Small Animal Imaging Facility Newsletter Biomedical Research Imaging Center

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1 Small Animal Imaging Facility Newsletter Biomedical Research Imaging Center Volume 2. Issue. 2 May, 2013 SAI Facility News and Updates 1. The BRIC website has a new look (h p://bric.unc.edu). There were some minor modifica ons on Small Animal Imaging service and scheduling pages, but no major changes on the contents. Please visit our website and let us know if you have any comments. 2. New radioisotope Zr-89 has been added into our radia on license. We are now able to do Zr-89 PET imaging. Zr-89 is an a rac ve radionuclide with 3.3 days of half life and is ideal to track long blood circula- on an bodies or par cles. 3. The scheduled op cal imaging training in this quarter will be on May 6th, June 17th, and July 8th, from 2:00-3:30pm in BRIC building room 122. Please send to bricsa@med.unc.edu for registra on. Inside this issue SAI Facility News & Updates New Optical Imaging Probes Featured Animal Imaging Techniques -MRI.2-3 Imaging Study Highlight..4 Contact information... 5 NEW Optical Imaging Probes Op cal imaging is an important molecular imaging modality. Many near-infrared fluorescence probes have been developed to monitor disease progression and explore biological mechanisms on the molecular level. Knowing what has been developed might be very helpful. Below is a list of some newly developed and commercially available fluorescence probes. Contact SAI for a consulta on on which probe to choose or which op cal imaging system to use. Name Target Excita on/emission (nm) Half life FolateRSense a Folate Receptor 670/685 5 min TLec nsense a Vascular membrane glycoprotein 670/ hr BacteriSense a Gram-nega ve or posi ve bacteria infec on 645/ min PSA 750 FAST a Prostate-Specific An gen (PSA) 750/770 NA Her2sense a Her2 protein 645/661 9 hr Hypoxisense a Carbonic anhydrase IX 670/685 NA BombesinRSense a Bombesin receptor 670/ hr Neutrophil probe b Formylpep de receptor of neutrophil 745/800 2 hr Fluorescent protein c Plasmid transfected to targeted DNA 690/713 NA a: Available from Perkin-Elmer; b: Available from KeraFast.com; c: Available from Addgene.org

2 Small Animal Imaging Facility Newsletter Volume 2. Issue. 2 Featured Animal Imaging Technique Magnetic Resonance Imaging Bruker Biospec 9.4 Tesla, 30 cm Bore Small Animal MRI system BGA-9S gradient insert (up to 74 G/cm) allowing high resolu on MRI 35, 72, and 150 mm quad-transceiver volume coil for uniform RF excita on and body imaging 4-channel receive only phase array coil for brain imaging Quad-receive only coil for mouse brain imaging Real me respiratory and cardiac ga ng Animal temperature monitoring -What Can we do at BRIC SAI facility? 9.4T MRI system in the BRIC SAI facility Imaging Applica on 1: High Resolu on Anatomy Various protocols have been developed for high resolu on anatomical MR imaging, including tradi onal T1-weighted, T2- weighted, or diffusion tensor imaging (DTI). The DTI technique allows iden fica on of water mobility in vivo or ex vivo and has been shown a useful tool to study white ma er structure in the brain. Left: T2-weighted image showing anatomical details of the rat brain at 50x50 micron resolution. Bottom: DTI of the rat brain at 75x75 micron resolution using a multi-shot EPI sequence. First column: mean diffusivity (a measure of diffusion magnitude in mm 2 /s unit); middle column: fractional anisotropy (a measure of the diffusion directionality); third column: color-coded fractional anisotropy (red color: medial-lateral, blue: anterior-posterior, green: dorsal-ventral). Imaging Applica on 2: Quan ta ve Cerebral Blood Flow Measurement Con nuous arterial spin labeling (CASL) technique can be used to magne cally label blood at the caro d artery, and measure blood flow. This technique is completely noninvasive. It does not require exogenous contrast agent and can provide up to 3 sec temporal resolu on. High resolution cerebral blood flow maps of the rat brain (50x50 m resolution) using CASL protocol. Pixel value ranged from 0-2 ml/g/min.

3 Imaging Applica on 3: Func onal Magne c Resonance Imaging (fmri) fmri has become an emerging tool for neuroscience research, as it provides non-invasive, quantitative mapping of dynamic brain functions at a whole-brain scale. Blood-oxygenation-level-dependent (BOLD) fmri is based on the paramagnetic nature of deoxyhemoglobin in blood and neuron activation-related blood oxygenation changes either in activation state or resting state. This technique does not require any exogenous contrast agent. Above: BOLD fmri of subthalamic nucleus deep brain stimulation, demonstrating brain responses to deep brain stimulation. Yellow-shaded epochs indicate stimulation period. Above: Resting-state fmri. In vivo functional connectivity maps to identify brain network in resting state. (PI: Drs. Wei Gao & Ian Shih) Left: Cerebral blood volume weighted fmri of optogenetics. Functional blood volume changes can be detected with MRI by pre-injecting blood-pool type iron-oxide nanoparticles. Transient optogenetic activation of dopaminergic neurons within the midbrain caused significant regional blood volume increases in downstream targets of the ventral tegmental area including the caudate putamen, cingulate cortex, and numerous cortical regions in ChR2-EYFP rats. (PI: Drs. Garret Stuber & Ian Shih). A Imaging Applica on 4: Func onal tract tracing and mapping calciumweighted neural ac vity using manganese enhanced MRI Manganese enhanced MRI (MEMRI) is an emerging modality of fmri. It has been shown that manganese ion can be transported between neurons via voltage-gated calcium channels and the transport rate is associated with the func- onality of the area. Right A: Tract-tracing MEMRI shows enhanced manganese accumulation in the barrel cortex (arrow) when manganese was injected into the ventral posteriomedial thalamic nuclei. B Right B: Systemic MEMRI in a mouse shows global enhancement in areas with high calcium-weighted activity. (All the images except the marked ones are provided by Dr. Ian Shih, the Director of SAI MRI section.)

4 Imaging Study Highlights Ultrasound/PET Imaging on spontaneous pancreatic tumor mouse model FDG PET High resolution ultrasound Car- High resolution ultrasound imaging was used for initial diagnosis of lesion size on a genetically engineered mouse (GEM) pancreatic cancer model. FDG PET imaging was used to further validate the lesion and detect possible metastasis. The tumor shoed FDG avid characteristics and multi-nodules were found in FDG PET images (yellow arrow). (PI: Dr. Jenjen Yeh) A Multimodality registered CT/optical imaging on gastrointestinal cancer GEM model Registered contrast-enhanced microct imaging and cathepsin optical molecular imaging depict tumor burden and expression of cathepsin in Apc/min+ mutant gastrointestinal cancer model. Ex -vivo fluorescence imaging was used for validation. (PI: Dr. Kay Lund) Mouse embryo imaging High resolution ultrasound imaging was used to monitor the growth of embryo in mouse with loss of function of a mirna and mir-137. Image showed day15 embryo with MM550S ultrasound probe(~50mhz). (PI: DR. Patrick Sullivan)

5 Imaging service list 9.4T MRI PET/CT SPECT/CT Op cal Imaging Ultrasound Imaging microct on live animal microct on specimens Imaging Study Design Image data processing Animal handling and care Carbon fiber weaves in the bed Contact Information SAI Facility Director Hong Yuan SAI MRI Director Yen-Yu Ian Shih General Contact/User Support Jon Frank/Kevin Guley/Carla Johnson Website h p://bric.unc.edu/services/small-animalimaging Address Medical Research Building D 124 Mason Farm Road Chapel Hill, NC Pub. Date: May 1st, 2013