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=== Molecular imaging by MRI === {{Main|Molecular imaging}} MRI has the advantages of having very high spatial resolution and is very adept at morphological imaging and functional imaging. MRI does have several disadvantages though. First, MRI has a sensitivity of around 10<sup>β3</sup> [[concentration#Molarity|mol/L]] <!--is this what M was supposed to be, molarity? if not, explain and link as appropriate--> to 10<sup>β5</sup> mol/L, which, compared to other types of imaging, can be very limiting. This problem stems from the fact that the population difference between the nuclear spin states is very small at room temperature. For example, at 1.5 [[tesla (unit)|teslas]], a typical field strength for clinical MRI, the difference between high and low energy states is approximately 9 molecules per 2 million. Improvements to increase MR sensitivity include increasing magnetic field strength and [[Hyperpolarization (physics)|hyperpolarization]] via optical pumping or dynamic nuclear polarization. There are also a variety of signal amplification schemes based on chemical exchange that increase sensitivity.<ref name="Gallagher2010">{{cite journal | vauthors = Gallagher FA | title = An introduction to functional and molecular imaging with MRI | journal = Clinical Radiology | volume = 65 | issue = 7 | pages = 557β66 | date = July 2010 | pmid = 20541655 | doi = 10.1016/j.crad.2010.04.006 }}</ref> To achieve molecular imaging of disease biomarkers using MRI, targeted MRI [[contrast agent]]s with high specificity and high relaxivity (sensitivity) are required. To date, many studies have been devoted to developing targeted-MRI contrast agents to achieve molecular imaging by MRI. Commonly, peptides, antibodies, or small ligands, and small protein domains, such as HER-2 affibodies, have been applied to achieve targeting. To enhance the sensitivity of the contrast agents, these targeting moieties are usually linked to high payload MRI contrast agents or MRI contrast agents with high relaxivities.<ref>{{cite journal | vauthors = Xue S, Qiao J, Pu F, Cameron M, Yang JJ | title = Design of a novel class of protein-based magnetic resonance imaging contrast agents for the molecular imaging of cancer biomarkers | journal = Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology | volume = 5 | issue = 2 | pages = 163β79 | year = 2013 | pmid = 23335551 | pmc = 4011496 | doi = 10.1002/wnan.1205 }}</ref> A new class of gene targeting MR contrast agents has been introduced to show gene action of unique mRNA and gene transcription factor proteins.<ref name="pmid17234603">{{cite journal | vauthors = Liu CH, Kim YR, Ren JQ, Eichler F, Rosen BR, Liu PK | title = Imaging cerebral gene transcripts in live animals | journal = The Journal of Neuroscience | volume = 27 | issue = 3 | pages = 713β22 | date = January 2007 | pmid = 17234603 | pmc = 2647966 | doi = 10.1523/JNEUROSCI.4660-06.2007 }}</ref><ref name="pmid24115049">{{cite journal | vauthors = Liu CH, Ren J, Liu CM, Liu PK | title = Intracellular gene transcription factor protein-guided MRI by DNA aptamers in vivo | journal = FASEB Journal | volume = 28 | issue = 1 | pages = 464β73 | date = January 2014 | pmid = 24115049 | pmc = 3868842 | doi = 10.1096/fj.13-234229 | doi-access = free }}</ref> These new contrast agents can trace cells with unique mRNA, microRNA and virus; tissue response to inflammation in living brains.<ref name="pmid19295156">{{cite journal | vauthors = Liu CH, You Z, Liu CM, Kim YR, Whalen MJ, Rosen BR, Liu PK | title = Diffusion-weighted magnetic resonance imaging reversal by gene knockdown of matrix metalloproteinase-9 activities in live animal brains | journal = The Journal of Neuroscience | volume = 29 | issue = 11 | pages = 3508β17 | date = March 2009 | pmid = 19295156 | pmc = 2726707 | doi = 10.1523/JNEUROSCI.5332-08.2009 }}</ref> The MR reports change in gene expression with positive correlation to TaqMan analysis, optical and electron microscopy.<ref name="pmid23150521">{{cite journal | vauthors = Liu CH, Yang J, Ren JQ, Liu CM, You Z, Liu PK | title = MRI reveals differential effects of amphetamine exposure on neuroglia in vivo | journal = FASEB Journal | volume = 27 | issue = 2 | pages = 712β24 | date = February 2013 | pmid = 23150521 | pmc = 3545538 | doi = 10.1096/fj.12-220061 | doi-access = free }}</ref>
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