has good spatial resolution, up to 100 μm and even 25 μm in very high strength magnetic fields. It also has excellent contrast resolution to distinguish between normal and pathological tissue. Micro-MRI can be used in a wide variety of applications,
199:
is the visualization of living animals for research purposes, such as drug development. Imaging modalities have long been crucial to the researcher in observing changes, either at the organ, tissue, cell, or molecular level, in animals responding to physiological or environmental changes. Imaging
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simultaneous PET-MR. However, in sequential PET-MR systems, the PET ring itself is easy to clip-on or off and transfer between rooms for independent use. The researcher requires sufficient knowledge to interpret images and data from the two different systems and would require training for this.
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quantification and translational studies. A PET-MR preclinical system can be used for simultaneous multi-modality imaging. Use of cryogen-free magnet technology also greatly reduces infrastructure requirements and dependency on the availability of increasingly hard to obtain cryogenic coolants.
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in response to anti-tumor therapy, since it is the only imaging modality that has instantaneous image acquisition. Because of its real-time nature, micro-ultrasound can also guide micro-injections of drugs, stem cells, etc. into small animals without the need for surgical intervention. Contrast
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has a half-life of 110 min and limits the radioactive exposure to the animal or human. Optical imaging allows for higher resolution with sub-cellular resolution of ~270 nm, or the diffraction limit of light, to allow for imaging of single cells and localizing cellular location on the cell
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The combination of MRI, which is used as a non-invasive imaging technique, and SPECT provide results far more quickly when compared to using one technique at a time. Images from the two modalities may also be registered far more precisely, since the time delay between modalities is limited for
256:
High-frequency micro-ultrasound works through the generation of harmless sound waves from transducers into living systems. As the sound waves propagate through tissue, they are reflected back and picked up by the transducer, and can then be translated into 2D and 3D images. Micro-ultrasound is
948:
have been specifically designed to be optimally excited in this area. Optical imaging, fluorescence has a resolution limited to the diffraction of light of ~270 nm and bioluminescence has a resolution of ~1–10 mm, depending on time of acquisition, compared to MRI at 100 μm, and
943:
A major weakness of optical imaging has been the depth of penetration, which, in the case of visible dyes is only a few millimeters. Near-infrared fluorescence has allowed depths of several centimeters to be feasible. Since light in the infrared region has the best penetration depth, numerous
457:
One of the biggest drawbacks of micro-MRI is its cost. Depending on the magnetic strength (which determines resolution), systems used for animal imaging between 1.5 and 14 teslas in magnetic flux density range from $ 1 million to over $ 6 million, with most systems costing around $ 2 million.
381:
is often needed, in addition to hours of anesthesia, mechanical ventilation, etc. which significantly alters experimental parameters. For this reason, many researchers have been content to sacrifice animals at different time points and study brain tissue with traditional histological methods.
297:
Unlike micro-MRI, micro-CT, micro-PET, and micro-SPECT, micro-ultrasound has a limited depth of penetration. As frequency increases (and so does resolution), maximum imaging depth decreases. Typically, micro-ultrasound can image tissue of around 3 cm below the skin, and this is more than
827:
As this is a combination of imaging systems the weaknesses associated with each imaging modality are largely compensated for by the other. In sequential PET-MR, the operator needs to allow a little time to transfer the subject between the PET and MR acquisition positions. This is negated in
876:
sequential SPECT-MR systems, and effectively non-existent for simultaneous systems. This means that there is little to no opportunity for gross movement of the subject between acquisitions. With separate, independent operation of the MRI and SPECT systems workflow can easily be increased.
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The combination of MR and PET imaging is far more time efficient than using one technique at a time. Images from the two modalities may also be registered far more precisely, since the time delay between modalities is limited for sequential PET-MR systems, and effectively non-existent for
518:
dosage placed on test animals. Although this is generally not lethal, the radiation is high enough to affect the immune system and other biological pathways, which may ultimately change experimental outcomes. Also, radiation may affect tumor size in cancer models as it mimics
908:
works on the basis of fluorochromes inside the subject that are excited by an external light source, and which emit light of a different wavelength in response. Traditional fluorochromes include GFP, RFP, and their many mutants. However significant challenges emerge
204:
have become especially important to study animal models longitudinally. Broadly speaking, these imaging systems can be categorized into primarily morphological/anatomical and primarily molecular imaging techniques. Techniques such as high-frequency micro-ultrasound,
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analysis, it requires a craniotomy and only provides a few hundred micrometres of penetration depth. Furthermore, it is focused on one area of the brain, while research has made it apparently clear that brain function is interrelated as a whole. On the other hand,
869:
SPECT-MR. However, for sequential SPECT-MR, when the SPECT module is clipped on it is easy to clip-on or off and transfer between rooms. The researcher has to have sufficient knowledge to interpret two different system outputs and would require training for this.
420:(MRI) exploits the nuclear magnetic alignments of different atoms inside a magnetic field to generate images. MRI machines consist of large magnets that generate magnetic fields around the target of analysis. These magnetic fields cause atoms with non-zero
287:(VEGFR), in order to provide molecular visualization. Thus, it is capable of a wide range of applications that can only be achieved through dual imaging modalities such as micro-MRI/PET. Micro-ultrasound devices have unique properties pertaining to an
932:
Optical imaging is fast and easy to perform, and is relatively inexpensive compared to many of the other imaging modalities. Furthermore, it is extremely sensitive, being able to detect molecular events in the 10–15 M range. In addition, since
1285:"Novel single-chain antibody-targeted microbubbles for molecular ultrasound imaging of thrombosis: validation of a unique noninvasive method for rapid and sensitive detection of thrombi and monitoring of success or failure of thrombolysis in mice"
400:
is extremely expensive, and offers dismal resolution and image acquisition times when scanning the entire brain. It also provides little vasculature information. Micro-PAT has been demonstrated to be a significant enhancement over existing
913:
due to the autofluorescence of tissue at wavelengths below 700 nm. This has led to a transition to near-infrared dyes and infrared fluorescent proteins (700 nm–800 nm) which have demonstrated much more feasibility for
653:
Micro-SPECT is often used in cancer research for molecular imaging of cancer-specific ligands. It can also be used to image the brain because of its penetration power. Since newer radioisotopes involve nanoparticles such as
451:
including anatomical, functional, and molecular imaging. Furthermore, since micro-MRI's mechanism is based on a magnetic field, it is much safer compared to radiation based imaging modalities such as micro-CT and micro-PET.
232:
These days, many manufacturers provide multi-modal systems combining the advantages of anatomical modalities such as CT and MR with the functional imaging of PET and SPECT. As in the clinical market, common combinations are
386:
longitudinal study, many more animals are needed to obtain significant results, and the sensitivity of the entire experiment is cast in doubt. As stated earlier, the problem is not reluctance by researchers to use
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Nourse J, Tokalov S, Kohkhar S, Khan E, Schott LK, Hinz L, Eder L, Arnold-Schild D, Probst HC, Danckwardt S (2021). "Non-invasive imaging of gene expression and protein secretion dynamics in living mice".
271:. To image capillaries, this resolution can be further increased to 3–5 μm with the injection of microbubble contrast agents. Furthermore, microbubbles can be conjugated to markers such as activated
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with subcellular resolution (see Figure of multicolor HeLa cells). Multiple instruments are required to image PET, whole organ fluorescence, and single cell fluorescence with sub-cellular resolution.
972:
Multi-color fluorescence imaging of living HeLa cells with labelled mitochondria (red), actin (green), and nuclei (bue). Each cell is ~10 um and images show optical imaging allows for resolution ≤1 um.
925:(CCD) cameras cooled up to −150 °C, making them extremely light-sensitive. In events where more light is produced, less sensitive cameras or even the naked eye can be used to visualize the image.
921:
Bioluminescence imaging, on the other hand, is based on light generated by chemiluminescent enzymatic reactions. In both fluorescence and bioluminescence imaging, the light signals are captured by
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Sajedi S, Zeraatkar N, Moji V, Farahani MH, Sarkar S, Arabi H, et al. (March 2014). "Design and development of a high resolution animal SPECT scanner dedicated for rat and mouse imaging".
635:
Micro-SPECT still has considerable radiation which may affect physiological and immunological pathways in the small animals. Also, radiation may affect tumor size in cancer models as it mimics
444:
Since 2012, the use of cryogen-free magnet technology has greatly reduced infrastructure requirements and dependency on the availability of increasingly hard to obtain cryogenic coolants.
1905:
Magota K, Kubo N, Kuge Y, Nishijima K, Zhao S, Tamaki N (April 2011). "Performance characterization of the Inveon preclinical small-animal PET/SPECT/CT system for multimodality imaging".
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Micro-ultrasound is the only real-time imaging modality per se, capturing data at up to 1000 frames per second. This means that not only is it more than capable of visualizing blood flow
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imaging does not require excitation of the reporter, but rather the catalysis reaction itself, it is indicative of the biological / molecular process and has almost no background noise.
618:
directly, instead of from annihilation events of a positron and electron. These rays are then captured by a γ-camera rotated around the subject and subsequently rendered into images.
624:
The benefit of this approach is that the nuclear isotopes are much more readily available, cheaper, and have longer half-lives as compared to micro-PET isotopes. Like micro-PET,
527:. In addition, the contrast resolution of micro-CT is quite poor, and thus it is unsuitable for distinguishing between similar tissue types, such as normal vs. diseased tissues.
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conjugated to specific biological molecules. Furthermore, it is non-invasive and can be quickly performed, making it ideal for longitudinal studies of the same animal.
1248:
Foster FS, Mehi J, Lukacs M, Hirson D, White C, Chaggares C, Needles A (October 2009). "A new 15–50 MHz array-based micro-ultrasound scanner for preclinical imaging".
960:
with genetically engineered light-emitting reporter genes. This also allows the identification of mechanisms for tissue-selective gene targeting in cancer and beyond.
534:
thus it is rarely used in molecular imaging techniques. As such, micro-CT is often combined with micro-PET/SPECT for anatomical and molecular imaging in research.
331:(fMRI). fUS can be used for brain angiography, brain functional activity mapping, brain functional connectivity from mice to primates including awake animals.
2369:"New Dioxaborolane Chemistry Enables [(18)F]-Positron-Emitting, Fluorescent [(18)F]-Multimodality Biomolecule Generation from the Solid Phase"
592:
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also decent in terms of image acquisition times, which can be in the range of minutes for small animals. In addition, micro-CT is excellent for bone imaging.
284:
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van der Zwaag W, Francis S, Head K, Peters A, Gowland P, Morris P, Bowtell R (October 2009). "fMRI at 1.5, 3 and 7 T: characterising BOLD signal changes".
2074:
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Wang X, Fowlkes JB, Carson PL (2008). "Experimental evaluation of a high-speed photoacoustic tomography system based on a commercial ultrasound unit".
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Guo H, Harikrishna K, Vedvyas Y, McCloskey JE, Zhang W, Chen N, Nurili F, Wu AP, Sayman HB, Akin O, Rodriguez EA, Aras O, Jin MM, Ting R (May 2019).
643:. Micro-SPECT can also be up to two orders of magnitude less sensitive than PET. Furthermore, labeling compounds with micro-SPECT isotopes require
391:
imaging modalities, but rather a lack of suitable ones. For example, although optical imaging provides fast functional data and oxy- and deoxy
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Micro-MRI is often used for anatomical imaging in stroke and traumatic brain injury research. Molecular imaging is a new area of research.
38:
291:, where users of these devices get access to raw data typically unavailable on most commercial ultrasound (micro and non-micro) systems.
1103:
1024:
2425:"18F-positron-emitting/fluorescent labeled erythrocytes allow imaging of internal hemorrhage in a murine intracranial hemorrhage model"
132:
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1586:"Simultaneous detection and separation of hyperacute intracerebral hemorrhage and cerebral ischemia using amide proton transfer MRI"
802:
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Beekman F, van der Have F (February 2007). "The pinhole: gateway to ultra-high-resolution three-dimensional radionuclide imaging".
75:
2485:"18F]-positron-emitting agent for imaging PMSA allows genetic reporting in adoptively-transferred, genetically-modified cells"
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now be feasible. Often, investigation of specific protein expression in cancer and drug effects on these expressions are studied
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functional and molecular imaging which would be extremely useful in tumor quantification and cell-centered therapeutic analysis.
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agents can be injected into the animal to perform real-time tumor perfusion and targeted molecular imaging and quantification of
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simultaneous systems. This means that there is little to no opportunity for gross movement of the subject between acquisitions.
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Schober O, Rahbar K, Riemann B (February 2009). "Multimodality molecular imaging—from target description to clinical studies".
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Wang M, Kommidi H, Tosi U, Guo H, Zhou Z, Schweitzer ME, Wu LY, Singh R, Hou S, Law B, Ting R, Souweidane MM (December 2017).
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Nuclear
Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment
1854:
Nuclear
Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment
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emitted from within the subject. The source of the radiation comes from positron-emitting-bound biological molecules, such as
1635:"Using functional and molecular MRI techniques to detect neuroinflammation and neuroprotection after traumatic brain injury"
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membrane, endosomes, cytoplasm, or nuclei (see FIgure of multicolor HeLa cellls). The technique can label small molecules,
1011:, respectively. A Human-Derived, Genetic, Positron-emitting and Fluorescent (HD-GPF) reporter system uses a human protein,
2606:"18F-Radiolabeled Panobinostat Allows for Positron Emission Tomography Guided Delivery of a Histone Deacetylase Inhibitor"
1283:
Wang X, Hagemeyer CE, Hohmann JD, Leitner E, Armstrong PC, Jia F, Olschewski M, Needles A, Peter K, Ahrens I (June 2012).
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by micro-PET, as long as it can be conjugated to a radioisotope, which makes it suitable towards studying novel pathways.
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such as hydrogen, gadolinium, and manganese to align themselves with the magnetic dipole along the magnetic field. A
2129:"A systematic approach to the development of fluorescent contrast agents for optical imaging of mouse cancer models"
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The study of brain cancers has been significantly hampered by the lack of an easy imaging modality to study animals
2751:
Kommidi H, Guo H, Nurili F, Vedvyas Y, Jin MM, McClure TD, Ehdaie B, Sayman HB, Akin O, Aras O, Ting R (May 2018).
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also extremely sensitive to molecular details, and thus only nanograms of molecular probes are needed for imaging.
417:
206:
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The following small-animal SPECT systems have been developed in different groups and are available commercially:
658:-labelled iron oxide nanoparticles, they could potentially be combined with drug delivery systems in the future.
1958:
van der Have F, Vastenhouw B, Ramakers RM, Branderhorst W, Krah JO, Ji C, Staelens SG, Beekman FJ (April 2009).
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2179:"Comparison of visible and near-infrared wavelength-excitable fluorescent dyes for molecular imaging of cancer"
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44:
2704:"18F]-Positron-Emitting, Fluorescent, Cerebrospinal Fluid Probe for Imaging Damage to the Brain and Spine"
806:
The image shows a 3T preclinical MRI multi-modality imaging system with a clip-on PET for sequential imaging.
1202:
Willmann JK, van
Bruggen N, Dinkelborg LM, Gambhir SS (July 2008). "Molecular imaging in drug development".
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1031:-cells, in an entire mouse. The combining of these imaging modalities was predicted by 2008 Nobel Laureate,
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imaging due to the much lower autofluorescence of tissue and deeper tissue penetration at these wavelengths.
257:
specifically developed for small animal research, with frequencies ranging from 15 MHz to 80 MHz.
2753:"18F-Positron Emitting/Trimethine Cyanine-Fluorescent Contrast for Image-Guided Prostate Cancer Management"
2534:"18F-Positron Emitting/Trimethine Cyanine-Fluorescent Contrast for Image-Guided Prostate Cancer Management"
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Del Guerra A, Belcari N (December 2007). "State-of-the-art of PET, SPECT and CT for small animal imaging".
591:
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272:
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Wang W, Zhang H, Lee DH, Yu J, Cheng T, Hong M, Jiang S, Fan H, Huang X, Zhou J, Wang J (August 2017).
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Adams KE, Ke S, Kwon S, Liang F, Fan Z, Lu Y, Hirschi K, Mawad ME, Barry MA, Sevick-Muraca EM (2007).
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allows for anatomical imaging for location of labelled cells in entire animals or humans because the
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High resolution Tc-MDP mouse SPECT scan: animated image of rotating maximum intensity projections.
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Kommidi H, Tosi U, Maachani UB, Guo H, Marnell CS, Law B, Souweidane MM, Ting R (February 2018).
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1019:) and fluorescent for dual modality PET and fluorescence imaging of genome modified cells, e.g.
2236:"Mammalian expression of infrared fluorescent proteins engineered from a bacterial phytochrome"
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1770:"Molecular imaging in living subjects: seeing fundamental biological processes in a new light"
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314:. Recently, micro-ultrasound has even been shown to be an effective method of gene delivery.
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Deng CX, Sieling F, Pan H, Cui J (April 2004). "Ultrasound-induced cell membrane porosity".
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2293:"Hyaluronidase expression induces prostate tumor metastasis in an orthotopic mouse model"
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Wang Y, An FF, Chan M, Friedman B, Rodriguez EA, Tsien RY, Aras O, Ting R (March 2017).
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Boone JM, Velazquez O, Cherry SR (July 2004). "Small-animal X-ray dose from micro-CT".
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It may require cleanup to comply with
Knowledge (XXG)'s content policies, particularly
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emitted from within the subject. Unlike PET, the radioisotopes used in SPECT (such as
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Shu X, Royant A, Lin MZ, Aguilera TA, Lev-Ram V, Steinbach PA, Tsien RY (May 2009).
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Kommidi H, Guo H, Nurili F, Vedvyas Y, Jin MM, McClure TD, et al. (May 2018).
1394:
1145:
1133:
1050:
1000:
894:
636:
520:
268:
214:
147:
2670:
1362:
Li ML, Oh JT, Xie X, Ku G, Wang W, Li C, Lungu G, Stoica G, Wang LV (March 2008).
487:
2768:
2549:
2128:
1999:
Ivashchenko O, van der Have F, Goorden MC, Ramakers RM, Beekman FJ (March 2015).
1098:
removal, and genome edited cells expressing a genetically encoded human protein,
1015:
and non-immunogenic, and a small molecule that is positron-emitting (boron bound
1960:"U-SPECT-II: An Ultra-High-Resolution Device for Molecular Small-Animal Imaging"
1125:
1091:
1066:
1062:
1016:
1008:
984:
353:
323:
then be used to infer neuronal activity through the neurovascular coupling. The
143:
2500:
2308:
2061:
1873:
440:
7T cryogen free preclinical MRI imaging system – this shows the MRS 7000 series
2347:
2017:
2000:
1976:
1959:
1918:
1822:
1733:
1650:
1386:
1124:
allows for two imaging agents that compensate for the weakness of the others.
1028:
639:, and thus extra control groups might be needed to account for this potential
523:, and thus extra control groups might be needed to account for this potential
392:
378:
311:
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2144:
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515:
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2110:
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1985:
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1703:
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1345:
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1136:
small molecules allow for permanent signal when stored in the dark and not
1065:, is within the animal or human for nearly unlimited depth of penetration.
615:
607:
549:
1497:
1071:
988:
980:
234:
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1769:
1584:
Wang M, Hong X, Chang CF, Li Q, Ma B, Zhang H, et al. (July 2015).
2719:
553:
2655:"18[F]-Positron Emitting, Fluorescent Derivative of Dasatinib"
2367:
Rodriguez EA, Wang Y, Crisp JL, Vera DR, Tsien RY, Ting R (May 2016).
2291:
Kovar JL, Johnson MA, Volcheck WM, Chen J, Simpson MA (October 2006).
2203:
2178:
1927:
1601:
2702:
Kommidi H, Guo H, Chen N, Kim D, He B, Wu AP, Aras O, Ting R (2017).
2075:'Magnifying Results: Preclinical Tech Advances Disease Understanding'
1079:
1020:
1004:
647:
molarities which may alter their biochemical or physical properties.
242:
238:
213:(CT) are usually used for anatomical imaging, while optical imaging (
2127:
Kovar JL, Simpson MA, Schutz-Geschwender A, Olive DM (August 2007).
1215:
479:
1530:'Honey, I shrunk the magnet: Preclinical 7T MRI runs cryogen-free'
842:
801:
655:
590:
486:
478:
435:
1140:. Currently, there is not a single instrument that can image the
1035:, to compensate for the weaknesses of single imaging techniques.
397:
116:
59:
18:
1364:"Simultaneous molecular and hypoxia imaging of brain tumors
1907:
European
Journal of Nuclear Medicine and Molecular Imaging
1811:
European
Journal of Nuclear Medicine and Molecular Imaging
1722:
European
Journal of Nuclear Medicine and Molecular Imaging
2581:
Tsien RY (September 2003). "Imagining imaging's future".
2089:
Weissleder R, Mahmood U (May 2001). "Molecular imaging".
1887:
1481:"Non-invasive in vivo imaging in small animal research"
229:(SPECT) are usually used for molecular visualizations.
74:
A major contributor to this article appears to have a
700:
LEHR parallel hole collimator, Rat and Mice imaging
548:(PET) images living systems by recording high-energy
491:
Volume rendering of reconstructed CT of a mouse skull
16:
Visualization of living animals for research purposes
1892:
Design & Development of
Medical Imaging Systems
2001:"Ultra-high-sensitivity submillimeter mouse SPECT"
855:requirements and vulnerability to cryogen supply.
2172:
2170:
2122:
2120:
2084:
2082:
1166:Small Animal Imaging: Basics and Practical Guide
275:(GPIIb/IIIa) receptors on platelets and clots, α
847:A preclinical imaging system with clip-on SPECT
514:One of the major drawbacks of micro-CT is the
327:(fUS) technique can be seen as an analogue to
2478:
2476:
2474:
2472:
2470:
2468:
2429:Journal of Cerebral Blood Flow and Metabolism
2418:
2416:
2414:
2412:
2362:
2360:
2358:
1368:using spectroscopic photoacoustic tomography"
428:(RF) signal is applied closely matching the
8:
979:Dioxaborolane chemistry enables radioactive
285:vascular endothelial growth factor receptors
606:(SPECT) also images living systems through
469:Stroke and traumatic brain injury research:
53:Learn how and when to remove these messages
1763:
1761:
1759:
1715:
1713:
1197:
1195:
1193:
1191:
1189:
1187:
1185:
964:Combined PET-optical imaging, fluorescence
604:single photon emission computed tomography
227:single photon emission computed tomography
146:. Please do not remove this message until
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2508:
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2016:
1975:
1926:
1785:
1658:
1609:
1506:
1496:
1479:Koo V, Hamilton PW, Williamson K (2006).
1300:
184:Learn how and when to remove this message
166:Learn how and when to remove this message
105:Learn how and when to remove this message
1243:
1241:
967:
752:75 pinholes in 5 rings, no multiplexing
665:
142:Relevant discussion may be found on the
1156:
2583:Nature Reviews. Molecular Cell Biology
1454:
1444:
1406:
1404:
1768:Massoud TF, Gambhir SS (March 2003).
1474:
1472:
1470:
1468:
329:functional magnetic resonance imaging
200:modalities that are non-invasive and
7:
1357:
1355:
1326:Ultrasound in Medicine & Biology
1250:Ultrasound in Medicine & Biology
356:responses, and even track molecular
1128:has a half-life of 110 min and the
750:three stationary NaI(Tl) crystals,
318:Functional ultrasound brain imaging
2103:10.1148/radiology.219.2.r01ma19316
1338:10.1016/j.ultrasmedbio.2004.01.005
1262:10.1016/j.ultrasmedbio.2009.04.012
14:
2297:The American Journal of Pathology
1302:10.1161/CIRCULATIONAHA.111.030312
726:0.5mm single pinhole collimators
34:This article has multiple issues.
1555:10.1016/j.neuroimage.2009.05.015
1164:Kiessling F, Pichler BJ (2011).
949:micro-ultrasound at 30 μm.
893:Optical imaging is divided into
779:two rotating NaI(Tl) detectors,
743:2009, Ivashchenko et al., 2015,
121:
85:. Please discuss further on the
64:
23:
2610:ACS Medicinal Chemistry Letters
2385:10.1021/acs.bioconjchem.6b00164
1413:2008 IEEE Ultrasonics Symposium
42:or discuss these issues on the
2757:Journal of Medicinal Chemistry
2622:10.1021/acsmedchemlett.7b00471
2538:Journal of Medicinal Chemistry
1590:Magnetic Resonance in Medicine
1204:Nature Reviews. Drug Discovery
1:
2671:10.1158/1535-7163.MCT-17-0423
2659:Molecular Cancer Therapeutics
1639:Brain, Behavior, and Immunity
325:functional ultrasound imaging
289:ultrasound research interface
2769:10.1021/acs.jmedchem.8b00240
2550:10.1021/acs.jmedchem.8b00240
2183:Journal of Biomedical Optics
997:positron emission tomography
698:Pixelated CsI(Tl) crystals,
546:Positron Emission Tomography
305:used to detect and quantify
223:positron emission tomography
2005:Journal of Nuclear Medicine
1964:Journal of Nuclear Medicine
433:of different tissue types.
148:conditions to do so are met
2834:
2501:10.1021/acschembio.9b00160
2309:10.2353/ajpath.2006.060324
2062:10.1016/j.nima.2007.08.187
1874:10.1016/j.nima.2014.01.001
1168:(1st ed.). Springer.
1041:Combines the strengths of
883:
584:
465:expression in the system.
418:Magnetic resonance imaging
207:magnetic resonance imaging
2348:10.1101/2021.07.08.451623
2018:10.2967/jnumed.114.147140
1977:10.2967/jnumed.108.056606
1919:10.1007/s00259-010-1683-y
1888:"Medical imaging systems"
1823:10.1007/s00259-006-0248-6
1734:10.1007/s00259-008-1042-4
1651:10.1016/j.bbi.2017.04.019
1387:10.1109/JPROC.2007.913515
1132:signal is not permanent.
2441:10.1177/0271678X16682510
2145:10.1016/j.ab.2007.04.011
1696:10.1162/1535350042380326
1421:10.1109/ULTSYM.2008.0298
678:Radius of Rotation (cm)
343:Photoacoustic tomography
2260:10.1126/science.1168683
2133:Analytical Biochemistry
1774:Genes & Development
2373:Bioconjugate Chemistry
973:
848:
807:
684:Sensitivity (cps/MBq)
596:
492:
484:
441:
1894:. Parto Negar Persia.
971:
923:charge-coupled device
846:
805:
741:van der Have et al.,
594:
490:
482:
439:
283:integrin, as well as
273:glycoprotein IIb/IIIa
83:neutral point of view
2489:ACS Chemical Biology
906:Fluorescence imaging
641:confounding variable
525:confounding variable
2252:2009Sci...324..804S
2195:2007JBO....12b4017A
2054:2007NIMPA.583..119D
1866:2014NIMPA.741..169S
1787:10.1101/gad.1047403
1498:10.1155/2006/245619
1415:. pp. 1234–7.
1088:cerebrospinal fluid
995:, which allows for
781:various apertures
770:Del Guerra et al.,
675:System description
499:Computed tomography
422:spin quantum number
211:computed tomography
197:Preclinical imaging
135:of this article is
2720:10.7150/thno.19408
2585:. Suppl: SS16-21.
974:
849:
808:
724:NaI(Tl) crystals,
597:
493:
485:
442:
2665:(12): 2902–2912.
2204:10.1117/1.2717137
1684:Molecular Imaging
1602:10.1002/mrm.25690
1485:Cellular Oncology
1430:978-1-4244-2428-3
1175:978-3-642-12944-5
1144:signal and image
839:Combined SPECT-MR
795:
794:
587:Preclinical SPECT
430:Larmor precession
194:
193:
186:
176:
175:
168:
115:
114:
107:
78:with its subject.
57:
2825:
2791:
2790:
2780:
2763:(9): 4256–4262.
2748:
2742:
2741:
2731:
2714:(9): 2377–2391.
2699:
2693:
2692:
2682:
2650:
2644:
2643:
2633:
2601:
2595:
2594:
2578:
2572:
2571:
2561:
2544:(9): 4256–4262.
2529:
2523:
2522:
2512:
2495:(7): 1449–1459.
2480:
2463:
2462:
2452:
2420:
2407:
2406:
2396:
2379:(5): 1390–1399.
2364:
2353:
2352:
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2337:
2331:
2330:
2320:
2288:
2282:
2281:
2271:
2231:
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2174:
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2124:
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2114:
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2020:
1996:
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1408:
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1359:
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1349:
1321:
1315:
1314:
1304:
1280:
1274:
1273:
1245:
1236:
1235:
1199:
1180:
1179:
1161:
953:Cancer research:
873:Cancer research:
832:Cancer research:
681:Resolution (mm)
666:
651:Cancer research:
602:Similar to PET,
574:Cancer research:
531:Cancer research:
462:Cancer research:
371:Cancer research:
302:Cancer Research:
249:Micro-ultrasound
189:
182:
171:
164:
160:
157:
151:
125:
124:
117:
110:
103:
99:
96:
90:
76:close connection
68:
67:
60:
49:
27:
26:
19:
2833:
2832:
2828:
2827:
2826:
2824:
2823:
2822:
2818:Medical imaging
2813:Medical physics
2798:
2797:
2794:
2750:
2749:
2745:
2701:
2700:
2696:
2652:
2651:
2647:
2603:
2602:
2598:
2580:
2579:
2575:
2531:
2530:
2526:
2482:
2481:
2466:
2422:
2421:
2410:
2366:
2365:
2356:
2339:
2338:
2334:
2290:
2289:
2285:
2246:(5928): 804–7.
2233:
2232:
2228:
2176:
2175:
2168:
2126:
2125:
2118:
2088:
2087:
2080:
2073:
2069:
2039:
2038:
2034:
1998:
1997:
1993:
1957:
1956:
1952:
1904:
1903:
1899:
1886:
1885:
1881:
1851:
1850:
1846:
1808:
1807:
1803:
1767:
1766:
1757:
1719:
1718:
1711:
1681:
1680:
1676:
1632:
1631:
1627:
1583:
1582:
1578:
1540:
1539:
1535:
1528:
1524:
1478:
1477:
1466:
1453:
1443:
1431:
1410:
1409:
1402:
1370:
1361:
1360:
1353:
1323:
1322:
1318:
1295:(25): 3117–26.
1282:
1281:
1277:
1247:
1246:
1239:
1216:10.1038/nrd2290
1201:
1200:
1183:
1176:
1163:
1162:
1158:
1154:
1122:optical imaging
1096:prostate cancer
1084:red blood cells
1047:optical Imaging
993:red blood cells
966:
935:bioluminescence
899:bioluminescence
888:
886:Optical imaging
882:
880:Optical imaging
841:
800:
798:Combined PET-MR
715:Magota et al.,
689:Sajedi et al.,
589:
583:
540:
483:Micro-CT system
477:
426:radio frequency
412:
382:Compared to an
358:contrast agents
337:
320:
282:
278:
251:
219:bioluminescence
190:
179:
178:
177:
172:
161:
155:
152:
141:
126:
122:
111:
100:
94:
91:
80:
69:
65:
28:
24:
17:
12:
11:
5:
2831:
2829:
2821:
2820:
2815:
2810:
2800:
2799:
2793:
2792:
2743:
2694:
2645:
2616:(2): 114–119.
2596:
2573:
2524:
2464:
2435:(3): 776–786.
2408:
2354:
2332:
2303:(4): 1415–26.
2283:
2226:
2166:
2116:
2078:
2067:
2032:
1991:
1970:(4): 599–605.
1950:
1897:
1879:
1844:
1801:
1755:
1709:
1674:
1625:
1576:
1549:(4): 1425–34.
1533:
1522:
1464:
1455:|journal=
1429:
1400:
1351:
1316:
1275:
1256:(10): 1700–8.
1237:
1210:(7): 591–607.
1181:
1174:
1155:
1153:
1150:
1102:, for imaging
1033:Roger Y. Tsien
987:) labeling of
965:
962:
927:
926:
919:
884:Main article:
881:
878:
840:
837:
799:
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793:
792:
789:
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767:
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719:
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708:
705:
702:
696:
693:
686:
685:
682:
679:
676:
673:
670:
612:technetium-99m
585:Main article:
582:
579:
539:
536:
476:
473:
411:
408:
377:. To do so, a
336:
333:
319:
316:
307:cardiotoxicity
280:
276:
250:
247:
192:
191:
174:
173:
129:
127:
120:
113:
112:
72:
70:
63:
58:
32:
31:
29:
22:
15:
13:
10:
9:
6:
4:
3:
2:
2830:
2819:
2816:
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2811:
2809:
2806:
2805:
2803:
2796:
2788:
2784:
2779:
2774:
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2766:
2762:
2758:
2754:
2747:
2744:
2739:
2735:
2730:
2725:
2721:
2717:
2713:
2709:
2705:
2698:
2695:
2690:
2686:
2681:
2676:
2672:
2668:
2664:
2660:
2656:
2649:
2646:
2641:
2637:
2632:
2627:
2623:
2619:
2615:
2611:
2607:
2600:
2597:
2592:
2588:
2584:
2577:
2574:
2569:
2565:
2560:
2555:
2551:
2547:
2543:
2539:
2535:
2528:
2525:
2520:
2516:
2511:
2506:
2502:
2498:
2494:
2490:
2486:
2479:
2477:
2475:
2473:
2471:
2469:
2465:
2460:
2456:
2451:
2446:
2442:
2438:
2434:
2430:
2426:
2419:
2417:
2415:
2413:
2409:
2404:
2400:
2395:
2390:
2386:
2382:
2378:
2374:
2370:
2363:
2361:
2359:
2355:
2349:
2344:
2336:
2333:
2328:
2324:
2319:
2314:
2310:
2306:
2302:
2298:
2294:
2287:
2284:
2279:
2275:
2270:
2265:
2261:
2257:
2253:
2249:
2245:
2241:
2237:
2230:
2227:
2222:
2218:
2214:
2210:
2205:
2200:
2196:
2192:
2189:(2): 024017.
2188:
2184:
2180:
2173:
2171:
2167:
2162:
2158:
2154:
2150:
2146:
2142:
2138:
2134:
2130:
2123:
2121:
2117:
2112:
2108:
2104:
2100:
2097:(2): 316–33.
2096:
2092:
2085:
2083:
2079:
2076:
2071:
2068:
2063:
2059:
2055:
2051:
2048:(1): 119–24.
2047:
2043:
2036:
2033:
2028:
2024:
2019:
2014:
2010:
2006:
2002:
1995:
1992:
1987:
1983:
1978:
1973:
1969:
1965:
1961:
1954:
1951:
1946:
1942:
1938:
1934:
1929:
1924:
1920:
1916:
1913:(4): 742–52.
1912:
1908:
1901:
1898:
1893:
1889:
1883:
1880:
1875:
1871:
1867:
1863:
1859:
1855:
1848:
1845:
1840:
1836:
1832:
1828:
1824:
1820:
1817:(2): 151–61.
1816:
1812:
1805:
1802:
1797:
1793:
1788:
1783:
1780:(5): 545–80.
1779:
1775:
1771:
1764:
1762:
1760:
1756:
1751:
1747:
1743:
1739:
1735:
1731:
1728:(2): 302–14.
1727:
1723:
1716:
1714:
1710:
1705:
1701:
1697:
1693:
1690:(3): 149–58.
1689:
1685:
1678:
1675:
1670:
1666:
1661:
1656:
1652:
1648:
1644:
1640:
1636:
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1617:
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1607:
1603:
1599:
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1587:
1580:
1577:
1572:
1568:
1564:
1560:
1556:
1552:
1548:
1544:
1537:
1534:
1531:
1526:
1523:
1518:
1514:
1509:
1504:
1499:
1494:
1491:(4): 127–39.
1490:
1486:
1482:
1475:
1473:
1471:
1469:
1465:
1460:
1448:
1440:
1436:
1432:
1426:
1422:
1418:
1414:
1407:
1405:
1401:
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36:Please help
33:
2139:(1): 1–12.
1645:: 344–353.
1289:Circulation
1134:Fluorescent
1114:Weaknesses:
1108:CAR T-cells
1106:edited and
1104:CRISPR/Cas9
1092:hemorrhages
1025:CRISPR/Cas9
1009:hemorrhages
1003:imaging of
941:Weaknesses:
866:Weaknesses:
825:Weaknesses:
764:13000 best
747:U-SPECT II
633:Weaknesses:
626:micro-SPECT
581:Micro-SPECT
567:Weaknesses:
512:Weaknesses:
455:Weaknesses:
364:Weaknesses:
354:hemodynamic
295:Weaknesses:
225:(PET), and
2802:Categories
1928:2115/48719
1860:: 169–76.
1543:NeuroImage
1152:References
1116:Combining
1072:antibodies
1059:radiolabel
1039:Strengths:
999:(PET) and
989:antibodies
977:Principle:
930:Strengths:
891:Principle:
859:Strengths:
852:Principle:
818:Strengths:
811:Principle:
788:0.62 best
759:0.25 best
695:HiReSPECT
669:Reference
622:Strengths:
600:Principle:
560:Strengths:
543:Principle:
505:Strengths:
496:Principle:
448:Strengths:
415:Principle:
393:hemoglobin
379:craniotomy
349:Strengths:
340:Principle:
312:biomarkers
261:Strengths:
254:Principle:
209:(MRI) and
133:neutrality
39:improve it
2091:Radiology
1457:ignored (
1447:cite book
1375:Proc IEEE
645:chelating
538:Micro-PET
516:radiation
410:Micro-MRI
335:Micro-PAT
156:June 2016
144:talk page
95:June 2016
87:talk page
45:talk page
2787:29676909
2738:28744321
2689:28978723
2640:29456798
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2403:27064381
2327:17003496
2278:19423828
2221:39806507
2213:17477732
2161:16426577
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2111:11323453
2027:25678487
1986:19289425
1945:19890309
1937:21153410
1839:32330635
1831:17143647
1796:12629038
1750:25389532
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1704:15530250
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1439:42410198
1346:15121254
1311:22647975
1270:19647922
1232:37571813
1224:18591980
981:fluoride
776:X-SPECT
475:Micro-CT
235:SPECT/CT
137:disputed
2808:Imaging
2778:6263152
2729:5525743
2680:6287766
2631:5807872
2559:6263152
2510:6775626
2450:5363488
2394:4916912
2343:bioRxiv
2318:1698854
2269:2763207
2248:Bibcode
2240:Science
2191:Bibcode
2050:Bibcode
1862:Bibcode
1660:5572149
1611:4608848
1508:4617494
1395:1815688
1366:in vivo
958:in vivo
916:in vivo
911:in vivo
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721:Inveon
691:2014,
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1080:cancer
1021:cancer
1005:cancer
717:2011,
672:Brand
616:γ-rays
608:γ-rays
550:γ-rays
396:micro-
243:PET/MR
239:PET/CT
2217:S2CID
2157:S2CID
1941:S2CID
1835:S2CID
1746:S2CID
1567:S2CID
1435:S2CID
1391:S2CID
1371:(PDF)
1228:S2CID
1076:cells
1029:CAR T
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1982:PMID
1933:PMID
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1792:PMID
1738:PMID
1700:PMID
1665:PMID
1616:PMID
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1459:help
1425:ISBN
1342:PMID
1307:PMID
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1007:and
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130:The
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